The assessment of hepatocellular carcinoma risk in patients with chronic hepatitis B under antiviral therapy

Abstract

Hepatocellular carcinoma (HCC) is a primary concern for patients with chronic hepatitis B (CHB). Antiviral therapy has been reasonably the focus of interest for HCC prevention, with most studies reporting on the role of the chronologically preceding agents, interferon-alfa and lamivudine. The impact of interferon-alfa on the incidence of HCC is clearer in Asian patients and those with compensated cirrhosis, as several meta-analyses have consistently shown HCC risk reduction, compared to untreated patients. Nucleos(t)ide analogues also seem to have a favorable impact on the HCC incidence when data from randomized or matched controlled studies are considered. Given that the high-genetic barrier agents, entecavir and tenofovir, are mainly used in CHB because of their favorable effects on the overall long-term outcome of such patients, the most clinically important challenge is the identification of patients who require close HCC surveillance despite on-therapy virological remission. Several risk scores have been developed for HCC prediction in CHB patients. Most of them, such as GAG-HCC, CU-HCC and REACH-B, have been developed and validated in Asian untreated and treated CHB patients, but they do not seem to offer good predictability in Caucasian CHB patients for whom a newer score, PAGE-B, has been recently developed.

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…24,25 Long-term therapy with NAs appears to favourably impact HCC incidence when data from randomised or matched controlled studies are considered. 24,25 After the first 5 years of ETV or TDF therapy in CHB patients, recent data suggest that the HCC incidence is decreasing further, with the decrease being more evident in patients with baseline cirrhosis. 93 In addition, HCC seems to be the only factor affecting longterm survival in ETV or TDF treated CHB patients with or without compensated cirrhosis.…”

“…121 In addition, old cohort studies with standard IFNa and systematic reviews show that the incidence of HCC is decreased in IFNa treated compared to untreated CHB patients, with such an effect being clearer in Asian patients and those with sustained off-treatment responses and/or compensated cirrhosis. 1,24 Cohort studies in both HBeAg-positive and HBeAg-negative CHB have shown that courses of standard IFNa treatment result in improved overall long-term outcomes including survival in patients with sustained off-treatment responses. 1 Survival data are not available for PegIFNa therapy, but the same favourable outcomes are expected if sustained off-treatment responses are achieved.…”

“…23 HCC is currently the main concern for diagnosed CHB patients and may develop even in patients who have been effectively treated. 24 The risk of developing HCC is higher in patients with one or more factors that relate to the host (cirrhosis, chronic hepatic necroinflammation, older age, male sex, African origin, alcohol abuse, chronic co-infections with other hepatitis viruses or human immunodeficiency virus [HIV], diabetes or metabolic syndrome, active smoking, positive family history) and/or to HBV properties (high HBV DNA and/or HBsAg levels, HBV genotype C > B, specific mutations). 24 The above factors seem to affect the progression to cirrhosis in untreated CHB patients.…”

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“…12 Along these lines, inhibiting the replication of HBV or completely eliminating HCV from the body could prevent hepatocarcinogenesis in patients with viral hepatitis. 9,[20][21][22] Several clinical trials and observational studies have reported the beneficial effects of antiviral treatment for preventing HCC through persistent viral suppression. 21,22 Although current antivirals' elimination effect on covalently closed circular DNA is imperfect, inhibiting viral replication and improving necroinflammatory activity using antivirals are expected to reduce substantially the risk of HCC in patients with chronic HBV infection.…”

The summarized of EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…Unfortunately, HCC may still develop. Previous studies have shown that long-term ETV or TDF monotherapy appears to favorably affect the incidence of HCC (8,10,11), especially in those patients, who have received more than 5 years of antiviral therapy (11). Since HCC seems to be the only predictive factor affecting long-term survival in-treated patients, the main clinical challenge is to identify the patients at risk of HCC who require close surveillance.…”