Correlation between two chemiluminescence based assays for quantification of hepatitis B surface antigen in patients with chronic hepatitis B infection.

Purpose: Hepatitis B surface Antigen (HBsAg) is the hallmark in diagnosing hepatitis B virus (HBV) infection. In India many commercial assays are available for detection of HBsAg but very few can measure it quantitatively. The present study presents the comparative evaluation of two methods and their correlation with serum HBsAg in chronic hepatitis B (CHB) patients. Materials and Methods: Consecutive patients of CHB were included and there HBsAg levels were measured by two methods: (i) Elecsys, Roche Diagnostics, a qualitative assay and (ii) Architect, Abbott Diagnostics, a quantitative assay. The HBV DNA was measured by real-time polymerase chain reaction (qPCR). Results: Total of 136 patients were included in the study and there was a signifi cant overall correlation between both the assays (correlation coeffi cient [r] = 0.83; P < 0.001). Assays correlated well with each other across all subgroups of CHB: treatment naïve (r = 0.73; P < 0.001, n = 32), on treatment (r = 0.56; P < 0.05, n = 104), hepatitis Be (HBe) antigen positive (r = 0.67; P < 0.001, n = 62) and anti-HBe positive (r = 0.61; P < 0.05, n = 74) group. On correlation with serum HBV DNA, Architect assay demonstrated good correlation (r = 0.73; P < 0.001, n = 136) as compared to the Elecsys assay (r = 0.27; P = 0.068, n = 136). Architect HBsAg QT assay (A1) also correlated well with HBV DNA in the treatment naïve group (r = 0.69; P < 0.001, n = 32). Conclusions: Our study hence proved that both the assays are comparable and a simple qualitative assay with in-house modifi cation can be used easily for quatitation of HBsAg in clinical samples.

Serum hepatitis B surface antigen levels correlate with high serum HBV DNA levels in patients with chronic hepatitis B: A cross-sectional study.

Purpose : The hallmark of chronic hepatitis B (CHB) infection is the presence of hepatitis B surface antigen (HBsAg) positivity for at least 6 months. Recently, serum levels of HBsAg have been compared with serum HBV DNA as a surrogate marker to monitor CHB patients. However, data correlating these two markers are scarce. Hence, the present study was done to correlate HBV DNA with HBsAg in CHB patients. Materials and Methods: Consecutive patients of CHB were included. HBV DNA was measured by real-time polymerase chain reaction (PCR). Serum HBsAg was measured by Architect HBsAg. Results: Of the 198 patients enrolled, 166 fulfilled the inclusion criteria (mean age 43 ± 14 years, 87% males) and the median HBV DNA was 1.7 × 10 3 (range 6.0-1.1 × 10 8 ) IU/ml. Median HBsAg was 8.7 × 10 3 (range 5.0-3.2 × 10 5) IU/ml. Overall correlation between HBV DNA and HBsAg was weak but significant (Spearman ρ = 0.443, P < 0.01). Correlation in HBe antigen-positive group was better (ρ = 0.402, P < 0.01) in comparison to HBe antigen-negative group (ρ = 0.193 P = 0.05). Good correlation existed in treatment-naïve group (ρ = 0.538, P < 0.01) .Correlation was regardless of normal or raised alanine transaminase (ALT). Eighty (48%) patients had high HBV DNA (≥2000 IU/ml). Correlation in high DNA group was significant (P < 0.01). The best cut-off of HBsAg for diagnosing high DNA is 3.36 ×10 3 IU/ml. Conclusions: Serum HBsAg correlates with HBV DNA in CHB patients, especially in high serum HBV DNA, HBe antigen-positive and treatment-naïve group. HBsAg levels can be used for predicting high serum HBV DNA levels.

Is cirrhosis of the liver reversible?

Extensive and persistent hepatic fibrosis has for a long time been considered irreversible. Accumulating evidence suggests that liver fibrosis is reversible and that recovery from cirrhosis may be possible. The application of molecular techniques to models of reversible fibrosis are helping to establish the events and processes that are critical to recovery. The problem consists in identifying and eliminating its cause. Although fibrosis in the liver has little functional significance by itself, its severity derives from associated vascular changes. Disappearance of fibrosis can be accompanied by remodeling of vascular changes. However, depending on its duration, the fibrosis may be irreversible.

Cholestatic liver injury due to ibuprofen.

Ibuprofen is a member of the propionic acid class of NSAID. We report a 35-year-old man with ibuprofen-induced acute severe cholestatic liver injury. He recovered after seven months.

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.

Diaphragm disease of duodenum following long-term NSAIDs use: endoscopic management.

We report our experience with endoscopic management of 3 men (aged 62, 63 and 65 years) with duodenal diaphragm disease following NSAID use for 5-15 years. In the first patient a 24 F through-the-scope balloon dilatation was attempted but failed; he subsequently underwent gastro-jejunostomy. The other two patients subsequently underwent radial incisions of the web with mixed cutting and coagulation current using a standard 5 F sphincterotome.

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.

Profile of asymptomatic chronic HBV infection in India.

BACKGROUND & OBJECTIVES: In India, horizontal transmission in early childhood has been shown to be a significant mode of transmission of hepatitis B virus (HBV). This prospective, cross-sectional study was undertaken to study the biochemical, serological and histological profile of incidentally detected asymptomatic HBsAg positive subjects (IDAHS) picked up at a tertiary care referral centre. METHODS: In 157 (M:F::123:34) HBsAg positive subjects, clinical, biochemical, virological and histological assessment was done. The histological activity index (HAI) of > 3 was considered as chronic hepatitis. Serum was tested for HBsAg, HBeAg, HBeAb, HBV DNA and alanine transaminase (ALT). RESULTS: Seventy (45%) subjects were HBeAg and 83 (53%) anti-HBe positive. While 71 per cent of the subjects with elevated ALT had an HAI > 3, only 36 per cent with normal ALT showed significant histological changes (P < 0.001). Significant histopathological lesions in the liver biopsy were seen in 92 (59%) subjects, with moderate to severe lesions in 14. IDAHS who were HBeAg +ve were more likely to have significant histological lesion than those who were anti-HBe +ve (P < 0.01). In the anti-HBe +ve group, 35 of 57 (61%) subjects for whom HBV-DNA was available, were HBV-DNA positive. Anti-HBe+ve, HBV-DNA+ ve IDAHS with elevated ALT were more likely to have chronic hepatitis vis-a-vis those subjects in this group who had a normal ALT (P < 0.001). INTERPRETATION & CONCLUSION: ALT is a reliable discriminant of significant histological lesion in IDAHS. The relatively young mean age of Anti-HBe +ve IDAHS suggests an early age of infection and hence, early seroconversion or mutant virus infection in this cohort. A significant proportion of these IDAHS have HBV-DNA positivity and HAI > 3. Our results clearly demonstrate ongoing liver disease in asymptomatic, so-called "HBV carriers". We propose that the term hepatitis B 'carrier' should be abandoned and replaced by 'chronic HBV 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.

Clinical, biochemical and histological profile of nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) has often been described in obese women with diabetes and/or hyperlipidemia. We evaluated the clinical, biochemical and histological profile of NASH. METHODS: 52 patients with persistently elevated ALT (>40 IU/L) for >6 months with no history of significant alcohol consumption and negative serological work-up for hepatitis B and C and HIV were enrolled. Twenty-five patients were diagnosed as having NASH and their clinical, biochemical, and histological profile was evaluated. RESULTS: Of the 25 patients with NASH (mean age 33 years), 24 were men. Three were obese, seven had hyperlipidemia and two had impaired glucose tolerance. Thirteen patients presented with pain in the right hypochondrium, three with fatigue and weakness, and nine were asymptomatic. No patient had evidence of portal hypertension or liver cell failure. Mild elevation of ALT was the most common biochemical abnormality. Twenty-three of the 25 patients had ALT/AST ratio >1.0. Liver histology revealed macrovesicular steatosis in all, with mild inflammatory activity in the majority (70%). Fibrosis was seen in 12 patients-portal fibrosis in six, periportal fibrosis in three and bridging fibrosis in another three patients. None of the patients had features of cirrhosis. None of the factors was found to be associated with fibrosis except serum AST level, which was significantly higher in patients with fibrosis as compared to those without (89 [52] vs. 54 [18] IU/L; p<0.05). CONCLUSIONS: NASH is often seen in men, in the absence of obesity, diabetes and hyperlipidemia, and its severity is better assessed by liver histology than clinical assessment.

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.

Blood transfusion practices in India: results of a national survey.

BACKGROUND: Blood transfusion may lead to serious clinical consequences for the recipient, if the transfused blood is not safe. To assess the functioning of the blood banks in India, a nation-wide, questionnaire-based study was conducted between November 1995 and November 1996 under the auspices of the Indian Association for Study of the Liver. METHODS: Of 604 blood banks in 31 states and union territories to whom the questionnaires were sent, responses wereobtained from 78 (13%) blood banks in 17 (54.8%) states, providing information on 275,000 donors. RESULTS: A majority (58%) of donors in these blood banks were replacement donors, followed by voluntary (39.3%) donors. About 87% of the respondent blood banks screen blood for hepatitis B, 95% for HIV, 94% for syphilis, 67% for malaria, and only 6% for hepatitis C. Marked heterogeneity in the test methods was observed with only 13% using ELISA kits for HBsAg. Only 21% of the blood banks prepare blood-derived components. Feedback to the blood banks on the occurrence of transfusion-associated hepatitis is given on less than 40% of occasions. CONCLUSIONS: Testing for transfusion-transmitted infections is unsatisfactory and poorly regulated in India. Reporting of adverse events after transfusion is poor and no stringent donor deferral system exists.

Histological comparison of chronic hepatitis B and C in an Indian population.

Many studies have shown that steatosis, lymphoid aggregates or follicles and bile duct injury on histology are more consistently associated with chronic hepatitis C than chronic hepatitis B. We compared liver biopsies of 30 patients of chronic hepatitis B with an equal number of age matched patients with chronic hepatitis C. Steatosis, lymphoid aggregates or follicles and bile duct injury were noted in 66.6%, 36.6% and 26.6% cases respectively of chronic hepatitis B as compared to 70%, 33.3% and 30% cases respectively of chronic hepatitis C. Thus none of the features were considered distinctive of HCV infection.