Real-world data reveal a diagnostic gap in non-alcoholic fatty liver disease

Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. It affects an estimated 20% of the general population, based on cohort studies of varying size and heterogeneous selection. However, the prevalence and incidence of recorded NAFLD diagnoses in unselected real-world health-care records is unknown. We harmonised health records from four major European territories and assessed age- and sex-specific point prevalence and incidence of NAFLD over the past decade.MethodsData were extracted from The Health Improvement Network (UK), Health Search Database (Italy), Information System for Research in Primary Care (Spain) and Integrated Primary Care Information (Netherlands). Each database uses a different coding system. Prevalence and incidence estimates were pooled across databases by random-effects meta-analysis after a log-transformation.ResultsData were available for 17,669,973 adults, of which 176,114 had a recorded diagnosis of NAFLD. Pooled prevalence trebled from 0.60% in 2007 (95% confidence interval: 0.41–0.79) to 1.85% (0.91–2.79) in 2014. Incidence doubled from 1.32 (0.83–1.82) to 2.35 (1.29–3.40) per 1000 person-years. The FIB-4 non-invasive estimate of liver fibrosis could be calculated in 40.6% of patients, of whom 29.6–35.7% had indeterminate or high-risk scores.ConclusionsIn the largest primary-care record study of its kind to date, rates of recorded NAFLD are much lower than expected suggesting under-diagnosis and under-recording. Despite this, we have identified rising incidence and prevalence of the diagnosis. Improved recognition of NAFLD may identify people who will benefit from risk factor modification or emerging therapies to prevent progression to cardiometabolic and hepatic complications.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1103-x) contains supplementary material, which is available to authorized users.

Patatin‐Like Phospholipase Domain‐Containing Protein 3 I148M and Liver Fat and Fibrosis Scores Predict Liver Disease Mortality in the U.S. Population

“…In addition, alcohol intake may interact with genetic variants that predispose to liver injury. For instance, PNPLA3 148M homozygosity conferred significant additional mortality risk in patients with severe alcoholic hepatitis . Similar to our previous studies, we did not exclude persons based on reported alcohol use; instead, we adjusted for alcohol intake in multivariate analyses to present a more comprehensive picture of the FLD epidemic …”

“…In another report, 148M homozygosity doubled the risk of hepatic decompensation and liver disease mortality in patients with FLD‐associated portal hypertension . In patients with severe alcoholic hepatitis, 148M homozygosity conferred a 70% higher mortality risk …”

“…(38) In patients with severe alcoholic hepatitis, 148M homozygosity conferred a 70% higher mortality risk. (39) In contrast to I148M, a missense variant resulting in loss of triglyceride hydrolysis function leading to HS, (40) PNPLA3 rs2281135-G>A is an intronic variant in linkage disequilibrium with I148M in blacks, whites, and Mexican Americans. (19) rs2281135 is less well studied, but associations with liver disease were reported.…”

“…For instance, PNPLA3 148M homozygosity conferred significant additional mortality risk in patients with severe alcoholic hepatitis. (39) Similar to our previous studies, we did not exclude persons based on reported alcohol use; instead, we adjusted for alcohol intake in multivariate analyses to present a more comprehensive picture of the FLD epidemic. (7,8) A limitation of using NHANES to study noninvasive liver disease markers is reliance on hepatic fat and fibrosis scores, derived from single rather than serial measurements of serum markers and other clinical characteristics, without a histological diagnosis.…”

Non‐alcoholic fatty liver disease in men

“…For this reason it is often underdiagnosed. 9 If identified at its early stages and appropriate intervention initiated, NAFLD, NASH and fibrosis can be reversible. Independent risk factors for a recorded diagnosis of NAFLD include male sex, diabetes, hypertension and rising BMI category.…”