Efficacy of combination therapy of antiviral and immunosuppressive drugs for the treatment of severe acute exacerbation of chronic hepatitis B

Abstract

The early introduction of sufficient doses of corticosteroids and nucleoside analogs could be one option for reversing the potential deterioration of patients with clinically severe, life-threatening exacerbation of chronic hepatitis B.

Evaluation of the efficacy of steroid therapy on acute liver failure

“…HBV DNA is reduced rapidly following the administration of NUCs; however, the improvement to liver function is delayed by a few weeks to a few months. During this time, an excessive immune and inflammatory reaction may continue and liver cell injury may progress (17). Thus, antiviral treatment with NUCs cannot rapidly prevent disease progression and may only help to improve the short-term SS rate of acute hepatitis B-associated liver failure (25,26).…”

“…When large numbers of degenerated hepatocytes have already been destroyed, the introduction of steroids may not be effective in improving the prognosis of liver failure (17). Fujiwara et al (17) reported that none of the eight patients studied recovered when steroids were administered >10 days after the diagnosis of SAE of chronic hepatitis B; however, 88.2% (15/17) of the patients recovered when steroids were administered within 10 days of an SAE diagnosis. The present results revealed that the time interval from the onset of symptoms to the initiation of steroid use was significantly shorter in survivors than in non-survivors.…”

“…Fujiwara et al (17) reported that a combined therapy of NUCs and corticosteroids was unable to improve the recovery rates of patients with SAE of chronic hepatitis B, but shortened the treatment period of corticosteroids. The current results indicated that the SS rate in patients receiving neither steroids nor NUCs was significantly lower than that of patients who received a combined treatment of NUC and corticosteroids.…”

“…Corticosteroids have several other hepatoprotective roles, including preventing cytolysis of ballooned hepatocytes and protecting hepatocytes against apoptosis induced by cadmium toxicity (12)(13)(14). Previous work by the present authors and other groups has revealed that corticosteroids are effective in treating pre-acute-on-chronic liver failure (pre-ACLF) associated with HBV and severe acute exacerbation (SAE) of chronic hepatitis B (15)(16)(17). Therefore, treating ALF and SALF with corticosteroids is a reasonable treatment regimen.…”

Prognoses of patients with acute-on-chronic hepatitis B liver failure are closely associated with altered SOCS1 mRNA expression and cytokine production following glucocorticoid treatment

“…16,17 As an optional therapy for ACHBLF, corticosteroid treatment has received much attention. [18][19][20][21] Glucocorticoids suppresses inflammation by controlling and preventing the immune-correlated damages. The upregulation of SOCS1 by corticosteroids has been established both in vivo and in vitro, [22][23][24] which suggests that cortisol may be playing a key role in suppressing cytokine signaling and the associated inflammatory response through SOCS1.…”