Hepatitis C and NAFLD as Main Causes of Liver-Related Morbidity and Mortality in the French General Population: A Nationwide Study (NASH-CO Study)

Oumarou Nabi (1) , Nathanaël Lapidus (1) , Jerome Boursier (1) , Philippe Mathurin (2) , Victor de Ledinghen (3) , Jean-Michel Petit (4) , Sofiane Kab (5) , Adeline Renuy (5) , Marie Zins (5) , Lawrence Serfaty (6) , Karine Lacombe (1)

1 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
2 CHU Angers - Centre Hospitalier Universitaire d'Angers
3 CHU Bordeaux
4 CHU Dijon
5 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
6 Hôpital de Hautepierre [Strasbourg]

Background: The impact of NAFLD on health status and mortality has yet to be documented at the general population level. This study aimed to assess whether NAFLD was associated with hepatic and extrahepatic diseases and overall mortality, on the one hand, and to estimate its impact on health status and mortality compared to other liver-related diseases such as chronic hepatitis C or alcohol abuse, on the other hand. Methods: The study population consisted of 154,900 participants from the nationwide Constances cohort. Non-invasive diagnosis of NAFLD and advanced fibrosis was performed using the fatty liver index and Forns index, respectively. Constances data were linked to hospitalization data to identify liver-related events, cardiovascular diseases (CVDs), extrahepatic cancers (EHCs), and chronic kidney disease (CKDs). Causal inference methods were used to estimate the impact of NAFLD on morbidity and mortality. Results: The prevalence of NAFLD was 18·3% in subjects without other chronic liver diseases, among whom 2·7% had advanced fibrosis. A history of chronic hepatitis C (HCV) and B (HBV) was observed in 669 (0·4%) and 1311 (0·9%) subjects, respectively, whereas 15,714 (10·1%) individuals were recognized as heavy drinkers. The prevalence of advanced fibrosis was higher in HCV and NAFLD subjects (4·7% vs 2·7% vs 1·7% vs 1·6%, respectively, in HCV, NAFLD, heavy drinkers, and subjects with HBV). HCV remains the leading cause of hepatic-related complications (HR 9·75, 95% CI 6·63–14·33) before NAFLD (HR 2·63, 95% CI 1·96–2·87). NAFLD (HR 1·43, 95% CI 1·25–1·65) is the third leading cause of death behind HCV (HR 2·17, 95% CI 1·25–3·76) and binge drinking (HR 4·50, 95% CI 2·95–6·84). However, NAFLD remains the leading cause of CVD (HR 2·33, 95% CI 1·20–2·78) and CKD (HR 1·89, 95% CI 1·48–2·40). Conclusion: This large general population-based cohort showed that NAFLD was associated with excess morbidity and mortality and demonstrated the fastest-growing trend. It challenges HCV infection in terms of hepatic morbidity and overall mortality.

Keywords: gamma glutamyl-transferase NAFLD advanced fibrosis Fatty Liver Index Forns Index cardiovascular diseases chronic kidney disease extrahepatic malignancies; mortality; gamma glutamyl-transferase NAFLD; advanced fibrosis; Fatty Liver Index; Forns Index; cardiovascular diseases; chronic kidney disease; extrahepatic malignancies

Domains: Life Sciences [q-bio]

Oumarou Nabi, Nathanaël Lapidus, Jerome Boursier, Philippe Mathurin, Victor de Ledinghen, et al.. Hepatitis C and NAFLD as Main Causes of Liver-Related Morbidity and Mortality in the French General Population: A Nationwide Study (NASH-CO Study). SSRN Electronic Journal, 2022, ⟨10.2139/ssrn.4161708⟩. ⟨hal-04566601⟩