ObjectiveTo investigate the efficacy and safety of N-acetylcysteine （NAC） in the treatment of severe alcoholic hepatitis （SAH）， and to provide a basis for clinical medication for SAH. MethodsA prospective randomized controlled trial was conducted among 172 SAH patients with a Maddrey discriminant function score of >32 points who were recruited by The Fifth Medical Center of Chinese PLA General Hospital from June 2015 to June 2018， and these patients were divided into NAC group with 84 patients and control group with 86 patients. NAC （8 g/day， 28 days） was assessed in terms of its safety in SAH patients， its impact on 28-day biochemical parameters， and its role in improving 28- and 180-day survival rates. A further analysis was performed to investigate the effect of NAC on the 28- and 180-day survival rates of SAH patients with acute-on-chronic liver failure （ACLF-SAH patients） and those without acute-on-chronic liver failure （non-ACLF-SAH patients）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate independent influencing factors. ResultsNo serious adverse events were observed during NAC treatment， suggesting that NAC had a good safety profile. Compared with the control group， NAC did not significantly improve the 28-day biochemical parameters （all P>0.05） and survival rate of SAH patients （P=0.081）， but it could improve the 180-day survival rate of SAH patients （67.4% vs 81.0%， χ²=4.280， P=0.039）. NAC did not improve the 28- and 180-day survival rates of ACLF-SAH patients （both P>0.05）； NAC did not improve the 28-day survival rate of non-ACLF-SAH patients （P>0.05）， but it could improve the 180-day survival rate of these patients （68.4% vs 88.9%， χ²=4.883， P=0.027）. The multivariate Cox regression survival analysis showed that NAC treatment （hazard ratio ［HR］=2.530， 95% confidence interval ［CI］： 1.334‍ ‍— 4.796， P=0.004，）， Maddrey discriminant function score （HR=3.852， 95%CI： 2.032 — 7.304， P<0.001）， and serum sodium level （HR=1.948， 95%CI： 1.079‍ ‍—‍ ‍3.517， P=0.027） were independent influencing factors for 180-day survival rate in SAH patients. ConclusionNAC has a good safety profile in the treatment of SAH and can improve the 180-day survival rate of SAH patients， and in particular， non-ACLF-SAH patients can benefit from NAC treatment in terms of middle- and long-term survival rates.

ObjectiveTo investigate the value of MELD 3.0， MELD， and MELD-Na scores in assessing the 90-day prognosis of patients with acute-on-chronic liver failure （ACLF） through a comparative study. MethodsA retrospective analysis was performed for the clinical data of 605 patients with ACLF who were treated in Tianjin Third Central Hospital， The Fifth Medical Center of Chinese PLA General Hospital， and Beijing YouAn Hospital from November 2012 to June 2019， and according to the 90-day follow-up results after admission， they were divided into survival group with 392 patients and death group with 213 patients. The receiver operating characteristic （ROC） curve， the area under the ROC curve （AUC）， net reclassification improvement （NRI）， integrated discrimination improvement （IDI）， and decision curve analysis （DCA） curve were used to investigate the value of MELD 3.0， MELD， and MELD-Na scores at baseline， day 3， week 1， and week 2 in predicting the prognosis of the disease. ResultsAt day 3 and week 1， MELD 3.0 score had an AUC of 0.775 and 0.808， respectively， with a better AUC than MELD score （P<0.05）. At day 3， week 1， and week 2， MELD 3.0 score showed an NRI of 0.125， 0.100， and 0.081， respectively， compared with MELD in predicting the prognosis of ACLF patients， as well as an NRI of 0.093， 0.140， and 0.204， respectively， compared with MELD-Na score in predicting prognosis. At baseline， day 3， week 1， and week 2， MELD 3.0 showed an IDI of 0.011， 0.025， 0.017， and 0.013， respectively， compared with MELD in predicting the prognosis of ACLF patients. At day 3 and week 2， MELD 3.0 showed an IDI of 0.027 and 0.038， respectively， compared with MELD-Na in predicting the prognosis of ACLF patients. All the above NRIs and IDIs were >0， indicating a positive improvement （all P<0.05）. DCA curves showed that MELD 3.0 was superior to MELD at day 3 and was significantly superior to MELD-Na at week 2. There was no significant difference in the ability of the three scores in predicting the prognosis of ACLF patients with different types， and there was also no significant difference in the ability of the three scores in predicting the prognosis of ACLF patients with the etiology of HBV infection， alcohol， or HBV infection combined with alcohol， while MELD 3.0 was superior to MELD for ACLF patients with other etiologies （P<0.05）. ConclusionMELD 3.0 score is better than MELD and MELD-Na scores in predicting the 90-day survival of patients with ACLF， but with limited superiority.

Objective To investigate the risk factors for acute variceal bleeding (AVB) in acute-on-chronic liver failure (ACLF) and its influence on prognosis. Methods A total of 1409 ACLF patients who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from 2009 to 2015 were followed up for 6 months, and according to the presence or absence of AVB, they were divided into AVB group and non-AVB group. The Student's t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier curves were plotted and the Log-rank test was performed to analyze mortality rate and progression during follow-up, and a binary Logistic regression analysis was used to investigate the risk factors for AVB. Results Among these 1409 patients, 167 (11.85%) experienced AVB. The 30-day survival rate was 43.42% in the AVB group and 67.79% in the non-AVB group ( χ 2 =33.558, P < 0.001), and the 180-day survival rate was 18.91% in the AVB group and 53.97% in the non-AVB group ( χ 2 =76.881, P < 0.001). The Log-rank test showed significant differences in 30- and 180-day survival rates between the AVB group and the non-AVB group ( χ 2 =40.950 and 89.320, both P < 0.05). The Logistic regression analysis showed that pleural effusion (odds ratio [ OR ]=1.522, 95% confidence interval [ CI ]: 1.071-2.162, P =0.019), acute kidney injury (AKI) ( OR =2.201, 95% CI : 1.415-3.426, P < 0.001), ABC subtype of ACLF ( OR =2.491, 95% CI : 1.489-4.168, P =0.001), ACLF stage ( OR =2.403, 95% CI : 1.687-3.421, P < 0.001), and urea( OR =2.567, 95% CI : 1.570-4.196, P < 0.001)were independently associated with AVB in ACLF patients. Conclusion AVB is an important influencing factor for the short-term survival of ACLF patients, and pleural effusion, AKI, BC subtype of ACLF, advanced ACLF, and urea are independent risk factors for the onset of AVB.

Objective:To investigate the risk factors of anemia and prognostic value of different grades of anemia in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).Methods:Anemia grades of 1 163 patients with HBV-ACLF were analyzed and the effect of different grades on prognosis were evaluated. The risk factors related to anemia were evaluated by Spearman rank correlation analysis and logistic regression analysis.Results:Among 1 163 patients, 942 (80.99%) patients had anemia. The incidence of grade 2 and 3 (moderate and severe) anemia in type B and C HBV-ACLF patients was significantly increased ( χ2=72.908, P<0.001). The incidence of macrocytic anemia among type A, B and C HBV-ACLF ranged from 13.0% to 43.98% and 58.33%, respectively( χ2=46.823, P <0.001). The 1-year cumulative survival rate of patients with grade 2 and 3 anemia decreased significantly( χ2=50.179, P<0.001); Spearman rank correlation analysis showed that the correlation coefficient between ABC type and anemia grade was 0.319, P<0.001. Logistic regression analysis showed that gastrointestinal bleeding, acute kidney injury (AKI) and ABC types were independently associated with grade 2 and 3 anemia in patients with HBV-ACLF. Conclusions:Anemia grade is closely related to the prognosis in patients with HBV-ACLF. Gastrointestinal bleeding, AKI and ABC types are independent risk factors for grade 2 and 3 anemia in patients with HBV-ACLF.

Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

Liver function of patients with pre-hepatic failure deteriorates rapidly, and with this there exists a risk of liver failure and high rates of mortality. This paper summarizes the concept of pre-hepatic failure, particularly the advances in early warning and treatment of pre-hepatic failure developing into hepatic failure, with a view to enhance clinicians' concerns to pre-hepatic failure for promoting the advancement of liver failure prevention and treatment, and improving the success rate of liver failure treatment.

Objective:To investigate the clinical characteristics, incidence trend, underlying diseases, causative drug and prognosis of drug-induced liver injury (DILI), so as to provide basis for its prevention and treatment.Methods:A retrospective study was conducted on 2 820 DILI cases who were admitted to our hospital from January 2002 to December 2015, and their clinical characteristics, incidence trends, underlying related diseases, causative drug, treatment and outcome were analyzed.Results:Among 2 820 DILI cases, the ratio of male to female was 1:1.44, and the age was (44.00±16.32) years old. According to the clinical classification of DILI, there were 2 353 cases (83.43%) of hepatocyte injury, 353 cases (12.51%) of cholestatic type and 114 cases (4.04%) of mixed type. In the three clinical classification of DILI, there was no statistically significant difference in the ratio of male to female (χ 2 = 3.032, P > 0.05). However, the difference in the ratio of male to female between different age groups was statistically significant (χ 2 = 48.367, P < 0.001). Among the patients with liver disease and acute liver disease admitted to our hospital from January 2002 to December 2015, the proportion of DILI and acute DILI showed an overall upward trend. The main underlying related diseases of 2 820 DILI cases were fever (15.14%), skin diseases (11.84%), cardiovascular and cerebrovascular diseases (11.17%). Chinese herbal patent medicines (37.49%), antibiotics (15.85%), antipyretic-analgesics (14.37%), and so on were the main causative drugs involved, and the prognostic differences among the three clinical classifications of DILI in terms of cure, improvement, ineffectiveness, and death were statistically significant ( H = 61.300, P < 0.001). Conclusion:In recent years, among the patients with liver disease in our hospital, the proportion of DILI has shown an obvious upward trend, involving a variety of underlying diseases and causative drugs, and thus it needs clinical attention.

Liver failure is one of the most serious diseases in clinical practice and has a low treatment success rate. The concept of precision medicine provides more enlightenment for the treatment of liver failure. An accurate understanding of the scientific connotation of precision medicine and the application of advanced techniques can improve the accurate diagnosis of liver failure. This article elaborates on the search for new treatment targets, blockade of hepatocyte necrosis, and the application of genetic technology to realize accurate medication and individualized biotherapy for liver failure. It is pointed out that the accurate diagnosis and treatment of liver failure can improve the level of treatment.

Objective: To study the long-term prognosis of the convalescent patients with hepatitis B virus (HBV) associated acute-on-chronic liver failure (HBV-ACLF). Methods: A 72-month follow-up study of HBV-ACLF recovery patients recruited between January 2005 and December 2009 was performed in our hospital. According to the results of imaging examination at the first visit, the enrolled patients were divided into two groups, the liver cirrhosis ACLF (Lc-ACLF) group and chronic hepatitis B related ACLF (CHB-ACLF) group. In both groups, the occurrence of cirrhosis, decompensated cirrhosis or ACLF and hepatocellular carcinoma (HCC) were observed. Results: The media time of cirrhosis formation, decompensated cirrhosis and HCC occurrence in CHB-ACLF group were 12.5, 23 and 43 months, respectively. However, the median time of LC-ACLF patients developing to decompensated cirrhosis and HCC were 7 and 14 months, which was significantly shorter than that in CHB-ACLF group (P=0.009, 0.040, with statistical significance). Furthermore, the blood chemical parameters including serum albumin (ALB), cholinesterase (CHE) and total cholesterol (TC), triglyceride (TG), as well as platelet count (PLT), the anti-viral treatment compliance and the virus mutation were significantly related to the clinical endpoint events, respectively (P<0.05). Moreover, results from the logistic regression model demonstrated that the patient age, with or without liver cirrhosis, HBV mutation and the anti-viral treatment compliance were the independent risk factors for the long-term prognosis of patients with hepatitis B associated liver failure (OR=1.035, 0.510, 2.462, respectively. P< 0.05). The cumulative risk of Lc-ACLF patients progressed to decompensate cirrhosis, acute-on-chronic liver failure or HCC was significantly higher than that of CHB-ACLF patients (χ²=21.603, 4.423, P=0.000, 0.035, respectively). Conclusions Considering the importance of patients with or without liver cirrhosis, HBV mutation and the anti-viral treatment compliance in the long-term prognosis of HBV-ACLF patients, it is necessary and important to monitor the virus mutation and anti-viral treatment compliance of HBV- ACLF patients during antiviral therapy and those processes would benefit the improvement of long term prognosis of the patients with ACLF.

Objective: To study the clinical value of serum cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase (MMP)-9/NGAL-1 measurements for early diagnosis of acute kidney injury (AKI) in patients with acute-on-chronic liver failure (ACLF). Methods: This study included 102 patients with hepatitis B virus related ACLF and 31 patients with chronic hepatitis B (CHB) were enrolled as controls. Biomarkers including serum cystatin C, NGAL and MMP-9/NGAL-1 were measured twice in the patients with ACLF at admission and at the time progressed to AKI and once in the controls. Results: In patients with ACLF, serum cystatin C levels was higher than that of the CHB control (t=3.609, P=0.000), whereas NGAL and MMP-9/NGAL-1 levels were lower in patients with ACLF than that of CHB controls (t=3.016, P=0.003; t=7.514, P=0.000, respectively). Thirty-three patients (32.4%) progressed to AKI during hospitalization period. In AKI group of the patients serum cystatin C levels was higher than that of non-AKI group of the patents (t=4.543, P=0.000). MMP-9/ NGAL-1 and NGAL levels were not different in patients with and without AKI (t=0.905, P=0.368; t=0.061, P=0.952). Serum cystatin C in patients with mild AKI (serum creatinine<1.5 mg/dl) and AKI serum creatinine>1.5 mg/dl were 33.59± 9.19 ng/ml and 43.32±9.02 ng/ml respectively. That was higher than that of non-AKI patients (27.94±7.93 ng/ml, P=0.022, 0.000, respectively). Serum cystatin C was the independent risk factors associated with development of AKI by a multivariate logistic regression in patients with ACLF. Conclusions Serum cystatin C measurement may contribute to more earlier diagnosis of AKI even in patients with S. creatinine<1.5 mg/dl. NGAL and MMP-9/NGAL-1 may be the biomarker of progress for ACLF.