LBP-13-Effect of treatment of hepatitis B patients with tenofovir disoproxil or entecavir on risk of hepatocellular cancer death in a U.S. Cohort

Gordon, Stuart C.; Zhou, Yueren; Li, Jia; Rupp, Loralee B; Boscarino, Joseph A.; Daida, Yihe G.; Schmidt, Mark; Trudeau, Sheri; Lu, Mei

doi:10.1016/s0618-8278(19)30259-2

Cited by 11 publications

(23 citation statements)

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“…Sensitivity analysis by excluding each South Korean study one at a time ( 11,12,21,23,26 ) did not significantly change the overall summary estimate (HR, 1.16; 95% CI, 0.94‐1.44; P = 0.17). Sensitivity analysis by excluding Gordon et al, the only study with adjusted data that enrolled treatment‐experienced patients, ( 19 ) did not change the overall summary estimate (HR, 1.26; 95% CI, 1.00‐1.59). We further conducted subgroup analysis using adjusted or propensity score–matched data in the subset of patients with cirrhosis, when data were available.…”

Section: Resultsmentioning

confidence: 95%

“…There was no evidence of publication bias (; Egger’s test P = 0.92). Sensitivity analysis by excluding studies that enrolled treatment‐experienced patients ( 19,21,24 ) did not significantly change the point estimate (IRR, 1.40; 95% CI, 0.93‐2.12).…”

Section: Resultsmentioning

confidence: 96%

“…The majority of the studies only included treatment‐naive patients, with a few exceptions. Observational studies by Kim et al, ( 22 ) Gordon et al ( 19 ) and Riveiro‐Barciela et al . ( 24 ) explicitly included all‐comers, including nucleos(t)ide‐experienced patients.…”

Section: Resultsmentioning

confidence: 99%

“…( 14 ) An additional seven studies were added by manual searches. After applying the inclusion and exclusion criteria, a total of 14 studies ( 10‐13,17‐26 ) met inclusion criteria. The study selection flow diagram is shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…However, adjusted analysis for age and sex may mitigate some of this confounding. Furthermore, it has also been postulated ( 19 ) that variation in hepatocarcinogenesis may have a racial/ethnic association. This was not explored in our study; notably, eight of 14 studies were conducted in predominantly Asian populations.…”

Section: Discussionmentioning

confidence: 99%

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Comparative Effectiveness of Entecavir Versus Tenofovir for Preventing Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: A Systematic Review and Meta‐Analysis

et al. 2020

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Background and Aims Chronic hepatitis B (CHB) can lead to hepatocellular carcinoma (HCC). While both tenofovir disoproxil (TDF) and entecavir (ETV) have been shown to reduce the risk of HCC, their comparative effectiveness is unclear. We estimated the comparative effectiveness of these two agents in reducing the risk of HCC in patients with CHB, through a systematic review and meta‐analysis. Approach and Results We searched multiple electronic databases from January 1, 1998, to October 31, 2019, for randomized controlled trials and observational comparative effectiveness studies in adults with CHB treated with ETV compared to TDF, reporting the incidence of HCC (minimum follow‐up 12 months). Primary outcome was incidence of HCC, calculated as incidence rate ratio (IRR) with 95% confidence interval (CI, unadjusted analysis) and hazard ratio (HR) with 95% CI (adjusted analysis, where reported). Of 1,971 records identified, 14 studies (263,947 person‐years) were included for quantitative analysis. On unadjusted meta‐analysis of 14 studies, the risk of HCC was not statistically different between ETV and TDF (IRR, 1.28; 95% CI, 0.99‐1.66). When using available adjusted data (multivariate or propensity‐matched data), the risk of HCC among patients treated with ETV was 27% higher when compared to TDF (seven studies; 95% CI, 1.01‐1.60, P = 0.04). Additional analysis of adjusted data when separately reported among patients with cirrhosis demonstrated an adjusted HR of 0.90 (95% CI, 0.66‐1.23), suggesting no difference between ETV‐treated and TDF‐treated groups. The overall confidence in estimates was very low (observational studies, high heterogeneity). Conclusions TDF may be associated with lower risk of HCC when compared to ETV.

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Comparative Effectiveness of Entecavir Versus Tenofovir for Preventing Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: A Systematic Review and Meta‐Analysis

et al. 2020

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Secondary prevention for hepatocellular carcinoma in patients with chronic hepatitis B: are all the nucleos(t)ide analogues the same?

2020

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Reducing the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is the key ultimate goal set in essentially all treatment guidelines. There has been solid evidence supporting the relationship between serum hepatitis B virus (HBV) DNA level and risk of HCC. Antiviral treatment with oral nucleos(t)ide analogues (NAs) leads to sustained viral suppression and hence is often adopted as the secondary prevention for HCC in CHB patients. The first-generation NA, lamivudine, reduced the risk of HCC at 3 years compared to placebo; yet, its high emergence of antiviral resistance has made it no longer recommended in the international guidelines. Recent heated debate is about the two current first-line NAs—entecavir and tenofovir disoproxil fumarate (TDF)—Are they just as good to reduce HCC risk in CHB patients? A handful of cohort studies show two different kinds of observations—TDF is better than entecavir in lowering HCC risk, or these two NAs have led to similarly low risk of HCC. Tenofovir alafenamide (TAF), a modified version of TDF higher rate of ALT normalization, would be another potent nucleotide analogue is the treatment of choice for secondary prevention for HCC.

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Residual risk of HCC during long-term oral nucleos(t)ide analogues (NUCs) in patients with CHB – Is one NUC better than the other?

Wong

Lampertico

2019

Journal of Hepatology

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Antiviral therapy with oral nucleos(t)ide analogues (NUCs) is recommended by international guidelines for patients with chronic hepatitis B (CHB) who have treatment indications, 1-3 as NUCs are effective in suppressing HBV DNA and reducing the risk of hepatic events and hepatocellular carcinoma (HCC). 4,5 Entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are the 3 recommended NUCs, with high genetic barriers to resistance as well as favorable safety profiles. 1,3,6 In a recent issue of Journal of Hepatology, Kim and co-workers reported the findings of a retrospective cohort study of 2,897 patients with CHB recruited from 4 academic teaching hospitals in South Korea. 7 The authors compared the 5-year cumulative probabilities of HCC and death or liver transplantation in patients with or without compensated cirrhosis who had received ETV and TDF as the first antiviral agent. With several statistical approaches, including propensity score (PS)-matched and inverse probability of treatment weighting analyses, the authors did not demonstrate any difference in HCC incidence nor in other clinical outcomes. 7 The yearly HCC rates were approximately 4.3% and 3.4% for ETV-and TDF-treated patients with compensated cirrhosis (adjusted hazard ratio [aHR] 0.83; 95% CI 0.60-1.13; p = 0.25) and 0.58% and 0.76% for the corresponding patients without cirrhosis (aHR 1.60; 95% CI 0.95-2.71, p = 0.07).This study adds fuel to the heated debate: is TDF better than ETV in terms of risk reduction of HCC? An earlier report from the same country reported different observations. 8 Choi and co-workers showed a significantly lower HCC risk in TDF-treated patients, compared to ETV-treated patients, in a nationwide historical population cohort study of 24,156 previously treatment-naïve patients with CHB (11,464 started with ETV, 12,692 started with TDF), as well as a hospital cohort of 2,701 patients with CHB (1,560 ETV, 1,141 TDF). 8 The authors reported a consistent HCC risk reduction with TDF treatment,

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LBP-13-Effect of treatment of hepatitis B patients with tenofovir disoproxil or entecavir on risk of hepatocellular cancer death in a U.S. Cohort

Cited by 11 publications

References 0 publications

Comparative Effectiveness of Entecavir Versus Tenofovir for Preventing Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: A Systematic Review and Meta‐Analysis

Comparative Effectiveness of Entecavir Versus Tenofovir for Preventing Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: A Systematic Review and Meta‐Analysis

Secondary prevention for hepatocellular carcinoma in patients with chronic hepatitis B: are all the nucleos(t)ide analogues the same?

Residual risk of HCC during long-term oral nucleos(t)ide analogues (NUCs) in patients with CHB – Is one NUC better than the other?

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