ABSTRACT
Background/Aims@#Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. @*Methods@#This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. @*Results@#68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. @*Conclusions@#48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.
ABSTRACT
Expanding antiviral therapy is currently the new trend for the diagnosis and treatment of chronic hepatitis B, and related research evidence should be studied and discussed. Reducing the threshold of alanine aminotransferase (ALT) for initiating antiviral therapy is one of the most important changes during the expansion of antiviral therapy. Chronic hepatitis B patients with a low-level increase in ALT or a high normal level of ALT still have a higher risk of liver cancer and thus require further intervention. At present, nucleos(t)ide analogues show a certain clinical effect in some patients in terms of virological inhibition and improvement in fibrosis, while reducing ALT threshold places higher requirements for biochemical response after treatment. In addition, although the mechanism and definition of low-level viremia (LLV) after treatment remain unclear, further intervention of LLV is an important strategy for optimizing patient management in clinical practice. Switch to another potent nucleos(t)ide analogue may improve the virologic response rate of patients with LLV, and nucleos(t)ide analogues combined with interferon or other new targeted drugs will be an important research direction for the treatment of LLV in the future.
ABSTRACT
Noninvasive methods for the evaluation of liver fibrosis have been widely validated with liver biopsy as the gold standard. This article elaborates on the application of various imaging methods in the evaluation of liver fibrosis and their prospects in evaluating the reversal of liver fibrosis. Transient elastography is the main imaging method for evaluating the reversal of liver fibrosis and can show the improvement in liver fibrosis via liver stiffness measurement, but the association between the reduction in liver stiffness measurement and the improvement of liver fibrosis remains unclear.
ABSTRACT
Objective@#To investigate the prevalence and risk factors of non-alcoholic fatty liver disease(NAFLD) in patients with chronic hepatitis B(CHB) receiving antiviral treatment.@*Methods@#The cross-sectional study included 3 477 cases with CHB who received antiviral therapy. The prevalence of NAFLD was investigated, and then the risk factors were screened and analyzed by stepwise regression method in CHB patients with NAFLD as the dependent variable and the related influencing factors as independent variables.@*Results@#The prevalence of NAFLD was 24.1% in CHB patients who received antiviral therapy. After adjusting for age and gender, central obesity (OR: 7.44, 95%CI: 6.06 ~ 9.14), hypertension (OR: 1.74, 95%CI: 1.51 ~ 2.20), and triglyceride (OR: 1.52, 95%CI: 1.18 ~ 1.96) were positively associated with NAFLD, and cirrhosis was negatively associated with NAFLD (OR: 0.42, 95%CI: 0.34 ~ 0.53). Patients with long-term antiviral therapy had increased risk of NAFLD.@*Conclusion@#A significant proportion of CHB patients receiving antiviral therapy have suffered from NAFLD. Therefore, CHB patients receiving long-term antiviral treatment should pay more attention to the prevalence of NAFLD.
ABSTRACT
Objective To evaluate the value of transient elastography (TE) for predicting severity of liver fibrosis in patients with chronic hepatitis B (CHB).Methods A total of 969 patients with CHB was enrolled and recruited for analysis,which had been received TE scan,including 258 patients of liver biopsy,and 117 patients of gastric endoscopy.Results A total of 35 patients was excluded from analysis due to TE failure or unreliable TE.Liver stiffness measurement (LSM) was independently influenced by bilirubin,AST,liver fibrosis and inflammation,ultrasonic score and albumin.TE predicted Child-Pugh C,B/C,liver fibrosis S4,≥S3 and ≥ S2 with respective area under receiver operating characteristics curves (AUROC)0.907 (95% CI 0.886-0.928 ),0.920 ( 95% CI 0.899-0.940 ),0.871 ( 95% CI 0.819-0.923 ),0.852(95%CI0.805-0.899) and 0.807(95% CI0.749-0.865),respectively.While LSM <32.2 kPa excluded Child-Pugh C with 99.4% probability,LSM ≥35.3 kPa determined Child-Pugh B/C with positive predictive value (PPV) 0.820.For compensated CHB,cut-offs of LSM 23.3,15.2 and 10.8 kPa diagnosed cirrhosis,liver fibrosis ≥S3 and ≥S2 with positive likelihood ratio nearly 10.0 and PPV 0.692,0.882 and 0.980,respectively; and cut-offs 8.8 kPa,6.6 kPa excluded cirrhosis,liver fibrosis ≥ S3 with negative likelihood ration nearly 0.1 and negative predictive value 0.977 and 0.903,respectively.Correlation coefficient between LSM and grades of esophageal varices was only 0.180,and AUROC for TE predicting EV was of no clinical value.ConclusionTE relatively make accurate prediction in the severity of liver fibrosis and classification of Child-Pugh.Patients with LSM ≥ 10.8 kPa should be considered for receiving antivirus treatment.