Hepatitis: Liang TJ

Koh C, Liang TJ. · No affiliation provided · J Hepatol. · Pubmed #19014877 links to  free full text

This publication has no abstract.

Liang TJ. · No affiliation provided · N Engl J Med. · Pubmed #17625131 No free full text.

This publication has no abstract.

Promrat K, Liang TJ. · No affiliation provided · Hepatology. · Pubmed #14647045 No free full text.

This publication has no abstract.

Liang TJ, Ghany M. · No affiliation provided · N Engl J Med. · Pubmed #12124411 No free full text.

This publication has no abstract.

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. · J Hepatol. · Pubmed #18457898 links to  free full text

Abstract: 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.

Loomba R, Rowley A, Wesley R, Liang TJ, Hoofnagle JH, Pucino F, Csako G. · National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland 20892, USA. · Ann Intern Med. · Pubmed #18378948 links to  free full text

Abstract: BACKGROUND: Lamivudine is increasingly being used to prevent hepatitis B reactivation in patients with cancer who test positive for hepatitis B surface antigen (HBsAg) and are undergoing chemotherapy. PURPOSE: To determine whether preventive lamivudine reduces chemotherapy-induced hepatitis B virus (HBV)-related morbidity and mortality in patients with cancer who test positive for HBsAg. DATA SOURCES: MEDLINE, Ovid MEDLINE, TOXNET, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched in all languages until June 2007. STUDY SELECTION: Clinical trials and cohort studies that reported the efficacy of preventive lamivudine versus control on HBV reactivation in patients who tested positive for HBsAg and were receiving chemotherapy were included. Additional requirements included minimum sample size (>5 participants per treatment group) and reported HBV-related morbidity and mortality data. DATA EXTRACTION: Two investigators independently did literature searches and data extraction, and 2 other investigators independently confirmed study eligibility and data retrieval. DATA SYNTHESIS: Fourteen studies (2 randomized, controlled trials; 8 prospective cohort studies; and 4 retrospective cohort studies) met the predefined criteria for analysis. There were 275 patients in the preventive lamivudine group and 475 control participants for the primary end point of HBV reactivation. With preventive lamivudine, the relative risk for both HBV reactivation and HBV-related hepatitis ranged from 0.00 to 0.21. None of the patients in the preventive lamivudine group developed HBV-related hepatic failure (0 of 108 patients vs. 21 of 162 patients), and only 4 deaths were attributable to HBV (4 of 208 patients vs. 27 of 394 patients) in the preventive lamivudine group. Lamivudine was well tolerated, and no adverse effects were noted. LIMITATIONS: The studies included in the meta-analysis did not consistently report all of the outcomes of interest. Sample sizes were small and only 2 studies had a randomized, controlled design. CONCLUSION: Preventive therapy with lamivudine for patients who test positive for HBsAg and are undergoing chemotherapy may reduce the risk for HBV reactivation and HBV-associated morbidity and mortality.

Loomba R, Liang TJ. · Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MA, USA. · Antivir Ther. · Pubmed #18284181 No free full text.

Abstract: Hepatitis B virus (HBV) infection is the leading cause of chronic liver disease and hepatocellular carcinoma worldwide. Approximately 350 million individuals are infected with HBV and >500,000 deaths per year can be attributed to HBV. Although universal vaccination has reduced HBV incidence in many countries, it still remains a major public health problem, especially in parts of Asia and Africa. Improved understanding of HBV virology and virus-host interactions has revolutionized chronic hepatitis B therapy in the past two decades. Development of oral nucleoside/nucleotide analogues heralds a new era of safe and effective treatment of this disease. On the basis of these advances, new guidelines for the treatment of chronic hepatitis B have been issued. Successful long-term treatment of chronic hepatitis B may rest on combination therapy that is based on molecular approaches targeting various stages of the HBV life-cycle. In this review, we summarize the current modalities and highlight important issues in the treatment of chronic hepatitis B monoinfection.

Pawlotsky JM, Dusheiko G, Hatzakis A, Lau D, Lau G, Liang TJ, Locarnini S, Martin P, Richman DD, Zoulim F. · French National Reference Center for Viral Hepatitis B, C and delta, Department of Virology, Henri Mondor Hospital, University of Paris XII, Créteil, France. · Gastroenterology. · Pubmed #18242209 links to  free full text

Abstract: Treatment of chronic hepatitis B virus (HBV) infection is aimed at suppressing viral replication to the lowest possible level, and thereby to halt the progression of liver disease and prevent the onset of complications. Two categories of drugs are used in HBV therapy: the interferons, including standard interferon alfa or pegylated interferon alfa, and specific nucleoside or nucleotide HBV inhibitors that target the reverse-transcriptase function of HBV-DNA polymerase. The reported results of clinical trials have used varying definitions of efficacy, failure, and resistance based on different measures of virologic responses. This article discusses HBV virologic markers and tests, and their optimal use both for planning and reporting clinical trials and in clinical practice.

Modi AA, Liang TJ. · The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. · Oral Dis. · Pubmed #18173443 No free full text.

Abstract: Hepatitis C is a major cause of chronic liver disease. It has been recognized as a global health problem because of the progression to cirrhosis and hepatocellular cancer. Chronic hepatitis C is usually asymptomatic but can cause considerable liver damage before its recognition. This review discusses the natural history, clinical features, diagnosis, therapy, treatment responses and the side effects associated with the treatment of hepatitis C.

Ghany M, Liang TJ. · Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. · Gastroenterology. · Pubmed #17408658 No free full text.

Abstract: Chronic hepatitis B continues to be a major cause of end-stage liver disease and hepatocellular carcinoma worldwide. Nucleos(t)ide analogues have proven to be effective in controlling the disease and perhaps decreasing the incidence of hepatocellular carcinoma. However, development of drug resistance is a major limitation to their long-term effectiveness. Understanding the mechanisms of drug resistance are important for designing new agents and devising strategies to manage and prevent the development of antiviral drug resistance. The development of resistance is determined by an interplay of viral, host, and drug characteristics Homology of the HBV polymerase to the human immunodeficiency virus-1 reverse transcriptase has allowed predictions to be made on the effect mutations have on HBV polymerase structure. In vitro functional studies provide complementary information. Several broad principles on the mechanism of resistance have emerged from these studies. First, most of the primary mutations cluster in the vicinity of the incoming nucleotide and act by directly affecting the position or stability of the bound substrate, template, or primer. In contrast, secondary mutations tend to occur away from the nucleotide-binding pocket. Finally, the structural and functional consequences of mutations are quite variable among the different agents. This paper reviews the key mutations and mechanisms associated with resistance to the nucleos(t)ide analogues approved for clinical use and discuss new targets for drug development.

Hoofnagle JH, Doo E, Liang TJ, Fleischer R, Lok AS. · Liver Disease Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. · Hepatology. · Pubmed #17393513 No free full text.

Abstract: Chronic hepatitis B is caused by persistent infection with the hepatitis B virus (HBV), a unique DNA virus that replicates through an RNA intermediate produced from a stable covalently closed circular DNA molecule. Viral persistence appears to be due to inadequate innate and adaptive immune responses. Chronic infection has a variable course after several decades resulting in cirrhosis in up to one-third of patients and liver cancer in a proportion of those with cirrhosis. Sensitive assays for HBV DNA levels in serum have been developed that provide important insights into pathogenesis and natural history. Therapy of hepatitis B is evolving. Peginterferon induces long-term remissions in disease in one-third of patients with typical hepatitis B e antigen (HBeAg) positive chronic hepatitis B, but a lesser proportion of those without HBeAg. Several oral nucleoside analogues with activity against HBV have been shown to be effective in suppressing viral levels and improving biochemical and histological features of disease in a high proportion of patients with and without HBeAg, at least in the short term. What is uncertain is which agent or combination of agents is most effective, how long therapy should last, and which criteria should be used to start, continue, switch or stop therapy. Long-term therapy with nucleoside analogues may be the most appropriate approach to treatment, but the expense and lack of data on long-term safety and efficacy make recommendations difficult. Clearly, many basic and clinical research challenges remain in defining optimal means of management of chronic hepatitis B.

Barth H, Liang TJ, Baumert TF. · Department of Medicine II, University of Freiburg, Freiburg, Germany. · Hepatology. · Pubmed #16941688 No free full text.

Abstract: With an estimated 170 million infected individuals, hepatitis C virus (HCV) has a major impact on public health. A vaccine protecting against HCV infection is not available, and current antiviral therapies are characterized by limited efficacy, high costs, and substantial side effects. Binding of the virus to the cell surface followed by viral entry is the first step in a cascade of interactions between virus and the target cell that is required for the initiation of infection. Because this step represents a critical determinant of tissue tropism and pathogenesis, it is a major target for host cell responses such as antibody-mediated virus-neutralization-and a promising target for new antiviral therapy. The recent development of novel tissue culture model systems for the study of the first steps of HCV infection has allowed rapid progress in the understanding of the molecular mechanisms of HCV binding and entry. This review summarizes the impact of recently identified viral and host cell factors for HCV attachment and entry. Clinical implications of this important process for the pathogenesis of HCV infection and novel therapeutic interventions are discussed.

Loomba R, Liang TJ. · Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. · Antivir Ther. · Pubmed #16518955 No free full text.

Abstract: Hepatitis B is one of the most prevalent viral diseases in the world. It leads to chronic liver disease in 10% of infected individuals, putting them at an increased risk for liver-related morbidity and mortality from complications of cirrhosis and hepatocellular carcinoma. Despite the success of universal hepatitis B vaccination in many countries, this disease remains a major public health problem, resulting in more than 500,000 deaths per year. Although the current therapy for chronic hepatitis B (CHB) is effective, it is not optimal; novel approaches to the management of CHB are needed. An improved understanding of virus-host interactions, advances in gene therapy, the development of molecular therapies targeted at different stages of the hepatitis B virus life cycle, and new insights into various approaches of immune modulation will lead to the development of better therapeutic agents for the management of CHB. These advances herald a new era of combination therapy. In this review, we will discuss emerging therapies and potential mechanisms, and highlight the promises and pitfalls of these new treatment strategies.

Feld JJ, Liang TJ. · Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. · Hepatology. · Pubmed #16447261 No free full text.

Abstract: Hepatitis C follows a variable course with some patients developing progressive liver fibrosis, cirrhosis and hepatocellular carcinoma, while others have minimal or no significant liver disease after decades of infection. Studies have identified both host and viral factors associated with disease progression. The importance of general factors such as age at infection, gender, immune status and alcohol consumption has long been recognized; however recently, polymorphisms in a wide array of genes have also been shown to be associated with progressive fibrosis. How specific viral proteins may contribute to disease progression has also been studied. This review highlights what is currently known about the factors associated with progressive liver injury in patients with hepatitis C. A greater understanding of the determinants of disease progression will hopefully lead to improved utilization of existing treatments and ultimately may aid in identification of new therapeutic targets.

Feld JJ, Liang TJ. · No affiliation provided · Hepatology. · Pubmed #15690477 No free full text.

This publication has no abstract.

Locarnini S, Hatzakis A, Heathcote J, Keeffe EB, Liang TJ, Mutimer D, Pawlotsky JM, Zoulim F. · Victorian Infectious Diseases Reference Laboratory, North Melbourne, Vic., Australia. · Antivir Ther. · Pubmed #15535405 No free full text.

Abstract: A meeting of physicians and scientists involved in the management of chronic hepatitis B (CHB) was held to review current scientific data regarding antiviral resistance in hepatitis B virus (HBV) infection. The goals of the meeting were to describe current treatments for CHB, discuss emerging issues in HBV drug resistance and to delineate patient monitoring, including markers for resistance, during administration of antiviral therapy. The aim of this review article is to provide treating physicians with a framework for the management of CHB in the context of antiviral resistance. Definitions of primary and secondary antiviral treatment failure can be used to aid monitoring and early diagnosis of drug resistance before disease progression occurs as a consequence of viral breakthrough. Primary antiviral treatment failure is defined as failure of a drug to reduce HBV DNA levels by > or = 1 x log10 IU/ml within 3 months following initiation of therapy, and secondary antiviral treatment failure as a rebound of HBV replication of > or = 1 x log10 IU/ml from nadir in patients with an initial antiviral treatment effect (> or = 1 x log10 IU/ml decrease in serum HBV DNA). Confirmation of antiviral drug failure can be established by sequencing the HBV DNA polymerase and identifying specific genetic markers of antiviral drug resistance. In addition to virological assays, HBV resistance can be assessed from a clinical perspective including increased serum alanine aminotransferase levels and the development of systemic symptoms or signs of liver failure. Potential strategies to prevent the emergence of resistance and how to manage drug-resistant HBV once it emerges are discussed.

Liang TJ, Heller T. · Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. · Gastroenterology. · Pubmed #15508105 No free full text.

Abstract: Epidemiologic, clinical, and virologic data have shown a close association between chronic infection with hepatitis C virus (HCV) and the development of hepatocellular carcinoma (HCC). In many countries of the developed world, HCV infection accounts for more than half of the cases of HCC. HCC usually arises after 2-4 decades of infection, typically in the context of an underlying cirrhosis. Treatment of hepatitis C with interferon-alfa can lead to sustained clearance of HCV, and small prospective studies as well as larger retrospective analyses suggest that interferon therapy leads to a decrease in the incidence of HCC. Without a reliable tissue culture system or a small animal model of HCV infection, analysis of the mechanisms by which HCV leads to cancer has been difficult. Nevertheless, both in vitro expression systems and in vivo transgenic mice studies suggest that HCV has an inherent carcinogenic potential. Understanding the pathogenesis of HCV-associated HCC is important in developing effective means of prevention and treatment of this highly malignant form of cancer.

Milich D, Liang TJ. · Vaccine Research Institute of San Diego, San Diego, CA 92109, USA. · Hepatology. · Pubmed #14578844 No free full text.

Abstract: The function of the hepatitis B e antigen (HBeAg) is largely unknown because it is not required for viral assembly, replication, or infection. In this report we chronicle clinical and experimental studies in an attempt to understand the role of HBeAg in natural infection. These studies largely have focused on clinical-pathologic features of HBeAg-negative variants in acute and chronic HBV infection, mutational analysis in animal models of hepadnavirus infection, and the use of transgenic murine models. The clinical and experimental data suggest that serum HBeAg may serve an immunoregulatory role in natural infection. To the contrary, cytosolic HBeAg serves as a target for the inflammatory immune response. These dual roles of the HBeAg and its ability to activate or tolerize T cells show the complexity of the interactions between the HBeAg and the host during HBV infection.

Lau JY, Tam RC, Liang TJ, Hong Z. · Research and Development, ICN Pharmaceuticals Inc., Costa Mesa, CA 92626, USA. · Hepatology. · Pubmed #11981750 No free full text.

This publication has no abstract.

Doo E, Liang TJ. · Liver Diseases Section, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. · Gastroenterology. · Pubmed #11231955 No free full text.

Abstract: Synthesis of the hepatitis B virus (HBV) DNA genome occurs within the viral nucleocapsid in a mechanistically ordered fashion. The nucleocapsid contains small pores that permit influx of nucleotide triphosphates and metabolites of nucleoside analogues such as lamivudine for DNA synthesis. Lamivudine is a potent inhibitor of HBV and human immunodeficiency virus (HIV) reverse transcriptases, but substitutions of isoleucine or valine for methionine within the tyrosine-methionine-aspartate-aspartate (YMDD) motif are associated with virologic and clinical resistance to lamivudine therapy. Under lamivudine selection pressure, the high viral production rate and the low fidelity viral polymerase contribute to frequent development of the YMDD mutants. However, the pattern and dynamics of emergence of the mutant viruses over the wild-type virus are determined by multiple factors including replication efficiency, host immune response, and availability of replication space. Structural modeling of HIV reverse transcriptase has permitted key insights into the molecular basis of lamivudine resistance of HBV based on evolutionary relatedness of HIV and HBV. The side groups of isoleucine and valine of the YMDD mutants sterically prevent lamivudine from appropriately configuring into the nucleotide binding site of the reverse transcriptase. Aminotransferase flares are associated with lamivudine therapy and may signify clinical resistance with emergence of YMDD mutants. They may also herald the recovery phase with seroconversion and viral clearance. Reconstitution of the endogenous anti-HBV immune response may be equally important in the control of viral replication by lamivudine and other nucleoside analogues.

Lechmann M, Liang TJ. · Liver Diseases Section, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1800, USA. · Semin Liver Dis. · Pubmed #10946425 No free full text.

Abstract: Given the global disease burden and public health impact of hepatitis C, the development of an effective vaccine is of paramount importance. However, many challenging obstacles loom ahead of this goal. The hepatitis C virus (HCV), being an RNA virus, can mutate rapidly in adaptation to the environment, thus contributing to the high sequence divergence of multiple viral isolates in the world. The highest heterogeneity has been found in the hypervariable region of the envelope glycoprotein 2, which contains a principal neutralization epitope. HCV also causes persistent infection in a high percentage of immunocompetent hosts despite active immune response. The lack of an efficient tissue culture system for propagating HCV and testing neutralizing antibodies adds further complexity to the task of vaccine development. The immunologic correlates associated with disease progression or protection are yet to be defined, but recent studies suggest that a vigorous multispecific cellular immune response is important in the resolution of infection. Induction of high-titer, long-lasting, and cross-reactive antienvelope antibodies and a vigorous multispecific cellular immune response that includes both helper and cytotoxic T lymphocytes may be necessary for an effective vaccine. Several promising approaches have been used to develop an HCV vaccine. Novel vaccine candidates based on molecular technology such as recombinant proteins, peptides, viruslike particles, naked DNA, and recombinant viruses are being explored. The final vaccine product may require multiple components that target various aspects of protective immunity. Finally, sterilizing immunity may not be necessary if a vaccine can be developed to prevent chronic infection, which is the major cause of morbidity and mortality from this disease.

Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH. · Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1800, USA. · Ann Intern Med. · Pubmed #10681285 links to  free full text

Abstract: Approximately 4 million persons in the United States and probably more than 100 million persons worldwide are infected with hepatitis C virus. The virus has the unique ability to cause persistent infection in susceptible hosts after parenteral or percutaneous transmission, and its underlying mechanisms are not well understood. The immunologic correlates of protection and viral clearance and the pathogenesis of liver injury are yet to be defined, but recent studies suggest the importance of cell-mediated immune responses. Although 70% to 80% of infected persons become chronic carriers, most have relatively mild disease with slow progression. However, chronic and progressive hepatitis C carries significant morbidity and mortality and is a major cause of cirrhosis, end-stage liver disease, and liver cancer. Development of an effective hepatitis C virus vaccine is not imminent, but recent advances in technology and basic knowledge of molecular virology and immunology have engendered novel approaches to the fundamental problems encountered in vaccine development. Current therapy for hepatitis C, although effective in some patients, is problematic and still evolving. Advances in modern biology and immunology promise new therapies for this important disease.

Loomba R, Rowley AK, Wesley R, Smith KG, Liang TJ, Pucino F, Csako G. · Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. · Clin Gastroenterol Hepatol. · Pubmed #18456569 No free full text.

Abstract: BACKGROUND & AIMS: HBV recurrence increases morbidity and mortality in HBsAg+ patients undergoing liver transplantation. We aimed to estimate the relative efficacy of combined therapy with hepatitis B immunoglobulin (HBIG) and lamivudine (LAM) versus HBIG monotherapy for preventing HBV-related morbidity and mortality in this setting. METHODS: We performed a meta-analysis of clinical trials that met the prespecified criteria and provided data for risk estimation of HBV recurrence in HBsAg+ liver transplant patients receiving HBIG and LAM versus HBIG alone. Databases searched until May 2007 included MEDLINE (Ovid), PubMed, Embase, Toxnet, Scopus, and Web of Science. Literature search and data extraction were conducted independently by 2 study investigators; then 2 other investigators reviewed and screened eligible studies. Odds ratios (ORs) for the risk reduction with HBIG and LAM versus HBIG alone were calculated by using a random-effects model. RESULTS: Two prospective and 4 retrospective studies were included in the meta-analysis. The OR showing risk reduction in HBV recurrence with HBIG and LAM (n = 193) versus HBIG alone (n = 124) was 0.08 (95% confidence interval [CI], 0.03-0.21). HBV-related death and all-cause mortality could only be assessed in 3 studies each. The ORs showing HBV-related death and all-cause mortality reduction with HBIG and LAM versus HBIG alone were 0.08 (95% CI, 0.02-0.33) and 0.02 (95% CI, 0.06-0.82), respectively. CONCLUSIONS: Although this meta-analysis was limited by small studies and varying levels of immunosuppression, it is apparent that adding LAM to HBIG improved HBV-related morbidity and mortality in HBsAg+ recipients of liver transplants.

Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, Doo E, Ghany M, Premkumar A, Park Y, Liang TJ, Yanovski JA, Kleiner DE, Hoofnagle JH. · Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. · Hepatology. · Pubmed #14752837 No free full text.

Abstract: Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease for which there is no known effective therapy. A proportion of patients with NASH progress to advanced fibrosis and cirrhosis. NASH is considered one of the clinical features of the metabolic syndrome in which insulin resistance plays a central role. This prospective study evaluates the role of insulin-sensitizing agent in treatment of NASH. Eighteen nondiabetic patients with biopsy-proven NASH were treated with pioglitazone (30 mg daily) for 48 weeks. Tests of insulin sensitivity and body composition as well as liver biopsies were performed before and at the end of treatment. By 48 weeks, serum alanine aminotransferase values fell to normal in 72% of patients. Hepatic fat content and size as determined by magnetic resonance imaging decreased, and glucose and free fatty acid sensitivity to insulin were uniformly improved. Histological features of steatosis, cellular injury, parenchymal inflammation, Mallory bodies, and fibrosis were significantly improved from baseline (all P < 0.05). Using strict criteria, histological improvement occurred in two-thirds of patients. Pioglitazone was well tolerated; the main side effects were weight gain (averaging 4%) and an increase in total body adiposity. In conclusion, these results indicate that treatment with an insulin-sensitizing agent can lead to improvement in biochemical and histological features of NASH and support the role of insulin resistance in the pathogenesis of this disease. The long-term safety and benefits of pioglitazone require further study.

Hoofnagle JH, Ghany MG, Kleiner DE, Doo E, Heller T, Promrat K, Ong J, Khokhar F, Soza A, Herion D, Park Y, Everhart JE, Liang TJ. · Liver Diseases Section, Digestive Diseases Branch, and Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. · Hepatology. · Pubmed #12829988 No free full text.

Abstract: To assess the efficacy and safety of maintenance therapy with ribavirin alone in chronic hepatitis C, 108 patients were treated with the combination of interferon alfa and ribavirin for 24 weeks; those who failed to have a virologic response were offered enrollment in a randomized, double-blind, controlled trial of ribavirin (1,000-1,200 mg daily) versus placebo for the subsequent 48 weeks. Patients were monitored at regular intervals with symptom questionnaires, serum aminotransferase levels, hepatitis C virus (HCV) RNA levels, and complete blood counts and underwent liver biopsy at the completion of therapy. Among 108 patients, 50 were still HCV RNA positive after 24 weeks of treatment, of whom 34 agreed to be randomized to continue either ribavirin monotherapy or placebo. Among 17 patients who received placebo, there was no overall improvement in symptoms, serum alanine aminotransferase (ALT) levels, HCV RNA levels, or hepatic histology. Among the 17 patients who received ribavirin, serum ALT levels and necroinflammatory features of liver histology were improved, whereas symptoms, HCV RNA levels, and hepatic fibrosis scores were not changed significantly from baseline. Responses to ribavirin seemed to be categorical, such that 8 patients (47%) had definite improvement in liver histology. Patients with improved histology had improvements in serum ALT levels both on combination therapy and after switching to ribavirin monotherapy. In conclusion, continuation of ribavirin monotherapy may maintain serum biochemical improvements that occur during interferon-ribavirin combination therapy in some patients and that these improvements are often associated with decreases in necroinflammatory changes in the liver. Whether these improvements will ultimately result in prevention of progression of hepatitis C requires further study.