Factors associated with hepatocellular carcinoma occurrence after HCV eradication in patients without cirrhosis or with compensated cirrhosis

Abstract

The present study aimed to investigate the incidence of hepatocellular carcinoma (HCC) and factors related to HCC occurrence after direct-acting antiviral (DAA) treatment in the Fukushima Liver Academic Group (FLAG). We conducted a multicenter retrospective cohort study of 1068 patients without cirrhosis (NC) or with compensated liver cirrhosis (LC) who achieved a sustained virologic response (SVR). First, we compared the cumulative HCC incidence and survival rates in NC (n = 880) and LC (n = 188) patients without a history of HCC treatment. Second, we performed multivariate analysis of factors related to HCC occurrence after DAA treatment. Overall, the average age was 65 years, and the male/female ratio was 511/557. Thirty-nine (4%) patients developed HCC. The cumulative 4-year HCC incidence and survival rates were 3.0% and 99.8% in NC patients and 11.5% and 98.5% in LC patients, respectively. The independent factors affecting HCC occurrence identified by multivariate analysis were the serum albumin (ALB) level before SVR for NC patients and the ALBI score, platelet count, and diabetes before SVR for LC patients. The factors related to HCC occurrence differed between NC and LC patients. Careful surveillance of post-SVR patients with these risk factors is needed.

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

“…Finally, 5 authors reported data on patients with advanced fibrosis, defined through histology (F3-F4), non-invasive tests or criteria for chronic advanced liver disease (cACLD) 11 , 36 , 43–46 ( Table 2 ). Eight out of these studies enrolled only patients with an SVR, 10 , 21 , 30 , 33 , 37 , 44–46 whilst in one study data could be extrapolated. 34 In studies including also non-SVR patients, rates of treatment failure ranged between 1.9% and 10% ( Table 2 ).…”

“…In F3-F4 patients, Alonso Lopez et al found that both baseline FIB-4 >3.7 and FIB-4 >3.3 one year after treatment were associated with de-novo HCC 45 ( Table 7 ). Other NITs had been investigated as predictors of HCC in several studies: the albumin-bilirubin (ALBI) score grade 2–3 29 , 37 , 42 and AST to platelet (PLT) ratio index (APRI) >2.5 11 emerged as independent risk factors for de-novo HCC in patients with cirrhosis and advanced fibrosis, respectively.…”

“… 38 Thus, among indirect markers of PH were both biochemical tests and clinical features. For example, albumin 20 , 31 , 37 , 44 , 45 and PLT 20 , 21 , 27 , 29 were independently associated with HCC occurrence, either as single predictors or when included in predictive scores ( Tables 6 and 7 ). The presence of esophageal varices (EV) 28 or ascites was associated with an increased the risk of de-novo HCC.…”

“…Clinical scores incorporating these parameters, such as Child-Pugh-Turcotte (CPT) 25 , 36 and Model for End Stage Liver Disease (MELD) 41 or ALBI scores 29 , 37 , 42 were independently associated with de-novo HCC in cirrhotics ( Table 7 ). Some studies provided different CumI of de-novo HCC according to the combination of one or more variables associated with portal hypertension (see below).…”

“…In US cohorts, a role of non-African American ethnicity has been suggested, 34 , 41 although this association deserves further confirmation. Among comorbidities, diabetes mellitus (DM) has been associated with an increased risk of HCC in several cohorts; 22 , 26 , 31 , 36 , 37 Abe et al incorporated DM status in a multivariable HCC risk score (see below) ( Table 7 ). Other factors such as alcohol consumption, 21 , 41 and viral co-infections 11 are likely to influence post-SVR HCC risk, although these patients were systematically excluded from most clinical trials.…”