Renal Function During Treatment for Hepatitis B/D
Renal Function During Treatment for Hepatitis B/D
Long-term safety of treatment with hepatitis B virus (HBV) polymerase inhibitors is a concern. Adefovir dipivoxil (ADV) therapy has previously been associated with impairment of renal function. Limited data are available on the safety of combination therapy with nucleos(t)ide analogues and interferon alfa (IFNα). The aim of this analysis was to assess the renal function during combination therapy with peginterferon alfa-2a (PegIFNα-2a) plus ADV vs either drug alone in patients with hepatitis B/D co-infection. We performed a retrospective analysis of renal function data of patients treated in the Hep-Net/International Delta Hepatitis Intervention Trial 1(HIDIT-1-trial), a European multicenter study to investigate the efficacy of 48 weeks of therapy with PegIFNα-2a+ADV vs either drug alone in 90 patients with chronic hepatitis B/D co-infection. Glomerular filtration rates (GFR) were calculated by Cockcroft–Gault (CG), abbreviated Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. After 48 weeks of therapy GFR values were significantly lower in patients receiving adefovir-containing treatment vs PegIFNα-2a alone [mean difference 16.1 mL/min (CG) and 10.2 mL/min (MDRD), respectively, P < 0.05] while no differences were observed between patients receiving adefovir alone vs combination treatment. Twenty-four weeks after treatment GFR values did not differ between treatment arms. A decrease in GFR ≥20% was observed more often in patients during adefovir-containing treatment vs PegIFNα-2a alone (P < 0.05) which was confirmed by Kaplan–Meier analysis. Adefovir-containing but not PegIFNα-2a treatment was associated with a decrease in GFR values in about one-fifth of patients. Combination treatment of PegIFNα-2a+ADV in chronic hepatitis B/D co-infection did not lead to any further impairment of kidney function.
Well accepted treatment guidelines for hepatitis B virus (HBV) infection have been established in recent years. Therapeutic approaches for chronic hepatitis B consist of administration of interferon alfa (IFNα) or HBV polymerase inhibitors. One problem of nucleos(t)ide analogue therapy is that treatment duration is not well defined and long-term safety profiles are a concern for some of the approved compounds.
The ultimate goal of HBV treatment should be loss of hepatitis B surface antigen (HBsAg) with development of anti-HBs (HBs seroconversion), which, however, is only achieved in <10% of patients treated with IFNα and in a small subgroup of patients treated with the current oral therapies. One possibility to increase HBs seroconversion could be to combine IFNα with nucleos(t)ide analogues, although adding lamivudine to peginterferon alfa-2a (PegIFNα-2a) did not lead to further HBsAg decline compared to PegIFN alone. However, no study has yet investigated in detail the safety profile of combination therapies. Recently, unexpected cases of neuropathy were observed during combination of PegIFN and telbivudine, while adding lamivudine to PegIFN seems to be safe.
Adefovir dipivoxil (ADV) therapy has previously been associated with an impairment of renal function in Asian–American patients with chronic hepatitis B. No study had investigated in detail renal function during combination therapy of ADV and PegIFN. We recently reported the results of a treatment trial investigating the efficacy of PegIFNα-2a in combination with ADV vs either drug alone in HBV/HDV co-infected patients. Compared to chronic HBV monoinfection, chronic hepatitis B/D co-infection usually leads to more severe liver disease with an accelerated course of fibrosis progression, an increased risk of hepatocellular carcinoma and early decompensation in case of established liver cirrhosis.
Renal function can be monitored by the determination of creatinine. The glomerular filtration rate (GFR) is usually estimated from equations by using serum creatinine level, age, race, sex and body weight. The first equation has been developed and evaluated by Cockcroft and Gault. Another widely used formula is the Modification of Diet in Renal Disease (MDRD) study equation. Both equations were evaluated in patients with chronic kidney disease and may not accurately estimate (over- or underestimate) GFR in healthy people. Recently, a new equation from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) has been introduced, which might be more accurate in people without underlying kidney disease and thus replace the MDRD study equation in the future.
The aim of this analysis was to assess the renal function during combination therapy with PegIFNα-2a plus adefovir vs either drug alone in patients with hepatitis B/D co-infection. No detailed safety data of either pegylated IFNα and/or adefovir are available in this particular severe form of chronic viral hepatitis.
Abstract and Introduction
Abstract
Long-term safety of treatment with hepatitis B virus (HBV) polymerase inhibitors is a concern. Adefovir dipivoxil (ADV) therapy has previously been associated with impairment of renal function. Limited data are available on the safety of combination therapy with nucleos(t)ide analogues and interferon alfa (IFNα). The aim of this analysis was to assess the renal function during combination therapy with peginterferon alfa-2a (PegIFNα-2a) plus ADV vs either drug alone in patients with hepatitis B/D co-infection. We performed a retrospective analysis of renal function data of patients treated in the Hep-Net/International Delta Hepatitis Intervention Trial 1(HIDIT-1-trial), a European multicenter study to investigate the efficacy of 48 weeks of therapy with PegIFNα-2a+ADV vs either drug alone in 90 patients with chronic hepatitis B/D co-infection. Glomerular filtration rates (GFR) were calculated by Cockcroft–Gault (CG), abbreviated Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. After 48 weeks of therapy GFR values were significantly lower in patients receiving adefovir-containing treatment vs PegIFNα-2a alone [mean difference 16.1 mL/min (CG) and 10.2 mL/min (MDRD), respectively, P < 0.05] while no differences were observed between patients receiving adefovir alone vs combination treatment. Twenty-four weeks after treatment GFR values did not differ between treatment arms. A decrease in GFR ≥20% was observed more often in patients during adefovir-containing treatment vs PegIFNα-2a alone (P < 0.05) which was confirmed by Kaplan–Meier analysis. Adefovir-containing but not PegIFNα-2a treatment was associated with a decrease in GFR values in about one-fifth of patients. Combination treatment of PegIFNα-2a+ADV in chronic hepatitis B/D co-infection did not lead to any further impairment of kidney function.
Introduction
Well accepted treatment guidelines for hepatitis B virus (HBV) infection have been established in recent years. Therapeutic approaches for chronic hepatitis B consist of administration of interferon alfa (IFNα) or HBV polymerase inhibitors. One problem of nucleos(t)ide analogue therapy is that treatment duration is not well defined and long-term safety profiles are a concern for some of the approved compounds.
The ultimate goal of HBV treatment should be loss of hepatitis B surface antigen (HBsAg) with development of anti-HBs (HBs seroconversion), which, however, is only achieved in <10% of patients treated with IFNα and in a small subgroup of patients treated with the current oral therapies. One possibility to increase HBs seroconversion could be to combine IFNα with nucleos(t)ide analogues, although adding lamivudine to peginterferon alfa-2a (PegIFNα-2a) did not lead to further HBsAg decline compared to PegIFN alone. However, no study has yet investigated in detail the safety profile of combination therapies. Recently, unexpected cases of neuropathy were observed during combination of PegIFN and telbivudine, while adding lamivudine to PegIFN seems to be safe.
Adefovir dipivoxil (ADV) therapy has previously been associated with an impairment of renal function in Asian–American patients with chronic hepatitis B. No study had investigated in detail renal function during combination therapy of ADV and PegIFN. We recently reported the results of a treatment trial investigating the efficacy of PegIFNα-2a in combination with ADV vs either drug alone in HBV/HDV co-infected patients. Compared to chronic HBV monoinfection, chronic hepatitis B/D co-infection usually leads to more severe liver disease with an accelerated course of fibrosis progression, an increased risk of hepatocellular carcinoma and early decompensation in case of established liver cirrhosis.
Renal function can be monitored by the determination of creatinine. The glomerular filtration rate (GFR) is usually estimated from equations by using serum creatinine level, age, race, sex and body weight. The first equation has been developed and evaluated by Cockcroft and Gault. Another widely used formula is the Modification of Diet in Renal Disease (MDRD) study equation. Both equations were evaluated in patients with chronic kidney disease and may not accurately estimate (over- or underestimate) GFR in healthy people. Recently, a new equation from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) has been introduced, which might be more accurate in people without underlying kidney disease and thus replace the MDRD study equation in the future.
The aim of this analysis was to assess the renal function during combination therapy with PegIFNα-2a plus adefovir vs either drug alone in patients with hepatitis B/D co-infection. No detailed safety data of either pegylated IFNα and/or adefovir are available in this particular severe form of chronic viral hepatitis.