Combined glycyrrhizin, tenofovir therapy safe and effective in SAE of chronic hepatitis B
Early introduction of glycyrrhizin in combination with tenofovir in the treatment of patients with severe acute exacerbation (SAE) of chronic hepatitis B (CHB) is safe and effective, reducing serum transaminases rapidly in the first 2 weeks when compared with tenofovir alone, according to the results of an open-label trial.
In a cohort of 60 patients (77 percent male) with SAE of CHB, those treated with tenofovir plus intravenous glycyrrhizin (glycyrrhizin arm; n=30) fared significantly better in terms of the primary endpoint of a reduction in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and in model for end-stage liver disease (MELD) score compared with patients given tenofovir alone (tenofovir only arm; n=30). The reductions were observed at day 3 and were sustained thereafter until day 15 (p<0.05 for all). [Clin Trans Gastroenterol 2017;doi:10.1038/ctg.2017.29]
Specifically, significant improvements in MELD score were observed as early as the first week of treatment in the glycyrrhizin arm, whereas no changes from baseline were seen at weeks 1 and 2 in the tenofovir only arm. By week 24, one patient (33 percent) in the glycyrrhizin arm died while three died and one underwent liver transplant in the tenofovir only arm.
MELD score emerged as an independent factor for mortality or receipt of liver transplantation (p=0.021) in multivariate Cox proportional hazards analysis. The rates of grade 3 hypertension, hypokalaemia and ascites did not differ significantly between the two treatment arms.
Patients in the glycyrrhizin arm had a mean age of 49.1 years, while those in the tenofovir only arm had a mean age of 45.3 years. Tenofovir was administered at 300 mg daily in both arms, while the glycyrrhizin arm was given 10 days of intravenous glycyrrhizin. Mean baseline MELD score was 16.7 in the glycyrrhizin arm vs 17.4 in the tenofovir only arm, with 13 overall having MELD score >20. All patients were followed for at least 24 weeks from treatment initiation.
“Despite no statistical significance in mortality/transplantation-free rate, our data provide the first evidence that glycyrrhizin can significantly improve MELD score, even in more severe cases with higher baseline MELD score (>20),” the investigators said.
“In general, glycyrrhizin was safe and well tolerated. Although glycyrrhizin could induce hypokalaemia (<3.5 mmol/l), most patients had a mild degree without clinical symptoms,” they added.
An aqueous extract of liquorice root, glycyrrhizin has been shown to be hepatoprotective in vitro. This effect is achieved by supposedly preventing changes in cell membrane permeability and providing membrane stabilization, as have been demonstrated in previous animal studies. [World J Gastroenterol 2007;13:462–466; Arch Histol Cytol 2008;71:163–178]
“In a recent small study, corticosteroid treatment in combination with nucleotide analogue has sufficient virological effect against SAE of CHB, and a rapid decline of HBV-DNA is conspicuous in [survivors]. However, the increased risk of infectious complications after corticosteroid treatment should be a serious concern, particularly because sepsis is one of the most important causes of death in CHB with SAE,” the investigators noted. [J Viral Hepat 2015;22:94–102; World J Gastroenterol 2012;18:5078–5083]
“By contrast, our study medication ‘glycyrrhizin’ appears to be safe and the expected side effects associated with pseudoaldosteronism are usually minor and reversible,” they said.
Given the presence of limitations in the study, including the relatively small sample size and a follow-up duration that prevented assessment of long-term impact of the study medication on progression of liver disease, the investigators said additional studies are warranted to further examine the survival benefit of glycyrrhizin in CHB with SAE.