Pegylated-interferon and ribavirin in liver transplant candidates and recipients with HCV cirrhosis: systematic review and meta-analysis of prospective controlled studies.

SUMMARY: Pegylated interferon with ribavirin (Peg/R) is the most effective therapy for chronic hepatitis C virus (HCV) but its utility and effectiveness after liver transplantation has been difficult to assess. We evaluated efficacy, tolerability, and safety of Peg/R in liver transplant candidates and recipients with HCV cirrhosis. We searched medical databases and conference proceedings between January 1999 and January 2008 selecting randomized and nonrandomized studies. Primary end points meta-analytically were: (1) sustained viral response (SVR) and (2) histological response. Secondary end points were: (1) treatment discontinuation, (2) mortality, and (3) rejection episodes. Pegylated interferons using either 1-1.5 mcg/kg of pegylated interferon alpha-2b or 180 microg (pegylated interferon alpha-2a combined with ribavirin 800-1200 mg/day were the most effective compared to any other regimen or no therapy. In three pretransplant studies the median SVR was 19.6% (19.6-50%). In six postransplant studies where a meta-analysis was done the cumulative risk difference in SVR was 0.31% (95% CI, 0.18-0.44, p < 0.001). However histological response was not significantly better compared to no therapy or other antiviral regimens. There were no significant differences in discontinuation of therapy, acute or chronic rejection or mortality between optimal Peg/R vs no treatment or other regimens. Hence pegylated interferon plus ribavirin in full doses is effective pre and post transplant but has a low SVR rate. To date no significant histological improvement has been reported.

Muscle cramps in cirrhosis: the therapeutic value of quinine. Is it underused?

Muscle cramps are a common and recurring symptom in patients with cirrhosis. Although, the pathophysiology has not been specifically studied in cirrhosis, this is thought to be the same for cramps in general, originating in the motorneurone, with high frequency firing of motor unit action potentials. However precise pathophysiological mechanisms are not known. Risk factors in cirrhosis have been little studied. Neither aetiology, nor pre-ascitic or ascitic stage, nor electrolyte disturbances, nor use of diuretic therapy has been found to have a statistical association with cramps in patients with cirrhosis. Effective treatments, from this literature review, are albumin, which however is expensive and has little applicability as preventative therapy and oral quinine or quinidine. Quinine is little used in Italy but licensed in the UK for the therapy of muscle cramps. There is evidence for the efficacy of quinine in patients without cirrhosis and in healthy subjects. In cirrhosis quinidine (isomer of quinine) has also been shown to be effective versus placebo. Its major effect is in the prevention of cramps. More widespread use of quinine and further studies are needed, particularly in Italy and other countries, in which its use has been limited, as it is effective therapy in many patients with cirrhosis.

Intrahepatic cholestasis after liver transplantation.

Biochemical cholestasis after liver transplantation is common and often has no clinical significance if biliary anastomosis strictures and leaks have been excluded. There is no agreed upon definition for severe cholestasis, but it is associated with a worse mortality. There has been little evaluation on risk factors, but these include cryoprecipitate and platelet transfusion intraoperatively, nonidentical blood group, suboptimal graft appearance, inpatient status before transplant, and bacteremia within the first month. Associated causes considered as early (<6 months) include ischemia-reperfusion injury, primary nonfunction, small-for-size graft syndrome, infection, drugs and acute cellular rejection. Late causes include hepatic artery thrombosis, chronic rejection, biliary complications, recurrent viral and cholestatic disease, and posttransplant lymphoproliferative disorder.

Models for non-alcoholic fatty liver disease: a link with vascular risk.

Non alcoholic fatty liver disease (NAFLD) is often part of the metabolic syndrome which includes central obesity, dyslipidaemia, insulin resistance/type 2 diabetes mellitus and hypertension. In turn, NAFLD may be associated with an increased vascular risk. Several experimental models which express histological steatosis or steatohepatitis with fibrosis have been described. This review identifies those models of NAFLD with features of vascular risk.