Editorial: Unveiling new horizons for liver steatosis genetic variants beyond hepatocellular carcinoma diagnosis - exploring the potential of HSD17B13 inhibition

Article Gastroenterology & Hepatology

A phase I/II study of ARO-HSD, an RNA interference therapeutic, for the treatment of non-alcoholic steatohepatitis

Lung-Yi Mak et al.

Summary: In this study, the effects of ARO-HSD were evaluated in both normal healthy volunteers and patients with NASH. The results showed that ARO-HSD treatment was well tolerated and effectively reduced hepatic HSD17#13 mRNA and protein expression, leading to reductions in alanine aminotransferase levels.

JOURNAL OF HEPATOLOGY (2023)

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Article Multidisciplinary Sciences

Inhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis

Panu K. Luukkonen et al.

Summary: The HSD17B13 rs72613567-A variant is associated with a reduced risk of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). The protective effect is related to decreased pyrimidine catabolism mediated by dihydropyrimidine dehydrogenase. Inhibition of pyrimidine catabolism could mimic the protective effect of HSD17B13, suggesting it as a potential therapeutic target against liver fibrosis in NAFLD.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2023)

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Review Gastroenterology & Hepatology

Review article: the role of HSD17B13 on global epidemiology, natural history, pathogenesis and treatment of NAFLD

Maral Amangurbanova et al.

Summary: The loss-of-function polymorphisms of HSD17B13 gene are associated with a reduced risk of NAFLD progression. Further understanding the mechanisms and utilizing this knowledge in the treatment of NAFLD is of great importance.

ALIMENTARY PHARMACOLOGY & THERAPEUTICS (2023)

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Article Gastroenterology & Hepatology

The rs72613567:TA polymorphism in HSD17B13 is associated with survival benefit after development of hepatocellular carcinoma

Hamish Innes et al.

Summary: This study investigated the association between genetic polymorphisms and prognosis of hepatocellular carcinoma (HCC), and found that the rs72613567:TA polymorphism in HSD17B13 was significantly associated with all-cause mortality risk in HCC patients. Other associated factors included Baveno stage 3-4 and HCC treatment with curative intent. The findings suggest that therapeutic inhibition of HSD17B13 may improve the survival of individuals with HCC.

ALIMENTARY PHARMACOLOGY & THERAPEUTICS (2023)

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Review Pharmacology & Pharmacy

PNPLA3 as a therapeutic target for fatty liver disease: the evidence to date

Alessandro Cherubini et al.

Summary: The interaction between metabolic triggers and inherited predisposition plays a crucial role in the development and progression of non-alcoholic fatty liver disease. Among specific NAFLD risk variants, the PNPLA3 rs738409 C>G variant is of significant interest due to its association with lipid accumulation, lipotoxicity, fibrosis, and carcinogenesis. Targeting PNPLA3 p.I148M could be a promising therapeutic approach for NAFLD progression.

EXPERT OPINION ON THERAPEUTIC TARGETS (2021)

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Review Gastroenterology & Hepatology