HBV-related Liver Cirrhosis
Conditions
Keywords
Telbivudine, renoprotective efficacy, liver cirrhosis
Brief summary
Chronic hepatitis B virus (HBV) infection is a serious clinical problem because of its worldwide distribution and potential adverse outcome, including cirrhosis, which is a major cause of HBV related death. Studies show the use of nucleot(s)ide analogs treatment can alleviate, even reverse the progress of HBV-related cirrhosis. In cirrhosis stage, some potential factors, including endocrine disorder, renin, aldosterone, vasopressin increasing, hepatitis B virus related nephritis, hepatorenal syndrome, may cause renal damage. With the exposure of NAs, adverse reports of rhabdomyolysis, renal dysfunction, and lactic acidosis are increasing. So when choosing NAs, the potential renal function impairment should be considered. Recently, Gane, Xiaoxi Li have separately reported that Telbivudine can improve estimate of glomerular filtration rate (eGFR) of patients with chronic hepatitis B, while eGFR of patients with Lamivudine, adefovir and entecavir have a trend of decrease, which suggested Telbivudine may have renal protective effects. This effect on patients with HBV-related liver cirrhosis has not been studied, which is not clear now. This study is a randomized controlled study to prospectively observe Telbivudine's effect on renal function, which aims to provide evidence in antiviral treatment for the patients with cirrhosis.
Interventions
DRUGTelbivudine
600 mg monotherapy supplied in film-coated tablets.
DRUGEnecavir
0.5 mg monotherapy supplied in tablets.
DRUGAdefovir
10 mg monotherapy supplied in tablets.
Sponsors
Novartis
Lin Bingliang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Subjects eligible for enrolment in the study must meet all of the following criteria: * eGFR in baseline less than 90 ml.min-1.1.73m2 * Aged between 18-75 years (inclusive). * Male or female. * Subjects with positive HBsAg for more than 6 months and anti-HBs negative regardless of HBeAg status. If eAg+, HBV DNA ≥2×104 IU/ml and \<2×108 IU/ml; If eAg-, HBV DNA ≥2×103 IU/ml and \<2×106 IU/ml. * Subjects with HBV-related liver cirrhosis, including compensated cirrhosis and decompensated, but only Child-Pugh A or B. Cirrhosis was diagnosed by the evidence of a small, nodular liver, as shown by ultrasound, computerized omography (CT), and magnetic resonance (MR), with the exclusion of primary biliary cirrhosis and cirrhosis caused by schistosome. * The ablility to understand and sign a written informed consent prior to any study related procedure and comply with the requirements of the study.
Exclusion criteria
Subjects meeting any of the following criteria must not be enrolled in the study * History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures * Patient is pregnant or breastfeeding. * Subjects with non-HBV cirrhosis * Co-infection with HAV/HCV/HDV/ HIV * Patients who have previously been involved in a trial with telbivudine. * Patient has received nucleoside or nucleotide drugs whether approved or investigational at any time. * Patient has received IFN or other immunomodulatory treatment in the 6 months before Screening for this study. * Patient has a history of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. Patients with previous findings suggestive of possible hepatocellular carcinoma (HCC), should have the disease ruled out prior to entrance into the study. * Patient has one or more additional known primary or secondary causes of liver disease other than CHB, including steatohepatitis，autoimmune hepatitis and so on. Gilbert's syndrome and Dubin-Johnson syndrome are not considered
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of estimate of glomerular filtration rate (eGFR)* and Serum creatinine in week 4,12,18,24,48,72,96 in each Group. | up to 2years | NO. |
Secondary
| Measure | Time frame |
|---|---|
| Liver function change (ALB/GLB, ALT/AST, TB) in each Group | up to 2 years |
Other
| Measure | Time frame |
|---|---|
| Percentage of subjects with ALT normalization rate at year 1and year 2 in each Group. | up to 2 years |
| The rate of complications (ascites, hepatorenal syndrome and so on) | up to 2 years |
Outcome results
None listed