Hepatocellular Carcinoma Evaluation and Management for Physicians: Joint Gastroenterology Research Society and Association of Physicians of India Guidelines.

Hepatocellular carcinoma (HCC) is the most common cause of, and accounts for almost 90% of all liver cancers. Data from India is limited especially due to cancer not being a reportable disease and in view of wide variation in diagnostic modalities. This document is a result of a consensus meeting comprising Hepatologists, Interventional Radiologists, Hepatobiliary surgeons, medical and surgical Oncologists nominated by the Association of Physicians of India and Gastroenterology Research Society of Mumbai. The following Clinical Practice Guidelines for practicing physicians is intended to act as an up to date protocol for clinical management of patients with hepatocellular carcinoma. The document comprises seven sections with statements and sub-statements with strength of evidence and recommendation.

Prevalence of non A to E hepatitis in Mumbai, India / Prevalencia de la hepatitis no A /E en Mumbai, India

Introduction: Acute viral hepatitis is a common problem in India. World wide data shows that 5 to 20 percent of this is caused by non A-E hepatitis. There is no data in India regarding non A-E hepatitis. We carried out this study to evaluate the epidemiology, clinical features, risk factors and outcome of non A-E hepatitis. Material and methods: In this single centre study, we evaluated all patients admitted with features of acute viral hepatitis at our hospital between the period of February to July 2015. A detailed history about the epidemiology, risk factors and clinical features was done. Patients were evaluated with bilirubin, transaminases and prothrombin time. Each patient was investigated for IgM HAV, IgM HEV, HBsAg and Antibody against hepatitis C. Patients turning out negative were investigated for presence of autoimmune hepatitis or Wilson's disease. All viral markers were repeated a week later to confirm non A-E status. Results: A total 265 patients were included of which 41 (15.4%) patients were non A-E hepatitis. They had higher age (28.55 vs 34.99, p<0.05) but similar gender and sub urban location. Median SEC classification was A2 in hepatitis A/E group as compared to A3 in non A-E group. The duration of symptoms and clinical features between the two groups were similar with Anorexia, Malasie, Nausea/vomiting being most common. The risk factors between the two groups were similar. The bilirubin and transaminases were non significantly lower than hepatitis A/E patients while albumin levels were significantly lower. The outcomes of both groups were similar with no mortality or fulminant hepatitis. Conclusion: Non A-E hepatitis patients tends to be older, lower SEC class and had lower albumin levels as compared to hepatitis A/E

Introdución: La hepatitis viral aguda es un problema común en la India. Los datos mundiales indican que el 5 al 20% es causada por hepatitis no A-E. No hay datos en la India sobre hepatitis no A-E. Objetivo: Se realiza este estudio para evaluar la epidemiología, clínica, factores de riesgo y pronóstico de la hepatitis no A-E. Material y métodos: En este estudio de un solo centro evaluamos a todos los pacientes que se admitieron con clínica de hepatitis viral aguda en nuestro hospital en el periodo de febrero a julio del 2015. Se realizó una historia detallada para evaluar la epidemiología, características clínicas. Se les tomó bilirrubinas, transaminasas y tiempo de protrombina. A cada paciente se le realizó HAV IgM, HEV IgM, HbsAg y anticuerpo anti hepatitis C. Los que fueron negativos se les estudió para hepatitis autoinmune y enfermedad de Wilson. Todos los marcadores virales se repitieron a la semana para confirmar hepatitis no A-E. Resultados: Se incluyeron 256 pacientes, 41 de ellos (15,4%) fueron hepatitis no A-E. Tuvieron más edad (28,55 vs 34,99, p<0,05), pero el mismo género y ubicación urbana. La clasificación media SEC fue A2 en el grupo hepatitis A/E, comparada con 3 en el grupo de no A-E. La duración de los síntomas y el desarrollo clínico fue similar en ambos grupos, siendo la anorexia el malestar general, las náuseas y los vómitos los más frecuentes. El factor de riesgo fue similar, al igual que las transaminasas, mientras que la albúmina fue significativamente menor. El resultado fue similar sin caso alguno de hepatitis fulminante. Conclusión: Los pacientes con hepatitis no A-E tienden a ser mayores, de clase SEC más baja y con valores de albumina más bajos que los pacientes con hepatitis A-E

Fibrosis assessment in patients with chronic hepatitis B virus (HBV) infection.

Chronic hepatitis B virus (HBV) infection is a major cause of liver morbidity and mortality worldwide. While a proportion of the 250 million individuals chronically infected with HBV will not come to significant harm or require therapy, many others risk developing complications of the end-stage liver disease such as decompensated cirrhosis and hepatocellular carcinoma (HCC), without intervention. Due to the complex natural history of HBV infection, patients require an expert assessment to interpret biochemistry, viral serology and appropriately stage the disease, and to initiate monitoring and/or therapy where indicated. The detection and quantification of liver fibrosis is a key factor for disease management and prognostication for an individual with HBV. The reliance on invasive liver biopsy to stage disease is diminishing with the advent of robust non-invasive blood- and imaging-based algorithms which can reliably stage disease in many cases. These tests are now incorporated into International guidelines for HBV management and relied upon daily to inform clinical judgement. Both blood- and imaging-based approaches have advantages over liver biopsy, including minimal risks, lower cost, better patient acceptance and speed of results, while disadvantages include lower diagnostic accuracy in intermediate disease stages and variability with co-existing hepatic inflammation or steatosis. This review outlines the methods of fibrosis assessment in chronic HBV infection and focuses on the most commonly used blood- and imaging-based non-invasive tests, reviewing their diagnostic performance and applicability to patient care.

Gender differences in liver disease and the drug-dose gender gap.

Although gender-based medicine is a relatively recent concept, it is now emerging as an important field of research, supported by the finding that many diseases manifest differently in men and women and therefore, might require a different treatment. Sex-related differences regarding the epidemiology, progression and treatment strategies of certain liver diseases have long been known, but most of the epidemiological and clinical trials still report results only about one sex, with consequent different rate of response and adverse reactions to treatment between men and women in clinical practice. This review reports the data found in the literature concerning the gender-related differences for the most representative hepatic diseases.

Comparison of Tissue Elastography With Magnetic Resonance Imaging T2* and Serum Ferritin Quantification in Detecting Liver Iron Overload in Patients With Thalassemia Major.

BACKGROUND & AIMS: We investigated whether tissue elastography (TE) can be used as an alternative to magnetic resonance imaging (MRI) T2* analysis to determine the degree of iron overload in patients with thalassemia major. METHODS: We conducted a prospective study of 154 patients (99 male; mean age, 12 ± 3.6 years) with thalassemia major requiring chronic blood transfusion and on iron chelator therapy. The study was performed at a tertiary hospital in India from January 2015 through June 2015. We performed routine blood sample analyses, measurements of serum levels of ferritin, and TE within 1 month of MRI T2* analysis of the liver. The Spearman correlation test and linear regression analysis were used to evaluate the correlation between TE liver stiffness measurements and R2* MRI results or serum ferritin levels. RESULTS: The subjects' mean total serum levels of bilirubin, alanine aminotransferase, aspartate aminotransferase, and albumin were 1.4 ± 0.6 mg/dL, 65.0 ± 51.8 IU/L, 62.9 ± 44 IU/L, and 4.2 ± 0.2 g/d, respectively. Mean liver stiffness measurement, MRI T2* (3 T), corresponding MRI R2* (3 T), and ferritin values were 8.2 ± 4.4 kPa, 3.18 ± 2.6 milliseconds, 617.3 ± 549 Hz, and 4712 ± 3301 ng/mL, respectively. On the basis of MRI analysis, 67 patients (43.5%) had mild iron overload, 49 patients (31.8%) had moderate iron overload, and 22 patients (14.3%) had severe iron overload. Fibroscan liver stiffness measurements correlated with MRI R2* values (r = 0.85; P < .001). TE results identified the patients with severe, moderate, and mild iron overload with area under the receiver operating characteristic curve values of 94.8%, 84.5%, and 84.7%, respectively. Liver stiffness measurements greater than 13.5, 7.8, and 5.5 kPa identified patients with severe, moderate, and mild iron overload, respectively; the sensitivity and specificity values were 92% and 93% for severe overload, 82% and 82% for moderate overload, and 73% and 75% for mild overload. No correlation was found between TE results and serum level of ferritin (r = 0.19; P = .11). CONCLUSIONS: Results of TE correlate with those from MRI T2* analysis. TE is cheaper and more available than MRI and might be used to estimate hepatic iron overload, especially moderate to severe overload in patients with thalassemia major who require chronic transfusion.

The role of capsule endoscopy in etiological diagnosis and management of obscure gastrointestinal bleeding.

BACKGROUND/AIMS: To investigate the various etiologies, yields, and effects of capsule endoscopy (CE) on management and complications, along with follow up of patients with obscure gastrointestinal (GI) bleeding. METHODS: The study group of patients included those having obscure, overt, or occult GI bleeding. The findings were categorized as (A) obvious/definitive, (B) equivocal, or (C) negative. Any significant alteration in patient management post CE in the form of drug or surgical intervention was noted. RESULTS: Total patients included in the study were 68 (48 males and 20 females). The ratio of male:female was 2.4:1. The age ranged between 16 years to 77 years. Mean age for males was 62±14 years, for females 58±16 years. The total yield of CE with definitive lesions was in 44/68 (65.0%) of patients. In descending order (A) angiodysplasia 16/68 (23.53%), (B) Crohn's disease 10/68 (14.70%), (C) non-steroidal anti-inflammatory drug enteropathy 8/68 (11.76%), (D) small bowel ulcers 4/68 (5.88%), (E) jejunal and ileal polyps 2/68 (2.94%), (F) intestinal lymphangiectasis 2/68 (2.94%), and (G) ileal hemangiomas 2/68 (2.94%) were followed. Equivocal findings 12/68 (17.65%) and negative study 12/68 (17.65%) was found. Complications in the form of capsule retention in the distal ileum were noted in 2/68 (2.94%) subjects. Statistically, there was a higher probability of finding the etiology if the CE was done during an episode of bleeding. CONCLUSIONS: CE plays an important role in diagnosing etiologies of obscure GI bleeding. Its role in influencing the management outcome is vital.

CROSS SECTIONAL STUDY OF PREVALENCE AND RISK FACTORS OF HEPATITIS B AND HEPATITIS C INFECTION IN A RURAL VILLAGE OF INDIA

Background - Hepatitis B virus and hepatitis C virus are among the principal causes of severe liver disease. There is limited data of epidemiology of Hepatitis B in community, more so in rural population. Objective - To find the prevalence of hepatitis B and C infection in community and study the risk factors for their transmission. Methods - This was a community based cross sectional study. A total of 1833 randomly selected subjects from a rural area were interviewed for risk factors for transmission and tested for markers of hepatitis B and hepatitis C infection. All the positive card tests were confirmed by ELISA. Results - Out of 2400 subjects, rate for participation was 76.38%. None of the subjects was positive for anti hepatitis C virus antibody. Point prevalence for HBsAg positivity was 0.92. Being healthcare worker and having tattoo were significantly associated with HBsAg positive results. Nose and ear piercing was reported by almost. History of blood or blood product transfusion, I/V drug abuse, multiple sexual partners, unsafe Injections, hemodialysis and any h/o surgery was not associated with HBsAg positivity. Conclusion - Health care workers are at high risk for transmission of hepatitis B. Educating common people regarding mode of transmission of Hepatitis B and C will help to reduce their transmission.

Contexto - O vírus da hepatite B e o vírus da hepatite C estão entre as principais causas de doença grave do fígado. Há dados limitados de epidemiologia da hepatite B na comunidade observada, mais ainda na população rural. Objetivo - Encontrar a prevalência de infecção de hepatite B e C em uma comunidade da India e pesquisar os fatores de risco para sua transmissão. Métodos - Feito estudo de corte transversal em uma comunidade. Um total de 1833 sujeitos selecionados aleatoriamente em uma área rural foram entrevistados para fatores de risco para transmissão e testados para marcadores da infecção por hepatite B e C. Todos os testes positivos de cartão foram confirmados por ELISA. Resultados - Dos 2400 pacientes objetivados houve uma taxa de participação de 76.38%. Nenhum dos indivíduos foi positivo para anticorpo anti vírus da hepatite C. A prevalência pontual para a positividade do HBsAg foi de 0,92. Ser trabalhador na área de saúde e ter tatuagem foram significativamente associados com resultados positivos de HBsAg. "Piercing" em nariz e orelha foram relatados por quase todos. História de transfusão de sangue ou uso de hemoderivados, abuso de drogas via endovenosa, múltiplos parceiros sexuais, injeções inseguras, hemodiálise e história prévia de cirurgia, não estiveram associadas à positividade do HBsAg. Conclusão - Os trabalhadores de saúde estão em alto risco para a transmissão de hepatite B. Educar pessoas comuns sobre o modo de transmissão de hepatite B e C ajudará a reduzir a sua transmissão.

Autoimmune Hepatitis Triggered by Treatment With Pegylated Interferon α-2a and Ribavirin for Chronic Hepatitis C.

Hepatitis flare is rarely observed during treatment with pegylated interferon alpha for hepatitis C virus (HCV) infection. A 49-year-old man receiving pegylated interferon α-2a for HCV infection had icterus and hyperbiliru-binemia in the 14th week of therapy, with HCV RNA undetectable after the 12th dose. Liver biopsy was suggestive of chronic hepatitis with cirrhosis without interface pattern. Pegylated interferon was discontinued; a few weeks later, his aminotransferases and immunoglobulin levels increased significantly. Antibody to cytosolic liver antigen-1 was positive, and liver biopsy revealed lymphoplasmacytic infiltrate with intense interface hepatitis, consistent with autoimmune hepatitis.

Serum ferritin levels predict histological severity in patients with nonalcoholic fatty liver disease in India.

AIM: The aims of the study were to determine the levels of serum ferritin which predict fibrosis in Indian patients with nonalcoholic fatty liver disease (NAFLD) and to establish correlation between Fibroscan values and serum ferritin levels. METHODS: The clinical, biochemical, radiologic, and histological findings of consecutive adult NAFLD patients accessed at a tertiary care center over a 3-year period were analyzed. Those with concurrent liver diseases were excluded. Fifty-five of 250 NAFLD patients with fatty liver on ultrasound and raised enzymes (>40 IU/L) underwent liver biopsy. Patients were stratified into two groups based on their histological stage steatosis (with or without inflammation) but no fibrosis and nonalcoholic steatohepatitis (NASH) with fibrosis/cirrhosis. Serum ferritin levels were measured at the same time as getting liver biopsy. Fibroscan was carried out in each of these patients. These were compared with 50 age- and sex-matched controls with normal ultrasound, liver enzymes, and no history of alcohol. Student's t test was used as the test for significance. RESULTS: Fifty-five NAFLD patients diagnosed on ultrasound and with raised enzymes underwent biopsy. Steatosis (with or without inflammation, but no fibrosis/ballooning) was seen in 35 patients, fibrosis/ballooning in 14 patients, and cirrhosis in 6 patients. Mean ferritin levels in groups with nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) were 39.4 and 72.7 ng/mL, respectively (p < 0.001). The mean ferritin levels in NAFLD and controls were 51.2 and 35.2 ng/mL, respectively (p < 0.05). The area under the curve (AUC) of serum ferritin at value 48.0 ng/mL was 0.779. The coefficient of correlation between Fibroscan and serum ferritin levels was 0.9864 while that with alanine transaminase and aspartate aminotransferase was 0.69. Serum ferritin at the cutoff of 48 ng/mL differentiated significantly patients with fibrosis and higher Fibroscan levels. CONCLUSION: Serum ferritin was low in Indian individuals, and levels even within apparently normal range indicated fibrosis and cirrhosis. A cutoff level of 48.0 IU/mL distinguished fibrosis in NAFLD. Fibroscan correlated well with serum ferritin levels.

A Rare Case of an Intraductal Papillary Mucinous Neoplasm of Pancreas Fistulizing Into Duodenum With Adult Polycystic Kidney Disease.

Intraductal papillary mucinous neoplasm (IPMN) accounts for 20-50% of all cystic neoplasms of the pancreas. Rarely, IPMN, whether benign or malignant, can fistulize into adjacent organs like duodenum, stomach or common bile duct. IPMN can be associated with other diseases like Peutz-Jeghers syndrome and familial adenomatous polyposis. Association with adult polycystic kidney disease (ADPKD) is extremely rare. We report a case of a 60-year-old male with a large IPMN in the head of the pancreas diagnosed by magnetic resonance imaging, endoscopic ultrasound and cyst fluid analysis. It was complicated by fistula formation into the second part of the duodenum. Patient was simultaneously having adult polycystic kidney disease. There is only one case report of uncomplicated IPMN with ADPKD in the literature so far. And even rarer, there is no any case report of fistulizing IPMN with ADPKD reported so far, to the best of our knowledge.

CROSS SECTIONAL STUDY OF PREVALENCE AND RISK FACTORS OF HEPATITIS B AND HEPATITIS C INFECTION IN A RURAL VILLAGE OF INDIA.

BACKGROUND: Hepatitis B virus and hepatitis C virus are among the principal causes of severe liver disease. There is limited data of epidemiology of Hepatitis B in community, more so in rural population. OBJECTIVE: To find the prevalence of hepatitis B and C infection in community and study the risk factors for their transmission. METHODS: This was a community based cross sectional study. A total of 1833 randomly selected subjects from a rural area were interviewed for risk factors for transmission and tested for markers of hepatitis B and hepatitis C infection. All the positive card tests were confirmed by ELISA. RESULTS: Out of 2400 subjects, rate for participation was 76.38%. None of the subjects was positive for anti hepatitis C virus antibody. Point prevalence for HBsAg positivity was 0.92. Being healthcare worker and having tattoo were significantly associated with HBsAg positive results. Nose and ear piercing was reported by almost. History of blood or blood product transfusion, I/V drug abuse, multiple sexual partners, unsafe Injections, hemodialysis and any h/o surgery was not associated with HBsAg positivity. CONCLUSION: Health care workers are at high risk for transmission of hepatitis B. Educating common people regarding mode of transmission of Hepatitis B and C will help to reduce their transmission.