Primary liver cancer is more aggressive in HIV-HCV coinfection than in HCV infection. A prospective study (ANRS CO13 Hepavih and CO12 Cirvir)

OBJECTIVE: Since HAART, primary liver cancer has emerged as an increasing cause of morbidity and mortality in patients with HIV infection. Our aim was to compare characteristics and outcome of primary liver cancer according to HIV status in HCV cirrhotic patients submitted to periodic ultrasonographic surveillance. METHODS: All patients with primary liver cancer and cirrhosis were selected from two prospective cohorts (ANRS CO12 Cirvir, viral cirrhosis, n=1081; ANRS CO13 Hepavih, HIV-HCV coinfection, n=1175). Cirrhosis was diagnosed by liver biopsy in monoHCV group and biopsy and/or non-invasive tests in HIV-HCV group. Ultrasonographic surveillance was performed every 6 months. Diagnosis of primary liver cancer was established according to EASL-AASLD guidelines. RESULTS: Primary liver cancer was diagnosed in 32 patients, 16 in each group, and corresponded to hepatocellular carcinoma in all except for two cholangiocarcinomas in HIV-HCV patients. Ultrasonographic follow-up was similar (median time since last ultrasonographic without focal lesion: 237 days in HIV-HCV group (n=12) versus 208 days in HCV group, NS). At primary liver cancer diagnosis HIV-HCV patients were markedly younger (48 vs. 60 yrs, P<0.001), primary liver cancer was more advanced in HIV-HCV patients (single nodule: 43% vs. 75%, P=0.07; mean diameter of main nodule: 24 vs. 16 mm, P=0.006; portal obstruction: 3 vs. 0). Curative treatment was performed in four HIV-HCV patients versus 11 HCV patients (P=0.017). During follow-up, 10 HIV-HCV patients died versus only one HCV patient (P=0.0005). CONCLUSIONS: This result suggests more aggressiveness for tumors in HIV infected patients and, if confirmed, could result in shortening the length between ultrasonographic examinations

Complications and competing risks of death in compensated viral cirrhosis (ANRS CO12 CirVir prospective cohort)

International audienceUnlabelled - Various critical events, liver related or not, occur in patients with compensated cirrhosis, but their respective burden remains to be prospectively assessed. The aim of this prospective cohort study involving 35 French centers was to capture the whole spectrum of complications occurring in compensated viral cirrhosis (VC) using competing risks analyses. Inclusion criteria were: histologically proven cirrhosis resulting from hepatitis C virus (HCV) or hepatitis B virus (HBV); Child-Pugh A; and no previous hepatic complications. The cohort was considered as a multistate disease model, cumulative incidences (CumIs) of events were estimated in a competing risks framework. A total of 1,654 patients were enrolled from 2006 to 2012 (HCV, 1,308; HBV, 315; HCV-HBV, 31). During a median follow-up of 34 months, at least one liver nodule was detected in 271 patients, confirmed as hepatocellular carcinoma (HCC) in 128 (4-year cumI: 10.5%) and cholangiocarcinoma in 3. HCC incidence was higher in HCV (4-year cumI: 11.4% vs. 7.4%; P = 0.05). HCC fulfilled Milan criteria in 79.3%, leading to curative treatment in 70.4%. Liver decompensation occurred more frequently in HCV patients (4-year cumI: 10.8% vs. 3.6%; P = 0.0004). Virological eradication/control was achieved in 34.1% of HCV and 88.6% of HBV patients and was associated with a marked decrease in HCC, decompensation, and bacterial infection incidences. Survival was shorter in HCV patients (4-year cumI: 91.6% vs. 97.2%; P = 0.0002). Death (n = 102; missing data: 6) was attributed to liver disease in 48 (47%; liver cancer: n = 18; miscellaneous, n = 30) and extrahepatic causes in 48 (47%; bacterial infection: n = 13; extrahepatic cancers: n = 10; cardiovascular events: n = 5; miscellaneous, n = 20). Conclusion - After 3 years of follow-up, extrahepatic events still explained half of deaths in patients with compensated VC. A strong decrease in complications was linked to virological eradication/control

Nomogram for individualized prediction of hepatocellular carcinoma occurrence in hepatitis C virus cirrhosis (ANRS CO12 CirVir)

International audienceUnlabelled - The aim of this work was to develop an individualized score for predicting hepatocellular carcinoma (HCC) in patients with hepatitis C (HCV)-compensated cirrhosis. Among 1,323 patients with HCV cirrhosis enrolled in the French prospective ANRS CO12 CirVir cohort, 720 and 360 were randomly assigned to training and validation sets, respectively. Cox's multivariate model was used to predict HCC, after which a nomogram was computed to assess individualized risk. During follow-up (median, 51.0 months), 103 and 39 patients developed HCC in the training and validation sets, respectively. Five variables were independently associated with occurrence of HCC: age > 50 years (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.16; 3.25; P = 0.012); past excessive alcohol intake (HR, 1.55; 95% CI, 1.02; 2.36; P = 0.041); low platelet count (<100 Giga/mm(3) : HR, 2.70; 95% CI, 1.62; 4.51; P < 0.001; [100; 150] Giga/mm(3) : HR, 1.87; 95% CI, 1.10; 3.18; P = 0.021); gamma-glutamyl transpeptidase above the upper limit of normal (HR, 1.96; 95% CI, 1.11; 3.47; P = 0.021); and absence of a sustained virological response during follow-up (HR, 3.02; 95% CI, 1.67; 5.48; P < 0.001). An 11-point risk score was derived from the training cohort and validated in the validation set. Based on this score, the population was stratified into three groups, in which HCC development gradually increased, from 0% to 30.1% at 5 years for patients with the lowest (≤3) and highest (≥8) scores (P < 0.001). Using this score, a nomogram was built enabling individualized prediction of HCC occurrence at 1, 3, and 5 years. Conclusion - This HCC score can accurately predict HCC at an individual level in French patients with HCV cirrhosis. (Hepatology 2016;64:1136-1147)