The role of oral antiviral therapy in hepatitis B-related hepatocellular carcinoma

Abstract

Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) in places where chronic hepatitis B infection is endemic. Oral nucleos(t)ide analog (NA) therapy can reduce the risk of HCC, but cannot completely prevent its development. For HBV-related HCCs, viral inhibition by NAs can preserve or improve liver function, thereby increasing the chance of therapeutic intervention. After surgical resection, NAs can prevent reactivation of HBV, and also reduce the chance of de novo development of HCC in the remnant liver. For those who undergo liver transplantation, NAs are essential to prevent reactivation and graft hepatitis, but is not likely to prevent HCC recurrence, which is due to metastatic disease. The role of NAs for non-curable advanced HCC is less well defined. These include patients undergoing locoregional therapy, chemotherapy, or palliation. Although antiviral therapy can preserve liver function, which may be compromised by HBV, it is unable to prevent disease progression from HCC. At the time of HCC diagnosis, most patients will already be receiving NAs, and these patients should be maintained on therapy. For patients not on antiviral therapy at the time of HCC diagnosis, the decision to commence therapy is often determined by the stage of HCC and life expectancy. Patients undergoing curative therapy, or locoregional therapy/chemotherapy with reasonable life expectancy, should be commenced on antiviral therapy. Key words:Antiviral therapy, hepatitis B virus, hepatocellular carcinoma ABSTRACTArticle history:

The optimal timing and management of hepatitis B and C in patients with hepatocellular carcinoma

“…Active viral replication of the HBV is associated with increased liver inflammation resulting in a risk of hepatocellular cancer even in the absence of underlying cirrhosis. This is thought to be due to the HBV deoxyribonucleic acid (DNA)'s integration into the host genome, which leads to genetic damage and malignant transformation (4,5). Metabolic syndrome, central obesity, and type 2 diabetes have also been independently associated with increased HCC risk in HBV-infected patients in China (6).…”

“…Even in the case of HCC, viral inhibition of HBV can help preserve or improve liver function, increasing the patient's chances of getting therapeutic intervention for their HCC (5). Although historically, interferon-α played a role in the treatment of chronic HBV, it is not used in the settings of cirrhosis or HCC given the risk of decompensation (5). Currently, studies support nucleos(t)ide analogue (NA) therapy, which is well tolerated and has a good safety profile, in patients with HBV-related HCC.…”

“…Currently, studies support nucleos(t)ide analogue (NA) therapy, which is well tolerated and has a good safety profile, in patients with HBV-related HCC. In the case of HCC, treatment of HBV is typically life-long and as such, only NAs with high potency and higher barriers to resistance such as entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide are recommended (5). Kim et al have demonstrated that in such patients, entecavir has demonstrated overall improved survival, decompensationfree survival, and recurrence-free survival compared to lamivudine (7).…”

“…If a patient is already on an NA at the time of their diagnosis of HCC, it is usually continued irrespective of the planned HCC management (5). If they are not on treatment yet, the decision to start an NA is based on the treatability of their HCC and overall prognosis since the purpose of treating HBV in these situations is to preserve liver function and prevent de novo or recurrent HCCs (5). The role of starting NAs for incurable, advanced HCC is not well defined, and their use in these situations may be futile.…”

Outcomes and Quality of Life of Systemic Therapy in Advanced Hepatocellular Carcinoma

“…Nonetheless, in a recent study, Cabibbo et al [58] argued that treatment of hepatitis C in patients with "active" HCC remains controversial as these patients were usually excluded in clinical trials. For HBV-related HCCs, treatment of hepatitis can preserve or improve liver function, and may be beneficial for patients undergoing curative therapy, or locoregional therapy/chemotherapy with reasonable life expectancy [59]. In HCC patients with variceal bleeding, 1-year and 2.5-year survival rates were 56.6% and 28.3%, respectively [52].…”