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 determining the clinical outcome of acute variceal bleed in cirrhotic patients.

Variceal bleed is a severe complication of portal hypertension. We studied the predictors of failure to control variceal bleed and re-bleed in patients with cirrhosis. We reviewed the case records of 382 consecutive patients admitted with variceal bleed from January 2001 to December 2005. Diagnosis of cirrhosis was made on clinical, laboratory, and radiological parameters. Acute variceal bleeding, failure to control bleed, and re-bleeding were defined according to Baveno III consensus report. Failure to control bleed was observed in 39 (10.2%) patients while in hospital re-bleed occurred in 49 (12.8%) patients. Thirty-four patients died. Diabetes was present in 148 (39%) patients. On multivariate logistic regression analysis, predictors of failure to control bleed were presence of diabetes mellitus and active bleeding at the time of endoscopy; predictors of in-hospital re-bleed were diabetes mellitus and serum bilirubin >3 mg/dL. Diabetes mellitus, active bleeding at endoscopy and bilirubin >3 mg/dL are bad prognostic factors for initial control of variceal bleed, and recurrent bleed in patients with cirrhosis.

Hepatitis C in Pakistan: magnitude, genotype, disease characteristics and therapeutic response.

Hepatitis C virus is one of the most common blood-borne viruses and is associated with significant morbidity and mortality. It affects 170 million people worldwide and 2.4%-6.5% people in Pakistan. Therapeutic injections by contaminated, re-used syringes, transfusion of unsafe blood and re-use of razors are major factors responsible for the spread of hepatitis C in the general population. Genotype 3 is the most common genotype in Pakistan and is most responsive to interferon and ribavirin combination therapy. HCV is the leading cause of chronic liver disease and hepatocellular carcinoma in Pakistan. Appropriate steps need to be taken in the country to control factors responsible for the spread of hepatitis C.

Hepatitis B vaccination status in health care workers of two university hospitals

Hepatitis B virus [HBV] infection is the leading cause of hepato-cellular carcinoma and acute liver failure in Asia. It usually transmits through parenteral routes. The health personnel are at high risk for acquiring HBV infection. This study was designed to determine the immunization status for HBV infection in healthcare workers [HCWs] of two university hospitals in Sindh, Pakistan. The healthcare workers of two university hospitals [Liaquat University Hospital, Jamshoro and Isra University Hospital, Hyderabad] were selected and divided into ten different groups. There were total 923 participants including 649 [70%] males and 274 [30%] females. The mean age of participants was 29.6 years. A total of 596 [64.6%] participants were immunized for HBV infection and 392 [66.2%] were inoculated three or more than three doses of vaccine. The pre vaccination HBSAg status was checked in 380 [41.2%] and it was positive in 18 [4.7%] participants. The frequency of immunization was highest in doctors [92.4%] and lowest in nursing assistants [18.9%]. A good number of HCWs is vaccinated against HBV infection in these two university hospitals of Sindh compared to general population of Pakistan. This study shows the need for a more aggressive approach to get HCWs vaccinated, because a significant percentage of them is not protected

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.