Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with type 2 diabetes mellitus (T2DM) as a major predictor. Insulin resistance and chronic inflammation are key pathways in the pathogenesis of T2DM leading to NAFLD and vice versa, with the synergistic effect of NAFLD and T2DM increasing morbidity and mortality risks. This meta-analysis aims to quantify the prevalence of NAFLD and the prevalence of clinically significant and advanced fibrosis in people with T2DM. METHODS: MEDLINE and Embase databases were searched from inception until 13 February 2023. The primary outcomes were the prevalence of NAFLD, non-alcoholic steatohepatitis (NASH) and fibrosis in people with T2DM. A generalised linear mixed model with Clopper-Pearson intervals was used for the analysis of proportions with sensitivity analysis conducted to explore heterogeneity between studies. RESULTS: 156 studies met the inclusion criteria, and a pooled analysis of 1 832 125 patients determined that the prevalence rates of NAFLD and NASH in T2DM were 65.04% (95% CI 61.79% to 68.15%, I2=99.90%) and 31.55% (95% CI 17.12% to 50.70%, I2=97.70%), respectively. 35.54% (95% CI 19.56% to 55.56%, I2=100.00%) of individuals with T2DM with NAFLD had clinically significant fibrosis (F2-F4), while 14.95% (95% CI 11.03% to 19.95%, I2=99.00%) had advanced fibrosis (F3-F4). CONCLUSION: This study determined a high prevalence of NAFLD, NASH and fibrosis in people with T2DM. Increased efforts are required to prevent T2DM to combat the rising burden of NAFLD. PROSPERO REGISTRATION NUMBER: CRD42022360251.

Natural history of NASH cirrhosis in liver transplant waitlist registrants.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) cirrhosis is rapidly growing as an indication for liver transplant(ation) (LT). However, the natural history of NASH cirrhosis among LT waitlist registrants has not been established. The present study aimed to define the natural history of NASH cirrhosis using the Scientific Registry of Transplant Recipients database. METHODS: The study cohort comprised patients registered on the LT waitlist between 1/1/2016 to 12/31/2021. The primary outcomes included probability of LT and waitlist mortality, comparing NASH (n = 8,120) vs. non-NASH (n = 21,409) cirrhosis. RESULTS: Patients with NASH cirrhosis were listed with lower model for end-stage liver disease (MELD) scores despite bearing a greater burden of portal hypertension, especially at lower MELD scores. The overall transplant probability in LT waitlist registrants with NASH [vs. non-NASH] cirrhosis was significantly lower at 90 days (HR 0.873, p <0.001) and 1 year (HR 0.867, p <0.001); this was even more pronounced in patients with MELD scores >30 (HR 0.705 at 90 days and HR 0.672 at 1 year, p <0.001 for both). Serum creatinine was the key contributor to MELD score increases leading to LT among LT waitlist registrants with NASH cirrhosis, while bilirubin was in patients with non-NASH cirrhosis. Finally, waitlist mortality at 90 days (HR 1.15, p <0.001) and 1 year (1.25, p <0.001) was significantly higher in patients with NASH cirrhosis compared to those with non-NASH cirrhosis. These differences were more pronounced in patients with lower MELD scores at the time of LT waitlist registration. CONCLUSIONS: LT waitlist registrants with NASH cirrhosis are less likely to receive a transplant compared to patients with non-NASH cirrhosis. Serum creatinine was the major contributor to MELD score increases leading to LT in patients with NASH cirrhosis. IMPACT AND IMPLICATIONS: This study provides important insights into the distinct natural history of non-alcoholic steatohepatitis (NASH) cirrhosis among liver transplant (LT) waitlist registrants, revealing that patients with NASH cirrhosis face lower odds of transplantation and higher waitlist mortality than those with non-NASH cirrhosis. Our study underscores the significance of serum creatinine as a crucial contributor to model for end-stage liver disease (MELD) score in patients with NASH cirrhosis. These findings have substantial implications, emphasizing the need for ongoing evaluation and refinement of the MELD score to more accurately capture mortality risk in patients with NASH cirrhosis on the LT waitlist. Moreover, the study highlights the importance of further research investigating the impact of the implementation of MELD 3.0 across the US on the natural history of NASH cirrhosis.