Historia natural de la cirrosis hepática compensada diagnosticada por elastografía hepática transitoria en pacientes coinfectados por el virus de la inmunodeficiencia humana y el virus de la hepatitis C

Patients and Methods Multicenter prospective cohort study conducted in 7 hospitals from Andalusia. From February 2006, all consecutive HIV-infected patients with active chronic HCV infection diagnosed of cirrhosis on the basis of a LS ≥14 kPa were included in the study, provided that they did not have a previous or simultaneous liver decompensation (LD) at the date of the diagnosis of cirrhosis. Patients were prospectively followed-up until death, liver transplant or the censoring date (31 January 2015). The associations between variables, including baseline LS, and the time to LD or death was analysed by means of the log-rank test. Multivariate Cox regression models were built to identify independent predictors of LD and death. Besides, the ability of LS to predict outcomes was compared to that of other classical prognostic scores, as the Child-Turcotte-Pugh (CTP) or the MELD score, by means of the comparisons of the area under the receiver operating characteristic curve (AUROC) and the integrated discrimination improvement (IDI) between models. Results: Four hundred and forty-six patient were included in the study. After a median (Q1-Q3) follow-up of 49 (25-68) months, 80 (17.9%; 95% confidence interval [CI]: 14.2-21.6) patients developed a first LD. Baseline LS values were associated with the probability of the emergence of a LD during follow-up. Thus, the probability of LD at 3 years was 5% in patients with baseline LS < 21 kPa, 13% in those harbouring a LS between 21 and 39,9 kPa and 28% in patients with baseline LS ≥ 40 kPa (p< 0.0001). After multivariate analyses, the variables that showed an independent association with the emergence of LD were age (hazard ratio [HR] 1.06, 95% CI: 1.02-1.10; p=0.001), hepatitis B virus coinfection (HR 6.93, 95% CI: 2.17-18.76; p=0.001), the consecution of sustained virological response (SVR) during follow-up (HR 0.34, 95% CI: 0.13-9.87; p=0.024), clinical AIDS (HR 1.67, 95% CI: 1.05-2.66; p=0.028), CTP stage B (vs A) (HR 4.18; 95% CI: 2.38-7.32; p<0.0001) and baseline LS (comparison group: LS < 21 kPa) (LS 21-39,9 kPa: HR 2.48, 95% CI: 1.31-4.66, p=0.005; LS ≥ 40 kPa: HR 3.68, 95% CI: 1.88-7.19, p< 0.0001). Comparisons of the ability of LS to predict a LD with that of CTP or MELD scores yielded a better performance of LS than MELD (IDI 3.3%; p=0.01) and a similar performance of LS and CTP (IDI 0.13%; p=0.9). By contrast, the combination of LS and CTP stage in a new predictive variable improved the ability to predict outcomes, being the AUROC of the model including this new variable higher than that of the model only based on the CTP stage (AUROC [95% CI] 0.612 [0.544-0.681] vs AUROC 0.575 [0.501-0.648]; p=0.06). Sixty-one (13.6%, 95% CI: 10.3-16.9) patients died during follow-up. In 37 (8.3%, 95% CI: 5.7-10.9) patients, death was liver-related. Besides, 3 patients underwent a liver transplant. Thus, 40 patients developed a liver-related death or a liver transplant. The variables independently associated with this outcome were a platelet count < 50.000/mm3 (HR 2.97, 95% CI: 1.33-6.62; p=0.008), a baseline LS ≥ 21 kPa (HR 2.17, 95% CI: 0.98-4.78, p=0.054) and the consecution of SVR during follow-up (HR 0.14, 95% CI: 0.02-1.05; p=0.057). LS was not independently associated with overall mortality. Independent predictors of overall death were age (HR 1.04, 95% CI: 1.01-1.08; p=0.035), a platelet count < 50.000/mm3 (HR 2.15, 95% CI: 1.05-4.38; p=0.034), MELD score (HR 5.24, 95% CI: 2.74-10.03; p< 0.0001) and the consecution of SVR (HR 0.25, 95% CI: 0.07-0.81; p=0.020). Fifteen (3.4%, 95% CI: 1.7-5) patients developed a first bleeding episode related to portal hypertension during follow-up. In all cases, baseline LS was ≥ 21 kPa. Thus, the NPV of a LS < 21 kPa to predict a bleeding episode during follow-up was 100%. At the moment of the bleeding episode, LS was also above this threshold. Conclusions: LS is an independent predictor of LD and liver-mortality in HIV/HCV-coinfected patients with compensated cirrhosis and provides additional prognostic information to that provided by CTP or MELD scores. The combination of LS and CTP stage in a new predictive index improves the ability of CTP to predict outcome. Besides, a LS < 21 kPa identifies HIV/HCV-coinfected patients with compensated cirrhosis with a very low risk of presenting a variceal bleeding episode, allowing to spare upper endoscopy aimed to screen for esophagueal varices in these patients, provided that LS maintains below this level. Our observations provide new evidence that support the inclusion of periodic LS determinations in the routine clinical care of these patients.