Hepatocellular carcinoma risk in patients with chronic hepatitis B receiving tenofovir- vs. entecavir-based regimens: Individual patient data meta-analysis

1. Download : Download high-res image (366KB)
2. Download : Download full-size image

     

Post-treatment HBsAg decline predicts high rate of HBsAg loss after stopping entecavir or tenofovir in HBeAg-negative patients without retreatment

Background/AimsLittle is known about the role of post-treatment HBsAg decline in HBsAg loss following nucleos(t)ide analogues cessation.MethodsHBeAg-negative patients without cirrhosis who previously received entecavir or tenofovir disoproxil fumarate (TDF) were enrolled (n=530). All patients were followed-up post-treatment for >24 months.ResultsOf the 530 patients, 126 achieved sustained response (Group I), 85 experienced virological relapse without clinical relapse and retreatment (Group II), 67 suffered clinical relapse without retreatment (Group III) and 252 received retreatment (Group IV). The cumulative incidence of HBsAg loss at 8 years was 57.3% in Group I, 24.1% in Group II, 35.9% in Group III and 7.3% in Group IV. Cox regression analysis showed that nucleos(t)ide analogue experience, lower HBsAg levels at end-of-treatment (EOT) and higher HBsAg decline at 6 months after EOT were independently associated with HBsAg loss in Group I and Groups II+III. The rates of HBsAg loss at 6 years in patients with HBsAg decline >0.2 log IU/mL in Group I and HBsAg decline >0.15 log IU/mL in Group II+III at 6 months after EOT were 87.7% and 47.1%, respectively.ConclusionThe HBsAg loss rate was high and post-treatment HBsAg decline could predict high HBsAg loss rate among HBeAg-negative patients who discontinued entecavir or TDF and did not need retreatment.     

Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study

Background and aimPlasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions.Methods and resultsCase-cohort study from the PREDIMED trial involving participants aged 55–80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20–1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12–1.58) for fumarate and 1.47 (95%CI:1.21–1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32–1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention.ConclusionPlasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk.Clinical trial numberISRCTN35739639     

Differential Relapse Patterns After Discontinuation of Entecavir vs Tenofovir Disoproxil Fumarate in Chronic Hepatitis B

Background and AimsWhether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differentially affect relapse and outcomes following treatment discontinuation across different patient subpopulations remains unclear. We aimed to compare rates of off-therapy hepatitis B surface antigen (HBsAg) loss, virological and clinical relapse, and retreatment between chronic hepatitis B (CHB) patients who discontinued TDF or ETV therapy.MethodsThis study included 1402 virally suppressed CHB patients who stopped either ETV (n = 981) or TDF (n = 421) therapy between 2001 and 2020 from 13 participating centers across North America, Europe, and Asia. All patients were hepatitis B e antigen–negative at treatment discontinuation. Inverse probability of treatment weighting was used to balance the treatment groups. Outcomes were analyzed using survival methods.ResultsDuring a median off-treatment follow-up of 18 months, HBsAg loss occurred in 96 (6.8%) patients overall. Compared with ETV, TDF was associated with a higher rate of HBsAg loss (P = .03); however, the association was no longer significant after statistical adjustment (P = .61). Virological relapse occurred earlier among TDF-treated patients (P < .01); nonetheless, rates became comparable after the first year off therapy (P = .49). TDF was significantly associated with a higher clinical relapse rate than ETV throughout follow-up (P < .01). The development of a virological or clinical relapse did not affect the rate of HBsAg loss. Retreatment rates were not significantly different between the treatment groups.ConclusionsTDF and ETV have differential relapse patterns but are associated with similar rates of HBsAg loss and retreatment following discontinuation. Finite therapy can be considered for CHB patients on either TDF or ETV therapy.