Hepatitis B virus (HBV) viral load, liver and renal function in adults treated with tenofovir disoproxil fumarate (TDF) vs. untreated: a retrospective longitudinal UK cohort study

Abstract

Background Current clinical guidelines recommend treating chronic hepatitis B virus (HBV) infection in a minority of cases, but there are relatively scarce data on evolution or progression of liver inflammation and fibrosis in cases of chronic HBV (CHB) that do not meet treatment criteria. We aimed to assess the impact of TDF on liver disease, and the risk of renal impairment in treated CHB patients in comparison to untreated patients. Methods We studied a longitudinal ethnically diverse CHB cohort in the UK attending out-patient clinics between 2005 and 2018. We examined TDF treatment (vs. untreated) as the main exposure, with HBV DNA viral load (VL), ALT, elastography scores and eGFR as the main outcomes, using paired tests and mixed effects model for longitudinal measurements. Additionally, decline of eGFR during follow-up was quantified within individuals by thresholds based on clinical guidelines. Baseline was defined as treatment initiation for TDF group and the beginning of clinical follow-up for untreated group respectively. Results We included 206 adults (60 on TDF, 146 untreated), with a median ± IQR follow-up duration of 3.3 ± 2.8 years. The TDF group was significantly older (median age 39 vs. 35 years, p = 0.004) and more likely to be male (63% vs. 47%, p = 0.04) compared to the untreated group. Baseline difference between TDF and untreated groups reflected treatment eligibility criteria. As expected, VL and ALT declined significantly over time in TDF-treated patients. Elastography scores normalised during treatment in the TDF group reflecting regression of inflammation and/or fibrosis. However, 6/81 (7.4%) of untreated patients had a progression of fibrosis stage from F0-F1 to F2 or F3. There was no evidence of difference in rates or incidence of renal impairment during follow-up in the TDF vs. untreated group. Conclusions Risk of liver inflammation and fibrosis may be raised in untreated patients compared to those receiving TDF, and TDF may benefit a larger percentage of the CHB population.

Effect of pegylated interferon-α2b add-on therapy on renal function in chronic hepatitis B patients: A real-world experience

“…Patients receiving ADV and TDF therapy even experience more rapid loss in eGFR ( Udompap et al, 2018 ). In contrast, several studies suggested that TDF is not associated with greater degree of kidney injury compared with other NAs ( Trinh et al, 2019 ; Fischer et al, 2021 ) and untreated HBV-infected individuals ( Wang et al, 2021 ). LdT has been demonstrated to improve renal function in CHB patients ( Gane et al, 2014 ), in liver transplant recipients for HBV-related cirrhosis ( Cholongitas et al, 2015 ), and in liver transplant recipients with long-term chronic kidney disease ( Lee et al, 2017 ).…”

Cohort Profile: The National Institute for Health Research Health Informatics Collaborative: Hepatitis B Virus (NIHR HIC HBV) research dataset

“… 22 Using this dataset, we have reported a bimodal viral load distribution 23 and found evidence of a virological set point in untreated patients. 23 , 24 In a comparison of tenofovir disoproxil fumarate (TDF)-treated vs untreated patients, we reported variable ethnicity distributions across the two groups and some evidence for liver fibrosis progression in the untreated group, highlighting a need for further evidence for expanded treatment. 24 A study of HBsAg and HBeAg clearance dynamics demonstrated that these markers may contribute to prognostication and patient-stratified care and provide a foundation for advancing insights into mechanisms of disease control.…”

“… 23 , 24 In a comparison of tenofovir disoproxil fumarate (TDF)-treated vs untreated patients, we reported variable ethnicity distributions across the two groups and some evidence for liver fibrosis progression in the untreated group, highlighting a need for further evidence for expanded treatment. 24 A study of HBsAg and HBeAg clearance dynamics demonstrated that these markers may contribute to prognostication and patient-stratified care and provide a foundation for advancing insights into mechanisms of disease control. 25 The list of publications is available in [ https://hic.nihr.ac.uk ] with ongoing/planned studies presented in Table 2 .…”

Hepatitis B Virus: Infection, liver disease, carcinogen or syndemic threat? Remodelling the clinical and public health response

“…Viewing HBV primarily as an infectious agent builds on established approaches for other chronic blood-borne viruses, such as HCV and HIV, as well as containment approaches to other viruses that threaten population health. Suppressing or clearing HBV or HCV lowers the long-term risks of cirrhosis and liver cancer, liver enzymes and fibrosis scores can improve over time [9], and there is a benefit to quality of life [10]. Approaches to BBV prevention are unified by common principles, as reductions in viraemia translate into a lowered transmission risk.…”