Hepatitis: Khuroo MS

Khuroo MS, Khuroo MS. · Digestive Disease Centre, Dr Khuroo's Medical Clinic, Srinagar, India. · Curr Opin Infect Dis. · Pubmed #18725805 No free full text.

Abstract: PURPOSE OF REVIEW: Hepatitis E is an emerging infectious disease. This review will focus on recent advances in the zoonotic transmission, global distribution and control of hepatitis E. RECENT FINDINGS: Hepatitis E virus infection is known to cause waterborne epidemics and sporadic infections in developing countries. Recently, there have been several reports on zoonotic foodborne autochthonous infections of hepatitis E in developed countries. Hepatitis E typically causes self-limited acute infection. Recent reports have documented hepatitis E virus causing chronic hepatitis and cirrhosis in patients after solid organ transplantation. High incidence and severity of hepatitis E in pregnant women have been re-confirmed. The reason for high mortality in pregnant women remains ill understood. A recombinant hepatitis E vaccine has been evaluated in a phase 2, randomized, placebo-controlled trial in Nepal and was found to be well tolerated and efficacious. SUMMARY: There has been considerable advance in understanding the epidemiology of hepatitis E virus infections in western countries. The occurrence of chronic hepatitis in organ transplant recipients opens a new chapter in hepatitis E epidemiology. The report on an efficacious and well tolerated recombinant vaccine gives hope for control of the disease in the near future.

Khuroo MS, Khuroo MS. · Digestive Disease Centre, Dr Khuroo's Medical Clinic, Srinagar, India. · Curr Opin Infect Dis. · Pubmed #18725805 No free full text.

Abstract: PURPOSE OF REVIEW: Hepatitis E is an emerging infectious disease. This review will focus on recent advances in the zoonotic transmission, global distribution and control of hepatitis E. RECENT FINDINGS: Hepatitis E virus infection is known to cause waterborne epidemics and sporadic infections in developing countries. Recently, there have been several reports on zoonotic foodborne autochthonous infections of hepatitis E in developed countries. Hepatitis E typically causes self-limited acute infection. Recent reports have documented hepatitis E virus causing chronic hepatitis and cirrhosis in patients after solid organ transplantation. High incidence and severity of hepatitis E in pregnant women have been re-confirmed. The reason for high mortality in pregnant women remains ill understood. A recombinant hepatitis E vaccine has been evaluated in a phase 2, randomized, placebo-controlled trial in Nepal and was found to be well tolerated and efficacious. SUMMARY: There has been considerable advance in understanding the epidemiology of hepatitis E virus infections in western countries. The occurrence of chronic hepatitis in organ transplant recipients opens a new chapter in hepatitis E epidemiology. The report on an efficacious and well tolerated recombinant vaccine gives hope for control of the disease in the near future.

Khuroo MS. · Department of Medicine, King Faisal Specialist Hospital & Research Centre, P.O. Box 3354, Riyadh, Saudi Arabia. · Int J Antimicrob Agents. · Pubmed #12615378 No free full text.

Abstract: Viral hepatitis is caused by a number of unrelated hepatotrophic viruses, known and unknown. Five hepatitis viruses namely HAV, HBV, HCV, HDV and HEV have been well characterized and the epidemiology and disease pattern of each agent has been defined. In the West, HAV, HBV and HCV are major causes of viral hepatitis. In the East, HEV is the most common cause of viral hepatitis. HAV is ubiquitous in childhood in such countries and accounts for less than 4% of disease in adults. Viral hepatitis becomes a problem to an international traveller when he envisages a journey from low endemic to high endemic area and is susceptible to the infection endemic at his destination. Millions of such potentially susceptible travellers from Europe, the USA, Canada, Japan, Australia, and New Zealand visit endemic areas every year for various reasons. Viral hepatitis is the most common reported immunization-preventable disease among travellers to developing countries. Imported viral hepatitis incapacitates the incumbents for an average of 4-10 weeks. Considering the magnitude of the travel, the number of cases of viral hepatitis and case fatality of around 2%, the disease causes significant morbidity and mortality in such communities. It has been estimated that viral hepatitis occurs 100 times more frequently than typhoid fever and 1,000 times more often than cholera in travellers to developing countries. Hepatitis A is the most common form of viral hepatitis in travellers and cumulative data have shown a risk of 3-6 cases/1,000 persons/month of stay whereas the risk of acquiring hepatitis B is 10 times lower.

Alfaleh FZ, Hadad Q, Khuroo MS, Aljumah A, Algamedi A, Alashgar H, Al-Ahdal MN, Mayet I, Khan MQ, Kessie G. · College of Medicine, King Saud University, Riyadh, Saudi Arabia. · Liver Int. · Pubmed #15566506 No free full text.

Abstract: AIM: Comparing the efficacy of peginterferon alpha-2b plus ribavirin with interferon alpha -2b plus ribavirin in Saudi patients with chronic hepatitis C virus (HCV) commonly infected with genotype 4. METHODS: A total of 96 patients with chronic HCV infection were randomly assigned to two treatment groups. Forty-eight patients received once weekly 100 microg of peginterferon alpha-2b plus ribavirin given orally 800 mg/day (peginterferon group). Another 48 patients received thrice weekly 3 million units of interferon alpha-2b plus ribavirin 800 mg/day (interferon group). At the end of treatment (48 weeks) and sustained (72 weeks) biochemical and virologic responses were determined. RESULTS: In the peginterferon group, 70.8% (34/48) patients attained both biochemical and virologic responses at the end of the treatment as against 52.1% (25/48) patients in the interferon group. (P=0.09 for both). Similarly, sustained biochemical and virologic responses in the peginterferon group were attained in 52.1% (25/48) and 43.8% (21/48) patients as against 43.8% (21/48) and 29.2% (14/48) patients in the interferon group, respectively (P=0.54 and 0.20, respectively). The sustained virologic response rates in patients with genotype 4 were 42.9% (12/28) in the peginterferon group and 32.3% (10/31) in the interferon group (P=0.43). Patients in peginterferon group had higher, although statistically not significant adverse reactions. CONCLUSIONS: Saudi patients with chronic HCV attained a higher, although statistically not significant sustained virologic response with pegylated interferon plus ribavirin compared with interferon plus ribavirin.

Khuroo MS, Kamili S, Khuroo MS. · Digestive Diseases Centre, Dr Khuroo's Medical Clinic, Srinagar, Kashmir, J&K, India. · J Viral Hepat. · Pubmed #19228284 No free full text.

Abstract: Infection with the hepatitis E virus (HEV) causes a self-limiting acute hepatitis. However, prolonged viremia and chronic hepatitis has been reported in organ transplant recipients. Vertically transmitted HEV infection is known to cause acute hepatitis in newborn babies. The clinical course and duration of viremia in vertically transmitted HEV infection in neonates in not known. We studied 19 babies born to HEV infected mothers. Babies were studied at birth and on a monthly basis to evaluate clinical profile, pattern of antibody response and duration of viremia in those infected with HEV. Fifteen (78.9%) babies had evidence of vertically transmitted HEV infection at birth (IgM anti-HEV positive in 12 and HEV RNA reactive in 10) and three had short-lasting IgG anti-HEV positivity because of trans-placental antibody transmission. Seven HEV-infected babies had icteric hepatitis, five had anicteric hepatitis and three had high serum bilirubin with normal liver enzymes. Seven babies died in first week of birth (prematurity 1, icteric HEV 3, anicteric HEV 2 and hyperbilirubinemia 1). Nine babies survived and were followed up for clinical, biochemical, serological course and duration of viremia. Five of 9 babies who survived were HEV RNA positive. HEV RNA was not detectable by 4 weeks of birth in three babies, by 8 weeks in one and by 32 weeks in one. All surviving babies had self-limiting disease and none had prolonged viremia. Thus HEV infection is commonly transmitted from mother-to-foetus and causes high neonatal mortality. HEV infection in survivors is self-limiting with short lasting viremia.

Khuroo MS, Kamili S, Khuroo MS. · Digestive Diseases Centre, Dr Khuroo's Medical Clinic, Srinagar, Kashmir, J&K, India. · J Viral Hepat. · Pubmed #19228284 No free full text.

Abstract: Infection with the hepatitis E virus (HEV) causes a self-limiting acute hepatitis. However, prolonged viremia and chronic hepatitis has been reported in organ transplant recipients. Vertically transmitted HEV infection is known to cause acute hepatitis in newborn babies. The clinical course and duration of viremia in vertically transmitted HEV infection in neonates in not known. We studied 19 babies born to HEV infected mothers. Babies were studied at birth and on a monthly basis to evaluate clinical profile, pattern of antibody response and duration of viremia in those infected with HEV. Fifteen (78.9%) babies had evidence of vertically transmitted HEV infection at birth (IgM anti-HEV positive in 12 and HEV RNA reactive in 10) and three had short-lasting IgG anti-HEV positivity because of trans-placental antibody transmission. Seven HEV-infected babies had icteric hepatitis, five had anicteric hepatitis and three had high serum bilirubin with normal liver enzymes. Seven babies died in first week of birth (prematurity 1, icteric HEV 3, anicteric HEV 2 and hyperbilirubinemia 1). Nine babies survived and were followed up for clinical, biochemical, serological course and duration of viremia. Five of 9 babies who survived were HEV RNA positive. HEV RNA was not detectable by 4 weeks of birth in three babies, by 8 weeks in one and by 32 weeks in one. All surviving babies had self-limiting disease and none had prolonged viremia. Thus HEV infection is commonly transmitted from mother-to-foetus and causes high neonatal mortality. HEV infection in survivors is self-limiting with short lasting viremia.

Khan MQ, Al-Ashgar H, Khuroo MS, Farahat K, Al-Omari M, Khalaf HA, Khalaf H, Al-Fadda M. · Section of Gastroenterology and Hepatology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. · Ann Saudi Med. · Pubmed #17019089 No free full text.

This publication has no abstract.

Khuroo MS, Khuroo MS, Dahab ST. · Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. · Aliment Pharmacol Ther. · Pubmed #15521839 links to  free full text

Abstract: BACKGROUND: Guidelines for treatment of patients infected with hepatitis C virus genotype 4 are not available. AIM: To perform a meta-analysis of randomized controlled trials comparing peginterferon plus ribavirin with interferon plus ribavirin treatment in treatment-naive patients infected with chronic hepatitis C virus genotype 4. METHODS: The outcome measure was sustained virologic response. The measure of association employed was relative risk calculated by the random-effect model, with heterogeneity, sensitivity and subgroup analyses. RESULTS: Of the 565 studies screened, six randomized controlled trials including 424 patients (peginterferon plus ribavirin 219, interferon plus ribavirin 205) were analysed. Duration of therapy was 1 year in all trials. Sustained virological response obtained with peginterferon plus ribavirin (55%) was significantly higher than with interferon plus ribavirin (30%) [relative risk, 1.71 (95% confidence interval, 1.15-2.56); P = 0.0088]. In the subgroup analyses, sustained virological response in trials using standard-dose ribavirin (1000 or 1200 mg/day) was 72% as against 45.8% in trials using low-dose ribavirin (800 mg/day) (P = 0.01). Further sub-group analyses for treatment duration, body weight, viral load and cirrhosis could not be performed because of lack of relevant data. CONCLUSION: Treatment-naive patients infected with hepatitis C virus genotype 4 should be treated with peginterferon plus standard-dose ribavirin for 1 year, with an expected sustained virological response rate of 72%.

Khuroo MS, Khuroo MS, Dahab ST. · Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. · Aliment Pharmacol Ther. · Pubmed #15521839 links to  free full text

Abstract: BACKGROUND: Guidelines for treatment of patients infected with hepatitis C virus genotype 4 are not available. AIM: To perform a meta-analysis of randomized controlled trials comparing peginterferon plus ribavirin with interferon plus ribavirin treatment in treatment-naive patients infected with chronic hepatitis C virus genotype 4. METHODS: The outcome measure was sustained virologic response. The measure of association employed was relative risk calculated by the random-effect model, with heterogeneity, sensitivity and subgroup analyses. RESULTS: Of the 565 studies screened, six randomized controlled trials including 424 patients (peginterferon plus ribavirin 219, interferon plus ribavirin 205) were analysed. Duration of therapy was 1 year in all trials. Sustained virological response obtained with peginterferon plus ribavirin (55%) was significantly higher than with interferon plus ribavirin (30%) [relative risk, 1.71 (95% confidence interval, 1.15-2.56); P = 0.0088]. In the subgroup analyses, sustained virological response in trials using standard-dose ribavirin (1000 or 1200 mg/day) was 72% as against 45.8% in trials using low-dose ribavirin (800 mg/day) (P = 0.01). Further sub-group analyses for treatment duration, body weight, viral load and cirrhosis could not be performed because of lack of relevant data. CONCLUSION: Treatment-naive patients infected with hepatitis C virus genotype 4 should be treated with peginterferon plus standard-dose ribavirin for 1 year, with an expected sustained virological response rate of 72%.

Khuroo MS, Kamili S, Yattoo GN. · Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. · J Gastroenterol Hepatol. · Pubmed #15209625 No free full text.

Abstract: AIM: To address the issue of whether or not hepatitis E virus (HEV) is transmitted parenterally. METHODS: We conducted a retrospective study which involved 145 multiple transfused patients and 250 healthy controls. A prospective study was also undertaken involving 50 hospitalized patients, 25 of whom were transfused with 107 blood units, while the other 25 did not receive any transfusions. RESULTS: In our retrospective study, markers of acute HEV infection (IgM anti-HEV and HEV RNA) were detected in a significantly higher number of multiple transfused patients (13 of 145) compared to controls (two of 250) (P < 0.001; OR = 12.21 [95% confidence interval: 2.71-54.70]). All 13 HEV-infected patients had been transfused at least once in a 3-month period before testing. Overall, patients positive for any of the HEV markers (IgG, IgM or HEV RNA) had received more blood transfusions, had higher occurrence of icteric disease and higher serum alanine aminotransferase levels. In our prospective study, IgG anti-HEV was detected in 11 of 107 donor samples, three of 25 patients in their pretransfusion samples (one sample was positive for IgM anti-HEV as well) and two of 25 control patients. Post-transfusion HEV infection developed in three of 22 susceptible (IgG anti-HEV negative) transfused patients; the infection was traced to their four respective donors who were asymptomatic, HEV RNA positive (4/4) and IgM anti-HEV positive (3/4). In contrast, none of the non-transfused patients developed HEV infection during the follow-up period. CONCLUSION: Frequent transmission of HEV by blood transfusion places recipients at risk and warrants redefining of the donor screening policy by blood banks, especially in endemic areas.

Khuroo MS, Kamili S. · Department of Gastroenterology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar Kashmir, India. · J Viral Hepat. · Pubmed #12753342 No free full text.

Abstract: The early prognostic indicators for acute liver failure in endemic zones for hepatitis E virus have not been determined. All consecutive patients with acute liver failure from a geographically defined region endemic for hepatitis E virus were studied over the period April 1989-April 1996. Demographic, clinical and biochemical parameters were recorded at presentation and serum samples were analysed for known viral hepatitis (A-E) markers. Multiple parameters were compared in survivors and non-survivors in a univariate analysis. All significant factors on univariate analysis were entered into a stepwise logistic regression analysis to identify independent variables of prognosis. The sensitivity and specificity of significant prognostic factors was then assessed. A total of 180 [69 males and 111 females: age (mean +/- SD) 31.1 +/- 14.7 years] with acute liver failure were studied. Of these, 131 (72.8%) patients died. Hepatitis E virus was the aetiological cause in 79 (43.9%) patients, while hepatitis A virus, hepatitis B virus, hepatitis C virus and non-A, non-E agent/'s could be incriminated in four (2.1%), 25 (13.9%), 13 (7.2%) and 56 (31.1%) patients respectively. Of 83 women in childbearing age, 49 (59.0%) were pregnant, 33 (67.3%) of these were in the third trimester. Forty-seven (95.8%) pregnant women had HEV infection. Nine variables differed significantly between survivors and non-survivors on univariate analysis. Of these, four variables which predicted the adverse outcome on multivariate analysis were non-hepatitis-E aetiology, prothrombin time >30 s, grade of coma >2 and age >40 years in that order of significance. Pregnancy per se or duration of gestation did not adversely affect the prognosis. In endemic areas, hepatitis E virus is the commonest cause of acute liver failure. Acute liver failure occurs in a high proportion of pregnant women, mostly in third trimester. Early predictors of a poor outcome are non-E aetiology, prothrombin time >30 s, grade of coma >2 and age >40 years.

Khuroo MS, Kamili S. · Section of Gastroenterology, Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. · J Viral Hepat. · Pubmed #12558914 No free full text.

Abstract: Hepatitis E causes large-scale epidemics in endemic areas. The disease, during epidemics, has increased incidence and severity in pregnant women. Sporadic acute viral hepatitis (AVH) is common in endemic areas. The relationship of sporadic AVH and pregnancy has not been well studied. Over a 3-year period we prospectively studied 76 pregnant women and 337 non-pregnant women of childbearing age with sporadic acute viral hepatitis for aetiology, clinical course and outcome of disease. The aetiology in sporadic AVH was hepatitis A virus (HAV) in six (1.5%), hepatitis B virus (HBV) in 62 (15%), hepatitis C virus (HCV) in seven (1.7%), hepatitis D virus (HDV) co-infection in six (1.5%), hepatitis E virus (HEV) in 205 (49.6%), and hepatitis non-A-to-E (HNAE) in 127 (30.7%). Sixty-five (85.5%) pregnant women and 140 (41.5%) nonpregnant women had hepatitis E. The proportion of pregnant women was 31.7% in HEV group and 5.3% in non-HEV group [P < 0.001; OR=8.3 (95%C1 4.2-16.3)]. The prevalence of HEV in pregnant women in first trimester (76.9%), second trimester (88.9%), third trimester (83.8%) and puerperium (100%) did not differ significantly (P=0.09). Forty-seven (61.8%) of the 76 pregnant women developed fulminant hepatic failure (FHF), 69.2% in HEV group and 10% in non-HEV group (P < 0.001). Thirty-four (10.1%) nonpregnant women developed fulminant hepatic failure, 10% in HEV group and 9.7% in non-HEV group (P=0.86). FHF had occurred in four (40%) of 10 patients with HE in first trimester as against 41 (74.5%) of 55 patients in second trimester and beyond (P=0.015). Amongst the major complications of fulminant hepatic failure, cerebral oedema (53.2%) and disseminated intravascular coagulation (21.3%) occurred more often in pregnant women than in nonpregnant women (29.4% and 2.8%; P=0.03 and 0.016, respectively) while infections occurred more often in nonpregnant women (36.1%) than in pregnant women (10.6%; P=0.003). Fifty (61.7%) patients with FHF died [25 (53.2%) pregnant women and 25 (69.5%) nonpregnant women (P=0.06)]. Cerebral oedema and HEV aetiology were independent variables of survival in patients with FHF. Patients with cerebral oedema had worse prognosis and patients with HEV aetiology had best chances of survival. Hence HEV was the most common cause of sporadic AVH in this endemic area. High proportion of pregnant women and increased severity of disease in pregnancy were limited to patients with hepatitis E. Sporadic AVH caused by agents other than HEV did not show any special predilection to or increased severity in pregnancy. FHF in pregnant women caused by HEV was an explosive disease with short pre- encephalopathy period, rapid development of cerebral oedema and high occurrence of disseminated intravascular coagulation and may represent a severe manifestation of a Schwartzmann-like phenomenon.