Atorvastatin Rapidly Reduces Hepatitis B Viral Load in Combination with Tenofovir: A Prospective Clinical Trial

Abstract

Objective and Aim. Atorvastatin inhibits cholesterol synthesis which is critically important in the formation of the viral envelope and secretion. The efficacy and safety of giving atorvastatin (40 mg/day) as an adjunct to tenofovir in the treatment of hepatitis B (HBV) were assessed. Method. In this single-blind clinical trial, 40 patients with active chronic hepatitis B were randomly allocated to treatment or control groups. The treatment group received the standard treatment for chronic HBV (300 mg tenofovir twice a day) along with 40 mg/day atorvastatin for 12 months, while the control group received a placebo once daily in addition to the standard tenofovir regimen. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and HBV DNA copy numbers were measured at the beginning of the treatment and 1, 3, 6, 9, 12 months later. Results. One month after starting the treatment, the HBV copy number in the atorvastatin + tenofovir-treated group was significantly lower, by 200×, compared with the control group. After three months of the treatment, there was no detectable HBV DNA in 50% of the atorvastatin + tenofovir-treated group compared with 30% in the control group. The half-life of plasma viral load was 2.03 and 3.32 months in the atorvastatin + tenofovir-treated and control groups, respectively. No adverse events due to taking atorvastatin were observed. Conclusions. The combination of atorvastatin with tenofovir increased antiviral activity and led to a faster recovery from viral infection. Therefore, this modality can be recommended as a safe combination therapy for chronic hepatitis B patients.

Statins in Chronic Liver Disease: Review of the Literature and Future Role

“…55,56 Statins have anti-virologic effects in HBV and HCV. 15,57,58 Combining statin with nucleotide analogues (lamivudine, adefovir, tenofovir, and entecavir) inhibits HBV replication. 58 While these combinations were superior to statin monotherapy, they were not more effective than nucleotide analogues alone, with the exception of tenofovir.…”

“…58 Atorvastatin combined with tenofovir was 200 times superior in reducing HBV viral load ( p = 0.035), and led to undetectable HBV DNA level after only 9 months of treatment, which was not observed in the control group who had persistent viremia despite 12 months of tenofovir monotherapy. 15 Interestingly, contrary to its viral clearance effects, few case reports described HBV reactivation associated with statin initiation with at least one reporting subsequent HBV clearance within 1 month of statin cessation. 59 60 While the data are limited, these observations suggest an immunomodulating role of statins in HBV.…”

“…11 12 Myopathy and rhabdomyolysis are rarely observed with low-intensity statins use in patients with CLD. 13 14 15 More recently, statin use has also been linked to new-onset diabetes, driving more work on this subject, especially given the association of diabetes with hepatocellular carcinoma (HCC). 16 17 Other than aforementioned side effects, statin-related drug-induced liver injury (DILI) is an important adverse event among patients with CLD, which is discussed in details in the following section.…”

“…37 When 40mg of atorvastatin was used with tenofovir over the 12-month period, hepatocellular injury was never detected. 15 Similarly, in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), low-intensity statin use was not associated with significant elevation in transaminases or DILI risk. [38][39][40] In a sub-study of St Francis Heart Study, of the 229 subjects who received 20mg of atorvastatin daily, only 3 developed elevated transaminases after 2 years, which normalized by year 4.…”