Etiology and Impact of Hepatic Steatosis in Pakistan: Role of Hepatitis C Virus Genotype 3 Infection

Introduction: Hepatic steatosis has emerged as an important histological finding in patients with deranged liver function. It may be an important factor for the progression of hepatitis C virus-associated liver disease, particularly in genotype 3 infections. Aims: To determine the etiology and impact of hepatic steatosis in our patients presenting with chronic hepatitis. Methods: All liver biopsies performed at our hospital during 2010-2014 were analyzed by a single pathologist using histological activity index (HAI) scores and Brunt’s classification for steatosis. Patients were evaluated for factors reported to be associated with steatosis, including the prevalence of HCV. Results: Biopsies of 439 patients (284 male, mean ages 38.5 ± 11.2 years) were studied. Hepatic steatosis was present in 324 (73.8%) biopsies. It was mild in 190/439 (43.3%), moderate in 88/439 (20%) and severe in 46/439 (10.5%) cases. On univariate analysis, steatosis was associated with HCV infection (p=0.023), BMI >25 (p=0.008) and raised ALT (p=0.003), but not with diabetes, hypertriglyceridemia, HBV infection or alcohol intake. On multiple logistic regression HCV and BMI >25 were independent risk factors for steatosis. There was a linear ascending association of hepatic steatosis with grade and stage of liver disease (p ≤ 0.001). Among 369 HCV patients, 280 (76%) had steatosis. It was mild in 159/369 (43%), moderate in 82/369 (22.2%) and severe in 39/369 (10.6%) cases. There were only 32 non-alcoholic, non-viral hepatitis patients and 8/32 (25%) had moderate or severe steatosis. Conclusions: Significant hepatic steatosis is present in 30.5% of our patients with chronic hepatitis. HCV genotype 3 infection is the predominant factor for hepatic steatosis in Pakistan. Steatosis has a linear ascending correlation with hepatic inflammation and fibrosis.

Impact of a bleeding care pathway in the management of acute upper gastrointestinal bleeding.

Objectives Upper gastrointestinal (UGI) bleeding carries high morbidity and mortality. The use of a bleeding care pathway (BCP) may improve outcomes, but the results are inconsistent in various studies. Methods A BCP for patients with UGI bleed with admission in a bleeding care unit (BCU) has been in use at our hospital since 2005. Prior to this, a high dependency unit was used for management of all emergencies including UGI bleeding. We compared the length of stay in the bleeding care/high dependency unit, total hospital stay, time to UGI endoscopy after admission, and survival between pre-2005 and post-2005 patients. Results Five hundred and fifty-one patients were admitted with acute UGI bleed in the last 5 years; 121 belonged to pre- BCP (2004) period and 430 after implementation of the pathway (2005–2008). The mean (SD) time to UGI endoscopy improved from 21.3 (7.4) hours in the pre-BCU era to 9.4 (9.9) hours in BCU, p<0.001. BCU stay was shorter from 2.41 (1.4) days pre-BCP to 1.93 (1.32) days post-BCP, (p<0.001). The total hospital stay in pre-BCU (4.0 [2.08] days) as compared to BCU (4.13 [2.62] days; p=0.58) was similar; there was no impact of BCU on survival. Conclusion A BCU implementation showed improvement in time to UGI endoscopy, and did not reduce BCU stay or impact survival.

Sustained virological response to pegylatedinterferon and ribavirin in patients with genotype3 HCV cirrhosis.

Background: Chronic hepatitis C (CHC) virus infection in patients with cirrhosis is difficult to treat. There is limited data on the outcome of treatment for genotype 3 HCV infection with cirrhosis. Aims: To determine sustained virological response (SVR) and its predictive factors in patients with cirrhosis due to genotype 3 HCV infection treated with pegylated interferon and ribavirin (RBV). Methods: Consecutive patients with compensated cirrhosis due to HCV genotype 3 with positive HCV RNA treated with peg-IFN and RBV in our Gastroenterology Clinics during November 2005 to December 2006 were included in this study. Cirrhosis was diagnosed on the basis of liver biopsy and/or biochemical testing and ultrasound of abdomen. Primary end point of treatment was SVR. Results: Of 66 patients, 32 (48.5%) were male. The mean age was 46.2±10.1 years; there were 61 (92.4%) patients with Child’s A cirrhosis followed by 5 (7.6%) with Child’s B type. 33 (50%) patients received pegylated interferon alfa-2a (180 μg/wk) with ribavirin and 33 (50%) received pegylated interferon alfa 2b (1 μg /kg/week) with ribavirin. EVR was achieved in 44 (66.7%), and ETR in 46 (69.7%); overall SVR was achieved in 38 (57.6%) patients. Factors predictive of SVR were age (p value = 0.03), treatment naïve status (p value = 0.04) and EVR (p value<0.001). Five patients were unable to complete the treatment due to side effects or cytopenias. Conclusions: Treatment of patients with HCV genotype 3, compensated cirrhosis, with pegylated interferon and ribavirin is effective and well tolerated.

Factors predicting in-hospital mortality in patients with cirrhosis hospitalized with gastro-esophageal variceal hemorrhage.

AIM : To identify factors at the time of admission that predict in-hospital mortality in patients with gastro-esophageal variceal hemorrhage. METHODS : Case records of patients admitted with gastro-esophageal variceal hemorrhage between January 1998 and October 2003 were retrospectively analyzed. Relevant clinical and laboratory parameters and their relationship to mortality, were studied. Clinical parameters assessed included Child-Pugh class, ascites, portosystemic encephalopathy (PSE) and occurrence of rebleed within 24 hours of esophago-gastroduodenoscopy. The laboratory parameters assessed were: hemoglobin, prothrombin time, serum bilirubin, creatinine and albumin. RESULTS : Of the 343 patients admitted during the study period, 30 (8.7%) died in hospital. Serum bilirubin (2.4 versus 1.6 mg/dL) and serum creatinine (2.1 vs 1.1 mg/dL) levels were higher among non-survivors than among survivors. Non-survivors were also more likely to suffer from PSE (53%) than survivors (17%), while re-bleeding within 24 hours of endoscopy occurred in 40% and 5% of these groups, respectively. On multivariate analysis, serum creatinine > 1.5 mg/dL at the time of admission (p < 0.001), serum bilirubin > 3 mg/dL (p < 0.001), presence of PSE (p = 0.003) and rebleed within 24 hours of endoscopy (p < 0.001) were significant predictors of mortality. CONCLUSION : Serum creatinine and bilirubin levels, presence of PSE and re-bleeding within 24 hours of initial endoscopy are independent predictors of mortality in patients with gastro-esophageal variceal bleeding.

Sclerotherapy plus octreotide versus sclerotherapy alone in the management of gastro - oesophageal variceal hemorrhage

There are different ways for controlling oesophageal variceal bleed which include pharmacological and endoscopic methods. In this study we compare efficacy of octreotide [50 g/hr for 48 hours] combined with sclerotherapy versus sclerotherapy alone in patients with acute bleeding from gastro-oesophageal varices [GOV]. It was a randomized clinical controlled trial conducted at Aga Khan University Hospital, Karachi, from January 1997 to December 1998. We evaluated the role of octreotide [50mcg/hr for 48 hours] combined with sclerotherapy versus sclerotherapy alone in a total of 105 adult cirrhotic patients who had acute bleeding from GOV. Patients were assigned to receive octreotide plus sclerotherapy or sclerotherapy alone. Primary outcome measure was 5-day survival without rebleeding. The hospital stay in days and blood transfusion requirements were also compared in the combined treatment group versus sclerotherapy alone group. Initial control of bleeding was achieved in 46/51 [90.2%] patients who received combined treatment compared to 41/54 [75.9%] patients [p=0.05] in sclerotherapy alone group. Rebleeding after the first 48 hours was less in the octreotide treated patients 2/46 vs. 8/41 patients [p=0.003]. The octreotide treated patients had a better short term [5 days] survival without rebleeding 44/51 vs. 33/54 [p=0.003] and shorter hospital stay, 5.31 +/- 3.87 days vs. 6.63 +/- 3.86 [p=0.008] as compared to sclerotherapy alone group. The blood transfusion requirement was also less in the combined treatment group 3.88 +/- 2.80 vs. 5.37 +/- 3.15 units [p=0.002]. 1] The combination of sclerotherapy, and octreotide infusion over 48 hours is more effective than sclerotherapy alone in the treatment of acute variceal bleeding and prevention of early rebleed in cirrhotic patients. 2] It leads to shorter hospital stay and 3] less blood transfusion requirements. 4] Although early survival without rebleeding is improved, the overall mortality at the end of hospitalization period is similar in the two groups of treated patients

Yet another cause of chronic viral hepatitis?

The clinical features, course and histology of liver in 20 patients; mostly middle aged to elderly females, closely resembling chronic Non A Non B hepatitis is presented. They presented quite late in their disease and therefore, complications such as variceal bleeds, ascites and encephalopathy were frequent. Our patients were negative for hepatitis B and C virus serology. Metabolic and immune causes of chronic liver disease were also ruled out. To the best of our knowledge, this is the first study of its kind elaborating the clinical features, course and histology of liver in chronic Non B Non C hepatitis and raises a number of questions as to the nature of the infecting virus and the epidemiology of disease