Changing Etiologies And Outcome Of Liver Failure In Southwest China

Liver failure is a serious acute or chronic liver insufficiency induced by a variety of causes, which is characterized with high mortality and great difficulty in treatment. There are high diversity on the definition, classification and criteria of liver failure in different countries. In China, liver failure is classified into acute liver failure(ALF), sub-acute liver failure(SALF), acute-on-chronic liver failure(ACLF) and chronic liver failure.The main causal agents of liver failure show wide geographical variation, and depend on the prevalent hepatotropic virus infections and patterns of drug use. Otherwise, the prognosis of liver failure depends greatly on the underlying cause. Therefore, it is important to perform a survey on the changing etiologies and trigger factors of liver failure in China. However, there are few epidemiological and etiological studies regarding ACLF. China is a region of high prevalence of hepatitis B virus(HBV) infection. HBV associated ACLF is the most common clinical type of liver failure in China. However, there were few data about the prognosis, etiologies or trigger factors of liver failure in China based on long-term and large samples cohorts. Otherwise, it is also not consistent about the association of prognosis with etiologies, sex and age in previously published data. With the widespread use of antiviral drugs, the proportion of antiviral therapy related ACLF in HBV-related liver failure is unclear. In order to clarify the prognosis and epidemiological characteristics of liver failure and provide basic data for the prevention strategies in China, which included transplant-free or spontaneous survival(SS) rate, etiologies, sex, age and their association. In this study, we performed an extensive investigation on 3171 liver failure patients admitted in our department from 2000 to 2012.The major results as follows:1. For ALF, the three leading causes were HBV infection(46.7%), indeterminate(20.0%) and DILI(17.3%). For SALF, the three leading causes were indeterminate(29.3%), HBV infection(25.3%) and DILI(25.3%). For ACLF, 96.5% cases were associated with HBV infection. For HBV associated ACLF, 37.5% cases had more than one precipitating factor. The first leading cause of HBV associated ACLF was spontaneous SAE of CHB(62.5%), and the second leading cause was alcohol(15.4%), and the third leading cause was withdrawal of NUCs(7.5%). The percentages of patients with at least two precipitating factors were significantly higher in ACLF(36.7%) than those in ALF(6.7%) and SALF(1.7%), P<0.01.2. The percentage of NUCs withdrawal 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 2012.3. The ratio of male to female was 5.6:1 in ACLF, which was significantly higher than that in ALF(1.3:1) and SALF(0.9:1), P<0.01. Patients with ACLF(42.4±11.7) were older than those with ALF(33.7±17.5) and SALF(37.4±17.4), P < 0.01. There were no significant difference with age(P=0.122) and sex(P=0.269) between SALF and ALF.4. The ratio of male to female was 5.9:1 in HBV associated liver failure, which was significantly higher than that(0.9:1) in non-HBV associated liver failure(P<0.01),and male patients(41.5±11.3) tended to be younger than female(45.3±13.0) cases(P<0.01).5. The average 3-month SS rates of liver failure were 31.4%, and it showed a gradually increased trend. SS rate of ALF was 17.3%(13/75), which was significantly lower than 29.3% of SALF and 31.9% of ACLF(P=0.047, 0.007).6. In HBV associated ACLF, SS rate of patients induced by alcohol, drugs, NUCs withdrawal and resistance to NUCs was 29.1%, which was significantly lower than S-SAE(34.1%) and hepatotropic viruses superinfection(38.5%), P=0.014, 0.030. There were no significant difference with SS rates between spontaneous SAE and hepatotropic viruses superinfection groups(P=0.314). Steroids and interferon use induced ACLF cases had the SS rate of 11.1%,36.4% respectively.7. Survivors(36.9±17.3 years) were younger than the non-survivors whether in non-HBV(36.9±17.3 years versus 42.2±18.7 years, P=0.035) or HBV associated liver failure(38.6±11.0 versus 43.6±11.6, P<0.01). There was no significant difference with SS rate between male and female(P=0.865) in non-HBV associated liver failure. In HBV associated liver failure, SS rate was higher in female(35.4%) than male(31.1%), but having no statistically significant difference(P=0.08).8. In HBV associated liver failure. 81.1% male patients were aged 25-55 years, but 67.2% female patients were aged 25-55 years, the ratio of male to female was 7.1:1.For male, SS rate was the highest in those aged 20-24 years(63.1%, 53/84), then decreased progressively with increasing age. For male, SS rate was significantly higher in patients aged 30-34 years(41.8%) than 30.3% of aged 35-39 years group(P=0.001).Conclusions:1. 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.2. 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.3. 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.4. 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.