Treatment and survival of non-alcoholic steatohepatitis associated hepatocellular carcinoma

Weinmann, Arndt; Alt, Y; Koch, Sandra; Nelles, Carina; Düber, Christoph; Lang, Hauke; Otto, Gerd; Zimmermann, Tim; Marquardt, Jens U.; Galle, Peter R.; Wörns, Marcus A.; Schattenberg, Jörn M.

doi:10.1186/s12885-015-1197-x

Cited by 94 publications

(92 citation statements)

References 32 publications

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“…NASH is the most rapidly increasing indication of liver transplantation for HCC in the USA [7]. It is still undetermined whether therapeutic outcome is comparable to other liver disease etiologies [8,9]. …”

Section: Changing Landscape Of Hcc Demographicsmentioning

confidence: 99%

Molecular classification of hepatocellular carcinoma: potential therapeutic implications

2015

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Genomic profiling of hepatocellular carcinoma (HCC) tumors has elucidated recurrent molecular aberrations common or specific to disease etiology, patient race or geographic regions, allowing the classification of HCC tumors into subclasses sharing similar molecular and clinical characteristics. Previously reported transcriptome-based molecular subclasses have highlighted several common themes. Aggressive tumors are characterized by TP53 inactivation mutations and activation of pro-oncogenic signaling pathways, and further subclassified according to expression of stemness markers. The stemness marker-negative aggressive tumors display preferential TGF-β activation. Another group of less aggressive tumors contains a subclass characterized by CTNNB1 mutations accompanied with overexpression of liver-specific WNT targets such as GLUL. Molecular therapies selectively targeting features of the HCC subclasses have suggested their utility in enriching potential responders in clinical trials and guiding therapeutic decision-making for HCC patients.

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Section: Changing Landscape Of Hcc Demographicsmentioning

confidence: 99%

Molecular classification of hepatocellular carcinoma: potential therapeutic implications

2015

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“…non-alcoholic steatohepatitis (NASH) and for the evaluation of hepatic fibrosis [77]. Moreover, it has been reported that NAFLD/NASH may progress to hepatocellular carcinoma (HCC) also in the absence of apparent cirrhosis [77,78].…”

Section: Non-alcoholic Fatty Liver Diseasementioning

confidence: 99%

The potential of silymarin for the treatment of hepatic disorders

et al. 2016

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Silymarin has long been used as a hepatoprotective remedy. Chronic toxicity studies in rodents have confirmed that silymarin has a very low toxicity. These data support its history as a safe medication in hepatic diseases. In the last years, several studies expanded our understanding of the pharmacology of silymarin and its molecular mechanisms of action. These new insights may affect the handling of silymarin in clinical studies and daily practice. Additionally, scientific knowledge in hepatology is constantly evolving with, particularly, an increase in the field of non-alcoholic fatty liver disease which is considered today as the most frequent liver disease worldwide. In this review, we will describe scientific evidence for the effectiveness of silymarin in hepatic disorders. We will focus on silymarin's pharmacological effects in non-alcoholic fatty liver disease and on its well described effects in alcoholic liver disease and acute intoxications, e.g. with Amanita species. We will discuss the relevance of pharmacological data as a function of doses or concentrations required for a given effect and of concentrations achieved in the target tissues. Many pharmacological effects of silymarin can be attributed to effects downstream or upstream of its antioxidative and membrane-stabilizing properties. However, despite promising new experimental and clinical data further clinical studies are required including long-term observations and the application of hard clinical endpoints such as survival rates, to further support silymarin's use for the treatment of hepatic diseases.

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“…These data support the idea that biological mechanisms and risk factors contributing to hepatocarcinogenesis in these two steatohepatitis variants are similar. In particular we found that age, Hispanic ethnicity, T2DM, and not being diagnosed with hyperlipidemia were associated with presence of HCC . While the precise age may vary, increased screening for HCC in patients with NASH and ALD starting at 60 years of age may be warranted.…”

Section: Discussionmentioning

confidence: 99%

Metabolic factors affecting hepatocellular carcinoma in steatohepatitis

Zarrinpar

Faltermeier

Agopian

et al. 2018

Liver International

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Background & Aims: With the rising prevalence of alcoholism, obesity and metabolic syndrome, steatohepatitis will become the leading cause of end-stage liver disease and hepatocellular carcinoma in the United States by 2025. Patients with non-alcoholic steatohepatitis and alcoholic liver disease have similar clinical and histopathological presentations, whether these similarities persist in non-alcoholic steatohepatitis and alcoholic liver disease patients with hepatocellular carcinoma remains unknown. Methods: A retrospective analysis of the clinical features of adult patients from a large transplant center who underwent liver transplantation for steatohepatitis due to non-alcoholic steatohepatitis and alcoholic causes (alcoholic liver disease) between 1/1/02 and 1/1/12 was performed. Clinical features, explant histopathology, and clinical outcomes were compared. Results: Hepatocellular carcinoma was present in 80 of 317 patients, who underwent liver transplantation for steatohepatitis with equivalent distribution in non-alcoholic steatohepatitis and alcoholic liver disease patients (24% vs 26%; P = 0.8). On multivariate analysis, significant predictors of hepatocellular carcinoma included age, ethnicity (Hispanic), and diabetes, but not BMI, hypertension or smoking. A lower risk of hepatocellular carcinoma was associated with a clinical history of hyperlipidemia. Clinical parameters were similar between patients with alcoholic liver disease-hepatocellular carcinoma and non-alcoholic steatohepatitis-hepatocellular carcinoma, except sex and presence of metabolic syndrome. non-alcoholic steatohepatitis-hepatocellular carcinoma livers retained histopathological features of non-alcoholic steatohepatitis such as ballooning and Mallory bodies, while alcoholic liver disease-hepatocellular carcinoma livers did not. There were no significant differences in hepatocellular carcinoma recurrence rates or post-transplant overall survival. Conclusions: We report the largest single-center study evaluating clinical, histopathological and outcome measures of patients undergoing liver transplantation for steatohepatitis. Older patients, diabetics, and Hispanics may warrant more frequent cancer screening due to increased risk of hepatocellular carcinoma.

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Treatment and survival of non-alcoholic steatohepatitis associated hepatocellular carcinoma

Cited by 94 publications

References 32 publications

Molecular classification of hepatocellular carcinoma: potential therapeutic implications

Molecular classification of hepatocellular carcinoma: potential therapeutic implications

The potential of silymarin for the treatment of hepatic disorders

Metabolic factors affecting hepatocellular carcinoma in steatohepatitis

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