Chapters authored
Hepatitis C–Associated Diabetes Mellitus
Diabetes type 2 mellitus (T2DM) is the most common extrahepatic association of hepatitis C virus (HCV) infection. Substantial research has suggested that insulin resistance (IR) has crucial importance in development of type 2 diabetes in HCV-infected patients. Several pathophysiological mechanisms are proposed, such as direct effect of HCV proteins on inhibition of the insulin-signaling pathway inducing central insulin resistance (IR), while overproduction of inflammatory cytokines and increased lipolysis promote peripheral IR. IR in HCV-infected patients is associated with impaired sustained virologic response (SVR) and higher incidence of hepatocellular carcinoma (HCC). Some, but not all, studies have shown improvements in achieving SVR in patients with interferon/ribavirin (RBV) therapy co-treated with metformin or pioglitazone as well as beneficiary effect on the incidence of hepatocellular carcinoma. Recent studies indicate that response to the new direct-acting antiviral (DAA) treatments is unaffected by insulin resistance thus diminishing importance of IR in the new era of DAA. Additionally, viral eradication by DAAs has been shown to ameliorate insulin resistance, attenuating the risk of new-onset diabetes type 2. However, those metabolic improvements are sustainable long after the treatment remains unclear.
Part of the book: Update on Hepatitis C
Pharmacogenomic Testing in the Era of Patient-Tailored HCV Treatment
Hepatitis C affects approximately 180 million people worldwide, with 3–4 million newly infected each year. Hepatitis C virus (HCV) has been classified into seven different genotype categories, wherein HCV genotype 1 (HCV-1) is the most prevalent. To date, there is still no vaccine available against HCV infection. Until recently, combination therapy of pegylated interferon-a (PegIFN) and ribavirin (RBV) has been the standard of care. Nevertheless, for many patients, particularly those infected with HCV genotype 1 (HCV-1), this treatment has resulted with unsatisfactory treatment response rates and high adverse drug reaction (ADR) rates. Many clinical factors, including pharmacogenetics, influence the treatment response rate. This review focuses on the association between pharmacogenetics and HCV antiviral therapy in patients infected with HCV genotype 1 and other genotypes (GT); patients reinfected with HCV after liver transplantation; and patients coinfected with HCV and human immunodeficiency virus. Data considering triple therapy in HCV-infected patients are also reviewed. Additionally, various genetic polymorphisms, with an emphasis to IL-28B, and their association with pharmacogenetic testing in HCV are discussed.
Part of the book: Update on Hepatitis C