Ryan B. Perumpail

Hepatocellular Carcinoma in the Setting of Non-cirrhotic Nonalcoholic Fatty Liver Disease and the Metabolic Syndrome: US Experience

BackgroundType 2 diabetes mellitus, obesity, and the metabolic syndrome (MS) have been growing in prevalence in the USA and are independent risk factors for the development of hepatocellular carcinoma (HCC). Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the MS, with or without nonalcoholic steatohepatitis (NASH) can predispose to HCC in the absence of cirrhosis or advanced fibrosis. Nevertheless, the US literature investigating non-cirrhotic HCC in the setting of NAFLD/NASH and MS is lacking.AimTo describe a retrospective case series of patients who developed HCC without cirrhosis in the setting of NAFLD/NASH or features of the MS.MethodsWe identified NAFLD/NASH-associated HCC cases arising in the absence of cirrhosis between January 2010 and September 2012 from a tumor board database at Brooke Army Medical Center (BAMC).ResultsOf 44 cases of HCC reviewed, six cases of non-cirrhotic HCC associated with NAFLD/NASH and/or MS were identified. Only one patient underwent partial hepatectomy with curative intent. The other five might have been candidates for potential curative partial hepatectomy or liver transplantation had they been diagnosed earlier.ConclusionOur case series highlights the development of NAFLD/NASH and MS-associated HCC in the absence of cirrhosis in the US population and raises the important question of HCC screening for this at-risk group.

Sofosbuvir and simeprevir combination therapy in the setting of liver transplantation and hemodialysis

We report safety, tolerability, and 12‐week sustained virologic response with half‐standard dose sofosbuvir and standard‐dose simeprevir combination therapy in a hepatitis C virus genotype 1a‐infected liver transplant recipient on hemodialysis – uncharted territory for sofosbuvir‐based therapy. The patient was a non‐responder to prior treatment with pegylated interferon plus ribavirin. Sofosbuvir efficacy was maintained despite pill‐splitting and administration of half‐standard dose, 200 mg per day. No drug–drug interactions were noted with tacrolimus‐based immunosuppression. Laboratory tests remained stable or improved during therapy. Our observation, if reproduced in a larger study, may lead to significant improvement in clinical outcomes and cost savings in this patient population.

Advances in hepatocellular carcinoma: Nonalcoholic steatohepatitis-related hepatocellular carcinoma.

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.

Update on hepatitis C: Direct-acting antivirals

Hepatitis C virus (HCV) was discovered 26 years ago. For decades, interferon-based therapy has been the mainstay of treatment for HCV. Recently, several direct-acting antivirals (DAAs) have been approved for treatment of HCV-infected patients and to help combat the virus. These drugs have revolutionized the management of HCV as all-oral regimens with favorable side effect profiles and superior rates of sustained virological response. Emerging real-world data are demonstrating results comparable to registration trials for DAA agents. Suddenly, the potential for eradicating HCV is on the horizon.

Treatment of patients waitlisted for liver transplant with all‐oral direct‐acting antivirals is a cost‐effective treatment strategy in the United States

All‐oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with hepatitis C virus (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre‐LT versus post‐LT. The objective of this study was to analyze the cost‐effectiveness of pre‐LT versus post‐LT treatment with an all‐oral DAA regimen among HCV patients with hepatocellular carcinoma (HCC) or decompensated cirrhosis (DCC). We constructed decision‐analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age of 50 over a 30‐year time horizon from a third‐party US payer perspective and estimated their health and cost outcomes based on pre‐LT versus post‐LT treatment with an all‐oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained virological response rates were sourced from ASTRAL‐4, SOLAR‐1, and SOLAR‐2. Costs were sourced from RedBook, Medicare fee schedules, and published literature. In the HCC analysis, the pre‐LT treatment strategy resulted in 11.48 per‐patient quality‐adjusted life years and

Pathogenesis of hepatocarcinogenesis in non-cirrhotic nonalcoholic fatty liver disease: Potential mechanistic pathways.

365,948 per patient lifetime costs versus 10.39 and

Future Therapy for Hepatitis B Virus: Role of Immunomodulators

283,696, respectively, in the post‐LT arm. In the DCC analysis, the pre‐LT treatment strategy resulted in 9.27 per‐patient quality‐adjusted life years and

Treatment strategies for chronic hepatitis C prior to and following liver transplantation.

304,800 per patient lifetime costs versus 8.7 and

Nonalcoholic Fatty Liver Disease: Epidemiology, Natural History, and Diagnostic Challenges.

283,789, respectively, in the post‐LT arm. As such, the pre‐LT treatment strategy was found to be the most cost‐effective in both populations with an incremental cost‐effectiveness ratio of

Advances in cirrhosis: Optimizing the management of hepatic encephalopathy.

74,255 (HCC) and