Hepatol Int. 2026 Jun 19. doi: 10.1007/s12072-026-11106-3. Online ahead of print.
ABSTRACT
BACKGROUND: Nutrition supplementation and exercise are the current approaches for managing sarcopenia in patients with cirrhosis. There are limited data on benefits, if any, of supplementing testosterone in cirrhosis with sarcopenia and frailty.
METHODS: 127 patients with cirrhosis and sarcopenia were randomized to receive either nutrition and structured exercise with intramuscular testosterone undecanoate 1000 mg administered at 0, 6, 12, 16, 20, and 24 weeks (NExT group, n = 64) or only structured exercise and nutrition (NEx group, n = 63). Of these, 102 patients completed the 24-week study period as per protocol (NExT, n = 50; NEx, n = 52). The primary endpoint was a ≥ 10% increase in appendicular skeletal muscle index (ASMI) at 24 weeks, assessed by dual-energy X-ray absorptiometry (DEXA).
RESULTS: The mean age, MELD (median 14), CTP score (Child A 15.7%, Child B 64.7%, Child C 19.6%) were comparable between groups. On intention-to-treat analysis, a ≥ 10% increase in ASMI was achieved in 41/64 (64.1%) patients in the NExT group compared with 16/63 (25.3%) in the NEx group (p < 0.001). Similar findings were observed in the per-protocol analysis (33/50 [66%] vs. 13/52 [25%]; p < 0.001). A greater proportion of patients in the NExT group demonstrated improvement in hand-grip strength (92% vs. 67.3%, p = 0.002), 6-min walk distance (82% vs. 63.5%, p = 0.04), and reduction in serum ammonia (64% vs. 25%, p = 0.01). Liver frailty index improved significantly in the NExT group compared with the NEx group at 24 weeks (3.98 ± 0.27 to 3.32 ± 0.21 vs. 3.93 ± 0.24 to 3.68 ± 0.22, respectively; p = 0.01). Hospitalization rates were lower in the NExT group (18% vs. 34.6%, p = 0.05), with no apparent major adverse-events with testosterone use.
CONCLUSION: The addition of testosterone therapy to nutrition and structured exercise protocols significantly improves the appendicular muscle mass, reduces frailty and need of rehospitalization in cirrhosis patients with sarcopenia and frailty.
PMID:42319724 | DOI:10.1007/s12072-026-11106-3