Syed Hissar

A randomized controlled trial of lamivudine to treat acute hepatitis B

The role of antivirals in patients with acute viral hepatitis B (AVH‐B) has not been evaluated in controlled trials. The aim of this study was to evaluate the efficacy of lamivudine in patients with AVH‐B. AVH‐B patients with serum bilirubin of more than 5 mg/dL were randomized to receive either 100 mg of lamivudine daily for 3 months (group 1, n = 31) or placebo (group 2, n = 40). Patients were considered to have severe AVH‐B if they fulfilled 2 of 3 criteria: (1) hepatic encephalopathy; (2) serum bilirubin ≥ 10.0 mg/dL; and (3) international normalized ratio (INR) ≥ 1.6. At week 4, HBV DNA levels were significantly lower (P = 0.037) in group 1 (median: 3.6721 log copies/mL) than group 2 (median: 4.2721 log copies/mL). Thereafter, HBV DNA levels were comparable in the 2 groups. The improvement in serum bilirubin, ALT, and INR values was similar in the 2 groups. Twenty‐two patients (71%) in group 1 and 25 patients (62.5%) in group 2 had severe AVH‐B. Results were similar when patients with severe AVH‐B were analyzed separately. After 12 and 18 months, 93.5% and 92.5%, respectively, of patients in the lamivudine group and 96.7% and 97.5%, respectively, of patients in the placebo group lost HBsAg. There were no deaths in either group. After 1 year, 21 patients (67.7%) in group 1 and 34 patients (85%) in group 2 developed protective anti‐HBs titers (P = 0.096). All HBeAg‐positive patients in both groups lost e antigen and anti‐HBe developed in 71% and 87.5% of patients in groups 1 and 2, respectively (P = 0.132). Conclusion: Though lamivudine causes a greater decrease in levels of HBV DNA, it does not cause significantly greater biochemical and clinical improvement as compared to placebo in patients with acute hepatitis B. HEPATOLOGY 2007;45:97–101.)

Risk factors analysis for hepatocellular carcinoma in patients with and without cirrhosis: a case-control study of 213 hepatocellular carcinoma patients from India.

Aim:  To assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol intake as risk factors for hepatocellular carcinoma (HCC) in the presence or absence of cirrhosis in Indian population.

Effect of lowering HBV DNA levels by initial antiviral therapy before adding immunomodulator on treatment of chronic hepatitis B.

BACKGROUND:Lower hepatitis B virus DNA (HBV DNA) levels are associated with better responses in chronic hepatitis B (CHB). It is unclear whether an initial phase of antiviral treatment to lower HBV DNA levels before adding immunomodulator therapy is more effective than the strategy of using immunomodulators from the beginning.AIM:The aim of the study was to compare the efficacy of lamivudine followed by pegylated-interferon (peg-IFN) therapy with placebo followed by peg-IFN therapy in HBeAg-positive CHB patients.PATIENTS AND METHODS:Sixty-three treatment-naive HBeAg-positive patients with histologically proven CHB and alanine aminotransferase (ALT) > 1.2 × upper limit of normal (ULN) received placebo for 4 wk followed by peg-IFN 1.0 μg/kg/wk for next 24 wk (group A, N = 27; age 32 ± 11yr; M:F = 25:2) or lamivudine 100 mg per day for 4 wk followed by peg-IFN 1.0 μg/kg/wk for next 24 wk (group B, N = 36; age 32.5 ± 10.5 yr; M:F = 31:5). Patients were followed for next 24 wk after completion of treatment. Biochemical and virologic responses were assessed at weeks 4, 28, and 52 and analysis was done on intention-to-treat basis.RESULTS:At wk 4, mean ± SD of log change in DNA from baseline was 0.2594 ± 1.7873 in group A and 1.2186 ± 1.6347 in group B, respectively (P = 0.032). At week 28, undetectable HBV DNA was seen in eight (29.6%) and 16 (44.4%) patients in groups A and B, respectively (P = 0.298). At week 28, HBeAg loss occurred in eight (29.6%) in group A and 15 (41.7%) in group B (P = 0.43). Six months posttherapy, at week 52, undetectable HBV DNA was seen in four (14.8%) and 18 (50%) in groups A and B, respectively (P = 0.028) and HBeAg loss was maintained in four (14.8%) and 14 (38.9%) (P = 0.05) patients. Normal ALT was seen in five (18.5%) and 10 (27.8%) at week 28 (P = 0.552) and five (18.5%) and 13 (36.1%) at week 52 (P = 0.159) in groups A and B, respectively. There was a significant correlation among achievement of HBeAg loss, anti-HBe appearance, and undetectable HBV DNA levels at week 28 (P = 0.008) and 52 (P < 0.001) and HBV DNA levels at week 4.CONCLUSIONS:The strategy of using an antiviral initially to decrease HBV DNA levels before adding an immunomodulatory agent leads to improved sustained virological response as compared with using immunomodulator from the start.

Insulin resistance in chronic hepatitis B virus infection.

OBJECTIVES:Chronic hepatitis C virus infection is associated with insulin resistance (IR), and both host and viral factors are important in its development. The association and the predictors of IR in chronic hepatitis B virus (CHBV) infection remain unclear.METHODS:A total of 69 CHBV-infected subjects were examined to study the relationship between histological findings and anthropometric and biochemical data, including IR determined by the homeostasis model assessment (HOMA–IR). To assess the influence of CHBV infection on IR independent of any effect of hepatic fibrosis, overweight, or sex we also compared fasting serum insulin, C-peptide, HOMA–IR, HOMA-β (measure of β-cell function) and C-peptide–insulin ratio (to distinguish impaired insulin degradation (low ratio) from insulin hypersecretion (normal ratio)) levels between the subset of 14 male normal weight (body mass index, BMI<23) CHBV patients with stage 0 or 1 hepatic fibrosis and 50 male normal weight healthy controls matched by age and anthropometry (BMI and waist circumference).RESULTS:A total of 31 (44.9%) CHBV-infected patients were overweight (BMI>23 kg/m2) and 18 (26.1%) were obese (BMI>25 kg/m2). IR was seen in 34 (49.3%) patients. BMI (Spearmans coefficient=−0.436; P<0.001) and serum triglyceride levels (Spearmans coefficient=−0.307; P=0.010) were univariate predictors of IR. In multiple linear regression analysis, only BMI (P<0.001) was an independent predictor of HOMA–IR. The subgroup of CHBV-infected patients and the controls had comparable levels of all markers of IR, including fasting glucose, insulin, C-peptide, and HOMA–IR.CONCLUSIONS:IR in CHBV-infected patients is a reflection of the host metabolic profile and CHBV infection is not in itself correlated with IR.

Steatosis in chronic hepatitis B: Prevalence and correlation with biochemical, histologic, viral, and metabolic parameters

BACKGROUND AND AIMS Hepatic steatosis (HS) is highly prevalent in chronic hepatitis C and is an important variable predicting progression of histological injury, insulin resistance, and reduced response to antiviral therapy. There are limited data on HS in patients with chronic hepatitis B (CHB). This is relevant since response to current antiviral therapies for CHB is rather limited. We investigated the spectrum and predictors of HS in CHB patients. MATERIALS AND METHODS Liver biopsies of consecutive patients of chronic Hepatitis B Virus (HBV) infection were studied and were categorized as: Group I - hepatosteatosis (>5%) and Group II - no steatosis (£5%). Anthropometric, histological, biochemical, virological, and metabolic determinants were compared. Logistic regression analysis was applied to identify variables that were independently associated with the presence of steatosis. RESULTS Of the 350 patients, 118 (33.7%) liver biopsies showed steatosis (Group I); 65 (55.1%) had mild (6 to <25%) and 53 (44.9%) had moderate to severe steatosis ((3)25%). Patients in group I, compared with group II, were older (35.5 ± 10.5 vs 27.9 ± 14.0 years, P < 0.01), predominantly male (M: F, 10.8: 1 vs 4.8: 1, P = 0.035), obese (75.0% vs 23.4%, P P < 0.01), with higher triglycerides (138.8 ± 62.1 vs 88.0 ± 27.9, P = 0.02), with higher cholesterol (171.9 ± 43.5 vs 139.3 ± 37.6, P = 0.017), and with higher serum insulin (13.1 ± 9.1 vs 9.1 ± 6.0, P < .027) levels. HBV DNA level was significantly lower in group I than group II; however, HBV genotype did not influence HS. By multivariate regression analysis, only high serum triglyceride level was independent parameter associated with HS. CONCLUSIONS Steatosis is seen in one-third cases with HBV-related chronic liver disease and is associated with host metabolic factors, especially serum triglyceride levels, whereas HBV DNA level negatively correlated with HS.

HEPATITIS B VIRUS GENOTYPES AND HEPATITIS B SURFACE ANTIGEN MUTATIONS IN FAMILY CONTACTS OF HEPATITIS B VIRUS INFECTED PATIENTS WITH OCCULT HEPATITIS B VIRUS INFECTION

Background:  The association and profile of surface gene mutations with viral genotypes have been studied in patients with chronic hepatitis B virus (HBV) but not in subjects with occult HBV infection.

Spontaneous increases in alanine aminotransferase levels in asymptomatic chronic hepatitis B virus-infected patients.

BACKGROUND & AIMS No information is available about the frequency or factors that predict spontaneous increases in alanine aminotransferase (ALT) levels in asymptomatic Indian patients with chronic hepatitis B virus (HBV) infection who are HB e antigen (HBeAg) negative and have normal ALT levels. METHODS We followed 217 asymptomatic patients with chronic HBV who were HBeAg negative, anti-HBe antigen (anti-HBe) positive, and had normal ALT levels. Spontaneous increases in ALT levels (ALT flares) were considered to be >2-fold the upper limit of normal (ULN) and were accompanied by HBV DNA levels>or=10(5) copies/mL or a 100-fold increase from the previously measured level. RESULTS During a median follow-up period of 69.0 months, spontaneous ALT flares occurred in 43 patients (an annual rate of 4.3%), with cumulative probabilities of 10.8% and 47.3% after 5 and 10 years, respectively. Based on multinomial logistic regression, the probability of an ALT flare correlated with age>or=30 years at presentation (odds ratio [OR], 5.31; 95% confidence interval [CI]: 1.53-18.39; P=.008), male sex (OR, 4.54; 95% CI: 1.01-20.76; P=.05), and presence of a precore mutation (OR, 10.99; 95% CI: 3.67-32.92; P<.001). The median time to spontaneous ALT flare after enrollment was 25 months (range, 1-128 months; 10th percentile=3.4 months). CONCLUSIONS In asymptomatic patients with chronic HBV infection who have normal ALT levels and are HBeAg negative, the annual rate of ALT flares was 4.3%. Precore mutants, male sex, and age>or=30 years at presentation are independent predictors for an ALT flare. A follow-up every 3 months can capture up to 90% of flares and would help identify patients who require antiviral therapy.

Hepatic venous pressure gradient as a predictor of fibrosis in chronic liver disease because of hepatitis B virus.

Background: Liver biopsy has been considered to be a gold standard for assessing hepatic fibrosis. Sample variability, interobserver variability and step‐wise evaluation limit its use. Hepatic venous pressure gradient (HVPG) correlates with hepatic fibrosis in chronic liver disease (CLD) because of hepatitis C.

Gene expression signatures of peripheral CD4+ T cells clearly discriminate between patients with acute and chronic hepatitis B infection†

CD4+ T and regulatory T cells (Tregs) seem to play a key role in persistence of hepatitis B virus (HBV) infection. However, the molecular events by which Tregs exert their modulatory activity are largely unknown. The transcriptional profiles of CD4+ T cells of healthy controls (HCs) and patients affected by acute hepatitis B (AVH‐B) or chronic hepatitis B (CHB) infection were established using a custom expression array consisting of 350 genes relevant for CD4+ T cell and Treg function. These studies were complemented by real‐time reverse‐transcription polymerase chain reaction. Peripheral blood mononuclear cells (PBMCs) were also analyzed for the presence of Tregs, which were more abundant in the acute stage of the disease (7%) than in HCs and CHB infection (HCs versus AVH‐B, P = 0.003; AVH‐B versus CHB, P = 0.04). One hundred eighteen genes (34%) intrinsically differentiate HBV‐infected patients from HCs. Using gene ontology, we identified T cell receptor signaling and clusterization, mitogen‐activated protein kinase kinase signaling, cell adhesion, cytokines and inflammatory responses, cell cycle/cell proliferation, and apoptosis as the most prominent affected modules. A higher expression of CCR1, CCR3, CCR4, CCR5, and CCR8 was seen in AVH‐B than in CHB‐infected patients and HCs. Annotation of the interconnected functional network of genes provided a unique representation of global immune activation during acute infection. Almost all genes were down‐regulated in patients with CHB infection. Conclusion: The fingerprints enable clear discrimination between patients suffering from AVH‐B or CHB infection. The observed profiles suggest accumulation of effector T cells with a potential role in necro‐inflammation during the acute stage. Subsequent down‐regulated effector functions support the hypothesis of suppressed CD4+ effector T cells favoring viral persistence in the chronic infection stage. (HEPATOLOGY 2009.)

Comparison of low‐dose pegylated interferon versus standard high‐dose pegylated interferon in combination with ribavirin in patients with chronic hepatitis C with genotype 3: An Indian experience

Background and Aims:  In chronic hepatitis C virus (HCV) infection with genotype 3, therapy with pegylated interferon (peg‐IFN) alfa‐2b in a dose of 1.5 μg/kg/week and ribavirin (800–1000 mg/day) is recommended for 24 weeks. Reduced doses of peg‐IFN may increase compliance and decrease cost and adverse events. This study aimed to assess the safety and efficacy of two different regimens of peg‐IFN alfa‐2b, in combination with ribavirin, in genotype 3 patients.