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. 2022 Apr;15(2):301-309.
doi: 10.1007/s12328-021-01578-1. Epub 2022 Jan 31.

HSD17B13 and other liver fat-modulating genes predict development of hepatocellular carcinoma among HCV-positive cirrhotics with and without viral clearance after DAA treatment

Michela E Burlone  1 , Mattia Bellan  1   2 , Matteo N Barbaglia  2 , Ginevra Mocchetti  2 , Venkata R Mallela  2 , Rosalba Minisini  2 , Cristina Rigamonti  1   2 , Mario Pirisi  3   4
Affiliations

HSD17B13 and other liver fat-modulating genes predict development of hepatocellular carcinoma among HCV-positive cirrhotics with and without viral clearance after DAA treatment

Michela E Burlone et al. Clin J Gastroenterol. 2022 Apr.

Abstract

Background: Genetic predisposition to accumulate liver fat (expressed by a polygenic risk score, GRS, based on the number of at-risk alleles of PNPLA3, TM6SF2, MBOAT7 and GCKR) may influence the probability of developing hepatocellular carcinoma (HCC) after hepatitis C treatment. Whether this holds true taking into account carriage of the HSD17B13:TA splice variant, also affecting lipogenesis, and achievement of viral clearance (SVR), is unknown.

Methods: PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13 variants were determined in a cohort of 328 cirrhotic patients free of HCC before starting treatment with direct acting antivirals (DAA).

Results: SVR in the study cohort was 96%. At the end of follow-up, N = 21 patients had been diagnosed an HCC; none of the genes included in the GRS was individually associated with HCC development. However, in a Cox proportional hazards model, a GRS > 0.457 predicted HCC independently of sex, diabetes, albumin, INR and FIB4. The fit of the model improved adding treatment outcome and carriage of the HSD17B13:TA splice variant, with sex, GRS > 0.457, HSD17B13:TA splice variant and failure to achieve an SVR (hazard ratio = 6.75, 4.24, 0.24 and 7.7, respectively) being independent predictors of HCC.

Conclusion: Our findings confirm that genes modulating liver fat and lipogenesis are important risk factors for HCC development among cirrhotics C treated with DAA.

Keywords: Gene polymorphisms; Hepatitis C virus; Hepatocarcinogenesis; Prognosis; Therapy.

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