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Showing papers in "World Journal of Hepatology in 2011"


Journal ArticleDOI
TL;DR: This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors.
Abstract: Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called “isoprenoids”) are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed.

288 citations


Journal ArticleDOI
TL;DR: The contemporary state of infectious complications during the post-operative period is reviewed, with particular emphasis on those that occur most commonly during the first 6 mo after liver transplantation.
Abstract: Liver transplantation is a standard life-saving procedure for the treatment of many end-stage liver diseases. The success of this procedure may be limited by infectious complications. In this article, we review the contemporary state of infectious complications during the post-operative period, with particular emphasis on those that occur most commonly during the first 6 mo after liver transplantation. Bacteria, and less commonly Candida infections, remain the predominant pathogens during the immediate post-operative period, especially during the first month, and infections caused by drug-resistant strains are emerging. Infections caused by cytomegalovirus and Aspergillus sp. present clinically during the "opportunistic" period characterized by intense immunosuppression. As newer potent immunosuppressive therapies with the major aim of reducing allograft rejection are developed, one potential adverse effect is an increase in certain infections. Hence, it is essential for liver transplant centers to have an effective approach to prevention that is based on predicted infection risk, local antimicrobial resistance patterns, and surveillance. A better understanding of the common and most important infectious complications is anticipated to lead to improvements in quality of life and survival of liver transplant recipients.

128 citations


Journal ArticleDOI
TL;DR: Radiofrequency ablation has proven its clinical impact not only in hepatocellular carcinoma but also in metastatic disease such as colorectal cancer (CRC) and with the increasing number of HCC and CRC, RFA might play an even more important role in the future.
Abstract: Over the past decade, radiofrequency ablation (RFA) has evolved into an important therapeutical tool for the treatment of non resectable primary and secondary liver tumors. The clinical benefit of RFA is represented in several clinical studies. They underline the safety and feasibility of this new and modern concept in treating liver tumors. RFA has proven its clinical impact not only in hepatocellular carcinoma (HCC) but also in metastatic disease such as colorectal cancer (CRC). Due to the increasing number of HCC and CRC, RFA might play an even more important role in the future. Therefore, the refinement of RFA technology is as important as the evaluation of data of prospective randomized trials that will help define guidelines for good clinical practice in RFA application in the future. The combination of hepatic resection and RFA extends the feasibility of open surgical procedures in patients with extensive tumors. Adverse effects of RFA such as biliary tract damage, liver failure and local recurrence remain an important task today but overall the long term results of RFA application in treating liver tumors are promising. Incomplete ablation of liver tumors due to insufficient technology of ablation needles, tissue cooling by the neighbouring blood vessels, large tumor masses and ablation of tumors in close vicinity to heat sensitive organs remain difficult tasks for RFA. Future solutions to overcome these limitations of RFA will include refinement of ultrasonographic guidance (accuracy of probe placement), improvements in needle technology (e.g. needles preventing charring) and intraductal cooling techniques.

103 citations


Journal ArticleDOI
TL;DR: There is no specific therapy for acute hepatitis E as treatment remains supportive, and there are vaccine candidates that had been shown to be safe and efficacious in clinical trials, but none are approved currently for use.
Abstract: Hepatitis E is caused by the hepatitis E virus (HEV), the major etiologic agent of enterically transmitted non-A hepatitis worldwide. HEV is responsible for major outbreaks of acute hepatitis in developing countries, especially in many parts of Africa and Asia. The HEV is a spherical, non-enveloped, single-stranded, positive sense RNA virus that is approximately 32 nm to 34 nm in diameter and is the only member in the family Hepeviridae and genus Hepevirus. There are four distinct genotypes of HEV (genotypes 1-4). While genotype 1 is predominantly associated with large epidemics in developing countries, genotype 3 has recently emerged as a significant pathogen in developed countries. The clinical manifestations and the laboratory abnormalities of hepatitis E are not distinguishable from that caused by other hepatitis viruses. However, high mortality among pregnant women particularly during the third trimester distinguishes HEV from other causes of acute viral hepatitis. Specific etiologic diagnosis among infected cases can be made by serological testing or detection of viral nucleic acid by reverse transcription polymerase chain reaction. Although there are vaccine candidates that had been shown to be safe and efficacious in clinical trials, none are approved currently for use. There is no specific therapy for acute hepatitis E as treatment remains supportive.

100 citations


Journal ArticleDOI
TL;DR: In this paper, the authors reviewed features of insulin resistance in relationship to chronic liver disease and discussed the impact of anti-diabetic agents on interferon treatment and hepatocarcinogenesis.
Abstract: Increased insulin resistance is frequently associated with chronic liver disease and is a pathophysiological feature of hepatogenous diabetes. Distinctive factors including hepatic parenchymal cell damage, portal-systemic shunting and hepatitis C virus are responsible for the development of hepatogenous insulin resistance/diabetes. Although it remains unclear whether insulin secretion from pancreatic beta cells is impaired as it is in type 2 diabetes, retinopathic and cardiovascular risk is low and major causes of death in cirrhotic patients with diabetes are liver failure, hepatocellular carcinoma and gastrointestinal hemorrhage. Hemoglobin A1c is an inaccurate marker for the assessment and management of hepatogenous diabetes. Moreover, exogenous insulin or sulfonylureas may be harmful because these agents may promote hepatocarcinogenesis. Thus, pathogenesis, cause of death, assessment and therapeutic strategy for hepatogenous insulin resistance/diabetes differ from those for lifestyle-related type 2 diabetes. In this article, we review features of insulin resistance in relationship to chronic liver disease. We also discuss the impact of anti-diabetic agents on interferon treatment and hepatocarcinogenesis.

93 citations


Journal ArticleDOI
TL;DR: The epidemiology and magnitude of ALD in general and AH in particular are discussed, with the presence of cirrhosis at presentation or its development on follow up a major factor determining the outcome in the long run.
Abstract: Alcoholic liver disease (ALD) is a major cause of alcohol-related morbidity and mortality. Its presentation ranges from fatty liver to alcoholic hepatitis (AH), cirrhosis, and hepatocellular carcinoma. Although the amount and pattern of alcohol consumption is a well recognized predisposing factor for the development of serious liver pathology, environmental factors and the host’s genetic make-up may also play significant roles that have not yet been entirely explored. Continuing alcohol consumption is a major factor that influences the survival of patients with AH. The presence of cirrhosis at presentation or its development on follow up is a major factor determining the outcome in the long run. This chapter deals with the epidemiology and magnitude of ALD in general and AH in particular.

87 citations


Journal ArticleDOI
TL;DR: A global review of HO and its main pathophysiological, epidemiological and therapeutic aspects was conducted by a systematic literature search of the PubMed database.
Abstract: Hepatic osteodystrophy (HO) is the generic term defining the group of alterations in bone mineral metabolism found in patients with chronic liver disease. This paper is a global review of HO and its main pathophysiological, epidemiological and therapeutic aspects. Studies examining the most relevant information concerning the prevalence, etiological factors, diagnostic and therapeutic aspects involved in HO were identified by a systematic literature search of the PubMed database. HO generically defines overall alterations in bone mineral density (BMD) (osteoporosis or osteopenia) which appear as a possible complication of chronic liver disease. The origin of HO is multifactorial and its etiology and severity vary in accordance with the underlying liver disease. Its exact prevalence is unknown, but different studies estimate that it could affect from 20% to 50% of patients. The reported mean prevalence of osteoporosis ranges from 13%-60% in chronic cholestasis to 20% in chronic viral hepatitis and 55% in viral cirrhosis. Alcoholic liver disease is not always related to osteopenia. HO has been commonly studied in chronic cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis). Several risk factors and pathogenic mechanisms have been associated with the loss of BMD in patients with chronic liver disease. However, little information has been discovered in relationship to most of these mechanisms. Screening for osteopenia and osteoporosis is recommended in advanced chronic liver disease. There is a lack of randomized studies assessing specific management for HO.

70 citations


Journal ArticleDOI
TL;DR: Strict monitoring and sustainment of cardiorespiratory function, frequent assessment of graft performance, timely recognition of unexpected complications and the institution of prophylactic measures to prevent extrahepatic organ system dysfunction are mandatory in the immediate post-operative period.
Abstract: Advances in pre-transplant treatment of cirrhosis-related organ dysfunction, intraoperative patient management, and improvements in the treatment of rejection and infections have made human liver transplantation an effective and valuable option for patients with end stage liver disease. However, many important factors, related both to an increasing “marginality” of the implanted graft and unexpected perioperative complications still make immediate post-operative care challenging and the early outcome unpredictable. In recent years sicker patients with multiple comorbidities and organ dysfunction have been undergoing Liver transplantation; appropriate critical care management is required to support prompt graft recovery and prevent systemic complications. Early post-operative management is highly demanding as significant changes may occur in both the allograft and the “distant” organs. A functioning transplanted liver is almost always associated with organ system recovery, resulting in a new life for the patient. However, in the unfortunate event of graft dysfunction, the unavoidable development of multi-organ failure will require an enhanced level of critical care support and a prolonged ICU stay. Strict monitoring and sustainment of cardiorespiratory function, frequent assessment of graft performance, timely recognition of unexpected complications and the institution of prophylactic measures to prevent extrahepatic organ system dysfunction are mandatory in the immediate post-operative period. A reduced rate of complications and satisfactory outcomes have been obtained from multidisciplinary, collaborative efforts, skillful vigilance, and a thorough knowledge of pathophysiologic characteristics of the transplanted liver.

53 citations


Journal ArticleDOI
TL;DR: HCV genotypes and duration of HCV infection differed between B-NHL subtypes, suggesting indolent lymphomas can be managed with antiviral treatment, while DLBCL is not affected by theHCV infection.
Abstract: AIM: To evaluate if indolent B cell-non Hodgkin’s lymphoma (B-NHL) and diffuse large B-cell lymphoma (DLBCL) in hepatitis C virus (HCV) positive patients could have different biological and clinical characteristics requiring different management strategies. METHODS: A group of 24 HCV related B-NHL patients (11 indolent, 13 DLBCL) in whom the biological and clinical characteristics were described and confronted. Patients with DLBCL were managed with the standard of care of treatment. Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed. The outcomes of the different approaches were compared. RESULTS: Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype. Five of the 9 patients with indolent HCV-related

45 citations


Journal ArticleDOI
TL;DR: To critically review the actual knowledge of BCS management, there is some concern about treatment of some subgroup of patients, especially regarding the risk of recurrence after liver transplantation.
Abstract: Budd-Chiari syndrome (BCS) is a rare disease whose management should follow a step by step strategy. Anticoagulation and medical therapy should be the first line treatment. Revascularization or TIPS are indicated in case of no response to medical therapy. OLT should be indicated as a rescue therapy and anticoagulation be started soon after OLT. However, no clear indication can actually be given about the timing of different treatments. Moreover, there is some concern about treatment of some subgroup of patients, especially regarding the risk of recurrence after liver transplantation. The topic of this paper is to critically review the actual knowledge of BCS management.

44 citations


Journal ArticleDOI
TL;DR: There is now enough evidence to support that hepatitis B patients should be considered for treatment if they show persistently elevated abnormal aminotransferase levels in the last 6 mo, checked on at least three separate occasions, and a serum hepatitis B virus DNA level of > 2000 IU/mL.
Abstract: Hepatitis B is one of the leading causes of chronic hepatitis in developing countries, with 5% to 15% of the population carrying virus. The high prevalence is due to failure to adopt appropriate measure to confine the spread of infection. Most hepatitis B patients present with advanced diseases. Although perinatal transmission is believed to be an important mode, most infections in the developing world occur in childhood and early adulthood. Factors in developing countries associated with the progression of chronic hepatitis B (CHB) include co-infections with human immunodeficiency virus, delta hepatitis virus, hepatitis C virus, alcohol intake and aflatoxin. Treatment protocols extrapolated from developed countries may need modifications according to the resources available. There is some controversy as to when to start treatment, with what medication and for how long? There is now enough evidence to support that hepatitis B patients should be considered for treatment if they show persistently elevated abnormal aminotransferase levels in the last 6 mo, checked on at least three separate occasions, and a serum hepatitis B virus DNA level of > 2000 IU/mL. Therapeutic agents that were approved by Pure Food and Drug Administration are now available in many developing countries. These include standard interferon (INF)-α, pegylated INF-α, lamivudine, adefovir, entecavir and telbivudine. Drug resistance has emerged as a major challenge in the management of patients with CHB. The role of the universal vaccination program for effective control of hepatitis B cannot be emphasized enough.

Journal ArticleDOI
TL;DR: This review summarizes recent advances in the basic understanding of the role of angiogenesis in HCC as well as clinical trials with novel therapeutic approaches targetingAngiogenesis and EGFR-related pathways.
Abstract: Hepatocellular carcinoma (HCC) has a poor prognosis and systemic chemotherapies have disappointing results. The increasing knowledge of the molecular biology of HCC has resulted in novel targets, with the vascular endothelial growth factor and epidermal growth factor receptor (EGFR)-related pathways being of special interest. New blood vessel formation (angiogenesis) is essential for the growth of solid tumors. Anti-angiogenic strategies have become an important therapeutic modality for solid tumors. Several agents targeting angiogenesis-related pathways have entered clinical trials or have been already approved for the treatment of solid tumors. These include monoclonal antibodies, receptor tyrosine kinase inhibitors and immunomodulatory drugs. HCC is a highly vascular tumor, and angiogenesis is believed to play an important role in its development and progression. This review summarizes recent advances in the basic understanding of the role of angiogenesis in HCC as well as clinical trials with novel therapeutic approaches targeting angiogenesis and EGFR-related pathways.

Journal ArticleDOI
TL;DR: HCV and HBV infections and diabetes are the main determinants of HCC development in North Africa and an active surveillance and secondary prevention programs for patients with chronic hepatitis and nutrition-associated metabolic liver diseases are the most important steps to reduce the risk of H CC in the region.
Abstract: AIM: To assess the role of the major risk factors for hepatocellular carcinoma (HCC) development in the western part of North Africa. METHODS: A multicenter case control study was conducted in Tunisia, Morocco and Algeria in collaboration with Pasteur Institutes in these countries. A total of 164 patients with HCC and 250 control subjects without hepatic diseases were included. Prevalences of HBsAg, anti-hepatitis C virus (HCV) and diabetes were assessed. HCV and HBV genotyping were performed for anti-HCV and HBsAg positive patients. RESULTS: The mean age of patients was 62 ± 10

Journal ArticleDOI
TL;DR: The available trials on use of corticosteroids and pentoxifylline with their current status are described and an algorithm with clinical approach to management of patients who present with clinical syndrome of AH is described.
Abstract: The treatment of choice for patients with severe alcoholic hepatitis (AH) is use of corticosteroids. Many randomized well designed studies have been reported from all over the world on the use of corticosteroids in the treatment of AH. However, the data on the efficacy of corticosteroids in these patients have been conflicting. Initial meta-analyses also failed to show beneficial effects of corticosteroids. Based on individual data meta-analysis showing clear benefit of corticosteroids amongst patients with severe AH (modified discriminant function of 32 or more), led American College of Gastroenterology to recommend use of corticosteroids as the first line treatment option amongst patients with severe AH. However, corticosteroids are relatively contraindicated amongst patients with severe AH and coexistent sepsis, gastrointestinal bleeding, and acute pancreatitis. These patients may be candidates for second line treatment with pentoxifylline. Further, specific treatment of AH with corticosteroids far from satisfactory with as many as 40%-50% of patients failing to respond to steroids, thus classified as non-responsive to steroids. The management of these patients is a continuing challenge for physicians. Better treatment modalities need to be developed for this group of patients in order to improve the outcome of patients with severe AH. This article describes at length the available trials on use of corticosteroids and pentoxifylline with their current status. Route of administration, dosage, adverse effects, and mechanisms of action of these two drugs are also discussed. Finally, an algorithm with clinical approach to management of patients who present with clinical syndrome of AH is described.

Journal ArticleDOI
TL;DR: Hepatotoxicity is described in a 35-year-old female, following bee sting therapy for multiple sclerosis, presented to the clinic 3 wk after therapy with a history of progressive jaundice, and has been attending the clinic now for the last 9 mo.
Abstract: The use of bee venom as a therapeutic agent for the relief of joint pains dates back to Hippocrates, and references to the treatment can be found in ancient Egyptian and Greek medical writings as well. Also known as apitherapy, the technique is widely used in Eastern Europe, Asia, and South America. The beneficial effects of bee stings can be attributed to mellitinin, an anti-inflammatory agent, known to be hundred times stronger than cortisone. Unfortunately, certain substances in the bee venom trigger allergic reactions which can be life threatening in a sensitized individual. Multiple stings are known to cause hemolysis, kidney injury, hepatotoxicity and myocardial infarction. The toxicity can be immediate or can manifest itself only weeks after the exposure. We describe hepatotoxicity in a 35-year-old female, following bee sting therapy for multiple sclerosis. She presented to our clinic 3 wk after therapy with a history of progressive jaundice. The patient subsequently improved, and has been attending our clinic now for the last 9 mo.

Journal ArticleDOI
TL;DR: The time is ripe to re-evaluate the policy of LT in patients with AH, with encouraging data on the usefulness of LT for patients who are non-responders to corticosteroid and/or pentoxifylline therapy.
Abstract: Acute alcoholic hepatitis (AH) is a distinct clinical entity amongst patients with chronic alcohol abuse. Patients with severe AH are at risk of dying in about 20%-25% cases despite specific treatment with corticosteroids and/or pentoxifylline. Clearly, a need for an additional more effective treatment option is unmet currently. Liver transplantation (LT), a definitive treatment option for alcoholic cirrhosis requires 6 mo abstinence. However, this rule cannot be applied to patients with AH as these patients are actively drinking prior to their presentation. Shortage of donors, ethical issues, and fear of recidivism after transplantation with less than 6 mo pre-transplant abstinence are some of the reasons behind this rule of 6 mo of abstinence and hesitancy of transplanting patients with AH. These issues are debated at length in this manuscript. Further, retrospective studies have shown that patients undergoing transplantation for alcoholic cirrhosis and having histological changes of AH have been shown to fare as well when compared to patients without these histological changes. Recently, French workers have reported a case matched prospective study showing encouraging data on the usefulness of LT for patients who are non-responders to corticosteroid and/or pentoxifylline therapy. Future studies are needed to identify patients with severe AH who are going to benefit most with LT. In the light of emerging data on the efficacy of LT in improving survival of patients with severe acute AH who do not respond to corticosteroids, the time is ripe to re-evaluate our policy of LT in patients with AH.

Journal ArticleDOI
TL;DR: Herbal preparations may offer a cost effective protective alternative to individuals known to have a high risk for HCC and possibly other cancers, through maintaining cell integrity, reversing oxidative stress and modulating different molecular pathways in preventing carcinogenesis.
Abstract: In this review we outline the different mechanisms mediating hepatocarcinogenesis. We also discuss possible targets of bioactive herbal agents at different stages of hepatocarcinogenesis and highlight their role at each individual stage. We gathered information on the most common herbal prescriptions and extracts thought to be useful in prevention or sensitization for chemotherapy in management of hepatocellular carcinoma (HCC). The value of this topic may seem questionable compared to the promise offered for HCC management by chemotherapy and radiation. However, we would recommend the use of herbal preparations not as alternatives to common chemo /and or radiotherapy, but rather for prevention among at-risk individuals, given that drug/herb interactions are still in need of extensive clarification. The bioactive constituents of various herbs seem to be promising targets for isolation, cancer activity screening and clinical evaluation. Finally, herbal preparations may offer a cost effective protective alternative to individuals known to have a high risk for HCC and possibly other cancers, through maintaining cell integrity, reversing oxidative stress and modulating different molecular pathways in preventing carcinogenesis.

Journal ArticleDOI
TL;DR: It is concluded that HBV vaccine is efficient in controlling HBV infection among children and adults and a booster dose of vaccine is recommended, probably four years after initial vaccination.
Abstract: AIM: To evaluate the impact of mass vaccination against the hepatitis B virus (HBV) in Egypt, and to search for vaccinee asymptomatic breakthrough HBV infection and its genotype. METHODS: Seven hundred serum samples from vaccinated children and adults (aged 2-47 years) were used for quantitative and qualitative detection of HBsAb by ELISA. Three hundred and sixty serum samples representing undetectable or low or high HBsAb were screened for markers of active HBV infection (HBsAg, HBcAb (IgG) and HBeAb by ELISA, plus HBsAg by AxSYM) and HBV-DNA genotyping by nested multiplex PCR and by DNA sequencing. RESULTS: It was found that 65% of children aged 2-4 years, and 20.5% aged 4-13 years, as well as 45% adults were good responders to HBV vaccination mounting protective level HBsAb. Poor responders were 28%, 59.5% and 34%, and non-responders were 7%, 20% and 21% respectively, in the three studied groups. Markers of asymptomatic HBV infections were HBsAg detected by ELISA in 2.5% vs 11.39% by AxSYM. Other markers were HBcAb (IgG) in 1.38%, HBeAb in 0.83%, and HBV-DNA in 7.8%. All had HBV genotype E infection. CONCLUSION: It is concluded that HBV vaccine is efficient in controlling HBV infection among children and adults. The vaccine breakthrough infection was by HBV genotype E. A booster dose of vaccine is recommended, probably four years after initial vaccination.

Journal ArticleDOI
TL;DR: This group investigated the ezetimibe-orlistat combination treatment in overweight and obese patients with hypercholesterolemia, with beneficial effects on NAFLD biochemical markers, and results are promising for patients withNAFLD, who usually have increased cardiovascular disease risk and need a multifactorial treatment.
Abstract: Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis, advanced fibrosis and inflammatory changes. Ezetimibe inhibits cholesterol absorption from the intestinal lumen into enterocytes. The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1). Human NPC1L1 is abundantly expressed in the liver and may facilitate the hepatic accumulation of cholesterol. Ezetimibe exerts beneficial effects on several metabolic variables. Ezetimibe treatment attenuates hepatic steatosis and is beneficial in terms of NAFLD biochemical markers. The combination of ezetimibe with other interventions may also be beneficial in NAFLD patients. Our group investigated the ezetimibe-orlistat combination treatment in overweight and obese patients with hypercholesterolemia, with beneficial effects on NAFLD biochemical markers. These results are promising for patients with NAFLD, who usually have increased cardiovascular disease risk and need a multifactorial treatment. However, it should be mentioned that most results are from animal studies and, although modest elevation of liver function tests may raise the suspicion of NAFLD, none of these tests are sensitive to establish the diagnosis of NAFLD with great accuracy.

Journal ArticleDOI
TL;DR: Clinical presentation after abstinence for more than 3 m should raise doubts about the diagnosis of AH and dictate the need for considering other causes of liver disease, decompensation of alcoholic cirrhosis, sepsis and malignancy as the cause of patient's clinical profile.
Abstract: Although there is not one specific sign or symptom related to alcoholic hepatitis (AH), a constellation of symptoms and signs can help make the diagnosis of AH with reasonable accuracy. Documentation of chronic and active alcohol abuse is paramount in making a diagnosis of AH. Clinical presentation after abstinence for more than 3 m should raise doubts about the diagnosis of AH and dictate the need for considering other causes of liver disease, decompensation of alcoholic cirrhosis, sepsis and malignancy as the cause of patient’s clinical profile.

Journal ArticleDOI
TL;DR: Novel therapies aimed at these pathways may prevent, decrease, or delay the complications of alcoholic hepatitis.
Abstract: Inflammatory signaling and oxidative stress are two major components in the pathogenesis of alcoholic hepatitis. Alcohol consumption results in translocation of gut bacteria into the portal system along with lipopolysaccharides that interact with toll-like receptors and results in the production of inflammatory and immunogenic mediators such as tumor necrosis factor-alpha (TNF-α) and interferons. Chronic consumption of alcohol causes priming of this process in which there is enhanced production of cytokines, interferon, interleukins, and TNF-α. Oxidative stress, genetic predisposition, and the unfolded protein response are other contributory mechanisms. Novel therapies aimed at these pathways may prevent, decrease, or delay the complications of alcoholic hepatitis.

Journal ArticleDOI
TL;DR: This case highlights the potential for thrombosis at unusual sites in ulcerative colitis patients even in the absence of classical coagulation abnormalities, and provides a brief review of previously reported cases of Budd-Chiari Syndrome occurring in patients with inflammatory bowel disease.
Abstract: We report a case of 27 year old female patient who was admitted to the hospital with an acute flare up of ulcerative colitis. The patient presented with complaints of persistent abdominal pain and bloody diarrhea despite aggressive therapy for her ulcerative colitis. A CT scan of the abdomen on admission revealed hepatic vein thrombosis, suggesting a diagnosis of Budd-Chiari syndrome. Significantly, an associated thrombosis of the inferior mesenteric vein was also detected. Based on imaging data and clinical assessment, the patient was started on anticoagulation therapy and an extensive work-up for hypercoagulability was initiated. Up to the time of publication, no significant findings suggesting this patient has an underlying coagulation disorder have been found. Based on our search of PUBMED, this report is one of only five reported adult cases of Budd-Chiari Syndrome associated with ulcerative colitis in the English literature in living patients without evidence of a co-existing coagulation disorder. This case highlights the potential for thrombosis at unusual sites in ulcerative colitis patients even in the absence of classical coagulation abnormalities. In addition to the case presented, we provide a brief review of previously reported cases of Budd-Chiari Syndrome occurring in patients with inflammatory bowel disease.

Journal ArticleDOI
TL;DR: Some of the challenges and opportunities for hepatitis B control at the end of the first decade of the third millennium are reviewed and it is argued for closer East - West collaborations to bring in fresh perspectives, avoid duplications of effort and to help answer many of the remaining challenges in making hepatitis B history.
Abstract: Despite being ten times more common than HIV infection, viral hepatitis has so far not commanded the same public health response worldwide, so a global viral hepatitis treatment program is still a long way from becoming a reality. However, much progress has occurred over the last few decades, with the screening of blood products, sound infection control practices and the introduction of disposable needles and syringes leading to significant reductions in nosocomial hepatitis B transmission in the developed world and increasingly in other countries. The introduction of hepatitis B vaccination in the 1980s and its integration into the Expanded Immunization Program have led to substantial reductions in chronic hepatitis B infection rates in children and to millions of lives saved. The availability of effective antiviral treatment has revolutionized treatment prospects, although access to treatment remains a significant challenge for most developed countries and remains out of reach for developing nations. Some of these breakthroughs have occurred in Asian countries, others in the West, but their unifying features are innovative research, timely clinical translation and a commitment to apply their findings to improve the health of populations, not just individuals. This paper reviews some of the challenges and opportunities for hepatitis B control at the end of the first decade of the third millennium and argues for closer East - West collaborations, to bring in fresh perspectives, avoid duplications of effort and in order to help answer many of the remaining challenges in making hepatitis B history.

Journal ArticleDOI
TL;DR: Asymptomatic PBC patients do not have a greater frequency of cardiovascular disease; nor do patientssuffering with fatigue; nor does patients suffering with fatigue.
Abstract: AIM: To estimate the prevalence of cardiovascular events in Primary biliary cirrhosis (PBC) and to determine whether this risk is higher within specific subgroups of patients with PBC. METHODS: We included 180 patients with PBC (cases) and 151 patients seen for HCV infection (controls). Medical records were reviewed and statistical analyses were performed as appropriate. RESULTS: When compared to controls, PBC patients were older, leaner and had higher serum levels of total cholesterol, high density lipoprotein and low density cholesterol. There were more females in the PBC group (91.7% vs 43%, P < 0.001). More control subjects had smoked than the PBC patients (63.6% vs 35%, P < 0.001). The prevalence of hypertension, diabetes, coronary artery disease and stroke was similar between the two groups. Seven percent of controls and 10% of cases developed any type of cardiovascular disease (P = 0.3). Only 36.7% were asymptomatic at diagnosis. Three cardiovascular events were documented among asymptomatic patients (4.5%) and fifteen among symptomatic patients (13.2%; P = 0.06). Among PBC patients with fatigue, 10 (13.5%) had a cardiovascular event compared to 7 (6.7%) among patients without fatigue (P = 0.1). CONCLUSION: Asymptomatic PBC patients do not have a greater frequency of cardiovascular disease; nor do patients suffering with fatigue.

Journal ArticleDOI
TL;DR: Liver steatosis and fibrosis can occur in individuals with normal weight and there was no significant concordance between severity of liver histology and the presence of predictors for liver fibrosis including metabolic risk factors.
Abstract: CONCLUSION: Liver steatosis and fibrosis can occur in individuals with normal weight. There was no significant concordance between severity of liver histology and the presence of predictors for liver fibrosis including metabolic risk factors.

Journal ArticleDOI
TL;DR: The article does not objectively support a causal relationship between the reported cases of liver injury and Herbalife products or ingredients.
Abstract: In the November 27, 2010 issue of the World Journal of Hepatology (WJH), three case reports were published which involved patients who had consumed various dietary supplements and conventional foods generally marketed as weight loss products. The reference to Herbalife products as contaminated and generally comparable to all dietary supplements or weight loss products is not scientifically supported. The authors provided an insufficient amount of information regarding patient histories, concomitant medications and other compounds, dechallenge results, and product specifications and usage. This information is necessary to fully assess the association of Herbalife products in the WJH case reports. Therefore, the article does not objectively support a causal relationship between the reported cases of liver injury and Herbalife products or ingredients.

Journal ArticleDOI
TL;DR: Osteopenia/osteoporosis is common in advanced liver disease and low serum IGF-1 is weakly predictive but serum cytokine and MELD score fail to predict the severity of bone disease.
Abstract: MELD score, insulin-like growth factor 1 and cytokines on bone density in end-stage liver disease

Journal ArticleDOI
TL;DR: The results strongly support the use of prophylaxis as a means to decrease early post TIPS infections and risk factors associated with bacteremia include failure to use proPHylactic antibiotics, hypothyroidism, HCV and a long procedure.
Abstract: AIM: To identify all cases of bacteremia and suspected endotipsitis after Transjugular intrahepatic portosystemic shunting (TIPS) at our institution and to determine risk factors for their occurrence. METHODS: We retrospectively reviewed records of all patients who underwent TIPS in our institution between 1996 and 2009. Data included: indications for TIPS, underlying liver disease, demographics, positive blood cultures after TIPS, microbiological characteristics, treatment and outcome. RESULTS: 49 men and 47 women were included with a mean age of 55.8 years (range 15-84). Indications for TIPS included variceal bleeding, refractory ascites, hydrothorax and hepatorenal syndrome. Positive blood cultures after TIPS were found in 39/96 (40%) patients at various time intervals following the procedure. Seven patients had persistent bacteremia fitting the definition of endotipsitis. Staphylococcus species grew in 66% of the positive cultures, Candida and enterococci species in 15% each of the isolates, and 3% cultures grew other species. Multi-variate regression analysis identified 4 variables: hypothyroidism, HCV, prophylactic use of antibiotics and the procedure duration as independent risk factors for positive blood cultures following TIPS (P < 0.0006, 0.005, 0.001, 0.0003, respectively). Prophylactic use of antibiotics before the procedure was associated with a decreased risk for bacteremia, preventing mainly early infections, occurring within 120 d of the procedure. CONCLUSION: Bacteremia is common following TIPS. Risk factors associated with bacteremia include failure to use prophylactic antibiotics, hypothyroidism, HCV and a long procedure. Our results strongly support the use of prophylaxis as a means to decrease early post TIPS infections.

Journal ArticleDOI
TL;DR: Old age, T2DM and cirrhosis were suggested to be prerequisite for MO because these factors were depicted in common among two other cases with MO of HCC under NASH in the literature.
Abstract: CONCLUSION: The putative predisposing factors and necessary preconditions for synchronous MO of HCC in NASH were suggested in this study. Further investigations are required to clarify the accurate prevalence and predictors of MO to establish better strategies for treatment and prevention leading to the prognostic improvement in NASH.

Journal ArticleDOI
TL;DR: A case of ductopenia-related sarcoidosis in which primary biliary cirrhosis and extrahepatic cholestasis have been carefully excluded and ursodesoxycholic acid appears to improve liver biochemistry it does not preclude the rapid occurrence of extensive fibrosis.
Abstract: Sarcoidosis is a systemic granulomatous disease which may involve many organs. In approximately 95% of patients there is liver involvement, with noncaseating hepatic granulomas occurring in 21 to 99% of patients with sarcoidosis. Liver involvement is usually asymptomatic and limited to mild to moderate abnormalities in liver biochemistry. The occurrence of jaundice in sarcoidosis is rare; extensive imaging procedures and the examination of liver biopsies permit a precise diagnostic. Ductopenia associated with sarcoidosis has been reported in less than 20 cases and can lead to biliary cirrhosis and liver- related death. We report here on a case of ductopenia-related sarcoidosis in which primary biliary cirrhosis and extrahepatic cholestasis have been carefully excluded. The patient follow up was 8 years. Although ursodesoxycholic acid appears to improve liver biochemistry it does not preclude the rapid occurrence of extensive fibrosis. A review of the literature of reported cases of ductopenia related to sarcoidosis is provided.