HCV cure by IFN-free DAAs is associated with increased survival in patients with HCV-related - PowerPoint Presentation

1. HCV cure by IFN-free DAAs is associated with increased survival in patients with HCV-related HCCHansen Dang,1,2* Yee Hui Yeo,1* Satoshi Yasuda,3 Chung-Feng Huang,4 Etsuko Iio,5 Charles Landis,6 Dae Won Jun,7 Masaru Enomoto,8 Eiichi Ogawa,9 Pei-Chien Tsai,4 An Le,1 Matthew Liu,6 Mayumi Maeda,1 Brian Nguyen,1 Nathan Ramrakhiani,1 Linda Henry,1 Ramsey Cheung,1,10 Akihiro Tamori,8 Takashi Kumada,3 Yasuhito Tanaka,5 Ming-Lung Yu,4 Hidenori Toyoda,3 Mindie H. Nguyen.1 Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USAUniversity of California, Davis, Davis, CA, USADepartment of Gastroenterology, Ogaki Municipal Hospital, Ogaki, JapanHepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanDepartment of Gastroenterology, University of Washington Medical Center, Seattle, Washington, USADepartment of Gastroenterology, Hanyang University, Seoul, South KoreaDepartment of Hepatology, Osaka City University Graduate School of Medicine, Osaka, JapanDepartment of General Internal Medicine, Kyushu University Hospital, Fukuoka, JapanDivision of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USAHansen DangStanford University

2. Financial disclosuresFunding: No external funding to disclose

3. BackgroundHepatitis C virus (HCV) affects approximately 71.1 million worldwide1Leading cause for liver cancer-related deaths2Interferon (IFN)-based therapy: improved survival in HCV-related HCC patients with compensated cirrhosis3However, IFN therapy utilization is limited due to its side effect profileDirect acting antivirals (DAAs): well tolerated, high sustained virologic response (SVR) rates even in decompensated and HCC patients4,5Polaris Observatory. Lancet Gastroenterol Hepatol. 2017Stanaway JD, et al. Lancet. 2016.Bruno S, et al. Liver Int. 2017Ji F, et al. Aliment Pharmacol Ther. 2018.Curry MP, et al. NEJM. 2015.

4. AimsCompare the survival rates between HCV-related HCC patients who did not receive any antiviral therapy (untreated group) vs. those who achieved SVR with IFN-free DAA therapy (SVR group)HCV-related HCC patientsVS.Treatment naïve to antiviral therapyDAA-treated with SVR

5. Individual chart review real-world cohort retrospective study*Patients were matched by age, sex, study country, cirrhosis, ALBI score, Milan Criteria, HCC treatment, and AFP

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7. TimeCensor date:Time of death or lost to follow-upIndex date: HCC diagnosisInitiated DAA prior to HCC diagnosisKeep if achieved SVR ≤ 6 months prior to HCC diagnosis6 monthsUnexposed period in SVR cohort: Time from HCC diagnosis to DAA initiationInitiated DAA post HCC diagnosis(Time-varying adjustment)Exposed period in SVR cohort: Time from DAA initiation to Censor date

8. DefinitionsHCV: positive HCV RNA PCR, HCV antibody test, history of anti-HCV therapy, or documented history of HCV. Cirrhosis: pathology reports, radiology reports, laboratory records, endoscopy, or physician notes HCC: confirmed based on the AASLD guidelinesSVR: undetectable HCV RNA (<25 IU/mL) after 12 weeks from treatment end dateHCC treatment: curative (liver transplant, surgical resection, or radiofrequency ablation with curative intent), palliative [transarterial chemoembolization (TACE) or sorafenib]

9. Overall cohort: Baseline characteristicsCharacteristicsUntreated for HCV (n = 1239)SVR (n = 437)P-valueAge66.77 ± 9.6365.92 ± 9.380.11Male 796 (64.25)261 (59.73)0.092Body mass index (kg/m2) (n = 1381)24.82 ± 5.0224.77 ± 5.090.89Race/EthnicityNon-Asian340 (27.44)136 (31.12)0.14Asian899 (72.56)301 (68.88)Diabetes mellitus (n = 1577)327 (28.02)131 (31.95)0.13Cirrhosis (n = 1641)977 (81.15)367 (83.98)0.19Child-Pugh class (n = 1497)   A641 (55.93)256 (72.93)<0.001B449 (39.18)85 (24.22)C56 (4.89)10 (2.85)Model for end-stage liver disease score (n = 1486)8.74 (7.29 – 11.24)8.19 (6.79 – 10.19)<0.001ALBI grade (n = 1544)   1229 (19.46)120 (32.70)<0.0012774 (65.76)218 (59.40)3174 (14.78)29 (7.90)

10. Overall cohort: Tumor characteristicsCharacteristicsUntreated for HCV (n = 1239)SVR (n = 437)P-valueAlpha fetoprotein (log10 ng/mL) (n = 1537)1.75 ± 1.061.36 ± 0.71<0.001BCLC stage (n = 1445)  0/A628 (57.35)280 (80.00)<0.001B235 (21.46)41 (11.71)C/D232 (21.19)29 (8.29)Milan criteria792 (63.92)347 (79.41)<0.001HCC treatment (n = 1648)  Palliative treatment810 (65.38)111 (27.14)<0.001Curative treatment429 (34.62)298 (72.86)

11. PSM cohort: Baseline characteristicsCharacteristicsUntreated for HCV (n = 321)SVR(n = 321)P-valueAge65.92  9.1366.39  9.090.52Male194 (60.44)197 (61.37)0.81Body mass index (kg/m2) (n = 533)24.59  4.4124.87  5.060.50Race/Ethnicity   Non-Asian108 (33.64)100 (31.15)0.50Asian213 (66.36)221 (68.85)Diabetes mellitus (n = 612)80 (26.58)98 (31.51)0.18Cirrhosis265 (82.55)262 (81.62)0.76CPT class (n = 494)   A167 (68.44)168 (67.20)0.79B66 (27.05)73 (29.20)C11 (4.51)9 (3.60)Median MELD score (n = 491)8.41 (6.87-10.64)8.47 (7.34-10.71)0.26ALBI grade   1100 (31.15)102 (31.78)0.912191 (59.50)192 (59.81)330 (9.35)27 (8.41)*Patients were matched by age, sex, study country, cirrhosis, ALBI score, Milan Criteria, HCC treatment, and AFP

12. PSM cohort: Tumor characteristicsCharacteristicsUntreated for HCV (n = 321)SVR(n = 321)P-valueAFP (log10 ng/mL)1.35  0.861.39  0.740.61BCLC stage (n = 588)   0/A209 (72.57)239 (79.67)0.13B45 (15.62)35 (11.67)C/D34 (11.81)26 (8.67)Milan248 (77.26)259 (80.69)0.29HCC treatment   Palliative treatment97 (30.22)92 (28.66)0.67Curative treatment224 (69.78)229 (71.34)*Patients were matched by age, sex, study country, cirrhosis, ALBI score, Milan Criteria, HCC treatment, and AFP

13. PSM cohort: Lower 5-year overall mortality and liver-related mortality in SVR patients vs untreated patients90.90% vs. 68.76% 87.78% vs. 66.05%All-cause mortalityLiver-related mortality

14. Predictors of mortality in HCV-related HCC patientsType of mortalityHCV treatment statusAdjusted HR* (95% CI) P-valueAll-cause Untreated for HCVReferentReferentSVR0.37 (0.16 – 0.83)0.016Liver-related Untreated for HCVReferentReferentSVR0.34 (0.13 – 0.88)0.026*Adjusted for age, sex, race/ethnicity, study country/region, diabetes, cirrhosis, MELD score, HCC diagnosis year, AFP, BCLC stage, and HCC treatment type

15. ConclusionsIn well-matched SVR and untreated HCV-related HCC patients, SVR from IFN-free DAA therapy had 60-70% improvement in both all-cause and liver-related 5-year survival compared to untreated patients. Patients eligible for HCC therapy (curative or palliative) should also be considered for DAAs.

16. SummarySummary

17. Dr. Mindie H. Nguyen (Mentor), Dr. Ramsey Cheung, Hansen Dang, Dr. Yee Hui Yeo, An Le, Dr. Mayumi Maeda, Brian Nguyen, Nathan Ramrakhiani, Dr. Linda Henry Dr. Hidenori Toyoda, Dr. Takashi Kumada, Dr. Satoshi YasudaDr. Ming-Lung Yu, Dr. Chung-Feng Huang, Dr. Pei-Chien TsaiDr. Yasuhito Tanaka, Dr. Etsuko IioDr. Charles Landis, Matthew LiuDr. Dae Won JunDr. Masaru Enomoto, Dr. Akihiro TamoriDr. Eiichi Ogawa

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