Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis: A longitudinal study of 1893 biopsy-proven nonalcoholic fatty liver disease subjects.

Javier Ampuero ,Desam Escudero ,Luis Ibáñez ,R Aller ,Germán Soriano ,José Miguel Rosales ,J García‐Samaniego ,Raquel García Latorre ,Rosa Morillas ,Javier Crespo ,Salvador Augustín ,Javier Salmerón ,Pamela Estévez ,María Jesús Pareja‐Megia ,Francisco Jorquera ,Joan Caballería ,Juan Turnés ,Rubén Francés ,Oreste Lo Iacono ,Manuel Romero‐Gómez ,Judith Gómez‐Camarero ,Javier Abad ,Salvador Benlloch ,Águeda González‐Rodríguez ,Rosa María Martín-Mateos ,Rocío Gallego‐Durán ,Patricia Aspichueta ,Raúl J Andrade ,M Diago ,Conrado Fernández‐Rodríguez ,Jesús M Bañales ,Manuel Hernández‐Guerra ,Hepamet Registry

doi:10.1111/liv.14898

Abstract

Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD). Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7±3.8years). Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P=.0001). More than 70% of non-NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P<.0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P=.015). Death and decompensated cirrhosis were similar between these. The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.

Highlights

Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of histological features that range from simple steatosis to nonalcoholic steatohepatitis (NASH) and, cirrhosis.[1]
In a Spanish large cohort of individuals with biopsy-proven nonalcoholic fatty liver disease (NAFLD) followed-up during 4.7 years, we aimed to assess the prevalence of NASH and its components across the fibrosis stages and link them with prognostic outcomes to determine if NAS score ≥4 reflects a reliable scenario in clinical practice as inclusion criterium in NAFLD clinical trials
We analyzed the distribution of severe steatosis (Grade 3), ballooning and lobular inflammation according to the fibrosis stage (Figure 1A)

Summary

| INTRODUCTION

Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of histological features that range from simple steatosis to nonalcoholic steatohepatitis (NASH) and, cirrhosis.[1] Splitting NAFLD into three successive stages (steatosis, non-cirrhotic NASH and cirrhotic NASH) has provided a convenient conceptual framework for improving the diagnostic methods and identifying areas of potential future drug development.[2] the diagnosis of NAFLD is challenging sometimes, so we need to consider a more pragmatic approach to targeting these individuals In this scenario, the term “metabolic- associated fatty liver disease” (MAFLD) has been recently proposed.[3] The diagnosis of MAFLD is based on recognizing underlying alterations in metabolism,[4] beyond the histological classification of NAFLD. In a Spanish large cohort of individuals with biopsy-proven NAFLD followed-up during 4.7 years, we aimed to assess the prevalence of NASH and its components (steatosis, ballooning and lobular inflammation) across the fibrosis stages and link them with prognostic outcomes to determine if NAS score ≥4 reflects a reliable scenario in clinical practice as inclusion criterium in NAFLD clinical trials

| METHODS

| Objectives

Findings

| DISCUSSION