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

被引：182

作者：

Nahon, Pierre ^{[1
,2
,3
]}

Layese, Richard ^{[4
,5
]}

Bourcier, Valerie ^{[1
]}

Cagnot, Carole ^{[6
]}

Marcellin, Patrick ^{[7
]}

Guyader, Dominique ^{[8
]}

Pol, Stanislas ^{[9
,10
,11
]}

Larrey, Dominique ^{[12
]}

De Ledinghen, Victor ^{[13
]}

Ouzan, Denis ^{[14
]}

Zoulim, Fabien ^{[15
,16
]}

Roulot, Dominique ^{[17
]}

Tran, Albert ^{[18
,19
]}

Bronowicki, Jean-Pierre ^{[20
]}

Zarski, Jean-Pierre ^{[21
]}

Riachi, Ghassan ^{[22
]}

Cales, Paul ^{[23
]}

Peron, Jean-Marie ^{[24
]}

Alric, Laurent ^{[25
]}

Bourliere, Marc ^{[26
]}

Mathurin, Philippe ^{[27
]}

Blanc, Jean-Frederic ^{[28
]}

Abergel, Armand ^{[29
]}

Serfaty, Lawrence ^{[30
]}

Mallat, Ariane ^{[31
]}

Grange, Jean-Didier ^{[32
]}

Attali, Pierre ^{[33
]}

Bacq, Yannick ^{[34
]}

Wartelle, Claire ^{[35
]}

Thong Dao ^{[36
]}

Thabut, Dominique ^{[37
]}

Pilette, Christophe ^{[38
]}

Silvain, Christine ^{[39
]}

Christidis, Christos ^{[40
]}

Nguyen-Khac, Eric ^{[41
]}

Bernard-Chabert, Brigitte ^{[42
]}

Zucman, David ^{[43
]}

Di Martino, Vincent ^{[44
]}

Sutton, Angela ^{[45
,46
,47
]}

Roudot-Thoraval, Francoise ^{[4
,5
]}

Audureau, Etienne ^{[4
,5
]}

机构：

[1] Hop Jean Verdier, AP HP, Serv Hepatol, Bondy, France

[2] Univ Paris 13, Sorbonne Paris Cite, Equipe Labellisee Ligue Canc, F-93206 St Denis, Reunion, France

[3] INSERM, UMR 1162, Genom Fonct Tumeur Solides, F-75000 Paris, France

[4] Hop Henri Mondor, AP HP, Dept Sante Publ, F-94000 Creteil, France

[5] Univ Paris Est, A TVB DHU, CEpiA Clin Epidemiol & Aging, Unit EA4393,UPEC, F-94000 Creteil, France

[6] France REch Nord & Sud Sida HIV Hepatites FRENSH, ANRS, Unit Basic & Clin Res Viral Hepatitis, Clichy, France

[7] Hop Beaujon, AP HP, Serv Hepatol, Clichy, France

[8] CHU Pontchaillou, Serv Hepatol, Rennes, France

[9] Hop Cochin, AP HP, Dept Hepatol, Paris, France

[10] INSERM, UMS20, Paris, France

[11] Univ Paris 05, Inst Pasteur, U1223, Paris, France

[12] Hop St Eloi, Serv Hepatol, Montpellier, France

[13] Hop Haut Leveque, Serv Hepatol, Bordeaux, France

[14] Inst Arnaud Tzanck, Serv Hepatol, St Laurent Du Var, France

[15] Hosp Civils Lyon, Serv Hepatol, Lyon, France

[16] Univ Lyon, Lyon, France

[17] Hop Avicenne, AP HP, Serv Hepatol, Bobigny, France

[18] CHU Nice, Serv Hepatol, F-06202 Nice 3, France

[19] INSERM, U1065, C3M, Hepat Complicat Obes,Team 8, F-06204 Nice 3, France

[20] Univ Lorraine, CHU Nancy, Inserm 954, Vandoeuvre Les Nancy, France

[21] Hop Michallon, Serv Hepatol, Grenoble, France

[22] Hop Charles Nicolle, Serv Hepatol, Rouen, France

[23] CHU Angers, Serv Hepatogastroenterol, Angers, France

[24] Hop Purpan, Serv Hepatol, Toulouse, France

[25] CHU Toulouse, Serv Med Interne, Pole Digestif, UMR 152, Toulouse, France

[26] Hop St Joseph, Serv Hepatol, Marseille, France

[27] Hop Claude Huriez, Serv Hepatol, Lille, France

[28] Hop St Andre, Serv Hepatol, Bordeaux, France

[29] Hop Hotel Dieu, Serv Hepatol, Clermont Ferrand, France

[30] Hop St Antoine, AP HP, Serv Hepatol, Paris, France

[31] Hop Henri Mondor, AP HP, Serv Hepatol, Creteil, France

[32] Hop Tenon, AP HP, Serv Hepatol, Paris, France

[33] Hop Paul Brousse, AP HP, Serv Hepatol, Villejuif, France

[34] CHRU Tours, Hop Trousseau, Unite Hepatol, Tours, France

[35] Hop Aix En Provence, Serv Hepatol, Aix En Provence, France

[36] Hop Cote Nacre, Serv Hepatol, Caen, France

[37] Grp Hosp La Pitie Salpetriere, AP HP, Serv Hepatol, Paris, France

[38] CHU Le Mans, Serv Hepatol, Le Mans, France

[39] CHU Poitiers, Serv Hepatol, Poitiers, France

[40] Inst Mutualiste Montsouris, Serv Hepatol, Paris, France

[41] Hop Amiens Nord, Serv Hepatol, Amiens, France

[42] Hop Robert Debre, Serv Hepatol, Reims, France

[43] Hop Foch, Serv Med Interne, Suresnes, France

[44] Hop Jean Minjoz, Serv Hepatol, Besancon, France

[45] Grp Hosp Paris Seine St Denis, CRB Liver Dis Biobank, BB-0033-00027, Paris, France

[46] Hop Jean Verdier, AP HP, Serv Biochim, Bondy, France

[47] Univ Paris 13, INSERM, U1148, Bobigny, France

来源：

GASTROENTEROLOGY | 2018年 / 155卷 / 05期

关键词：

ANRS; CirVir; Liver Cancer; Risk Factors; CHRONIC HEPATITIS-C; SUSTAINED VIROLOGICAL RESPONSE; MARGINAL STRUCTURAL MODELS; ALL-CAUSE MORTALITY; REDUCES RISK; ASSOCIATION; SURVIVAL; RECURRENCE; MANAGEMENT; INFECTION;

D O I：

10.1053/j.gastro.2018.07.015

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

BACKGROUND & AIMS: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

引用

页码：1436 / +

页数：21

共 38 条

[1] Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: Data from three ANRS cohorts [J].