Prospective study of hepatocellular carcinoma in nonalcoholic steatohepatitis in comparison with hepatocellular carcinoma caused by chronic hepatitis C.
ABSTRACT This study was performed to clarify the outcomes and recurrence of hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) in comparison with the data for HCC caused by hepatitis C virus (HCV) infection.
Data for 34 NASH patients with HCC (NASH-HCC) were analyzed prospectively, and data for 56 age- and sex-matched patients with HCC due to HCV chronic liver disease (HCV-HCC) were collected retrospectively. After the initial treatment for HCC, patients were followed regularly at least every 4 months by performing clinical examinations, serum liver function tests, monitoring alpha-fetoprotein and des-gamma-carboxy prothrombin, and utilizing various imaging modalities.
The five-year survival rate was 55.2% and the cumulative recurrence of HCC at 5 years was 69.8% in treated cases of NASH-HCC. The NASH-HCC and HCV-HCC groups showed similar survival and recurrence rates. Of the 16 NASH-HCC patients curatively treated, recurrence was detected more than 2 years after the initial treatment in 9. Three patients showed intrahepatic recurrences away from the initial HCC, and 3 patients showed a change in tumor marker production after treatment of the initial HCC. The size of the HCC and the stage of fibrosis were significant risk factors for HCC recurrence in NASH-HCC.
HCC recurrence was very high in NASH, and the HCC may be of multicentric origin, similar to HCC based on viral hepatitis. Regular screening for HCC is extremely important for NASH patients with HCC, even after curative treatment. This study confirmed that NASH-HCC has a similar course to that of HCV-HCC.
- [Show abstract] [Hide abstract]
ABSTRACT: The high prevalence of nonalcoholic fatty liver disease (NAFLD) has made the condition an important public health issue. Two clinical entities are manifestations of NAFLD, namely nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The former tends to be benign and non-progressive while the latter can progress to cirrhosis, which in rare cases gives rise to hepatocellular carcinoma. The diagnosis of NAFLD is based on 1) a history of no or limited daily alcohol intake (<20 g for women and <30 g for men), 2) presence of hepatic steatosis by imaging or by histology, and 3) exclusion of other liver diseases. NAFL is defined histologically by the presence of bland, primarily macrovesicular hepatocellular fatty change, while NASH features fatty change with inflammation and evidence of hepatocyte injury, such as ballooning degeneration. Presence of fibrosis is a sign of chronicity. Thus, the diagnosis of NAFL/NASH rests on clincopathological criteria; it always requires both clinical and biopsy-based information. NAFLD could be both the result and the cause of metabolic syndrome, with a vicious cycle operating between these conditions. Remaining challenges are 1) the lack of a clear threshold alcohol intake for defining "nonalcoholic", 2) a lacking consensus for the classification of fatty liver disease, and 3) absence of a histological definition of NASH, which currently remains the gold standard for the diagnosis. Further challenges include the overlap of the criteria for NAFLD and alcoholic liver disease as many obese individuals also consume considerable volumes of alcohol.Hepatology Research 03/2014; · 2.07 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The clinical aspects of cryptogenic hepatocellular carcinoma (HCC), defined as HCC in patients without hepatitis B, C or alcoholism, are not clear. We investigated its clinical presentations, long-term survival and prognostic predictors. A total of 2645 HCC patients were studied. One-to-one matched pairs between viral/alcoholic and cryptogenic HCC patients were generated by using the propensity model. The survival analysis was performed with the Kaplan-Meier method and log-rank test, and hazard ratios were calculated with Cox proportional hazards model. Among 366 (14%) patients with cryptogenic HCC, 34% of patients were presented with abdominal discomfort, and 31% of patients were identified incidentally. Compared to patients with viral/alcoholic HCC, cryptogenic HCC patients were significantly older (p<0.0001), with poorer performance status (p = 0.0031) and less often underwent curative treatment (p = 0.0041). They also had larger tumor burden (p<0.0001), poorer renal function (p<0.0001), lower α-fetoprotein level (p<0.0001), and more advanced Barcelona Clinic Liver Cancer stages (p<0.0001). With propensity score model, 366 pairs of similar HCC patients were selected and similar long-term survival between the two groups of patients was found (p = 0.1038). For cryptogenic HCC patients, α-fetoprotein ≧49 ng/mL (hazard ratio [HR]: 1.955, p = 0.0002), Child-Turcotte-Pugh class B/C (HR: 2.798, p<0.0001), performance status ≧1 (HR: 2.463, p<0.0001) and vascular invasion (HR: 1.608, p = 0.0257) were independent predictors of poor prognosis. Patients with cryptogenic HCC are usually diagnosed with poor general condition at late stages. However, cryptogenic HCC patients have similar prognostic predictors and long-term survival compared with viral/alcoholic HCC patients. Diagnosis at an early stage may improve their clinical outcomes.PLoS ONE 01/2014; 9(2):e89373. · 3.73 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: To evaluate the histopathological findings of type C liver disease to determine risk factors for development of hepatocellular carcinoma (HCC). We studied 232 patients, who underwent liver biopsy for type C chronic liver disease between 1992 and 2009, with sustained virological response (SVR) after interferon therapy. The patients were divided into two groups according to the F stage 0 + 1 + 2 group (n = 182) and F3 + 4 group (n = 50). We prospectively observed and compared the incidence of HCC of the patients with SVR in the F0 + 1 + 2 and F3 + 4 groups. Then, the background factors and liver histopathological findings, including the degree of fibrosis, F stage, inflammation, necrosis, bile duct obstruction, fat deposition, and degree of irregular regeneration (IR) of hepatocytes, were correlated with the risk of developing HCC. HCC developed in three of 182 (1.6%) patients in the F0 + 1 + 2 group, and four of 50 (8.0%) in the F3 + 4 group. The cumulative incidence of HCC in the former group was found to be significantly lower than in the F3 + 4 group (log rank test P = 0.0224). The presence of atypical hepatocytes among IR of hepatocytes in the F3 + 4 group resulted in a higher cumulative incidence of HCC, and was significantly correlated with risk of HCC development (RR = 20.748, 95%CI: 1.335-322.5, P = 0.0303). Atypical hepatocytes among the histopathological findings of type C liver disease may be an important risk factor for HCC development along with progression of liver fibrosis.World Journal of Gastroenterology 08/2013; 19(30):4887-96. · 2.55 Impact Factor