Evolution of liver disease severity and portal hypertension during REP 2139-Mg treatment in 3 patients with chronic hepatitis D : Case reports.

Treatment options for chronic hepatitis D (CHD) are limited in patients who do not respond to recommended treatment with bulevirtide ± pegylated interferon. The use of REP 2139-Mg is a novel treatment option that has recently demonstrated efficacy and safety in phase 2 trials and a compassionate access program that included three patients treated at the Vienna General Hospital with compensated advanced chronic liver disease and clinically significant portal hypertension (CSPH). Long-term outcome of CSPH patients treated with REP 2139-Mg is unknown; thus, surrogate endpoints are of interest in this population. In the 3 patients receiving REP 2139-Mg for 12 months at our center, we monitored the hepatic venous pressure gradient (HVPG) as the strongest prognostic surrogate biomarker in compensated cirrhosis at baseline, and after 3 and 12 months of treatment. The HVPG dynamics alongside additional liver function tests observed are summarized in this report and two out of three patients achieved undetectable hepatitis-D-virus(HDV)-RNA and low hepatitis B surface Antigen (HBsAg) following pronounced alanine aminotransferase (ALT) flares during REP 2139-Mg treatment. The first patient showed virologic non-response and no HVPG dynamics during treatment. The second patient developed jaundice upon treatment initiation, resulting in a transient increase in HVPG despite virologic response. The third patient achieved virologic response that was paralleled by sustained reductions in HVPG.