OBJECTIVES: Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is the most common type of liver failure in China, with a high mortality. Early rapid reduction of HBV-DNA load can improve the survival rate of HBV-ACLF patients. At present, the commonly used drugs are nucleoside (acid) analogues, such as entecavir (ETV), tenofovir, and so on. The newly listed tenofovir alafenamide fumarate (TAF) has attracted great attention of clinicians because of its stronger antiviral effect, higher transaminase normalization rate, better bone and kidney safety, and zero drug resistance. However, there are few clinical research data on the efficacy and safety of TAF in the treatment of Chinese HBV-ACLF patients, and there is a lack of pharmacoeconomic evaluation. This study aims to compare the efficacy, safety, and cost-effectiveness between TAF and ETV in patients with HBV-ACLF. METHODS: The data were collected from 196 HBV-ACLF patients (80 patients in the TAF group and 116 patients in the ETV group) who were hospitalized in Xiangya Hospital, Central South University from May 2020 to March 2021. Biochemistry and virology were detected before and after treatment (at baseline, Week 2, 4, and 12). Clinical features, disease prognosis, and cost-effectiveness were compared between the 2 groups. According to the baseline, HBV-ACLF patients were divided into 4 stages including pre-liver failure stage, early stage, medium stage, and end stage. And the liver transplantation rate and mortality was also compared. Pharmacoeconomic evaluation was taken using cost-effectiveness analysis and cost minimization analysis．. RESULTS: After 4 weeks of treatment, there were no significant differences in the efficacy (liver function, viral load) between the 2 groups (all P>0.05). The TAF group showed lower creatinine [(80.35±18.77) μmol/L vs (105.59±82.32) μmol/L, P<0.05] and higher estimated glomerular filtration rate (eGFR) levels [(95.65±23.21) mL/(min·1.73 m²) vs (82.68±26.32) mL/(min·1.73 m²), P<0.05] than the ETV group. After 12 weeks of treatment, the analysis of overall the liver transplantation rate and mortality between the 2 groups showed similar conclusion. However, the TAF group had a lower the liver transplantation rate and mortality than the ETV group in patients with pre-liver failure (0vs13.89%, P<0.05). No evident distinction was found in the liver transplantation rate and mortality during the early, medium, or end stages of liver failure (13.04% vs 17.65%, 37.50% vs 37.04%, and 54.55% vs 68.42%, respectively). Ratio of cost to effectiveness in the ETV group was higher than that in the TAF group. CONCLUSIONS TAF is not more efficient than ETV group in improving liver function and reducing viral load for HBV-ACLF patients and they also show similar safety. However, TAF has a greater advantage over ETV not only in preserving renal function, but also in reducing the liver transplantation rate and mortality in patients with pre-liver failure. TAF can provide economic benefit to patients with HBV-ACLF.
Acute-On-Chronic Liver Failure/drug therapy* ; Alanine/therapeutic use* ; Antiviral Agents/therapeutic use* ; Guanine/analogs & derivatives* ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Humans ; Tenofovir/analogs & derivatives* ; Treatment Outcome

Acute-on-chronic liver failure (ACLF) is a form of complex syndrome with acute deterioration of liver function that occurs on the basis of chronic liver disease, and is accompanied by hepatic and extrahepatic organ failure with high mortality rate. The short-term mortality rate of comprehensive internal medicine treatment is as high as 50%-90%. This paper summarizes the current common definitions and diagnostic criteria, early-warning prediction models, and pathogenesis of ACLF.
Acute-On-Chronic Liver Failure/therapy* ; Humans ; Prognosis

Acute-On-Chronic Liver Failure/therapy* ; Gastroenterology ; Humans ; United States

In January 2022, the American College of Gastroenterology released its first clinical guidelines, integrating the latest research, summarizing the three current definitions characteristics, and proposing recommendations and core viewpoints with important clinical practice value to guide diagnosis, treatment, and management of acute-on-chronic liver failure. This article interprets and summarizes the highlights of the guideline, raises controversial issues, and suggests directions for future research.
Acute-On-Chronic Liver Failure/therapy* ; Gastroenterology ; Humans ; United States

OBJECTIVETo evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction (, YCZFD) in the treatment of acute-on-chronic liver failure caused by hepatitis B virus (HBV-ACLF) with cold pattern in Chinese medicine (CM).

METHODSThis is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine (WM) for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM (integrative treatment) or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage Liver disease (MELD) score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported.

RESULTSThe mortality was decreased 14.28% in the integrative treatment group compared with WM group (χ(2) =6.156, P=0.013). The integrative treatment was found to signifificantly improve the MELD score (t=2.353, P=0.020). There were statistically signifificant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups (P<0.05 or P<0.01). The complications of ascites (χ(2)=9.033, P=0.003) and spontaneous bacteria peritonitis (χ(2)=4.194, P=0.041) were improved signifificantly in the integrative treatment group. No serious adverse event was reported.

CONCLUSIONSThe integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle "treating cold pattern with hot herbs" remains valuable to the clinical therapy. (Trial registration No. ChiCTR-TRC-10000766).

Acute-On-Chronic Liver Failure ; complications ; drug therapy ; mortality ; virology ; Adult ; Ascites ; complications ; Demography ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Electrolytes ; Female ; Hepatitis B ; complications ; drug therapy ; mortality ; physiopathology ; Hepatitis B virus ; physiology ; Humans ; Integrative Medicine ; Liver ; drug effects ; pathology ; physiopathology ; virology ; Liver Function Tests ; Male ; Peritonitis ; complications ; Time Factors ; Treatment Outcome

Acute-On-Chronic Liver Failure ; diagnosis ; virology ; Antiviral Agents ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Nucleosides ; therapeutic use ; Nucleotides ; therapeutic use ; Prognosis

BACKGROUND/AIMS: Hepatitis-B-related acute-on-chronic liver failure has a poor prognosis. However, the advent of potent oral antiviral agents means that some patients can now recover with medical treatment. We aimed to identify the prognostic factors for hepatitis-B-related acute-on-chronic liver failure including the initial as well as the dynamically changing clinical parameters during admission. METHODS: Sixty-seven patients were retrospectively enrolled from 2003 to 2012 at Samsung Medical Center. The patients were classified into three categories: Recovery group (n=23), Liver transplantation group (n=28), and Death group (n=16). The Liver transplantation and Death groups were combined into an Unfavorable prognosis group. We analyzed the prognostic factors including the Model for End-Stage Liver Disease (MELD) scores determined at 3-day intervals. RESULTS: A multivariable analysis showed that the unfavorable prognostic factors were a high initial MELD score (> or =28) (odds ratio [OR] =6.64, p=0.015), moderate-to-severe ascites at admission (OR=6.71, P=0.012), and the aggravation of hepatic encephalopathy during hospitalization (> or =grade III) (OR=15.41, P=0.013). Compared with the baseline level, significant reductions in the MELD scores were observed on the 7th day after admission in the Recovery group (P=0.016). CONCLUSIONS: Dynamic changes in clinical parameters during admission are useful prognostic factors for hepatitis-B-related acute-on-chronic liver failure.
Acute-On-Chronic Liver Failure/*diagnosis/drug therapy/etiology ; Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antiviral Agents/therapeutic use ; Cyclophosphamide/therapeutic use ; DNA, Viral/analysis ; Doxorubicin/therapeutic use ; Female ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*diagnosis/drug therapy ; Hospitalization ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Prednisone/therapeutic use ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Vincristine/therapeutic use ; Young Adult

OBJECTIVETo evaluate the clinical efficacy and safety of integrative medical program based on blood cooling and detoxification recipe (BCDR) in treating patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) of heat-toxicity accumulation syndrome (HTAS).

METHODSAdopting randomized controlled clinical design, a total of 105 HBV-ACLF patients of HTAS were randomly assigned to the trial group (64 cases) and the control group (41 cases). Patients in the control group were treated with comprehensive Western therapy, while those in the trial group were treated with comprehensive Western therapy plus BCDR. All were treated for 8 weeks and followed up for 40 weeks. Effect and safety of the treatment were assessed, including fatality, liver functions [total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), and aspartate transaminase (AST)], and prothrombin activity (PTA) after treatment and at week 48 of follow-ups.

RESULTSAfter 8-week treatment, there was statistical difference in the overall fatality rate (15.63% vs 34.15%), the fatality rate in the mid-term (25.0% vs 64.7%), TBIL at week 8 (64.54 +/- 79.75), AST [at week 2: (178.97 +/- 44.24) U/L vs (288.48 +/- 58.49) U/L; at week 4: (61.65 +/- 27.36) U/L vs (171.12 +/- 89.11) U/L] and PTA [at week 4: (58.30 +/- 15.29) vs (42.56 +/- 15.27); at week 6: (60.77 +/- 20.40) vs (43.08 +/- 12.79)] (all P < 0.05). At week 48 of the followup, the fatality rate of the trial group (21.88%) decreased by 17. 14% when compared with that of the control group (39.02%; P < 0.05). No obvious adverse event occurred in the two groups during the 8-week treatment period.

CONCLUSIONBCDR could significantly reduce the mortality of HBV-ACLF patients.

Acute-On-Chronic Liver Failure ; drug therapy ; virology ; Adult ; Drugs, Chinese Herbal ; therapeutic use ; End Stage Liver Disease ; Female ; Hepatitis B virus ; Hepatitis B, Chronic ; drug therapy ; Humans ; Male ; Middle Aged ; Phytotherapy ; Young Adult

To observe the therapeutic effects of lamivudine treatment in patients with early- to mid-stage hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Clinical data of 73 hospitalized patients with HBV-ACLF were retrospectively analyzed. Prothrombin time (PT, active coagulation), HBV DNA, and model for end-stage liver disease (MELD) score data from treatment weeks 4, 8, 24, and 48 were collected and analyzed using the statistical t-test. During the treatment duration, the complete virologic response rates were 57.5% (42/73) at 4 weeks, 71.0% (44/62) at 8 weeks, 83.1% (49/59) at 24 weeks, and 86.5% (45/52) at 48 weeks. The partial virologic response rates were 30.1% (22/73) at 4 weeks, 25.8% (16/62) at 8 weeks, 17.0% (10/59) at 24 weeks, and 13.5% (7/52) at 48 weeks. At week 48, the survival rate was 71.2% (52/73) and the probability of survival was higher in the complete virological response rate (VRR) group than in the partial VRR group [45/73 (61.6%) vs. 7/73 (30.1%), respectively; P = 0.000]. In addition, there were significant improvements in the serum normalization rate of HBV DNA, alanine aminotransferase, aspartate aminotransferase, albumin, total bilirubin, PT and MELD score in surviving patients compared to baseline (P less than 0.05) and in the complete VRR group compared to the partial VRR group (P less than 0.05). Antiviral therapy using lamivudine may be an effective therapeutic option for patients with HBV-ACLF.
Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis B, Chronic ; complications ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Liver Failure, Acute ; drug therapy ; etiology ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Young Adult

Hepatitis A virus is a major cause of viral hepatitis worldwide. The prevalence of hepatitis A in young adults has recently been increasing in Korea. Hepatitis A infection rarely complicates fulminant hepatitis, acute pancreatitis, and acute renal failure. We experienced a case of multiple organ failure involving fulminant hepatitis, acute pancreatitis, and acute renal failure complicating a hepatitis A superinfection in a chronic hepatitis B patient. The patient was a 38 year old man who presented with febrile sense and myalgia. He was initially alert, but became confused and developed acute renal failure and acute pancreatitis. He received continuous renal replacement therapy and conservative treatment and completely recovered from the multiple organ failure. It is important to consider a variety of potential complications in hepatitis A patients, especially in those with underlying chronic liver disease.
Acute Kidney Injury ; Hepatitis ; Hepatitis A ; Hepatitis A virus ; Hepatitis B ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Korea ; Liver Diseases ; Multiple Organ Failure ; Pancreatitis ; Prevalence ; Renal Replacement Therapy ; Superinfection ; Young Adult