The relationship between liver histology and long-term clinical outcomes in patients with non-alcoholic steatohepatitis: a real-world cohort study (vol 76, pg S1, 2022)

Liver biopsies are key for assessing treatment effects in clinical trials of non-alcoholic steatohepatitis (NASH), but few studies have examined the risk of long-term clinical outcomes based on liver histology. This real-world cohort study investigated long-term outcomes in patients with NASH by baseline histology. Patients aged 18–89 years ascertained from the de-identified electronic medical records (EMRs) of Vanderbilt University Medical Center’s Synthetic Derivative database from June 1984–2021 were followed from date of first liver biopsy with histologic evidence of NASH as interpreted by a pathologist from the biopsy report until first clinical event or last EMR entry date (median follow up 4.7 years). We ascertained liver-related outcomes (hepatocellular carcinoma, Model for End-Stage Liver Disease score ≥15 and hepatic decompensation events) and progression to cirrhosis (F4 at baseline excluded) as a function of baseline histology: fibrosis (F0–1, F2, F3, F4), lobular inflammation (LI0, 1, 2–3), hepatocyte ballooning (HB0, 1, 2), and steatohepatitis (SH0–1, 2, 3) using Fine-Gray modeling adjusted for sex, baseline age, diabetes, and weight-loss surgery (WLS) status. Incidences of cardiovascular-related outcomes were examined in separate analyses. A total of 702 patients were included (at index: 70% female; median age 50 years; median body mass index 44 kg/m2; 68% had WLS at or prior to index). Lower fibrosis stages were associated with significantly lower hazard ratios (HRs) for liver-related outcomes vs higher stages (Figure); no significant differences were seen across baseline LI, HB, and SH stages. The rate of incident cirrhosis was lower for: lower vs higher fibrosis (data not shown), LI1 vs 2–3, and HB1 vs 2 (Figure). Lower vs higher fibrosis stage was associated with lower HRs for liver-related outcomes and cirrhosis regardless of WLS status. Lower vs higher LI stage was associated with lower HRs for liver-related outcomes in patients who underwent WLS only. Analyses of HB and SH by WLS status were limited by sample size or number of events. Consistent with previous findings, lower vs higher baseline fibrosis stage was associated with reduced risk of liver-related outcomes, supporting the use of fibrosis regression or halting progression to cirrhosis as endpoints in clinical trials. Lower vs higher LI and HB stages were associated with lower incidence of cirrhosis, highlighting the relevance of achieving NASH resolution.