Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis.

BACKGROUND: Although non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, it is increasingly being identified in non-obese individuals. We aimed to characterise the prevalence, incidence, and long-term outcomes of non-obese or lean NAFLD at a global level. METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Library from inception to May 1, 2019, for relevant original research articles without any language restrictions. The literature search and data extraction were done independently by two investigators. Primary outcomes were the prevalence of non-obese or lean people within the NAFLD group and the prevalence of non-obese or lean NAFLD in the general, non-obese, and lean populations; the incidence of NAFLD among non-obese and lean populations; and long-term outcomes of non-obese people with NAFLD. We also aimed to characterise the demographic, clinical, and histological characteristics of individuals with non-obese NAFLD. FINDINGS: We identified 93 studies (n=10 576 383) from 24 countries or areas: 84 studies (n=10 530 308) were used for the prevalence analysis, five (n=9121) were used for the incidence analysis, and eight (n=36 954) were used for the outcomes analysis. Within the NAFLD population, 19·2% (95% CI 15·9-23·0) of people were lean and 40·8% (36·6-45·1) were non-obese. The prevalence of non-obese NAFLD in the general population varied from 25% or lower in some countries (eg, Malaysia and Pakistan) to higher than 50% in others (eg, Austria, Mexico, and Sweden). In the general population (comprising individuals with and without NAFLD), 12·1% (95% CI 9·3-15·6) of people had non-obese NAFLD and 5·1% (3·7-7·0) had lean NAFLD. The incidence of NAFLD in the non-obese population (without NAFLD at baseline) was 24·6 (95% CI 13·4-39·2) per 1000 person-years. Among people with non-obese or lean NALFD, 39·0% (95% CI 24·1-56·3) had non-alcoholic steatohepatitis, 29·2% (21·9-37·9) had significant fibrosis (stage ≥2), and 3·2% (1·5-5·7) had cirrhosis. Among the non-obese or lean NAFLD population, the incidence of all-cause mortality was 12·1 (95% CI 0·5-38·8) per 1000 person-years, that for liver-related mortality was 4·1 (1·9-7·1) per 1000 person-years, cardiovascular-related mortality was 4·0 (0·1-14·9) per 1000 person-years, new-onset diabetes was 12·6 (8·0-18·3) per 1000 person-years, new-onset cardiovascular disease was 18·7 (9·2-31·2) per 1000 person-years, and new-onset hypertension was 56·1 (38·5-77·0) per 1000 person-years. Most analyses were characterised by high heterogeneity. INTERPRETATION: Overall, around 40% of the global NAFLD population was classified as non-obese and almost a fifth was lean. Both non-obese and lean groups had substantial long-term liver and non-liver comorbidities. These findings suggest that obesity should not be the sole criterion for NAFLD screening. Moreover, clinical trials of treatments for NAFLD should include participants across all body-mass index ranges. FUNDING: None.

Risk factors for mortality in cirrhotic patients with sepsis.

BACKGROUND: Patients with cirrhosis and sepsis had increased mortality. AIM: Determine factors associated with increased in-hospital mortality in cirrhotic patients admitted for sepsis. METHODS: All cirrhotic patients admitted from 2004 to 2007 for sepsis were identified from hospital electronic database. Patients were included if they had liver cirrhosis and sepsis, defined as identified sources of infection, and at least one of fever, altered total white cell count, or raised C-reactive protein. Baseline characteristics, investigations, infections, and outcomes were collected. Main outcome measure was in-hospital mortality. RESULTS: A total of 205 admissions in 153 patients were included. In-hospital mortality rate was 24.4%. In predicting in-hospital death, area under the receiver-operating-characteristic curve for Child-Pugh score was 0.934, with optimum cut-off at 10 and above, while for model for end-stage liver disease (MELD) score was 0.751, with optimum cut-off at 17 and above. Four factors were significantly associated with in-hospital mortality on multivariate analysis: presence of >1 site of infection, pneumonia, Child's C status, and MELD score 17 and above. In-hospital mortality rate increased with more factors: 0% with no factor, 7% with one factor, 21% with two factors, 87% with three factors, and 100% with four factors. The mortality of those with <3 risk factors was significantly lower than those with three or more risk factors (7 vs. 91%, p = 0.000). CONCLUSIONS: Septic cirrhotic patients with pneumonia, >1 site of infection, Child's C cirrhosis, and high MELD score had a high mortality risk.