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1.
J Clin Gastroenterol ; 54(2): 192-199, 2020 02.
Article in English | MEDLINE | ID: mdl-30789853

ABSTRACT

GOALS AND BACKGROUND: International guidelines recommend prioritized treatment initiation in hepatitis C virus (HCV)-infected patients with advanced liver disease. We aimed to evaluate whether the widespread usage of direct acting antivirals (DAAs) has led to a decrease in late presentation for care. STUDY: Data derived from the multicenter German Hepatitis C Cohort (GECCO) was analyzed. Treatment naive HCV-infected patients initiating DAA-based treatment between January 2014 and September 2017 were included. Advanced liver disease was defined by aspartate aminotransferase to platelet ratio index score ≥1.5, METAVIR≥F3, or FibroScan ≥9.5 kPa. Period prevalence and risk factors for late presentation were evaluated. RESULTS: Six hundred fifty-three HCV-monoinfected and 210 HIV/HCV-coinfected patients (mean age, 48.6±12.7 y; 65.5% male) were included. Overall 32.5% of patients had advanced liver disease. In 2014 39.4% of patients presented with advanced liver disease, decreasing to 30.1%, 34.4%, and 26.4% in the years 2015, 2016, and 2017 (P=0.057), respectively. Patients with and without advanced liver disease differed in age (P<0.0001), CD4 ≤350/µL (P=0.027), genotype (P=0.005), transmission route (P=0.047), body mass index (P<0.001), and time since diagnosis (P=0.007). In the multivariable binary logistic regression analysis GT3, age above 45 years and being diagnosed >2 years ago were positively and HCV transmission through men who have sex with men was negatively associated with advanced liver disease. CONCLUSIONS: Overall 32.5% of patients presented with advanced liver disease. We observed a trend toward a lower proportion of patients starting treatment late.GT3, age, years since HCV diagnosis and HCV transmission route were identified as risk factors for presentation with advanced liver disease.


Subject(s)
Coinfection , HIV Infections , Hepatitis C, Chronic , Hepatitis C , Sexual and Gender Minorities , Adult , Antiviral Agents/therapeutic use , Coinfection/drug therapy , Female , Germany/epidemiology , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Hepacivirus , Hepatitis C/complications , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Homosexuality, Male , Humans , Male , Middle Aged
2.
Clin Infect Dis ; 71(5): 1248-1254, 2020 08 22.
Article in English | MEDLINE | ID: mdl-31562816

ABSTRACT

BACKGROUND: Micro-elimination of the hepatitis C virus (HCV) includes treatment in populations at risk of ongoing HCV transmission, such as men who have sex with men (MSM) or people who inject drugs (PWID). We analyzed the HCV reinfection incidence rates of participants in the German hepatitis C cohort (GECCO) and compared our data to previous findings from the interferon era. METHODS: Patients with HCV reinfections in the multi-centric GECCO cohort were compared to patients in whom no reinfection occurred. The HCV reinfection incidence rate in MSM was also compared to the incidence rate in the interferon era (using data from the European Acquired Immunodeficiency Syndrome Treatment Network [NEAT]). RESULTS: Between January 2014 and April 2018, 48 HCV reinfections occurred in 2298 individuals (2%), with 2346 cured HCV episodes. The median time to reinfection was 500 days (range 16-1160) and the overall HCV reinfection incidence rate was 1.89 per 100 person-years (py; 95% confidence interval [CI], 1.41-2.48). In a multivariate analysis, the transmission risk in MSM was the only independent risk factor of HCV reinfection (odds ratio, 39.3; 95% CI, 4.57-334.40; P = .001). The incidence rate in MSM was 9.02 (95% CI, 6.48-12.26) per 100 py, compared to 1.14 per 100 py in PWID (95% CI, .56-2.09). The incidence rate for a first HCV reinfection in MSM was similar in the direct-acting antiviral era, compared to the interferon era, with a hazard ratio of 1.05 (95% CI, .64-1.74; P = .831). CONCLUSIONS: HCV reinfection remains a frequent finding among MSM in Germany. In addition to behavioral interventions, early HCV treatment and retreatment should be implemented for this subgroup to prevent HCV transmission.


Subject(s)
HIV Infections , Hepatitis C, Chronic , Hepatitis C , Pharmaceutical Preparations , Sexual and Gender Minorities , Substance Abuse, Intravenous , Antiviral Agents/therapeutic use , Germany/epidemiology , HIV Infections/drug therapy , HIV Infections/epidemiology , Hepacivirus , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C, Chronic/drug therapy , Homosexuality, Male , Humans , Incidence , Interferons/therapeutic use , Male , Recurrence , Reinfection , Substance Abuse, Intravenous/drug therapy
3.
J Med Virol ; 90(2): 304-312, 2018 02.
Article in English | MEDLINE | ID: mdl-28710853

ABSTRACT

There are limited data regarding the real world effectiveness of direct acting antivirals (DAA) for the therapy of chronic genotype 3 hepatitis C virus (HCV) infection. All HCV genotype 3 infected patients from the German hepatitis C cohort (GECCO), which is a prospective database of nine German hepatitis C treatment centers, were included in the study. Three hundred forty-two chronically infected HCV genotype 3 patients were analyzed (253 males [74.0%], mean age 47.3 years, 127 cirrhotic patients [37.1%] mostly with Child A cirrhosis, 113 treatment experienced patients [37.1%], 38 HCV/HIV co-infected patients [11.1%]). SVR12 rates in the "intention-to-treat" analysis were as follows: sofosbuvir/ribavirin 69.4% (75/108), sofosbuvir/peginterferon/ribavirin 80.6% (58/72), sofosbuvir/daclatasvir ± ribavirin for 12 weeks 88.3% (53/63), sofosbuvir/daclatasvir ± ribavirin for 24 weeks 79.3% (23/29), sofosbuvir/ledipasvir ± ribavirin for 12 weeks 71.4% (10/14), and sofosbuvir/ledipasvir ± ribavirin for 24 weeks 86.7% (26/30). Forty patients were lost to follow-up, 23 patients had a relapse, 4 patients stopped treatment prematurely and 1 patient died. Female sex (P = 0.038) and treatment with two different DAAs (P = 0.05) were predictors for SVR12 in the multivariate analysis. In conclusion, sofosbuvir/daclatasvir ± ribavirin for 12 weeks and sofosbuvir/ledipasvir ± ribavirin for 24 weeks are effective for the treatment of HCV genotype 3 infected patients including cirrhotic, treatment-experienced or HIV/HCV co-infected patients.


Subject(s)
Antiviral Agents/therapeutic use , Genotype , Hepacivirus/classification , Hepatitis C, Chronic/drug therapy , Sofosbuvir/therapeutic use , Adult , Aged , Drug Therapy, Combination/methods , Female , Hepacivirus/genetics , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , Sustained Virologic Response , Treatment Outcome
4.
Liver Int ; 37(10): 1468-1475, 2017 10.
Article in English | MEDLINE | ID: mdl-28247572

ABSTRACT

BACKGROUND & AIMS: There are few large-scale, prospective studies comparing liver-associated events in treated and untreated patients with CHC managed in routine clinical practice. METHODS: Patients with CHC were prospectively enrolled in a non-interventional study. Data from patients with available documentation who had either achieved a sustained virological response, or were non-responders, relapsers, or had virological breakthrough following treatment with peginterferon alfa-2a±ribavirin, or who had been diagnosed but never treated at least 3 years previously, and who remained under medical observation were analyzed. Primary endpoint was liver-associated events (composite of decompensation/liver failure, ascites, hepatocellular carcinoma, or liver transplant/placement on a transplant list). RESULTS: In all, 1444 eligible patients were identified. Mean follow-up was 4.7 (standard deviation; SD 1.1) years. Patients with sustained virological response had a lower incidence of liver-associated events vs non-responders, relapsers, or virological breakthrough and never treated patients (1.7% vs 4.7% and 4.7% respectively). The proportion of patients with cirrhosis increased from baseline in the non-responders, relapsers, or virological breakthrough (6.8%-10.5%) and never treated group (3.7%-8.4%), with an associated increase in severity, but was unchanged in the sustained virological response group (2.1%). Event-free survival was significantly higher in sustained virological response patients (P=.0082). CONCLUSIONS: In this "real-world" cohort, the achievement of sustained virological response almost eliminated liver-related morbidity and mortality compared with patients who failed to achieve sustained virological response and those who were untreated. Overall, the LOTOS cohort highlights the importance of timely and effective treatment for patients with CHC.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Adult , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/virology , Databases, Factual , Female , Germany , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/mortality , Hepatitis C, Chronic/virology , Humans , Liver Failure/mortality , Liver Failure/surgery , Liver Failure/virology , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Liver Neoplasms/virology , Liver Transplantation , Male , Middle Aged , Product Surveillance, Postmarketing , Prospective Studies , Recombinant Proteins/therapeutic use , Recurrence , Risk Factors , Sustained Virologic Response , Time Factors , Treatment Outcome
5.
Antivir Ther ; 21(1): 81-88, 2017.
Article in English | MEDLINE | ID: mdl-27685337

ABSTRACT

BACKGROUND: HCV has complex interactions with human lipid metabolism leading to down regulation of cholesterol levels. Interferon (IFN) therapy has been shown to decrease cholesterol even further. With the availability of second-generation direct-acting antiviral agents (DAA) the effect of suppressing and eliminating HCV on lipid metabolism warrants reevaluation. METHODS: Prospective German multicentre cohort on HCV- and HIV-HCV-infected patients treated with direct-antiviral agents (GECCO). Lipids were assessed at baseline, during and after therapy. Wilcoxon test corrected for multiple testing was used. RESULTS: For the analysis, 520 patients with chronic hepatitis C were available. Patients with chronic hepatitis C were treated as follows: sofosbuvir (SOF)/pegylated IFN (PEG-IFN)/ribavirin (RBV; HCV=34, HIV-HCV=36), SOF/RBV (HCV=47, HIV-HCV=16), SOF/simeprevir (HCV=9, HCV-HIV=2), SOF/daclatasvir +/- RBV (HCV=27, HIV-HCV=47), SOF/ledipasvir +/- RBV (HCV=147, HCV-HIV=100) and ombitasvir/paritaprevir/ritonavir +/- dasabuvir +/- RBV (2D, HCV=2, HCV-HIV=6; 3D, HCV=39, HCV-HIV=8). On treatment there was a statistically significant increase in total cholesterol for any IFN-free DAA regimen, which was maintained after end of therapy. Changes of total cholesterol were driven by changes in low-density lipoprotein cholesterol, whereas high-density lipoprotein cholesterol remained unchanged. In contrast, total cholesterol decreased on SOF/PEG-IFN/RBV and increased after end of therapy above baseline levels. Triglycerides increased during treatment with SOF/PEG-IFN/RBV, but not on DAA-only regimens. CONCLUSIONS: Suppressing and eliminating HCV with IFN-free DAA regimens increased cholesterol levels, but had no effect on triglycerides. In contrast IFN-based therapy decreased cholesterol and increased triglycerides during treatment and led to increases in cholesterol after achieving sustained virological response.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C/blood , Hepatitis C/drug therapy , Lipid Metabolism/drug effects , Lipids/blood , Adult , Antiviral Agents/pharmacology , Biomarkers , Coinfection , Comorbidity , Drug Therapy, Combination , Female , Genotype , HIV Infections/drug therapy , Hepacivirus/genetics , Hepatitis C/virology , Humans , Male , Middle Aged , Risk Factors , Treatment Outcome , Viral Load
6.
Clin Infect Dis ; 63(10): 1320-1324, 2016 11 15.
Article in English | MEDLINE | ID: mdl-27535952

ABSTRACT

BACKGROUND: Shortening the duration of treatment with HCV direct-acting antivirals (DAAs) leads to substantial cost reductions. According to the label, sofosbuvir and ledipasvir can be prescribed for 8 weeks (SL8) in noncirrhotic women or men with HCV genotype 1 and low viral loads. However, real-world data about the efficacy and safety of SL8 are largely missing. METHODS: Interim results from an ongoing prospective, multicenter cohort of 9 treatment centers in Germany (GECCO). All patients started on treatment with HCV DAAs since January 2014 were included. This report describes safety and efficacy outcomes in 210 patients with HCV monoinfection and 35 with human immunodeficiency virus (HIV)-HCV coinfection given SL8 in a real-world setting. RESULTS: Of 1353 patients included into the GECCO cohort until December 2015, a total of 1287 had complete data sets for this analysis; 337 (26.2%) fulfilled the criteria for SL8 according to the package insert, but only 193 (57.2%) were eventually treated for 8 weeks. Another 52 patients did not fulfill the criteria but were treated for 8 weeks. SL8 was generally well tolerated. The overall sustained virologic response rate 12 weeks after the end of treatment was 93.5% (186 of 199). The on-treatment response rate was 99.4% (159 of 160) in HCV-monoinfected and 96.4% (27 of 28) in HIV-HCV-coinfected patients. Ten patients were lost to follow-up. CONCLUSIONS: SL8 seems highly effective and safe in well-selected HCV-monoinfected and HIV-HCV-coinfected patients in a real-world setting.


Subject(s)
Antiviral Agents , Benzimidazoles , Coinfection/drug therapy , Fluorenes , HIV Infections/complications , Hepatitis C, Chronic/drug therapy , Sofosbuvir , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Benzimidazoles/administration & dosage , Benzimidazoles/therapeutic use , Female , Fluorenes/administration & dosage , Fluorenes/therapeutic use , Germany/epidemiology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , Prospective Studies , Sofosbuvir/administration & dosage , Sofosbuvir/therapeutic use , Viral Load , Young Adult
7.
J Gastrointestin Liver Dis ; 25(1): 15-24, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27014750

ABSTRACT

BACKGROUND AND AIMS: Smoking has multiple effects on factors influencing hepatitis C and antiviral therapy, including lipid metabolism, fibrosis, platelet count and adherence aspects. The aim of this analysis was to determine the impact of smoking on hepatitis C virus antiviral therapy. METHODS: Data of two cohorts of an observational multicenter study including therapy-naïve patients infected with genotype 1 hepatitis C virus (HCV) treated with dual antiviral therapy (n=7,796) with pegylated interferon alpha 2a in combination with ribavirin, or triple antiviral therapy (n=1,122) containing telaprevir or boceprevir, were analysed. RESULTS: In the univariate matched pair analysis of dual antiviral therapy patients (n=584), smoking was significantly associated with lower sustained viral response rates (p=0.026, OR 0.69 CI: 0.50 - 0.96). The effect of smoking on sustained viral response remained significant (p=0.028, OR 0.67 CI: 0.47 - 0.96) in the multivariate analysis when adjusting for all other baseline parameters with a significant association in the univariate analysis, i.e. diabetes, fibrosis, body mass index, transaminases and baseline viral load. Under protease inhibitors the influence of smoking on virological response did not arise. CONCLUSIONS: Smoking has a negative impact on antiviral therapy in naïve patients infected with HCV genotype 1 independently of age, gender, history of drug use or alcoholic liver disease. The effects of smoking might be overcome by the new antiviral agents.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/drug effects , Hepatitis C/drug therapy , Interferon-alpha/therapeutic use , Oligopeptides/therapeutic use , Polyethylene Glycols/therapeutic use , Proline/analogs & derivatives , Protease Inhibitors/therapeutic use , Smoking/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/adverse effects , Drug Therapy, Combination , Female , Genotype , Germany , Hepacivirus/enzymology , Hepacivirus/genetics , Hepatitis C/diagnosis , Hepatitis C/virology , Humans , Interferon-alpha/adverse effects , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Oligopeptides/adverse effects , Polyethylene Glycols/adverse effects , Proline/adverse effects , Proline/therapeutic use , Protease Inhibitors/adverse effects , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Ribavirin/therapeutic use , Risk Factors , Time Factors , Treatment Outcome , Viral Load , Young Adult
8.
Dig Dis Sci ; 61(10): 3061-3071, 2016 10.
Article in English | MEDLINE | ID: mdl-26576555

ABSTRACT

BACKGROUND AND AIMS: Multiple clinical trials have demonstrated the efficacy and safety of tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB). However, long-term efficacy and safety data for TDF in real-life clinical practice are limited. METHODS: Prospective German field practice study in CHB-mono-infected patients. Patients were TDF-naïve but could have been treated previously with other HBV antivirals. RESULTS: Efficacy analysis included 400 patients; 301 (75 %) completed 36 months of TDF treatment. Both treatment-naïve and treatment-experienced patients showed a rapid decline in HBV DNA within 3 months of TDF initiation. After 36 months, HBV DNA < 69 IU/mL was achieved by 91 % of treatment-naïve patients (90 and 92 % in hepatitis B "e" antigen [HBeAg]-positive and [HBeAg]-negative, respectively) and 96 % of treatment-experienced patients (93 and 97 %, respectively). Three patients experienced virologic breakthrough, all with reported non-compliance. Overall, 5.7 % HBeAg-positive and 2.2 % HBeAg-negative patients lost hepatitis B surface antigen. Safety data were consistent with the known TDF safety profile; the most commonly reported adverse events possibly related to TDF were fatigue (2.0 %) and headache (2.0 %). Few patients (1.3 %) experienced renal-related adverse reactions. Creatinine clearance remained relatively stable over time; patients responded favorably where TDF was dose adjusted per label for decreased creatinine clearance. CONCLUSIONS: TDF showed a favorable tolerability profile and induced rapid and sustained suppression of HBV DNA in patients with CHB treated for up to 3 years in routine clinical practice, irrespective of treatment history. Efficacy and safety in this heterogeneous patient population were consistent with data from clinical trials.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B, Chronic/drug therapy , Tenofovir/therapeutic use , Adult , Creatinine/blood , DNA, Viral/blood , Elasticity Imaging Techniques , Fatigue/chemically induced , Female , Germany , Headache/chemically induced , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/diagnostic imaging , Humans , Kidney Diseases/blood , Kidney Diseases/chemically induced , Liver/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/etiology , Male , Middle Aged , Prospective Studies , Treatment Outcome , Viral Load
9.
World J Gastroenterol ; 20(31): 10984-93, 2014 Aug 21.
Article in English | MEDLINE | ID: mdl-25152602

ABSTRACT

AIM: To evaluate the safety and efficacy of pegylated interferon alfa-2a and ribavirin therapy in elderly patients with chronic hepatitis C infection. METHODS: Patients characteristics, treatment results and safety profiles of 4859 patients with hepatitis c virus (HCV) infection receiving treatment with pegylated interferon alfa-2a and ribavirin were retrieved from a large ongoing German multicentre non-interventional study. Recommended treatment duration was 24 wk for GT 2 and GT 3 infection and 48 wk for GT 1 and GT 4 infection. Patients were stratified according to age (< 60 years vs ≥ 60 years). Because of limited numbers of liver biopsies for further assessment of liver fibrosis APRI (aspartate aminotransferase - platelet ratio index) was performed using pre-treatment laboratory data. RESULTS: Out of 4859 treated HCV patients 301 (6.2%) were ≥ 60 years. There were more women (55.8% vs 34.2%, P < 0.001) and predominantly GT 1 (81.4% vs 57.3%, P < 0.001) infected patients in the group of patients aged ≥ 60 years and they presented more frequently with metabolic (17.6% vs 4.5%, P < 0.001) and cardiovascular comorbidities (32.6% vs 6.7%, P < 0.001) and significant fibrosis and cirrhosis (F3/4 31.1% vs 14.0%, P = 0.0003). Frequency of dose reduction and treatment discontinuation were significantly higher in elderly patients (30.9% vs 13.7%, P < 0.001 and 47.8% vs 30.8%, P < 0.001). Main reason for treatment discontinuation was "virological non-response" (26.6% vs 13.6%). Sustained virological response (SVR) rates showed an age related difference in patients with genotype 1 (23.7% vs 43.7%, P < 0.001) but not in genotype 2/3 infections (57.7% vs 64.6%, P = 0.341). By multivariate analysis, age and stage of liver disease were independent factors of SVR. CONCLUSION: Elderly HCV patients differ in clinical characteristics and treatment outcome from younger patients and demand special attention from their practitioner.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Age Factors , Antiviral Agents/adverse effects , Chi-Square Distribution , Drug Therapy, Combination , Female , Germany , Hepatitis C, Chronic/diagnosis , Humans , Interferon-alpha/adverse effects , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Polyethylene Glycols/adverse effects , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Ribavirin/adverse effects , Risk Factors , Severity of Illness Index , Time Factors , Treatment Outcome
10.
Hepatology ; 59(1): 46-8, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23813604

ABSTRACT

UNLABELLED: In clinical trials with telaprevir (TLV) and boceprevir (BOC) renal impairment was not reported as a relevant adverse event. The PAN study is a noninterventional study enrolling patients treated with peginterferon alfa-2a/ribavirin (PEG/RBV) with or without TVL or BOC. Here we restrict the analysis to hepatitis C virus genotype 1 patients having completed 12 (n = 895) or 24 weeks (n = 591) of treatment. For estimation of glomerular filtration rate (eGFR) the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was chosen. Patients on TLV 38/575 (6.6%) and BOC 10/211 (4.7%) more frequently experienced a decrease in eGFR to <60 mL/min compared to patients on PEG/RBV 1/109 (0.9%) (P < 0.05). Risk factors associated with eGFR <60 mL/min in multiple logistic regression analysis were age (P < 0.001), arterial hypertension (P < 0.05), higher serum creatinine at baseline (P < 0.001), and being on triple therapy with TLV or BOC (P < 0.01). Patients with an eGFR of <60 mL/min had a lower absolute mean hemoglobin at week 12 compared to patients with an eGFR >60 mL/min (9.7 g/dL ± 1.4 g/dL versus 11.0 g/dL ± 1.7 g/dL) (P < 0.001). Most patients on TLV with a decrease of eGFR <60 mL/min showed a marked improvement in renal function after discontinuation of TLV. CONCLUSION: Renal impairment has not been reported as a safety signal in clinical trials with TVL or BOC. However, in this large cohort including patients with risk factors for renal impairment a marked decline in renal function was observed in about 5% of patients on triple therapy. In addition to being a safety concern, substantial ribavirin dose reductions have to be considered in these patients, as anemia was more pronounced in patients with impaired renal function.


Subject(s)
Hepatitis C, Chronic/drug therapy , Oligopeptides/adverse effects , Proline/analogs & derivatives , Renal Insufficiency/chemically induced , Adult , Antiviral Agents/therapeutic use , Drug Therapy, Combination , Female , Glomerular Filtration Rate , Humans , Interferons/therapeutic use , Male , Middle Aged , Proline/adverse effects
12.
J Hepatol ; 55(6): 1235-40, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21703180

ABSTRACT

BACKGROUND & AIMS: Therapy of chronic hepatitis B with HBV-polymerase inhibitors, in particular tenofovir or adefovir, may affect renal function. To assess renal function more accurately in the normal range, we used the recently validated, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula to calculate the estimated glomerular filtration rate (eGFR). METHODS: Patient subgroups included: patients with HBV-monoinfection treated with lamivudine (n=36), adefovir (n=32), entecavir (n=32), or tenofovir (n=37). HBsAg-positive untreated patients (n=60) served as control. For comparison HIV-monoinfected patients treated with tenofovir (n=120) or zidovudine (n=52) based antiretroviral therapy and antiretroviral naive patients (n=109) were assessed. CKD-EPI equation was used to calculate eGFR. In a more sensitive approach, we modeled the individual change in eGFR over time with linear mixed effects models (LME). RESULTS: Yearly predicted median changes in individual eGFR according to the LME model were: HBV untreated -2.05 ml/min, HBV lamivudine -0.92 ml/min, HBV adefovir -1.02 ml/min, HBV entecavir -1.00 ml/min, and HBV tenofovir -0.92 ml/min (p<0.01 for HBV untreated vs. HBV treated). In HIV-monoinfected patients: HIV untreated -0.62 ml/min, HIV treated with tenofovir -2.64 ml/min, HIV treated with zidovudine -1.0 ml/min (p=0.017 for tenofovir vs. no treatment, p<0.001 for tenofovir vs. zidovudine). CONCLUSIONS: Therapy of HBV infection irrespective of medication seems to result in a milder decrease of renal function. In contrast tenofovir as part of HIV combination therapy seems to impair renal function in this Caucasian population.


Subject(s)
Gene Products, pol/antagonists & inhibitors , Glomerular Filtration Rate/drug effects , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/physiopathology , Reverse Transcriptase Inhibitors/therapeutic use , Adenine/adverse effects , Adenine/analogs & derivatives , Adenine/therapeutic use , Adolescent , Adult , Aged , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Case-Control Studies , Female , HIV Infections/drug therapy , HIV Infections/physiopathology , Humans , Linear Models , Male , Middle Aged , Organophosphonates/adverse effects , Organophosphonates/therapeutic use , Reverse Transcriptase Inhibitors/adverse effects , Tenofovir , Young Adult
13.
Clin Gastroenterol Hepatol ; 7(10): 1028-36; quiz 1022, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19447199

ABSTRACT

Prospective, randomized, controlled, phase 3 clinical trials establish pegylated interferon (PEG-IFN) alfa plus ribavirin as the standard of care for patients with chronic hepatitis C. Such clinical trials are conducted in a highly regimented manner; patients must meet strict inclusion/exclusion criteria, and treatment is administered under rigid protocols with close monitoring by study personnel. Whether the results of phase 3 trials can be generalized or achieved in everyday clinical practice is questioned in several therapeutic areas. The efficacy of PEG-IFN alfa plus ribavirin therapy observed in pivotal phase 3 trials has been confirmed in several community-based trials conducted in North America and Europe, demonstrating consistent overall rates of sustained virologic response across a wide range of patient populations. Sustained virologic response rates stratified by genotype, viral load, fibrosis score, age, and ethnicity, factors known to impact treatment outcome, are consistent between these trials and comparable to those reported in clinical trials. The United States-based WIN-R trial confirmed the value of combining weight-based ribavirin dosing with weight-based PEG-IFN alfa-2b dosing across a spectrum of patient body weights. Large Canadian trials (POWeR and EAP), a German trial (AWB), a French study (Hepatys), and an Italian study demonstrated that PEG-IFN alfa plus ribavirin produces excellent efficacy in difficult-to-treat patient populations. Collectively, these results confirm the efficacy of current standard treatment regimens in a wide range of community-based settings, affording clinicians confidence that they can attain results similar to those of rigidly controlled randomized trials.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Humans , Interferon alpha-2 , Randomized Controlled Trials as Topic , Recombinant Proteins , Treatment Outcome
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