Management Of Chronic Hepatitis Research Articles

SASLT practice guidelines: Management of hepatitis C virus infection

This guideline has been approved by the Saudi Association for the Study of Liver diseases and Transplantation and represents the position of the Association. These practice guidelines have been written to assist physicians and other health care providers to aid in the recognition, diagnosis, and management of chronically infected hepatitis C virus (HCV) patients. They are based on a formal review and analysis of published literature on the topic that impact the management of chronic HCV infection, and the experience of the authors in hepatitis C. In addition, various international practice guidelines and consensus documents on management of chronic hepatitis C were considered in the development of these guidelines. The recommendations contained herein suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care related to the disease. Our understanding of the natural history of HCV infection and the potential for therapy of the resultant disease is continuously improving. However, despite the increasing knowledge, areas of uncertainty still exist and therefore clinicians, patients, and public health authorities must continue to make choices on the basis of the evolving evidence. Therefore, these guidelines are intended to be flexible and may be updated periodically as new information becomes available.

Towards the eradication of hepatitis C virus

The 5th Paris Hepatitis Conference (PHC) held on January 30 and 31, 2012, is a special edition dedicated to the management of patients with hepatitis C. This supplement of Liver International includes review articles on the most up-to-date information on the clinical care of these patients, which was presented at this conference. Spectacular progress has recently been made in the management of chronic hepatitis C. The results of phase 3 studies of triple therapy with first generation protease inhibitors, telaprevir or boceprevir, in treatment-naïve and treatment-experienced patients with hepatitis C virus (HCV) genotype 1 chronic infection have shown that these triple therapies improve treatment efficacy by approximately 30% with sustained virological response (SVR) rates of 70%. We know that SVR means eradication of viral infection. In addition, more than half of the patients – those with a rapid virological response – may benefit from a shorter duration of therapy (24 instead of 48 weeks). The safety profile of these triple therapies is comparable to the profile of combination pegylated interferon (PEG-IFN) and ribavirin (RBV) with, however, an increased incidence of generally moderate and reversible, rash, dysgueusia and anaemia. Thus, triple therapy has now become the new standard of care in this population of patients. However, many questions remain: What are the indications of triple therapy? Is there still a role for conventional treatment with pegylated interferon and ribavirin? What are the predictors of response to triple therapy? How should patients be monitored to optimize treatment and prevent resistance? How should side effects be managed? All these questions have been addressed in the articles in this supplement to provide clinicians with guidelines to optimize the use of triple therapy. Current triple therapy is targeted to HCV genotype 1. However, in many countries, there are large, sometimes highly predominant, populations infected with HCV non-1 genotypes. Indeed, throughout the world, most patients are infected with non-1 genotypes. Thus, several reviews in the supplement discuss the optimal management of patients infected with genotypes 2, 3 or 4. Treatment of hepatitis C is evolving rapidly. Many new direct antiviral agents (DAA) are under evaluation, and the results of DAA combinations have been spectacular in genotype 1 as well as other genotypes. Schematically, four classes of DAA are now under evalu-ation: protease inhibitors, non-nucleoside polymerase inhibitors, nucleoside polymerase inhibitors and NS5a inhibitors. Interestingly, these different classes of DAA have different antiviral targets and different properties. More importantly, they have synergistic effects, and preliminary studies have shown that combinations of these molecules improve antiviral efficacy, decrease the risk of resistance and are effective in different genotypes with a good safety profile. These preliminary data strongly suggest that these combinations will completely change the paradigm of HCV therapy. We are convinced that in the near future, safe combinations of oral DAA, administered for a short duration (1–3 months), will eradicate HCV infection, whatever the genotype, in almost all patients. Hopefully, these therapies will be available at a reasonable cost worldwide to cure all patients with this disease. Both Guest Editors are speakers and investigators for BMS, Boehring-Ingelheim, Tibotec, Janssen, Gilead, Roche and Merck.

Staging Liver Fibrosis in Hepatitis C: A Challenge for This Decade

The limitations of and the invasive nature of liver biopsy has spurred extensive interest in the development of non-invasive tests to measure liver fibrosis in patients with chronic hepatitis C. Clinically applicable non-invasive tests, including radiological studies, elastography, and serum markers, all of which perform extremely well in excluding significant disease and diagnosing cirrhosis. FibroScan and acoustic radiation force impulse elastography are two elastography-based tests that show promise. In this new era of increased cure rates with newly Food and Drug Administration-approved drugs and the availability of multiple non-invasive tests of liver fibrosis, we anticipate a decreasing need for liver biopsies in the management of chronic hepatitis C.

The COBAS® TaqMan® hepatitis C virus assays: automated systems for accurate and sensitive viral load quantification

In recent years, the real time-based TaqMan® technology has allowed the development of highly sensitive hepatitis viral load tests with broad dynamic ranges. The increasing applications of these tests in clinical diagnostics have shown the utility of viral load as a predictive marker of treatment response and proven its key role in invidualized antiviral therapies. Future refinement in viral load assays, including higher sensitivity, genotype inclusivity, standardization and automation, will further foster the concept of personalized healthcare in the clinical management of chronic hepatitis C.

Cost-Effectiveness Assessment of Telaprevir Combination Treatment Compared to Pegylated-Interferon+Ribavirin Alone in the Management of Chronic Hepatitis C in Treatment-naïve Patients

Purpose: The addition of telaprevir (T) to the combination of peginterferon alfa-2a/ribavirin (PR) for the treatment of genotype 1 chronic HCV in treatment-naïve patients substantially increased SVR compared to PR alone in the Phase 3 pivotal study ADVANCE. Based on this improvement in SVR rates, an Excel®-based decision-analytic model was developed to explore the potential long-term clinical and economic consequences of telaprevir combination treatment in treatment-naïve patients. Methods: A two-part (Treatment; Post-treatment) model was developed to project incremental clinical and economic consequences of T/PR versus PR alone treatment options. For Treatment, parallel hypothetical cohorts of 1,000 patients were generated and assigned to one of the treatment options. Based on intention-to-treat SVR rates from the ADVANCE trial, a proportion of each cohort was deemed to achieve SVR. Cohorts were directed into the Post-treatment part where long-term treatment consequences and associated economic implications were estimated for remaining lifetimes using a cyclic Markov process. In any cycle, patients could remain in or transition among health states: absence of cirrhosis, cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and death. Baseline patient characteristics and SVR rates by baseline fibrosis scores were based on ADVANCE data. Age- and gender-specific health state transition probabilities, which varied with achievement of SVR, mortality, health state utilities, and cost data were obtained from published sources. The perspective of the analysis was that of a third-party payor. Results: The model projected an improvement in life expectancy and qualityadjusted life-years (QALYs) with T/PR treatment versus PR over the lifetime of the patient mainly due to reductions in HCV-related complications (20.1 LYs and 17.2 QALYs versus 19.3 LYs and 16.0 QALYs, respectively). While T/PR treatment was estimated to increase the treatment costs, most of this increase was offset by a reduction in the costs of the management of long-term complications: additional per patient cost associated with T/PR was ˜$16,000 over the patient's lifetime compared to PR alone. Estimated incremental cost-effectiveness ratios in this patient population were $13,500/QALYs and ˜$19,500/LYsgained. Conclusion: Modeling results suggested that telaprevir combination treatment is a cost-effective treatment strategy compared to peginterferon alfa-2a/ribavirin alone in treatment-naïve patients. The cost-effectiveness of telaprevir combination treatment was well within the limits of conventional willingness-to-pay thresholds in the U.S. Disclosure: Mr Deniz is an employee and stock holder of Vertex Pharmaceuticals, Dr. Brogan, Mr. Miller, Ms. Talbird and Mr. Thompson are employees of RTI Health Solutions. This research was performed by RTI Health Solutions and funded by Vertex Pharmaceuticals Incorporated.

Management of Chronic Hepatitis B in Special Populations: Immunosuppressed Patients and Chronic Kidney Disease

Hepatitis B virus (HBV) infection remains an important cause of liver disease in the population with chronic kidney disease, including patients on long-term dialysis and renal transplant (RT) recipients. Diminished survival due to hepatitis B has been observed after RT. A thorough evaluation, including liver biopsy as well as assessment of serum markers of HBV replication (ie, hepatitis B e antigen and/or HBV DNA) is required before transplantation. Tolerance to interferon is poor both in dialysis patients and after renal transplant. Oral antiviral therapy now permits safe and potent antiviral treatment of HBV-related liver disease in chronic kidney disease patients with prevention of progressive liver disease. Preliminary evidence shows an improved survival of HBsAg positive renal allograft recipients on antiviral therapy. However, numerous issues concerning the treatment of hepatitis B in the population with chronic kidney disease remain unclear and further clinical trials are needed.

A review of chronic hepatitis B epidemiology and management issues in selected countries in the Middle East

Experts from seven countries convened as a Specialist Panel for the Middle East to share information on practical issues relating to the epidemiology, diagnosis and management of chronic hepatitis B (CHB) infection. The Middle East is regarded as a region of high-to-intermediate epidemicity; however, infant vaccination programmes have successfully lowered the prevalence of hepatitis B infection in most countries to that of low-to-intermediate endemicity. Vaccine issues still to be addressed included improving coverage in some rural/poor communities, instituting hepatitis B vaccine at birth and providing vaccines for high-risk population groups. Hepatitis B infection in the Middle East primarily occurs as a result of perinatal infection, horizontal transmission between family members and transmission from injections. Blood transfusion services have broadly efficient screening programmes, but immunocompromised and haemodialysis patients are at risk. The cost of screening, monitoring and treating CHB influences practice in a number of Middle East countries, and there is a need for information on the most cost-effective options.

Recent Advances in the Management of Chronic Hepatitis B

There are seven approved treatments for adults with chronic hepatitis B virus infection in the United States and European countries: interferon-α, pegylated interferon-α, lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate. At present, two new analogues, entecavir and tenofovir are recommended as the first line therapy by the guidelines of European Association for the Study of the Liver and American Association Study for the Liver Diseases. On the other hand, regarding interferon therapy, use of pegylated interferon-α is recommended as the first line therapy instead of standard interferon-α by both guidelines. Therefore, the main scientific interests and unmet medical needs for treatment of chronic hepatitis B have been narrowed down to long-term efficacy and safety of the two said analogues-entecavir and tenofovir-and combination therapy of pegylated interferon-α with the two analogues. To put it concretely, further studies are needed to assess (1) the long-term efficacy and safety and resistance to entecavir and tenofovir; (2) the efficacy of different durations (24 weeks to 2 years) and lower doses of pegylated interferon-α; (3) the role of combination therapy with two analogues to reduce resistance; and (4) the efficacy and safety of the two analogues with decompensated cirrhosis. Herein, we review the recent available data and results.

Current management and recommendations on hepatitis B therapy in HIV-coinfected patients

The match between the real-life therapeutic management of chronic hepatitis B (CHB) in HIV-infected patients and the recommendations that existed at the time has never been assessed on a case-by-case basis. A total of 73 HBV-HIV coinfected patients, 34 of whom were first followed in 2003-2005 and 39 in 2006-2008 (before and after the 2005 European Consensus Conference on the treatment of chronic viral hepatitis in HIV coinfected patients), were included. All the data were retrospectively collected from their first visit to October 2008 through a standardised questionnaire. Baseline HBV DNA quantification and/or liver histology were missing in 44.1 and 28.2% of cases before and after 2005, respectively (p=0.16). The observed management significantly differed from the recommendations for the whole population (p=0.009), for the 2003-2005 group (p=0.02), and tended to differ for the 2006-2008 group (p=0.07). Therapeutic management of CHB was in accordance with the recommendations in 27 (57.4%) cases, with a higher rate of untreated patients in the 2003-2005 group, and a high rate of patients on dual therapy in both groups despite the fact that HBV therapy was not recommended. Even though global management of HBV-HIV coinfected patients is improving, baseline evaluation of CHB though necessary is still often insufficient. The strong rationale for early dual anti-HIV and anti-HBV therapy, and the reality of everyday clinical practice, bring support to the recent simplification of the recommendations widening the use of tenofovir and emtricitabine in HBV-HIV coinfected patients, irrespective of immunological, virological, or histological considerations.

Current understanding of insulin resistance in hepatitis C

Important breakthroughs have been made in recent years into understanding the close interaction between hepatitis C virus (HCV) infection and glucose homeostasis. Both cross-sectional and longitudinal studies have demonstrated that infection with HCV is associated with an increased risk of developing insulin resistance and Type 2 diabetes. A direct effect of HCV on hepatocyte insulin signaling has been shown in experimental models. Some preliminary observations seem to suggest that indirect mechanisms involving extrahepatic organs might also play a role. The interaction between HCV and glucose metabolism has significant clinical consequences. Insulin resistance and Type 2 diabetes not only accelerate the histological and clinical progression of chronic hepatitis C, but also reduce the virological response to IFN-α-based therapy. Thus, understanding the mechanisms underlying HCV-associated glucose metabolism derangements is of paramount interest in order to improve the clinical management of chronic hepatitis C. This article will focus on the studies that consistently argue in favor of an interrelation between HCV and insulin resistance and will highlight the latest discoveries in this field.

The use of transient elastography in the management of chronic hepatitis B

There has been increasing interest in noninvasive methods of assessing liver fibrosis over the last decade. The use of transient elastography in measuring liver stiffness has become the forefront of a wide range of noninvasive tools. Most of the other methods are based on measurements of biomarkers associated with fibrosis. There are several reasons for its wide acceptance, including the ease of performing a scan, the short procedure time, the results being immediately available on completion of the examination, and its reproducibility. For chronic hepatitis B (CHB), the cut-off values for F3 and F4 fibrosis range between 7.5–12.0 and 11.0–13.4 kPa, respectively, although the cut-offs may be slightly lower in those with normal ALT. In addition to measuring liver fibrosis, recent studies have demonstrated several other roles for transient elastography, including selecting patients who will benefit from antiviral therapy, monitoring response to antiviral therapy, and predicting long-term outcomes. However, there are limitations associated with transient elastography, including the confounding effects of inflammatory activity, and to a lesser extent, steatosis, on liver stiffness. There is also reduced accuracy observed in lower fibrosis stages (F0–F2). Furthermore, the incidences of failed and unreliable scan have been reported to be ~ 3 and 16%, respectively. Although liver biopsy can be avoided in an estimated 50–60% using transient elastography, in situations where liver stiffness measurement is nondiagnostic or inconsistent with the clinical picture, a biopsy is still recommended. Further studies are needed to consolidate the role of transient elastography in the management of CHB, and for incorporation of this method into current treatment guidelines.

Tenofovir disoproxil fumarate for the treatment of chronic hepatitis B monoinfection

Resistance in nucleoside/nucleotide analog (NA) therapy has always been a challenge in the management of chronic hepatitis B (CHB). Initially developed for the treatment of HIV infection, early in vitro and clinical observational studies had shown tenofovir disoproxil fumarate (TDF) to be also active against CHB. Recent data from various multicenter phase 3 and 4 clinical trials have confirmed TDF being able to achieve a high viral suppression in both NA-naive and -experienced CHB patients. There are also emerging data on the efficacy of TDF in decompensated CHB. Although there are in vitro studies identifying certain mutation loci associated with a reduced susceptibility to TDF, there have so far been no reports of virologic resistance to TDF in clinical studies. TDF has a favorable safety profile, although more long-term data would be needed. TDF has the makings of an "ideal" first-line drug for the treatment of CHB.

Long term experience using tenofovir and entecavir in the management of chronic hepatitis B in teaching hospital practice

IntroductionIn the first 12 months of treatment for chronic hepatitis B (CHB) infection tenofovir and entecavir have been reported as the most potent antiviral agents for HepBeAg-positive patients; tenofovir is...

Is there a role for MICA in ulcerative colitis?

on the management of chronic hepatitis B: a 2008 update. Hepatol. Int. 2008; 3: 263–83. 4 Wong VW, Wong GL, Yan KK et al. Durability of peginterferon alfa-2b treatment at 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology 2010; 51: 1945–53. 5 Song BC, Suh DJ, Lee HC, Chung YH, Lee YS. Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea. Hepatology 2000; 32: 803–6. 6 Chien RN, Yeh CT, Tsai SL, Chu CM, Liaw YF. Determinants for sustained HBeAg response to lamivudine therapy. Hepatology 2003; 38: 1267–73. 7 Byun KS, Kwon OS, Kim JH et al. Factors related to post-treatment relapse in chronic hepatitis B patients who lost HBeAg after lamivudine therapy. J. Gastroenterol. Hepatol. 2005; 20: 1838–42. 8 Lee HW, Lee HJ, Hwang JS et al. Lamivudine maintenance beyond one year after HBeAg seroconversion is a major factor for sustained virologic response in HBeAg-positive chronic hepatitis B. Hepatology 2010; 51: 415–21. 9 Wang L, Liu F, Liu YD et al. Stringent cessation criterion results in better durability of lamivudine treatment: a prospective clinical study in hepatitis B e antigen-positive chronic hepatitis B patients. J. Viral Hepat. 2010; 17: 298–304. 10 Fung J, Lai CL, Tanaka Y et al. The duration of lamivudine therapy for chronic hepatitis B: cessation vs. continuation of treatment after HBeAg seroconversion. Am. J. Gastroenterol. 2009; 104: 1940–6; quiz 1947. 11 Ryu SH, Chung YH, Choi MH et al. Long-term additional lamivudine therapy enhances durability of lamivudine-induced HBeAg loss: a prospective study. J. Hepatol. 2003; 39: 614–19. 12 Liu F, Wang L, Li XY et al. Poor durability of lamivudine effectiveness despite stringent cessation criterion: a propsective clinical study in HBeAg-negative chronic hepatitis B. J. Gastroenterol. Hepatol. 2011; 26: 456–60. 13 Shouval D, Lai CL, Chang TT et al. Relapse of hepatitis B in HBeAg-negative chronic hepatitis B patients who discontinued successful entecavir treatment: the case for continuous antiviral therapy. J. Hepatol. 2009; 50: 289–95. 14 Chen CJ, Yang HI, Su J et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006; 295: 65–73. 15 Chen G, Lin W, Shen F, Iloeje UH, London WT, Evans AA. Past HBV viral load as predictor of mortality and morbidity from HCC and chronic liver disease in a prospective study. Am. J. Gastroenterol. 2006; 101: 1797–803. 16 Yuen MF, Tanaka Y, Fong DY et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J. Hepatol. 2009; 50: 80–8. 17 Reijnders JG, Perquin MJ, Zhang N, Hansen BE, Janssen HL. Nucleos(t)ide analogues only induce temporary hepatitis B e antigen seroconversion in most patients with chronic hepatitis B. Gastroenterology 2010; 139: 491–8.

Antiviral drugs for HBV liver disease

Introduction: Chronic hepatitis B (CHB) virus infection affects about 400 million people around the globe and is among the world's leading causes of death. The management of CHB has evolved rapidly, several therapeutic options are now available to prevent both progression of liver disease and anticipated liver morbidity and mortality.Areas covered: Current treatment modalities for CHB patients, together with suggestions from our own experience are summarized. The most relevant works published in recent years on pegylated interferon, nucleos(t)ides analogues (NUC) and the 2009 update of the American Association for the Study of Liver Diseases Practice Guidelines and the 2009 European Association for the Study of the Liver (EASL) Clinical Practice Guidelines on the management of chronic hepatitis B are discussed.Expert opinion: Pegylated interferon and NUC have advantages and limitations, as short-term interferon treatment induces a sustained virological response in a third of patients, whereas long-term suppressive therapy by NUC rapidly inhibits HBV replication in most patients but drug resistance and safety in the long-term will remain the most important unresolved questions. Careful evaluation of patient history, staging of liver disease and virological factors should guide the start of treatment and the choice to the most appropriate individualized treatment strategy in all CHB patients.

Pegylated Interferon and Ribavirin for the Treatment of Chronic Hepatitis C

The management of chronic hepatitis C (CHC) is a rapidly evolving field. New treatment paradigms are emerging due to an improved understanding of the host-viral interaction and the recent development of novel anti-viral therapies. Nevertheless, combination therapy with pegylated interferon (PEG-IFN) and ribarivin (RBV) remains the cornerstone of the treatment of CHC and will likely remain so for the foreseeable future. Over the past decade treatment regimens involving peginterferon plus ribavirin therapy have evolved from initial fixed dosing schedules to more recent individualized response-guided schedules that utilize on-treatment virological responses to determine treatment duration. The future of CHC treatment in the near to medium term is likely to involve the use of PEG-IFN and RBV in conjunction with potent and specific direct acting anti-viral agents (DAA) (protease +/- polymerase inhibitors). This review will focus on the use of PEG-IFN and RBV in the treatment of CHC as well as provide insight into how DAA agents may be used with this therapy as we enter the era of specifically targeted antiviral therapy for HCV.

Management of chronic hepatitis B

Hepatitis B virus (HBV) is the most important cause of chronic liver disease and hepatocellular carcinoma in India. During the past three decades, considerable advances in the diagnosis and treatment of HBV infection have been achieved. However, despite the remarkable improvements, medical management for HBV induced cirrhosis, and liver cancer remains unsatisfactory. In fact, it is becoming increasingly clear that as of now, there is no cure for hepatitis B infection. Management of chronic hepatitis B has changed considerably; currently, emphasis is in identifying and treating patients at high risk of disease progression since effective antiviral therapy arrests disease progression, reduces complications and can potentially reverse liver damage if given for sufficient duration. The treatment should be initiated with drugs that have high potency and high genetic barrier to resistance, and compliance should be ensured once decision to treat is initiated. Resistant patients are difficult to treat and preferably combination treatment with high potency and high genetic barrier drugs should be used to avoid treatment failure. Close monitoring of both treated and untreated patients for disease progression should be done, and early intervention is required to prevent complications in those who show progression over time.

Natural History of Hepatitis B Virus (HBV) Infection

hepatitis B is a global health burden and increasingly a public health concerns in US due to changing immigration pattern from mostly Western European immigrants to Asian, African and Eastern European where prevalence of chronic hepatitis B is higher. Therefore in these particular at risk populations, education of health providers and patients is vital in achieving successful disease prevention and control. Understanding the natural history of this complicated and dynamic disease will lay the ground works for comprehensive management of chronic hepatitis B. In this article, the natural history particularly the four phases of chronic hepatitis B and the outcome of the disease such as cirrhosis and HCC and the risk factors for disease progression and HCC development will be discussed. The importance of screening and vaccination is emphasized particularly the success of HCC prevention in countries with population-wide vaccination program. It is with the hope that this review will enhance and educate the primary health provider for the most at risk population of chronic hepatitis B in US and therefore alleviate the burden of this disease. with a solid knowledge of hepatitis B. The natural history of chronic hepatitis B has been studied extensively since the early 1980's even before the molecular technology of PCR (Polymerase Chain Reaction) became widely used in the study of hepatitis B. It is now clearly understood that the natural history of chronic hepatitis B represents a dynamic interaction between the host immune system and the virus. This makes the natural progression of chronic hepatitis B a very fluid situation. In this review, I will discuss the dynamic natural history of chronic HBV infection and identify factors that have been associated with disease progression and the development of hepatocellular carcinoma (HCC) and further to discuss disease prevention and control for this dreadful but preventable disease burden on Chinese community in US.

Newer molecules and new hopes in the management of chronic hepatitis C

Chronic hepatitis C is highly prevalent with prevalence rate of around 3% involving about 180 million people worldwide, despite major advances in its understanding of viral 1 pathogenesis and significant evolution in antiviral therapies. Most of the patients develop chronic infection because the virus evades the host immune response in majority of patients. Chronic HCV infection can lead to cirrhosis and hepatocellular carcinoma. Complications of HCV-related cirrhosis are the leading indication for liver transplantation in United States and Europe...... J Med Sci 2010;13(2): 39-40.

New Horizons and Perspectives in the Management of Chronic Hepatitis C

Hepatitis-C virus (HCV) infects 170 million people, 1 with worldwide sero prevalence of around 3%. Most of the patients develop chronic infection because the virus evades the host immune response in 55-85% of patients. Chronic HCV infection can lead to cirrhosis and hepato-cellular carcinoma. Complications of HCV-related cirrhosis are the leading indication for liver transplantation in United States and Europe... J Med Sci 2010;13(2):41-47