Among patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), treatment with potent, first-line antivirals entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) provides similar short- and long-term safety and efficacy, according to the results of a study published in BMC Infectious Diseases.
“Although current clinical guidelines recommend early intervention using oral antiviral treatment in HBV-related ACLF, the specific strategy of antiviral treatment is still unclear in newly approved TAF and some details of TDF in hepatorenal syndrome conditions, therefore data gap still exists with little evidence,” the study authors noted.
To better understand the safety and efficacy of nucleoside and/or nucleotide analogs, a team of investigators in China conducted an ongoing prospective cohort study (ClinicalTrials.gov Identifier: NCT03640728) to compare clinical outcomes in patients with HBV-ACLF treated with TAF, TDF, and ETV. The main outcome of the study was overall survival at weeks 12 and 48. Secondary outcomes were virologic and biochemical response.
A total of 44 patients, matched by gender and age, were assigned to TAF 200 mg/d (10 patients), TDF 300 mg/d (10 patients), or ETV 0.5 mg/d (20 patients). By week 12, 20% of the TAF cohort, 40% of the TDF cohort, and 15% of the ETV cohort either died or underwent liver transplantation, with 66.7% of these events occurring within 28 days.
Rates of liver-related complications such as ascites, spontaneous bacterial peritonitis, infection, gastrointestinal hemorrhage, hepatic encephalopathy, and hepatorenal syndrome were comparable between the 3 treatment groups. The cumulative rates of overall mortality or liver transplantation by week 48 were also comparable between the groups (P =.251).
Within the first 4 weeks, all 3 groups experienced a significant reduction in HBV DNA loads from baseline. Although viral load reduction was not statistically significantly different between the 3 groups, the fastest decline rate was observed in the ETV group. Following treatment for 12 weeks, 66.7% of TAF-treated patients, 50.0% of TDF-treated patients, and 60.0% of ETV-treated patients had virologically undetectable HBV DNA (< 20 IU/mL).
At week 4, biochemical responses were similar among the 3 groups; however, albumin levels were highest in the TAF group. Treatment with TAF resulted in significantly higher albumin levels compared with ETV treatment (P =.027); however, albumin levels were not statistically significantly different among the other groups. Of the 3 groups, TAF treatment also resulted in the highest level of cholesterol, although this was not found to be statistically significant.
At week 48, there were no reported drug-related adverse events, and none of the patients discontinued antiviral therapy due to drug-related adverse events. One patient was reported to switch from TAF to ETV at week 6 due to financial burden.
Because TDF may cause renal toxicity in long-term use, the investigators also tested changes in renal function markers in patients undergoing antiviral treatment. They found that TDF was associated with unfavorable renal safety even in short-term treatment, as expressed by increased serum urea, creatinine, and cystatin C, and a decrease in estimated glomerular filtration rate. However, these rates were not found to be significantly different between groups by week 4. Additionally, no renal-related adverse events, serious adverse renal events, or instances of proximal tubulopathy were reported in patients who continued to receive follow up to week 48.
A limitation of the study is its observational design. Although randomization can help eliminate bias and enhance data comparability, it can be unethical to perform a randomized clinical trial for life-threatening diseases such as ACLF. Another limitation of the study was the small sample size; however, this is partially due to the rarity of this disease.
“Our findings provided new evidence for antiviral treatment options for HBV-related ACLF,” noted the investigators. “Large multicenter prospective studies are required to evaluate the long-term efficacy and safety in HBV-related ACLF population,” the authors concluded.
Li J, Hu C, Chen Y et al. Short-term and long-term safety and efficacy of tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir treatment of acute-on-chronic liver failure associated with hepatitis B. BMC Infect Dis. 2021;21(1):567. doi:10.1186/s12879-021-06237-x