Clinical Edge Journal Scan

Consider hepatitis D testing for patients receiving nucleoside analogues

Dr. Damjanov scans the journals, so you don’t have to!

Publish date: May 17, 2021

Author(s):

Nevena Damjanov, MD

Clinical Edge Journal Scan: HCC May 2021 (1 of 9)

Nevena Damjanov, MD

This month’s articles investigate earlier diagnosis of new or recurrent hepatocellular carcinoma (HCC). The first study looked at patients with hepatitis B virus (HBV) infection, trying to identify those at higher risk for developing HCC despite treatment with antiviral therapy. It is well known that patients with chronic hepatitis B virus infection have a higher incidence of HCC than uninfected patients. In a single-center 1,349 patient retrospective analysis, Jang et al. evaluated the prevalence of hepatitis D virus (HDV) co-infection in patients who were receiving HBV treatment with nucleoside analogues, and the subsequent development of HCC. The prevalence of anti-HDV in these patients was 2.3%, while the rate of HDV RNA positivity was 1%. The authors found that the presence of detectable HDV RNA increased the five-year cumulative rate of HCC to 22.2%, compared to the 7.3% incidence of HCC in patients with undetectable HDV RNA (p=0.01). Their conclusion was that testing for hepatitis D virus should be considered in patients who are receiving nucleoside analogues for the treatment of HBV, since that identifies patients who remain at higher risk of developing HCC.

The next study explored ways to identify patients who have HCC using PIVKA-II (prothrombin induced by vitamin K deficiency/antagonist – II), a promising marker that may be more sensitive/specific than AFP in identifying patients with liver cancer. Feng et al. used enzyme-linked immunosorbent assay (ELISA) to measure serum PIVKA-II levels in 168 patients with HCC, 150 patients with benign liver disease, and 153 healthy controls. Patients with HCC had significantly higher median PIVKA-II levels (181.50 mAu/mL), compared with atients with noncancerous liver disease (28.6 mAU/mL) or healthy controls 21.82 mAU/mL), with p<0.0001. In addition, PIVKA-II was more sensitive (83.9% vs 64.3%) and more specific (91.5% vs 84.7%) than AFP in identifying patients with HCC. When PIVKA-II and AFP were combined, sensitivity (81.95%) and specificity (89.3%) were increased more, suggesting that this combination of markers may be most useful in clinical practice to identify patients who have HCC.

Finally, in patients whose HCC was treated with orthotopic liver transplantation, acute organ rejection was found to be linked to HCC recurrence. Gul-Klein et al. identified 252 patients who underwent liver transplantation for HCC between 2001 and 2015, 91 of whom had confirmed acute rejection, and 47 of whom had recurrent HCC (the median time to HCC recurrence was 20 months). HCC recurrence was identified in 28.6% of patients with acute rejection, and in 13% of patients without acute rejection (p=0.002). Acute rejection within 20 months of liver transplantation was identified as a significant risk factor for HCC recurrence in multivariate analysis (hazard ratio of 2.91). The authors suggested that more intensive monitoring for HCC recurrence may be appropriate for patients who have evidence of acute rejection.