Low incidence of HCC in chronic hepatitis C patients with pretreatment liver stiffness measurements below 17.5 kilopascal who achieve SVR following DAAs

Abstract

Background and aims To evaluate the ability of pretreatment liver stiffness measurements (pLSM) to predict hepatocellular carcinoma (HCC), incident decompensation and all-cause mortality in chronic hepatitis C (CHC) patients who achieved sustained virological response (SVR) after treatment with direct-acting antivirals (DAAs). Methods 773 CHC patients with SVR after DAA treatment and no prior liver complications were identified retrospectively. Optimized cut-off of 17.5 kPa for incident HCC was selected by maximum Youden’s index. Patients were grouped by pLSM: <10 kPa [reference], 10–17.4 kPa and ≥17.5 kPa. Primary outcomes were incident hepatocellular carcinoma and secondary outcomes were incident decompensated cirrhosis and all-cause mortality, analyzed using cox-regression. Results Median follow-up was 36 months and 43.5% (336) had cirrhosis (LSM>12.5 kPa). The median pLSM was 11.6 kPa (IQR 6.7–17.8, range 2.5–75) and pLSM of <10 kPa, 10–17.4 kPa and 17.5–75 kPa was seen in 41.5%, 32.2% and 26.3%. During a median follow-up time of 36 months, 11 (1.4%) developed HCC, 14 (1.5%) developed decompensated cirrhosis, and 38 (4.9%) patients died. A pLSM of 17.5 kPa identified patients with a high risk of HCC with a negative predictive value of 98.9% and incidence rate of HCC in the 17.5–75 kPa group of 1.40/100 person years compared to 0.14/100 person years and 0.12/100 person years in the 10–17.4 kPa and <10 kPa groups, p<0.001. Conclusion Pretreatment LSM predicts risk of HCC, decompensation and all-cause mortality in patients with SVR after DAA treatment. Patients with a pLSM <17.5 kPa and no other risk factors for chronic liver disease appear not to benefit from HCC surveillance for the first 3 years after treatment. Longer follow-up is needed to clarify if they can be safely excluded from post treatment HCC screening hereafter.

Hepatitis C virus: A critical approach to who really needs treatment

“…Recent reports indicate that HCV patients may also die from liver-related complications even after SVR[ 154 , 177 ]. Likewise, all-cause mortality is still high after SVR in cirrhotic patients[ 178 ]. SVR after IFN-based treatment offered no survival benefit after 10 years of follow-up even in the specific group of hemophiliacs[ 142 ].…”

“…Maintenance of glycated hemoglobin level below 7.0% reduced the development of HCC[ 292 ]. Diabetes was independently associated with both de novo HCC occurrence and HCC recurrence after DAA treatment[ 178 , 293 ]. A systematic review of seven cohort and two case-control studies has confirmed the significant contribution of T2DM in the development of HCC in HCV-infected patients[ 278 ].…”

Predicting Hepatocellular Carcinoma Risk in Patients with Chronic HCV Infection and a Sustained Virological Response to Direct-Acting Antivirals

“…Baseline LSM obtained by Acoustic Radiation Force Impulse (ARFI) or TE, was associated with an increased risk of post-treatment HCC ( Table 5 ) in three studies analysing SVR patients. 53 , 56 , 57 Tachi et al identified the 1.73 m/s threshold as the optimal cut-off to stratify CHC patients according to their de-novo HCC risk 56 ( Table 5 ). In the other two studies, baseline LSM ≥20 kPa and ≥17.5 kPa were associated with HCC occurrence in 398 and 773 CHC patients from Japan and Denmark, respectively.…”

“…In both studies, the prevalence of cirrhosis was not reported. 53 , 57 Ogasawara et al reported that also SVR24-LSM (ie, LSM performed 24 weeks after EOT) ≥10 kPa was independently associated with de-novo HCC. 57 This finding was in line with two other Japanese studies, identifying in LSM ≥3.75 kPa obtained through Magnetic Resonance Elastography (MRE) 12 weeks after treatment completion (SVR12-MRE) an independent predictor of HCC occurrence.…”

“…Male gender and age independently predicted HCC occurrence also in CHC cohorts. Male gender was associated with de-novo HCC in 5 40 , 50 , 55 , 59 , 60 studies, and age in 7 40 , 41 , 48 , 52 , 53 , 55 , 58 ( Table 5 ). Although age was analysed as a continuous variable in multivariate analysis, different cut-offs were associated with increased risks of HCC (>60, >62, >75 years).…”