Dataset Information

NASH and Hepatocellular Carcinoma: Immunology and Immunotherapy.

ABSTRACT: The last 10 years have revolutionized our basic understanding of nonalcoholic fatty liver disease and consequent liver cancer. It has become clear that several innate and adaptive immune cells play an important role in initiating, maintaining, or exacerbating nonalcoholic steatohepatitis (NASH)-a disease that has been recently defined as autoaggressive. Despite improved disease management aimed at reducing the progression of fibrosis, NASH is set to become a leading cause for hepatocellular carcinoma (HCC). Preliminary data from preclinical studies suggest that immunotherapy efficacy may be reduced in NASH-related HCC compared with viral HCC; however, conclusive evidence supporting clinical translation of these findings is lacking. Comprehensive clinical and immunologic phenotyping of mechanisms linking NASH progression with carcinogenesis and therapeutic resistance is key to prevent progression to cirrhosis, improve monitoring and stratification of NASH according to predicted cancer risk, and ultimately increase survival of patients with NASH-HCC. In this review, we summarize the state of the art in the field of NASH and NASH-HCC with focus on immunobiology. We discuss preclinical and clinical findings underpinning NASH as an immunologically distinct pro-tumorigenic disease entity, and explore areas of potential therapeutic vulnerabilities in NASH-associated HCC.

SUBMITTER: Pinter M

PROVIDER: S-EPMC9890137 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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NASH and Hepatocellular Carcinoma: Immunology and Immunotherapy.

Pinter Matthias M Pinato David J DJ Ramadori Pierluigi P Heikenwalder Mathias M

Clinical cancer research : an official journal of the American Association for Cancer Research 20230201 3

The last 10 years have revolutionized our basic understanding of nonalcoholic fatty liver disease and consequent liver cancer. It has become clear that several innate and adaptive immune cells play an important role in initiating, maintaining, or exacerbating nonalcoholic steatohepatitis (NASH)-a disease that has been recently defined as autoaggressive. Despite improved disease management aimed at reducing the progression of fibrosis, NASH is set to become a leading cause for hepatocellular carc ...[more]

PMID: 36166660

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Project description:Hepatocellular carcinoma (HCC) is the most frequently found primary malignancy of the liver, showing an accelerated upward trend over the past few years and exhibiting an increasing relationship with metabolic syndrome, obesity, dyslipidemia and type 2 diabetes mellitus. The connection between these risk factors and the occurrence of HCC is represented by the occurrence of non-alcoholic fatty liver disease (NAFLD) which later, based on genetic predisposition and various triggers (including the presence of chronic inflammation and changes in the intestinal microbiome), may evolve into HCC. HCC in many cases is diagnosed at an advanced stage and can be an incidental finding. We present such a scenario in the case of a 41-year-old male patient who had mild obesity and mixed dyslipidemia, no family or personal records of digestive pathologies and who recently developed a history of progressive fatigue, dyspepsia and mild upper abdominal discomfort initially thought to be linked to post-COVID syndrome, as the patient had COVID-19 pneumonia a month prior. The abdominal ultrasound revealed a mild hepatomegaly with bright liver aspect of the right lobe (diffuse steatosis), a large zone of focal steatosis (segments IV, III and II) and a left lobe tumoral mass, highly suggestive of malignancy. Point shear wave elastography at the right lobe ruled out an end-stage chronic liver disease. Additional laboratory investigations, imaging studies (magnetic resonance imaging) and histopathological examination of liver fragments confirmed a highly aggressive HCC, with poorly differentiation-G3, (T4, N 1M 0) and stage IVA, associated with nonalcoholic steatohepatitis (NASH). A sorafenib course of treatment was attempted, but the patient discontinued it due to severe side effects. The subsequent evolution was extremely unfavorable, with rapid degradation, a few episodes of upper digestive bleeding, hepatic insufficiency and mortality in a couple of months. Conclusions: Diagnosis of NASH-related HCC is either an accidental finding or is diagnosed at an advanced stage. In order to earn time for a proper treatment, it becomes important to diagnose it at an early stage, for which regular check-ups should be performed in groups having the risk factors related to it. Patients suffering from obesity and mixed dyslipidemia should undergo periodic abdominal ultrasound examinations. This should be emphasized even more in the cases showing NASH. Complaints of any kind post-COVID-19 should be dealt with keenly as little is yet known about its virulence and its long-term side effects.

Dataset Information

NASH and Hepatocellular Carcinoma: Immunology and Immunotherapy.

Publications

NASH and Hepatocellular Carcinoma: Immunology and Immunotherapy.

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