Lower risk of hepatocellular carcinoma with tenofovir than entecavir treatment in subsets of chronic hepatitis B patients: an updated meta‐analysis

Abstract

Background and Aim Previous smaller meta‐analyses comparing the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF) versus entecavir (ETV) provided controversial results. This updated meta‐analysis aimed to reliably identify any difference in the HCC incidence between TDF‐treated or ETV‐treated CHB patients in general or in specific subgroups. Methods PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies with hazard ratios (HRs) for HCC between TDF‐treated and ETV‐treated CHB patients. Retrieved dates ranged from January 2009 to October 2021. HRs with or without adjustment were pooled with random‐effects model. Results Twenty‐four comparative studies involving 37 771 CHB patients treated with TDF and 72 094 treated with ETV were included. TDF was associated with lower risk of HCC compared with ETV, with pooled unadjusted HR of 0.76 (95% confidence interval [CI]: 0.67–0.86) (24 studies) and adjusted HR of 0.81 (95% CI: 0.72–0.91) (21 studies). In propensity score matching cohorts, the TDF superiority was confirmed for unadjusted HR 0.83 (95% CI: 0.71–0.97) (14 studies) and was close to significance for adjusted HR (0.78, 95% CI: 0.58–1.04) (8 studies). Subgroup analyses showed that TDF was associated with lower HCC risk than ETV treatment in CHB patients who were from Asia (adjusted HR: 0.76, 95% CI: 0.66–0.87; 15 studies) or nucleos(t)ide naïve (adjusted HR:0.74, 95% CI: 0.65–0.84; 18 studies). Conclusion Current evidence from a sizable population suggests that TDF is associated with significantly lower HCC risk compared with ETV treatment in patients who are from Asia and/or nucleos(t)ide naïve.

Letter: Entecavir versus tenofovir on serum lipoprotein levels of hepatitis B virus‐related hepatocellular carcinoma after curative hepatectomy

“…In addition to the trend of serum lipoprotein levels, the occurrence / recurrence of HCC between patients receiving TDF and ETV is controversial. Some studies found TDF to be associated with a lower risk of HCC occurrence than ETV in patients with chronic HBV infection, [3][4][5] but not others. 6 Similarly, one study found that both TDF and ETV showed similar recurrence-free and overall survival in patients with HBV-related HCC after hepatectomy, 7 but this was not found in another study.…”

Current Perspectives on Nucleos(t)ide Analogue Therapy for the Long-Term Treatment of Hepatitis B Virus

“… 60 A recent meta-analysis including 24 studies (37,771 CHB patients treated with TDF and 72,094 treated with ETV) has shown that TDF was associated with a lower HCC risk than ETV in Asian CHB patients (adjusted HR: 0.76, 95% CI: 0.66–0.87; 15 studies) or in NA-naïve patients (adjusted HR: 0.74, 95% CI: 0.65–0.84; 18 studies). 61 However, other studies have failed to demonstrate this association. 62 , 63 In Caucasian patients, the largest study including 1,935 patients from the PAGE-B cohort with a median follow-up of 7.5 years did not find differences on 5-year cumulative HCC incidence between ETV (5.4%) or TDF (6.0%).…”

“…In recent years, some studies have suggested that patients treated with TDF, compared to ETV, have a lower risk of developing HCC, especially in the Asian population, which has generated an intense debate with conflicting publications. [59][60][61][62][63][64] A large study including 29,350 patients from China showed a reduced HCC incidence in patients receiving TDF but only 1% of those with cirrhosis had received TDF. Moreover, important differences between groups regarding HCC risk factors were found; patients treated with TDF were younger, and more frequently HBeAg-positive, females, without cirrhosis, and without diabetes.…”

Development of hepatocellular carcinoma in treated and untreated patients with chronic hepatitis B virus infection

“…109 However, several studies have been shown that patients with tenofovir disoproxil fumarate had lower incidence rate of HCC development than those with entecavir. 110,111 For example, a meta-analysis with 14 studies and 263,947 person-years follow-up revealed that patients with entecavir treatment had higher HCC risk than those with tenofovir disoproxil fumarate treatment (HR: 1.27, 95% CI:1.01-1.60, P=0.04). 110 Therefore, it remains controversial whether different antivirals may have distinct risk of HCC development.…”