Clinical and Genetic Risk Factors of Recurrent Nonalcoholic Fatty Liver Disease After Liver Transplantation

Tran, Quynh; Kovalic, Alexander J.; Bontha, Sai Vineela; Jiang, Yu; Kedia, Satish; Karri, Saradashri; Mupparaju, Vamsee; Podila, Pradeep; Verma, Rajanshu; Maluf, Daniel G.; Mas, Valeria R.; Nair, Satheesh; Eason, James D.; Bridges, Dave; Kleiner, David E.

doi:10.14309/ctg.0000000000000302

Cited by 12 publications

(15 citation statements)

References 36 publications

(10 reference statements)

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“…Both variants confer a partial loss of function of HSD17B13 and are associated with decreased disease severity of NAFLD. Interestingly, a few human HSD17B13 genetic variants located in various non-coding areas, including rs10433879, rs6834314, rs3923441, rs9992651, and rs72613567 were also reported to be associated with reduced severity of NAFLD (Ma et al, 2019;Namjou et al, 2019;Whitfield et al, 2019;Anstee et al, 2020;Satapathy et al, 2021) (Table 1). It is worth mentioning that HSD17B13 rs6834314 (A > G) was a loci initially identified by GWAS in 61,089 individuals.…”

Section: Hsd17b13 In Nafld/nashmentioning

confidence: 99%

HSD17B13: A Potential Therapeutic Target for NAFLD

Zhang

et al. 2022

Front. Mol. Biosci.

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Nonalcoholic fatty liver disease (NAFLD), especially in its inflammatory form (steatohepatitis, NASH), is closely related to the pathogenesis of chronic liver disease. Despite substantial advances in the management of NAFLD/NASH in recent years, there are currently no efficacious therapies for its treatment. The biogenesis and expansion of lipid droplets (LDs) are critical pathophysiological processes in the development of NAFLD/NASH. In the past decade, increasing evidence has demonstrated that lipid droplet-associated proteins may represent potential therapeutic targets for the treatment of NAFLD/NASH given the critical role they play in regulating the biogenesis and metabolism of lipid droplets. Recently, HSD17B13, a newly identified liver-enriched, hepatocyte-specific, lipid droplet-associated protein, has been reported to be strongly associated with the development and progression of NAFLD/NASH in both mice and humans. Notably, human genetic studies have repeatedly reported a robust association of HSD17B13 single nucleotide polymorphisms (SNPs) with the occurrence and severity of NAFLD/NASH and other chronic liver diseases (CLDs). Here we briefly overview the discovery, tissue distribution, and subcellular localization of HSD17B13 and highlight its important role in promoting the pathogenesis of NAFLD/NASH in both experimental animal models and patients. We also discuss the potential of HSD17B13 as a promising target for the development of novel therapeutic agents for NAFLD/NASH.

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Section: Hsd17b13 In Nafld/nashmentioning

confidence: 99%

HSD17B13: A Potential Therapeutic Target for NAFLD

Zhang

et al. 2022

Front. Mol. Biosci.

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“…Satapathy et al studied the effect of HSD17B13 rs6834314 variant on prevalence of recurrent NAFLD in NASH transplant recipients. 89 Intriguingly, the results demonstrated that the presence of donor rs6834314 variant was associated with significantly decreased risk of moderate to severe NAFLD recurrence (OR 0.11, 95% CI 0.01-0.88; p = 0.036) 1 year after liver transplantation. Lastly, rs62305723 is a low-frequency missense variant that encodes substitution of proline to serine at position 260, which generates loss-of-function mutation and is associated with decreased ballooning and inflammation in patients with NAFLD.…”

Section: Studies That Described An Association Between Hsd17b13 Snp A...mentioning

confidence: 82%

“…Carriage of minor G allele of HSD17B14 rs6834314 is associated with reduced inflammation, fibrosis 67 and liver‐related complications 86 in patients with NAFLD. Satapathy et al studied the effect of HSD17B13 rs6834314 variant on prevalence of recurrent NAFLD in NASH transplant recipients 89 . Intriguingly, the results demonstrated that the presence of donor rs6834314 variant was associated with significantly decreased risk of moderate to severe NAFLD recurrence (OR 0.11, 95% CI 0.01–0.88; p = 0.036) 1 year after liver transplantation.…”

Section: The Role Of Hsd17b13 In the Natural History Of Nafldmentioning

confidence: 99%

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

Amangurbanova

Huang

Loomba

2022

Aliment Pharmacol Ther

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Background: Non-alcoholic fatty liver disease (NAFLD) occurs in around a quarter of the global population and is one of the leading causes of chronic liver disease. The phenotypic manifestation and the severity of NAFLD are influenced by an interplay of environmental and genetic factors. Recently, several inactivating variants in the novel 17-Beta hydroxysteroid dehydrogenase 13 (HSD17B13) gene have been found to be associated with a reduced risk of chronic liver diseases, including NAFLD. Aims:To review the existing literature on the epidemiology of HSD17B13 and discuss its role in the natural history, disease pathogenesis and treatment of NAFLD. Methods:We extensively searched relevant literature in PubMed, Google Scholar, clini caltr ials.gov and the reference list of articles included in the review.Results: HSD17B13 is a liver-specific, lipid droplet (LD)-associated protein that has enzymatic pathways involving steroids, pro-inflammatory lipid mediators and retinol.The estimated prevalence of the best characterised HSD17B13 variant (rs72613567) ranges from 5% in Africa to 34% in East Asia. Loss-of-function variants in HSD17B13 are protective against the progression of NAFLD from simple steatosis to nonalcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis and hepatocellular carcinoma. Emerging data from mechanistic and preclinical studies with RNA interference (RNAi) and small molecule agents indicate that inhibiting HSD17B13 activity may prevent NAFLD progression. Conclusions:The loss-of-function polymorphisms of the newly identified HSD17B13 gene mitigate the progression of NAFLD. It is important to understand the exact mechanism by which these variants exert a protective effect and implement the gathered knowledge in the treatment of NAFLD.

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“…[34][35][36][37][38][39][40][41][42][43][44][45] Most studies did not specify the diagnostic criteria for the metabolic comorbidities; however, the ones who specified it used similar criteria. Regarding obesity, non-Asian studies considered a BMI at least 30 kg/m 2 , [6,7,19,20,22,26,27,29,30,[34][35][36] whereas Asian studies used either 25 [8,9] or 27.5 kg/m 2 , [10] according to guidelines for Asian subjects. Definitions of diabetes mellitus (DM) was similar among studies that reported it, [7][8][9][10]20,26,27,29,30,34,35] with occasional glucose levels at least 200 mg/dL, fasting glucose at least 126 mg/dL, or hemoglobin HA1c at least 6.5%, according to accepted guidelines.…”

Section: Data Collection Processmentioning

confidence: 99%

“…The development of post-LT steatohepatitis was described in 23 studies, [6,8,[12][13][14]16,17,19,21,22,24,25,28,29,31,[33][34][35][36]39,[45][46][47][48] with highly variable results. In a pooled analysis, steatohepatitis occurred in 28.82% (19.62, 38.03) of patients who developed post-LT steatosis 7).…”

Section: Prognosis Of Post-lt Steatosismentioning

confidence: 99%

Hepatic steatosis after liver transplantation: a systematic review and meta-analysis

Silva

Nogueira

Machado

2023

Liver Transplantation

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NAFLD can occur after liver transplantation (LT), as recurrence or de novo hepatic steatosis (HS). We aimed to evaluate the literature on prevalence, risk factors, and prognosis of post-LT HS. Systematic review with meta-analysis through a search on: PUBMED, Scopus, and Web-of-Science, from inception until the September 30, 2021. Forty studies were included, representing 6979 patients. The post-LT HS prevalence was 39.76% (95% CI, 34.06–45.46), with a rising kinetics (11.06% increase per decade, p=0.04), and a geographical distribution (15.10% more prevalent in American continent compared with Europe and Asia). Recurrent HS was up to 5-fold more likely than de novo HS [OR: 5.38 (2.69–10.76)]. Metabolic disturbances were stronger risk factors in the post-LT recipient [obesity: OR: 4.62 (3.07–6.96); metabolic syndrome: OR: 3.26 (2.03–5.25)] as compared with pre-LT recipients, with the exception of diabetes mellitus, which doubled the risk at any set [pre-LT diabetes mellitus: OR: 2.06 (1.58–2.68); post-LT diabetes mellitus: OR: 2.12 (1.73–2.59)]. Donor factors were not the relevant risk factors for post-LT HS and the only immunosuppressive drug associated with increased risk was sirolimus [OR: 1.68 (1.07–2.64)]. The prevalence of post-LT steatohepatitis was 28.82% (19.62–38.03) and the strongest risk factor was pre-LT NAFLD. Limited outcomes data suggest that post-LT HS did not increase the risk for liver cirrhosis or mortality in these studies. Two out of 5 patients submitted to LT will develop post-LT HS, being recurrent HS more common than de novo HS. Diabetes mellitus and post-LT metabolic syndrome are the strongest risk factors for HS and baseline NAFLD for steatohepatitis. All transplanted patients should be enrolled in lifestyle interventions to prevent post-LT metabolic syndrome, and sirolimus should be avoided in high-risk patients.

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Clinical and Genetic Risk Factors of Recurrent Nonalcoholic Fatty Liver Disease After Liver Transplantation

Cited by 12 publications

References 36 publications

HSD17B13: A Potential Therapeutic Target for NAFLD

HSD17B13: A Potential Therapeutic Target for NAFLD

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

Hepatic steatosis after liver transplantation: a systematic review and meta-analysis

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