Hepatocellular carcinoma, decompensation, and mortality based on hepatitis C treatment: A prospective cohort study.

Prospective studies of the long-term outcomes of patients with hepatitis C virus (HCV) infection after treatment with interferon-based therapy (IBT) or direct-acting antivirals (DAA) are limited in many Asian countries. To elucidate the incidences of hepatocellular carcinoma (HCC) and death/transplantation based on treatment with IBT or DAA, to compare the outcomes of the sustained virologic response (SVR) to IBT and DAA, and to investigate outcome-determining factors after SVR. This cohort included 2054 viremic patients (mean age, 57 years; 46.5% male; 27.4% with cirrhosis) prospectively enrolled at seven hospitals between 2007 and 2019. They were classified as the untreated group (n = 619), IBT group (n = 578), and DAA group (n = 857). Outcomes included the incidences of HCC and death/transplantation. The incidences of the outcomes for each group according to treatment were calculated using an exact method based on the Poisson distribution. A multivariate Cox regression analysis was performed to determine the factors associated with HCC or death/transplantation, followed by propensity score matching to confirm the results. During a median of 4.1 years of follow-up, HCC and death/transplantation occurred in 113 and 206 patients, respectively, in the entire cohort. Compared with the untreated group, the incidences of HCC and death/transplantation were significantly lower in the IBT group [adjusted hazard ratio (aHR) 0.47, 95%CI: 0.28-0.80 and aHR 0.28, 95%CI: 0.18-0.43, respectively] and the DAA group (aHR 0.58, 95%CI: 0.35-0.96, and aHR 0.19, 95%CI: 0.20-0.68, respectively). Among 1268 patients who attained SVR with IBT (n = 451) or DAA (n = 816), the multivariable-adjusted analysis showed no differences in the risks of HCC (HR 2.03; 95%CI: 0.76-5.43) and death/transplantation (HR 1.38; 95%CI: 0.55-3.49) between the two groups. This was confirmed by a propensity score-matching analysis. Independent factors for HCC after SVR were age, genotype 1, and the presence of cirrhosis. Treatment and achieving SVR with either IBT or DAA significantly reduced the incidences of HCC and mortality in the Asian patients with HCV infection. The risks of HCC and mortality were not significantly different regardless of whether SVR was induced by IBT or DAA.

Choi GH ，Jang ES ，Kim YS ，Lee YJ ，Kim IH ，Cho SB ，Lee HC ，Jang JW ，Ki M ，Choi HY ，Baik D ，Jeong SH ... -  《-》

Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients.

The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), following successful treatment of early hepatocellular carcinoma (HCC), has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. We prospectively enrolled 163 consecutive patients with HCV-related cirrhosis and a first diagnosis of early Barcelona Clinic Liver Cancer stage 0/A HCC, who had achieved a complete radiologic response after curative resection or ablation and were subsequently treated with DAAs. DAA-untreated patients from the ITA.LI.CA. cohort (n = 328) served as controls. After propensity score matching, outcomes of 102 DAA-treated (DAA group) and 102 DAA-untreated patients (No DAA group) were compared. In the DAA group, 7/102 patients (6.9%) died, HCC recurred in 28/102 patients (27.5%) and hepatic decompensation occurred in 6/102 patients (5.9%), after a mean follow-up of 21.4 months. OS was significantly higher in the DAA group compared to the No DAA group (hazard ratio [HR] 0.39; 95% CI0.17-0.91; p = 0.03). HCC recurrence was not significantly different between the DAA and No DAA groups (HR0.70; 95% CI0.44-1.13; p = 0.15). A significant reduction in the rate of hepatic decompensation was observed in the DAA group compared with the No DAA group (HR0.32; 95% CI0.13-0.84; p = 0.02). In the DAA group, sustained virologic response was a significant predictor of OS (HR 0.02; 95% CI 0.00-0.19; p <0.001), HCC recurrence (HR 0.25; 95% CI 0.11-0.57; p <0.001) and hepatic decompensation (HR 0.12; 95% CI 0.02-0.38; p = 0.02). In patients with HCV-related cirrhosis who had been successfully treated for early HCC, DAAs significantly improved OS compared with No DAA treatment. We aimed to determine whether direct-acting antivirals (DAAs) significantly improve overall survival in patients with hepatitis C virus-related compensated cirrhosis and a first diagnosis of hepatocellular carcinoma (HCC) which has been successfully treated with curative resection or ablation. Using propensity-score matched patients, we found that DAAs improved overall survival and reduced the risk of hepatic decompensation. However, the risk of HCC recurrence was not significantly reduced.

Cabibbo G ，Celsa C ，Calvaruso V ，Petta S ，Cacciola I ，Cannavò MR ，Madonia S ，Rossi M ，Magro B ，Rini F ，Distefano M ，Larocca L ，Prestileo T ，Malizia G ，Bertino G ，Benanti F ，Licata A ，Scalisi I ，Mazzola G ，Di Rosolini MA ，Alaimo G ，Averna A ，Cartabellotta F ，Alessi N ，Guastella S ，Russello M ，Scifo G ，Squadrito G ，Raimondo G ，Trevisani F ，Craxì A ，Di Marco V ，Cammà C ，Rete Sicilia Selezione Terapia – HCV (RESIST-HCV) and Italian Liver Cancer (ITA.LI.CA.) Group ... -  《-》

Reduction of the Risk of Hepatocellular Carcinoma over Time Using Direct-Acting Antivirals: A Propensity Score Analysis of a Real-Life Cohort (PITER HCV).

Quaranta MG ，Cavalletto L ，Russo FP ，Calvaruso V ，Ferrigno L ，Zanetto A ，Mattioli B ，D'Ambrosio R ，Panetta V ，Brancaccio G ，Raimondo G ，Brunetto MR ，Zignego AL ，Coppola C ，Iannone A ，Biliotti E ，Rosselli Del Turco E ，Massari M ，Licata A ，Barbaro F ，Persico M ，Morisco F ，Pompili M ，Cerini F ，Puoti M ，Santantonio T ，Craxì A ，Kondili LA ，Chemello L ，On Behalf Of Piter Collaborating Investigators ... -  《Viruses-Basel》

Human Immunodeficiency Virus (HIV) Infection Is Associated With Lower Risk of Hepatocellular Carcinoma After Sustained Virological Response to Direct-acting Antivirals in Hepatitis C Infected Patients With Advanced Fibrosis.

The aim of this study was to assess the impact of human immunodeficiency virus (HIV) infection on the risk of developing hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) who achieve sustained virological response (SVR) with direct-acting antiviral (DAA). Multisite prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they met: (1) SVR with DAA-based combination; (2) liver stiffness (LS) ≥9.5 kPa previous to treatment; (3) LS measurement at the SVR time-point. The main endpoint was the occurrence of HCC. Propensity score (PS) was calculated to address potential confounders due to unbalanced distribution of baseline characteristics of HIV/HCV-coinfected and HCV-monoinfected patients. In total, 1035 HCV-infected patients were included, 667 (64%) coinfected with HIV. After a median (Q1-Q3) follow-up time of 43 (31-49) months, 19 (1.8%) patients developed HCC (11 [3.0%]; HCV-monoinfected, 8[1.2%]; HIV/HCV-coinfected individuals; P = .013). In the multivariable analysis, HIV coinfection was associated with a lower adjusted risk of developing HCC (subhazard ratio [sHR] = 0.27, 95% confidence interval [CI]: .08-.90; P = .034). Predictors of HCC emergence were: HCV genotype 3 (sHR = 7.9, 95% CI: 2.5-24.9; P < .001), MELD score at SVR >10 (sHR = 1.37, 95% CI: 1.01-1.86; P = .043) and LS value at SVR (sHR = 1.03, 95% CI: 1.01-1.06, for 1 kPa increase; P = .011). Using inverse probability weighting method on the PS, HIV-infected patients had a lower risk of HCC (powered HR = 0.33, 95% CI: .11-.85). Among HCV-infected patients with advanced fibrosis, who achieve SVR with DAA, HIV coinfection seems to be associated with a lower risk of HCC occurrence. The underlying causes for this finding need to be investigated.

Corma-Gómez A ，Macías J ，Lacalle-Remigio JR ，Téllez F ，Morano L ，Rivero A ，Serrano M ，Ríos MJ ，Vera-Méndez FJ ，Alados JC ，Real LM ，Palacios R ，Santos IL ，Imatz A ，Pineda JA ，RIS-HEP13 and GEHEP 011 study groups ... -  《-》

Incidence of Hepatocellular Carcinoma After Direct Antiviral Therapy for HCV in Patients With Cirrhosis Included in Surveillance Programs.

Retrospective studies have found an unexpectedly high incidence of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV)-associated cirrhosis who received direct-acting antiviral (DAA) agents. We analyzed data from the ANRS CO12 CirVir cohort to compare the incidence of HCC in patients with cirrhosis who received DAA therapy vs patients treated with interferon (IFN). Data were collected from 1270 patients with compensated biopsy-proven HCV-associated cirrhosis recruited from 2006 through 2012 at 35 centers in France. For descriptive purpose, patients were classified as follows: patients who received DAA treatment (DAA group, n = 336), patients who achieved a sustained virologic response (SVR) following an IFN-based regimen (SVR-IFN group, n = 495), or patients who never received DAA treatment and never had an SVR following IFN therapy (non-SVR group, n = 439). The patients were included in HCC surveillance programs based on ultrasound examination every 6 months, and clinical and biological data were recorded. To account for confounding by indication due to differences in patient characteristics at treatment initiation, we constructed a time-dependent Cox regression model weighted by the inverse probability of treatment and censoring (IPTCW) to assess the treatment effects of DAA on time until HCC. Compared with patients in the SVR-IFN group, patients in the DAA group were older, higher proportions had diabetes or portal hypertension, and liver function was more severely impaired. The crude 3-year cumulative incidences of HCC were 5.9% in the DAA group, 3.1% in the SVR-IFN group, and 12.7% in the non-SVR group (overall P < .001; unadjusted hazard ratio [HR] for HCC 2.03; 95% confidence interval [CI] 1.07-3.84; P = .030 for the DAA group vs the SVR-IFN group). HCC characteristics were similar among groups. Among patients with HCC, the DAA group received less-frequent HCC screening than the other 2 groups (P = .002). After Cox analyses weighted by the IPTCW, we found no statistically significant increase in risk of HCC associated with DAA use (HR 0.89; 95% CI 0.46-1.73; P = .73). Analysis of data from the ANRS CO12 CirVir cohort reveals that the apparent increase in HCC incidence observed in patients with cirrhosis treated with DAAs compared with patients who achieved SVR following an IFN therapy can be explained by patient characteristics (age, diabetes, reduced liver function) and lower screening intensity.

Nahon P ，Layese R ，Bourcier V ，Cagnot C ，Marcellin P ，Guyader D ，Pol S ，Larrey D ，De Lédinghen V ，Ouzan D ，Zoulim F ，Roulot D ，Tran A ，Bronowicki JP ，Zarski JP ，Riachi G ，Calès P ，Péron JM ，Alric L ，Bourlière M ，Mathurin P ，Blanc JF ，Abergel A ，Serfaty L ，Mallat A ，Grangé JD ，Attali P ，Bacq Y ，Wartelle C ，Dao T ，Thabut D ，Pilette C ，Silvain C ，Christidis C ，Nguyen-Khac E ，Bernard-Chabert B ，Zucman D ，Di Martino V ，Sutton A ，Roudot-Thoraval F ，Audureau E ，ANRS CO12 CirVir Group ... -  《-》