Risk of hepatocellular carcinoma in chronic hepatitis B: Assessment and modification with current antiviral therapy

Abstract

In the treatment of chronic hepatitis B (CHB), the ultimate goal is preventing hepatitis B virus (HBV)-associated liver disease, including hepatocellular carcinoma (HCC). Recently published studies show that in CHB patients treated with the currently recommended first-line nucleos(t)ide analogs (NAs) entecavir or tenofovir, annual HCC incidences range from 0.01% to 1.4% in non-cirrhotic patients, and from 0.9% to 5.4% in those with cirrhosis. In Asian studies including matched untreated controls, current NA therapy consistently resulted in a significantly lower HCC incidence in patients with cirrhosis, amounting to an overall HCC risk reduction of ∼30%; in non-cirrhotic patients, HCC risk reduction was overall ∼80%, but this was only observed in some studies. For patients of Caucasian origin, no appropriate comparative studies are available to date to evaluate the impact of NA treatment on HCC. Achievement of a virologic response under current NA therapy was associated with a lower HCC risk in Asian, but not Caucasian studies. Studies comparing entecavir or tenofovir with older NAs generally found no difference in HCC risk reduction between agents, except for one study which used no rescue therapy in patients developing lamivudine resistance. Overall, these data indicate that with the current, potent NAs, HCC risk can be reduced but not eliminated, probably due to risk factors that are not amenable to change by antiviral therapy, or events that may have taken place before treatment initiation. Validated pre- and on-therapy HCC risk calculators that inform the best practice for HCC surveillance and facilitate patient counseling would be of great practical value.

Deciphering the epidemiology of hepatocellular carcinoma through the passage of time: A study of 1,401 patients across 3 decades

“…A separate explanation to account for the decline of CHB‐related HCC is the positive impact of HBV treatment. Both interferon and nucleotide analogue‐based regimes have been shown to reduce the risk of HCC 22, 23, 24, 25. In addition, long‐term therapy with nucleotide analogues has been associated with the regression of fibrosis and cirrhosis, thus negating one of the important pathways of oncogenesis 26…”

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

“…It therefore represents the cornerstone endpoint of all our current therapeutic attempts. 1,25,[34][35][36][37][38][39][40] The level of HBV DNA suppression that should be attained in order to achieve these benefits is not well defined, but inferred that the lower, the better. Treatment-induced HBeAg loss and seroconversion to antiHBe characterises the induction of a partial immune control often leading to a low replicative phase of the chronic HBV 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.…”

“…Most of them, such as GAG-HCC, CU-HCC and REACH-B, have been developed and validated in Asian untreated CHB patients, 25 but they do not seem to offer good predictability in most studies including Caucasian CHB patients. 26,27 A recently developed and validated new score, PAGE-B, offers good predictability for HCC during the first 5 years of entecavir or tenofovir therapy in Caucasian, mostly European, CHB patients and can be easily applied in clinical practice, as it is based on widely available parameters (platelets, age, gender).…”

Management of Chronic Hepatitis B: An Overview of Practice Guidelines for Primary Care Providers

“…65 Recent data indicate that with the current potent NUCs, the risk of HCC risk can be reduced but not completely eliminated. 66 Thus regular HCC surveillance is recommended even in patients receiving anti-HBV treatment, and it has been shown to be a cost-effective strategy in CHB management. 67 The AASLD Practice Guidelines for Management of HCC recommend ultrasound every 6 months for HCC screening; ␣-fetoprotein, which has long been used for HCC diagnosis as well, has been shown to be insufficiently sensitive and specific for use as a surveillance assay.…”