Dataset Information

Effect of common genetic variants on the risk of cirrhosis in non-alcoholic fatty liver disease during 20 years of follow-up.

ABSTRACT:

Background and aims

Several genotypes associate with a worse histopathological profile in patients with non-alcoholic fatty liver disease (NAFLD). Whether genotypes impact long-term outcomes is unclear. We investigated the importance of PNPLA3, TM6SF2, MBOAT7 and GCKR genotype for the development of severe outcomes in NAFLD.

Method

DNA samples were collected from 546 patients with NAFLD. Advanced fibrosis was diagnosed by liver biopsy or elastography. Non-alcoholic steatohepatitis (NASH) was histologically defined. Additionally, 5396 controls matched for age, sex and municipality were identified from population-based registers. Events of severe liver disease and all-cause mortality were collected from national registries. Hazard ratios (HRs) adjusted for age, sex, body mass index and type 2 diabetes were estimated with Cox regression.

Results

In NAFLD, the G/G genotype of PNPLA3 was associated with a higher prevalence of NASH at baseline (odds ratio [OR] 3.67, 95% CI = 1.66-8.08), but not with advanced fibrosis (OR 1.81, 95% CI = 0.79-4.14). After up to 40 years of follow-up, the PNPLA3 G/G genotype was associated with a higher rate of severe liver disease (adjusted hazard ratio [aHR] 2.27, 95% CI = 1.15-4.47) compared with the C/C variant. NAFLD patients developed cirrhosis at a higher rate than controls (aHR 9.00, 95% CI = 6.85-11.83). The PNPLA3 G/G genotype accentuated this rate (aHR 23.32, 95% = CI 9.14-59.47). Overall mortality was not affected by any genetic variant.

Conclusion

The PNPLA3 G/G genotype is associated with an increased rate of cirrhosis in NAFLD. Our results suggest that assessment of the PNPLA3 genotype is of clinical relevance in patients with NAFLD to individualize monitoring and therapeutic strategies.

SUBMITTER: Holmer M

PROVIDER: S-EPMC9828463 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of common genetic variants on the risk of cirrhosis in non-alcoholic fatty liver disease during 20 years of follow-up.

Holmer Magnus M Ekstedt Mattias M Nasr Patrik P Zenlander Robin R Wester Axel A Tavaglione Federica F Romeo Stefano S Kechagias Stergios S Stål Per P Hagström Hannes H

Liver international : official journal of the International Association for the Study of the Liver 20221011 12

<h4>Background and aims</h4>Several genotypes associate with a worse histopathological profile in patients with non-alcoholic fatty liver disease (NAFLD). Whether genotypes impact long-term outcomes is unclear. We investigated the importance of PNPLA3, TM6SF2, MBOAT7 and GCKR genotype for the development of severe outcomes in NAFLD.<h4>Method</h4>DNA samples were collected from 546 patients with NAFLD. Advanced fibrosis was diagnosed by liver biopsy or elastography. Non-alcoholic steatohepatitis ...[more]

PMID: 36166317

Similar Datasets

Project description:ObjectiveAnterior temporal lobectomy (ATL) for medication-resistant localized epilepsy results in ablation or reduction of seizures for most patients. However, some individuals who attain an initial extended period of postsurgical seizure freedom will experience a later seizure recurrence. In this study, we examined the prevalence and some risk factors for late recurrence in an ATL cohort with extensive regular follow-up.MethodsIncluded were 449 patients who underwent ATL at Austin Health, Australia, from 1978 to 2008. Postsurgical follow-up was undertaken 2-3 yearly. Seizure recurrence was tested using Kaplan-Meier analysis, log-rank test, and Cox regression. Late recurrence was qualified as a first disabling seizure >2 years postsurgery. We examined risks within the ATL cohort according to broad pathology groups and tested whether late recurrence differed for the ATL cohort compared to patients who had resections outside the temporal lobe (n = 98).ResultsMedian post-ATL follow-up was 22 years (range = .1-38.6), 6% were lost to follow-up, and 12% had died. Probabilities for remaining completely seizure-free after surgery were 51% (95% confidence interval [CI] = 53-63) at 2 postoperative years, 36% (95% CI = 32-41) at 10 years, 32% (95% CI = 27-36) at 20 years, and 30% (95% CI = 25-34) at 25 years. Recurrences were reported up to 23 years postoperatively. Late seizures occurred in all major ATL pathology groups, with increased risk in the "normal" and "distant lesion" groups (p ≤ .03). Comparison between the ATL cohort and patients who underwent extratemporal resection demonstrated similar patterns of late recurrence (p = .74).SignificanceSome first recurrences were very late, reported decades after ATL. Late recurrences were not unique to any broad ATL pathology group and did not differ according to whether resections were ATL or extratemporal. Reports of these events by patients with residual pathology suggest that potentially epileptogenic abnormalities outside the area of resection may be implicated as one of several possible underlying mechanisms.

Project description:BACKGROUND:Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant genetic disorder with a wide variety of clinical manifestations due to the presence of multiple arteriovenous malformations in various tissues and organs. OBJECTIVE:To study the need for hospital admittance in a group of HHT patients and matched controls during a 20 years follow-up period commencing in 1995. METHODS:All HHT patients in the County of Funen, Denmark, were included. For each patient, three age and sex matched controls were identified at the time of enrolment. Data on all hospitalisations were extracted from the national health registers and compared with clinical records. The hospitalisations were grouped as HHT relevant or not HHT relevant based on the discharge diagnosis (International Classification of Diseases, ICD10) and with particular focus on infections, bleedings and thromboembolic events. Patients with HHT were compared with controls concerning the first time incidence of each discharge diagnosis. RESULTS:We included 73 HHT patients and 219 controls of which one control was lost to follow-up. HHT-patients had significantly more hospitalisations per person caused by infections in joints and bones, but not caused by infections in general. Bleeding episodes were, as expected, more frequent among the HHT-patients. The study revealed a similar incidence of abscesses and thromboembolisms, including in the central nervous system, among the HHT patients and controls. CONCLUSIONS:Based on this study Danish HHT patients had an increased comorbidity of infections in joints and bones and of bleeding episodes. However, the incidence of thromboembolisms, cerebral abscesses and other conditions commonly considered related to HHT was comparable between the patients and the controls. The patients included in this study were closely monitored at a highly specialised HHT Centre where they received relevant diagnostic evaluation, treatment and counselling. Since this is assumed to benefit the overall health of the patients, it may explain why these patients were less prone to comorbidity than other studies have suggested.

Dataset Information

Effect of common genetic variants on the risk of cirrhosis in non-alcoholic fatty liver disease during 20 years of follow-up.

Background and aims

Method

Results

Conclusion

Publications

Effect of common genetic variants on the risk of cirrhosis in non-alcoholic fatty liver disease during 20 years of follow-up.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets