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Hepatitis E virus (HEV) is an emerging pathogen and an increasingly recognized cause of graft hepatitis, especially in the post-orthotopic liver transplantation immunocompromised population. The exact incidence and prevalence of HEV infection in this population remains unclear but is certainly greater than historical estimates. Identifying acute HEV infection in this population is imperative for choosing the right course of management as it is very difficult to distinguish histologically from acute rejection on liver biopsy. Current suggested approach to manage acute HEV involves modifying immunosuppression, especially discontinuing calcineurin inhibitors which are the preferred immunosuppressive agents post-orthotopic liver transplantation. The addition of ribavirin monotherapy has shown promising success rates in clearing HEV infection and is used commonly in reported cases.

Hepatitis C virus (HCV)-related liver disease is the leading indication for liver transplantation (LT) worldwide. However, HCV is an independent predictor of lower survival following LT, and recurrence of HCV post-LT is virtually universal. The historic standard of care during the interferon era of HCV therapy was expectant management-initiation of antiviral therapy in the setting of documented disease progression following LT. With the advent of new direct acting antiviral (DAA) therapies for HCV, the paradigm of expectant treatment for recurrent HCV infection post-LT is shifting. The safety, tolerability, and efficacy of DAAs, even among the sickest patients with advanced liver disease, enables treatment of HCV in the pre-transplant setting among LT waitlist registrants. Finally, emerging data are supportive of preemptive therapy with DAAs in liver transplant recipients as the preferred approach. Expectant management of HCV following LT can rarely be justified in the modern era of HCV therapy.

Although hepatocellular carcinoma (HCC) primarily arises in the background of liver cirrhosis, the development of HCC in nonalcoholic fatty liver disease (NAFLD) without cirrhosis is increasingly recognized. The pathogenesis of NAFLD associated non-cirrhotic HCC is distinct from that of cirrhotic HCC because the metabolic syndrome (MS) along with obesity and insulin resistance (IR) underlie several unique mechanisms that promote tumorigenesis. IR associated with MS, NAFLD, and type 2 diabetes mellitus lead to the release of multiple pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6, leptin and resistin, as well as decreased amounts of adiponectin. These processes favor the development of hepatic steatosis and inflammation within the liver, which precede HCC development. Nevertheless, further investigation is necessary to elucidate the determinants for development of HCC in patients with NAFLD in the absence of cirrhosis.

An increase in the prevalence of obesity and diabetes mellitus has been associated with the rise in nonalcoholic fatty liver disease (NAFLD). Two-thirds of the obese and diabetic populations are estimated to develop NAFLD. Currently, NAFLD is the most common etiology for chronic liver disease globally. The clinical spectrum of NAFLD ranges from simple steatosis, an accumulation of fat greater than 5% of liver weight, to nonalcoholic steatohepatitis (NASH), a more aggressive form with necroinflammation and fibrosis. Among the patients who develop NASH, up to 20% may advance to cirrhosis and are at risk for complications of end-stage liver disease. One of the major complications observed in patients with NASH-related cirrhosis is hepatocellular carcinoma (HCC), which has emerged as the sixth most common cancer and second leading etiology of cancer-related deaths worldwide. The incidence of HCC in the United States alone has tripled over the last three decades. In addition, emerging data are suggesting that a small proportion of patients with NAFLD may be at higher risk for HCC in the absence of cirrhosis - implicating obesity and diabetes mellitus as potential risk factors for HCC.