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.

Coagulopathy in cirrhosis: A prospective study to correlate conventional tests of coagulation and bleeding following invasive procedures in cirrhotics.

BACKGROUND: Conventional tests of coagulation which only measure procoagulant factors do not correctly estimate the actual in vivo hemostatic balance in cirrhosis. This prospective multicenter study was conducted to evaluate safety of various invasive procedures in the presence of abnormal coagulation tests and to correlate conventional coagulation parameters with clinically significant bleeding in cirrhotics. METHODS: Three hundred and eighty patients (median age 54 years, 287 males) enrolled in the study were divided into two groups (A and B), according to the presence or absence of abnormal coagulation parameters (defined as INR ≥1.5 and/or platelet count ≤50,000/cum). RESULTS: One hundred and twenty-eight patients (33.68%) were qualified in group A. Alcohol was the predominant etiology of cirrhosis (40% and 32% in groups A and B, respectively). The two groups were similar in baseline characteristics other than tests of coagulation and severity of liver disease. Low risk procedures (abdominal paracentesis most common) were carried out in 47% and 53% patients in two groups, respectively. None of the patients in either group had clinically significant bleeding. Similarly, high risk procedures (central vein cannulation, liver biopsy, etc.) were carried out in 14% and 10%, respectively, in two groups. Three patients in group A developed clinically significant bleeding, however, the difference was statistically nonsignificant (p=0.061). None of our patients received periprocedural correction of abnormal coagulation parameters with plasma/platelet concentrate. CONCLUSIONS: Deranged conventional coagulation parameters did not predict clinically significant bleeding in cirrhosis. Whenever indicated, any invasive procedure could be safely carried out in patients with cirrhosis without prior correction of coagulation abnormalities.

Acute-on-chronic liver failure: a prospective study to determine the clinical profile, outcome, and factors predicting mortality.

BACKGROUND: Acute-on-chronic liver failure (ACLF), defined differently by different associations, lacks consensus on clinical profile, precipitating events and factors predicting mortality. This prospective multicentric study was conducted to determine the relevance of European Association for Study of Liver (EASL) and Asia Pacific Association for Study of Liver (APASL) definitions and to determine prognostic factors predicting the survival. METHODS: Consecutive patients over a 3-month period with any form of acute deterioration were evaluated for presence of ACLF, as defined by APASL or EASL-Chronic Liver Failure (CLIF) criteria. Those enrolled underwent complete evaluation for identifying the acute insults, underlying chronic etiologies, presence of organ failures, and short-term survival. RESULTS: Sixty-two patients (median age 53 years, 51 males) who presented with either raised bilirubin (n = 52), international normalized ratio (INR) >1.5 (n = 46), new onset ascites (n = 53), or hepatic encephalopathy (n = 39) were included in study. Forty-four patients (36 males, 25 alcoholics) satisfied APASL definition of ACLF, with a mortality rate of 43.1 %. Hepatic encephalopathy (p-value 0.022) was significantly associated with mortality. By CLIF-Sequential Organ Failure Assessment (SOFA) score criteria for organ failure, 50 patients (80.6 %) had at least 1 organ failure whereas 15 had ≥3 organ failures (mortality rate >75 %). Twenty-nine patients classified as ACLF (1, 2, or 3) as per EASL-CLIF criteria. Bacterial infection, >1 precipitating event, additional organ failure, total leukocyte count, INR, and serum creatinine were significantly higher in patients with ACLF across all grades. Mortality rates were 6.6 and >60 % in patients with ACLF only by APASL criteria vs. by both criteria, respectively. CONCLUSIONS: ACLF, as defined by APASL in terms of liver failure, identified some patients with better survival rates as compared to EASL-CLIF definition which identifies presence of additional organ failures and high mortality.

A multicenter prospective study of infections related morbidity and mortality in cirrhosis of liver.

BACKGROUND AND AIMS: Infections are a common and serious complication among patients with cirrhosis. We assessed the epidemiology, risk factors, and clinical consequences of bacterial infections in cirrhotic patients. METHODS: In this multicenter prospective study, all patients with cirrhosis of liver with different infections were analyzed. Infections were classified as community-acquired (CA), healthcare-associated (HCA), or hospital-acquired (HA). Site of infection and characteristics of bacteria were recorded; effect on liver function and 30-day survival were evaluated. RESULTS: One hundred and six out of 420 (25 %) patients with cirrhosis of liver had infection. Infection rate among indoor patients was 37.5 % (92/245) and among outdoor patients was 8 % (14/175). Out of 106 patients, CA, HCA, and HA were seen in 19.8 %, 50 %, and 30.2 %, respectively. Spontaneous bacterial peritonitis (31.1 %), urinary tract infections (22.6 %), and pneumonia and cellulitis (11.3 % each) were common infections. Gram-negative bacteria (54 %) were more common than Gram-positive cocci (46 %). Multidrug resistant (MDR) organisms were seen in 41.7 % of patients. Most of the MDR organisms were seen in HCA and HA patients. The degree of liver impairment was significantly more severe in patients with infection. Independent predictor of infection was high Child-Turcott-Pugh (CTP) class (p = 0.006, Child B vs. A (odds ratio (OR) 3.04 95 % CI = 1.63 to 5.68) and Child C vs. A (OR 4.17 95 % CI = 2.12 to 8.19). Overall in-hospital mortality was 7.6 %. Patients with infection had increased mortality at 30-day follow up compared to those without infection (23.5 % vs. 2.2 %; p<0.001). CONCLUSIONS: Infections are one of the important causes of morbidity and mortality in patients with cirrhosis of liver. The most frequent infections are HCA and HA. Infection predisposes to deterioration of liver function and increases mortality. Cirrhotic patients should be monitored closely for infections especially those with Child class B and C.

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.

Do different hepatitis C virus genotypes behave differently?

BACKGROUND: The natural history of hepatitis C genotype III infection, the predominant form in India, is not wholly understood. This study attempted to compare the natural history of diseases due to genotypes III and I. METHODS: This 10-year prospective follow-up study (mean follow-up period = 3.6 +/- 1.4, range = 1-10 years) included 108 patients of hepatitis C. Group 1 comprised 65 patients with hepatitis C genotype III infection (mean age = 46.1 +/- 11.3 years, male: female = 1.8 : 1) and group 2 comprised 43 patients with hepatitis C genotype I infection (mean age = 44.2 +/- 8.2 years, male: female = 2.1 : 1). Demographic features, clinical presentation and course, response to treatment (either interferon-ribavirin or peginterferon-ribavirin combination) and complications were noted for all patients. Data were analysed using the chi-square test and Student's t-test. RESULTS: The number of steatosis cases was larger in group 1 (32.3%, 21/65 patients) than in group 2 (18.6%, 8/43 patients) although statistically not significant. There was no significant difference in the mode of infection, presence of diabetes, obesity or alcoholism, clinical presentation, extra-hepatic manifestations, stage of liver disease, complications like decompensation or hepatocellular carcinoma and mortality. Overall, the sustained treatment response was significantly greater in group 1 patients [(87.5%, 21/24 treated patients vs. 56.2%, 9/16 treated patients in group 2; p = 0.0001)]. CONCLUSION: HCV with genotype III was associated with better treatment response. Although statistically not significant, more number of patients in genotype III had steatosis.

Guillain-Barre syndrome associated with acute hepatitis E.

A 58-year-old woman presented with a brief icteric illness followed by progressive bilateral symmetrical hypotonic areflexic muscular weakness and unilateral infranuclear facial palsy. She was diagnosed to be suffering from Guillain-Barre syndrome and acute hepatitis E. Such an association has not been described till date.

Monitoring and management of antituberculosis drug induced hepatotoxicity.

BACKGROUND: Hepatotoxicity to antituberculosis therapy (ATT) poses a major challenge. This often results in inadequate therapy. The risk of fulminant hepatic failure and mortality is high once icteric hepatitis develops. There is no consensus on monitoring protocols and for the reintroduction of ATT. METHODS: All patients (from the Department of Internal Medicine and Gastroenterology, Jagjivanram Hospital and the Department of Gastroenterology, Bombay Hospital, Mumbai, India) with a diagnosis of tuberculosis, who were to receive ATT during the study period, were included in the present study for prospective periodic laboratory monitoring for the development of hepatotoxicity. Those patients who developed hepatotoxicity formed Group A (n = 21), whereas those who did not develop hepatotoxicity were included in Group C (n = 179). For the purpose of comparison with Group A, all the patients who presented directly with ATT induced hepatotoxicity during the study period were categorized as Group B (n = 24). Group A and B were further studied after normalization of liver functions for sequential reintroduction with therapeutic doses at a weekly interval. RESULTS: In Group A, 66.6% (14 patients) of the patients were diagnosed in the asymptomatic period. Seven patients had symptomatic hepatitis, but none had icteric illness. There were no mortalities in Group A. In contrast, all the patients in Group B had symptomatic hepatitis (75% icteric hepatitis). There was a mortality rate of 16.6% (four patients). Of the 41 patients from Groups A and B who survived, reintroduction was successful in 38/39 (97.4%). In the remaining two patients who were in Group B, reintroduction was not attempted because of decompensated liver disease. CONCLUSIONS: Periodic laboratory monitoring is important in detecting hepatotoxicity at an early stage, thereby preventing mortality. Sequential reintroduction is often successful.

Antiviral therapy of decompensated cirrhosis due to hepatitis C viral infection.

BACKGROUND: For decompensated HCV cirrhosis, liver transplantation is the only available treatment. Only a few studies in world literature have used antiviral therapy in this situation. METHODS: During a 4-year period, we gave closely monitored antiviral therapy to all consecutive patients of HCV-related cirrhosis with episodes of decompensation. Patients who were excluded from the standard Interferon trials were treated. Patients were started on low dose Interferon alpha-2b (1 MIU tiw) and Ribavirin (800 mg/day) combination therapy or low-dose Interferon alpha- 2b (1 MIJ tiw) monotherapy (in the presence of renal failure) for 6 months to 1 year. Dose of Interferon was escalated gradually to a maximum dose of 3 MIU tiw according to clinical follow-up. RESULTS: A total of 18 patients (mean age = 51.6 +/- 9.8 years; male: female ratio= 10: 8) were treated. At baseline, mean Child-Pugh score was 9.4 +/- 0.8 (range = 7-12). Interferon monotherapy was given to 4 (22.2%) and combination therapy to 14 (77.8%) patients after clinical recovery from an episode of decompensation. Though 16 (88.9%) patients noticed some adverse events, 15 (83.3%) patients completed the treatment schedule. Premature discontinuation was warranted in 3 (16.7%) patients. Out of the 15 patients who completed the treatment schedule, mean maximum tolerated dose of Interferon was 1.73 +/- 0.6 MIU tiw, 10 patients had genotype II or III and 2 patients had genotype I. Of these, end-of-treatment virological response was seen in 11 (73.3 %) and sustained virological response (at 6 months) in 7 (46.6 %) patients. All these patients were followed up for a mean duration of 1.3 +/- 0.6 years (6 month to 3.5 years). During follow up, 7 non-responders had further episodes of decompensation, of whom 4 died. CONCLUSION: Although there is high intolerance to the treatment, closely-monitored low dose escalating Interferon and/ or Ribavirin therapy achieves good results.