R. Layese

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

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. Coxs 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/mm3: HR, 2.70; 95% CI, 1.62; 4.51; P < 0.001; [100; 150] Giga/mm3: 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)

Extrahepatic cancers are the leading cause of death in patients achieving hepatitis B virus control or hepatitis C virus eradication

Data on extrahepatic cancers (EHCs) in compensated viral cirrhosis are limited. The objective of the prospective multicenter Agence Nationale de Recherche sur le SIDA et les Hépatites virales CO12 CirVir cohort was to assess the occurrence of all clinical events in patients with compensated viral cirrhosis, including all types of cancer. Patients with the following inclusion criteria were enrolled in 35 French centers: (1) biopsy‐proven hepatitis B virus (HBV) or hepatitis C virus (HCV) cirrhosis, (2) Child‐Pugh A, or (3) absence of previous liver complications including primary liver cancer (PLC). Patients were followed up prospectively every 6 months. The standardized mortality ratio (SMR) was calculated according to age and gender using 5‐year periods. The impact of sustained viral response (SVR) in HCV patients and maintained viral suppression in HBV patients were assessed using time‐dependent analysis. A total of 1,671 patients were enrolled between 2006 and 2012 (median age, 54.9 years; men, 67.3%; HCV, 1,323; HBV, 317; HCV–HBV, 31). Metabolic features and excessive alcohol and tobacco consumption were recorded in 15.2%, 36.4%, and 56.4% of cases, respectively. After a median follow‐up of 59.7 months, 227 PLCs were diagnosed (5‐year cumulative incidence [CumI] 13.4%) and 93 patients developed EHC (14 patients with lymphoid or related tissue cancer and 79 with solid tissue cancer; 5‐year EHC CumI, 5.9%). Compared to the general French population, patients were younger at cancer diagnosis, with significantly higher risk of EHC in HCV patients (SMR, 1.31; 95 confidence interval [CI], 1.04‐1.64; P = 0.017) and after SVR (SMR = 1.57; 95% CI, 1.08‐2.22; P = 0.013). EHC was the fourth leading cause of death in the whole cohort and the first in patients with viral control/eradication. Conclusion: Compared to the general French population, HCV cirrhosis is associated with a higher risk of EHC and the first cause of death in patients with viral cirrhosis who achieve virological control/eradication. (Hepatology 2018).

Prognostic value of viral eradication for major adverse cardiovascular events in hepatitis C cirrhotic patients

Background The objective was to examine the role of a sustained virological response (SVR) on major adverse cardiovascular events (MACEs) in patients with compensated hepatitis C virus (HCV) cirrhosis. Methods Patients with the following criteria were enrolled in 35 French centers: (1) biopsy‐proven HCV cirrhosis; (2) Child‐Pugh A; (3) positive viremia; and (4) no prior liver complication, and then prospectively followed. All patients received HCV treatment after inclusion. MACEs included stroke, myocardial infarction, ischemic heart disease, heart failure, peripheral arterial disease, cardiac arrest, and cardiovascular death. SVR, defined as negative viremia 12 weeks posttreatment, was considered as a time‐dependent covariate, and its effect on MACE occurrence was assessed. The median follow up was 57.5 months, ending in December 2015. Results Sixty‐two of 878 (7.1%) patients presented a total of 79 MACEs. The main predictive baseline factors of MACEs were Asian ethnic origin, history of MACEs, arterial hypertension, diabetes mellitus, current smoking, low serum albumin level, high total bilirubin level, and low platelet count. In multivariate analysis, SVR was associated with a decreased risk of MACEs (hazard ratio = 0.35, 95% CI 0.09‐0.97, P = .044), whereas Asian ethnic origin, arterial hypertension, smoking, and low serum albumin level remained predictive of MACE occurrence. The 5‐year survival rate was 60.1% versus 87.5% in patients who did versus those who did not present a MACE (P < .001). Conclusions In patients with compensated HCV‐related cirrhosis, Asian ethnic origin, arterial hypertension, smoking, and low serum albumin are independent predictive factors of cardiovascular events, whereas an SVR is associated with a decreased rate of cardiovascular events.

Prognostic factors of survival in HIV/HCV co-infected patients with hepatocellular carcinoma: The CARCINOVIC Cohort

HIV/HCV co‐infected patients with hepatocellular carcinoma (HCC) have poorer survival than HCV mono‐infected patients. We aimed to evaluate the prognostic factors for survival.

Influence of Progenitor‐Derived Regeneration Markers on Hepatitis C Virus–Related Cirrhosis Outcome (ANRS CO12 CirVir Cohort)

Progenitor‐derived regeneration gives rise to the aberrant expression of biliary markers such as cytokeratin 7 (K7) and epithelial cell adhesion molecule (EpCAM) in hepatocytes. We aimed to describe the expression of these molecules in patients with compensated hepatitis C virus (HCV)–related cirrhosis and to investigate its potential influence on cirrhosis complications. Among patients with Child‐Pugh A uncomplicated HCV‐related cirrhosis enrolled in the prospective ANRS CO12 CirVir cohort, we selected individuals with a liver biopsy collected within 2 years before inclusion in the study. K7 and EpCAM immunostaining identified intermediate hepatobiliary cells. The influence of biliary marker expres‐sion in hepatocytes on decompensation events and the occurrence of hepatocellular carcinoma (HCC) was studied using a multivariate Cox proportional hazards regression model. Among the 337 patients eligible for the study (men, 67%; median age, 52 years), 198 (58.8%) had biopsies with K7‐positive hepatocytes including extensive staining in 40 (11.9%) and 203 had EpCAM‐positive hepatocytes (60.6%). During follow‐up (median, 54.2 months), 47 patients (14%) experienced a decompensation event, and HCC was diagnosed in 37 patients (11%). Extensive K7 staining was independently associated with the occurrence of a decompensation event (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.30‐6.89; P = 0.010). EpCAM expression was independently associated with HCC occurrence (HR, 2.37; 95% CI, 1.07‐5.23; P =0.033) along with age and a low prothrombin ratio. Conclusion: Progenitor‐derived regeneration depicted by K7 and EpCAM immunostaining of hepatocytes in liver biopsies of patients with compensated HCV‐related cirrhosis marks a cirrhosis stage more prone to develop complications. (HEPATOLOGY 2018; 68:1534‐1548).

Long-term quality of life in adult patients surviving purpura fulminans: an exposed-unexposed multicenter cohort study

Background Long-term Health-related Quality of Life (HR-QOL) of patients surviving the acute phase of purpura fulminans (PF) has not been evaluated. Methods A French multicenter exposed-unexposed cohort study enrolling patients admitted in 55 ICUs for a PF from 2010 to 2016. Adult patients surviving the acute phase of PF (exposed group) were matched 1:1 for age, SAPS II and gender with septic shock survivors (unexposed group). HR-QOL was assessed during a phone-interview using the SF-36 questionnaire, the Hospital Anxiety and Depression (HAD) scale, the Impact of Event Scale-Revised (IES-R) and the Activity of Daily Living (ADL) and Instrumental ADL (IADL) scales. The primary outcome measure was the physical component summary (PCS) of the SF-36 questionnaire. Results Thirty-seven survivors of PF and 37 of septic shock were phone-interviewed at 55 [35-83] and 44 [35-72] months of ICU discharge, respectively (p=0.23). The PCS of the SF-36 was not significantly different between exposed and unexposed patients (median [quartile1-quartile3]=47 [36-53] vs. 54 [36-57]; p=0.18). There was also no significant difference between groups regarding the mental component summary of the SF-36, and the HAD, IES-R, ADL and IADL scales. Among the 37 exposed patients, those who required limb amputation (n=12/37, 32%) exhibited lower PCS (34 [24-38] vs. 52 [42-56]; p=0.001) and IADL scores (7 [4-8] vs. 8 [7-8]; p=0.021) as compared to non-amputated patients. Conclusion Long-term HR-QOL does not differ between patients surviving PF and those surviving septic shock unrelated to PF. Amputated patients have an impaired physical HR-QOL but a preserved mental health. Clinical Trials NCT03216577.