Liver failure caused by hepatitis B virus (HBV) infection is common in China, among which acute-on-chronic liver failure (ACLF) is the main type.Because the pathogenesis is complex and the diagnosis and treatment is difficult,HBV related ACLF has high mortality.In recent years, some progress has achieved in diagnosis and therapy of ACLF.This article reviews the new strategies and advances about HBV related ACLF on basis of researches at home and abroad,including the definition, mechanisms, management and prognosis assessment of ACLF.

Hepatitis B virus (HBV)-related liver failure has an extremely high mortality rate and a complex pathogenesis,and since related mechanisms are not fully understood,it has been very difficult to diagnose and treat this disease in clinical practice.Apart from liver transplantation,there is still a lack of specific and effective drugs and therapies for the medical treatment of HBV-related liver failure.This article summarizes our experience and research achievements in the diagnosis and treatment of HBV-related liver failure,explores the association between host's genetic background and development and aggravation of chronic hepatitis B,and elaborates on the phenomenon of three attacks and the concept of four time phases.In the aspect of treatment,this article focuses on the clinical application of antiviral therapy,anti-infective therapy,glucocorticoids,and stem cell transplantation;for the evaluation of patients' condition,this article establishes a suitable system for evaluating the prognosis of HBV-related liver failure.

OBJECTIVETo evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) after failure of nucleoside-analogues (NAs).

METHODSA total of 30 CHB patients who had been previously treated with NAs and had subsequently completed a 48-week course of TDF were retrospectively investigated. Patients' data of HBV DNA level (log10 copies/ml) and rate of undetectable HBV DNA at treatment weeks 0 (baseline), 4, 12, 24, 36 and 48 were collected for evaluation. The lower limit of HBV DNA detection was 100 IU/ml. The serum alanine aminotransferase (ALT) normalization rate, hepatitis B e antigen (HBeAg) seroconversion rate, viral breakthrough (VBT) rate, viral response (VR) rate, and adverse events were determined upon treatment completion. Statistical analyses were carried out using the Student's t-test, the x² test or the Kaplan-Meier method.

RESULTSOver the 48-week treatment period, HBV DNA levels declined significantly from baseline (week 4:(2.11 ± 0.38) log10 IU/ml, t =5.582; week 12:(0.93 ± 0.31) log10 IU/ ml, t =9.303; week 24:(0.75 ± 0.20) log10 IU/ml, t =3.123; week 36:(0.16 ± 0.19) log10 IU/ml, t =10.759; week 48:(0.14 ± 0.25) log10 IU/ml, t =12.202) (all P less than 0.01). However, the rates of HBV DNA reduction and of cumulative reduction were comparable at weeks 24, 36 and 48 (all P more than 0.05). The most robust decline in HBV DNA levels was observed at week 4 ((2.11 ± 0.38) log10 IU/ml) and the highest cumulative HBV DNA reduction was observed at week 24 ((3.79 ± 0.37) log10 IU/ml). The rate of undetectable HBV DNA at week 4 (26.7%) was significantly lower than that at weeks 24 (87.5%, P less than 0.01), 36 (80.0%, P=0.007), and 48 (88.9%, P=0.001). The median time to achieving undetectable HBV DNA was 10.4 weeks (range:3.43-34.0 weeks). At week 48, the rates of VR, HBeAg seroconversion, and VBT were 88.9% ,6.7%, and 0% respectively. During treatment, the levels of creatine kinase were more than two times the upper limit normal in 9.2% of the patients, and were comparable at each time point examined (all P more than 0.05). All patients showed a normal level of serum creatinine throughout the treatment period.

CONCLUSIONFor CHB patients with non-response to NAs, TDF can suppress HBV DNA replication very quickly and achieve a high rate of ALT normalization with a low rate of adverse events.

Adenine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Male ; Middle Aged ; Organophosphonates ; administration & dosage ; therapeutic use ; Retrospective Studies ; Tenofovir ; Young Adult

Liver failure has various clinical types, a complex pathogenesis, and rapid disease progression, as well as a high mortality rate. Liver failure caused by hepatitis B virus infection is the most common type in China with severe conditions, various complications, and a mortality rate as high as 40%-90%. Invasive fungal disease secondary to acute-on-chronic liver failure can affect patients’ prognosis and increase mortality rate. This article introduces the research advances in hepatitis B-related liver failure, artificial liver, and invasive fungal disease secondary to acute-on-chronic liver failure in 2016.