[Prognostic value of a logistic regression model based on keratin 18 in patients with HBV-related liver failure].

Objective: To investigate the association between serum keratin 18 (K18) level and prognosis in patients with HBV-related acute-on-chronic liver failure (ACLF). Methods: A total of 120 patients who visited Department of Hepatology in Fuzhou Infectious Disease Hospital and were diagnosed with HBV-related ACLF from December 2012 to March 2014 were enrolled and followed up for 3 months. The patients were divided into death group and survival group. The serum levels of K18 fragments (M30 and M65) were measured and related laboratory data were collected to analyze the differences in M30, M65, M30/M65, and other laboratory markers. Binary logistic regression analysis was performed to screen out independent risk factors for death in patients with HBV-related ACLF, and the corresponding logistic regression model (LRM) was established. Another 51 patients with HBV-related ACLF from April to October, 2014 were enrolled; M30 and M65 were measured and related clinical data were collected to calculate LRM value and validate the diagnostic value of LRM. Results: The 120 patients with HBV-related ACLF were followed up for 3 months, and 40 of them died, resulting in a mortality rate of 33.3%. Compared with the survival group, the death group had significantly higher age, percentage of neutrophils, blood ammonia, international normalized ratio, Model for End-Stage Liver Disease (MELD) score, and M65, as well as significantly lower prothrombin time activity and alpha-fetoprotein level. The death group also had significantly higher incidence rates of underlying diseases and complications such as diabetes, liver cirrhosis, hepatic encephalopathy (HE), pulmonary infection, upper gastrointestinal bleeding, and hepatorenal syndrome than the survival group. Age, HE, upper gastrointestinal bleeding, direct bilirubin (DBil), and M30/M65 were independent risk factors for the prognosis of patients with HBV-related ACLF. The model established was LRM = 0.061 × age + 0.69 × HE + 4.11 × upper gastrointestinal bleeding + 3.201 × ln(DBil) - 3.875 × ln(M30/M65) - 24.248. The 51 patients with HBV-related ACLF were followed up for 3 months, and the LRM value and MELD score were calculated. The areas under the ROC curve for the LRM model and MELD score were 0.889 and 0.858, respectively, and there was no significant difference between them (Z = 0.417, P > 0.05). Conclusion: M30/M65 ratio has a high value in the diagnosis of HBV-related ACLF, and the LRM model containing M30/M65 ratio can well predict the short-term outcome of patients with HBV-related ACLF.

Increased intrahepatic quasispecies heterogeneity correlates with off-treatment sustained response to nucleos(t)ide analogues in e antigen-positive chronic hepatitis B patients.

Finite treatment with nucleos(t)ide analogues (NAs) remains a great challenge for chronic hepatitis B in the clinic. This study aimed to investigate the relationship between intrahepatic quasispecies heterogeneity and the NAs off-treatment outcomes in a prospective cohort. Eighteen HBeAg-positive patients with chronic hepatitis B who achieved the cessation criteria underwent liver biopsy, and stopped treatment thereafter. Patients were followed up prospectively for 1 year. The reverse transcriptase (RT) gene of intrahepatic hepatitis B virus (HBV) was cloned and sequenced. Intrahepatic quasispecies heterogeneity and specific gene mutations were analysed using bioinformatic methods. Ten patients achieved sustained response, and eight patients developed viral relapse. The intrahepatic quasispecies Shannon entropy and nucleotide diversity within either RT or the surface (S) region of patients with sustained response were significantly higher (p < 0.05) than those of patients who had a viral relapse. Intrahepatic quasispecies Shannon entropy at the nucleotide level predicted the sustained off-treatment response (area under receiver operating characteristics curve 0.925; 95% CI 0.807-1.000; p 0.003). More positive selection sites and N-glycosylation mutations within the S region were found in patients with sustained response than in the patients with viral relapse (p < 0.01). Most of the positive selection sites in patients with sustained response were located in reported HLA-I-restricted or HLA-II-restricted epitopes. Intrahepatic quasispecies heterogeneity at the end of treatment was correlated with off-treatment outcomes in HBeAg-positive patients with chronic hepatitis B. More immune escape mutations were found within the S region in patients with sustained response. The higher intrahepatic quasispecies heterogeneity indicated a more robust immune control over HBV, which in turn maintained a sustained response after withdrawal of NAs.