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.

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.

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.

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.

Clinical spectrum and natural history of non-alcoholic steatohepatitis with normal alanine aminotransferase values.

Non-alcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) is a well-established cause for chronic liver disease. In most studies on NASH, elevation in alanine aminotransferase (ALT) is taken as one of the diagnostic criteria. However, the clinical and histological spectrum and natural history of NAFLD with normal ALT are not well explored. This study was planned to define the clinical spectrum and natural history of patients with NAFLD with normal ALT, and to compare them with NAFLD with abnormal ALT. A prospective study including 81 consecutive patients with ahistological diagnosis ofNAFLD was planned during the period from 1999 to 2003. Consecutive (n=81) patients with the histological diagnosis of NAFLD were included in the study. In all the patients, clinical, anthropometric, laboratory, histological and imaging features were noted at the baseline. All these patients were followed up regularly at 6-month intervals. Of the 81 cases, 25 patients (including 60% cirrhotics) had persistently normal enzyme, whereas 56 (including 23% cirrhotics) had abnormal ALT. Both the groups were comparable with respect to distribution of age, gender, ethnicity, clinical features, imaging features, histological severity and laboratory features; except a higher incidence of diabetes and higher occurrence of advanced liver disease at baseline in NAFLD with normal ALT. Natural history of NAFLD was better in patients without cirrhosis irrespective of baseline ALT levels than in patients with cirrhosis; except for a higher incidence of decompensation in cirrhotics with normal ALT. The entire clinical and histological spectrum of NAFLD is seen in patients with normal ALT and is not different from patients with abnormal ALT. In patients with diabetes and hepatomegaly in the absence of other obvious liver diseases, even normal ALT may not rule out advanced liver disease, and liver biopsy may be necessary to identify the severity of liver disease.

Prevalence of metabolic syndrome in non-diabetic and non-cirrhotic patients with non-alcoholic steatohepatitis.

Recently, insulin resistance (IR) was proposed as a primary pathogenic mechanism in non-alcoholic steatohepatitis (NASH). The prevalence of IR and metabolic syndrome remains largely unstudied in patients with NASH and without diabetes and cirrhosis, both being conditions associated with IR. During a 1-year period, all non-diabetic and noncirrhotic patients seen in our institute with a diagnosis of NASH were subjected to anthropometric measurements, clinical examination, lipid profile and glucose tolerance test to define metabolic syndrome. All the patients underwent test for fasting glucose and insulin levels to define the insulin resistance by HOMA-R (homeostasis model assessment) method. Of the 25 patients with NASH, the metabolic syndrome was present in 17 (68%) and at least one criterion for the metabolic syndrome was present in all the patients. IR was present in 20 patients (80%). All the patients were either overweight (8%) or obese (92%). Because of the high prevalence of the metabolic syndrome and IR in patients with NASH, it is pertinent to test for IR and metabolic abnormalities in all patients with NASH. Also, all patients with metabolic syndrome should undergo liver function tests and, in the presence of abnormal transaminases, a liver biopsy to define NASH.