RESUMO
ABSTRACT Background. Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern. Objective. To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients. Material and methods. This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA. Results. No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (<-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture. Conclusion. Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.
Assuntos
Humanos , Antivirais/uso terapêutico , Fosfatos/sangue , Osso e Ossos/efeitos dos fármacos , Cálcio/sangue , Lamivudina/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Fatores de Crescimento de Fibroblastos/sangue , Tenofovir/uso terapêutico , Guanina/análogos & derivados , Antivirais/efeitos adversos , Fatores de Tempo , Deficiência de Vitamina D/induzido quimicamente , Osso e Ossos/metabolismo , Osso e Ossos/diagnóstico por imagem , Biomarcadores/sangue , Absorciometria de Fóton , Densidade Óssea/efeitos dos fármacos , Estudos Transversais , Fatores de Risco , Resultado do Tratamento , Remodelação Óssea/efeitos dos fármacos , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/sangue , Fraturas Ósseas/induzido quimicamente , Tenofovir/efeitos adversos , Guanina/efeitos adversos , Guanina/uso terapêuticoRESUMO
BACKGROUND: Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern. OBJECTIVE: To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients. MATERIAL AND METHODS: This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA. RESULTS: No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF-treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (<-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture. CONCLUSION: Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.
Assuntos
Antivirais/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Cálcio/sangue , Fatores de Crescimento de Fibroblastos/sangue , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Fosfatos/sangue , Tenofovir/uso terapêutico , Absorciometria de Fóton , Adulto , Idoso , Antivirais/efeitos adversos , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Estudos Transversais , Feminino , Fator de Crescimento de Fibroblastos 23 , Fraturas Ósseas/induzido quimicamente , Guanina/efeitos adversos , Guanina/uso terapêutico , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tenofovir/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Deficiência de Vitamina D/induzido quimicamenteRESUMO
Fibrosing cholestatic hepatitis (FCH) is a less common but well-recognized severe complication of recurrent hepatitis C virus (HCV) infection post-liver transplant. This condition is fatal without successful treatment and to date; post-transplant antiviral interferon-based antiviral therapy has been associated with guarded success. The new era of protease inhibitors in the treatment of chronic HCV infection may alter the dismal outcome of this condition. To date, however, the experience with protease inhibitors in this condition is unreported. We report a post-liver transplant recipient with HCV associated FCH treated successfully with boceprevir, peginteferon and ribavirin for severe FCH. The patient was young woman who was a null responder pre-transplant to peginterferon and ribavirin. The peak serum bilirubin 391 µmol/L normalized to 15 µmol/L by week 8 of therapy. The pre-treatment HCV viral load of > 78 million IU/mL, decreased to 78 IU/mL at week 8 of therapy and was undetectable by week 12 and at the end of 48 week of treatment. 12 weeks post treatment, the HCV viral load remains undetectable. Significant anemia and neutropenia were encountered. Tacrolimus dosage titrated to trough levels, required marked reduction to 0.5 mg three times weekly. Despite the suboptimal peginterferon and ribavirin dosing, limited by adverse effects, full boceprevir dosing was maintained, with resolution of liver dysfunction. Boceprevir was obtained on compassionate grounds from the manufacturer before its licensure in Canada and this was the first use of boceprevir in the world for post-transplant FCH.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Transplante de Fígado , Polietilenoglicóis/uso terapêutico , Prolina/análogos & derivados , Ribavirina/uso terapêutico , Carga Viral/efeitos dos fármacos , Adulto , Quimioterapia Combinada , Feminino , Hepacivirus , Humanos , Imunossupressores/uso terapêutico , Interferon alfa-2 , Prolina/uso terapêutico , RNA Viral/sangue , Proteínas Recombinantes/uso terapêutico , Tacrolimo/uso terapêutico , Resultado do TratamentoRESUMO
PURPOSE: Chronic hepatitis C virus (HCV) is a major problem affecting up to 170 million people worldwide. Two protease inhibitors have recently been approved that will revolutionize treatment. Our objective was to summarize and evaluate the literature pertaining to the pharmacokinetics of boceprevir and telaprevir, in order to provide clinicians with insight into the management of actual and potential drug interactions. SUMMARY: A standardized search using MEDLINE (1948-November 2011), EMBASE (1980-November 2011), IPA (1970-November 2011), Google, and Google Scholar that combined the search terms boceprevir, telaprevir, pharmacokinetics, drug interaction, and drug metabolism was performed. Manual reference searches of chosen articles were completed. Monographs and articles, conference proceedings, and abstracts were evaluated. Boceprevir and telaprevir are both substrates and inhibitors of cytochrome P450 3A4 and telaprevir is a substrate of p-glycoprotein. Levels of boceprevir are decreased in patients taking efavirenz but effects with other antiretrovirals are minimal or unknown. Coadministration with efavirenz may compromise telaprevir levels and should be avoided. Telaprevir may increase levels of cyclosporine, tacrolimus, atorvastatin, and amlodipine, which may expose patients to increased adverse effects. Conclusions. Significant drug-drug interactions occur with both boceprevir and telaprevir. Until studies are reported and experience is gained with these agents, clinicians will need to be careful when administering in high-risk populations and those receiving chronic therapy with interacting agents. Studies are urgently needed in HIV patients taking antiretrovirals and patients taking chronic immunosuppression as these populations are at increased risk of experiencing clinically significant interactions.