健康文摘

1
裸露是肉欲也是美术

2
WHO：近半数死亡发生在60岁以下

3
生吃六种蔬菜可极速瘦身

4
10 facts on sexually transmitted infections

5
手机辐射可损害精子DNA

6
揭开女人神秘的性爱愉悦点

7
长期熬夜的10大严重健康后果

8
北京现有百岁老人247位 “长寿秘诀”有七条

9
美国医生：披露14种食物助您健康长寿

10
肝病患者性生活注意要点

11
男人的性爱习惯：花样百出

12
美国研究人员：服用银杏叶汁可减低中风者脑受损

13
肝病自查小技巧

14
潘金莲只是性感吗? 揭密女性御夫术（图）

15
这才是“精致”的女孩子（图）

16
烟民庞大，数千万中国人将因肺病提前死亡

17
肝病的饮食疗法

18
性别比例失调_4000万男人娶不到老婆

19
刘史：中国妓女之多超过全世界妓女总数

20
婚外恋的成熟女人 （多图）

21
13种征兆预示肝脏疾病

22
中药治疗脂肪肝

23
乙肝感染者结婚和性生活注意事项

24
乙型肝炎

25
有损肝脏的十三种饮食习惯

26
韩媒：毒奶粉激发中国母乳喂养热

27
男女考堂：测测你的性福系数(图）

28
香港医院摆大乌龙 非乳癌病人被切乳房

29
中国湖北医师资格考试 33人作弊被处理

30
有感三鹿，不得不说的牛奶故事

31
国产牛奶还敢喝吗？顾客：以后自己养牛

32
三鹿奶粉事件：三位英雄三位昏官三个混蛋

33
性爱：卡得太紧，拔不出来(图）

34
三十多岁的女人在想什么

35
性欲强弱由什么因素决定的（图）

36
天津剖宫产率高达65% 远高于世卫组织推荐比例

37
从体型看女人的七情六欲（图）

38
“最离奇死亡”大盘点 被空中掉下毒蛇咬死

39
(组图) 乳房的诱惑

40
夏日乳景（图）

41
二战后，各国女间谍训练内容让人吃惊

42
揭黑医生妻离子散，剑指中国医改悲哀

43
八种姿态暗示女性需求

44
医疗简讯：对癌症风险的错误认识

45
女人偷情之后的外表特征

46
气质美女

47
性感的乳房与乳房的美学

48
图解世界上七对最棒的乳房

49
午睡时的五要四不要

50
让她性满意足

51
吃内脏补身当心“镉”损精不孕

52
保护好女性私处的防护系统

53
少妇自述：我如何提高老公的性能力

54
刚柔并济，性趣无穷

55
男人喜欢女人纯情还是调情

56
北京奥运后将实行更严格环保措施

57
旅法作家多次为刘晓庆人工受精秘闻

58
美利用干细胞造出了人血

59
基因甲基化检测 準确预测可能致癌的女性

60
女人最渴望被抚摸的敏感部位

61
台湾“排毒教父” 坑杀病患监两年半

62
完美性爱的多重元素

63
性爱的三个乐章

64
古代传奇美女中药美容秘方

65
China's first transgenic cow born to help fight cancer

66
让女性达到最最高潮的宝典

67
How the Heart Works

68
民间嬉春助性食谱秘方

69
男人性趣走跌

70
美承认低估新艾滋病感染人数

肝病研究进展--（近年发表的文献回顾）

1: Clin Rev Allergy Immunol. 2008 May 23. [Epub ahead of print]

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Bacteria and Primary Biliary Cirrhosis.

Bogdanos DP, Vergani D.

Liver Immunopathology, Institute of Liver Studies, King’s College London School of Medicine, King’s College Hospital, Denmark Hill Campus, London, SE5 9RS, UK.

Infectious agents have been postulated to play a pathogenic role in the loss of immunological tolerance and the induction of primary biliary cirrhosis, an immune-mediated cholestatic liver disease characterized by progressive destruction of the small intrahepatic bile ducts and subsequent cirrhosis and liver failure. This review discusses emerging issues implicating infectious agents such as Escherichia coli, mycobacteria, chlamydia, helicobacter species, lactobacilli, Novosphingobium aromaticivorans, and betaretroviruses in the pathogenesis of primary biliary cirrhosis. We also review the immunopathological mechanisms responsible for the induction of the disease with special emphasis on the role of molecular mimicry and microbial/self immunological cross-reactivity.

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2: Br J Surg. 2008 May 21. [Epub ahead of print]

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Living related liver transplantation in children.

Heaton N, Faraj W, Melendez HV, Jassem W, Muiesan P, Mieli-Vergani G, Dhawan A, Rela M.

Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, Denmark Hill, London SE5 9RS, UK.

BACKGROUND:: Living related liver transplantation (LRLT) has become established for treating children with end-stage liver disease. The aim of this study was to review a single-centre experience of left lateral segment liver transplants from living donors in children. METHODS:: Fifty left lateral segment LRLT procedures have been performed since 1993. There were 17 girls and 33 boys, of median age 1.5 years (range 0.5 to 13 years), with a median weight of 10 (range 0.7-44) kg. Donors included 23 mothers, 26 fathers and one uncle, with a median age of 33 (range 19-46) years. RESULTS:: At a median follow-up of 86 months, there was no donor mortality and low morbidity. Patient and graft survival rates were 98, 96 and 96 per cent, and 98, 96 and 93 per cent at 1, 3 and 5 years respectively. Three children had a second transplant at a median of 9 years after the first. The incidence of hepatic artery thrombosis, portal vein thrombosis and biliary complications was 6, 4 and 14 per cent respectively. CONCLUSION:: Living related liver transplantation has good long-term results in children. Copyright (c) 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

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3: Radiology. 2008 Jun;247(3):896-902.

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Imaging findings after liver resection by using radiofrequency parenchymal coagulation devices: initial experiences.

McGahan JP, Khatri VP.

Departments of Radiology and Surgery, University of California Davis Medical Center, 4501 X St, Suite 3010, Sacramento, CA 95817, USA.

PURPOSE: To retrospectively evaluate the imaging features and potential pitfalls in interpreting the findings at the site of surgery in patients undergoing hepatic resection by using the InLine and TissueLink radiofrequency devices for parenchymal coagulation prior to transection. MATERIALS AND METHODS: This HIPAA-compliant study was approved by the Institutional Review Board with waiver of informed consent. Twenty-six patients (14 men, 12 women; mean age, 56 years), in whom intraoperative Inline and TissueLink devices were used for resection of hepatocellular carcinoma or metastatic liver disease or other liver tumors, were identified. Information such as tumor characteristics, diagnostic studies, surgical therapy, and surveillance methods were reviewed. All computed tomographic (CT) and positron emission tomographic (PET) scans and the single magnetic resonance and ultrasonographic images of the abdomen were retrospectively reviewed by a radiologist and compared with the initial interpreting physician's report. RESULTS: Of 35 CT scans, 33 revealed a hypodense line of demarcation (mean thickness, 13.2 mm) between the surgical resection clips and the normal liver parenchyma. This demarcation was interpreted as "could not exclude site recurrence" in three cases and "recurrence or probable recurrence" in five cases. In two CT scans, the hypodense demarcation was not present. In all seven PET scans, the uniform hypermetabolic activity associated with the demarcation was labeled as a recurrence. At follow-up CT (median, 12.5 months), marginal recurrence was not detected in 25 patients, though in one case there was a recurrence in close proximity to the surgical site. CONCLUSION: The use of InLine and TissueLink devices during hepatectomy is associated with a linear hypodense demarcation at the surgical margin that also demonstrates a symmetrical rimlike hypermetabolic activity seen on PET scans. (c) RSNA, 2008.

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4: Anat Rec (Hoboken). 2008 Jun;291(6):684-92.

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Hepatic microcirculation in Fatty liver disease.

Farrell GC, Teoh NC, McCuskey RS.

Gastroenterology and Hepatology Unit, and Australian National University Medical School, The Canberra Hospital, Garran, Australia. geoff.farrell@act.gov.au

Nonalcoholic fatty liver disease (NAFLD), the most common cause of steatosis, is associated with visceral obesity and insulin resistance. With more severe risk factors (obesity, type 2 diabetes [T2D], metabolic syndrome), steatosis may be complicated by hepatocellular injury and liver inflammation (steatohepatitis or NASH). NASH can lead to perisinusoidal fibrosis and cirrhosis. Fat-laden hepatocytes are swollen, and in steatohepatitis, further swelling occurs due to hydropic change (ballooning) of hepatocytes to cause sinusoidal distortion, as visualized by in vivo microscopy, reducing intrasinusoidal volume and microvascular blood flow. Involvement of other cell types (sinusoidal endothelial cells, Kupffer cells, stellate cells) and recruitment of inflammatory cells and platelets lead to dysregulation of microvascular blood flow. In animal models, the net effect of such changes is a marked reduction of sinusoidal space (approximately 50% of control), and a decrease in the number of normally perfused sinusoids. Such microvascular damage could accentuate further liver injury and disease progression in NASH. The fatty liver is also exquisitely sensitive to ischemia-reperfusion injury, at least partly due to the propensity of unsaturated fatty acids to undergo lipid peroxidation in the face of reactive oxygen species (ROS). This has important clinical consequences, particularly limiting the use of fatty donor livers for transplantation. In this review, we discuss available data about the effects of steatosis and steatohepatitis on the hepatic microvascular structure and sinusoidal blood flow, highlighting areas for future investigation.

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5: Liver Int. 2008 May 14. [Epub ahead of print]

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Green tea consumption and liver disease: a systematic review.

Jin X, Zheng RH, Li YM.

Digestive Department, the First Affiliated Hospital, Medical School, Zhejiang University, Zhejiang, China.

Objectives: To present the effect of green tea consumption against liver disease. Data sources: Interventional and observational studies both in Western countries and in China and published between the years 1989 and December 2007. Review Methods: The articles were retrieved from Medline, Embase database, Chinese biomedicine web database and Chinese scientific journal's database using proper MESH headings and assessed by two independent investigators according to established inclusion criteria. The characteristics and outcomes of the chosen articles were displayed for further analysis and the quality of each study was also evaluated according to the widely acknowledged criteria. P<0.05 st="on">China, one from Japan and the other from the USA) with various outcomes such as liver cancer, cirrhosis and fatty liver disease were finally chosen. Among them, study designs differed in that there were four randomized-controlled clinical trials, two cohort, one case-control and three cross-sectional studies. The heterogeneity in the study design, outcomes, cofounders and amount of tea consumption precluded further meta-analysis. Nevertheless, eight studies showed a significant protective role of green tea against various liver diseases as determined by relative risk/odds ratio or P-value and among them, four studies showed a positive correlation between green tea intake and attenuation of liver disease. Moreover, the other two studies also presented the protective tendency of green tea against liver disease. Conclusions: An increased consumption of green tea may reduce the risk of liver disease.

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6: Stem Cell Rev. 2008 May 15. [Epub ahead of print]

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Therapeutic Potential of Adult Bone Marrow Stem Cells in Liver Disease and Delivery Approaches.

Xu YQ, Liu ZC.

Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.

Hematopoietic stem cells (HSCs) and mesenchymal stem cell (MSCs) are two main subtypes of bone marrow stem cells. Extensive studies have been carried out to investigate the therapeutic potential of BMSCs in liver disease. A number of animal and human studies demonstrated that either HSCs or MSCs could be applied to therapeutic purposes in certain liver diseases. The diseased liver may recruit migratory stem cells, particularly from the bone marrow, to generate hepatocyte-like cells either by transdifferentiation or cell fusion. Transplantation of BMSCs has therapeutic effects of restoration of liver mass and function, alleviation of fibrosis and correction of inherited liver diseases. There are still controversial results over the potential effects of BMSCs on liver diseases, and some of the discrepancies are thought to be lied in the differences of experimental protocols, differences in individual research laboratory, and the uncertainties of the techniques employed. Several potential approaches for BMSCs delivery in liver diseases have been proposed in animal studies and human trials. BMSCs can be delivered via intraportal vein, systemic infusion, intraperitoneal, intrahepatic, intrasplenic. The optimal stem cells delivery should be easy to perform, less invasive and traumatic, minimum side effects, and with high cells survival rate. In this review, we focus on the up-to-date evidence of therapeutic effects of BMSCs on liver disease, the characteristics of various delivery approaches, and the considerations for future studies.

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7: Am J Gastroenterol. 2008 May;103(5):1283-97; quiz 1298.

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Acute hepatitis C: a systematic review.

Kamal SM.

Department of Gastroenterology and Liver Disease, Ain Shams Faculty of Medicine, Cairo, Egypt.

INTRODUCTION: The annual incidence of acute hepatitis C virus (HCV) has fallen in recent years, primarily because of effective blood screening efforts and increased education on the dangers of needle sharing. However, hepatitis C infection is still relatively frequent in certain populations. Most patients infected with HCV are unaware of their exposure and remain asymptomatic during the initial stages of the infection, making early diagnosis during the acute phase (first 6 months after infection) unlikely. While some of those infections will have a spontaneous resolution, the majority will progress to chronic HCV. We scanned the literature for predictors of spontaneous resolution and treatment during the acute stage of HCV to identify factors that would assist in treatment decision making. METHODS: A medical literature search through MEDLINE was conducted using the keyword "acute hepatitis C" with a variety of keywords focused on (a) epidemiology, (b) natural history and outcome, (c) diagnosis, (d) mode of transmission, and (e) treatment. RESULTS: There are no reliable predictors for spontaneous resolution of HCV infection and a significant percentage of individuals exposed to HCV develop persistent infections that progress to chronic liver disease. An intriguing approach is to treat acute HCV and prevent the development of chronic hepatitis. Several clinical trials showed that treatment of hepatitis C infection during the acute phase is associated with high sustained virological response (SVR) rates ranging between 75% and 100%. Although there is a prevailing consensus that intervention during the acute phase is associated with improved viral eradication, relevant clinical questions have remained unanswered by clinical trials. Optimization of therapy for acute hepatitis C infection and identification of predictors of SVR represent a real challenge. CONCLUSION: With more than 170 million chronic hepatitis C patients worldwide and an increase in the related morbidity and mortality projected for the next decade, an improvement in our ability to diagnose and treat patients with acute hepatitis C would have a significant impact on the prevalence of chronic hepatitis and its associated complications particularly in countries with a high endemic background of the infection.

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8: J Anim Physiol Anim Nutr (Berl). 2008 Jun;92(3):272-83.

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Liver lipid metabolism.

Nguyen P, Leray V, Diez M, Serisier S, Le Bloc'h J, Siliart B, Dumon H.

Nutrition and Endocrinology Unit, National Veterinary School of Nantes, Nantes, France. pnguyen@vet-nantes.fr

The liver plays a key role in lipid metabolism. Depending on species it is, more or less, the hub of fatty acid synthesis and lipid circulation through lipoprotein synthesis. Eventually the accumulation of lipid droplets into the hepatocytes results in hepatic steatosis, which may develop as a consequence of multiple dysfunctions such as alterations in beta-oxidation, very low density lipoprotein secretion, and pathways involved in the synthesis of fatty acids. In addition an increased circulating pool of non-esterified fatty acid may also to be a major determinant in the pathogenesis fatty liver disease. This review also focuses on transcription factors such as sterol-regulatory-element-binding protein-1c and peroxisome proliferator-activated receptor alpha, which promote either hepatic fatty acid synthesis or oxidation.

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9: J Med Imaging Radiat Oncol. 2008 Jun;52(3):231-6.

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Fine-needle trucut biopsy versus fine-needle aspiration cytology with ultrasound guidance in the abdomen.

O'Connell AM, Keeling F, Given M, Logan M, Lee MJ.

Department of Radiology, Beaumont Hospital, and The Royal College of Surgeons, Dublin, Ireland.

Historically, fine-needle aspiration cytology (FNAC) has varying sensitivity, specificity and accuracy in the diagnosis of abdominal lesions with a high insufficient sampling rate. We compared 20-G fine-needle trucut biopsy (FNTB) with FNAC results in the biopsy of solid abdominal tumours. A retrospective review of 171 (128x 20-G FNTB and 43x FNAC) ultrasound-guided biopsies of abdominal tumours on 157 patients (male : female 85:72, mean age 61.25 years) were carried out. One hundred and seventy-one biopsies were carried out: liver 109, pancreas 19, lymph node 10, omentum 5, right iliac fossa mass 6, adrenal 6 and others 16. An average of 2.06 and 1.97 passes (range 1-4) were carried out per FNTB and FNAC, respectively. A definitive diagnosis was made in 122/128 biopsies (95.3%) and 32/43 biopsies (74.4%) for FNTB and FNAC, respectively. Diagnoses consisted of metastatic liver disease (74/171), pancreatic adenocarcinoma (10/171), lymphoma (8/171) and others (33/171) and benign (29/171). No significant complications occurred in either group. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 87, 100, 100, 50, 84.4 and 93.1, 100, 100, 60, 71.4 for FNTB and FNAC, respectively. A greater and more consistent positive diagnosis rate is yielded by 20-G FNTB (95.3%) than FNAC (74.4%). The diagnostic accuracy of FNTB is 84.4% compared with 69.8% for FNAC. A greater insufficient sampling rate occurs with FNAC (25.6%) than with FNTB (4.7%). For abdominal biopsy, 20-G FNTB needles have a much higher yield than FNAC with no increase in complications. FNTB is the preferred choice, particularly where cytological assistance at the time of biopsy is unavailable.

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10: Mini Rev Med Chem. 2008 Apr;8(4):307-18.

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Recent advances in antiviral agents: established and innovative therapies for viral hepatitis.

Balsano C.

Laboratory of Molecular Virology and Oncology, Fondazione A Cesalpino, University of Rome La Sapienza, Rome, Italy. Clara.Balsano@uniroma1.it

The management of HBV or HCV has improved dramatically over the last decade with the development of new drugs. This paper provides a review of new available and developing treatment options for HBV and HCV associated liver diseases. In the closer future the most realistic therapeutical option for most of the patients with HBV and HCV infection will be combination and/or long-term usage of the new, stronger antiviral drugs, if they maintain good safety profiles, achieve low resistance rates and will be available at lower prices.

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11: Curr Pharm Des. 2008;14(10):969-72.

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Advanced glycation end products (AGEs) and their involvement in liver disease.

Hyogo H, Yamagishi S.

Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. hidehyogo@aol.com

Advanced glycation end products (AGEs) are a heterogeneous group of molecules, formed in vivo both by non-oxidative and oxidative reactions of sugars and their adducts to proteins and lipids. It is now well established that formation and accumulation of AGEs progress during normal aging, and at an extremely accelerated rate under diabetes, thus being implicated in various types of AGEs-related disorders such as diabetic vascular complications, neurodegenerative diseases and cancers. There is a growing body of evidence that activation of RAGE (receptor for AGEs) system is also implicated in these devastating disorders. Indeed, the engagement of RAGE with AGEs is shown to elicit oxidative stress generation and subsequently evoke inflammatory responses in various types of cells including hepatocytes and hepatic stellate cells. Liver is not only a target organ, but also an important site for clearance and catabolism of circulating AGEs. Although there are several papers to suggest the involvement of AGEs-RAGE system in various types of liver diseases such as non-alcoholic steatohepatitis, liver cirrhosis and cancers, as far as we know, there are few comprehensive reviews to deal with this issue. Therefore, in this paper, we shortly review the pathological role of AGEs and RAGE in various liver diseases.

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12: Curr Med Chem. 2008;15(9):930-9.

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Viral hepatitis B: established and emerging therapies.

Balsano C, Alisi A.

Fondazione A. Cesalpino, c/o I Clinica Medica, Policlinico Umberto I, Viale del Policlinico n. 155, 00161 Rome, Italy. clara.balsano@uniroma1.it

Chronic hepatitis B virus (HBV) infection has a variable course leading to cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis and clinical outcome of HBV infection are strictly dependent on both viral factors, such as life cycle and genotypic variants, and host immune response (i.e. viral persistence). Although therapy of hepatitis B is evolving, which between single and/or combined agents are most effective, how long therapy should last, which criteria should be used to start or continue and switch or stop therapy are to be defined. Two major groups of therapies are currently utilized for chronic hepatitis: immunomodulatory (interferons) and antivirals (nucleoside and nucleotide analogues), all with their own advantages and limitations. In fact, the development of specific antiviral therapies has provoked the appearance of a relevant problem: drug resistances. The emerged antiviral drug-resistant strains of HBV leads to a poor prognosis for infected patients. Thus, many basic and clinical research challenges remain in defining optimal means of management of viral hepatitis B and its related liver diseases. This paper provides a review of new available and developing treatment options for HBV associated liver diseases. In the near future the most realistic therapeutic option for the majority of patients with HBV infection will be combination and/or long-term use of new and stronger antiviral drugs, if they maintain good safety profiles, achieve low resistance rates and will be available at lower prices.

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13: Gastroenterology. 2008 May;134(6):1741-51.

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Evaluation and management of end-stage liver disease in children.

Leonis MA, Balistreri WF.

Pediatric Liver Care Center, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.

End-stage liver disease in children presents a challenging array of medical and psychosocial problems for the health care delivery team. Many of these problems are similar to those encountered by caregivers of adults with end-stage liver disease, such as the development of complications of cirrhosis, including ascites, spontaneous bacterial peritonitis, and esophageal variceal hemorrhage. However, the natural history of disease progression in children and their responses to medical therapy can differ significantly from that of their adult counterparts. Children with end-stage liver disease are especially vulnerable to nutritional compromise; if not effectively managed, this can seriously impact long-term outcomes and survival both before and after liver transplantation. Moreover, close attention must be given to vaccination status and the clinical setting at which health care is delivered to optimize outcomes and the delivery of high-quality pediatric health care. In this review, we address important components of the evaluation and management of children with chronic end-stage liver disease.

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14: Gastroenterology. 2008 May;134(6):1641-54.

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Cellular and molecular mechanisms of liver injury.

Malhi H, Gores GJ.

Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA.

Derangements in apoptosis of liver cells are mechanistically important in the pathogenesis of end-stage liver disease. Vulnerable hepatocytes can undergo apoptosis via an extrinsic, death receptor-mediated pathway, or alternatively intracellular stress can activate the intrinsic pathway of apoptosis. Both pathways converge on mitochondria, and mitochondrial dysfunction is a prerequisite for hepatocyte apoptosis. Persistent apoptosis is a feature of chronic liver diseases, and massive apoptosis is a feature of acute liver diseases. Fibrogenesis is stimulated by ongoing hepatocyte apoptosis, eventually resulting in cirrhosis of the liver in chronic liver diseases. Endothelial cell apoptosis occurs in ischemia-reperfusion injury. Natural killer and natural killer T cells remove virus-infected hepatocytes by death receptor-mediated fibrosis. Lastly, activated stellate cell apoptosis leads to slowing and resolution of apoptosis. This review summarizes recent cellular and molecular advances in the understanding of the injury mechanisms leading to end-stage liver disease.

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15: Urology. 2008 May 9. [Epub ahead of print]

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Fungal Urosepsis After Ureteroscopy in Cirrhotic Patients: A Word of Caution.

Beck SM, Finley DS, Deane LA.

Department of Urology, University of California, Irvine, School of Medicine, Orange, California.

OBJECTIVES: Fungal sepsis after ureteroscopy (URS) is rarely reported. We report on 2 cases of acute fungemia that developed after routine ureteroscopic stone manipulation in patients with advanced liver cirrhosis. This represents a unique and high-risk population, and, to our knowledge, these are the first such cases reported. METHODS: We performed a retrospective review of the medical records of 2 patients with Child-Pugh class B and C liver cirrhosis who had undergone ureteroscopy (URS) and holmium laser lithotripsy for obstructing ureteral calculi. RESULTS: The treated stones measured 10 mm and 12 mm and were at the right ureteropelvic junction and left ureterovesical junction, respectively. Both patients had had indwelling ureteral stents in place for 1 and 2 months before URS plus holmium laser lithotripsy, with negative preoperative urine cultures. Each procedure was uncomplicated, and a ureteral stent was left in situ in each case. Within 12 hours of URS, each patient became tachycardic, hypotensive, and febrile. Blood, urine (proximal to the stone), and stone cultures were positive for Candida albicans in both patients. They were both successfully treated with intravenous fluconazole and subsequently discharged from the hospital on postoperative day 12 and 13, respectively. CONCLUSIONS: Patients with advanced liver disease appear to be at greater risk of fungal sepsis after otherwise uncomplicated URS and stone manipulation. Consideration should be given to prophylactic antifungal therapy, in addition to the standard antibacterial prophylaxis for such procedures.

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16: Hepatol Res. 2008 May 6. [Epub ahead of print]

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Non-invasive markers for the prediction of fibrosis in chronic hepatitis C infection.

Cross T, Antoniades C, Harrison P.

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, UK.

Liver fibrosis occurs as a result of chronic liver injury and is the hallmark of chronic liver disease. The final stage of progressive liver fibrosis is cirrhosis, which is implicated in portal hypertension, end-stage liver disease and hepatocellular carcinoma. Liver biopsy has historically been the gold standard test for the assessment of liver fibrosis for liver diseases such as viral hepatitis, autoimmune hepatitis and primary biliary cirrhosis. Improved serological tests have enhanced the diagnosis of these conditions and reduced the need for liver biopsy. Liver biopsy is unpopular among patients and clinicians. It is associated with morbidity and mortality, and in addition is subject to sampling error, inter- and intra-observer variability. There is therefore a need for non-invasive markers of liver fibrosis that are accurate, reliable, cheap and easy to use. The aim of this review is to examine the different non-invasive methods that can be used to estimate the severity of fibrosis. The methods evaluated include clinical examination, routine laboratory investigations, imaging tests, specialized tests of liver function and finally serum extra-cellular matrix markers of fibrosis. The review mainly focuses on fibrogenesis in the context of chronic hepatitis C infection.

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17: Curr Opin Lipidol. 2008 Jun;19(3):295-300.

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Hepatic triglyceride synthesis and nonalcoholic fatty liver disease.

Choi SS, Diehl AM.

aDivision of Gastroenterology, Department of Medicine, Duke University Medical Center bSection of Gastroenterology, Department of Medicine, Durham Veteran Affairs Medical Center, Durham, North Carolina, USA.

PURPOSE OF REVIEW: Nonalcoholic fatty liver disease is a spectrum of diseases ranging from simple steatosis to cirrhosis. The hallmark of nonalcoholic fatty liver disease is hepatocyte accumulation of triglycerides. We will review the role of triglyceride synthesis in nonalcoholic fatty liver disease progression and summarize recent findings about triglyceride synthesis inhibition and prevention of progressive disease. RECENT FINDINGS: Attempts to inhibit triglyceride synthesis in animal models have resulted in improvement in hepatic steatosis. Studies in animal models of nonalcoholic fatty liver disease demonstrate that inhibition of acyl-coenzyme A:diacylglycerol acyltransferase, the enzyme that catalyzes the final step in triglyceride synthesis, results in improvement in hepatic steatosis and insulin sensitivity. We recently confirmed that hepatic specific inhibition of acyl-coenzyme A:diacylglycerol acyltransferase with antisense oligonucleotides improves hepatic steatosis in obese, diabetic mice but, unexpectedly, exacerbated injury and fibrosis in that model of progressive nonalcoholic fatty liver disease. When hepatocyte triglyceride synthesis was inhibited, free fatty acids accumulated in the liver, leading to induction of fatty acid oxidizing systems that increased hepatic oxidative stress and liver damage. These findings suggest that the ability to synthesize triglycerides may, in fact, be protective in obesity. SUMMARY: Nonalcoholic fatty liver disease is strongly associated with obesity and peripheral insulin resistance. Peripheral insulin resistance increases lipolysis in adipose depots, promoting increased free fatty acid delivery to the liver. In states of energy excess, such as obesity, the latter normally triggers hepatic triglyceride synthesis. When hepatic triglyceride synthesis is unable to accommodate increased hepatocyte free fatty acid accumulation, however, lipotoxicity results. Thus, rather than being hepatotoxic, liver triglyceride accumulation is actually hepato-protective in obese, insulin-resistant individuals.

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18: Curr Opin Lipidol. 2008 Jun;19(3):257-62.

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Dietary phospholipids, hepatic lipid metabolism and cardiovascular disease.

Cohn JS, Wat E, Kamili A, Tandy S.

Nutrition and Metabolism Group, Heart Research Institute, Sydney, Australia.

PURPOSE OF REVIEW: An increasing number of studies in experimental animals suggest that dietary phospholipids might be of benefit in the treatment of fatty liver disease. This raises the possibility that synthetic or naturally occurring phospholipid isolates could be used as hepatoprotective nutraceuticals or functional foods. The aim of the present article is to review published data describing the beneficial effects of dietary phospholipids on hepatic lipid metabolism and their potential to affect atherosclerosis and cardiovascular disease. RECENT FINDINGS: Consistent results have been obtained supporting the concept that phospholipid from various sources (i.e., soybean, safflower, egg and fish roe) can reduce liver lipid levels. The primary site of action for this effect appears to be in the intestinal lumen, where dietary phospholipids are able to interfere with neutral sterol absorption. Results have also been obtained suggesting that dietary phospholipids can stimulate bile acid and cholesterol secretion. Additional work suggests that dietary phospholipids can have a beneficial effect on plasma lipid and lipoprotein levels. SUMMARY: The concept of using naturally occurring compounds such as phospholipid to treat or prevent hepatic steatosis is very attractive. Controlled human trials are, however, required to verify the efficacy of this approach. It is also important that additional research be conducted to determine the extent to which certain phospholipids have the ability to increase plasma HDL levels and potentially affect the onset or development of cardiovascular disease.

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19: J Hepatol. 2008 Apr 14. [Epub ahead of print]

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Mouse models for the study of HCV infection and virus-host interactions.

Barth H, Robinet E, Liang TJ, Baumert TF.

Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.

Hepatitis C virus (HCV) is a major cause of chronic liver disease including steatosis, cirrhosis and hepatocellular carcinoma. The development of transgenic mice expressing HCV proteins and the successful repopulation of SCID/Alb-uPA mice with human hepatocytes provides an important tool for unraveling virus-host interactions in vivo. Several of these mouse models exhibit aspects of HCV-related liver disease. Thus, these in vivo models play an important role to further understand the pathogenesis of HCV infection and to evaluate the pre-clinical safety and efficacy of new antiviral compounds against HCV. This review summarizes the most important mouse models currently used to study HCV pathogenesis and infection. Finally, the perspective of these models for future HCV research as well as the design of novel small animal models is discussed.

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20: Medscape J Med. 2008 Mar 12;10(3):61.

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The medical management of primary sclerosing cholangitis.

Michaels A, Levy C.

Division of Gastroenterology, Hepatology, and Nutrition, University of Florida-Gainesville, USA. Anthony.michaels@medicine.ufl.edu

Primary sclerosing cholangitis (PSC) is a rare, chronic cholestatic liver disease of uncertain etiology characterized by the destruction of the intrahepatic and/or extrahepatic ducts through inflammation and fibrosis. This ultimately leads to biliary complications including cirrhosis, cholangiocarcinoma, and eventually death. Given the uncertainty surrounding the pathogenesis of the disease, a number of different medical therapies have been studied in the treatment of PSC. However, there currently are no effective medical therapies known to halt the progression of disease. The only definitive therapy for PSC is liver transplantation. This review will primarily focus on the medical approaches that have been studied for the treatment of PSC as well as on the management of symptoms commonly associated with the disease.

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21: Curr Opin Anaesthesiol. 2008 Apr;21(2):111-21.

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Poly(ADP-ribose) polymerase: a new therapeutic target?

Gerö D, Szabó C.

CellScreen Applied Research Center, Semmelweis University Medical School, Budapest, Hungary.

PURPOSE OF REVIEW: To overview the emerging data in the literature showing the role of poly(ADP-ribose) polymerase (PARP) in the pathogenesis of critical illness. RECENT FINDINGS: PARP, an abundant nuclear enzyme involved in DNA repair and transcriptional regulation, is now recognized as a key regulator of cell survival and cell death in response to noxious stimuli in various forms of cardiovascular collapse. PARP becomes activated in response to oxidative DNA damage and depletes cellular energy pools, thus leading to cellular dysfunction in various tissues. The activation of PARP may also induce various cell death processes, and promotes an inflammatory response. In circulatory shock PARP plays a crucial role both in the development of early cardiovascular dysfunction and in the delayed systemic inflammatory response syndrome with associated multiple organ failure. Inhibition of PARP activity is protective in various models of circulatory shock. SUMMARY: A solid body of literature supports the view that PARP is an important target for therapeutic intervention in critical illness.

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22: World J Gastroenterol. 2008 Apr 28;14(16):2474-86.

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Nonalcoholic fatty liver disease: An overview of current insights in pathogenesis, diagnosis and treatment.

Schreuder TC, Verwer BJ, van Nieuwkerk CM, Mulder CJ.

Department of Gastroenterology and Hepatology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. t.schreuder@vumc.nl.

Estimates of people suffering from overweight (one billion) and obesity (300 million) are increasing. The accumulation of triglycerides in the liver, in the absence of excess alcohol intake, has been described in the early sixties. It was not until 1980, however, that Ludwig et al named this condition nonalcoholic steatohepatitis (NASH). Subsequently, nonalcoholic fatty liver disease (NAFLD) has been used as a general name for conditions ranging from simple steatosis through steatohepatitis to end-stage liver disease (cirrhosis). Many studies have demonstrated the significant correlation with obesity and insulin resistance. Other studies have revealed a significant correlation between hepatic steatosis, cardiovascular disease and increased intima-media thickness. WHO estimated that at least two million patients will develop cirrhosis due to hepatic steatosis in the years to come. Longitudinal cohort studies have demonstrated that those patients with cirrhosis have a similar risk to develop hepatocellular carcinoma as those with other causes of cirrhosis. Taken all together, NAFLD has become the third most important indication for liver transplantation. Therefore, training programmes in internal medicine, gastroenterology and hepatology should stress the importance of diagnosing this entity and treat properly those at risk for developing complications of portal hypertension and concomittant cardiovascular disease. This review will focus on the clinical characteristics, pathophysiology, imaging techniques and the readily available therapeutic options.

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23: Am J Health Syst Pharm. 2008 May 1;65(9):818-22.

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Rifaximin for the treatment of hepatic encephalopathy.

de Melo RT, Charneski L, Hilas O.

New York-Presbyterian Hospital, The University Hospital of Columbia and Cornell, New York, USA.

PURPOSE: The use of rifaximin for the treatment of hepatic encephalopathy (HE) is reviewed. SUMMARY: HE is observed in approximately 50-70% of all patients with cirrhosis. Clinical manifestations of HE range from altered mental status to deep coma. Most manifestations of this syndrome are reversible with medical treatment. Treatment measures focus on the resolution of ammonia accumulation and identification/ removal of precipitating factors. Lactulose has been the mainstay of HE treatment in the acute and chronic settings, though its use is limited by poor patient tolerance and compliance. Chronic administration of antibiotics has also proven to be effective in HE. Historically, neomycin or metronidazole has been used, but both carry the risk of serious adverse effects. Rifaximin is a nonabsorbed derivative of rifamycin with a broad spectrum of activity against aerobic and anaerobic gram-positive and gram-negative organisms. Clinical trials have compared rifaximin to lactulose or neomycin for the treatment of HE. Rifaximin shows a general trend toward better efficacy versus lactulose or neomycin. In addition, rifaximin seems to offer a better safety and tolerability profile than that of lactulose and possibly neomycin. CONCLUSION: While no randomized, placebo-controlled studies have assessed the efficacy and long-term safety outcomes of rifaximin in the treatment of HE, rifaximin has demonstrated better efficacy and safety profiles compared with lactulose and neomycin. Future studies should assess HE outcomes with more consistent indexes and measurements and should compare the efficacy and safety of rifaximin with those of metronidazole.

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24: J Chin Med Assoc. 2008 Apr;71(4):186-90.

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Liver Transplantation at a Small-volume Procedure Center---Preliminary Results from Taipei Veterans General Hospital.

Lin NC, Hsia CY, Loong CC, Liu CS, Tsai HL, Lui WY, Wu CW.

Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.

Background: Liver transplantation is a challenging procedure that is associated with perioperative morbidity and mortality, so it is justifiable to perform such a procedure in high-volume procedure centers. Organ shortage remains a major issue in Taiwan. Due to the difficulty in establishing a high-volume procedure center, it is important to review the overall outcome of patients undergoing liver transplantation at a small-volume procedure center to determine if performing such a procedure is justified. Methods: Between April 2001 and May 2005, 26 adults underwent deceased donor liver transplantation at Taipei Veterans General Hospital. The overall outcomes were reviewed in terms of 90-day mortality, 1-year and 3-year survival rates. In addition, the patients were divided into a hepatocellular carcinoma (HCC) group (n = 12) and a benign end-stage liver disease (ESLD) group (n = 14). The clinical demographics, 90-day mortality, 1-year and 3-year survival rates were reviewed and compared between the 2 groups. Results: The 90-day mortality was 15.3% in the whole series, 8.3% in the HCC group and 18.7% in the ESLD group. The overall 1-year and 3-year survival rates were 76.9% and 63.5%, respectively, for the whole series. For the 2 groups, the respective 1-year and 3-year survival rates were 83.3% and 71.4% in the HCC group, and 71.4% and 57.1% in the ESLD group. The survival difference was not significant (p = 0.319) between the 2 groups. In the HCC group, the 1-year and 3-year disease-free survival rates were 88.9% and 71.1%, respectively. Conclusion: The survival rates between ESLD and HCC patients undergoing liver transplantation at a small-volume procedure center were comparable. The results of the whole series were not satisfactory, but the results for the HCC group were acceptable.

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25: Ugeskr Laeger. 2008 Apr 14;170(16):1370-2.

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[Future perspectives in liver surgery]

[Article in Danish]

Bergenfeldt M, Gandrup P.

Herlev Hospital, Kirurgisk Gastroenterologisk Afdeling D, Herlev. maber@heh.regionh.dk

Resection of colorectal liver metastases will increase due to increased life expectancy and widened indications. Complex combinations of chemotherapy, surgery, and local ablation are used in advanced disease. Advances in laparoscopic and telerobotic liver resection are expected. Hepatocellular carcinoma is rare, results are poor, and better treatment is needed. The complex management of liver neoplasms requires a centralized effort. Further advances in xenotransplantation, artificial liver, and stem cell technology may influence liver transplantation as well as cancer surgery.

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26: Ugeskr Laeger. 2008 Apr 14;170(16):1366-9.

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[Surgical treatment of children with hepatic tumours]

[Article in Danish]

Rasmussen A, Kvist N, Kirkegaard P, Rechnitzer C.

Rigshospitalet, Abdominalcentret, Kirurgisk Gastroenterologisk Klinik C, København Ø. allan.rasmussen@dadlnet.dk

INTRODUCTION: In this paper we review the results of surgical treatment of children with hepatic tumours. MATERIALS AND METHODS: The study comprises 33 children who have undergone lever resection or liver transplantation since 1990. 26 patients had hepatoblastoma, 3 had hepatocellular carcinoma, 2 had rhabdomyosarcoma, 1 had a mesenchymal tumour, and 1 had a giant haemangioma. RESULTS: Because of the number of patients, we only analyzed the results of the treatment in the hepatoblastoma group. The survival was the same after resection (77.3%) and liver transplantation (75%). There was no difference in survival dependent on the type of resection, and there was no impact of the extension of tumour growth at the time of diagnosis. CONCLUSION: The combination of neoadjuvant chemotherapy followed by liver resection or liver transplantation is the treatment of choice in all children with hepatoblastoma. The results have improved dramatically over the last decades. The results in Denmark compare well with international results. Since 2000, very effective chemotherapy has downstaged all referred patients, so subsequent liver resection have been possible.

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27: Ugeskr Laeger. 2008 Apr 14;170(16):1356-8.

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[Synchronous resection of colorectal cancer and liver metastasis]

[Article in Danish]

Pless TK, Nielsen HO.

Odense Universitetshospital, Kirurgisk Afdeling A, Odense. tpless@dadlnet.dk

Twenty percent of colorectal cancer patients present disease in both bowel and liver. Traditionally, bowel cancer was resected and patients then re-staged for liver resection. This brief review presents literature to evaluate the support for either synchronous or staged operation. No randomised controlled studies have been published, but recently published case control trials show that synchronous resection can be performed with low morbidity and mortality. The question of whether the synchronous procedure is better than the staged operation is a non-solved matter in literature.

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28: Ugeskr Laeger. 2008 Apr 14;170(16):1353-6.

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[Combined surgical and oncological management of colorectal liver metastases]

[Article in Danish]

Bergenfeldt M, Jensen BV.

Herlev Hospital, Afdelingen for Kirurgisk Gastroenterologi, Herlev. maber@heh.regionh.dk

Isolated colorectal liver metastases should be referred for multispecialist management at a liver centre. Long-time survival is possible after resection and adjuvant therapy. If unresectable, newer chemotherapy with oxaliplatin, irinitecan, bevacizumab and cetuximab may result in a median survival > 20 months. Selected patients may be down-staged and resected with good long-time survival. Bilateral, multiple and large metastases can also be treated by complex combinations of portal vein embolization/ligature, staged resections and local (radiofrequency) ablation.

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29: Ugeskr Laeger. 2008 Apr 14;170(16):1348-9.

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[Local treatment of liver tumors]

[Article in Danish]

Pless TK, Skjoldbye BO.

Odense Universitetshospital, Kirurgisk Afdeling A, Odense. tpless@dadlnet.dk

Local treatment of non-resectable liver tumors is common. This brief review describes the local treatment techniques used in Denmark. The techniques are evaluated according to the evidence in literature. The primary local treatment is Radiofrequency Ablation of both primary liver tumors and liver metastasis. Radiofrequency treatment is based on case-control studies, but the impact of the treatment seems obvious. However, randomized controlled studies are necessary in the future in order to guide indications according to different stages of disease, techniques and treatment regimes.

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30: Antivir Ther. 2008;13 Suppl 1:31-6.

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Future directions in therapy for chronic hepatitis C.

Jensen DM, Ascione A.

Center for Liver Diseases, University of Chicago Hospitals, Chicago, IL, USA. djensen@medicine.bsd.uchicago.edu

The development of new antiviral therapies in the treatment of hepatitis C virus (HCV) is reviewed, including a discussion of the potential advances that this treatment will bring. Data from new molecules in Phase I and II clinical trials, specifically polymerase and protease inhibitors, will be discussed. The potential for resistance has been reported when these have been used as monotherapy. However, their use in combination with pegylated interferon, particularly in the presence of ribavirin, has resulted in significant improvements in antiviral activity. Preliminary studies have confirmed that the new molecules are well tolerated and further clinical studies are underway to evaluate their efficacy. Nevertheless, because of its critical role at all stages of therapy, pegylated interferon is likely to remain the cornerstone of HCV therapy.

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31: Antivir Ther. 2008;13 Suppl 1:23-30.

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Ribavirin considerations in treatment optimization.

Dusheiko G, Nelson D, Reddy KR.

Royal Free Hospital, London, United Kingdom.

Ribavirin is a guanosine analogue that has little antiviral activity when used alone, but considerably enhances the efficacy of conventional and pegylated interferon in the treatment of hepatitis C virus (HCV). The precise mode of action of ribavirin is not fully understood; however, it is crucial for the achievement of high sustained virological response (SVR) rates by enhancing virological response and reducing relapse rates. Data from several studies have confirmed that higher initial doses of ribavirin lead to higher SVR rates. Furthermore, intensified ribavirin dosing might also improve SVR rates in 'difficult-to-cure' patients. It is also important to minimize ribavirin dose reductions to promote high SVR rates and to maintain ribavirin levels throughout treatment to prevent viral breakthrough and relapse. The pharmacokinetic profile of ribavirin reveals a long elimination half-life due to accumulation in the blood, such that its side-effect profile includes haemolytic anaemia. Therefore, finding the optimal ribavirin dose requires a balance between efficacy and its associated side effects to ensure improved patient outcomes. Here, we discuss how optimizing the ribavirin component of combined therapy for HCV is an essential part of treatment optimization.

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32: Antivir Ther. 2008;13 Suppl 1:17-22.

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Optimizing outcomes in patients with hepatitis C virus genotype 2 or 3.

Berg T, Carosi G.

Charite Universitatsmedizin Berlin, Berlin, Germany. thomas.berg@charite.de

On-treatment predictors of response could be useful in optimizing treatment for patients with hepatitis C virus (HCV) genotype 2 or 3. Early virological response (EVR) has limited value as a predictor of response in genotype 2 or 3 patients, as it is achieved by 97% of this population. However, rapid virological response (RVR) measured at week 4 is a strong predictor of sustained virological response (SVR) in this group, and patients achieving an RVR may be suitable candidates for shorter treatment durations. Several small studies investigating the efficacy of shortened treatment durations in this population have been published; however, differences in study design have made their collective interpretation difficult. We discuss these studies, followed by a comparison of the data from ACCELERATE, the largest, randomized trial carried out to investigate abbreviated therapy in genotype 2 and 3 patients. The data confirm that RVR, and its use alongside significant baseline predictors, can assist in optimizing therapy. Patients achieving an RVR have high SVR rates and might be candidates for shorter treatment duration, particularly those displaying a low viral load at baseline; however, the need to consider the increased rate of relapse versus the benefits of abbreviated therapy must also be considered. Conversely, in patients who do not achieve an RVR there is evidence to suggest they may benefit from intensified therapy (longer therapy and/or increased doses). As in genotype 1 and 4 patients, response-guided therapy aims to optimize treatment outcomes for individuals, without compromising SVR rates.

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33: Antivir Ther. 2008;13 Suppl 1:9-16.

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Optimizing outcomes in patients with hepatitis C virus genotype 1 or 4.

Lee SS, Ferenci P.

Liver Unit, University of Calgary, Calgary, Alberta, Canada.

Currently, many decisions for the treatment of hepatitis C virus (HCV) are based on genotype, which is the most significant baseline predictor of response to therapy; however, it has become increasingly apparent that fixed treatment durations might not be appropriate for all patients. The use of on-treatment predictors such as rapid virological response (RVR) at week 4 and early virological response (EVR) at week 12 can be used to predict the likelihood of achieving a sustained virological response (SVR), helping to tailor treatment to the individual. Until now, EVR has been defined as achieving either undetectable HCV RNA (<> 2 log drop in HCV RNA, but still detectable, at week 12. However, rates of SVR in patients achieving an EVR are heterogeneous. It has recently been suggested that by subdividing EVR into RVR (<> 2 log drop in HCV RNA but still detectable [> 50 IU/ml] at week 12), it might be possible to further improve the prediction of patients likely to achieve an SVR and may allow for tailoring of treatment duration. Genotype 1 and 4 patients achieving an RVR have high rates of SVR and may be candidates for shorter treatment duration. Patients with a complete EVR achieve high SVR rates with the current treatment duration of 48 weeks, whereas patients achieving a partial EVR have lower rates of SVR and could benefit from treatment intensification to 72 weeks. Here, we discuss the importance of baseline predictors of response and the emerging concept of response-guided therapy in genotype 1 and 4 patients.

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34: Antivir Ther. 2008;13 Suppl 1:3-8.

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Hepatitis C virus therapy to date.

Foster G, Mathurin P.

Queen Mary Hospital, University of London, London, UK. g.r.foster@qmul.ac.uk

Chronic hepatitis C is a major contributor to cirrhosis and hepatocellular cancer worldwide, justifying the considerable research effort aimed at understanding the disease and refining its treatment. As a result, significant therapeutic advances have been made in the last decade, particularly with regard to the development of pegylated interferons and ribavirin. This review will discuss the physical properties, pharmacokinetics, viral kinetics and side-effect profiles of the different treatment options and how they have improved, culminating in the use of pegylated interferon and ribavirin combination therapy as the current standard of care.

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35: Radiology. 2008 May;247(2):311-30.

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MR Imaging of hepatocellular carcinoma in the cirrhotic liver: challenges and controversies.

Willatt JM, Hussain HK, Adusumilli S, Marrero JA.

Department of Radiology/MRI, University of Michigan Health System, UH-B2A209K, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0030, USA.

The incidence of hepatocellular carcinoma (HCC) is expected to increase in the next 2 decades, largely due to hepatitis C infection and secondary cirrhosis. HCC is being detected at an earlier stage owing to the implementation of screening programs. Biopsy is no longer required prior to treatment, and diagnosis of HCC is heavily dependent on imaging characteristics. The most recent recommendations by the American Association for the Study of Liver Diseases (AASLD) state that a diagnosis of HCC can be made if a mass larger than 2 cm shows typical features of HCC (hypervascularity in the arterial phase and washout in the venous phase) at contrast material-enhanced computed tomography or magnetic resonance (MR) imaging or if a mass measuring 1-2 cm shows these features at both modalities. There is an ever-increasing demand on radiologists to detect smaller tumors, when curative therapies are most effective. However, the major difficulty in imaging cirrhosis is the characterization of hypervascular nodules smaller than 2 cm, which often have nonspecific imaging characteristics. The authors present a review of the MR imaging and pathologic features of regenerative nodules and dysplastic nodules and focus on HCC in the cirrhotic liver, with particular reference to small tumors and lesions that may mimic HCC. The authors also review the sensitivity of MR imaging for the detection of these tumors and discuss the staging of HCC and the treatment options in the context of the guidelines of the AASLD and the imaging criteria required by the United Network for Organ Sharing for transplantation. MR findings following ablation and chemoembolization are also reviewed. (c) RSNA, 2008.

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36: Arch Surg. 2008 Apr;143(4):380-7; discussion 388.

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Use of vascular clamping in hepatic surgery: lessons learned from 1260 liver resections.

Ercolani G, Ravaioli M, Grazi GL, Cescon M, Del Gaudio M, Vetrone G, Zanello M, Pinna AD.

Department of Surgery and Transplantation, S Orsola Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. giorgio.ercolani@aosp.bo.it

HYPOTHESIS: Several techniques have been introduced to minimize intraoperative bleeding in hepatic surgery. Ischemia-reperfusion injuries and intestinal congestion are the main drawbacks of vascular clamping. We hypothesized possible negative effects on early postoperative outcomes associated with different types of vascular clamping during liver resections and evaluated how attitudes have changed in the past 20 years. DESIGN: Retrospective review. SETTING: Academic research institute. PATIENTS: Patients who underwent 1260 consecutive liver resections, 338 of them (26.8%) in patients with cirrhosis. MAIN OUTCOME MEASURES: Postoperative complications and mortality were analyzed relative to liver disease, blood transfusion, vascular clamping, and type of liver resection. RESULTS: Vascular clamping was applied in 594 patients (47.1%). Operative mortality was 4.4% in the vascular clamping group and 2.9% in the nonclamped group, a statistically nonsignificant difference. On multivariate analysis, blood transfusion, major hepatectomies, and the presence of cirrhosis were statistically significantly associated with postoperative complications. Among the overall cohort and among patients with cirrhosis, there was statistically significantly reduced use of vascular clamping and of blood transfusion during the past 20 years. The lowest incidences of severe complications occurred among cases of continuous or hemihepatic clamping. Among 338 patients with cirrhosis, 155 (45.9%) received some type of vascular control; morbidity and mortality rates were similar in the groups with vs those without vascular control. On multivariate analysis, only blood transfusion was statistically significantly associated with postoperative morbidity. Postoperative complications were statistically significantly reduced among patients receiving intermittent compared with continuous clamping. CONCLUSIONS: Vascular clamping can be applied without additional risk during partial hepatectomy. Intermittent or hemihepatic clamping is preferable in patients with cirrhosis.

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37: Med Decis Making. 2008 Apr 18. [Epub ahead of print]

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Health-State Utilities in Liver Disease: A Systematic Review.

McLernon DJ, Dillon J, Donnan PT.

OBJECTIVES: Health-state utilities are essential for cost-utility analysis. Few estimates exist for liver disease in the literature. The authors' aim was to conduct a systematic review of health-state utilities in liver disease, to look at the variation of STUDY DESIGN: s used, and to pool utilities for some liver disease states. METHODS: A search of MEDLINE, EMBASE, and CINAHL from 1966 to September 2006 was conducted including key words related to liver disease and utility measuring tools. Articles were included if health-state utility tools or expert opinion were used. Variance-weighted mean utility estimates were pooled using metaregression adjusting for disease state and utility assessment method. RESULTS: Thirty studies measured utilities of liver diseases/disease states. Half of these estimated utilities for hepatitis viruses: hepatitis A (n = 1), hepatitis B (n = 4), and hepatitis C (n = 10). Others included liver transplant (n = 6) and chronic liver disease (n = 5) populations. Twelve utility methods were used throughout. The EQ-5D (n = 10) was most popular method, followed by visual analogue scale (n = 9), time tradeoff (n = 6), and standard gamble (n = 4). Respondents were patients (n = 16), an expert panel (n = 10), non-liver diseases adults (n = 2), patient and expert (n = 1), and patient and healthy adult (n = 1). Type of perspective included community (n = 21), patient (n = 4), and both (n = 5). The pooled mean estimates in hepatitis C with moderate disease, compensated cirrhosis, decompensated cirrhosis, and post-liver transplant using the EQ-5D were 0.75, 0.75, 0.67, and 0.71, respectively. The change in these utilities using different methods were -0.07 (visual analogue scale), -0.01 (health utilities index version 3), +0.04 (standard gamble), +0.08 (health utilities index version 2), +0.12 (time tradeoff), and +0.15 (standard gamble-transformed visual analogue scale). CONCLUSIONS: The authors have created a valuable liver disease-based utility resource from which researchers and policy makers can easily view all available utility estimates from the literature. They have also estimated health-state utilities for major states of hepatitis C. Key words: health-state utility; liver disease; systematic review; meta-analysis; hepatitis C. (Med Decis Making XXXX;XX:xx-xx).

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38: Yi Chuan. 2008 Apr;30(4):389-99.

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[Recent development of metabonomics and its applications in clinical research.]

[Article in Chinese]

Li H, Jiang Y, He FC.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China E-mail: lihaoh@163.com.

In the post-genomic era, systems biology is central to the biological sciences. Functional genomics such as transcriptomics and proteomics can simultaneous determine massive gene or protein expression changes following drug treatment or other intervention. However, these changes can't be coupled directly to changes in biological function. As a result, metabonomics and its many pseudonyms (metabolomics, metabolic profiling, etc.) have exploded onto the scientific scene in the past several years. Metabonomics is a rapidly growing research area and a system approach for comprehensive and quantitative analysis of the global metabolites in a biological matrix. Analytical chemistry approach is necessary for the development of comprehensive metabonomics investigations. Fundamentally, there are two types of metabonomics approaches: mass-spectrometry (MS) based and nuclear magnetic resonance (NMR) methodologies. Metabonomics measurements provide a wealth of data information and interpretation of these data relies mainly on chemometrics approaches to perform large-scale data analysis and data visualization, such as principal and independent component analysis, multidimensional scaling, a variety of clustering techniques, and discriminant function analysis, among many others. In this review, the recent development of analytical and statistical techniques used in metabonomics is summarized. Major applications of metabonomics relevant to clinical and preclinical study are then reviewed. The applications of metabonomics in study of liver diseases, cancers and other diseases have proved useful both as an experimental tool for pathogenesis mechanism re-search and ultimately a tool for diagnosis and monitoring treatment response of these diseases. Next, the applications of metabonomics in preclinical toxicology are discussed and the role that metabonomics might do in pharmaceutical research and development is explained with special reference to the aims and achievements of the Consortium for Metabonomic Toxicology (COMET), and the concept of pharmacometabonomics as a way of predicting an individual's response to treatment is highlighted. Finally, the role of metabonomics in elucidating the function of the unknown or novel enzyme is mentioned.

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39: J Gastroenterol Hepatol. 2008 Apr 19. [Epub ahead of print]

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Autologous bone marrow cell infusion therapy for liver cirrhosis.

Sakaida I.

Department of Gastroenterology and Hepatology, Yamaguchi University, Graduate School of Medicine, Ube, Yamaguchi Prefecture, Japan.

The plasticity of bone marrow cells (BMC) has been confirmed by autopsy results of female recipients of BMC from male donors. To establish new clinical therapies for patients with liver cirrhosis using autologous BMC, we developed a new in vivo murine model using green fluorescent protein (GFP) and repeated carbon tetrachloride (CCl(4)) injection. We found that BMC infused through the tail vein, efficiently repopulated cirrhotic liver tissue and, under the influence of persistent liver damage induced by carbon tetrachloride, differentiated into albumin-producing hepatocytes. Moreover, such BMC infusions into mice with cirrhosis improved liver function and reduced mortality. The latter observation correlated with the strong expression of matrix metalloproteinases (MMP), particularly MMP-9, and reduced hepatic fibrosis. The results from the 'GFP/CCl(4) model' showed that cell therapy using autologous BMC has the potential to become an effective treatment for patients with liver failure due to advanced liver cirrhosis. This review summarizes previous findings plus these recent experimental results, as well as recent clinical trials of BMC transfusion into patients with end-stage chronic liver disease.

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40: Expert Opin Pharmacother. 2008 May;9(7):1229-36.

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Experience of nitisinone for the pharmacological treatment of hereditary tyrosinaemia type 1.

Santra S, Baumann U.

Birmingham Children's Hospital, The Liver Unit, Steelhouse Lane, Birmingham, B4 6NH, UK.

BACKGROUND: Hereditary tyrosinaemia type 1 is a rare inherited metabolic condition, which leads to a fatal multisystemic disease in childhood. Since 1992, nitisinone - a compound developed from work on triketone herbicides - has become an effective pharmacological treatment by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase. OBJECTIVES: This review examines recent pharmacological and clinical literature on nitisinone, and assesses its impact as a pharmacological treatment for hereditary tyrosinaemia type 1. METHODS: English language literature from MedLine and EmBase for nitisinone was searched from 1990 to 2008 for all papers relevant to the use of nitisinone in hereditary tyrosinaemia type 1. CONCLUSIONS: Nitisinone can prevent the development of liver disease and significantly reduce the risk of developing hepatocellular carcinoma; however, vigorous surveillance for the development of HCC needs to be continued lifelong.

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41: Expert Opin Pharmacother. 2008 May;9(7):1087-108.

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Pleiotropic effects of thiazolidinediones.

Rizos CV, Liberopoulos EN, Mikhailidis DP, Elisaf MS.

University of Ioannina, Department of Internal Medicine, School of Medicine, Ioannina, Greece.

BACKGROUND: Insulin resistance and hyperglycemia characterize type 2 diabetes mellitus. Type 2 diabetes mellitus is usually accompanied by concomitant disorders, such as dyslipidemia, hypertension and atherosclerosis. Thiazolidinediones are antidiabetic drugs that increase insulin sensitivity by activating the peroxisome proliferator-activated receptor gamma. There is evidence that thiazolidinediones exert a number of pleiotropic effects that may play an important role in the treatment of type 2 diabetes mellitus. OBJECTIVE: The purpose of the present article was to review the 'pleiotropic' effects of thiazolidinediones (i.e., their effects beyond glucose lowering). METHODS: The study involved searching PubMed up to February 2008 using relevant keywords. CONCLUSIONS: Thiazolidinediones favorably alter fat distribution and improve cardiovascular risk factors, such as blood pressure, inflammation markers and uric acid and they may also delay the progression of atherosclerosis. The effects on the lipid profile differ between the two thiazolidinediones studied with pioglitazone having more positive effects compared with rosiglitazone. Furthermore, thiazolidinediones improve diabetic complications, such as diabetic nephropathy and non-alcoholic fatty liver disease. Thiazolidinediones may also play a role in other diseases, such as polycystic ovary syndrome. These pleiotropic effects may prove to be clinically relevant. There has been recent debate about the possible differences between the two thiazolidinediones in terms of cardiovascular disease outcome. In this context, differences in the lipid effects between the two drugs may be relevant.

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42: Scott Med J. 2008 Feb;53(1):25-9.

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The management of renal failure in patients with liver disease. Experiences from a district general hospital.

Manning JJ, Hislop WS, McPeake JR.

Department of Gastroenterology, Borders General Hospital, Melrose. johnathan.manning@borders.scot.nhs.uk

AIM: To compare the pre-existing management of patients with Hepatorenal Syndrome (HRS) in the gastroenterology unit of the Royal Alexandra Hospital, Renfrewshire, with the published evidence based studies. METHOD: A retrospective, 6-month, case record review of patients diagnosed with HRS was performed. An evidence-based protocol for the diagnosis and management of HRS was introduced into the unit, to aid patient treatment prospectively. After 6 months, both compliance with the protocol, and patient outcomes were analysed. RESULTS: Eleven patients were identified in the first part of the audit cycle, all of whom died. Seven were identified in the second cycle. Two had their renal function successfully corrected and one was discharged from hospital. Renal impairment and staging of liver disease was equivalent in both groups. The second group received more appropriate and aggressive therapy. Alcohol was the causative aetiology of liver disease in all patients. CONCLUSIONS: Targetted therapy in patients with severe liver disease and HRS can improve renal parameters. Previous studies have shown this to be linked with improved patient outcomes.

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43: Atherosclerosis. 2008 Mar 6. [Epub ahead of print]

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Do we need to consider inflammatory markers when we treat atherosclerotic disease?

Athyros VG, Kakafika AI, Karagiannis A, Mikhailidis DP.

Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece.

This review considers the value of monitoring inflammatory markers as a guide to selecting appropriate drugs in patients at high risk of cardiovascular disease (CVD). Clinical and experimental studies investigated inflammation in patients with acute coronary syndromes (ACS), stable coronary artery disease (CAD) and diabetes mellitus (DM) or metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD) or systemic autoimmune diseases (SAD). Evidence suggests that in these high risk groups inflammation plays a role in the extent and severity of atherosclerosis. Simple inflammatory markers (e.g. C-reactive protein and fibrinogen) can be monitored cost effectively and may influence the selection of drugs that can normalize both traditional CVD risk factors and inflammation. However, this concept requires proof in appropriately designed trials that include clinically relevant end points.

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44: Chang Gung Med J. 2008 Jan-Feb;31(1):16-25.

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Hepatitis C virus genotypes: clinical relevance and therapeutic implications.

Lee CM, Hung CH, Lu SN, Changchien CS.

Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niaosong Township, Kaohsiung, Taiwan, ROC. chmolee@ms15.hinet.net

The incidence of hepatitis C virus (HCV) -related hepatocellular carcinoma (HCC) has been increasing in several countries including Taiwan. There are six main genotypes, each of which contains closely related subtypes. Molecular epidemiological studies have shown marked differences in the genotype distribution by geographical region and between patient groups. HCV genotype 1 may play a role in the development of HCC, although some studies have argued against this. A sustained virological response secondary to interferon monotherapy or interferon/ribavirin combination therapy may reduce the risk of HCC and improve survival in chronic hepatitis C patients. The HCV genotypes are associated with therapeutic response. Rapid virological response is also a predictor of therapeutic response. Although viral characteristics have consistently been shown to be important predictors of treatment response, identification of additional host immune and genetic factors involved in determining the outcome of antiviral therapy is necessary. Newly developed bio-techniques (microarray, proteomes, bioinformatics), drugs, and treatment strategies may elucidate the pathogenesis and improve the therapeutic response in HCV infection.

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45: Can J Infect Dis Med Microbiol. 2006 Mar;17(2):129-32.

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Vibrio vulnificus Septicemia After Handling Tilapia Species Fish: A Canadian Case Report and Review.

Vinh DC, Mubareka S, Fatoye B, Plourde P, Orr P.

Department of Medicine, Section of Infectious Diseases.

BACKGROUND: Vibrio vulnificus can cause a necrotizing soft tissue infection or primary septicemia; these infections are collectively known as vibriosis. This bacterium is commonly found within molluscan shellfish. Primary septicemia is often fatal, principally affecting persons with chronic liver disease. CASE PRESENTATION: A fatal case of V vulnificus sepsis that developed in a patient with chronic hepatitis B and chronic renal failure is reported. Diagnosis was made by isolation of the pathogen by blood culture. Upon further questioning, the patient's family recounted that the patient had handled and ingested Tilapia species fish in the hours preceding the patient's presentation. Despite treatment with doxycycline and cefotaxime, in conjunction with supportive care in the intensive care unit, the patient died on day 7 from multiple organ dysfunction. CONCLUSION: The present case highlights the need to consider V vulnificus in the microbiological differential diagnosis when a person presents with sepsis and bullous cutaneous lesions. The importance of educating patients with liver disease (and certain other chronic diseases) about the need to be cautious when handling or consuming seafood is underscored.

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46: Clin J Am Soc Nephrol. 2008 Apr 16. [Epub ahead of print]

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Calciphylaxis from Nonuremic Causes: A Systematic Review.

Nigwekar SU, Wolf M, Sterns RH, Hix JK.

Departments of Internal Medicine and Nephrology, Rochester General Hospital and University of Rochester School of Medicine, Rochester, New York; and Renal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

BACKGROUND AND OBJECTIVES: Calciphylaxis, or calcific uremic arteriolopathy, is a well-described entity in end-stage kidney disease and renal transplant patients; however, little systematic information is available on calciphylaxis from nonuremic causes. This systematic review was designed to characterize etiologies, clinical features, laboratory abnormalities, and prognosis of nonuremic calciphylaxis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A systematic review of literature for case reports and case series of nonuremic calciphylaxis was performed. Cases included met the operational definition of nonuremic calciphylaxis-histopathologic diagnosis of calciphylaxis in the absence of end-stage kidney disease, renal transplantation, or acute kidney injury requiring renal replacement therapy. RESULTS: We found 36 cases (75% women, 63% Caucasian, aged 15 to 82 yr) of nonuremic calciphylaxis. Primary hyperparathyroidism, malignancy, alcoholic liver disease, and connective tissue disease were the most common reported causes. Preceding corticosteroid use was reported for 61% patients. Protein C and S deficiencies were seen in 11% of patients. Skin lesions were morphologically similar to calcific uremic arteriolopathy. Mortality rate was 52%, with sepsis being the leading cause of death. CONCLUSION: Calciphylaxis should be considered while evaluating skin lesions in patients with predisposing conditions even in the absence of end-stage kidney disease and renal transplantation. Nonuremic calciphylaxis is reported most often in white women. Mineral abnormalities that are invoked as potential causes in calcific uremic arteriolopathy are often absent, suggesting that heterogeneous mechanisms may contribute to its pathogenesis. Nonuremic calciphylaxis is associated with high mortality, and there is no known effective treatment.

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47: Curr Gastroenterol Rep. 2008 Feb;10(1):73-80.

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Nonalcoholic fatty liver disease as a component of the metabolic syndrome.

Khashab MA, Liangpunsakul S, Chalasani N.

Indiana University School of Medicine, RG 4100, 1050 Wishard Boulevard, Indianapolis, IN 46202, USA.

Nonalcoholic fatty liver disease (NAFLD) is an important cause of liver-related morbidity and mortality. The association between NAFLD and the metabolic syndrome is well established: the presence of the metabolic syndrome signifies advanced histology in NAFLD patients. Emerging data indicate that patients with NAFLD have a significantly higher prevalence of cardiovascular disease. This article reviews the definitions of the two syndromes, their association, and the cardiovascular risk conferred by both when they occur separately and together. This review also discusses management options for the syndromes, including treating the individual components of the metabolic syndrome in NAFLD patients.

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48: Curr Gastroenterol Rep. 2008 Feb;10(1):67-72.

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The obesity epidemic and nonalcoholic fatty liver disease in children.

Dunn W, Schwimmer JB.

Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego Medical Center, 200 West Arbor Drive, San Diego, CA 92103, USA.

Childhood obesity is a worldwide health problem associated with an increase in the prevalence and severity of nonalcoholic fatty liver disease (NAFLD). This review covers the progress made between 2005 and 2007 in understanding the epidemiology, histology, and treatment of pediatric NAFLD. The number of children with NAFLD presents a major public health crisis. Noninvasive diagnostic tools offer future promise, but currently are unable to grade and stage disease. Therefore, pediatric NAFLD remains a clinico-pathological diagnosis requiring direct demonstration of liver steatosis and the exclusion of other causes of fatty liver and/or hepatitis. There are currently no proven therapies for NAFLD in children; however, TONIC (Treatment of Nonalcoholic Fatty Liver Disease in Children), the first multicenter clinical trial of pediatric NAFLD, is currently in progress. Such studies are imperative to address fundamental questions regarding cause and cure.

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49: Am J Med Sci. 2008 Apr;335(4):315-9.

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Bronchobiliary fistula in a cirrhotic patient: a case report and review of the literature.

Jamal Y, Tombazzi C, Waters B, Ismail MK.

Department of Gastroenterology and Internal Medicine, University of Tennessee, Memphis, Tennessee, USA.

Bronchobiliary fistula is defined as the passage of bile in the bronchi. The presence of bronchobiliary fistula in patient with cirrhosis is extremely rare. Management of these fistulas is often very difficult and can be associated with high morbidity and mortality. We are presenting a patient with ethanol related cirrhosis and biliptysis in whom a diagnosis of bronchobiliary fistula was made. A review of the literature including diagnosis and management is performed.

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50: J Gastroenterol Hepatol. 2008 May;23(5):687-98.

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Liver stem cells: a scientific and clinical perspective.

Dan YY, Yeoh GC.

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Hospital, Singapore. mdcdyy@nus.edu.sg

The promise of liver stem cells lie in their potential to provide a continual and readily available source of liver cells that can be used for gene therapy, cellular transplant, bioartificial liver-assisted devices, drug toxicology testing and use as an in vitro model to understand the developmental biology of the liver. Both the rodent and human embryonic stem cell, bone marrow hematopoietic stem cell, mesenchymal stem cell, umbilical cord blood cell, fetal liver progenitor cell, adult liver progenitor cell as well as the mature hepatocyte have been reported to be capable of self-renewal, giving rise to daughter hepatocytes both in vivo and in vitro. These cells can repopulate livers in animal models of liver injury and seemingly improve liver function. However, significant challenges still exist before these cells can be used in humans. These include lack of consensus in immunophenotype of liver progenitor cells, uncertainty of the physiological role of reported candidate stem/progenitor cell, practicality in obtaining sufficient quantity of cells for clinical use and concerns over ethics, long-term efficacy and safety. Current molecular techniques of stem cell identification are confounded by cell fusion, horizontal gene transfer, incomplete differentiation and fetal microchimerism. Reports of stem cell transplantation and phase 1 trials of bone marrow transplantation in humans for liver diseases are exciting but require more robust verification. We review the evidence for various candidate stem cells, human clinical trials reported to date and highlight the challenges facing clinicians in their quest to use liver stem cells to save lives.