In a meta-analysis of randomized controlled trials of NASH, patients given placebo have significant histologic, radiologic, and biochemical responses. The placebo response should be considered in designing trials of agents for treatment of NASH.

Background Serum fibrosis markers are useful in staging chronic hepatitis B (HBV) and C (HCV) but have not been evaluated in chronic hepatitis D (HDV). Aims We evaluated the utility of serum fibrosis markers (fibrosis-4 score [FIB-4], AST to ALT ratio [AAR], age-platelet index [API], AST-to-platelet-ratio-index [APRI] and Hui score) in HDV infection. Methods Clinical and histologic laboratory data from HBV, HCV and HDV patients were evaluated and serum fibrosis markers were calculated. The ability of fibrosis markers to detect advanced fibrosis (Ishak ≥4) and cirrhosis (Ishak =6) were evaluated and compared between viral infections. Results 1003 subjects (HCV=701, HBV=240 and HDV=62) with mean age of 46 ±11 and 66% male were evaluated. HDV subjects had higher ALT and AST than HCV and lower platelets than both HBV and HCV. Histologically, HDV had the greatest percentage of Ishak≥4 and necroinflammation. FIB-4 performed best in detecting advanced fibrosis and cirrhosis in all viral cohorts. In HDV, area under the receiver operator curve (AUROC) 95% confidence intervals for detecting advanced fibrosis were: FIB-4=0.70 (0.55–0.84), API=0.69 (0.55–0.82), APRI=0.68 (0.54–0.82), Hui score=0.63 (0.49–0.78), AAR=0.63 (0.48–0.77). The AUROC for detecting cirrhosis in HDV were: FIB-4=0.83(0.69–0.97), API=0.80(0.66–0.95), APRI=0.75(0.61–0.89), Hui score=0.70(0.49–0.91) and AAR=0.70(0.48–0.93). Adjustment of published cut-offs led to marginal improvements in FIB4 for advanced fibrosis and of APRI for cirrhosis in HDV. Conclusions Serum fibrosis markers have lower performance accuracy in chronic HDV infected patients compared to HBV and HCV patients. Other noninvasive fibrosis markers should be explored to assist in the management of these patients.

Loss‐of‐function mutations in genes that encode for components of the telomere repair complex cause accelerated telomere shortening. Hepatic involvement has been recognized as a cause of morbidity in telomere diseases, but very few studies have characterized the nature and extent of liver involvement in affected patients. We report the prevalence and characteristics of liver involvement in a large cohort of patients with telomere disease evaluated serially at the National Institutes of Health. One hundred twenty‐one patients with known or suspected telomere disease were screened; 40 patients with liver involvement were included in the current study. Median follow‐up was 2.4 years. Data were collected regarding their demographic information, laboratory analysis, imaging, and histopathology. Forty patients (40% of the cohort) with a median age of 42 years were found to have liver involvement. Liver enzyme elevation was cholestatic in pattern; 8 (21%) had drug‐related enzyme elevations. The most common imaging finding was increased hepatic echogenicity on ultrasound in 39% (9) of patients, followed by hepatomegaly in 26% (6). Biopsies were infrequent because of risk associated with thrombocytopenia, but in 6 patients, there were varying findings: nodular regenerative hyperplasia, steatohepatitis, hemosiderosis, cholestasis, and cirrhosis with hepatic steatosis. Almost half the cohort had pulmonary diffusion abnormalities, and 25% died during the follow‐up period. Conclusion: In patients with telomere disease, hepatic involvement is common and can present in diverse ways, including elevated liver enzymes as well as histopathologic and imaging abnormalities. Liver disease has important implications for morbidity and mortality in patients with telomere disease.