GEMA-Na and MELD 3.0 severity scores to address sex disparities for accessing liver transplantation: a nationwide retrospective cohort study.

Background: The Gender-Equity Model for liver Allocation corrected by serum sodium (GEMA-Na) and the Model for End-stage Liver Disease 3.0 (MELD 3.0) could amend sex disparities for accessing liver transplantation (LT). We aimed to assess these inequities in Spain and to compare the performance of GEMA-Na and MELD 3.0. Methods: Nationwide cohort study including adult patients listed for a first elective LT (January 2016-December 2021). The primary outcome was mortality or delisting for sickness within the first 90 days. Independent predictors of the primary outcome were evaluated using multivariate Cox's regression with adjusted relative risks (RR) and 95% confidence intervals (95% CI). The discrimination of GEMA-Na and MELD 3.0was assessed using Harrell c-statistics (Hc). Findings: The study included 6071 patients (4697 men and 1374 women). Mortality or delisting for clinical deterioration occurred in 286 patients at 90 days (4.7%). Women had reduced access to LT (83.7% vs. 85.9%; p = 0.037) and increased risk of mortality or delisting for sickness at 90 days (adjusted RR = 1.57 [95% CI 1.09-2.28]; p = 0.017). Female sex remained as an independent risk factor when using MELD or MELD-Na but lost its significance in the presence of GEMA-Na or MELD 3.0. Among patients included for reasons other than tumours (n = 3606; 59.4%), GEMA-Na had Hc = 0.753 (95% CI 0.715-0.792), which was higher than MELD 3.0 (Hc = 0.726 [95% CI 0.686-0.767; p = 0.001), showing both models adequate calibration. Interpretation: GEMA-Na and MELD 3.0 might correct sex disparities for accessing LT, but GEMA-Na provides more accurate predictions of waiting list outcomes and could be considered the standard of care for waiting list prioritization. Funding: Instituto de Salud Carlos III, Agencia Estatal de Investigación (Spain), and European Union.

Clinical outcomes of patients undergoing antiviral therapy while awaiting liver transplantation.

BACKGROUND & AIMS: Antiviral therapy for the treatment of hepatitis C (HCV) infection has proved to be safe and efficacious in patients with cirrhosis awaiting liver transplantation (LT). However, the information regarding the clinical impact of viral eradication in patients on the waiting list is still limited. The aim of the study was to investigate the probability of delisting in patients who underwent antiviral therapy, and the clinical outcomes of these delisted patients. METHODS: Observational, multicenter and retrospective analysis was carried out on prospectively collected data from patients positive for HCV, treated with an interferon-free regimen, while awaiting LT in 18 hospitals in Spain. RESULTS: In total, 238 patients were enrolled in the study. The indication for LT was decompensated cirrhosis (with or without hepatocellular carcinoma [HCC]) in 171 (72%) patients, and HCC in 67 (28%) patients. Sustained virologic response (SVR) rate was significantly higher in patients with compensated cirrhosis and HCC (92% vs. 83% in patients with decompensated cirrhosis with or without HCC, p=0.042). Among 122 patients with decompensated cirrhosis without HCC, 29 (24%) were delisted due to improvement. No patient with baseline MELD score >20 was delisted. After delisting (median follow-up of 88weeks), three patients had clinical decompensations and three had de novo HCC. Only two of the patients with HCC had to be re-admitted onto the waiting list. The remaining 23 patients remained stable, with no indication for LT. CONCLUSIONS: Antiviral therapy is safe and efficacious in patients awaiting LT. A quarter of patients with decompensated cirrhosis can be delisted asa result of clinical improvement, which appears to be remain stable in most patients. Thus, delisting is a safe strategy that could spare organs and benefit other patients with a more urgent need. LAY SUMMARY: Antiviral therapy in patients awaiting liver transplantation is safe and efficacious. Viral eradication allows removal from the waiting list of a quarter of treated patients. Delisting because of clinical improvement is a safe strategy that can spare organs for patients in urgent need.

Improved graft function in liver-transplanted patients after partial splenic embolization: reversal of splenic artery steal syndrome?

AIM: To describe the functional effect of partial splenic embolization (PSE) in liver-transplanted (LT) patients with hypersplenism and hepatitis C virus (HCV) recurrence. PATIENTS AND METHODS: From May 2002 to May 2005, five LT patients with persistent hypersplenism, viral recurrence and graft dysfunction underwent PSE prior to pegylated interferon/ribavirin (peg-IFN/RBV). RESULTS: The mean splenic size was 19.5 cm (16-21) and there was evidence of an enlarged splenic artery (10.7+/-1 mm). PSE produced a median splenic infarction of 90% and a significant reduction in the splenic artery diameter to 5.8+/-0.4 mm (p=0.04). PSE significantly improved hematologic parameters, bilirubin levels, prothrombin activity, international normalized ratio and the Model for End-stage Liver Disease (MELD) score despite high HCV-RNA (6.2 log10 IU/mL). It was demonstrated histologic amelioration of ischemic changes in all subjects. PSE allowed the safe use of full-dose peg-IFN plus RBV in all subjects. CONCLUSIONS: In HCV LT patients with chronic graft dysfunction and cholestasis the improvement in the liver function following PSE might be due to the reversal of an undiagnosed splenic artery steal syndrome related to chronic hypersplenism masked by HCV recurrence.

Is liver transplantation advisable for isoniazid fulminant hepatitis in active extrapulmonary tuberculosis?

Antituberculous treatment is a well-known cause of fulminant hepatic failure (FHF). This could lead to liver transplantation as the only possible treatment, which on the other hand could be contraindicated due to active tuberculosis. The risk of aggressive dissemination of the disease after transplantation is not clearly determined by the current second-line antituberculous therapies. We report a case of vertebral tuberculosis treated with rifampin, isoniazid and pyrazinamide. He developed an FHF that was treated with urgent liver transplantation. Despite the immunosuppression, the disease was well controlled with ciprofloxacin, ethambutol and streptomycin and the patient is in good health 23 months after transplantation. In conclusion, active extrapulmonary tuberculosis should perhaps be considered for liver transplantation when FHF develops due to anti-tuberculous drugs.

HCV clearance and treatment outcome in genotype 1 HCV-monoinfected, HIV-coinfected and liver transplanted patients on peg-IFN-alpha-2b/ribavirin.

BACKGROUND/AIMS: Differences in HCV-RNA clearance during therapy might explain the lower efficacy of peg-IFN/RBV in HIV/HCV-coinfection. There are limited data on HCV-RNA clearance and treatment outcomes in liver transplanted (LT) patients. METHODS: To assess the rates of SVR and baseline predictors of failure after 48 weeks of weight-adjusted peg-IFN-alpha-2b/RBV in 120 patients with HCV genotype 1: 61 HCV-monoinfected, 40 HIV-coinfected and 19 LT-patients. Viral clearance was evaluated in patients completing 24 weeks of therapy (n=112, 93%). RESULTS: SVR was significantly lower in HIV-coinfection than in HCV-monoinfection or LT (18 vs. 39 vs. 42%, P<0.02). By multivariate analysis, HIV-coinfection (OR 3.048, 95% CI 1.133-8.196; P=0.027), baseline HCV-RNA over 800,000 IU/ml (OR 2.800; 95% CI 1.121-6.993, P=0.027) and higher AST values (OR 1.009; 95% CI 1.001-1.018; P=0.028) were significantly associated to failure. Despite similar baseline HCV load (5.67 vs. 5.75 vs. 5.90 log10 IU/ml), HIV-coinfection showed significantly lower HCV-RNA decreases than HCV-monoinfection at weeks 4 (P=0.015), 12 (P=0.015) and 24 (P=0.0003), and than LT at weeks 12 (P=0.003) and 24 (P=0.023). 36/60 subjects (60%) reaching EVR by week 12 obtained SVR vs. 3/60 (5%) who did not. CONCLUSIONS: HIV-coinfection was independently associated to treatment failure, and led to a significantly slower HCV-RNA clearance.