ABSTRACT: Pruritus is a troublesome complication in patients with cholestatic liver disease. Several links to its pathogenesis have been proposed, including the role of bile acids, endogenous opioid and serotonins, and lysophosphatidic acid. The management of pruritus in cholestasis is challenging. Medical treatment of the underlying cholestatic condition may provide benefit. Extracorporeal albumin dialysis can be pursued for those who have a poor quality of life and failed the various therapeutic interventions, while awaiting liver transplantation. Experimental interventions, and the management of pruritus in certain conditions such as intrahepatic cholestasis of pregnancy and benign recurrent intrahepatic cholestasis, are also briefly reviewed.
Clinics in liver disease 05/2012; 16(2):331-46.
ABSTRACT: Ribavirin is a synthetic guanosine analogue, which acts against hepatitis C virus (HCV) through several mechanisms that include
1) immune modulation; 2) inhibition of inosine monophosphate dehydrogenase 3) inhibition of RNA-dependent RNA polymerase;
4) induction of HCV mutagenesis; and 5) modulation of interferon-stimulated gene expression. Addition of ribavirin to peginterferon-α
substantially improves sustained virologic response (SVR) and decreases relapse rates. Ribavirin can be associated with hemolytic
anemia. However, recent data suggest that SVR is not negatively impacted by treatment-induce anemia. Notably, optimal dosing
strategy and the proper management of anemia are crucial to achieve the best treatment outcome. Several advances have been
made in the areas relevant to ribavirin, such as the discovery of inosine triphosphatase gene as a promising pharmacogenetic
marker and a predictor of anemia, and the role for erythropoiesis-stimulating agent in the management of anemia related to
ribavirin use. Recent observations indicate that ribavirin will remain as a critical component of HCV therapy, even in the
context of direct acting antivirals.
KeywordsRibavirin–Hepatitis C Virus (HCV)–Treatment–Sustained Virologic Response (SVR)–Relapse–Mechanisms of action–IMPDH inhibitor–Mutagenesis–Ribavirin-induced anemia–Hemolysis–Pegylated interferon–Peginterferon-alfa–ITPA gene–Taribavirin–Interferon signaling pathway–Weight-based dosing–Direct Acting Anti-viral (DAA)–Erythropoiesis-stimulating agent–Epoetin
Current Hepatitis Reports 04/2012; 10(3):168-178.
ABSTRACT: Genotype 6 chronic hepatitis C (HCV) is encountered predominantly in Southeast Asia and data on optimal treatment strategy is limited. This study was aimed at assessing the rate and predictors of sustained virological response (SVR) in genotype 6 chronic HCV following 48 and 24 weeks of pegylated interferon and ribavirin therapy.
This investigator-initiated, open-label randomized trial was conducted in Vietnam between 2008 and 2010. One hundred and five treatment-naïve HCV genotype 6 patients were randomized to either 48-week (N=70) or 24-week (N=35) duration of pegylated interferon (PEG-IFN) alfa-2a 180 mcg/week and ribavirin (RBV) 15mg/kg/day; 92 patients completed the study (63 in the 48-week and 29 in the 24-week group, respectively). Primary outcome was sustained virological response (SVR) as intention-to-treat analysis.
There was no statistical difference in SVR between 48-week and 24-week treated groups (71% vs. 60%, respectively; p=0.24). In the 48-week and 24-week treatment groups, 81% and 80% of cases achieved rapid virological response (RVR) (p=0.86), and 86% and 80% achieved complete early virological response (p=0.45). Among those patients with RVR, SVR was in 86% (48-weeks), and 75% (24-weeks) of cases, whereas following non-RVR, only 8% of cases had an SVR with 48-week treatment duration.
Overall, RVR was achieved in the majority of genotype 6 patients and, in those patients, similar and high rates of SVR were noted following 24-week and 48-week therapy. This observation, however, needs validation in a larger study to demonstrate non-inferiority of the shorter duration therapy. In non-RVR patients, even 48-week therapy achieved low SVR rates.
Journal of Hepatology 01/2012; 56(5):1012-8. · 9.26 Impact Factor
Liver Transplantation 06/2011; 17(6):625-7. · 3.39 Impact Factor
ABSTRACT: Patients with cirrhosis are immunocompromised and susceptible to infections. Although detection and treatment of spontaneous bacterial peritonitis (SBP) have improved, overall survival rates have not increased greatly in recent decades-infection still increases mortality 4-fold among patients with cirrhosis. Hospitalized patients with cirrhosis have the highest risk of developing infections, especially patients with gastrointestinal (GI) hemorrhage. Bacterial infections occur in 32% to 34% of patients with cirrhosis who are admitted to the hospital and 45% of patients with GI hemorrhage. These rates are much higher than the overall rate of infection in hospitalized patients (5%-7%). The most common are SBP (25% of infections), urinary tract infection (20%), and pneumonia (15%). Bacterial overgrowth and translocation from the GI tract are important steps in the pathogenesis of SBP and bacteremia-these processes increase levels of endotoxins and cytokines that induce the inflammatory response and can lead to septic shock, multiorgan dysfunction, and death. A number of other bacterial and fungal pathogens are more common and virulent in patients with cirrhosis than in the overall population. We review the pathogenesis of infections in these patients, along with diagnostic and management strategies.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 03/2011; 9(9):727-38. · 5.64 Impact Factor