4.7 Article

Role of hepatitis D virus infection in development of hepatocellular carcinoma among chronic hepatitis B patients treated with nucleotide/nucleoside analogues

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SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-021-87679-w

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  1. Center for Liquid Biopsy [KMU-TC108B06]
  2. Center for Cancer Research [KMU-TC108A04-3]
  3. Cohort Research Center [KMU-TC108B07]
  4. Kaohsiung Medical University [KMU-DK109002, MOST 108-2314-B-037-066-MY3]
  5. Kaohsiung Medical University Hospital [KMUH108-8R05]

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This study found that hepatitis D virus (HDV) viremia plays a crucial role in the development of hepatocellular carcinoma (HCC) in chronic hepatitis B patients undergoing nucleotide/nucleoside analogues (NAs) therapy, particularly in cirrhotic patients.
Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course of chronic hepatitis B (CHB) patients. Its role in patients treated with nucleotide/nucleoside analogues (NAs) is unclear. We aimed to study the role of hepatitis D in the development of HCC in CHB patients treated with NAs. Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. The incidence and risk factors of HCC development were analyzed. Rates of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The strongest factor association with HCC development was liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI] 9.98/5.11-19.46, P<0.001), followed by HDV RNA positivity (HR/ CI 5.73/1.35-24.29, P=0.02), age>50 years old (HR/CI 3.64/2.03-6.54, P<0.001), male gender (HR/CI 2.69/1.29-5.60, P: 0.01), and body mass index (BMI, HR/CI 1.11/1.03-1.18, P=0.004). The 5-year cumulative incidence of HCC was 7.3% for patients with HDV RNA negativity compared to that of 22.2% for patients with HDV RNA positivity (P=0.01). In the subgroup of cirrhotic patients, the factors associated with HCC development were HDV RNA positivity (HR/CI 4.45/1.04-19.09, P=0.04) and BMI (HR/CI 1.11/1.03-1.19, P=0.01). HDV viremia played a crucial role in HCC development in CHB patients who underwent NA therapy.

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