Hepatic steatosis prevalence and impact in autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis

This is a systematic review and meta-analysis synthesizing data on patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The total sample size across included studies was 19,898 patients. The review assessed the pooled prevalence of concomitant hepatic steatosis (HS) and its clinical impact on treatment response and outcomes in these autoimmune liver diseases. The intervention or exposure was the presence of concomitant hepatic steatosis, and the comparator was patients without hepatic steatosis. The primary outcome was the prevalence of HS and its clinical impact on treatment response and outcomes. Key secondary outcomes included hepatic decompensation, hepatocellular carcinoma, and treatment response.

The meta-analysis reported specific prevalence rates for hepatic steatosis across the conditions. The pooled prevalence of HS in patients with AIH was 27.3%. In patients with PBC, the pooled prevalence was 32.9%. For patients with PSC, the pooled prevalence was 21.6%. A temporal trend analysis for PBC patients since 2010 showed that the prevalence of HS has significantly increased, with an annual percent change (APC) of +37.4%.

Regarding clinical outcomes, the review found that in patients with AIH, the risk of hepatic decompensation was higher in those with concomitant HS, with an odds ratio (OR) of 1.6 (95% CI: 1.3-2.1). The risk of hepatocellular carcinoma in AIH patients was also higher with HS, with an OR of 1.8 (95% CI: 1.3-2.6). In contrast, for patients with PBC, HS did not influence clinical outcomes. Treatment response in both AIH and PBC was not influenced by the presence of concomitant HS.

The review did not report data on safety, adverse events, serious adverse events, discontinuations, or tolerability, as these were not available in the synthesized studies. A key limitation noted was that available data on PSC with concomitant HS were insufficient to assess its association with clinical outcomes. The funding sources and potential conflicts of interest were not reported.

Comparing these results to prior landmark studies, the pooled prevalence of HS in AIH (27.3%) and PBC (32.9%) aligns with previous observational reports suggesting a high burden of metabolic comorbidities in autoimmune liver diseases. The increased temporal trend in PBC prevalence since 2010 (+37.4% APC) may reflect broader trends in metabolic syndrome but requires further validation. The finding that HS is associated with worse outcomes in AIH but not in PBC is consistent with some prior studies highlighting disease-specific interactions between metabolic and immune factors.

Key methodological limitations include the observational nature of the included studies, which precludes causal inference. The insufficient data on PSC is a major gap, limiting conclusions for that population. Potential biases include heterogeneity in HS definition and assessment across studies, and confounding by unmeasured metabolic factors.

Clinically, these results suggest that for patients with AIH, the presence of concomitant hepatic steatosis may indicate a higher risk of hepatic decompensation and hepatocellular carcinoma, warranting closer monitoring. For PBC patients, HS does not appear to modify clinical outcomes or treatment response, which may reassure clinicians managing this condition. However, the lack of data on PSC means that the impact of HS in this group remains unclear.

Unanswered questions include the mechanistic links between HS and disease progression in AIH, the optimal management strategies for patients with both conditions, and the long-term impact of HS on PSC outcomes. Future research should focus on prospective studies with standardized HS assessment and longer follow-up to clarify these associations.