How Can We Make Decision for Patients With Chronic Hepatitis B According to Hepatitis B Virus (HBV) DNA Level?

Background:

HBeAg negative hepatitis B infection exerts both inactive carrier state and chronic active hepatitis, which are sometimes difficult to differentiate. Serial hepatitis B virus (HBV) DNA quantification, alanine transaminase (ALT) measurement, and liver histology assessment can help to differentiate these forms of hepatitis B infection.

Objectives:

We aimed to clarify the clinical and laboratory characteristics of HBeAg negative hepatitis B patients.

Patients and Methods:

Patients with hepatitis B, referred to Tehran Blood Transfusion Hepatitis Clinic from 2011 to 2013, were included and followed for one year. Laboratory assessments including liver function tests, HBV DNA quantification, and liver biopsy (for some cases) were performed.

Results:

Two hundred forty-three HBeAg negative hepatitis B patients were stratified into three groups based on to their HBV DNA level including group 1 (G1) with HBV DNA level < 2000 IU/mL, group 2 (G2) with HBV DNA level 2000-20000 IU/mL, and group 3 (G3) with HBV DNA level > 20000 IU/mL. The G2 had more similarity to G1 than G3 regarding their clinical characteristics.

Conclusions:

It is concluded that most HBeAg negative hepatitis B patients with serum HBV DNA level of 2000-20000 IU/mL, persistent normal ALT concentration, and no or mild liver damage on biopsy can be clinically managed as HBV inactive carriers.     

Caesarean section to prevent transmission of hepatitis B: A meta-analysis

BACKGROUND:

Vertical transmission of hepatitis B virus (HBV) occurs in up to 10% to 20% of births.

OBJECTIVE:

To assess whether Caesarean section, compared with vaginal delivery, prevents HBV transmission.

METHODS:

A systematic review and meta-analysis was conducted. Two investigators independently searched PubMed, EMBASE and other databases for relevant studies published between 1988 and 2013. A manual search of relevant topics and major conferences for abstracts was also conducted. Randomized trials, cohort and case-control studies assessing the effect of delivery mode on vertical transmission of HBV were included. Studies assessing antiviral therapy and patients with coinfection were excluded. The primary outcome was HBV transmission rates according to delivery method.

RESULTS:

Of the 430 studies identified, 10 were included. Caesarean section decreased the odds of HBV transmission by 38% compared with vaginal delivery (OR 0.62 [95% CI 0.40 to 0.98]; P=0.04) based on a random-effects model. Significant heterogeneity among studies was found (I²=63%; P=0.003), which was largely explained by variation in hepatitis B immune globulin (HBIG) administration. Meta-regression showed a significant linear association between the percentage of infants receiving HBIG per study and the log OR (P=0.005), with the least benefit observed in studies with 100% HBIG administration. Subgroup analysis of hepatitis B e-antigen-positive women who underwent Caesarean section did not show a significant reduction in vertical transmission.

DISCUSSION:

Caesarean section may protect against HBV transmission; however, convincing benefit could not be demonstrated due to significant study heterogeneity from variable HBIG administration, highlighting the importance of HBIG in HBV prevention.

CONCLUSION:

More high-quality studies are needed before any recommendations can be made.     

A low viral load predicts a higher initial virologic response to adefovir in patients with Lamivudine-resistant chronic hepatitis B

Background/Aims

Adefovir (ADV) is the preferred drug for treating lamivudine (LAM)-resistant hepatitis B. However, not all patients who face virologic breakthrough during LAM treatment respond to ADV. The aim of this study was to determine the factors associated with efficacy of ADV in LAM-resistant hepatitis B patients.

Methods

The medical records of 231 patients who received ADV due to LAM-resistance were reviewed. Efficacy was assessed by the initial virologic response (IVR), defined as hepatitis B virus (HBV) DNA not being undetectable by real-time PCR at 6 months of ADV treatment.

Results

Seventy patients (30%) achieved IVR. While ''add-on'' modality, hepatitis B e antigen (HBeAg) negativity, and low baseline HBV DNA levels were associated with IVR in univariate analysis, multivariate analysis revealed HBeAg status and the DNA level to be the significant factors. The probability of IVR achievement increased sharply per each log₁₀ copies/mL decrement in the baseline viral load, which was 133 times in patients who had HBV DNA <10⁵ copies/mL compared with those who had ≥10⁸ copies/mL.

Conclusions

Factors associated with the IVR were HBeAg negativity and a low baseline viral load. Therefore, when virologic breakthrough with genotypic resistance emerges during LAM therapy, ADV treatment should be considered immediately before further increases in viral load. Additional long-term follow-up data are warranted.     

Efficacy and Safety of Telbivudine Compared to Entecavir Among HBeAg+ Chronic Hepatitis B Patients: a Meta-Analysis Study

Background

Hepatitis B virus (HBV) infection is a serious global health problem that is associated with huge social and economic costs. Early antiviral drugs, such as interferon-α2b, peginterferon-α2a, lamivudine, and adefovir, all have their limitations (such as low responses or safety concerns) in clinical application. Telbivudine and entecavir are two of the latest nucleotide drugs and both have been shown to have potent viral suppression. However, in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB), inconsistent results have been generated for efficacy between telbivudine and entecavir. Therefore, evidence-based medical data are required to compare the efficacies, in terms of virological and biochemical responses, and safety between telbivudine and entecavir.

Objectives

We aimed to compare the early antiviral efficacy and safety of telbivudine and entecavir in the treatment of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB).

Patients and Methods

A search for relevant randomized controlled trials (RCTs) on HBeAg-positive CHB patients treated with telbivudine and entecavir for 24 or 52 weeks, published before December 2011, was performed. Primary efficacy endpoint was the cumulative rate of undetectable HBV DNA, and secondary efficacy endpoints included rates of alanine aminotransferase (ALT) normalization, HBeAg disappearance, HBeAg seroconversion and adverse events. Meta-analysis was performed using the Review Manager v5.1.4 software package. We assessed the pooled risk ratios (RRs) and 95% confidence intervals (CIs) using the fixed-or random-effects model.

Results

Six randomized controlled trials (RCTs) involving 555 patients were included. Telbivudine was associated with significantly higher rates of HBeAg disappearance (RR = 1.46, 95% CI: 1.11 - 1.91) and HBeAg seroconversion (RR = 1.76, 95%CI: 1.25-2.48) than entecavir, but had higher adverse events (RR = 2.11, 95%CI: 1.23 - 3.60), compared with entecavir. There was no difference between telbivudine and entecavir in the rate of cumulative undetectable HBV DNA (RR = 0.99, 95% CI: 0.90 - 1.10) and ALT normalization (RR = 0.93, 95% CI: 0.85 - 1.00).

Conclusions

Telbivudine is associated with significantly higher rates of HBeAg disappearance and HBeAg seroconversion than entecavir, whereas entecavir is superior to telbivudine in safety. Both drugs have similar efficacy on rates of cumulative undetectable HBV DNA and ALT normalization.     

Prevalence of Hepatitis D Virus Infection Among Patients With Chronic Hepatitis B Attending Birjand Hepatitis Clinic (East of Iran) in 2012

Background

Hepatitis delta virus (HDV) is a defective RNA virus dependent on Hepatitis B virus (HBV) infection for its replication and expression. All patients with HBV infection should be tested for the presence of HDV infection. It is estimated that approximately 5% of hepatitis B surface antigen (HbsAg) carriers in the world are HDV infected patients. HBV-HDV co-infection may lead to more severe acute disease and higher risks of fulminant hepatitis, cirrhosis, and hepatocellular carcinoma than those having HBV infection alone. Also, HBV infected patients with HDV super-infection have a higher rate of progression to chronic disease and serious complications.

Objectives

Our aim was to determine the prevalence of HDV infection among chronic hepatitis B (CHB) patients attending Birjand Hepatitis Clinic, East of Iran.

Materials and Methods

A cross-sectional analytical study was conducted on 413 CHB patients in 2012. Serology test for anti-HDV was measured by ELISA in these patients. CHB patients had positive hepatitis B surface antigen for at least 6 months before the study entrance.

Results

The mean age of CHB patients was 38.5± 11.9 years and 55.9% of them (231 patients) were male. There were 13 cases (3.1%) with HDV infection. There was no association between positive anti-HDV serology and factors such as age, gender, carrier state, liver enzymes, and positive hepatitis B e antigen (HBeAg) serology.

Conclusions

Although HDV had a low prevalence in our area, it is important for healthcare providers and policy makers to plan preventive strategies for HDV spread as well as HBV prevention programs among high risk population.     

Efficacy of Tenofovir Disoproxil Fumarate Therapy in Nucleoside-Analogue Naive Iranian Patients Treated for Chronic Hepatitis B

Background:

Tenofovir disoproxil fumarate (TDF) is a new effective treatment option for patients with chronic hepatitis B (CHB).

Objectives:

To evaluate TDF efficacy in nucleos(t)ide analogues (NAs)-naive Iranian patients with CHB.

Patients and Methods:

The NA-naive patients received TDF for at least six months. The primary endpoint was the proportion of patients achieving a complete virological response (CVR) during the treatment. Multivariate Cox regression analysis determined predictive factors independently associated with the time to CVR. The secondary endpoints were biochemical and serological responses, frequency of virological breakthrough, genotypic resistance development, safety and tolerability.

Results:

In all, 93 patients (64.5% hepatitis B e antigen [HBeAg]-negative) were eligible. Of these, 70 patients completed 24 months of treatment. The cumulative CVR rates in HBeAg-negative and HBeAg-positive patients were 87% versus 53% at 24 months, respectively. The multivariate Cox regression model showed only HBeAg positivity at baseline and a high baseline HBV DNA level were independent factors predicting a CVR. No patient achieved hepatitis B surface antigen (HBsAg) and HBeAg loss or seroconversion and no virologic breakthrough occurred. A new amino acid substitution (rtD263E) was observed to develop in 60% of patients with viremia.

Conclusions:

The cumulative CVR rates showed that patients with HBeAg-negative have better virologic respond than those with HBeAg-positive during the same period. The rtD263E mutation might be associated with partial resistance to TDF.     

The Efficacy and Safety of Peginterferon-α-2a in Korean Patients with Chronic Hepatitis B: A Multicenter Study Conducted in a Real Clinical Setting

Background/Aims

Genotype C is the principal type of hepatitis B virus (HBV) in Koreans and is associated with poor prognosis for peginterferon α-2a therapy. The efficacy of and compliance to peginterferon α-2a therapy were investigated in Koreans with hepatitis B in a real clinical setting.

Methods

Hepatitis B patients treated with peginterferon α-2a from 2008 to 2011 at four university hospitals were consecutively enrolled.

Results

Eighty-eight patients were enrolled; 67 were hepatitis B e antigen (HBeAg)-positive. The mean treatment period was 36.1±15.2 weeks. In 26.1% of patients, treatment was discontinued due to insufficient antiviral effects and adverse events. At 24 weeks after treatment, 10/42 (23.8%) HBeAg-positive patients achieved both HBV DNA suppression to <2,000 IU/mL and HBeAg loss/seroconversion. For HBeAg-negative patients, 10/13 (76.9%) achieved HBV DNA suppression to <2,000 IU/mL at 24 weeks after treatment. During the follow-up period, 15 (30.6%) of the 49 patients who achieved HBV DNA suppression to 2,000 IU/mL developed a breakthrough HBV DNA level of >2×10⁶ IU/mL.

Conclusions

Peginterferon α-2a therapy in Koreans with hepatitis B in a real clinical setting resulted in a lower virologic response, as compared to Western individuals, but a favorable durability. There is a need to reduce the high rate of premature discontinuation compared to the controlled studies.     

Serolological Profile Among HBsAg-Positive Infections in Southeast China: A Community-Based Study

Background

Hepatitis B virus (HBV) infection has remained a significant public health problem. Generating a large-scale, community-based profile of HBV infection in China is essential to prevention of the disease.

Objectives

The current study was designed to investigate HBV-infected individuals at the community level and determine the age distribution, hepatitis B e antigen (HBeAg) positivity and its related risk factors, relationship among serological markers.

Patients and Methods

A cross-sectional, community-based survey was carried out without age restriction, in 12 communities of two counties. The study population was selected by random multistage cluster sampling. Serological samples and demographic information were collected from 8439 HB surface antigen (HBsAg)-positive individuals.

Results

The constituent ratio of individuals with HBsAg-positive infections was lowest among persons aged < 20 years (0.4%) and the highest among persons aged 40-49 years (33.2%). The HBeAg-positive rate among infected individuals was 18.5%, and the constituent ratio decreased with increasing of age. The HBeAg-positive rate in males (21.9%) was significantly higher than in females (14.7%), and was higher among coastland inhabitants (22.9%) than among plains inhabitants (12.9%). Among the 1561 HBeAg-positive individuals, 91.0% were HBV DNA-positive. However, of the 6878 HBeAg-negative individuals, only 45.4% were HBV DNA-positive, and the HBeAg-positive rate was significantly different at different levels of HBV DNA expression. The proportion of detectable HBV DNA levels was significantly higher in individuals with elevated ALT, compared to those with normal ALT, regardless of HBeAg-positivity.

Conclusions

The HBV prevalence remained high in the > 20 age group. The positivity of HBeAg was related to age, region, and sex. Testing HBeAg and serum ALT levels were effective ways to assess HBV infectiousness in community-level hospitals in China.     

G1896A Precore Mutation and Association With HBeAg Status,Genotype and Clinical Status in Patients With Chronic Hepatitis B

Background:

Precore stop codon (G1896A) mutation is one of the commonest mutations found in patients with chronic hepatitis B. However, over the years, this mutation was not reported much in Malaysia.

Objectives:

We therefore investigated the presence of G1896A mutation in Malaysian population and its association with HBeAg status, clinical stage, hepatitis B virus (HBV) genotype and e-seroconversion rate.

Patients and Methods:

Serum samples from 93 patients confirmed as hepatitis B carriers were collected for molecular assay. The whole genome of HBV was amplified by polymerase chain reaction and directly sequenced. The precore and basal core promoter regions were analyzed for presence of mutations.

Results:

The most commonly observed mutation in the precore region was C1858T with 64.5% prevalence. The precore mutation of interest (G1896A) was identified in 25.8% of isolates. The basal core promoter mutations detected were A1762T-G1764A (26.9%), C1653T (8.6%), A1752G (10.8%) and C1766T (2.2%). No significant association was observed between G1896A mutation and HBeAg-negativity. Nonetheless, G1896A was highly prevalent among HBV genotype B. Clinical association revealed that subjects with G1896A mutations were mainly detected in asymptomatic chronic hepatitis B (58.3%) and liver cirrhosis (41.7%). One subject was diagnosed with fulminant hepatitis (4.2%) and 8.3% had hepatocellular carcinoma (HCC).

Conclusions:

Our data suggested an intermediate prevalence of G1896A mutation among Malaysian hepatitis B carriers. The stop codon mutation has a significant association with genotype B and patients with chronic hepatitis B and liver cirrhosis.     

Efficacy and Safety of Tenofovir-Based Rescue Therapy for Chronic Hepatitis B Patients with Previous Nucleo(s/t)ide Treatment Failure

Background/Aims

We investigated the efficacy and safety of tenofovir disoproxil fumarate (TDF)-based treatment in chronic hepatitis B (CHB) patients who failed previous antiviral therapies.

Methods

Seventeen patients who failed to achieve virological responses during sequential antiviral treatments were included. The patients were treated with TDF monotherapy (four patients) or a combination of TDF and lamivudine (13 patients) for a median of 42 months. Hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) were measured, and renal function was also monitored.

Results

Prior to TDF therapy, 180 M, 204 I/V/S, 181 T/V, 236 T, and 184 L mutations were detected. After TDF therapy, the median HBV DNA level decreased from 4.6 log₁₀ IU/mL to 2.0 log₁₀ IU/mL and to 1.6 log₁₀ IU/mL at 12 and 24 months, respectively. HBV DNA became undetectable (≤20 IU/mL) in 14.3%, 41.7%, and 100% of patients after 12, 24, and 48 months of treatment, respectively. HBeAg loss was observed in two patients. Viral breakthrough occurred in five patients who had skipped their medication. No significant changes in renal function were observed.

Conclusions

TDF-based rescue treatment is effective in reducing HBV DNA levels and is safe for patients with CHB who failed prior antiviral treatments. Patients'' adherence to medication is related to viral rebound.     

Occult Hepatitis B (OBH) in Clinical Settings

Context

Occult hepatitis B (OHB), or persistent HBV DNA in patients who are hepatitis B surface antigen (HBsAg) negative, is a recently recognized entity. In an attempt to summarize the issues, this review presents an overview of the current proposed hypothesis on the clinical relevance and also updates the knowledge on the classification of OHB in different clinical settings.

Evidence Acquisition

OHB could be found in different population and clinical backgrounds including: viral co-infections (with either human immunodeficiency or hepatitis C viruses), HBV chronic carriers, dialysis patients, transplantation settings and certain clinical situations (named in here: special clinical settings) with no apparent distinguishable clinical parameters.

Results

The exact magnitude, pathogenesis, and clinical relevance of OHB are unclear. Even the possible role exerted by this cryptic infection on liver disease outcome, and hepatocellular carcinoma development remains unknown.

Conclusions

Monitoring of Individuals with positive anti-HBc, mass immunization programs and improvement in diagnostic tools seem to be important to control the probability of transmission of HBV through cryptic HBV infection.     

Factors predicting the efficacy of adefovir dipivoxil on treatment-naïve chronic hepatitis B patients at 48 weeks

Background/Aims

To reveal possible factors predicting the effect of adefovir dipivoxil (ADV) treatment on chronic hepatitis B (CHB) and optimize the utilization of ADV.

Methods

In total, 168 treatment-naïve CHB patients were enrolled, including 117 hepatitis B e antigen (HBeAg)-positive patients and 51 HBeAg-negative patients who met the inclusion criteria. All patients were treated with ADV 10 mg per day for 48 weeks. Multiple logistic regression analyses were used to investigate baseline factors, and responses at weeks 12 and 24 were analyzed as predictive values.

Results

Multiple regression analyses showed that baseline HBeAg status and HBV DNA levels significantly affected the virological response (VR) (p<0.05), baseline ALT levels were an independent predictor of serological response (SR) (p<0.05) and the body mass index (BMI) may affect the biochemical response (BR) (p<0.05). There was a statistically significant difference in the VR and SR between patients with a primary nonresponse (PNR) at week 12 and those with a VR at week 12 (p<0.01). Additionally, the VR was significantly different between patients with HBV DNA lower than 10³ copies/mL at week 24 and those with greater than 10³ copies/mL (p<0.01).

Conclusions

Patients with negative HBeAg, lower HBV DNA levels and higher ALT values at baseline are more suitable for ADV treatment, whereas patients with lower BMIs may be more amenable to ALT normalization. Adjustments for treatment strategy should be considered if PNR at week 12 or HBV DNA ≥10³ copies/mL at week 24 is observed.     

Prognostic Values of Fluctuations in Serum Levels of Alanine Transaminase in Inactive Carrier State of HBV Infection

Background:

Current guidelines introduce periodic monitoring of serum alanine transaminase (ALT) as the first-line modality in follow-up patients, with a hepatitis B virus (HBV) inactive carrier state.

Objectives:

This study aimed to determine the incidence rate and patterns of ALT fluctuations and prognostic values for the development of chronic HBV e antigen (HBeAg)-negative hepatitis B (CHB), HBV surface antigen (HBsAg) seroclearance, and liver-related complications.

Patients and Methods:

Treatment-naïve patients with a chronic HBV infection, HBeAg(-)/HBeAb(+), normal ALT levels, and HBV DNA < 2000 IU/mL, were followed-up every 6-12 months by assessing serum ALT levels. Serum HBV DNA was measured in cases of elevated ALT levels.

Results:

A total of 399 patients were followed-up for 8.9 years; ALT > upper limit of normal (ULN, i.e. 40 IU/L) was detected in 103 (25.8%) patients, with an annual incidence rate of 2.9%. ALT elevation was associated with; male gender, age, and higher serum ALT levels at study entry. Among the cases of ALT elevations, 16 (15.5%) patients had ALT levels > 2 × ULN. There were 38 (36.9%) patients who had ALT levels that remained > ULN over six months, and 21 (20.4%) patients experienced at least two episodes of ALT elevations. In 15 (14.6%) patients, elevated ALT levels were associated with increased HBV replication (i.e. HBV DNA > 2 000 IU/mL) and these were considered as CHB. However, elevation of ALT levels, even in the absence of HBV replication, increased the risk for the development of CHB up to 8-fold in prospective follow-ups. HBsAg seroclearance, cirrhosis, and hepatocellular carcinoma were detected in 43 (10.8%), 4 (1%), and 1 (0.25%) patients, respectively.

Conclusions:

Fluctuations in serum ALT levels may change the prognosis of a HBV inactive carrier state.     

Effect of Hepatitis B Virus Genotypes on the Efficacy of Adefovir Dipivoxil Antiviral Therapy

Background:

Hepatitis B is a common infectious disease in China. Many studies have shown that the genotype of hepatitis B virus (HBV) is probably associated with the efficacy of some antiviral drugs such as interferon α (IFN-α) and Lamivudine (LAM). However, the association between HBV genotype and adefovir dipivoxil (ADV) is controversial. ADV is the most popular antiviral drug in China due to its low price, good antiviral efficacy, few side effects, and convenient of administration.

Objectives:

This study focused on the effect of HBV genotypes on antiviral efficacy of ADV in patients with chronic hepatitis B infection (CHB).

Patients and Methods:

A total of 526 HBeAg-positive patients with CHB were randomly allocated into two groups. One group took ADV and another group took placebo. Nested Polymerase Chain Reaction (PCR) with multiple pairs of genotype-specific primers (nPCR-MPP) was used to analyze genotypes of HBV in these patients. Antiviral efficacy after treatment for three, six, 12 months was compared among the patients with different HBV genotypes.

Results:

Genotype B (73.6%) and genotype C (26.4%) were detected in these patients. After treatment for 12 months, the rate of HBV DNA seroclearance, ALT normalization, and HBeAg seroconversion were significantly higher in ADV group than in placebo group (P < 0.05). However, there were no significant differences in these three rates between patients infected with genotype B and C (P > 0.05).

Conclusions:

HBV genotypes B and C have no significant difference in virologic, biochemical, and immunologic response to ADV.     

Rapamycin Enhances HBV Production by Inducing Cellular Autophagy

Background:

Some reports revealed that rapamycin could reactivate HBV infection. However, the mechanism has not been clearly explained.

Objectives:

In this report, we studied the mechanism by which rapamycin enhances HBV replication and expression by inducing cellular autophagy.

Materials and Methods:

HepG2.2.15 cells were treated with rapamycin to induce autophagy. Autophagosomes were observed by fluorescence microscopy and transmission electron microscopy. Autophagy marker protein LC3-Ⅱ/LC3-Ⅰwas detected by Western blotting. HBV DNA and mRNA were determined by real time PCR and Southern blotting. HBsAg was evaluated by ELISA.

Results:

In HepG2.2.15 cells, HBV DNA and HBsAg increased when host cells were treated with rapamycin and the effect was reversed by autophagy inhibitor, 3-methyladenine (3-MA).

Conclusions:

These results indicated a potential explanation for reactivation of HBV infection when patients with hepatitis receive rapamycin.     

The prevalence and risk factors for hepatitis B surface ag positivity in pregnant women in eastern region of ghana

Background/Aims

The aim of this study was to evaluate the prevalence and risk factors for hepatitis B surface antigen (HBsAg) positivity in pregnant Ghanaian women.

Methods

We surveyed 1,500 pregnant women in Eastern region of Ghana. Direct interviews were performed by trained nurses using standardized questionnaires. Pregnant women were screened for human immunodeficiency virus (HIV) and hepatitis B infections, hemoglobin levels and sickle cell anemia as part of the antenatal check-up.

Results

The overall HBsAg positive rate was 10.6%, which varied among districts (13.8% for Kwahu West, 12.4% for Upper Manya, and 2.2% for Yilo Krobo). HBsAg positivity was significantly higher in women with depression (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.13 to 6.57) and HIV (OR, 2.03; 95% CI, 1.06 to 3.89). Age, education, and gravidity were not related to HBsAg positivity. Anti-hepatitis B immunoglobulin for newborns of HBsAg-positive mothers is not provided at birth in public health facilities in Ghana. However, hepatitis B vaccination is provided as part of a routine vaccination schedule starting at 6 weeks of age.

Conclusions

To prevent mother-to-child transmission of hepatitis B, screening tests for HBsAg in pregnant women and hepatitis B vaccination of newborns immediately after birth need to be performed in this region.     

Long-Term Treatment Efficacy and Safety of Clevudine Therapy in Na?ve Patients with Chronic Hepatitis B

Background/Aims

Clevudine (CLV) has potent antiviral activity against chronic hepatitis B (CHB) virus infection. The long-term efficacy and safety of CLV therapy in naïve patients with CHB were investigated.

Methods

In this retrospective study, 152 naïve Korean patients with CHB who received 30 mg of CLV once daily for at least 12 months were investigated.

Results

The cumulative rates at months 12, 24, and 36, respectively, were 65.8%, 74.7%, and 74.7% for undetectable serum hepatitis B virus (HBV) DNA (<12 IU/mL); 77.6%, 86.2%, and 86.2% for normalization of serum alanine aminotransferase (<40 IU/L); 17.6%, 23.5%, and 23.5% for hepatitis B e antigen (HBeAg) loss or seroconversion; and 6.6%, 22.5%, and 30.0% for viral breakthrough. HBeAg positivity (p=0.010), baseline serum HBV DNA level ≥6 log₁₀ IU/mL (p=0.032) and detectable serum HBV DNA (≥12 IU/mL) at week 24 (p=0.023) were independently associated with the development of viral breakthrough. During follow-up, CLV-induced myopathy developed in 5.9% of patients.

Conclusions

The results of long-term CLV therapy for the treatment of naïve patients with CHB showed a high frequency of antiviral resistance and substantial associated myopathy. Therefore, we advise that CLV should not be used as a first-line treatment for naïve patients given the availability of other more potent, safer antiviral agents.     

Identification of acute vaccine-preventable hepatitis in individuals with chronic hepatitis in British Columbia between 1991 and 2007

BACKGROUND:

In British Columbia (BC), hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccines are provincially funded for persons with chronic hepatitis infections.

PURPOSE:

To assess the effectiveness of BC public health follow-up of HBV and hepatitis C virus (HCV) cases and immunization policy by determining the number of vaccine-preventable acute hepatitis infections reported following a chronic HBV or HCV diagnosis, by examining demographic characteristics and by observing temporal trends.

METHODS:

All newly identified cases of HAV, HBV and HCV between 1991 and October 2007 were extracted from the BC integrated Public Health Information System and linked to ascertain cases of hepatitis suprainfection.

RESULTS:

Between 1991 and October 2007, 30 BC residents with chronic HBV and 104 with HCV were subsequently diagnosed with HAV. Acute HBV was identified in 162 persons previously diagnosed with HCV. Significantly more men than women developed hepatitis suprainfection (P<0.0001), but women were of a younger age when they were diagnosed with HAV (P=0.02) and acute HBV (P=0.0002). HAV suprainfection cases among those with HCV peaked in 1998 at 33 cases and declined to zero cases in 2007. In comparison, HBV suprainfection among individuals with chronic HCV peaked in 1996 at 26 cases and declined to two cases in 2007.

DISCUSSION:

Cases of HAV and acute HBV have declined among HCV-infected individuals. However, despite the availability of publicly funded vaccines for high-risk groups, a substantial number of acute HBV infections post-HCV identification are still identified, indicating that follow-up and vaccination coverage should be improved in these populations.     

Adiponectin and Its Receptors in Chronic Hepatitis B Patients With Steatosis in China

Background

HBV infection is a serious public health problem worldwide, which can contribute to the incidence of chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma (HCC).

Objectives

In the present report, we assessed the association between adiponectin, its receptors and hepatic steatosis, fibrosis, and inflammation with hepatitis B virus.

Patients and Methods

Liver biopsies from 89 patients with untreated chronic hepatitis B (34 steatosis vs. 55 without steatosis) were analyzed; liver biopsies from 50 healthy adults were used as control. The liver biopsies were subjected to routine histological examination, and stained immunohistochemically for adiponectin and adiponectin receptor2 (adipoR2).

Results

The two groups were found to be comparable with respect to demographic, biochemical, metabolic, histological, and viral characteristics. BMI, γ-GT, FPG, insulin, and insulin sensitivity estimated by the HOMA index were significantly higher in patients with steatosis. The viral load of HBV and HBeAg positivity was higher in patients with steatosis than those without steatosis. High serum adiponectin levels were significantly correlated with abnormal serum ALT level (vs. normal ALT, P = 0.000), and HBV genotype C (vs. genotype B, P = 0.018). In patients with chronic HBV, the insulin sensitizing adipokine adiponectin, and its receptor AdipoR2were associated with steatosis. While adiponectin may becorrelated with inflammation, adiponectin, and its receptors were not associated with viral factors.

Conclusions

Our results suggest that the role of adiponectin might be impaired in chronic hepatitis B with steatosis. Reduced hepatic expression of adiponectin and adipoR2 might be of pathophysiological relevance in CHB patients with steatosis. These findings indicated that reduced liver adiponectin expression may play an important role in the pathogenesis, and progression of CHB patients with steatosis. However, hepatic expression of adiponectin, and adipoR2 was not associated with various measures of HBV infection.