Impact of direct acting antivirals on occurrence and recurrence of hepatocellular carcinoma: Biologically plausible or an epiphenomenon?

Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Chronic hepatitis C virus infection (HCV) is the most common cause of HCC in many European countries, Japan and Pakistan. Introduction of the new direct acting antivirals (DAAs) has revolutionized the management of HCV worldwide, with high rates of sustained virologic response in patients who could not have tolerated the previous interferon based treatments. However, recently there have been reports raising caution about the long term effects of DAAs, particularly a possible increased risk of HCC. Therefore this review explores the current molecular studies as well as clinical data that investigate the impact of DAAs on occurrence and recurrence of HCC

Irritable Bowel Syndrome and Psychiatric Disorders in Pakistan: A Case Control Study

Background. The psychiatric disorders like anxiety and depression could have a profound influence on onset, expression, and course of Irritable bowel syndrome (IBS). Aim. To estimate the frequency and strength of association of common mental disorders (CMDs) in patients with IBS and patients with other chronic diseases, that is, migraine and hypertension. Method. This was a case control study. Individuals aged 18–70 years diagnosed as IBS were enrolled as cases. The control groups consisted of patients without IBS but diagnosed to have a chronic disease, that is, migraine or HTN. Self-Reporting Questonnaire-20(SRQ-20) was used as a screening tool for the detection of CMD. Results. 82 patients were enrolled in each group. Mean SRQ score was significantly higher in IBS group than controls (9.9 ± 4.5 versus 4.9 ± 3.6, P < 0.001). CMDs were more frequent (67.1% versus 22%) and the odds of CMD were 7.24 times higher among IBS patients than controls (95% CI 3.6–14.5, P < 0.001). No difference was found in frequency of CMDs among various subtypes of IBS. Conclusion. We found that CMDs are more common and strongly associated with IBS as compared to other chronic diseases. Early screening for CMDs might be useful for an effective management of IBS

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

Hepatocellular carcinoma in Native South Asian Pakistani population; trends, clinico-pathological characteristics & differences in viral marker negative & viral-hepatocellular carcinoma

Background HCC is the fifth most common cancer globally. Our study was conducted to (1)investigate the trends and clinico-pathological characteristics of Hepatocellular carcinoma among native South Asian patients in Pakistan, (2)to estimate the prevalence as well as the trends of viral marker negative HCC and (3) to compare the clinico-pathological, radiological characteristics, applicability of treatment at diagnosis and prognostic factors among patients with both viral marker negative and viral marker positive-HCC being consulted at Aga Khan University Hospital(AKUH), Karachi, Pakistan. Method Patients ≥18 years, already diagnosed to have HCC and visiting AKUH during 1999–2009 were identified using ICD code 1550. The diagnosis of HCC was made in the presence of characteristic features of HCC on triple-phasic CT scan/MRI or with histological findings on biopsy. Results 645 patients were enrolled. Of these 546(84.7%) were viral-HCC and 99(15.3%) were viral marker negative HCC. Among viral-HCC group underlying etiology of cirrhosis was HCV in 67.9%, HBV in 21.8% and concomitant HBV with HCV or HDV in 10.3% cases. Majority (62.8%) patients had advanced HCC. Larger tumor size (p \u3c 0.001), shorter duration between diagnosis of cirrhosis and HCC (p 0.03), concomitant Diabetes Mellitus (p \u3c 0.001) were found significant factors associated with viral marker negative HCC. Conclusion The burden of hepatocellular carcinoma is rising among native South Asian Pakistani population and the viral marker negative HCC are not uncommon in our population. Viral marker negative HCC tend not to be under surveillance as compared to viral-HCC and are diagnosed mostly at advanced stage & when they became symptomatic

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

Prevalence and risk of hepatitis E virus infection in the HIV population of Nepal

Background: Infection with the hepatitis E virus (HEV) can cause acute hepatitis in endemic areas in immune-competent hosts, as well as chronic infection in immune-compromised subjects in non-endemic areas. Most studies assessing HEV infection in HIV-infected populations have been performed in developed countries that are usually affected by HEV genotype 3. The objective of this study is to measure the prevalence and risk of acquiring HEV among HIV-infected individuals in Nepal. Methods: We prospectively evaluated 459 Human Immunodeficiency Virus (HIV)-positive individuals from Nepal, an endemic country for HEV, for seroprevalence of HEV and assessed risk factors associated with HEV infection. All individuals were on antiretroviral therapy and healthy blood donors were used as controls. Results: We found a high prevalence of HEV IgG (39.4%) and HEV IgM (15.3%) in HIV-positive subjects when compared to healthy HIV-negative controls: 9.5% and 4.4%, respectively (OR: 6.17, 95% CI 4.42-8.61, p \u3c 0.001 and OR: 3.7, 95% CI 2.35-5.92, p \u3c 0.001, respectively). Individuals residing in the Kathmandu area showed a significantly higher HEV IgG seroprevalance compared to individuals residing outside of Kathmandu (76.8% vs 11.1%, OR: 30.33, 95% CI 18.02-51.04, p = 0.001). Mean CD4 counts, HIV viral load and presence of hepatitis B surface antigen correlated with higher HEV IgM rate, while presence of hepatitis C antibody correlated with higher rate of HEV IgG in serum. Overall, individuals with HEV IgM positivity had higher levels of alanine aminotransferase (ALT) than IgM negative subjects, suggesting active acute infection. However, no specific symptoms for hepatitis were identified. Conclusion: HIV-positive subjects living in Kathmandu are at higher risk of acquiring HEV infection as compared to the general population and to HIV-positive subjects living outside Kathmandu

Re-structuring university hospital’s internship program using kern’s six-step model of Instructional design

Abstract Background: Internship is a phase of training wherein a graduate learns in the context of practice, acquiring skills under supervision so that he/she may become capable of functioning independently. We are reporting the process of curriculum restructuring for strengthening the Internship Program at this university hospital. Methodology: We used Kerns’ six-step model to evaluate and restructure the internship curriculum. Step 01: Problem Identification & General need assessment- Thorough literature review revealed Internship as the crucial year of training that needs to be fashioned around the competencies required to make good doctor

Prevalence and risk of hepatitis e virus infection in the HIV population of Nepal

Background: Infection with the hepatitis E virus (HEV) can cause acute hepatitis in endemic areas in immune-competent hosts, as well as chronic infection in immune-compromised subjects in non-endemic areas. Most studies assessing HEV infection in HIV-infected populations have been performed in developed countries that are usually affected by HEV genotype 3. The objective of this study is to measure the prevalence and risk of acquiring HEV among HIV-infected individuals in Nepal. Methods: We prospectively evaluated 459 Human Immunodeficiency Virus (HIV)-positive individuals from Nepal, an endemic country for HEV, for seroprevalence of HEV and assessed risk factors associated with HEV infection. All individuals were on antiretroviral therapy and healthy blood donors were used as controls. Results: We found a high prevalence of HEV IgG (39.4%) and HEV IgM (15.3%) in HIV-positive subjects when compared to healthy HIV-negative controls: 9.5% and 4.4%, respectively (OR: 6.17, 95% CI 4.42-8.61, p < 0.001 and OR: 3.7, 95% CI 2.35-5.92, p < 0.001, respectively). Individuals residing in the Kathmandu area showed a significantly higher HEV IgG seroprevalance compared to individuals residing outside of Kathmandu (76.8% vs 11.1%, OR: 30.33, 95% CI 18.02-51.04, p = 0.001). Mean CD4 counts, HIV viral load and presence of hepatitis B surface antigen correlated with higher HEV IgM rate, while presence of hepatitis C antibody correlated with higher rate of HEV IgG in serum. Overall, individuals with HEV IgM positivity had higher levels of alanine aminotransferase (ALT) than IgM negative subjects, suggesting active acute infection. However, no specific symptoms for hepatitis were identified. Conclusions: HIV-positive subjects living in Kathmandu are at higher risk of acquiring HEV infection as compared to the general population and to HIV-positive subjects living outside Kathmandu