Management Of Chronic Hepatitis Research Articles

Current recommendations of managing HBV infection in preconception or pregnancy.

Hepatitis B remains a leading cause of cirrhosis, hepatocellular carcinoma and liver transplantation worldwide. Management of chronic hepatitis B during pregnancy is challenging. Transmission of hepatitis B to infants still occurs perinatally although immunoprophylaxis is widely available for infants born to mothers with chronic hepatitis B infection. The emerging data suggest that initiation of antiviral therapy in the beginning of the third trimester in highly viremic mothers can prevent immunoprophylaxis failure in their infants. The available drug safety data show that lamivudine, telbivudine and tenofovir are generally safe to be used during the pregnancy. In order to minimize the fetal exposure to the antiviral medication, antiviral therapy during the pregnancy should be limited to a selected group of patients with cirrhosis, high hepatitis B viral load, or prior history immunoprophylaxis failure. An elective Caesarean section may reduce the risk of perinatal transmission. For those females planning for pregnancy or in early stage of pregnancy, communication and follow-up among obstetrician, gastroenterologist, and primary care physician are important. In this article, we will review the features of hepatitis B infection before, during and after the pregnancy; the risk factors that increase mother-to-child transmission; safety data on antiviral drug use during pregnancy; and the potential role of Caesarean section in selected cases.

Management of chronic hepatitis B in children: an unresolved issue.

Although a rather benign course of chronic hepatitis B virus (HBV) infection during childhood has been described, 3-5% and 0.01-0.03% of chronic carriers develop cirrhosis or hepatocellular carcinoma before adulthood. Considering the whole lifetime, the risk of hepatocellular carcinoma rises to 9-24% and the incidence of cirrhosis to 2-3% per year. The aim of this article is to review the current knowledge regarding the natural history and treatment of chronic hepatitis B in children and to focus on critical aspects and unresolved questions in the management of childhood HBV infection. A literature search was carried out on MEDLINE, EMBASE, and Web of Science for articles published in English in peer-reviewed journals from January 1980 to February 2013. The search terms used included "Hepatitis B virus infection," "children," "HBV," "interferon," "lamivudine," "adefovir," "entecavir," and "tenofovir." Articles resulting from these searches and relevant references cited in the articles retrieved were reviewed. The current goals of therapy are to suppress viral replication, reduce liver inflammation, and reverse liver fibrosis. Therapeutic options for children are currently limited, and the risk for viral resistance to current and future therapies is a particular concern. Based on the data available at this time, it is the consensus of the panel that it is not appropriate to treat children in the immune-tolerant phase or in the inactive carrier state. For children in the immune-active or reactivation phases, liver histology can help guide treatment decisions. Outside of clinical trials, interferon is the agent of choice in most cases; currently, available nucleoside analogs are secondary therapies.

A Novel Fibrosis Index Comprising a Non-Cholesterol Sterol Accurately Predicts HCV-Related Liver Cirrhosis

Diagnosis of liver cirrhosis is essential in the management of chronic hepatitis C virus (HCV) infection. Liver biopsy is invasive and thus entails a risk of complications as well as a potential risk of sampling error. Therefore, non-invasive diagnostic tools are preferential. The aim of the present study was to create a model for accurate prediction of liver cirrhosis based on patient characteristics and biomarkers of liver fibrosis, including a panel of non-cholesterol sterols reflecting cholesterol synthesis and absorption and secretion. We evaluated variables with potential predictive significance for liver fibrosis in 278 patients originally included in a multicenter phase III treatment trial for chronic HCV infection. A stepwise multivariate logistic model selection was performed with liver cirrhosis, defined as Ishak fibrosis stage 5–6, as the outcome variable. A new index, referred to as Nordic Liver Index (NoLI) in the paper, was based on the model: Log-odds (predicting cirrhosis) = −12.17+ (age×0.11) + (BMI (kg/m2)×0.23) + (D7-lathosterol (μg/100 mg cholesterol)×(−0.013)) + (Platelet count (x109/L)×(−0.018)) + (Prothrombin-INR×3.69). The area under the ROC curve (AUROC) for prediction of cirrhosis was 0.91 (95% CI 0.86–0.96). The index was validated in a separate cohort of 83 patients and the AUROC for this cohort was similar (0.90; 95% CI: 0.82–0.98). In conclusion, the new index may complement other methods in diagnosing cirrhosis in patients with chronic HCV infection.

Management of chronic hepatitis C (Chc) genotype 1 treatment-naïve patients in an era of rising opportunities and costs: A cost-effectiveness analysis

Management of chronic hepatitis C (Chc) genotype 1 treatment-naïve patients in an era of rising opportunities and costs: A cost-effectiveness analysis

Clinical outcomes in a cohort of anti-hepatitis C virus-positive patients with significant barriers to treatment referred to a Norwegian outpatient clinic

Objective. Patient selection and management of chronic hepatitis C (CHC) in Norwegian outpatient clinics is not well studied. The aim of the study was to characterize CHC patients referred to a large university hospital in Norway, identify treatment barriers, and investigate the course and outcomes of treatment. Material and methods. In this retrospective observational cohort study, all anti-HCV-positive patients referred to Haukeland University Hospital, Bergen, for treatment evaluation during the period 2007–2010 were included. Demographics, clinical, laboratory, and treatment results were obtained from electronic medical records. Results. A total of 256 patients were included. The patients were young (mean age 36 ± 10.3), with a high prevalence of genotypes 3 (55%) and 1 (43%) and low levels of fibrosis (77% <F2). The majority of patients were former or current injection drug users (85%). Treatment uptake among patients attending the clinic was 47% (n = 91). Treatment was significantly less common in patients who were unemployed, those who had nonattendances during clinical evaluation, those with genotypes 1 or 4, those ≥50 years of age, and patients with no biopsy. For patients initiating treatment, the total sustained virologic response (SVR) rate was 63% (by complete case analysis 73%). For genotypes 1 and 3, SVR was achieved in 44% and 75%, respectively, by intention to treat. Conclusions. A high treatment uptake of CHC patients in a cohort with high prevalence of injection drug use was found. Young age, low degrees of fibrosis, and good patient attendance ensured a high rate of SVR.

What physicians should know about the management of chronic hepatitis B in children: East side story.

Understanding the natural course of chronic hepatitis B virus (HBV) infection is very important for the management and treatment of chronic hepatitis B in children. Based on treatment guidelines, the management of HBV carriers and treatment of active hepatitis have been advancing and resulted in increased survival, as well as decreased risks of complications such as liver cirrhosis and hepatocellular carcinoma. Development of a continuing medical education (CME) program for primary physicians becomes an important responsibility of pediatric hepatologists. CME could prevent misdiagnosis and unnecessary treatment that could lead to liver complications or antiviral resistance. In addition, education of patients and their parents is necessary to achieve better therapeutic outcomes.

Management of chronic hepatitis B infection: current treatment guidelines, challenges, and new developments.

Chronic hepatitis B (CHB) virus infection is a global public health problem, affecting more than 400 million people worldwide. The clinical spectrum is wide, ranging from a subclinical inactive carrier state, to progressive chronic hepatitis, cirrhosis, decompensation, and hepatocellular carcinoma. However, complications of hepatitis B virus (HBV)-related chronic liver disease may be reduced by viral suppression. Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon, entecavir, or tenofovir, but the optimal treatment for an individual patient is controversial. The indications for treatment are contentious, and increasing evidence suggests that HBV genotyping, as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response. The likelihood of achieving a sustained virological response is also increased by extending treatment duration, and using combination therapy. Hence the paradigm for treatment of CHB is constantly evolving. This article summarizes the different indications for treatment, and systematically reviews the evidence for the efficacy of various antiviral agents. It further discusses the shortcomings of current guidelines, use of rescue therapy in drug-resistant strains of HBV, and highlights the promising clinical trials for emerging therapies in the pipeline. This concise overview presents an updated practical approach to guide the clinical management of CHB.

Non-invasive methods for the assessment of hepatic fibrosis: transient elastography, hyaluronic acid, 13C-aminopyrine breath test and cytokeratin 18 fragment

Background. In the management of chronic hepatitis C (CHC) patients, liver biopsy is the gold standard for liver fibrosis assessment despite some technical limits and risks. Non-invasive approaches have been proposed as alternative methods to evaluate structural liver damage.Aim. To investigate the diagnostic accuracy of transient elastography, 13C-aminopyrine breath test (13C-ABT), serum hyaluronic acid (HA) and cytokeratin 18 Asp396 fragment (CK-18) as non-invasive methods of liver fibrosis assessment ad their correlation to METAVIR score.Material and methods. In a cohort of 57 CHC patients, liver stiffness, cumulative percentage of administered dose of 13C-aminopyrine at 120 min, serum HA and serum CK-18 concentration were determined. Diagnostic accuracy in detecting significant fibrosis (F ≥ 2), severe fibrosis (F ≥ 3) and cirrhosis (F = 4) was assessed by the area under the receiver operating characteristic curve.Results. Liver fibrosis score showed a strong correlation with liver stiffness (r = 0.667; p < 0.0001) and a significant inverse correlation with 13C-ABT results (r = -0.418; p = 0.0012). A weaker correlation was found with CK18 (r = 0.329; p = 0.0126) and no correlation with HA. Areas under the curve of elastography, 13C-ABT, HA and CK18 were: 0.98, 0.75, 0.69, 0.64, respectively, for F ≥ 2; 0.97, 0.69, 0.80, 0.66, respectively, for F ≥ 3; 0.95, 0.64, 0.70, 0.56, respectively, for F = 4.Conclusion. Elastography has the best diagnostic accuracy for the assessment of the degree of liver fibrosis in CHC patients. Its application can provide an alternative useful tool for monitoring the disease evolution.

Management of chronic hepatitis B in severe liver disease.

In the past few decades, chronic hepatitis B (CHB) has evolved from a disease that was untreatable and progressive, to one that can be easily controlled with antiviral therapy. However, patients with severe liver disease still remain difficult to treat despite the availability of highly potent nucleos(t)ide analogs. These include those with underlying cirrhosis, severe flares of CHB, hepatocellular carcinoma (HCC), and for those undergoing liver transplantation. For those with established cirrhosis, antiviral therapy should be considered for all, as unpredictable flares can still occur, which can be fatal for those with advanced chronic liver disease. However, even with effective viral suppression, the development of HCC can still occur. For patients with severe flares of CHB, although the use of antiviral can improve long term outcomes, a significant proportion may still die without liver transplantation. The short term prognosis of these patients is dependent on both the severity of flare and underlying pre-existing liver disease. In patients with decompensated cirrhosis, liver failure secondary to severe flares, or those with HCC, liver transplantation may be curative. After liver transplantation, long term antiviral therapy is required to prevent graft loss from recurrent hepatitis B infection. The use of hepatitis B immune globulin (HBIG) in combination with an oral antiviral agent has been the mainstay of post-transplant antiviral regimen for over a decade. With newer and more potent antiviral agents such as tenofovir and entecavir, use of these agents along with HBIG have demonstrated to be effective in preventing significant recurrence in the long term.

Serum hepatitis B surface antigen levels predict treatment response to nucleos(t)ide analogues.

Quantification of hepatitis B surface antigen (HBsAg) has been suggested to be helpful in the management of chronic hepatitis B (CHB) patients. Nucleos(t)ide analogs (NAs) are the therapy of choice for CHB and are used in the majority of CHB patients. NAs are able to induce hepatitis B virus (HBV) viral suppression, normalization of alanine aminotransferase (ALT) levels, and improvement in liver histology. Automated quantitative assays for serum HBsAg have recently become available, facilitating standardized quantification of serum HBsAg. This has led to increased interest in the clinical application of quantitative serum HBsAg for predicting therapeutic response to NAs. Recent studies have shown that a decline in serum HBsAg levels in patients receiving peginterferon may signal successful induction of immune control over HBV, and can therefore be used to predict therapeutic response. NA treatment typically induces a less rapid decline in HBsAg than interferon treatment; it has been estimated that full HBsAg clearance can require decades of NA treatment. However, a rapid HBsAg decline during NA therapy may identify patients who will show clearance of HBsAg. Currently, there is no consensus on the clinical utility of serum HBsAg monitoring for evaluating patient responses to NA therapy. This review focuses on recent findings regarding the potential application of HBsAg quantification in the management of CHB patients receiving NA therapy.

Prolonged Combination Therapy is More Effective than Monotherapy in Management of Chronic Hepatitis B Patients With Sustained Virological Response: An Experience From a ‘Real-World’ Clinical Setting

Background:Little is known about the duration of combination therapy for patients with chronic hepatitis B (CHB) and suboptimal response to nucleos(t)ide analogues(NAs) monotherapy.Objectives:This study aimed to assess whether monotherapy could be used for treatment of CHB patients, who poorly responded to Adefovir Dipivoxil (ADV) but obtained good responses after at least 12-month lamivudine (LAM) or telbivudine (LdT) add-on therapy.Patients and Methods:Forty-five patients were enrolled, and the baseline time-point was determined according to enrollment data. Twenty-six patients chose to continue combination therapy (LAM+ADV or LdT+ADV, Group A) and 19 patients switched to single-drug maintenance therapy (LAM or LdT or ADV, Group B).Results:There were no significant differences between two groups in baseline characteristics (P > 0.05). At 12th month, sustained virological response rate was greater in group A compared to group B (96.2% vs. 47.4%, P < 0.001), and the rates of NAs-associated resistance were 0% in group A and 15.8% in group B. Alanine aminotransferase normalization rate was also significantly higher in group A compared with group B (92.3% vs. 36.8%, P < 0.001). Among hepatitis positive patients with Be antigen (HBeAg)-, 40% (4/10) in group A and 9.1% (1/11) in group B achieved HBeAg seroconversion at the 12th month. Of patients in group B with positive-HBeAg before the previous combination therapy and detectable HBV DNA at 6 months of previous combination therapy were associated with high risks of viral relapse after switching to single-drug maintenance therapy.Conclusions:Prematurely switching to single-drug maintenance therapy would be resulted in viral relapse, and prolonged combination therapy was effective to maintain sustained responses for patients with initial suboptimal response to ADV.

Review article: management of chronic hepatitis C in patients with contraindications to anti‐viral therapy

There are patients with chronic hepatitis C who are not eligible for the current interferon-based therapies or refuse to be treated due to secondary effects. To provide information on alternative treatments for the management of these patients. A PubMed search was performed to identify relevant literature. Search terms included hepatitis C virus, anti-inflammatory treatment, antioxidant, natural products and alternative treatment, alone or in combination. Additional publications were identified using the references cited by primary and review articles. Several approaches, such as iron depletion (phlebotomy), treatment with ursodeoxycholic acid or glycyrrhizin, have anti-inflammatory and/or anti-fibrotic effects. Life interventions like weight loss, exercise and coffee consumption are associated with a biochemical improvement. Other alternatives (ribavirin monotherapy, amantadine, silibinin, vitamin supplementation, etc.) do not have any beneficial effect or need to be tested in larger clinical studies. There are therapeutic strategies and lifestyle interventions that can be used to improve liver damage in patients with chronic hepatitis C who cannot receive or refuse interferon-based treatments.

End treatment response and sustained viral response in hepatitis C virus genotype 3 among Pakistani population

BACKGROUND AND OBJECTIVESThis study aimed to determine the end treatment response (ETR) and sustained viral response (SVR) to interferon (IFN) and ribavirin in hepatitis C virus (HCV) genotype 3 in the Pakistani population.DESIGN AND SETTINGSThis is an interventional study conducted from January 2010 to December 2012 in Lyari General Hospital and Abbasi Shaheed Hospital, Karachi, outpatients department.METHODSAll patients with chronic hepatitis C genotype 3 infections were included. Patients with decompensated chronic liver disease, or having coexisting hepatitis B virus/human immunodeficiency virus were excluded. All patients received IFN alpha, 3 million international units (MIU), subcutaneously 3 times weekly and ribavirin >800 mg/d for a period of 6 months. Outcome parameters included ETR (negative polymerase chain reaction [PCR] at the end of therapy), SVR (negative PCR both at the end of treatment and 6 months later), and relapse (PCR negative at the end of treatment but positive 6 months later) were determined.RESULTSA total of 1170 patients were included with a female to male ratio of 1.64:1 and a mean age of 31.6 (8.4) years. Among 1170 patients, 985 completed the therapy as per the protocol, 119 were defaulted (treatment abandoned before completion), and 66 had to stop treatment due to side effects. ETR was 74.1%, SVR was 98%, relapse rate was 1.5%, and 10.1% were nonresponders. SVR was seen only in patients who had achieved an ETR (n=867). SVR was achieved in 848 patients (out of 867) (98%), relapse was seen in 13 (1.5%), and 6 (0.7%) patients lost follow-up after stopping treatment. Patients achieving ETR and SVR had a mean serum alanine aminotransferase of 71.3 (57.1) and 71.0 (56.5), respectively, which is approximately twice the upper normal limit.CONCLUSIONThe conventional IFN and ribavirin therapy in genotype 3 chronic HCV-infected patients gives an ETR and SVR of 74.1% and 98%, respectively.

Antiviral triple therapy with boceprevir in a chronic hepatitis C haemodialysis patient awaiting kidney re-transplantation

Management of chronic hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD) is complicated by drug-related toxicity and interactions [1,2]. Dual antiviral therapy with pegylated interferon (Peg-IFN) and ribavirin (RBV) reached sustained virological response (SVR) rates of only ∼30% [1,2]. With the approval of the NS3/NS4a protease inhibitors (PI) telaprevir (TVR) and boceprevir (BOC), PI-based triple therapy as the new standard for antiviral therapy in non-haemodialysis (HD) HCV genotype 1 cohorts leads to significantly higher SVR rates of 66% and 75% in treatment-naive patients [3,4].

Strategic use of lamivudine in the management of chronic hepatitis B

Lamivudine is no longer recommended as first-line therapy for chronic hepatitis B. The same advice has been made for adefovir and telbivudine, due to their relatively weak anti-viral activity and low resistance barrier, respectively. Instead, either tenofovir or entecavir is the currently preferred anti-HBV agent, given their potent anti-viral activity and high barrier to resistance. However, these drugs are expensive and their long-term use is often unaffordable for many individuals, including most patients in developing regions, where hepatitis B is generally much more prevalent. Herein, we argue that lack of universal access to the current best anti-viral drugs for hepatitis B should not imply a suboptimal management of chronic hepatitis B which denies therapy to persons who really need it. A wise and strategic use of lamivudine may provide an opportunity to bring the benefit of therapy to large HBV-infected populations, while reducing health care costs.

Lamivudine Monotherapy in Chronic Hepatitis B Patients from the Indian Subcontinent: Antiviral Resistance Mutations and Predictive Factors of Treatment Response

Management of chronic hepatitis B is a global public health challenge. There are several updated guidelines proposed based on treatment outcome data from the respective study populations. In this study, we aim to characterize the antiviral resistance mutations to lamivudine monotherapy in patients diagnosed with chronic hepatitis B from the Indian subcontinent. A total of 147 lamivudine-treated patients with a median treatment duration of 13 (interquartile range 8-24) months were studied. Virological response was measured by hepatitis B virus (HBV) DNA levels. Antiviral resistance mutations were identified by sequencing HBV reverse transcriptase domains. Factors associated with virological response and antiviral resistance mutations were analyzed. Virological response was observed in 50 (35%) patients while 84 (57%) were non-responders. The virological response for the remaining 13 (9%) patients was undetermined. Forty patients (27%) developed lamivudine-resistant mutations. HBV genotypes, subgenotypes and hepatitis B surface antigen subtypes did not show significant association with virological response or lamivudine-resistant mutations. High HBV DNA levels and increased treatment duration were strongly associated with the development of lamivudine-resistant mutations (p=0.002 and p<0.001). Patients who continued to be positive for hepatitis B e antigen have an increased risk for treatment failure (p=0.010). High baseline aspartate transaminase levels were significantly associated with subsequent lamivudine response (p=0.037). Considering the limited potency and high resistance rates to lamivudine therapy, our study emphasizes the use of more potent drugs in the management of chronic hepatitis B in the Indian subcontinent.

Epidemiology and management of chronic hepatitis E infection in solid organ transplantation: a comprehensive literature review

Hepatitis E virus (HEV) infection has emerged as a global public health issue. Although it often causes an acute and self-limiting infection with low mortality rates in the western world, it bears a high risk of developing chronic hepatitis in immunocompromised patients with substantial mortality rates. Organ transplant recipients who receive immunosuppressive medication to prevent rejection are thought to be the main population at risk for chronic hepatitis E. Therefore, there is an urgent need to properly evaluate the clinical impact of HEV in these patients. This article aims to review the prevalence, infection course, and management of HEV infection after solid organ transplantation by performing a comprehensive literature review. In addition, an in-depth emphasis of this clinical issue and a discussion of future development are also presented.

Successful treatment of chronic hepatitis B and D with pegylated-interferon plus entecavir

Interferon-based regimen has been used to treat hepatitis D virus (HDV) super-infection on top of hepatitis B virus (HBV) carriers; however, viral relapse is frequent after stopping therapy. Recently, quantitative hepatitis B surface antigen (qHBsAg) was introduced to help the management of chronic hepatitis B (CHB). Little is known about its role in the treatment of HBV and HDV dual infection. Herein, we reported a 45-year-old male HBV carrier with HDV co-infection who received combination therapy of pegylated-interferon α-2a plus entecavir. The qHBsAg level was adopted as the treatment guidance and a consolidation therapy of 12 months was continued after HBsAg loss. The patient achieved HBsAg seroconversion with HDV RNA undetectable after 35 months of combination therapy and sustained therapeutic response 12 months post-therapy. Therefore, personalized response-guided therapy by using qHBsAg may be an option for the treatment for HBV and HDV dual infection.

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Antiviral Therapy for Chronic Hepatitis B in Pregnancy

The management of chronic hepatitis B (CHB) during pregnancy remains a challenge and involves various aspects of maternal-fetal care. Despite the standard immunoprophylaxis, a significant portion of infants born to highly viremic mothers remain infected with hepatitis B virus (HBV). Emerging data suggest that antiviral therapy in the third trimester can prevent immunoprophylaxis failure. To minimize fetal exposure to antiviral agents, antiviral therapy during pregnancy should be reserved for mothers with advanced disease or who are at risk for hepatic decompensation. Current safety data suggest that lamivudine, telbivudine, or tenofovir may be used during pregnancy. However, the timing in initiating antiviral therapy requires careful assessment of risks and benefit. The authors provide a systematic review of the features of HBV during pregnancy, risk factors for vertical transmission, and evidence-based data on antiviral use during pregnancy. They propose an algorithm to assess the need of antiviral treatment and monitor mothers with CHB.