Serum hepatitis B virus RNA detectability, composition and clinical significance in patients with ab initio hepatitis B e antigen negative chronic hepatitis B.

Background: Serum hepatitis B virus (HBV) RNA is a surrogate biomarker for intrahepatic covalently closed circular DNA (cccDNA) transcriptional activity and persistence. In this retrospective study, we investigated its presence, levels and composition in ab initio Hepatitis B e antigen (HBeAg) negative chronically infected patients and examined possible associations with disease activity and the outcome of nucleos(t)ide analogue (NA) discontinuation.

Methods: We developed a sensitive real time polymerase chain reaction (RT-PCR) for the specific detection of HBV pregenomic RNA (pgRNA) and precore (preC) mRNA and analyzed 220 serum specimens, 160 under NA treatment, from 116 Greek patients initially negative for HBeAg.

Hepatocellular carcinoma after treatment cessation in non-cirrhotic HBeAg-negative chronic hepatitis B: A multicentre cohort study.

Background And Aims: Scarce data exist on the effect of nucleos(t)ide analogue (NA) discontinuation on hepatocellular carcinoma (HCC) risk in HBeAg-negative chronic hepatitis B (CHBe-). Therefore, we assessed whether HCC risk is increased in non-cirrhotic CHBe- patients who discontinue compared to those remaining on NAs.

Methods: This cohort study included 650 consecutive non-cirrhotic Caucasian or Asian patients with CHBe- without a history of HCC who discontinued NAs after a median of 5 or 3 years (cases, n = 325; Caucasians: 143, Asians: 182) or remained on NA therapy beyond 5 or 3 years respectively (controls, n = 325; Caucasians: 223, Asians: 102).

Current practice and contrasting views on discontinuation of nucleos(t)ide analog therapy in chronic hepatitis B.

: Long-term, even indefinite treatment with nucleos(t)ide analogs (NAs) is the current first-line therapy for patients with chronic hepatitis B (CHB), regardless of its histological stage. Guidelines and recommendations on duration and endpoints of NA therapy in CHB are not identical and change over time.: The authors review NA discontinuation approaches and views with an emphasis on HBeAg-negative patients based on published studies relevant to the topic, stressing on whether or not the optimal endpoint of HBsAg loss is practically achievable.

Common ABCB1 polymorphisms in Greek patients with chronic hepatitis C infection: A comparison with hyperlipidemic patients and the general population.

Background: Hepatitis C virus infectivity and replication efficiency appears to be dependent on the lipid content and organization of the plasma membrane of the host cell, as well as of the intracellular membranous web. As there is increasing awareness of a role played by the efflux pump ABCB1 (p-glycoprotein, P-gp) in lipid homeostasis, its function could be a determinant of chronic HCV infection. The aim of the present study was to examine and compare the distribution of common ABCB1 genotypes in patients with chronic HCV infection (n=168), hyperlipidemic patients (n=168) and a control group (n=173), all from Greece.

Update on Hepatitis B Virus Infection: Focus on Treatment.

This review article is an update of the current treatment strategies available for chronic hepatitis B. In addition to achieving on-therapy clinical remission and suppression of HBV replication without resistance, the ultimate goal of therapy is the development of sustained remission and HBsAg loss after discontinuation of treatment. This is the closest possible to cure outcome for hepatitis B virus (HBV) infection.

Risk for hepatocellular carcinoma in the course of chronic hepatitis B virus infection and the protective effect of therapy with nucleos(t)ide analogues.

Hepatocellular carcinoma (HCC) is a major health problem worldwide, representing one of the leading causes of death. Chronic hepatitis B virus (HBV) infection (CHB) is the most important etiologic factor of this tumor, accounting for the development of more than 50% of the cases in the world. Primary prevention of HCC is possible by hepatitis B vaccination conferring protection from HBV infection.

Hepatitis B surface antigen quantification in chronic hepatitis B and its clinical utility.

Serum HBsAg levels have been quantified extensively in recent years with simple completely automated assays in the various phases of the natural course of chronic HBV infection, have been compared with cccDNA in the liver, with various markers of HBV replication and have been correlated with several viral, host and environmental variables. Low HBsAg levels in inactive carriers predict a spontaneous HbsAg loss. Quantification of HBsAg in serum at baseline and its decline under interferon-alfa based regimens, both in HBeAg-positive and HBeAg-negative CHB, provides important information on the prediction of sustained post-treatment outcomes and on subsequent HBsAg clearance.

The natural course of chronic hepatitis B virus infection and its management.

Chronic infection with the hepatitis B virus (HBV) runs a long natural course during which underlying changes in liver histology can progress to cirrhosis and hepatic decompensation, as well as to hepatocellular carcinoma. Therapeutic intervention is currently aiming at suppression of HBV replication by applying a number of pharmacological agents. For an optimum use of available therapies, good knowledge of the natural course of chronic infection, as well as of the role played by several viral, host, and environmental factors, is mandatory.

Response to peginterferon alfa-2a (40KD) in HBeAg-negative CHB: on-treatment kinetics of HBsAg serum levels vary by HBV genotype.

Background & Aims: We investigated whether HBV genotype influences on-treatment HBsAg kinetics and/or the end-of-treatment HBsAg levels associated with long-term virological response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a±lamivudine in the Phase III trial.

Methods: All patients (n=230) who participated in long-term follow-up were included according to the availability of HBsAg level measurements. Long-term virological response was defined as HBV DNA ≤ 10,000cp/ml (1786IU/ml) at 5 years post-treatment.

Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients.

Purpose: To investigate the durability of response to peginterferon alfa-2a up to 5 years post-treatment and factors associated with response in hepatitis B e-antigen (HBeAg)-negative patients.

Methods: HBeAg-negative patients received peginterferon alfa-2a (180 μg/week) ± lamivudine (100 mg/day) for 48 weeks as part of a multicenter, randomized study. The planned 5-year efficacy analysis included patients (n = 230) enrolled in the long-term follow-up study.

Safety profile of standard- vs. high-dose peginterferon alfa-2a plus standard-dose ribavirin in HCV genotype 1/4 patients: pooled analysis from 5 randomized studies.

Objective: This analysis examines the safety profile of standard- versus high-dose peginterferon alfa-2a.

Methods: Data were pooled from five trials including HCV genotype 1- or 4-infected naive and treatment-experienced patients (n = 2,940). Patients were randomized to receive peginterferon alfa-2a at 180 μg/week (standard-dose; n = 1,672) or 360 μg/week (high-dose; n = 1,268) plus ribavirin 1,000/1,200 mg/day for 12 weeks; after 12 weeks, all received standard dose.

Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir.

Background & Aims: Little is known about the biochemical and virological effects of stopping long-term nucleos(t)ide analogue therapy for hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB).

Methods: We performed a cohort observational study, following 33 HBeAg-negative patients with CHB, undetectable serum HBV DNA, and normal levels of aminotransferases after long-term (4 or 5 years) treatment with adefovir dipivoxil (ADV). All patients were followed for 5.

Safety of peginterferon alfa-2a plus ribavirin in a large multinational cohort of chronic hepatitis C patients.

Background & Aims: Peginterferon plus ribavirin has been the standard of care for chronic hepatitis C for a decade and an essential component of combination regimens for this disease. This large multinational open-label study aimed to better define the incidence of serious adverse events (SAEs) and non-serious adverse events of special interest in patients receiving peginterferon alfa-2a/ribavirin.

Methods: Patients were assigned at the investigator's discretion to 24- or 48-week treatment with peginterferon alfa-2a 180 μg/week and ribavirin 800 mg/day or 1000/1200 mg/day.

Refined prediction of week 12 response and SVR based on week 4 response in HCV genotype 1 patients treated with peginterferon alfa-2a (40KD) and ribavirin.

Background & Aims: It is unclear whether the magnitude of reduction in hepatitis C virus (HCV) RNA between baseline and week 4 of treatment influences the probability of achieving a sustained virological response (SVR) in patients without a week 4 rapid virological response (RVR).

Methods: Data were retrospectively analyzed from two studies in which treatment-naive patients received peginterferon alfa-2a (40KD) 180 μg/week plus ribavirin 1000/1200 mg/day for 48 weeks. Five hundred and fifty-eight genotype 1 patients with evaluable HCV RNA at baseline and week 4 were grouped according to RVR status: RVR (HCV RNA<50 IU/ml) or no RVR.

Treatment of special populations with chronic hepatitis B infection.

All therapeutic agents that are currently in use for the treatment of chronic hepatitis B have been administered to a large number of patients in clinical trials in order to be approved as efficacious and safe. Nevertheless, in these trials, many patients have been excluded either because they have decompensated cirrhosis, or they belong to groups with comorbidities that can seriously affect the underlying liver disease, or where the treatment for chronic hepatitis B virus infection can be contraindicated. Such groups of patients are those with hepatitis D virus, hepatitis C virus and HIV coinfections, patients who have undergone transplantation or are immunosuppressed due to chemotherapy or other treatment, patients with end-stage renal disease under dialysis, acute and fulminant hepatitis B and also, children and pregnant women.

Effect of antiviral therapy on the immunohistochemical expression of bcl-xL and bax protein in patients with HBeAg-negative chronic hepatitis B.

The effect of antiviral treatment on apoptosis in chronic hepatitis B (CHB) has not been clarified. We evaluated the hepatic immunohistochemical expression of the pro-apoptotic bax and the antiapoptotic bcl-xL protein in HBeAg-negative CHB patients before and after treatment. In our study we included 72 paired biopsies from 36 HBeAg-negative CHB patients: 29 treated (interferon-alfa: 17, adefovir: 12) and 7 untreated.

Management of hepatitis C virus genotype 4: recommendations of an international expert panel.

HCV has been classified into no fewer than six major genotypes and a series of subtypes. Each HCV genotype is unique with respect to its nucleotide sequence, geographic distribution, and response to therapy. Genotypes 1, 2, and 3 are common throughout North America and Europe.

Milestones and perspectives in viral hepatitis B.

There have been numerous research milestones since the discovery of the hepatitis B virus (HBV) in the 1960s. These mark major advances in the serology and epidemiology of HBV infection, in identifying the wide clinical spectrum of acute and chronic hepatic diseases as well as the extrahepatic conditions induced by this virus, the molecular biology of the virus including its variants and mutants, its molecular diagnosis and monitoring, the host immune responses to the infecting virus, the pathogenesis and immunopathogenesis of liver disease as well as its natural course and outcome. These landmark discoveries are the firm background for current and future developments in treatment.

Natural history of chronic hepatitis B in Euro-Mediterranean and African countries.

Data derived from population, case-control, and cohort studies conducted in several Euro-Mediterranean and African countries disclose impressive similarities in the age and modes of hepatitis B virus (HBV) transmission and in the prevalence, duration, and outcome of the four phases of the natural history of chronic infection. Perinatal HBV infection is rare while the vast majority of chronic infections originate from horizontal HBV transmission to infants and children. HBeAg loss and seroconversion to anti-HBe occur in a few years time, usually during the second decade of life.

Rapid virological response is the most important predictor of sustained virological response across genotypes in patients with chronic hepatitis C virus infection.

Background & Aims: The probability of response to peginterferon and ribavirin is associated with numerous host and virological factors. Attainment of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 during treatment with peginterferon and ribavirin, is highly predictive of sustained virological response (SVR). The aim of the present study was to determine the relative importance of the kinetics of antiviral response compared to baseline host and virological factors for predicting SVR.

The natural history of chronic HBV infection and geographical differences.

Although chronic HBV infection is a global health issue, there are geographical differences in the mode of transmission, prevalence and HBV genotype distribution. Chronic HBV infection is a dynamic state of interactions between HBV, hepatocytes and immune cells of the host. Accordingly, the natural history of chronic HBV infection typically starts with an immune tolerant phase, followed by an immune clearance phase and finally an inactive phase.

Definition of rapid virologic response with a highly sensitive real-time PCR-based HCV RNA assay in peginterferon alfa-2a plus ribavirin response-guided therapy.

Background & Aims: Assessing hepatitis C virus (HCV)-RNA levels is integral to response-guided therapy. Rules for early discontinuation and determination of treatment duration were mainly established with HCV-RNA assays with a detection limit of 50IU/ml (COBAS Amplicor HCV [CA]). The currently used real-time PCR-based COBAS Ampliprep/COBAS-TaqMan HCV (CAP-CTM) test has a detection limit of approximately 10IU/ml.

Efficacy and safety of peginterferon alfa-2a (40KD) plus ribavirin in hepatitis C patients with advanced fibrosis and cirrhosis.

Unlabelled: The objective of this study is to determine the efficacy and safety of peginterferon alfa-2a (40 KD)/ribavirin in patients with advanced fibrosis. Data from 341 genotype 1/4 patients (99 with bridging fibrosis/cirrhosis) treated for 48 weeks and 1547 genotype 2/3 patients (380 with bridging fibrosis/cirrhosis) treated for 16 or 24 weeks enrolled in three randomized international studies were analyzed. Sustained virological response (SVR) rates decreased progressively from 60% in genotype 1/4 patients without advanced fibrosis to 51% in those with bridging fibrosis and 33% in those with cirrhosis (trend test P = 0.