The risk of hepatocellular carcinoma within and beyond the first 5 years of entecavir in Korean patients with chronic hepatitis B

Kim, Byung Gyu; Park, Neung Hwa; Lee, Seung Bum; Jeon, Soyoung; Park, Jae Ho; Jung, Seok Won; Jeong, In Du; Bang, Sung-Jo; Shin, Jüng Woo

doi:10.1111/liv.13938

Cited by 23 publications

(21 citation statements)

References 36 publications

(47 reference statements)

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“…and Zhang et al 36 . In contrast, two recent long‐term studies 37,38 reported that there was no difference in the risk of cancer. One possible reason is that the incidence of HCC associated with the two drugs might be influenced by treatment time.…”

Section: Discussionmentioning

confidence: 97%

Comparison of tenofovir versus entecavir on reducing incidence of hepatocellular carcinoma in chronic hepatitis B patients: A systematic review and meta‐analysis

Yao

Shen

et al. 2020

J of Gastro and Hepatol

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Background and Aim: Studies had shown that tenofovir (TDF) and entecavir (ETV) are widely used as the first-line therapy to inhibit hepatitis B virus replication, which can reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients, but it was unclear which nucleos(t)ide analogue was most effective. Therefore, we performed a meta-analysis and a systematic review to compare the incidence of HCC in CHB patients who are either on TDF or ETV. Methods: For this study, the following databases were searched for clinical trials published from its inception until November 2019: PubMed, Web of Science, MEDLINE, Embase, and Cochrane Library. Results: A total of 11 eligible studies were selected, including 70 864 patients. The meta-analysis showed that TDF was superior to ETV with regard to the incidence of HCC, the incidence of death or transplantation, and virologic response. There were no significant differences in terms of biochemical response and loss of seroconversion response among the entire cohort. Conclusions: The conclusion was that CHB patients treated with TDF had a reduced incidence of HCC compared with patients treated with ETV.

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Section: Discussionmentioning

confidence: 97%

Comparison of tenofovir versus entecavir on reducing incidence of hepatocellular carcinoma in chronic hepatitis B patients: A systematic review and meta‐analysis

Yao

Shen

et al. 2020

J of Gastro and Hepatol

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“…Although direct comparison is difficult, this rate was lower than the annual incidence rate of HCC in cirrhotic patients (3-7%), [45][46][47] but was higher than the yearly incidence rate of HCC (0.7-1.7%) in chronic hepatitis B patients who received antiviral therapy (AVT) for 5 years. 48,49 For those with any risk factors, the HCC recurrence risk for the next 5 years (5-10 years) was substantial (24.5-71.4%). We also noticed that the HCC recurrence risk was substantial among 100 patients without HBV, HCV, or cirrhosis, even after 5 recurrence-free years.…”

Section: Discussionmentioning

confidence: 99%

Substantial risk of recurrence even after 5 recurrence-free years in early-stage hepatocellular carcinoma patients

et al. 2020

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Background/Aims: Although hepatocellular carcinoma (HCC) is notorious for its high recurrence rate, some patients do not experience recurrence for more than 5 years after resection or radiofrequency ablation for early-stage HCC. For those with five recurrence-free period, the risk of HCC recurrence within the next 5 years remains unknown.Methods: A total of 1,451 consecutive patients (median, 55 years old; males, 79.0%; hepatitis B virus-related, 79.3%) with good liver function (Child-Pugh class A) diagnosed with early-stage HCC by Barcelona Clinic Liver Cancer Staging and received radiofrequency ablation or resection as an initial treatment between 2005 and 2010 were analyzed.Results: During a median follow-up period of 8.1 years, 961 patients (66.2%) experienced HCC recurrence. The cumulative recurrence rates increased to 39.7%, 60.3%, and 71.0% at 2, 5, and 10 years, respectively, and did not reach a plateau. Five years after HCC diagnosis, 487 patients were alive without experiencing a recurrence. Among them, during a median of 3.9 additional years of follow-up (range, 0.1–9.0 years), 127 patients (26.1%) experienced recurrence. The next 5-year cumulative recurrence rate (5–10 years from initial diagnosis) was 27.0%. Male sex, higher fibrosis-4 scores, and alpha-fetoprotein levels at 5 years were associated with later HCC recurrence among patients who did not experience recurrence for more than 5 years.Conclusions: The HCC recurrence rate following 5 recurrence-free years after HCC treatment was high, indicating that HCC patients warrant continued HCC surveillance, even after 5 recurrence-free years.

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“…On the other hand, Kim et al reported that the annual HCC incidence did not decrease significantly within and after the first 5 years of ETV treatment in a single‐center cohort of Korean patients either with or without cirrhosis. However, the annual incidence of HCC was significantly lower after 7 years of treatment than within the first 7 years in patients with cirrhosis 13 . Kim et al conducted a multicenter retrospective cohort study from Korea to develop an HCC risk score (mPAGE‐B), indicating that the annual incidence of HCC decreased significantly after 4 years of ETV/TDF treatment compared with within the first 4 years treatment, both in low‐risk (mPAGE‐B score ≤ 8), intermediate‐risk (mPAGE‐B score 9–12), and high‐risk (mPAGE‐B score ≥ 13) patients 37 .…”

Section: Resultsmentioning

confidence: 85%

“…We identified four studies that addressed changes in the incidence rate of HCC over time during treatment, 13,36–38 and baseline characteristics were summarized in Table S4. Papatheodoridis et al reported in a multicenter European study that the annual HCC incidence was significantly lower after 5 years of treatment than within the first 5 years of ETV/TDF treatment in Caucasian patients with cirrhosis.…”

Section: Resultsmentioning

confidence: 99%

“…age and gender) and clinical variables (e.g. diabetes, serum platelet count, and dynamic change of virological markers during antiviral therapy) have been variably reported to be associated with HCC risk among treated patients 11–18 . Predictive risk scores have incorporated some of these determinants; however, the performance and generalizability of these scores are unclear.…”

Section: Introductionmentioning

confidence: 99%

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Magnitude of and prediction for risk of hepatocellular carcinoma in patients with chronic hepatitis B taking entecavir or tenofovir therapy: A systematic review

Tseng

Hsu

et al. 2020

J of Gastro and Hepatol

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Background and Aim: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have been shown to reduce incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This systematic review aims to evaluate the magnitude, change over time, and prediction of residual HCC risks in CHB patients treated with ETV/TDF therapy. Methods: Available literature was systematically reviewed through searches of PubMed and EMBASE databases from January 1, 2006 to September 1, 2019, to identify cohort studies that reported HCC incidence in CHB patients during ETV/TDF therapy. Studies were screened by title and abstract and then evaluated for eligibility in terms of full text. Results: We identified 141 studies for full-text review, and 34 were eligible for analysis. From 19 studies with data separated by cirrhosis status, the 5-year cumulative incidence of HCC was 0.5-6.9% in patients without cirrhosis, 4.5-21.6% in compensated cirrhosis, and 36.3-46.5% in decompensated cirrhosis. All four studies that addressed temporal changes in HCC risks consistently found the incidence rate decreased over time in patients with cirrhosis, although the findings were inconsistent in patients without cirrhosis. Six predictive scores were developed and validated to predict incident HCC during ETV/TDF therapy in CHB patients. Common scoring variables included age, sex, cirrhosis (fibrosis grade), and hepatic function. Conflicting results were reported in seven individual studies and two meta-analyses that compared ETV versus TDF. Conclusions: The residual risk of HCC remains during ETV/TDF treatment in CHB patients with cirrhosis but declines over time. Risk stratification is attainable by validated pre-Merck.

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The risk of hepatocellular carcinoma within and beyond the first 5 years of entecavir in Korean patients with chronic hepatitis B

Abstract: The incidence rate of HCC may not change significantly before and after 5 years of ETV therapy in Korean CHB patients. The risk of HCC in Asian CHB patients may remain in the long-term.

Cited by 23 publications

References 36 publications

Comparison of tenofovir versus entecavir on reducing incidence of hepatocellular carcinoma in chronic hepatitis B patients: A systematic review and meta‐analysis

Comparison of tenofovir versus entecavir on reducing incidence of hepatocellular carcinoma in chronic hepatitis B patients: A systematic review and meta‐analysis

Substantial risk of recurrence even after 5 recurrence-free years in early-stage hepatocellular carcinoma patients

Magnitude of and prediction for risk of hepatocellular carcinoma in patients with chronic hepatitis B taking entecavir or tenofovir therapy: A systematic review

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