Limitations
liver stiffness, cirrhosis, fibrosis
EVENTS, CIRRHOSIS, DISEASE CHARACTERISTIC, FIBROSIS
A limitation of this study was the short treatment duration, with only 12 days spent on the dose-escalated maintenance dose. This may explain why biomarkers of liver function and liver stiffness measurements remained unchanged; however, the primary end point of this study was to assess the safety and tolerability of BI 685509 and not to explore efficacy end points. In addition, the low number of included patients could have influenced the power of the exploratory outcomes. Furthermore, although most patients with CP-A cirrhosis did not show any clinical evidence of decompensation, some patients may have experienced self-limiting and resolved decompensation events ≥6 weeks before screening. During the study, some patients with CP-A cirrhosis may have had disease characteristics similar to patients with CP-B cirrhosis; however, only 2 patients with CP-A cirrhosis progressed to clinically evident CP-B during treatment. In addition, phosphatidylethanol blood alcohol testing was not conducted to confirm alcohol abstinence throughout the trial. However, participants were excluded if they had ongoing chronic alcohol or drug use.Although this trial did not show reductions in markers of fibrosis, preclinical studies of sGC modulation in various models have shown that promoting sGC activity and, thus increasing cyclic guanosine monophosphate production, can both decrease portal pressure and exert antifibrotic effects.