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Failure to Attain SVR With DAAs Tied to Shorter HCC-Free Survival
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AASLD, The Liver Meeting, November 12-15, 2021
Mark Mascolini
Failure to attain sustained virologic response (SVR) with direct-acting antivirals (DAAs) for HCV infection predicted worse 2-year hepatocellular carcinoma (HCC)-free survival in in a 2214-person prospective Italian cohort [1]. High pre-DAA liver stiffness predicted death with HCC.
Despite HCV eradication with DAAs in high proportions of treated people, risk of HCC persists in those with cirrhosis. To explore the medium- to long-term impact of DAA therapy on subsequent HCC diagnosis in people with cirrhosis, investigators working with the prospective observational multicenter PITER cohort in Italy [2,3] conducted this study.
From 30 clinical centers across Italy, PITER investigators chose consecutive DAA-treated cohort members with cirrhosis. Everyone had at least 1 year of follow-up after completing DAA therapy. The study excluded people who had a liver transplant or a previous HCC diagnosis.
The analysis involved 2214 people, 149 of whom (6.7%) had an HCC diagnosis after completing DAA therapy. Median follow-up since DAA therapy ended lasted 30 months (interquartile range 14 to 43 months). Overall HCC incidence stood at 2.8 per 100 person-years, meaning HCC developed in about 3 of every 100 people each year.
Compared with people who remained free of HCC, those with new HCC were older (median 67 vs 64 years, P = 0.002) and had a higher (worse) pre-DAA liver stiffness measurement (median 21.8 vs 18.8 kPa, P = 0.008), a higher proportion with a platelet count below 150,000/μL (87.6% vs 70.6%, P < 0.001), a higher proportion with albumin below 3.5 g/dL (44.4% vs 23.7%, P < 0.001), a lower proportion with FIB-4 below 3.25 (17.4% vs 33%, P < 0.001), a lower proportion with Child-Pugh class A (78.5% vs 85%, P = 0.035), a higher proportion with ascites (13.45 vs 7.1%, P = 0.005), a higher proportion with esophageal varices (35.6% vs 22.1%, P < 0.001), and a higher proportion with previous hepatic decompensation (17.5% vs 11.1%, P = 0.015). People with versus without an HCC diagnosis did not differ in body mass index, alcohol use, HCV genotype, or HBV or HIV coinfection.
A higher proportion of people without new HCC had a neuropsychiatric diagnosis (about 12% vs 5%, P = 0.015), but the groups did not differ in rates of other comorbidities like hematologic cancer, solid tumors, abnormal lipids, cerebrovascular disease, cardiovascular disease, or diabetes.
Kaplan-Meier analysis indicated 2-year HCC-free survival in a higher proportion of people who achieved SVR than in those who did not (98% vs 65%, P < 0.001). Cox forward stepwise selection analysis pinpointed 4 variables that independently predicted HCC after DAA therapy, at the following adjusted hazard ratios (aHR) (and 95% confidence intervals).
- Older age: aHR 1.06 (1.04 to 1.09)
- HCV genotype 3 (vs others): aHR 3.51 (1.70 to 6.86)
- Platelets below vs above 150,000/μL: aHR 2.43 (1.28 to 4.61)
- Albumin below vs above 3.5 g/dL: aHR 2.36 (1.52 to 3.67)
This analysis linked 3 other variables to HCC after DAA therapy, but these associations stopped short of statistical significance:
- Male sex: aHR 1.40 (0.90 to 2.19)
- Anti-HBc positivity: aHR 1.54 (0.96 to 2.48)
- Diabetes: aHR 1.53 (0.96 to 2.44)
This analysis did not consider attaining SVR.
Barcelona clinic liver cancer (BCLC) staging was stage B or C in 80% of cohort members in whom HCC developed. During follow-up in this study, 26% of participants died and 7.6% had a liver transplant. Among people alive at the end of follow-up, 38% had active HCC.
In participants who remained free of HCC during the study, baseline (pre-DAA) liver stiffness of 18 kPa fell to 13 kPa after DAA therapy. In people diagnosed with HCC, baseline liver stiffness of 22 kPa fell to 18 kPa after therapy (P < 0.05 for difference between no-HCC and HCC groups). An adjusted Cox regression model linked high pre-DAA liver stiffness (ranging from 17 to 31 kPa) to death (aHR 1.05, 95% CI 1.01 to 1.09).
The PITER researchers called for active post-DAA patient monitoring, "possibly with the aid of prognostic predictors," to detect and manage HCC quickly.
References
1. Kondili LA, Quaranta MG, Cavalletto L, et al. De novo hepatocellular carcinoma occurrence following the HCV viral eradication by direct acting antivirals (DAA): medium to long term observations from the ongoing PITER cohort. The Liver Meeting, November 12-15, 2021. Parallel session 14: Hepatitis C Oral Session.
2. ClinicalTrials.gov. Observational study in HCV chronic infection. ClinicalTrials.gov identifier NCT01945008. https://clinicaltrials.gov/ct2/show/NCT01945008
3. Quaranta MG, Ferrigno L, Tata X, et al. Liver function following hepatitis C virus eradication by direct acting antivirals in patients with liver cirrhosis: data from the PITER cohort. BMC Infect Dis. 2021. Article number 413. https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06053-3
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