Primary prophylaxis of variceal bleeding.

Gastroesophageal varices are present in almost half of patients with cirrhosis at the time of initial diagnosis. Variceal bleeding occurs in 25% to 35% of patients with cirrhosis. Effective and timely care can prevent variceal bleeding (primary prophylaxis). For example, clinical studies demonstrate that both beta-blockers and endoscopic variceal ligation are effective in preventing a first episode of variceal bleeding. The major challenge is to screen patients in a timely manner and institute a form of therapy that has the highest chance of success in terms of patient compliance and effectiveness.

Secular trends in the incidence of cholangiocarcinoma in the USA and the impact of misclassification.

BACKGROUND AND AIMS: It has been reported that the incidence of intrahepatic cholangiocarcinoma (ICC) has increased in the USA, while extrahepatic cholangiocarcinoma (ECC) has decreased or remained stable. However, neither the recent trends nor the effects of the misclassification of Klatskin tumors are known. METHODS: Using the Surveillance, Epidemiology, and End Results program databases, we calculated the average annual age-adjusted incidence rates (AA-IRs) of ICC and ECC in 4-year time periods (1992-1995, 1996-1999, 2000-2003, 2004-2007). These AA-IRs were calculated with misclassified as well as correctly classified Klatskin tumors. AA-IRs were also calculated based on age, sex, and race. Multivariable Poisson regression models were used to evaluate the secular trends of ICC and ECC. RESULTS: The AA-IR of ICC was 0.92 in 1992-1995 and 0.93 in 2004-2007, while the AA-IR of ECC increased from 0.70 in 1992-1995 to 0.95 in 2004-2007. There was no significant trend in AA-IR of ICC (p = 0.07), while there was a significant increase in ECC across the 4-year time periods (p < 0.001). Klatskin tumors comprised 6.7% of CCs with approximately 90 and 45% misclassified as ICC during 1992-2000 and 2001-2007, respectively. Adjusted Poisson models showed no significant differences in the temporal trend of ICC or ECC due to misclassification of Klatskin tumors. CONCLUSIONS: The incidence of ICC has remained stable between 1992 and 2007 with only slight fluctuations, while the incidence of ECC has been increasing. Misclassification of Klatskin tumors does not appear to play a significant role in the trends of CCs.

An overview of emerging therapies for the treatment of chronic hepatitis C.

Advances in our understanding of the HCV lifecycle and refinement of in vitro methods to select candidate compounds with anti-HCV activity have led to development of DAA agents and other novel antiviral therapies capable of increasing the curative SVR rates in patients with CHC. The use of the liner protease inhibitors telaprevir and boceprevir, in combination with Peg-IFN-a and ribavirin has become the new SOC for treatment of CHC genotype 1. Rapid development of new protease inhibitors, NI and NNI NS5B polymerase inhibitors, NS5A inhibitors, Peg-IFN-l, cyclophilin inhibitors, caspase inhibitors, and therapeutic vaccines promises to provide even safer and more effective therapy. Combination therapies with 2 or more oral agents may permit elimination of Peg-IFN-a in the near future. Introduction of DAA therapies will confront physicians and patients with regimens of increased complexity, a greater need for compliance, and the necessity of monitoring for virological resistance. Patients with CHC should continue to consider participation in clinical trials of new therapies to accelerate progress.

Liver transplantation in autoimmune liver diseases.

Liver transplantation is indicated for terminal phases of autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. Indications for transplantation in autoimmune liver diseases are similar to those used in other acute or chronic liver diseases. Therapeutic advances have reduced the need for transplantation for autoimmune hepatitis and primary biliary cirrhosis but not for primary sclerosing cholangitis. Overall, outcomes of transplantation for autoimmune liver diseases are excellent. However, recurrence of autoimmune liver diseases in the allograft has variable impacts on graft and patient survivals. Treatment of recurrent diseases requires changes in immunosuppression or addition of ursodeoxycholic acid. Among autoimmune liver diseases, only autoimmune hepatitis occurs de novo in recipients transplanted for other diseases. Patients transplanted for autoimmune hepatitis or primary sclerosing cholangitis are at risk for reactivation or de novo onset of ulcerative colitis. Better understanding of the pathogenesis of recurrent autoimmune liver diseases is needed to devise effective means of prevention and treatment.

An overview of emerging therapies for the treatment of chronic hepatitis C.

Chronic hepatitis C (CHC) is a leading cause of chronic hepatitis, cirrhosis, liver failure, and hepatocellular carcinoma (HCC) worldwide. Currently, pegylated interferon (Peg-IFN) and ribavirin therapy achieve curative responses in 40% to 80% of patients, depending on genotype. Recognition of new therapeutic targets for HCV therapy has led to development of novel therapies. The purpose of this review is to summarize the status of novel therapeutics for CHC that promise to increase the safety and efficacy of therapy.