Prospective, multicentre, randomised controlled trial comparing the seroclearance of HBsAg between combination therapy of peg-interferon alpha and tenofovir with tenofovir monotherapy in nucleos(t)ide analogue-experienced patients with HBV-related liver fibrosis: a study protocol

IntroductionCombination antiviral therapy of nucleos(t)ide analogue (NA) and pegylated interferon alpha (peg-IFN alpha) decrease hepatitis B virus (HBV) surface antigen (HBsAg) levels to achieve functional cure and improve long-term prognosis in chronic hepatitis B patients. However, for hepatitis B-related liver fibrosis, studies on combination of these two medicines are limited. This study was designed to compare the efficacy between peg-IFN alpha combined with tenofovir (TDF) and TDF monotherapy for the clearance of HBsAg in NA-experienced patients with HBV-related liver fibrosis.Methods and analysisThis study was designed to be a prospective, multicentre, open, randomised controlled study. A total of 272 patients with HBV-related liver fibrosis will be randomised into the combination therapy group or the monotherapy group at a 1:1 ratio. Participants in the combination group will receive subcutaneous injections of peg-IFN alpha 180 µg per week for 48 weeks combined with oral TDF 300 mg daily. Participants in the monotherapy group will receive 300 mg oral TDF daily alone. All participants will undergo long-term treatment with TDF and will be followed up at the outpatient department for 144 weeks after randomisation. Clinical symptoms, laboratory tests and examination indicators will be collected at each follow-up time point, and adverse events will be recorded. The primary endpoint is serological clearance rate of HBsAg at 48 weeks.Ethics and disseminationThe ethics committee of the Third Affiliated Hospital at Sun Yat-sen University approved this study (Approval Number: (2020)02-183-01). The results of the study will be presented at relevant meetings and published in an appropriate journal after the completion of the trial and the analysis of the data.Trial registration numberNCT04640129.

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Defining phenotypes of long-term lithium and valproate response, including combination therapy: a modified application of the Alda scale in patients with bipolar disorders

International Journal of Bipolar Disorders ◽

10.1186/s40345-020-00199-w ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

Jinyoung Lee ◽

Ji Hyun Baek ◽

Dongbin Lee ◽

Sung Woo Ahn ◽

So-Yung Yang ◽

...

Keyword(s):

Combination Therapy ◽

Treatment Response ◽

Mood Stabilizer ◽

Term Treatment ◽

Mood Stabilizers ◽

Combination Group ◽

Monotherapy Group ◽

Clinical Correlates ◽

Long Term Treatment

Abstract Background When evaluating the long-term treatment response to mood stabilizers using the Alda scale, mood stabilizer combination therapy is typically considered a confounding factor, and patients receiving combination therapy are excluded from the analysis. However, this may result in bias if those under combination therapy are worse treatment responders. This study aims to explore whether the Alda scale is applicable to patients taking lithium and valproate combination therapy. We compared long-term treatment response in patients receiving monotherapy and combination therapy of the two drugs, and investigated clinical correlates of the responses to each drug. Methods The study subjects consisted of 102 patients with bipolar I (BD-I) or bipolar II (BD-II) disorder who had been undergoing maintenance treatment with lithium and/or valproate for more than 2 years at a single specialized bipolar disorder clinic. Long-term treatment response was measured using the Alda scale and compared among the lithium monotherapy group, the valproate monotherapy group, and the mood stabilizer combination group. Clinical correlates of long-term treatment response were evaluated in lithium users and valproate users separately. Results There were no significant differences in terms of baseline illness characteristics among groups. The combination group showed the worst treatment response for all the response measurements applied. This group also had the higher rate of ‘poor responder’ with a statistically significant difference compared to valproate group. Older age at onset and (hypo)manic episode at onset showed significant positive associations with total Alda score in lithium users, while comorbid anxiety disorders, obsessive–compulsive disorder and mixed episode showed significant negative associations in valproate users. Conclusions The combination group had poorer long-term treatment response but did not show distinct clinical characteristics compared to the monotherapy groups. When exploring the long-term effects of mood stabilizers, excluding patients undergoing combination treatment could result in bias because they may represent a poor response group. The long-term treatment responses of lithium and valproate had different clinical correlates.

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LIVER FIBROSIS RESPONSE TO ENTECAVIR TREATMENT IN PATIENTS WITH HBV-RELATED COMPENSATED CIRRHOSIS

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2018.6.27 ◽

2018 ◽

Vol 8 (6) ◽

pp. 203-209

Author(s):

Trung Doan Hieu ◽

Chuong Tran Xuan

Keyword(s):

Hepatitis B Virus ◽

Liver Fibrosis ◽

Hepatitis B ◽

Acoustic Radiation ◽

Term Treatment ◽

Related Factors ◽

Compensated Cirrhosis ◽

Long Term Treatment ◽

B Virus

Background: Evaluating improvement of liver fibrosis response after anti HBV therapy in our country until now is very limited, especially in patients with cirrhosis. This study aimed at assessing the respone in liver fibrosis determined by ARFI and its related factors for patients with compensated HBV-related cirrhosis undergoing entecavir therapy. Subjects and methods: 60 patients with compensated HBV-related cirrhosis were enrolled at Da Nang Hospital from 06/2016 to 06/2018. All received entecavir 0,5mg a day 2 hours after breakfast and followed in 18 months. Liver fibrosis is measured by Acoustic Radiation Forced Imaging (ARFI). Results: Entecavir treatment may result in improvement of liver fibrosis in 20% after 12 months and 26.67% after 18 months in patients with compensated hepatitis B virus-related cirrhosis. The improvement in fibrosis levels was significant after at least 12 months of treatment. Factors associated with improvement of fibrosis response in this study included AST, ALT, AFP are high, HBeAg (+), low prothrombin time at baseline, and indetectable HBV DNA after 6 months of treatment. Conclusion: Entecavir treatment may help to improve liver fibrosis in patients with hepatitis B virus-related compensated cirrhosis, but long-term treatment is needed. Key words: Entecavir, HBV cirrhosis, liver fibrosis, ARFI

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