Carvedilol vs. esophageal variceal band ligation in the primary prophylaxis of variceal hemorrhage: a multicentre randomized controlled trial.

BACKGROUND & AIMS: Esophageal variceal bleed is a major problem in patients with cirrhosis. Endoscopic variceal ligation (EVL) has been shown to be equal to or better than propranolol in preventing first bleed. Carvedilol is a non-selective ß blocker with alpha-1 adrenergic blocker activity. Hemodynamic studies have shown carvedilol to be more effective than propranolol at reducing portal pressure. We compared efficacy of carvedilol with EVL for primary prophylaxis of esophageal variceal bleed. METHODS: Cirrhotic patients with esophageal varices were randomized to carvedilol 12.5mg daily or EVL at three university hospitals of Pakistan. End points were esophageal variceal bleeding, death or liver transplant. RESULTS: Two hundred and nine patients were evaluated. Eighty two and eighty six patients were randomized in carvedilol and EVL arms respectively. Mean age was 48 ± 12.2 years; 122 (72.7%) were males; 89.9% had viral cirrhosis; mean Child-Pugh score was 7.3 ± 1.6 and mean follow up was 13.3 ± 12.1 months (range 1-50 months). Both EVL and carvedilol groups had comparable variceal bleeding rates (8.5% vs. 6.9%), bleed related mortality (4.6% vs. 4.9%) and overall mortality (12.8% vs. 19.5%) respectively. Adverse events in carvedilol group were hypotension (n=2), requiring cessation of therapy, while transient nausea (n=18) and dyspnea (n=30) resolved spontaneously. In the EVL arm, post banding ulcer bleed (n=1) and chest pain (n=17), were termed as serious adverse events while transient dysphagia (n=58) resolved without treatment. CONCLUSIONS: Although our study is underpowered, the findings suggest that carvedilol is probably not superior to EVL in preventing first variceal bleed in patients with viral cirrhosis.

Consensus interferon plus ribavirin for hepatitis C genotype 3 patients previously treated with pegylated interferon plus ribavirin.

BACKGROUND: Not enough data are available about the effectiveness of consensus interferon (CIFN) among HCV genotype 3 patients who failed to respond to pegylated interferon and ribavirin. OBJECTIVES: We aimed to assess the efficacy and safety of CIFN and ribavirin in non-responders and relapsers to pegylated interferon with ribavirin therapy. PATIENTS AND METHODS: This open-label investigator-initiated study included 44 patients who received CIFN 15 µg /day plus ribavirin 800-1200 mg daily. In patients with an early virological response (EVR), the dose of CIFN was reduced to 15 µg thrice a week for further 36 weeks. Patients with delayed virological response continued to receive daily CIFN plus ribavirin to complete 48 weeks. The patients were considered "non-responders" if there were less than 2 log reduction in HCV RNA at 12 weeks and detectable HCV RNA at 24 weeks. RESULTS: Twenty-four patients (55%) were non-responders and 20 patients were relapsers to the previous treatment with pegylated interferon plus ribavirin (mean age 43.6 ± 9.4 years, males 25 (57%)). Nine patients were clinically cirrhotic (Child A). End of treatment virological response was achieved in 19 (43.1%) patients and sustained virological response (SVR) occurred in 12 (27.3%). Out of these 12 patients, eight were non-responders and four were relapsers to the previous treatment. Advanced fibrosis or clinical cirrhosis was associated with low SVR. Adverse events were fever, myalgia, anorexia, depression, and weight loss. Two patients received granulocyte colony stimulating factor for transient neutropenia. Seven patients were given erythropoietin to improve hemoglobin, and six were treated for mild depression. Two patients developed portosystemic encephalopathy. CONCLUSIONS: More than one-quarter of treatment-experienced patients with HCV genotype 3 achieved SVR after re-treatment with consensus interferon plus ribavirin.

Successful pregnancy in a kidney transplant recipient with chronic hepatitis B virus infection.

Overall success rate of pregnancies in kidney transplant recipients is higher than 90% if pregnancy goes beyond the 1st trimester. Risks to mother include hypertension, preeclampsia, infections, and worsening proteinuria, and those to the fetus are prematurity, intrauterine growth retardation, and low birth weight. Hepatitis B infection is associated with progressive liver disease and diminished survival in kidney transplant recipients. A 32-year-old woman had undergone living unrelated donor kidney transplant. Two years after transplantation, she presented with live gestation of 6 weeks. She was also found positive for hepatitis B surface antigen and extracellular antigen. Liver enzymes were normal and ultrasonography findings were normal. Cyclosporine dose was reduced and lamivudine was started. She was monitored closely until 33 weeks, when she gave birth to a healthy female baby through spontaneous vaginal delivery. The newborn received vaccination and immunoglobulins for hepatitis B virus. Mother's kidney allograft function remained stable throughout pregnancy.

Investigating an outbreak of acute viral hepatitis caused by hepatitis E virus variants in Karachi, South Pakistan.

Hepatitis E is a classic water-borne disease in developing countries. Detection of anti-HEV IgM and IgG antibodies, in addition to HEV RNA are useful epidemiological markers in diagnosis of hepatitis E. This study was conducted to investigate an outbreak of acute viral hepatitis in South-Pakistan. Anti-HEV IgM and IgG were assessed comparatively with serological kits manufactured by Abbott, Cosmic, TGH, and Wantai, selecting HEV RNA as reference assay. Molecular evolutionary analysis was performed by phylogeny and HEV spread time analysis by Bayesian Coalescent Theory approach. Of the 89 patients, 24 (26.9%) did not have acute hepatitis viral marker. Of the remaining 65 cases, 4 (6.1%) were positive for anti-HAV IgM, one (1.5%) for anti-HBc IgM, 2 (3%) for HCV, 53 (81.5%) for anti-HEV IgM, and 5 (7.7%) were hepatitis-negative. The Wantai test was 100% sensitive and specific followed by Cosmic (98.1% and 100%), TGH (98.1% and 97.2%) and Abbott (79.2% and 83.3%). Two HEV variant strains were detected by phylogeny responsible for this acute hepatitis outbreak. Estimates on demographic history of HEV showed that HEV in Pakistan has remained at a steady nonexpanding phase from around 1970 to the year 2005, in which it expanded explosively with the emergence of new HEV variants. In conclusion, the limited sensitivity of available assay (Abbott anti-HEV EIA) may be a concern in HEV diagnosis in Pakistan. This study cautions that the dissemination of the variant strains to other areas of Pakistan may lead to explosive HEV outbreaks.

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.

Successful outcome of a pregnancy in a woman with advanced cirrhosis due to hepatitis B surface antigenemia, delta super-infection and hepatitis C co-infection: a case report.

Pregnancy in women with advanced liver disease is rare. In this paper we described the case of a successful pregnancy in a young woman with advanced cirrhosis due to hepatitis B surface antigenemia, hepatitis delta super-infection and Hepatitis C co-infection. A brief review of the medical literature on pregnancy in women with cirrhosis is also presented.