Spectrum of hepatitis B and renal involvement.

Renal involvement in hepatitis B occurs in various spectrums and its knowledge is important for clinicians in management of patients. The renal diseases most commonly associated with hepatitis B virus (HBV) infection include membranous nephropathy, membranoproliferative glomerulonephritis and Polyarteritis nodosa. The widespread use of hepatitis B vaccination has decreased the incidence of HBV-related renal diseases. The incidence of HBV infection in dialysis patients has significantly decreased over the past few decades because of screening of blood products for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody, implementation of infection control measures and hepatitis B vaccination. The definition of acute kidney injury has been recently modified in cirrhotic population, helping in prognosis and prediction of mortality. The most common etiologies of acute kidney injury in this cirrhotic population, which account for 80% to 90% of all cases, include volume depletion, acute tubular necrosis and hepatorenal syndrome. Treatment with oral nucleoside/tide analogues (NA) brought a new paradigm in the management of HBsAg positive glomerulonephritis, kidney transplant recipients and dialysis patients, resulting in effective viral suppression, reduced hepatic complications and improved patient survival, without compromising renal allograft outcome. NAs are cleared by the kidneys and therefore their dosage has to be adjusted in all patients with impaired renal function. This article reviews the recent knowledge of the pathogenesis and treatment of HBV-related glomerulonephritis and discusses the management of hepatitis B in patients on dialysis, kidney transplant recipients and cirrhotics, which is continuously evolving.

Metastatic Crohn's Disease.

Metastatic cutaneous involvement is a rare extraintestinal manifestation of Crohn's disease. Presence of cutaneous noncaseating granulomas that are anatomically noncontiguous in location with a fistula or the gastrointestinal tract is a diagnostic hallmark. We present a case of inflammatory bowel disease initially diagnosed as ulcerative colitis, but later manifesting as intra-abdominal abscesses and ulcerated cutaneous lesions that on biopsy proved to be metastatic Crohn's disease. The patient promptly responded to corticosteroid therapy.

Immunoglobulin IgG4 and autoimmune hepatitis.

INTRODUCTION: IgG4 disease has been characterised by lymphoplasmacytic inflammation, rich in IgG4 plasma cells, elevated serum IgG4 and clinical improvement with steroid therapy. There is limited information about IgG4 plasma cells in autoimmune hepatitis (AIH). Aim of this study was to determine IgG4 plasma cells in autoimmune hepatitis and its impact on clinical course and treatment outcome. MATERIAL METHODS: Liver biopsies from 40 patients with AIH before therapy were subjected to IgG4 immunostaining. Clinical history, liver function tests and response to immunosuppressive therapy were recorded. Patients were monitored for 4 weeks. Liver biopsy from 23 non AIH patients served as control. Depending on the presence of IgG4 plasma cells on immunohistochemistry, patients of autoimmune hepatitis were grouped into IgG4 positive (group A) and IgG4 negative (group B). Both groups were compared before and after immunosuppressive therapy for clinicopathological features. RESULTS: Tissue IgG4 plasma cells > 5 per high power field (hpf) were seen in 10/40 (25%) and > 10 per hpf in 4/40 (10%) cases of AIH. None of the cases from control group (non AIH) were positive for IgG4 plasma cells. Group A patients were significantly younger than group B. (p < 0.05). There were no differences in histological severity but liver enzymes, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly higher in group A than group B. Post treatment biochemical improvement was similar in both groups. CONCLUSION: IgG4 positive AIH patients were younger with more abnormal liver enzymes. There was no difference in histology and response to treatment in both groups.

HLA - DQ genotyping in celiac disease in western India.

BACKGROUND AND AIMS: Very few human leukocyte antigen (HLA) studies have been carried out in celiac disease patients in India. The aim was to study the HLA DQ antigens in diagnosed celiac disease patients. METHODS: The cross sectional study analysed non-consecutive 34 celiac patients diagnosed as per modified ESPGHAN criteria at tertiary centre and compared with 25 controls. The HLA-DQ typing was carried out using Histo Spot SSO HLA DQ celiac disease kit by tissue typing department. RESULTS: Out of 34 celiac disease patients (26 females, age ± SD 38.79 ± 15.84 years), 59% presented with typical diarrheal disease. Anemia (76%) was most common extra intestinal manifestation followed by bone pain (53%), neurological (12%) and infertility (3%). All 34 patients were IgA antiendomysial antibody positive out of which 32 patients (94%) were HLA-DQ positive (31 patients were HLA-DQ 2 and 1 was HLA-DQ 8 positive).Among HLA positive patients 13, 9 and 10 patients had modified Marsh stage 1, 2 and 3 respectively. HLA DQ 2 and DQ8 positivity among celiac patients (94%) was statistically significant as compared to controls (12%) (P< 0.0001). HLA DQ 2.5 (DQA1*0501 :DQB1*0201 haplotype) and DQ 2 (DQB1*02) haplotypes were common accounting for 70% of patients followed by DQ X.5, DQ8 and DQ 2.2. CONCLUSION: Celiac disease in Indian patients is predominantly associated with HLA DQ 2 and DQ 8 genotype and has high positive predictive value for diagnosis when combined with serology in symptomatic patients.

Management of Chronic Hepatitis B Infection in India.

Chronic hepatitis B (CHB) infection is a substantial global health problem with highest prevalence observed in the sub-Saharan Africa and East Asia. India lies in the intermediate endemicity zone with prevalence ranging from 0.1% to 11.7%. The predominant route of transmission is horizontal and the most commonly occurring genotypes are A and D. The high mortality and morbidity associated with CHB constitutes significant health and economic burden in developing countries like India. Antiviral agents decrease HBV DNA load and prevent disease progression. Several regional and country expert associations have developed treatment guidelines for appropriate management of CHB; however, various factors like prevalence, disease awareness, immunization status, cost implications, availability of resources, type of transmission and emerging significance of HBV genotypes have influenced the management of CHB in a country. This article focuses on expert's recommendations on CHB management including initiation, monitoring and termination of treatment with emphasis on borderline cases. The article also throws light on the challenges to optimum management and provides preferred therapeutic approaches in Indian perspective.

Association of N-acetyltransferase 2 and cytochrome P450 2E1 gene polymorphisms with antituberculosis drug-induced hepatotoxicity in Western India.

BACKGROUND AND AIM: Tuberculosis (TB) is a major public health problem in India. Despite the treatment availability and monitoring, drug-induced hepatotoxicity (DIH) is a serious concern and can lead to discontinuation of treatment. Anti-TB DIH is well known and can aggravate because of pharmacokinetic and pharmacodynamic interactions. Genetic polymorphism in the drug-metabolizing enzyme genes is an important factor that predisposes certain fraction of the population to drug-induced toxicity. The purpose of this study was to assess the association of N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1) gene polymorphism with anti-TB DIH in Western Indian population. METHODS: A prospective cohort study of 215 patients taking treatment against TB was performed. The NAT2 and CYP2E1 genotypes were determined using polymerase chain reaction and restriction fragment length polymorphism methods. Logistic regression model was used to calculate odds ratio at 95% confidence interval and their respective P values. RESULTS: The risk of anti-TB DIH was significantly higher in slow acetylator (SA) than in intermediate and rapid acetylator of NAT2 genotypes (odds ratio: 2.3, P = 0.01). We also observed the homozygous point mutation at position 481, associated with higher risk of hepatotoxicity (P < 0.01). The major haplotype NAT2*4 seems to provide protection in DIH compared with non-DIH TB patients (P = 0.04). However, we did not find a significant association between CYP2E1 genotypes and anti-TB DIH. CONCLUSION: Increased susceptibility to isoniazid (INH)-induced hepatotoxicity due to presence of NAT2 SA polymorphism was demonstrated in Western Indian population. NAT2 genotyping can therefore serve as an important tool for identifying patients predisposed to anti-TB DIH.

Association of GST null genotypes with anti-tuberculosis drug induced hepatotoxicity in Western Indian population.

BACKGROUND: The first line anti-tubercular (anti-TB) treatment normally involves isoniazid, rifampicin, pyrazinamide, and ethambutol. Clearance of these drugs depends on the activity of several enzymes such as N-acetyl transferase 2, cytochrome P450 oxidase and glutathione S-transferase (GST). Some of these enzymes are highly polymorphic leading to significant inter-individual variation in their activity thereby increasing the risk of drug induced hepatotoxicity (DIH). AIM: To investigate the possible association of anti-TB DIH with genetic polymorphism of GST genes in Western Indian population. MATERIAL AND METHODS: A prospective case-control study was undertaken on patients who received anti-TB treatment. Cases (n = 50) were distinguished from controls (n = 246) based on occurrence of DIH during anti-tubercular treatment. A multiplex polymerase chain reaction was employed to identify homozygous null mutation at GSTM1 and GSTT1 loci. Results. Homozygous null mutation in GSTM1 gene alone or in both GSTM1 and T1 genes was found to be significantly associated with anti-TB DIH at p < 0.02 and p < 0.007, respectively, in our study population. CONCLUSIONS: This is the first study to report GSTM1 null and combined GSTM1 and T1 null genotypes to be risk factors of anti-TB DIH in Western Indian population. Screening of patients for these genotypes prior to anti-TB regimen would provide better control of hepatotoxicity.

Long Term Survival of Patients Undergoing TIPS in Budd-Chiari Syndrome.

BACKGROUND: There has been significant improvement in understanding the etiology and management of Budd-Chiari Syndrome (BCS). Patients with chronic or acute-on-chronic BCS need radiological interventions in the form of angioplasty, hepatic vein/inferior vena cava stenting or Transjugular Intrahepatic Portosystemic Shunt (TIPS). Data regarding the long term follow up of patients undergoing TIPS is limited. We thus prospectively followed-up BCS patients who underwent TIPS at our center. METHODS: This study included 42 patients with BCS who underwent TIPS with a covered stent between 2004 and 2014. We analyzed the etiology, symptoms, severity, laboratory parameters and imaging pre and post TIPS. All patients underwent surveillance for hepatocellular carcinoma. RESULTS: Patients demographics included 26 males and 16 females with a mean age of 40.5 years (19-68 years). The mean Model for End-Stage Liver Disease score of the entire cohort was 15.38 (range: 9-25). Thirty-four patients were grouped into Rotterdam Class 2 and remaining into Class 3. There was significant improvement in ascites, gastrointestinal bleed, renal function and transaminase levels post TIPS. There were 11 deaths over the follow-up period - 4 within one month, 2 within six months and the rest after 3 years following TIPS. Median duration from clinical presentation to TIPS was 2.1 weeks and median survival till follow-up was 45.5 months (0-130 months). 33/42 patients underwent TIPS prior to 2013, and their median survival till follow-up was 55 months. Six out of eleven deaths that occurred within six months post-TIPS were before 2006; when the technique of TIPS creation was evolving. The cumulative 1 year, 5 years and 10 years OLT-free survival was 86%, 81% and 76%, respectively. Two patients underwent a liver transplant at 4 and 7 years after TIPS. CONCLUSION: Our results validate the role of TIPS in the management of patients with BCS. With the accessibility of TIPS, the requirement for liver transplantation has become rare.

Changing spectrum of Budd-Chiari syndrome in India with special reference to non-surgical treatment.

AIM: To evaluate patterns of obstruction, etiological spectrum and non-surgical treatment in patients with Budd-Chiari syndrome in India. METHODS: Forty-nine consecutive cases of Budd-Chiari syndrome (BCS) were prospectively evaluated. All patients with refractory ascites or deteriorating liver function were, depending on morphology of inferior vena cava (IVC) and/or hepatic vein (HV) obstruction, triaged for radiological intervention, in addition to anticoagulation therapy. Asymptomatic patients, patients with diuretic-responsive ascites and stable liver function, and patients unwilling for surgical intervention were treated symptomatically with anticoagulation. RESULTS: Mean duration of symptoms was 41.5 +/- 11.2 (range = 1-240) mo. HV thrombosis (HVT) was present in 29 (59.1%), IVC thrombosis in eight (16.3%), membranous obstruction of IVC in two (4%) and both IVC-HV thrombosis in 10 (20.4%) cases. Of 35 cases tested for hypercoagulability, 27 (77.1%) were positive for one or more hypercoagulable states. Radiological intervention was technically successful in 37/38 (97.3%): IVC stenting in seven (18.9%), IVC balloon angioplasty in two (5.4%), combined IVC-HV stenting in two (5.4%), HV stenting in 11 (29.7%), transjugular intrahepatic portosystemic shunt (TIPS) in 13 (35.1%) and combined TIPS-IVC stenting in two (5.4%). Complications encountered in follow-up: death in five, re-stenosis of the stent in five (17.1%), hepatic encephalopathy in two and hepatocellular carcinoma in one patient. Of nine patients treated medically, two showed complete resolution of HVT. CONCLUSION: In our series, HVT was the predominant cause of BCS. In the last five years with the availability of sophisticated tests for hypercoagulability, etiologies were defined in 85.7% of cases. Non-surgical management was successful in most cases.

Diagnosis of Crohn's disease in India where tuberculosis is widely prevalent.

AIM: To define the parameters that positively predict diagnosis of Crohn's disease (CD) and differentiate it from gastrointestinal tuberculosis (GITB). METHODS: This prospective study over 3 years was carried out in the consecutive Indian patients with definite diagnosis of CD and equal numbers of patients with definite diagnosis of GITB. Demographic, clinical, laboratory, morphological and histological features were noted in all the patients. Serological tests such as p-ANCA, c-ANCA, IgA ASCA and IgG ASCA, were performed. Endoscopic biopsy and/or surgical tissue specimens were subjected to smear and culture for acid-fast bacilli (AFB) and tissue polymerase chain reaction for tuberculosis (TB PCR). Diagnosis of CD and GITB was based on the standard criteria. Data were analyzed using univariate Chi-square test and multiple logistic regression (MLR). RESULTS: The study is comprised of 26 patients with CD (age 36.6 +/- 8.6 year, male:female, 16:10) and 26 patients with GITB (age 37.2 +/- 9.6 year, male:female, 15:11). The following clinical variables between the two groups (CD vs TB) were significant in univariate analysis: duration of symptoms (58.1 +/- 9.8 vs 7.2 +/- 3.4 mo), diarrhoea (69.2% vs 34.6%), bleeding per rectum (30.7% vs 3.8%), fever (23.1% vs 69.2%), ascites (7.7% vs 34.6%) and extra-intestinal manifestations of inflammatory bowel disease (61.5% vs 23.1%). Of these, all except ascites and extra-colonic manifestations were found statistically significant by MLR. Accuracy of predicting CD was 84.62% based on the fever, bleeding P/R, diarrhoea and duration of symptoms while it was 63.4% when histology was reported as inflammatory bowel disease and 42.3% when there was recurrence of disease after surgery. Accuracy of predicting GITB was 73.1% when there was co-existing pulmonary lesions and/or abdominal lymphadenopathy; 75% when tuberculosis was reported in histology; 63.4% when granuloma was found in histology; 82.6% when TB PCR was positive; and 61.5% when smear and/ or culture was positive for AFB. Serological test was not useful in differentiation of CD from GITB. Positivity rates for CD and GITB were: p-ANCA- 3.8% and 3.8%, c-ANCA- 3.8% and 0%, IgA ASCA- 38.4% and 23.1%, and IgG ASCA- 38.4% and 42.3%, respectively. CONCLUSION: Simple clinical parameters like fever, bleeding P/R, diarrhoea and duration of symptoms have the highest accuracy in differentiating CD from GITB.

Impact of diabetes mellitus on outcome of HCC.

BACKGROUND: Diabetes mellitus (DM) is recently identified risk factor for development and progression of chronic liver disease as well as hepatocellular carcinoma (HCC). We planned a prospective analysis to identify impact of DM in Indian patients with HCC. METHODS: During last 10 years, 160 consecutive patients of HCC were evaluated. Demographic profile like age of presentation, clinical features, etiology of HCC, tumor size at presentation, management and ultimate outcome was compared diabetic with non-diabetic HCC patients. RESULTS: During last 10 years, 160 consecutive patients of HCC were evaluated (Mean age = 59.6 +/- 12.9 years, sex ratio (M: F) = 5.4: 1). Etiology for HCC were hepatitis B in 45 (28.2%), hepatitis C in 18 (11.3%), alcohol in 27 (16.8%), alcohol with hepatitis B in 12 (7.5%), alcohol with hepatitis C in 1 (0.6%), non-alcoholic steatohepatitis in 4 (2.5%) and cryptogenic in 53 (33.2%) patients. Patients of HCC with DM (group-A, n =46, age = 62.6 +/- 9.5 years, sex (M: F) = 6.6:1) were compared with patient of HCC without DM (group-B, n =114, age = 66.7 +/- 13.7 years, sex (M: F) = 5.4:1). Duration of diabetes in group-A was 7.6 +/- 3.2 years. Patients in group-A had more advanced HCC (size of lesion > 5 cm and >3 lesions of 3 cm or more diameter, portal vein thrombosis or intra-hepatic bile duct involvement) than group-B [34 (73.9%) vs 72 (54.3%)]. Mortality with in one year was significantly more in group-A compared to group-B [36 (78.2%) vs 56 (49.1%)]. CONCLUSION: DM is associated with more advanced lesion and poor outcome in patient with HCC.

Increased prevalence of type II diabetes mellitus in hepatitis C virus infection in western India.

BACKGROUND: Type II diabetes mellitus (DM) has been shown as more common in patients with hepatitis C virus infection (HCV). Similar data from India is not available. METHODS: This 3-year prospective study included consecutive Indian patients with HCV to detect the DM. In all patients, the presence of DM, duration of DM, probable duration of HCV, genotype of HCV, presence of steatosis and presence of cirrhosis were noted. Comparable numbers of consecutive patients with hepatitis B virus infection (HBV) and irritable bowel syndrome (IBS) were analysed for the presence of DM. RESULTS: A total of 200 patients with HCV were analysed: mean age = 45.9 +/- 9.8 years; male:female=1.3:1; genotype distribution (in 80 patients which included 17 patients of DM)--genotype 3 in 47 (58%), genotype 1 in 31 (39%) and genotype 2 in 2(3%) patients; probable duration (unknown in 40 patients) of HCV = 12.8 +/- 8.2 years; steatosis in 55(27.5%) patients; cirrhosis in 88 (44%) patients. Of these 200 patients, DM was present in 44(22%) patients with mean duration of DM of 6.1 +/- 2.3 years. HCV preceded DM in 29 patients by 10.8 +/- 2.3 years. Among HCV with genotype 3, DM was present in 11(23.4%) patients and with genotype 1, DM was present in 6(19.3%) patients. In patients with DM, cirrhosis and steatosis were present in 28(63.6%) and 20(45.4%) patients, respectively, as compared to 60 (38.4%) and 35 (22.4%) patients without DM. There was significantly lower presence of DM, 24 (12%) and 19 (9.5%), in 200 patients of HBV and 200 patients of IBS, respectively. CONCLUSION: There is increased prevalence of DM in patients with HCV. HCV precedes the development of DM by a decade.

Hepatobiliary tuberculosis in western India.

Tuberculous involvement of liver as a part of disseminated tuberculosis is seen in up to 50-80% cases, but localized hepatobiliary tuberculosis (HBTB) is uncommonly described. During 6 years, a total of 280 consecutive patients with TB were evaluated prospectively for the presence and etiology of liver involvement. Cases with miliary TB or immunosuppression and cases receiving anti-tuberculosis drugs prior to presentation to our unit were excluded (38 cases). Details of clinical, biochemical and imaging findings and histology/microbiology were noted. Of 242 included cases, 38 patients (15.7%; age 38.1 +/- 12.5 years; sex ratio 2.5:1) had HBTB, whereas 20 patients (9%; age 39.3 +/- 16.3 years; sex ratio 2.1:1) had other liver diseases. Diagnosis of HBTB was based on caseating granuloma on histology (18/23 procedures), positive smear/culture for acid-fast bacilli (21/39 procedures) and positive polymerase chain reaction for Mycobacterium tuberculosis (28/29 procedures) when diagnostic procedures were guided by imaging results. Thirty-eight cases with HBTB were classified as follows [patients (n), (%)]: (A) hepatic TB [20 (52.6%)]: (1) granulomatous hepatitis - 10 (26.3%), (2) liver abscesses or pseudotumors - 10 (26.3%) and (3) calcified hepatic granuloma - 0 (0%); (B) biliary TB [15 (39.4%)]: (1) biliary strictures - 2 (5.2%), (2) gall bladder involvement - 1 (2.6%) and (3) biliary obstruction due to lymph node masses - 12 (31.5%); (C) mixed variety [3 (7.8%)]: (1) simultaneous granulomatous hepatitis and biliary stricture - 1 (2.6%) and (2) simultaneous lymph node involvement and calcified hepatic granuloma - 2 (5.2%). All the cases responded well to standard anti-tuberculosis therapy. HBTB forms an important subgroup in TB cases. It requires a combination of imaging, histological and microbiological procedures to define the diagnosis. HBTB responds well to treatment.

Natural History of Cirrhosis of Liver after First Decompensation: A Prospective Study in India.

BACKGROUND AND AIMS: As liver cirrhosis is a dynamic condition, it is possible to improve survival in decompensated cirrhosis. Hence, we planned a prospective study to determine the natural history of cirrhosis after first decompensation. METHODS: We enrolled all patients of liver cirrhosis who presented with first episode of decompensation defined by the presence of ascites, either overt or detected by Ultrasonography (UD), Gastroesophageal Variceal Bleeding (GEVB), and Hepatic Encephalopathy (HE). All patients were followed up to death/liver transplant or at least for the period of 1 year. Multivariable Cox proportional hazards regression was used to analyze the risk of failure (death or Orthotopic Liver Transplantation (OLT)). RESULTS: In total of 110 cirrhotic patients (93 males, mean age 50 ± 11 years), the most frequent etiology was alcohol (48%), followed by nonalcoholic steatohepatitis/cryptogenic (26%), hepatitis B (10%), autoimmune hepatitis (7%), and hepatitis C (6%). The distribution of CTP classes was: 4%, 56%, and 41% in class A, B, and C, respectively. Ascites was the most common decompensation found in 88 patients (80%) followed by HE (14%) and GEVB (6%). At 1-year follow up, transplant free survival was 78%, 2 underwent OLT, 4 developed hepatocellular carcinoma, and 24 died. Cumulative incidence of failure (death or OLT) by type of decompensation after 1 year was: 22% overt ascites, 50% GEVB, 28% UD ascites, 20% HE, and 33% ascites and GEVB concomitant. CONCLUSIONS: Patients with UD ascites do not have a negligible mortality rate as compared to overt ascites. Patients with cirrhosis after first decompensation have better transplant free survival with treatment of etiology and complications than previously mentioned in literature.

Inflammatory Bowel Disease Across the Age Continuum: Similarity and Disparity.

OBJECTIVES: To identify similarities and differences between the pediatric-onset and adult-onset Inflammatory Bowel Disease (IBD) based cohorts and further characterize the pediatric cohort. METHODS: A retrospective analysis of pediatric patients attending the tertiary referral care gastroenterology center from 2004 to 2016 was conducted. All the patients were clinically evaluated, investigated and followed up at the centre. RESULTS: Sixty five patients with pediatric IBD were compared with 216 patients with adult-onset IBD. The Ulcerative colitis: Crohn's disease (UC:CD) ratio was higher in adult-onset population (2.29:1 vs. 1.7:1). Predominant symptoms in pediatric UC were diarrhea and passage of blood in stools; whereas those in pediatric CD were abdominal pain and failure to gain weight. Ulcerative proctitis was less common (2.4% vs. 18.8%; p = 0.009) and an extensive disease (pancolitis) was more common in the pediatric population (73.1% vs. 30.2%; p < 0.00001). Adult CD had higher L3 (33.3% vs. 46.1%; p = 0.28) disease; whereas in pediatric CD, L1 disease (37.5% vs. 32.3%; p = 0.65) was predominant. There was no difference with respect to penetrating and stricturing complications of CD in adults vs. children (20.8% vs. 23.1%; p = 0.974). 5-ASA agents were used more commonly in the pediatric IBD population (96.9% vs. 79.9%; p = 0.0034) as compared to adults whereas corticosteroids (87.5% vs. 76.9%; p = 0.28) and infliximab (25% vs. 9.2%; p = 0.054) were used more frequently in the pediatric CD subgroup as compared to adult CD subgroup. CONCLUSIONS: IBD has significant disease heterogeneity according to the age of onset. Pediatric IBD has distinctive features that set it apart from adult-onset IBD.

Risk factors for inflammatory bowel disease: A prospective multi-center study.

INTRODUCTION: Environmental risk factors have been associated with inflammatory bowel disease (IBD). With rising incidence, it is important to know risk factors associated with IBD in our population. This study was aimed to evaluate risk factors for IBD from western India. METHODS: This was prospective, multi-center case-control study which included 1054 patients with IBD of which 765 (72.5%) were ulcerative colitis (UC) and 289 (27.4%) Crohn's disease (CD). Asymptomatic individuals without a history of any major illness served as controls. The questionnaire containing risk factors for IBD was given to patients and control group. Odds ratio and 95% confidence interval were calculated for each variable. RESULT: Significant numbers of patients with CD were from rural area. Rural environment (OR 1.071, 0.82-1.38 and OR 1.441, 1.02-2.02), higher education (OR 1.830, 1.52-2.19 and OR 1.519, 1.16-1.97), professional by occupation (OR 1.754, 1.46-2.09 and OR 1.293, 0.99-1.67), annual family income >100,000 Indian national rupees (OR 2.185, 1.52-3.13 and OR 4.648, 3.10-6.95), history of appendectomy (OR 3.158, 1.71-5.80 and OR 3.158, 1.71-5.80), and family history of IBD (OR 4.510, 2.19-9.25 and OR 3.972, 1.58-9.96) were the risk factors for UC and CD, respectively. Vegetarian diet was protective factor for UC (OR 0.29, 0.27-0.39) and risk for CD (OR 1.179, 0.88-1.57). Smoking and chronic alcoholism were not found to be the risk factors. CONCLUSION: This study highlights association between socioeconomic, dietary factors, appendectomy, and family history as risk factors for IBD.

Telbivudine: a new treatment for chronic hepatitis B.

Three hundred and fifty million people worldwide are estimated to be chronically infected with hepatitis B virus. 15%-40% of these subjects will develop cirrhosis, liver failure or hepatocellular carcinoma during their life. The treatment of chronic hepatitis B has improved dramatically over the last decade merits to the advent of nucleoside/nucleotide analogues and the use of pegylated interferons. Approved drugs for chronic hepatitis B treatment include: standard interferon-alpha 2b, pegylated interferon-alpha 2a, lamivudine, adefovir dipivoxil, and entecavir. Unfortunately, these agents are not effective in all patients and are associated with distinct side effects. Interferons have numerous side effects and nucleoside or nucleotide analogues, which are well tolerated, need to be used for prolonged periods, even indefinitely. However, prolonged treatment with nucleoside or nucleotide analogues is associated with a high rate of resistance. Telbivudine is a novel, orally administered nucleoside analogue for use in the treatment of chronic hepatitis B. In contrast to other nucleoside analogues, Telbivudine has not been associated with inhibition of mammalian DNA polymerase with mitochondrial toxicity. Telbivudine has demonstrated potent activity against hepatitis B with a significantly higher rate of response and superior viral suppression compared with lamivudine, the standard treatment. Telbivudine has been generally well tolerated, with a low adverse effect profile, and at its effective dose, no dose-limiting toxicity has been observed. Telbivudine is one of the most potent antiviral agents for chronic hepatitis B virus and was approved by the FDA in late 2006.

Angiogenesis in chronic liver disease.

BACKGROUND: Chronic liver disease is characterized by inflammation and fibrosis. As a consequence angiogenesis leading to new vasculature may have prognostic value in disease progression. Interfering with angiogenesis may be a potential target to avoid progression of liver disease. Hence we planned to evaluate the CD34 and vascular endothelial growth factor (VEGF), the markers for angiogenesis in chronic liver disease. METHOD: Liver biopsies from 79 patients of chronic liver disease and 21 cases of HCC (M: F = 4:1, age range 22 to 80) were stained for routine HE, CD 34 and VEGF immunostaining (Dako Corp & Santa Cruz respectively). Etiologies of chronic liver disease were alcoholic liver disease, HBV, HCV infection, NAFLD, autoimmune liver disease, and cryptogenic liver disease. Thirty biopsies from normal liver obtained at autopsy were taken as controls. Expressions of CD 34 and VEGF were compared with the stage of fibrosis. RESULTS: Out of 79 patients, angiogenesis was seen in 45.5% cases of chronic liver disease. None of the case with normal liver histology was CD 34 or VEGF positive. No significant correlation of angiogenesis was found between any etiologies of chronic liver disease. CD 34 was positive in 18/21 (85.7%) cases of hepatocellular carcinoma. CD 34 and VEGF positivity was 20.9% and 46.5% in stage 1 and 2 fibrosis while it was 75% and 80% in stage 3 and 4 fibrosis respectively. VEGF appeared more common as compared to CD 34 in early fibrosis. CONCLUSION: Angiogenesis was present in 45.5% cases of chronic liver disease. It was proportional to the increase in stage of fibrosis. Expression of VEGF was commonly found in early stages of fibrosis. Hence, therapeutic strategies of inhibiting VEGF expression may be of importance in preventing the progression of chronic liver disease in its early stage.

Primary mesenteric venous thrombosis: a study from western India.

INTRODUCTION: The prevalence and clinical spectrum of mesenteric venous thrombosis (MVT) in India is largely unknown. METHODS: We retrospectively re-viewed the case records of patients with primary mesenteric venous thrombosis seen over a 10-year period and retrieved information on clinical picture, underlying hypercoagulable states and outcome. RESULTS: The 28 cases (mean age 41.2 [SD 10.2] years; 19 male) included 13 with acute MVT, 10 with subacute MVT and 5 with chronic MVT. Ten patients had past thromboembolic events (multiple events in five); four patients had isolated superior mesenteric vein involvement and 14 had multiple vessel involvement. Hypercoagulable state was identified in 17 patients, with multiple etiologies in 7 patients. Pre-operative diagnosis was made in all patients. Ten patients needed surgical management; the rest were managed medically initially, but 2 required surgery on follow up. Seven patients died during a follow up of up to 10 years, with in-hospital mortality during index admission in six. CONCLUSIONS: Most of the patients with MVT have multiple intra-abdominal vessel involvement and underlying hypercoagulable state. The policy of early treatment with anticoagulation in all and surgical treatment as per need, achieves low mortality.

Monotherapy with peginterferon alpha-2b {12 kDa} for chronic hepatitis C infection in patients undergoing haemodialysis.

BACKGROUND: A combination of Peginterferon and Ribavirin is the standard treatment for patients with chronic hepatitis C viral infection (HCV). Ribavirin is contraindicated in patients with chronic renal failure (CRF). Conventional Interferon monotherapy is effective in around 30% of such patients. There is scanty data on the use of Peginterferon monotherapy in them. METHODS: We describe our preliminary experience of monotherapy with Peginterferon alpha- 2b {12 kDa} (Peg-IFN) for HCV patients undergoing haemodialysis for CRF. They were treated with Peg-IFN 1 microg/kg body weight subcutaneously once a week for 24 weeks. In all patients, clinical (age, sex, mode of acquiring HCV, pattern of haemodialysis) and virological (HCV RNA quantitative-PCR and genotype) profile was noted at baseline. Early virological response at 12 weeks (EVR), end-of-treatment virological response at 24 weeks (ETVR) and sustained virological response after 6 months of stopping treatment (SVR) were noted during the follow-up period. RESULTS: The clinical and virological characteristics of patients were as follows: Of a total number of 6 patients, 5 were male and 1 was female with an age range of 35 to 62 years. The duration of haemodialysis was from between 5 and 12 months before the start of treatment and its frequency lay between 1 and 3 times a week. The mode of acquiring HCV was blood transfusion (100%). All 6 cases suffered from chronic hepatitis. The genotype distribution was genotype 3 in 3 (50%), genotype 1 in 1 (16.7%) and genotype none of 6 in 2 (33.3%) patients. All the patients (100%) completed treatment. EVR was seen in all 6 patients (100%). ETVR was seen in 5 of 6 patients (83.3%). A follow-up period of more than 1 year was available in 4 patients. 3 of these 4 patients (75%) had SVR. A virological response was maintained in all 3 (100%) patients with SVR even after 6 months of renal transplantation. CONCLUSION: Peg-IFN monotherapy is safe and effective in patients with HCV who are on haemodialysis for CRF.