OBJECTIVES: To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored. RESULTS: Within 90 days after diagnosis, 53 (29.4%) of the patients died and 127 (70.6%) survived. The deceased patients had significantly lower baseline serum tryptophan levels than the survivors (7.31±3.73 pg/mL vs 13.32±7.15 pg/mL, P<0.001). Multivariate analysis suggested that serum tryptophan level was an independent factor correlated with mortality of HBV-ACLF after adjustment for confounding variables. The patients with serum tryptophan levels below the median level (10.14 pg/mL) at admission had significantly higher 90-day mortality risks than those with higher tryptophan levels (43.3% vs 15.6%, HR: 3.157, 95% CI: 1.713-5.817), and the complication by kidney dysfunction further increased the risk to 73.3% as compared with patients with higher serum tryptophan levels with normal kidney function (15.0%; HR: 7.558, 95% CI: 3.369-16.960). Serum tryptophan levels had an area under the receiver operating characteristic curve of 0.771 (95% CI: 0.699-0.844) for predicting 90-day mortality. CONCLUSIONS Serum tryptophan level is closely correlated with the survival outcomes of patients with HBV-ACLF, and a decreased tryptophan level indicates a high 90-day mortality risk, which can be further increased by the complication by kidney dysfunction.
Humans ; Tryptophan/blood* ; Retrospective Studies ; Acute-On-Chronic Liver Failure/virology* ; Male ; Female ; Middle Aged ; Adult ; Prognosis ; Hepatitis B/complications* ; Hepatitis B virus

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

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

OBJECTIVECell-free DNA (cfDNA) was shown to be a prognostic marker for diverse pathological states in the Intense Care Unit, but little is known of the role of cfDNA in HBV-related acute-on-chronic liver failure (ACLF). We hypothesize that cfDNA can also be a promising prognostic as well as a diagnostic marker in patients with HBV-related ACLF.

METHODSThirty-eight patients with HBV-related ACLF admitted in the Intense Care Unit were enrolled in the study. The patients were divided, according to the improvement of liver function at discharge, into favorable prognosis group (group 1, n=17) and poor prognosis group (group 2, n=19). Plasma samples were collected from each patient at hospitalization and at discharge to measure cfDNA by real-time quantitative PCR. MELD score was calculated at the same time points.

RESULTSThe average level of cfDNA of group 1 was lower than that of group 2 both at the time of hospitalization (P=0.044) and at discharge (P<0.001). There was no difference in MELD score between the two groups at hospitalization. Significant correlations were found of cfDNA levels with the MELD score, TBIL, CRE and INR both at hospitalization (γ=0.662, P<0.001; γ=0.356, P=0.033; γ=0.360, P=0.031; γ=0.570, P<0.001, respectively) and at discharge (γ=0.854, P<0.001; γ=0.821, P<0.001; γ=0.650, P<0.001; γ=0.638, P<0.001, respectively). The ROC curve showed that cfDNA level at discharge was optimal in diagnosing ACLF with an area under curve (AUC) value of 0.96, followed by δcfDNA (AUC value of 0.923) and cfDNA level at hospitalization (AUC value of 0.667). The MELD scores had an AUC value of only 0.545 at the time of hospitalization.

CONCLUSIONcfDNA may serve as a promising prognostic and diagnostic marker for predicting in-hospital prognosis of HBV-related ACLF within 2 to 8 weeks.

Acute-On-Chronic Liver Failure ; diagnosis ; virology ; Adult ; DNA, Viral ; blood ; End Stage Liver Disease ; diagnosis ; Female ; Hepatitis B ; complications ; Hepatitis B virus ; genetics ; Humans ; Male ; Middle Aged ; Pilot Projects ; Plasma ; chemistry ; Prognosis ; Severity of Illness Index

Acute-On-Chronic Liver Failure ; complications ; virology ; Adult ; DNA Mutational Analysis ; Female ; Genetic Variation ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; complications ; virology ; Humans ; Male ; Middle Aged

OBJECTIVETo investigate the short-term prognostic value of the indocyanine green clearance test when used in combination with the model for end-stage liver disease (MELD) scoring system to assess patients with hepatitis B virus acute-on-chronic liver failure (HBV-ACLF).

METHODSClinical data of 105 patients diagnosed with HBV-ACLF were retrospectively analyzed. The indocyanine green retention rate at 15 minutes (ICGR15), clinical data within 24 h after diagnosis, Child-Turcotte-Pugh (CTP) classification, MELD score, MELD combined with sodium concentration (MELD-Na) score, and King's Hospital (KCH) criteria data were collected for analysis. Measurement data were assessed by t-test and count data by the chi-square test. Short-term predictive accuracy for patients with HBV-ACLF was compared between different models using the area under the receiver operating characteristic (ROC) curve (AUC).

RESULTSThe mortality rate for all patients was 45.71%. Comparison of the survivors versus the non-survivors showed that age, total bilirubin, albumin, cholinesterase, creatinine, international normalized ratio, and incidence positive rate of relative complications (hepatorenal syndrome, hepatic encephalopathy) were significantly different between the two groups (all, P less than 0.05). The ICGR15 was found to be positively correlated with MELD score (r = 0.205, P less than 0.05). The MELD-ICGR15 model constructed by logistic regression analysis was: Logit(P) = 0.193 * MELD + 0.130 * ICGR15 - 11.256. The AUC was 0.880 and the cut-off was -0.706, with 89.6% sensitivity and 75.4% specificity. The AUC of the MELD-ICGR15 model was significantly higher than that of the ICGR15 (0.820), MELD score (0.779), MELD-Na score (0.761), KCH criteria (0.680), and CTP classification (0.631) (all, P less than 0.05).

CONCLUSIONICGR15, MELD score, and MELD-Na score had higher predictive values for HBV-ACLF than did CTP classification or KCH criteria. Furthermore, the MELD-ICGR15 model was better than any single parameter model for predicting the short-term prognosis of patients with HBV-ACLF.

Acute-On-Chronic Liver Failure ; diagnosis ; virology ; Adult ; Aged ; End Stage Liver Disease ; Female ; Hepatitis B ; complications ; Humans ; Indocyanine Green ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Young Adult

OBJECTIVETo investigate the dynamics and clinical significance of serum hepatitis B virus (HBV) DNA levels during the terminal phase of acute-on-chronic liver failure (ACLF) with different hepatitis B e antigen (HBeAg) status.

METHODSOne-hundred-and-seven patients with terminal ACLF were tested for HBeAg status by electrochemiluminescence immunoassay and serum HBV DNA levels by real-time PCR at three chronological time ranges, representing increasing severity of disease phases prior to death (day 0): 29-56 d, 15-28 d, and 0-14 d.

RESULTSIn the 37 HBeAg(+) patients, HBV DNA levels at above-mentioned phases were 6.10+/-1.63, 5.61+/-1.50, and 5.29+/-1.96 log10 copies/mL. In the 70 anti-HBe(+) patients, HBV DNA levels were 4.63+/-1.82, 5.81+/-1.78, and 4.93+/-1.73 log10 copies/mL. Phase to phase comparisons revealed that the HBV DNA level in the HBeAg(+) group was significantly higher than that in the anti-HBe(+) group at 29-56 d (P less than 0.05), and that 15-28 d and 0-14 d were not significantly different (P more than 0.05). Intragroup comparisons of phases revealed no significant differences in the HBeAg(+) group (P more than 0.05), but a significant difference between 15-28 d and 0-14 d (P less than 0.05) for the anti-HBe(+) group.

CONCLUSIONSerum levels of HBV DNA in patients with HBeAg positivity are higher than those in patients with anti-HBe positivity as the disease phase of ACLF nears fatality. Following the deterioration to liver failure, the HBV DNA load in HBeAg(+) patients remains stable while that in anti-HBe(+) patients decreases.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; DNA, Viral ; blood ; End Stage Liver Disease ; blood ; virology ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; pathology ; Humans ; Liver Failure, Acute ; blood ; virology ; Male ; Middle Aged ; Viral Load ; Young Adult

Critical Illness ; DNA, Viral ; blood ; genetics ; Genotype ; Hepatitis B Surface Antigens ; blood ; genetics ; Hepatitis B virus ; classification ; genetics ; physiology ; Hepatitis B, Chronic ; pathology ; virology ; Humans ; Liver Failure, Acute ; pathology ; virology ; Mutation ; Promoter Regions, Genetic ; genetics ; Virus Replication

Antiviral Agents ; therapeutic use ; Critical Illness ; Genotype ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; etiology ; prevention & control ; virology ; Humans ; Liver Failure, Acute ; etiology ; prevention & control ; virology ; Mutation ; Virus Replication