Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

New Diagnostic and Prognostic Models for the Development of Alcoholic Cirrhosis Based on Genetic Predisposition and Alcohol History

Monica Mischitelli
,
Alessandra Spagnoli
,
Aurelio Abbatecola
,
Claudia Codazzo
,
Marta Giacomelli
,
Simona Parisse
ORCID logo ,
Rosellina Margherita Mancina
ORCID logo ,
Claudia Rotondo
,
Fabio Attilia
,
Stefano Ginanni Corradini
* ORCID logo ,
Flaminia Ferri
ORCID logo
Version 1 : Received: 4 July 2023 / Approved: 5 July 2023 / Online: 5 July 2023 (11:54:29 CEST)

A peer-reviewed article of this Preprint also exists.

Mischitelli, M.; Spagnoli, A.; Abbatecola, A.; Codazzo, C.; Giacomelli, M.; Parisse, S.; Mancina, R.M.; Rotondo, C.; Attilia, F.; Ginanni Corradini, S.; Ferri, F. New Diagnostic and Prognostic Models for the Development of Alcoholic Cirrhosis Based on Genetic Predisposition and Alcohol History. Biomedicines 2023, 11, 2132. Mischitelli, M.; Spagnoli, A.; Abbatecola, A.; Codazzo, C.; Giacomelli, M.; Parisse, S.; Mancina, R.M.; Rotondo, C.; Attilia, F.; Ginanni Corradini, S.; Ferri, F. New Diagnostic and Prognostic Models for the Development of Alcoholic Cirrhosis Based on Genetic Predisposition and Alcohol History. Biomedicines 2023, 11, 2132.

Abstract

Liver cirrhosis development is a multifactorial process resulting by a combination of environmental and genetic factors. The aim of the study was to develop accurate non-invasive diagnostic and prognostic models for alcoholic cirrhosis. Consecutive subjects with at-risk alcohol intake were retrospectively enrolled (110 cirrhotic patients and 411 non-cirrhotics). At enrollment, the data about the lifetime drinking history were collected and all patients were tested for PNPLA3 rs738409, TM6SF2 rs58542926 and HSD17B13 rs72613567 variants. In cross-sectional analyses, models for the diagnosis of cirrhosis were developed using multivariate logistic regression. A predictive score for cirrhosis development over 24 years was built by evaluating time-dependent AUC curves. The best diagnostic accuracy was demonstrated by the model which also includes daily alcohol consumption, duration of hazardous alcohol use and genetic variants, with AUCs of 0.951 (95% CI 0.925-0.977) and 0.887 (95% CI 0.925-0.977) for cirrhosis and compensated cirrhosis, respectively. The predictive model for cirrhosis future development (AUC of 0.836 95% CI: 0.769 - 0.904) accounted for age at onset of at-risk alcohol consumption and the number of PNPLA3 and HSD17B13 variant alleles. We have developed accurate genetic and alcohol consumption models for the diagnosis of alcoholic cirrhosis and the prediction of its future risk.

Keywords

alcoholic liver disease,;cirrhosis diagnosis; cirrhosis prediction; genetics; HSD17B13; PNPLA3

Subject

Medicine and Pharmacology, Gastroenterology and Hepatology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.