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Abstract Background The use of Lamivudine in chronic hepatitis B (CHB) is well known, however the reported rate of HBeAg sero-conversion and its durability post-treatment have varied considerably. We undertook the present study to study the effect of Lamivudine on HBeAg loss and seroconversion rates in Indian patients of CHB in relation to frequency, predictors and durability. Methods We treated 60 patients of e antigen positive CHB (with active viral replication and ongoing necro-inflammatory activity) with Lamivudine. They were followed up by monthly aminotransferases, and 3 monthly HBeAg and anti-HBe. Those who attained HBeAg sero-conversion were advised to discontinue Lamivudine after 6 months and followed up every 3 months thereafter, to see for relapse. Treatment was given for maximum of 3 years if not sero-converted. Results The annual incremental loss of HBeAg in patients receiving Lamivudine was 25 (41.6%) at end of 1st year, 33 (55%) at 2nd year and 35 (58.3%) at 3rd year. The corresponding rates for full sero-conversion were 17/60 (28.6%), 22/60 (36.6%) and 24/60 (40%) in the 3 years. HBeAg loss correlated with increased pre-therapy ALT levels (p = 0.002) and decreased pretreatment HBV-DNA levels (p = 0.004). The presence of cirrhosis had no influence on the rate of HBeAg loss. Relapse occurred in 35% (7/20) post-treatment at median time of 6 months. Conclusion Indian patients showed a higher rate of HBeAg sero-conversion in the first year of Lamivudine treatment. This correlated with baseline ALT and inversely with HBV-DNA levels. Relapse rate after treatment was high and occurred soon after stopping treatment.

Management of complications in patients with Roux-en-Y reconstruction is still today an important surgical and endoscopic challenge. Various techniques have been employed to manage biliary strictures and intrahepatic calculi in patients with Roux-en-Y hepaticojejunostomy (RYHJ). We report the case of a 24-year-old female who had undergone RYHJ reconstruction 3 years back for choledochal cyst, admitted with the diagnosis of obstructive jaundice due to anastomotic stricture and multiple hepatic duct calculi. She was successfully treated with laparoscopic-assisted transjejunal endoscopic management of intrahepatic calculi and anastomotic stricture, which appears to be safe and useful procedure for anastomotic stricture and hepatic duct calculi in patients with surgically altered anatomy., Competing Interests: None

Background: Hepatitis E is caused by infection with hepatitis E virus (HEV), which has four well-known genotypes. Genotypes 1 and 2 HEV have been reported from human cases in areas where the disease is highly endemic. By contrast, genotypes 3 and 4 HEV, which primarily infect several animal species worldwide, have been reported mainly from sporadic human cases in non-endemic areas such as Japan and high-income countries of Europe and North America. To determine whether genotype 3/4 HEV cause sporadic disease in India, a disease-endemic area, we determined HEV genotype in a group of patients with such disease., Methods: A part of the HEV open reading frame (ORF) 1 was amplified and sequenced from sera of 74 patients with sporadic acute viral hepatitis E from four cities in India. The sequences were compared with prototype sequences for various HEV genotypes and subgenotypes and analyzed using phylogenetic tools to determine the genotype of the isolates. For 12 specimens, a part of HEV ORF2 was also similarly analyzed., Results: Partial ORF1 sequences of all the 74 isolates belonged to genotype 1 HEV, with 88.2% to 100% nucleotide identity with the prototype genotype 1 isolates. Partial ORF2 sequences for all the 12 isolates also belonged to genotype 1 HEV. On phylogenetic analysis, 71 isolates clustered with prototype genotype 1a HEV; the remaining three isolates were located between subgenotypes 1a and 1c but were closer to the former., Conclusion: Human sporadic acute hepatitis E in India is caused almost exclusively by genotype 1 HEV.

Objectives: Although celiac disease (CeD) affects 1% of people in the northern part of India, it is believed to be uncommon in the southern and northeastern parts because of significant differences in dietary pattern and ethnicity. We estimated the prevalence of CeD in these three populations. In a subset, we also investigated differences in the prevalence of HLA-DQ 2/8 allelotype and dietary grain consumption., Methods: A total of 23,331 healthy adults were sampled from three regions of India-northern (n=6207), northeastern (n=8149), and southern (n=8973)-and screened for CeD using IgA anti-tissue transglutaminase antibody. Positive tests were reconfirmed using a second ELISA. CeD was diagnosed if the second test was positive and these participants were further investigated. A subsample of participants was tested for HLA-DQ2/-DQ8 and underwent detailed dietary evaluation., Results: Age-adjusted prevalence of celiac autoantibodies was 1.23% in northern, 0.87% in northeastern, and 0.10% in southern India (P<0.0001). Prevalence of CeD and latent CeD, respectively, was 8.53/1,000 and 3.70/1,000 in northern, 4.66/1,000 and 3.92/1,000 in northeastern, and 0.11/1,000 and 1.22/1,000 in the southern part. The population prevalence of genes determining HLA-DQ2 and/or -DQ8 expression was 38.1% in northern, 31.4% in northeastern, and 36.4% in southern India. Mean daily wheat intake was highest in northern (455 g) compared with northeastern (37 g) or southern part (25 g), whereas daily rice intake showed an inverse pattern., Conclusions: CeD and latent CeD were most prevalent in northern India and were the least in southern India. The prevalence correlated with wheat intake and did not reflect differences in the genetic background.

The estimated prevalence of hepatitis C virus (HCV) infection in India is between 0.5 and 1.5% with hotspots showing much higher prevalence in some areas of northeast India, in some tribal populations and in certain parts of Punjab. Genotype 3 is the most prevalent type of infection. Recent years have seen development of a large number of new molecules that are revolutionizing the treatment of hepatitis C. Some of the new directly acting agents (DAAs) like sofosbuvir have been called game-changers because they offer the prospect of interferon-free regimens for the treatment of HCV infection. These new drugs have not yet been approved in India and their cost and availability is uncertain at present. Till these drugs become available at an affordable cost, the treatment that was standard of care for the whole world before these newer drugs were approved should continue to be recommended. For India, cheaper options, which are as effective as the standard-of-care (SOC) in carefully selected patients, are also explored to bring treatment within reach of poorer patients. It may be prudent to withhold treatment at present for selected patients with genotype 1 or 4 infection and low levels of fibrosis (F1 or F2), and for patients who are non-responders to initial therapy, interferon intolerant, those with decompensated liver disease, and patients in special populations such as stable patients after liver and kidney transplantation, HIV co-infected patients and those with cirrhosis of liver.

Globally, around 150 million people are infected with hepatitis C virus (HCV). India contributes a large proportion of this HCV burden. The prevalence of HCV infection in India is estimated at between 0.5% and 1.5%. It is higher in the northeastern part, tribal populations and Punjab, areas which may represent HCV hotspots, and is lower in western and eastern parts of the country. The predominant modes of HCV transmission in India are blood transfusion and unsafe therapeutic injections. There is a need for large field studies to better understand HCV epidemiology and identify high-prevalence areas, and to identify and spread awareness about the modes of transmission of this infection in an attempt to prevent disease transmission.

Introduction: Endoscopic glue (N-butyl-2-cyanoacrylate) injection has emerged as promising therapy for bleeding gastric varices (GV). We evaluated safety and long term efficacy of this technique in patients with portal hypertension and large bleeding GV., Patient and Methods: 170 patients (mean age 40.9 +/- 14y; 132 male; 142 had cirrhosis, 40 Child A, 62 Child B, 40 Child C) underwent glue injection into GV (F3 140, F2 30; fundal 114) as emergency procedure for active bleeding in 62 and electively for prevention of rebleeding in 108. Glue was injected intra-variceally under endoscopic vision, 0.5-4 ml/aliquot, repeated at 3 weeks till varices were eradicated/solidified. The efficacy was assessed by hemostasis at 48 h, primary, secondary, definitive success and treatment failure., Results: The overall hemostasis rate at 48h was 82.3% (51/62). Follow up was available in 158 patients for mean of 30.7 + 17.2 months. Repeat injections were performed in 76. The mean number of injections were 1.9 +/- 1.0 (1-4); total volume was 2.5 +/- 1.7 ml/patient. The status of GVs at last follow up was: disappeared in 32 (22.6%); F1 solidified in 46 (32.3%); F2 solidified in 64 (45.0%). Bleeding recurred in 14.5% (23/158); 60% within 2 weeks of injection. The primary, secondary and definitive success rates were 85.4% (135/158), 4.4% (7/158) and 89.9% (142/158) respectively and treatment failure rate was 10% (16/158). No significant complications were noticed except for injection site ulceration in 32. Twenty patients died on follow up (9 died of uncontrolled bleeding, 11 died of liver failure)., Conclusion: Endoscopic glue injection into bleeding GVs was effective in achieving hemostasis in 82% with a definitive success rate of 90% and had a good safety profile on long-term follow up.

Background and Aim: Gallbladder cancer (GBC) is a common abdominal malignancy in India with an obscure etiology. However, long-standing stones and chronic infection in gallbladder have been suspected as possible etiologic factors. As carcinogenesis complicating chronic inflammation proceeds through the stages of dysplasia and metaplasia, mutation in the K-ras gene may be an important marker for GBC. The aim of the present study was to detect K-ras mutation in cytological smears from GBC., Methods: Malignant cells were marked on slides of cytological smears obtained from 39 patients with cytologically proven GBC. Marked cells were scraped off and DNA was extracted. Polymerase chain reaction coupled with restriction fragment length polymorphism (RFLP) analysis was performed to detect the point mutation in codon 12 of the K-ras gene., Results: Mutation in codon 12 of K-ras oncogene was detected in eight (38%) of 21 PCR amplified samples by this technique. Six of eight specimens with K-ras (codon 12) mutation corresponded to coexisting gallstone disease. Five patients with K-ras (codon 12) mutation were found to have stage IV malignancy., Conclusions: Mutation in codon 12 of the K-ras oncogene occurs in more than one-third of GBC in northern India. Its detection from fine-needle aspirates may prove useful as an adjunct to cytological examination. The presence of this mutation suggests that chronic inflammation may play an etiologic role in gallbladder carcinogenesis., (Copyright 2004 Blackwell Publishing Asia Pty Ltd)

We report a 2-year-old girl with spontaneous perforation of choledochal cyst. Preoperative diagnosis was possible by hepatobiliary scintigraphy. In view of emergency presentation and bile peritonitis, management was a staged procedure with peritoneal lavage and T-tube drainage of the biliary system, followed by excision of the cyst and Roux-en-Y hepatico-jejunostomy 3 months later.

Apart from increased blood ammonia, alterations in various other substances have been implicated in the pathogenesis of hepatic encephalopathy (HE). The role of trace elements like zinc and manganese has been described recently. Zinc is an essential trace element and functions as an antioxidant. Low zinc concentrations have been reported in patients with cirrhosis of the liver, particularly those with HE. Patients with fulminant hepatic failure and subacute hepatic failure have also been shown to have low serum zinc levels. In animal experiments, zinc supplementation leads to a reduction in blood ammonia. Zinc deficiency also leads to alteration of neurotransmitters like gamma aminobutyric acid and norepinephrine. Zinc supplementation has been tried in HE. It may have a role in mild chronic HE, though further trials are necessary. Increased serum manganese levels have been shown in acute and chronic hepatitis, cirrhosis and congenital disorders like Alagille's syndrome. High manganese content has been reported in the globus pallidus in animals as well as brain tissues of patients dying of HE. Miners with chronic manganese exposure have encephalopathy and extra-pyramidal features similar to HE. It has been postulated that manganese impairs neuronal oxidative metabolism. The role of manganese in the pathogenesis of HE and the possibility of its chelation as treatment need further study.

Introduction: Data on therapeutic endoscopy and radiologic interventions for the management of childhood pancreatic disorders are relatively limited. This study focuses on the multidisciplinary approach to the management of pancreatitis in children., Patients and Methods: Children with pancreatic disorders were studied from January 1992 to May 2001. Acute pancreatitis (AP) was diagnosed by clinical evaluation, serum amylase more than three times normal, and morphologic abnormalities of the pancreas on imaging. Children with recurrent abdominal pain, pancreatic calcification or ductal stones on imaging, and pancreatic ductal changes on endoscopic retrograde cholangiopancreatography (ERCP) were diagnosed with chronic pancreatitis (CP). Patients were treated by gastroenterologists, surgeons, and interventional radiologists. Pancreatic exocrine insufficiency was diagnosed in appropriate settings., Results: Fifteen children--6 with AP (posttrauma, 3; gallstone disease, 1; and viral, 1), 7 with CP, and 2 with pancreatic exocrine insufficiency--were diagnosed. Local complications observed in children with AP included pseudocyst in three, and infected acute fluid collection, right-sided pleural effusion, and ascites in one patient each. Complications of AP were managed with percutaneous catheter drainage (n = 3; pseudocyst, 2; infected fluid collection, 1), additional pancreatic duct stenting (n = 2), surgical drainage (n = 1), and octreotide for pleural effusion (n = 1). Signs of CP included abdominal pain (n = 7), obstructive jaundice resulting from lower common bile duct stricture (n = 2), and bleeding from gastroduodenal artery pseudoaneurysm (n = 1). Pancreatic duct stenting relieved pain in one patient, and steel coil embolization arrested bleeding from the pseudoaneurysm. Common bile duct strictures were managed by surgical bypass (n = 2), one of which required preoperative endoscopic bile duct stenting for management of cholangitis. Two other patients with CP required no intervention., Conclusion: A multidisciplinary approach of radiologic and endoscopic interventions and surgery are complimentary to each other in achieving successful outcomes of complicated childhood pancreatitis.

Portal hypertension (PHT) is common in children and a majority of cases in India are constituted by extrahepatic portal venous obstruction or cirrhosis of liver. Morbidity and mortality in this condition is related to variceal bleeding, most commonly from esophageal varices. Acute variceal bleeding is best controlled by endoscopic therapy. Somatostatin and octreotide are useful in acute variceal bleeding as a supplementary therapy. Acute variceal bleeding uncontrolled by medical therapy merits preferably a shunt surgery or devascularization depending upon etiology of PHT and expertise of the surgeon. Acute variceal bleeding originating from gastric varices can be effectively controlled by endoscopic injection of tissue adhesive agent (n-butyl 2 cyanoacrylate). Eradication of esophageal varices by endoscopic measures (sclerotherapy or band ligation) is successful in prevention of recurrence of bleeding. Surgical portosystemic shunts especially in non-cirrhotic PHT are successful in achieving portal decompression and significant reduction in recurrence of variceal bleeding. Role of beta-blockers in primary prophylaxis of variceal bleeding in children still remains to be substantiated.

Pseudoaneurysms of the hepatic or gastroduodenal arteries may cause Haemobilia. Mitral valve prolapse associated with mycotic pseudoaneurysm of cerebral and extracerebral arteries have been reported. We report a case of gastroduodenal artery pseudoaneurysm presenting as haemobilia. The patient was successfully treated with indigenously fabricated steel coil embolization followed by surgery.

Background and Aim: Autoimmune liver disease (AILD) in children progresses to cirrhosis and liver failure if not diagnosed and managed in time. We prospectively analyzed our patients with liver disease for autoimmune etiology and their outcome with treatment., Methods: All patients with liver disease were evaluated with liver function tests, abdominal ultrasonography, endoscopy, liver biopsy, viral markers and investigations for Wilson's disease. Immunoglobin (Ig)M hepatitis A virus, hepatitis E virus (HEV) and IgM hepatitis B core antibody were tested if acute viral hepatitis was suspected. Antinuclear antibody (ANA), antismooth muscle antibody (SMA), and liver kidney microsomal antibody (anti-LKM-1) were done in all cases. Autoimmune liver disease was diagnosed when one or more autoantibodies tested positive (> 1:40), and no other etiology of liver disease was identified. We also applied criteria proposed by the International Autoimmune Hepatitis Group. Cases diagnosed to have AILD were treated with immunosuppressive drugs., Results: Autoimmune liver disease constituted 3.9% (6/153; median age and duration of illness 8.5 years and 3 months, respectively) of chronic liver disease cases. Four patients had acute hepatitis-like presentation. Of the six cases, two each were ANA and SMA +; one was anti-LKM-1 +, and the other was positive for both SMA and anti-LKM-1. Three of the patients achieved remission with combination therapy of oral prednisolone (OP) and azathioprine (AZT), and one with only OP. The other two patients were not treated. Two of the patients in remission have been weaned off from immunosuppressive therapy, and one is in a withdrawal phase. Another patient, while in biochemical remission developed superimposed anicteric acute HEV infection., Conclusion: Although AILD is uncommon in children, its search is rewarding, as remission is achieved with immunosuppressive therapy. Superimposed acute viral hepatitis can occur in endemic areas.

Acute hepatitis E and falciparum malaria can each present with fulminant hepatic failure and are common in tropical countries. However, co-existence of these two conditions has not been reported. We report a 20-year-old girl who presented with fever and altered sensorium. Peripheral smear was positive for Plasmodium falciparum, and IgM anti-HEV was positive. She died despite antimalarial drugs and supportive management. Postmortem liver tissue showed changes suggestive of acute viral hepatitis.

Till date only three series of immunoproliferative small intestinal disease (IPSID) describing 22 patients have been reported from India. Seven patients with IPSID in two tertiary referral centers in India are included in the study. Diagnosis was based on typical clinical features [diarrhoea (7/7), weight loss (7/7), clubbing (6/7), fever (3/7), abdominal pain and lump (3/7)], biochemical evidence of malabsorption and duodenal biopsy findings. All patients were young males (mean age 29.8 +/- 11.8 years, range 17-53). Atypical features included gastric involvement (1/7), colonic involvement (1/7) and appearance of pigmented nails following anti-cancer chemotherapy (1/7) which disappeared six months after omitting doxorubin from chemotherapy regimen. Parasitic infestation was common. Ascaris lumbricoides (1/7), Giardia lamblia and hookworm (1/7), Strongyloides stercoralis and Trichuris trichura (1/7). In the latter patient S. stercoralis became disseminated after anti-malignant chemotherapy. One patient had gastric H. pylori infection. Four of the seven patients who were misdiagnosed as tropical sprue were treated with tetracycline. This raises doubt on efficacy of tetracycline alone in treatment of IPSID. One other patient was misdiagnosed and treated as intestinal tuberculosis. Early diagnosis and administration of chemotherapy may improve survival in this disease.

Tuberculous infection of the stomach is uncommon and the diagnosis is often missed due to its non-specific presentation. We report a case of gastric tuberculosis which presented as a non-healing gastric ulcer.

Ulcerative colitis is known to be associated with autoimmune diseases. We report two patients with coexistent ulcerative colitis and immune thrombocytopenia, a rare association.