Impact Of Nucleos(t)Ide Analogues On The Estimated Glomerular Filtration Rate In Patients With Chronic Hepatitis B

Hepatitis B virus (HBV) causes worldwide endemic or epidemic of viral hepatitis. As the chronic Hepatitis B has a complicated natural history, the infected patients appeared different morbid states, including asymptomatic HBV carrier, acute or chronic he- patitis, fulminant hepatitis, liver cirrhosis and even leading to the development of hep- atocellular carcinoma (HCC). Despite the prophylactic vaccine for viral Hepatitis B has proved its safety and effectiveness in preventing HBV infection and thus widely used worldwide, the treatment of chronic hepatitis B (CHB) still remains a clinical cha-Ilenge. An immediate goal of antiviral therapy is to suppress HBV DNA level as low as possible with an ultimate goal of preventing advanced liver sequelae. Antiviral thera-py is the only option to control and suppress disease progression in patients with chronic HBV infection. Nucleos(t)ide analogs (NAs) including Lamivudine (LAM), Adefovir (ADV), Entecavir (ETV) and Telbivudine (LdT) target the reverse transcriptase (RT) of HBV and are potent inhibitors of HBV replication. However, the treatment is impossible to completely eradicate HBV. The majority of CHB patients will require long-term treatment. Therefore, the safety profiles of these drugs are of paramount importance, especially on the effect of the renal function. Recently, the estimated glomerular filtration rate (eGFR) has been recommended to evaluate renal function. Up to now, there has not been a head-to-head controlled study to assess renal function using eGFR in Chinese CHB patients treated with different NAs. In the first part of the thesis, there is a prospective cohort study on Impact of nucleos(t)ide analogues on the estimated glomerular filtration rate in naive patients with chronic hepatitis B. In the second part of the thesis, there is a retrospective real-life study on Impact of nucleos(t)ide analogues combination therapy on the estimated glomerular filtration rate in patients with chronic hepatitis B.Part oneImpact of nucleos(t)ide analogues on the estimated glomerular filtration rate in naive patients with chronic hepatitis B (Accepted by Journal of Viral Hepatitis in Dec.2013)Objective:To evaluate the long-term effects of NAs on eGFR in Chinese CHB patients.Methods:This prospective cohort study included 275 CHB patients. Patient subgroups included those treated with lamivudine (n=50), adefovir (n=60), telbivudine (n=68), and entecavir (n=61); untreated patients (n=36) served as control. The data was calculated by Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulasResults:After an average follow-up duration of 23 months, eGFR calculated by CG and MDRD formulas increased by 18.35 ml/min and 19.34 ml/min (P<0.0001) in the telbivudine group, respectively, and decreased by 10.95 ml/min and 12.17 ml/min (P =0.0001) in the adefovir group, respectively. Even if renal function was normal or mildly impaired at baseline, eGFR increased significantly more in the telbivudine group than in the other groups (P<0.001). More patients in the adefovir group (23%) had a ≥20% decrease in eGFR (CG) than the other groups (P<0.0001). More patients in the telbivudine group (31%) had a ≥20% elevation in eGFR (CG) than the other groups (P<0.0001).Conclusion:Prolonged telbivudine therapy resulted in improved eGFR, while adefovir therapy was associated with decreased eGFR. Lamivudine and entecavir therapy did not significantly influence eGFR.Part TwoImpact of nucleos(t)ide analogues combination therapy on the estimated glomerular filtration rate in patients with chronic hepatitis B (Submitted to Journal of Gastroenterology and Hepatology)Objectives:Due to viral resistant or poor virological response, the chronic hepatitis B (CHB) patients need the nucleos(t)ide anologues (NAs) combination therapy. All available NAs may affect estimated glomerular filtration rates (eGFR). To date, few studies assess eGFR in combination therapy. We aimed to evaluate the long-term effects of NAs combination therapy on eGFR in Chinese CHB patients.Methods:This retrospective cohort study included 195 patients. Patients subgroups included those treated with lamivudine plus adefovir (n=73), telbivudine plus adefovir (n=51), entecavir plus adefovir (n=35); untreated patients (n=36) served as control. The data was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of diet in Renal Disease (MDRD) formulas.Results:After an average follow-up duration of 24 months, eGFR calculated by CKD-EPI and MDRD formulas decreased by -11.08 ml/min,-18.34 ml/min (P< 0.0001) in the lamivudine plus adefovir group, decreased by -3.73 ml/min,-10.04 ml/min (P=0.012) in the entecavir plus adefovir group, and elevated by 0.91 ml/min, 2.12 ml/min (P=0.4647) in the telbivudine plus adefovir group, respectively. Interestingly, the eGFR decrease due to adefovir monotherapy could be rescued by add-on of telbivudine. And the eGFR increase due to telbivudine monotherapy could be compromised by add-on of adefovir.Conclusion:Lamivudine plus adefovir or entecavir plus adefovir therapy was significantly associated with decreased eGFR, while telbivudine could rescue the eGFR decrease due to adefovir treatment.