Role of HBV genotype in predicting response to lamivudine therapy in patients with chronic hepatitis B.

BACKGROUND: Predictors of response of chronic hepatitis B (CHB) to lamivudine therapy need better definition. Whether hepatitis B virus (HBV) genotypes could serve as such a predictor has not been well studied. AIM: To study the association of HBV genotypes with the outcome of lamivudine treatment in patients with CHB. METHODS: Seventy-six patients with CHB (45 HBeAg +ve) received lamivudine 100 mg/day, orally for 12 mo. Infecting HBV genotypes were determined in pre-treatment specimens using restriction fragment length polymorphism. End-of-treatment response (ETR) and sustained viral response (SVR) were defined as undetectable HBV DNA (< 0.5 pg/mL) at 12 and 18 months, respectively. RESULTS: ETR was observed in 26 (34%) and SVR in 11 (14%) patients receiving lamivudine. The pre-treatment characteristics of the responders and non-responders were comparable. Genotypes A and D were observed in 28 (37%) and 48 (63%) patients, respectively. The frequency of genotypes A and D was comparable between responders (28.6% vs. 37.5%) and non-responders (71.4% vs. 62.5%), respectively (p=ns). Of the 26 responders, SVR could be evaluated in 20 subjects; 9 (45%) relapsed and 11 achieved SVR. Patients with genotype D achieved higher SVR rate than genotype A (10 of 48, 28.8% vs. 1 of 28, 3.5% p =0.0359). CONCLUSIONS: Forty-five percent of Indian patients with CHB who achieve ETR relapse, and SVR to lamivudine therapy is achieved in 14%. Patients with genotype D achieve higher SVR rate than with genotype A.

Prevalence of hepatitis B infection within family contacts of chronic liver disease patients--does HBeAg positivity really matter?

BACKGROUND: The risk of infectivity is known to be high in contacts of HBeAg positive chronically infected patient. We investigated and compared the frequency and significance of transmission of HBV infection from chronic liver disease patients (CLD) with HBeAg or anti-HBe and HBV DNA positive status. MATERIAL AND METHODS: Four hundred and seventy nine contacts [first degree blood relatives (n=278), second degree contacts (n=139) and sexual contacts (n=62)] of 92 HBV-related, liver biopsy proven, CLD patients were studied. Three hundred and seventy three belonged to 65 index patients with HBsAg+ve, HBeAg+ve, HBV DNA+ve, HBV DNA+ve infection and 106 belonged to 27 index patients with (HBsAg+ve, HBeAg-ve, anti-HBe+ve, HBV DNA+ve infection). One hundred and seventy six family members, age and sex matched, belonging to 38 healthy individuals, with no history of liver disease or HBV positivity, served as controls. Viral serology and quantitative DNA estimation was done in index patients. RESULTS: Forty nine of 65 (75.4%) families of HBeAg+ve and 63% families of HBeAg-ve index patients had one or more family member exposed to HBV (positive family, p=ns). The chronic HBV infection (HBsAg+ve) and past-exposure (only IgG anti-HBc+ve) rates in the contacts of HBeAg+ve and HBeAg-ve index patients were 17.4% and 19.8% (p=ns), and 31% and 14.2% respectively, both being significantly higher (P < 0.01) than the prevalence rates in the control group (chronic HBV infection 2.3%, past-exposure 10.2%). Overall, 48.5% and 34% (p < 0.05) of contacts in the HBeAg+ve and HBeAg-ve groups had markers of HBV infection. The quantitative HBV DNA levels were comparable between HBeAg+ve and HBeAg-ve index patients (1712 +/- 356 pg/ml vs 1802 +/- 812 pg/ml). First degree relatives had higher chronic HBV infection rates than second degree contacts (29% vs. 0%, p < 0.05). The duration of symptomatic illness of HBeAg+ve index patients was longer than HBeAg-ve (p < 0.05). A significant proportion of HBsAg+ve first degree relatives of HBeAg+ve (33%) and HBeAg-ve (40%) patients, had evidence of CLD. CONCLUSIONS: (i) The frequency of transmission of HBV infection is nearly similar in contacts of HBeAg+ve and HBeAg-ve infected patients, more so in first degree relatives, (ii) these observations make family contacts a very high risk group, requiring priority screening and vaccination against HBV.

High seroprevalence and clinical significance of hepatitis B and C infection in hospitalized patients with alcoholic cirrhosis.

OBJECTIVES: Patients with alcoholic cirrhosis (AC) are frequently infected with hepatotropic viruses which could alter the clinical spectrum of the disease. We studied the seroprevalence of hepatitis B (HBV) and hepatitis C virus (HCV) and their impact on the clinical profile of patients with AC. METHODS: Two hundred and ten hospitalized patients of AC were studied and screened for markers of HBV and HCV infection. Clinical, biochemical and virological correlation was done. RESULTS: One hundred and forty (66.6%) patients had no viral infection Group I, 50 (23.8%) were positive for HBsAg Group II and 20 (9.5%) for anti-HCV Group III. All patients were males with comparable ages (43.9 years, 44 years and 45.9 years respectively). The amount of alcohol consumed by patients in Group III (130 +/- 115 g/d) was significantly less than Group II (204 +/- 130 g/d, P < 0.05) and Group I (281 +/- 188 g/d, p < 0.001). The duration of alcohol abuse was shorter in Group II and III, although not statistically significant. Presentation as jaundice was common in Group II and III (p < 0.05). The AST and ALT values (IU/L) were significantly higher in Group II (239 +/- 351, 197 +/- 266) and III (157 +/- 170, 86 +/- 52) than Group I (89 +/- 78, 66 +/- 54) (P < 0.05). The serum alkaline phosphatase (IU/L) was higher in Group III (349 +/- 223) as compared to Group II (263 +/- 186) and Group I (162 +/- 62) (P < 0.05). There was however, no difference in Child's grade or the discriminant function between the three groups of patients. CONCLUSIONS: (i) One-third of the hospitalized patients with AC are infected with HBV or HCV infection, (ii) these infections hasten clinical presentation of patients with alcoholic liver disease, with lesser amount of alcohol consumption and (iii) jaundice, raised ALT/AST and alkaline phosphatase are more common with superadded viral infection.

Clinical implications of viral activity in dual infection with hepatitis B and C in chronic liver disease.

BACKGROUND: There is limited information on the clinical and biochemical profile of chronic liver disease due to dual infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. There are variable reports on the severity of liver disease in dual infections. This is important, from clinical and therapeutic point of view. The present study analyzes liver disease in dual infections as compared to HBV and HCV infection present alone. MATERIAL AND METHODS: Out of 186 histologically proven non-alcoholic chronic liver disease patients, 30 (16.1%) were serologically diagnosed to be HBV and HCV dual infection (Group A, n=30). The clinical profile of these patients was compared with consecutively seen HBV related (Group B, n=30) and HCV related chronic liver disease (Group C, n=30) patients. Patients with dual infection were further grouped based on predominant HBV or HCV viral activity. RESULTS: Patients with dual infection were younger than those with chronic HCV infection (38.4 +/- 14.4 vs. 45.9 +/- 14.7 years, p < 0.05); with male predominance (p=0.06). Patients with chronic HCV infection more often presented with low-grade fever than dual infection group (60% vs. 30%, p < 0.05). Ascites and variceal bleeding were common presentations of HBV related cirrhosis. Patients with dual infection had significantly more deranged liver functions. The duration of illness was shorter in these patients compared with chronic HCV (2.9 +/- 1.6 vs. 7.3 +/- 1.4 year, p < 0.05). When patients with dual infection were subgrouped on HBV DNA and HCV RNA positivity, there was a tendency for increased biochemical derangement with active HBV infectionity. CONCLUSIONS: Our results highlight the fact that patients with HBV and HCV dual infection related chronic liver disease have a more aggressive course. There is a tendency for a more severe liver disease when HBV is active in the dual infection group.

Increased frequency of gallstones in cirrhotic and non-cirrhotic portal hypertension.

BACKGROUND: The prevalence of gallstones is high in cirrhotics compared with the general population. It is not clear whether cirrhosis per se or presence of portal hypertension influences this increased frequency. MATERIAL AND METHODS: Six hundred and fifteen patients with portal hypertension; 412 cirrhosis (69 alcoholic and 343 non-alcoholic), 88 non-cirrhotic portal fibrosis (NCPF) and 115 extrahepatic portal vein obstruction (EHPVO) were prospectively studied by using real time ultrasound to investigate the prevalence of gallstones in comparison to a matched healthy population. RESULTS: Gallstones were observed in 44 (7.2%) portal hypertension patients compared with 19 (3.1%) controls (p < 0.01), the risk ratio was 2.41 (CI=1.35-4.35, OR 95%). The prevalence of gallstones was 6.8% in cirrhosis, 10.2% in NCPF and 4.3% in EHPVO patients. The overall prevalence was similar in cirrhosis and non-cirrhotics (6.8% vs 6.6%). Gallstones were slightly more common in alcoholic than non-alcoholic cirrhotics (8.3% vs. 6.0%), patients with Child's C than A and B disease (8.2% vs. 5.4%), the differences were however, not significant. Portal pressure as assessed by intravariceal pressure estimation (n=102) was comparable in patients with cirrhosis, NCPF and EHPVO. CONCLUSIONS: (i) Gallstones are more than two times common in portal hypertension patients compared to the control population, and (ii) since gall stones are equally common in cirrhotic and non-cirrhotic portal hypertension; a role of portal hypertension per se in the genesis of gallstones needs to be considered.

Prevalence of hepatitis GB virus C/hepatitis G virus infection in blood donors in India.

BACKGROUND: Hepatitis GBV-C/HGV is a newly described RNA virus with a parenteral route of transmission. It has been implicated in fulminant hepatitis and chronic viral hepatitis. We undertook to study the prevalence of GBV-C/HGV infection in blood donors of a tertiary care hospital in India. METHOD: Serum of 221 consecutive blood donors was tested for HBsAg, anti-HCV by EIA and HGV RNA by RT-PCR. Two sets of primers; one from the 5'non-coding region and other from NS5a region of the HGV genome, were used for amplification. RESULTS: Prevalence of HGV RNA was found to be very low in healthy blood donors. Only two of the 221 (0.9%) donors were found to be HGV RNA positive. HBsAg and AntiHCV were found to be present in 5.43% (12/221) and 1.31% (3/221) respectively. Dual infection was seen in two of the 221 (0.9%) patients; one patient had HBsAg and HGV RNA positivity, while the other, had HBsAg and AntiHCV positivity. CONCLUSION: GBV-C/HGV is an uncommon infection in healthy blood donors in India, especially when compared to the prevalence of HBV and HCV infection. It is therefore unlikely to be an important cause of transfusion associated hepatitis in India.

Low prevalence of hepatitis C viral infection in patients with non-alcoholic chronic liver disease in India.

To investigate the prevalence and profile of chronic liver disease due to hepatitis B (HBV) and C (HCV) infection in patients with non-alcoholic chronic liver disease in North India, 148 biopsy proven patients (73 with a history of transfusion and 75 non-transfused) were studied. Detection of hepatitis B included HBsAg, AntiHBc, and HBV DNA testing. Presence of HCV infection was investigated by EIA using second generation tests and confirmed by RIBA III and HCV RNA testing. Eighty three (56.1%) patients had cirrhosis related to hepatitis B, 13 (15.7%) of them had precore (HBeAg -ve, HBVDNA +ve) and 11 (13%) had surface (HBsAg-ve, IgM antiHBc-ve, HBVDNA +ve) mutation. Antibodies to HCV were found in 16 (10.8%) patients. Dual infection with HBV and HCV was seen in 20 (13.5%) patients. Twenty nine (19.5%) patients, had cryptogenic cirrhosis as none of the markers for HBV or HCV infection was positive. In conclusion, our results demonstrate that HBV was the most prevalent viral infection associated with chronic liver disease patients in North India. Prevalence of HCV infection was low. Studies to detect HBV mutants and other viruses should be done in patients with suspected cryptogenic cirrhosis of the liver.