Abstract. The effects of corticosteroids in the treatment of patients with acute or subacute liver failure (ALF or SALF) are controversial. The aims of the present study were to evaluate the efficacy of corticosteroids in improving spontaneous survival (SS) rate in patients with ALF and SALF, and to determine the groups with the highest rates of response to, and the most effective timing of, corticosteroid administration. A retrospective analysis was performed of all patients with ALF and SALF who were hospitalized in the Department of Infectious Diseases, Southwest Hospital, Chongqing, China from 2000-2012. The most common result of this was SS. A total of 238 patients were studied, including 73 patients with ALF (n=34 steroids, n=39 no steroids) and 165 patients with SALF (n=21 steroids, n=144 no steroids). Corticosteroids improved rates of SS in patients with liver failure (steroids vs. no steroids, 38.2 vs. 20.2%; P= 0.011), including patients with ALF (steroids vs. no steroids, 29.4 vs. 5.1%; P=0.013) and with SALF (steroids vs. no steroids, 52.4 vs. 24.3%; P=0.013), patients with viruses (steroids vs. no steroids, 32.4 vs. 14.1%; P=0.042) and patients without viruses (steroids vs. no steroids, 50.0 vs. 24.1%; P=0.043). SS rates were extremely low for patients with coma grade 4 or Model for End-stage Liver Disease (MELD) scores ≥35 (2.2 vs. 11.8%; P=0.180). A significantly improved rate of SS associated with steroid use was observed among patients who had alanine aminotransferase (ALT) levels ≥30 x the upper limit of normal and coma grade <4 and MELD scores <35 (65.0 vs. 17.4%; P= 0.002). SS associated with steroid use was significantly higher in patients with an illness duration ≤2 weeks compared with patients with an illness duration >2 weeks (51.4 vs. 15.0%; P=0.010). Corticosteroids improved the prognosis of patients with ALF and SALF. The highest rates of response were observed in patients with a lower MELD score and coma grade but who had extremely high ALT levels. The most effective treatment time was within 2 weeks of the onset of symptoms.

BackgroundThe prognosis of liver failure depends greatly on the underlying cause, and there were few data about the prognosis, etiologies or trigger factors of liver failure in China based on long-term and large samples cohorts.MethodsWe screened out 3171 liver failure cases from 25467 patients hospitalized in our department between 2000 and 2012 according to Chinese criteria, and determined their etiologies and prognosis.Results97.3 % cases were associated with at least one of 25 identified factors. The 3 leading etiologies were HBV (91.6 %), alcohol (18.1 %) and antiviral therapy (AVT) related hepatitis B flares (6.7 %). Acute-on-chronic liver failure (ACLF) accounted for 92.1 % of all cases. 96.5 % ACLF cases were associated with HBV, in which the percentage of AVT related flares increased from 0 % in 2000 up to 11.5 % in 2012, and hepatitis virus superinfection declined from peak 19.3 % in 2002 down to 2.5 % in 2012. Three-month spontaneous survival (SS) rate of 3171 cases was 31.4 %, but improved from 17.4 % in 2000 up to 40.4 % in 2012. SS was significantly different among various etiological groups (P = 0.000). In HBV related liver failure aged 25 to 54 years, males accounted for 87.6 %, and had a progressively decreased SS with increasing age. From 25 to 54 years, SS was lower in male than in female HBV related liver failure, and having significant difference in cases of ages 40 to 44 years (27.6 % versus 50.9 %, P = 0.001).ConclusionEtiologies of liver failure were numerous and varied in southwest China. HBV was the most leading cause of liver failure, especially in ACLF. AVT related flares had become the third leading cause of ACLF. The prognosis of liver failure remained poor, but had markedly improved in recently 3 years. Middle-aged male HBsAg carriers had an extremely higher risk for liver failure and worse prognosis compared to female.Etiologies of liver failure were numerous and varied in southwest China. HBV infection is the main cause of liver failure in southwest China, especially the major cause of ACLF. Antiviral related liver failure, especially the NUCs withdrawal induced ACLF were extremely increased, which has replaced the superinfection as the third important cause of HBV-ACLF.The prognosis of liver failure is still poor, but the spontaneous survival rate showed a trend of steady rise in recent years. The prognosis of patients with liver failure caused by different causes also exists certain difference, the more damage factors bulls the worse prognosis.The prognosis of the HBV and HCV reactivation induced by the steroids was poor.Interferon treatment of CHB in ACLF although rare, but should be taken into consideration seriously.Patients with liver failure caused by different etiologies showed larger differences of gender and age distribution. Gender and age are the important factors with the occurrence and prognosis of HBV-ACLF.

Glucocorticoids are effective for the treatment of acute-on-chronic pre-liver failure, severe chronic hepatitis B and acute liver failure; however, the mechanism underlying the effects of treatment by glucocorticoids remains to be fully elucidated. The role and detailed mechanism of how glucocorticoids prevent liver disease progression can be elucidated by investigating the apoptosis of hepatocytes following glucocorticoid treatment. P‑glycoproteins (P‑gps) also confer resistance to apoptosis induced by a diverse range of stimuli. Glucocorticoids, particularly dexamethasone (DEX), upregulate the expression of P‑gp in several tissues. In the present study, the normal human L‑02 liver cell line was used, and techniques, including immunocytochemistry, western blot analysis, flow cytometry and reverse transcription‑quantitative polymerase chain reaction analysis were used for determining the expression levels of P‑gps, and for evaluating the effect of DEX pretreatment on the expression of P‑gps. DEX (1‑10 µM) was added to the cell culture media and incubated for 24‑72 h. The results revealed that DEX upregulated the mRNA and protein levels of P‑gp in a dose‑ and time‑dependent manner. Subsequently, tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) was used for the induction of apoptosis in the cells, followed by a terminal deoxynucleotidyl transferase dUTP nick end labeling assay to assess the apoptotic stages. The results demonstrated that apoptosis in the group of cells, which were pre‑treated with DEX was significantly lower than that in the control group. Treatment with tariquidar, a P‑gp inhibitor, reduced the anti‑apoptotic effects of DEX. These results established that DEX protects normal human liver cells from TRAIL‑induced apoptosis by upregulating the expression of P-gp. These observations may be useful for elucidating the mechanism of DEX for preventing the progression of liver disease.