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Veena Malhotra

Publications and source records attributed to Veena Malhotra.

18 recordsLinked to original sources

Hepatitis C virus genotype 3 predominates in North and Central India and is associated with significant histopathologic liver disease.

Hepatitis C virus (HCV) genotypes help to tailor the treatment response, but their influence on the disease severity and association with hepatic steatosis is not well understood. The prevalence of HCV genotypes and their correlation with the histopathological severity of liver disease and steatosis in Indian patients were studied. HCV-RNA and genotyping was carried out in 398 patients with chronic hepatitis C. Liver biopsy was available in 292 (73.4%) patients. The severity of liver disease was graded on the basis of the histological activity index and the stage of hepatic fibrosis. The patients were categorized as having mild (histological activity index < or =5 and/or fibrosis < or =2) or severe (histological activity index > or =6 and/or fibrosis > or =3) liver disease. Steatosis was graded in 106 patients as 0 (no steatosis), 1 (<33% of hepatocytes affected), 2 (33%-66% of hepatocytes affected), or 3 (>66% of hepatocytes affected). HCV genotype 3 was detected in 80.2% patients (3a:24.4%, 3b:3.3%, 3c:0.5%, 3a/3b:36.7%, and un-subtypable 3:15.3%), genotype 1 in 13.1% (1a:3%, 1b:5.5%, 1a/1b:0.3%, and un-subtypable 1:4.3%), genotype 4 in 3% patients (4a:1.5%, 4b:0.3%, 4a/4c:0.5%, and un-subtypable 4:0.8%), 2 in 2.5% and mixed genotypes (more than one genotype) in 1.3% of patients. The median histological activity index and fibrosis scores were: 5 and 2 in genotype 1; 4 and 2 in genotype 2; 5 and 2 in genotype 3; 7 and 3 in genotype 4; and 5 and 2 in mixed genotypes, respectively. Severe liver disease was present in 17 of 38 (45%) with genotype 1; in 1 of 3 (33%) with genotype 2; in 128 of 236 (54%) with genotype 3; 7 of 10 (70%) with genotype 4; and in 1 of 4 (25%) with mixed genotype. Hepatic steatosis grade > or =2 was found in 28.1% of genotype 3; 23.5% of genotype 1; 20% of genotype 4; and in none of genotype 2 and mixed genotypes. In conclusion, genotype 3 is the most prevalent genotype in patients with chronic hepatitis C in North and Central India and this is associated with significant hepatic steatosis and fibrosis.

Adolescent↗

Primary biliary cirrhosis in India.

BACKGROUND: Primary biliary cirrhosis (PBC) is a rare cause of chronic liver disease in India. We analyzed the clinical, biochemical, serological and histological features of patients with PBC for over a 10-year period. METHODS: PBC was diagnosed by the presence of raised level of serum alkaline phosphatase (ALP), anti-mitochondrial antibody (AMA) positivity (1:40 dilution), and/or diagnostic liver histology. RESULTS: Fifteen female patients with mean age of 46.5+/-11 years were studied. Pruritus (80%) followed by jaundice (67%), skin changes (pigmentation, coarsening, xanthelesma and vitiligo) (67%) and fatigue (60%) were common symptoms. The mean duration of the symptoms was 3.5+/-5.4 years (3 months to 20 years). Dryness of eyes was observed in only 2 patients. Hepatomegaly was noted in 87% of the patients and ascites at presentation in 40%. Mean levels of bilirubin and albumin at the time of diagnosis were 3.4+/-3.3 mg/dl and 3.5+/-0.8 g/dl, respectively. The level of serum ALP ranged from 54 to 2400 IU/L, with a median being 552 IU/L (2 x ULN). In all the 15 patients with AMA positive, 8 (53%) were also positive for either anti-nuclear or anti-smooth muscle antibodies. Two patients presented with persistently elevated SAP after an acute hepatitic illness. Liver biopsy was available in 13 patients, diagnostic of PBC II & III (8) and with evidence of cirrhosis (5). Associated autoimmune disorders were observed in 5 patients (33%). The mean time for follow-up was 26+/-21 months (1 to 87 months). In 4 deaths, 3 were due to liver related causes. CONCLUSION: PBC is a rare cause of chronic liver disease in India. PBC in India, unlike in the West, presents late, often with features of cirrhosis and decompensation.

Adult↗

Nonalcoholic steatohepatitis--a histological perspective.

Nonalcoholic Steatohepatitis (NASH) is a progressive liver disease that has gained recognition in the last two decades. It may even account for some of the cases previously diagnosed as cryptogenic cirrhosis. Association of this entity,with obesity, insulin resistance and type II diabetes is well documented. In this review we clarify the terminology and describe the histological features associated with NASH. Criteria for diagnosis, grading and staging systems and role of liver biopsy is also discussed.

Adult↗

Factors predicting advanced hepatic fibrosis in patients with postcholecystectomy bile duct strictures.

HYPOTHESIS: Simplified evaluation based on clinical and biochemical variables might predict the degree of hepatic fibrosis in patients with postcholecystectomy bile duct strictures. DESIGN: Prospective cohort study. SETTING: Tertiary care referral and teaching hospital. PATIENTS: Sixty-four patients with postcholecystectomy bile duct strictures undergoing definitive repair. Prospectively collected information included demographics, disease-related characteristics, and serial liver function tests. Hepatic histologic features (fibrosis, cholestasis, portal inflammation, and ductular proliferation) were independently graded by 2 pathologists masked to clinical data using a previously validated scale. Patients were dichotomized into groups based on degree of hepatic fibrosis. Univariate and multivariate analyses were performed. MAIN OUTCOME MEASURE: Identification of variables that predict the presence of advanced hepatic fibrosis (grade 2-3). RESULTS: Thirty-five patients (55%) had early hepatic fibrosis (grade 0-1), and the remaining 29 (45%) had advanced fibrosis (grade 2-3). Univariate analysis demonstrated that duration of biliary obstruction, presence of portal hypertension, basal alanine aminotransferase (ALT) levels, and time to normalization of serum total bilirubin, ALT, and alkaline phosphatase levels after surgical drainage were statistically significantly associated with the presence of advanced hepatic fibrosis. However, multivariate analysis revealed that only duration of biliary obstruction (odds ratio [OR], 1.6048; P =.009), basal ALT levels (OR, 0.9634; P =.02), and time to normalization of ALT levels after surgical drainage (OR, 1.6680; P =.006) were significant predictors of advanced hepatic fibrosis. CONCLUSION: Duration of biliary obstruction, basal ALT level, and time to normalization of ALT level after surgical repair are independent predictors of advanced hepatic fibrosis (grade 2-3) in patients with postcholecystectomy bile duct strictures.

Adolescent↗

Association of TNF-beta polymorphism with disease severity among patients infected with hepatitis C virus.

The pathogenesis of chronic hepatitis C virus (HCV) infection remains unclear. Tumour necrosis factor alpha (TNF-alpha) is alleged to contribute in the pathogenesis of chronic HCV infection. Single nucleotide polymorphism in TNF-alpha and -beta genes could influence the outcome of HCV infection. The aim was to study single nucleotide polymorphism in TNF-alpha promoter region and Nco I polymorphisms in the TNF-beta gene in patients with chronic hepatitis C. Fifty-two patients with histologically proven chronic hepatitis, who had raised ALT levels (>1.5 x ULN) and were HCV RNA positive, were studied. Genotyping of -308 promoter variant of TNF-alpha was performed by PCR with primers that incorporated an Nco I restriction site. For PCR typing of the TNF-beta Nco I restriction fragment length polymorphism, sequence specific primers were used. Polymorphism in the TNF-alpha G/G, G/A and A/A allele was not different between HCV patients and healthy controls. TNF-beta A/A allele was significantly more common (P = 0.02) in patients (28.8%) as compared to controls (12.8%), whereas no significant difference was observed for TNF-beta G/A and G/G alleles [corrected]. Nco I TNF-beta A/A was strongly associated with -308 TNF-alpha G/G (RR of HCV persistence = 4.9), indicating possible linkage between TNF-beta A/A and TNF-alpha G/G allele. Patients with severe hepatic fibrosis more frequently had the TNF-beta A/A allele as compared to patients with mild disease (P = 0.04). Immunogenetic factors, such as single nucleotide polymorphisms in TNF-beta (A/A allele), may affect the natural course of HCV infection, in particular, the disease progression. Larger studies including cytokine expression profiles are needed to fully understand the contribution of the polymorphisms described in the pathogenesis of chronic hepatitis C.

Alleles↗

Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been incriminated to play an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Pentoxifylline, a TNF-alpha inhibitor could prove useful in treating patients with NASH. METHODS: Eighteen patients (mean age, 34 +/- 7.8 yr) with histologically proven NASH and with persistently elevated ALT (>1.5 times) were given pentoxifylline at a dosage of 400 mg t.i.d. for 6 months. No lipid-lowering agent or antioxidants were concurrently advised. RESULTS: Impaired fasting glycemia, impaired glucose tolerance, diabetes mellitus, and hypertriglyceridemia were noted in 6, 35, 17, and 53% of the patients, respectively. After 6 months of therapy, fatigue improved (55.6 vs 20%, p= 0.016), but serum triglyceride (182 +/- 66 vs 160 +/- 55 mg/dl, p= 0.397), cholesterol (173 +/- 46 vs 162 +/- 40 mg/dl, p= 0.440), and body mass index (BMI) (27.3 +/- 3.1 vs 26 +/- 3.1 kg/m(2), p= 0.087) remained unchanged. Mean AST (66 +/- 29 vs 33 +/- 11 IU/l, p < 0.0001) and ALT (109 +/- 44 vs 47 +/- 20 IU/l, p < 0.0001) reduced significantly. ALT normalized in 23% at month 1 (p= 0.125), 35% at month 2 (p= 0.125), and 60% at month 6 (p= 0.008) of treatment. The insulin resistance index assessed by homeostatic metabolic assessment (HOMA(IR)) improved (5.1 +/- 3.4 vs 2.6 +/- 2, p = 0.046) and the serum TNF-alpha reduced significantly after therapy (22.15 +/- 2.49 vs 17 +/- 2.58 pg/ml, p = 0.011). The drug was well tolerated. CONCLUSIONS: In patients with NASH, pentoxifylline therapy effectively achieved significant clinical and biochemical improvement with reduction in HOMA(IR). These benefits are possibly mediated through suppression of TNF-alpha.

Adult↗

Histological spectrum of chronic hepatitis in precore mutants and wild-type hepatitis B virus infection.

This study compares the histology of liver biopsies in precore mutant (PCM) and wild-type hepatitis B virus (HBV) infection. Thirty cases of PCM and 60 cases of wild-type HBV infection were included. Patients were diagnosed on the basis of serological profile and HBV DNA assessment. Liver biopsies in each case were assessed for histological activity and stage of fibrosis using a modification of Knodell's scoring system. There was no statistically significant (P=0.14) difference in histological activity in the two groups. The difference in stage of fibrosis in the two groups was statistically significant (P=0.001). Quantitative estimation of viral load did not show any correlation with liver histology. PCM HBV showed greater stage of fibrosis compared with wild-type infection, and this may be related to disease progression and lack of response to therapy.

Adult↗

A randomized trial of a 4- vs 12-week daily interferon dose regimen combined with ribavirin in treatment of patients with chronic hepatitis C.

BACKGROUND: Standard combination-therapy of ribavirin with alternate day interferon (IFN) in patients with chronic hepatitis C (CHC) has been reported to achieve 30%-55% sustained viral response. Early reduction of viral load by daily dosage of IFN could enhance viral clearance. However, the duration of daily dosage protocol and the likely side-effects have not been well studied. We compared the efficacy and safety of a 4- vs 12-week daily IFN dosage in patients with CHC. METHODS: Fifty-nine, histologically proven CHC patients having ALT levels >1.5 x ULN were divided randomly into 2 groups, group I was given IFN 3 MIU daily for 4 weeks, followed by tiw up to 12 months and group II was given IFN 3 MIU daily for 12 weeks, followed by tiw up to 12 months. Ribavirin was given in a dose of 800-1200 mg/d for 12 months. RESULTS: Fifty-two of the 59 patients (group I=28; group II=24) completed the study. The pretreatment variables and the prevalence of HCV genotype 1 were comparable between the groups. Nine patients (29%) in group I and 6 (25%) in group II had stage 3, 4 fibrosis. At the end of 4, 12, 24 and 52 weeks, HCV RNA negativity was observed in 27%, 54%, 65% and 71% in group I and 38%, 54%, 71% and 75% in group II, respectively (P=ns). Four of the eight (50%) patients with genotype 1 and 30 (69.8%) of 43 patients with genotype non-1 responded to therapy (P=ns). Sustained viral response was achieved in 61% and 71% in groups I and II, respectively. None of the variables predicted non-response precisely. No serious adverse effects were observed and they were comparable between the two groups. CONCLUSION: Daily IFN dosage with ribavirin is safe and can achieve response in up to 65% patients. Since the efficacy of a 4-week daily dosage of IFN is comparable to a 12-week schedule, we recommend the former regimen.

Adult↗

Distribution of hepatitis C virus genotypes in patients with chronic hepatitis C infection in India.

BACKGROUND & OBJECTIVES: Hepatitis C virus (HCV), an important cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, shows a considerable genetic heterogeneity among hepatitis C virus isolates from all over the world. At least six main groups of sequence variants are recognized. The natural history of disease and response to treatment may be related to the genotype of HCV in a particular patient. Antigenic differences between genotypes also have implications for optimal design of serological sequencing and confirmatory assays for HCV. The present study was undertaken with the objective to find out various genotypes of hepatitis C virus prevalent in Indian patients with chronic hepatitis C infection. METHODS: Thirty six consecutive newly diagnosed patients with chronic hepatitis C infection were included in the study. HCV RNA was extracted from the serum by standard guanidinium thiocyanate method. Following reverse transcription and amplification, the HCV genotypes were determined by line probe assay (INNO-LiPA HCV II). RESULTS: Of the 36 patients, genotype 3 was found in 24 (66.6%). Of these 24 patients, 3a was seen in 5 patients (13.8%), 3b in two (5.5%) and mixed subtype 3a and 3b in 17 patients (47.2%). Genotype 1 was found in 5 patients (13.8%), with 1b in 1 and 1a in rest four cases. Two patients (5.5%) were infected with genotype 2 (subtype 2a and mixed subtype 2a, 2b respectively). One (2.7%) was infected with genotype 4 (4a). Mixed genotype infection was found in 4 patients (11.1%). INTERPRETATION & CONCLUSION: The present findings showed that genotype 3 of hepatitis C virus was the most prevalent genotype in patients with chronic hepatitis C in this part of India.

DNA, Viral↗

A rabbit model of non-cirrhotic portal hypertension by repeated injections of E.coli through indwelling cannulation of the gastrosplenic vein.

BACKGROUND: Non-cirrhotic portal hypertension is a common cause of portal hypertension in developing countries. To understand its etiopathogenesis we developed an animal model by repeated portal endotoxemia induced through the gastrosplenic vein. METHODS: Twenty-nine rabbits (1.5-2.0 kg) were divided into control (group I, n=13) and experimental (group II, n=16) groups. Heat killed E.coli were injected through an indwelling cannula into the gastrosplenic vein in pre-sensitized animals. The animals were sacrificed at 1, 3 and 6 months. RESULTS: The mean portal pressure in group II animals was significantly (P<0.05) higher than in group I at 1 (17.5+/-3.4 vs 10.4+/-2.2 mmHg), 3 (17.8+/-1.3 vs 7.2+/-3.6 mm Hg), and 6 (19.8+/-3.1 vs 10.3+/-4.8 mmHg) months. Similarly, the mean splenic weight in group II was significantly greater than in group I (P<0.05). Histopathologically, the spleen showed medullary congestion, hemosidrin-laden macrophages and mild fibrosis. Histologically, the liver had normal parenchyma with mild portal lymphocytic infiltrates and kupffer cell hyperplasia. No significant anomalies were detected by liver function tests. CONCLUSIONS: The rabbit model showed significant splenomegaly with a persistent increase in portal pressure and mild fibrosis without hepatic parenchymal injury, quite akin to non-cirrhotic portal fibrosis as seen in humans. Recurrent intra-abdominal infection may play an important role in the pathogenesis of non-cirrhotic portal fibrosis.

Animals↗

Molecular epidemiology and transmission of hepatitis B virus in close family contacts of HBV-related chronic liver disease patients.

There is limited data on the patterns of HBV mutation in family contacts of chronic liver disease (CLD) patients in India. DNA sequence analysis is an important tool to study this viral epidemiology. Transmission and prevalence of mutations in the S and pre-C gene region in HBV infected close family contacts of HBV-related CLD patients were studied. Twelve HBsAg(+) index patients and their 20 HBV DNA contacts were studied in detail. The S ORF and the pre-C region were sequenced using direct PCR products. S-gene sequencing included 32 specimens (12 index cases and all 20 contacts). Pre-C gene sequencing included 26 specimens (12 index cases and all the 14 HBsAg(+) contacts irrespective of their HBeAg status). More than 98% sequence homology was found between the index patients and their contacts. The in-depth study of 12 families revealed that the transmission pattern was primarily horizontal in 6 (50%) and vertical in 2 (17%) families (P < 0.05). The remaining four families had evidence of both horizontal and vertical transmission. Mutations in the S-gene were found in 80% of HBsAg(+) and 17% HBsAg(-) subjects (P < 0.05). A total of 22-point mutations at different nucleotide positions were found. In these, 16 (72%) were mutation of the "a" determinant region and 14 (64%) resulted in missense mutations. The commonest S-gene mutations were T118V and A128V, present in 44 and 38% specimens, respectively. T143M and G145R mutations in the second loop of the "a" determinant were found in 9% of the specimens. Novel mutations, C137stp and C138stp were found in only one HBsAg(-) subject. Mutations in the pre-C gene were common (91%) in patients with HBeAg(-) phenotype. G1896A mutation was found in 7 of 11 (64%) specimens changing amino acid tryptophane (W) to stop codon. Other mutations were at codons 25 and 29. The results of the study, demonstrate (1) clustering of Pre-C and S-gene mutations in the families, (2) horizontal mode of transmission and a common source infection appears to be frequent as evidenced by sequence homology and detailed history, (3) T118V and A128V were the commonest mutations in the S-gene region, while (4) M2 (G1896A) was the commonest pre-C gene mutation, and (5) long-term follow-up evaluation of these mutations suggested.

Adolescent↗

Primary rhabdoid tumor of the gallbladder: report of a case.

A 46-year-old man was operated on for cholelithiasis with chronic cholecystitis. On gross inspection of the resected gallbladder, a slight thickening in the body wall, in an area measuring about 1 x 0.5 cm, was noted. On light microscopic and immunohistochemical examinations, the lesion was diagnosed to be a rhabdoid tumor. After a thorough review of the literature we failed to find any reference to such a lesion in the gallbladder. This is the first known case report of a rhabdoid tumor of the gallbladder.

Gallbladder↗

Alcohol consumption, hepatic iron load and the risk of amoebic liver abscess: a case-control study.

OBJECTIVE: It is unknown why most amoebic liver abscess (ALA) cases occur in alcohol drinkers. In experimental studies, the presence of 'iron' potentiates the in-vitro growth of Entamoeba histolytica (E. histolytica), and is also known to increase its in-vivo invasiveness in animal infections. Chronic alcoholism increases the hepatic iron deposition. We hypothesized that ALA occurs more commonly in livers with a high iron load as in alcoholics. To test this hypothesis we compared the levels of iron between ALA and non-ALA cases belonging to alcoholic and non-alcoholic groups. METHODS: Out of a total of 48 ALA cases, 34 (70%) were alcoholics and 14 (30%) were non-alcoholics. After applying exclusion criteria, serum iron and liver iron stores were quantified in 20 ALA cases (10 alcoholic and 10 non-alcoholics) and compared with 20 non-ALA cases (10 alcoholics and 10 non-alcoholics). RESULTS: All patients of ALA had serum iron values within the normal range but higher than non-ALA cases. In the liver tissue, most patients with ALA had higher (grade II or III) iron deposition, than non-ALA cases (mostly grade I). Thus, patients with ALA, with or without alcohol indulgence, had higher iron levels when compared to the non-ALA cases. CONCLUSION: It appears that the higher incidence of ALA in alcoholic livers is possibly due to their higher iron content.

Adult↗

Histological profile of liver disease in patients with dual hepatitis B and C virus infection.

UNLABELLED: There is limited information on the histological profile of chronic liver disease due to dual infection with hepatitis B virus and hepatitis C virus infection. Few studies have indicated higher histological activity with dual infection as compared to HBV and HCV infection present alone. This study aims at reviewing the histological profile of liver biopsies in the three groups. Liver biopsies of 25 patients serologically diagnosed as HBV and HCV dual infection (Group I), were compared with 25 age and sex matched cases of HBV infection (Group II) and HCV infection (Group III). RESULTS: Mean Histological Activity Score in group I was 8, which was higher than the scores of group II (6.2) and group III (7.3). The mean stage of fibrosis was also slightly higher in group I (2.3) as compared to group II (1.9) and group III (1.7). However, when stage 3 and 4 fibrosis (extensive fibrosis) were combined and compared with the number of patients with stage 1 and 2 fibrosis in each group, we found Group I (dual infection) had larger number of patients with extensive fibrosis (48%) than in Groups II and III (20% and 36% respectively). In addition, there was no significant difference in presence of features like fatty change, bile duct injury and lymphoid aggregates in the three groups. CONCLUSION: Patients with dual HBV and HCV infection are more likely to have an advanced stage of disease than those with a single infection, however there is no significant difference in histologic activity or any other histological parameter between these groups.

Adult↗

Profile, spectrum and significance of HBV genotypes in chronic liver disease patients in the Indian subcontinent.

BACKGROUND AND AIM: Certain hepatitis B virus (HBV) genotypes have been alleged to be associated with the development of cirrhosis and hepatocellular carcinoma (HCC), and the response to interferon therapy in Taiwanese patients. We undertook to study the prevalence and significance of HBV genotypes in the Indian subcontinent. METHODS: One hundred and thirty histopathologically proven chronic HBV-infected patients, including 52 incidentally detected asymptomatic hepatitis B surface antigen (HBsAg)-positive subjects (IDAHS) with chronic HBV infection (group I), 48 cirrhotics (group II) and 30 hepatocellular carcinoma (HCC; group III) patients were studied. Hepatitis B virus genotypes were determined by using restriction fragment length polymorphism, and direct sequencing of the s gene including the 'a' determinant region. RESULTS: Only genotypes A (46%) and D (48%) were found in the chronic HBV-infected patients. A mixed infection with genotypes A and D was seen in 6% of patients. Genotype A was found in 42, 48 and 50%, and genotype D in 48, 50 and 47% of group I, II and III patients, respectively (P = NS). The patients who had mixed genotypes were significantly younger (P < 0.05). In group I (IDAHS) patients infected with genotype D, none had a histological activity index (HAI) of < four. Genotype D was significantly more common in group I patients with HAI > 4 as compared to genotype A (53 vs 32%, P < 0.05). Similarly, genotype D was associated with more severe liver diseases (61 vs 30%, P < 0.05). Genotype D was more prevalent in HCC patients of < 40 years of age, as compared to IDAHS (63 vs 44%, P = 0.06). CONCLUSIONS: (i) Hepatitis B virus genotypes A and D are prevalent in chronic liver disease patients of Indian origin; and (ii) HBV genotype D is associated with more severe diseases and may predict the occurrence of HCC in young patients.

Adult↗

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.

Adult↗

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'.

Adolescent↗