Response to HCV Therapy in Patients With HCV/HIV Coinfection
Response to HCV Therapy in Patients With HCV/HIV Coinfection
There are few data about the long-term histological outcome of HIV-/HCV-coinfected patients after therapy with interferon and ribavirin. We performed an observational study of 216 patients who received therapy against HCV and who had at least three successive transient elastographies (TE) during the follow-up. The primary endpoint was confirmed fibrosis regression, defined as a reduction of at least 1 point in Metavir fibrosis score, confirmed and without worsening in successive TE. At baseline, 23% had fibrosis stage 4 or cirrhosis. Overall, 82 (38%) achieved sustained virological response (SVR), without differences in baseline fibrosis or time of follow-up. Confirmed fibrosis regression was observed in 55% of patients, higher for SVR (71% vs 44%; P < 0.01), and the likelihood of achieving fibrosis regression at 3, 5 and 7 years was 0.17, 0.51 and 0.67, respectively, for SVR patients, in comparison with 0.02, 0.23 and 0.41 for no SVR patients (P < 0.01, log-rank test at any time point). Progressive regression, defined as continuous improvement in successive TE, was observed in 62% of patients with advanced liver fibrosis or cirrhosis who achieved SVR. In a Cox regression model, only SVR (HR, 4.01; 95% CI, 2.33–7.57; P < 0.01) and a younger age (HR, 1.14; 95% CI, 1.05–1.25; P < 0.01; per year) were associated with fibrosis regression. This study confirms that the rate of liver fibrosis regression increases during the follow-up after SVR to interferon therapy in HIV-/HCV-coinfected patients.
Human immunodeficiency virus (HIV) infection is cause of more rapid progression of fibrosis and development of cirrhosis in patients coinfected with hepatitis C virus (HCV). For this reason, HIV-infected individuals with positive HCV RNA determinations should be considered as potential candidates for anti-HCV treatment.
Together with the disappearance of HCV replication, it is already known that response to antiviral therapy with interferon or ribavirin reduces liver complications in chronic hepatitis C, and there is sufficient evidence of histological improvement in HCV-monoinfected patients after sustained virological response (SVR). However, little is known about the long-term evolution of liver fibrosis in HIV-/HCV-coinfected patients following therapy against HCV, taking into account the differences in fibrogenesis or viral kinetics, and the influence of immunosuppression. There could be expected slight changes in fibrosis, a similar outcome to that of monoinfected, or even better if the role of inflammation is higher.
In addition, during the last years, a noninvasive technique, transient elastography (TE), has been shown to identify fibrosis stage accurately. Liver stiffness measurement through TE is reproducible and independent of the operator and explores a volume of liver parenchyma, which can be approximated to a cylinder of 1 cm in diameter and 4 cm in length. This volume is 100 times larger than the biopsy specimen volume and is thus much more representative of the entire hepatic parenchyma. Therefore, this technique could permit to repeat fibrosis evaluation in treated and untreated patients, evaluating changes along the time in liver fibrosis, without the biopsy-associated risk of morbidity.
Thus, the aim of this study was to determine the effect of achieving an SVR on long-term histological outcomes, specifically in terms of progressive fibrosis improvement, and the usefulness of TE in the follow-up of HIV-/HCV-coinfected patients.
Abstract and Introduction
Abstract
There are few data about the long-term histological outcome of HIV-/HCV-coinfected patients after therapy with interferon and ribavirin. We performed an observational study of 216 patients who received therapy against HCV and who had at least three successive transient elastographies (TE) during the follow-up. The primary endpoint was confirmed fibrosis regression, defined as a reduction of at least 1 point in Metavir fibrosis score, confirmed and without worsening in successive TE. At baseline, 23% had fibrosis stage 4 or cirrhosis. Overall, 82 (38%) achieved sustained virological response (SVR), without differences in baseline fibrosis or time of follow-up. Confirmed fibrosis regression was observed in 55% of patients, higher for SVR (71% vs 44%; P < 0.01), and the likelihood of achieving fibrosis regression at 3, 5 and 7 years was 0.17, 0.51 and 0.67, respectively, for SVR patients, in comparison with 0.02, 0.23 and 0.41 for no SVR patients (P < 0.01, log-rank test at any time point). Progressive regression, defined as continuous improvement in successive TE, was observed in 62% of patients with advanced liver fibrosis or cirrhosis who achieved SVR. In a Cox regression model, only SVR (HR, 4.01; 95% CI, 2.33–7.57; P < 0.01) and a younger age (HR, 1.14; 95% CI, 1.05–1.25; P < 0.01; per year) were associated with fibrosis regression. This study confirms that the rate of liver fibrosis regression increases during the follow-up after SVR to interferon therapy in HIV-/HCV-coinfected patients.
Introduction
Human immunodeficiency virus (HIV) infection is cause of more rapid progression of fibrosis and development of cirrhosis in patients coinfected with hepatitis C virus (HCV). For this reason, HIV-infected individuals with positive HCV RNA determinations should be considered as potential candidates for anti-HCV treatment.
Together with the disappearance of HCV replication, it is already known that response to antiviral therapy with interferon or ribavirin reduces liver complications in chronic hepatitis C, and there is sufficient evidence of histological improvement in HCV-monoinfected patients after sustained virological response (SVR). However, little is known about the long-term evolution of liver fibrosis in HIV-/HCV-coinfected patients following therapy against HCV, taking into account the differences in fibrogenesis or viral kinetics, and the influence of immunosuppression. There could be expected slight changes in fibrosis, a similar outcome to that of monoinfected, or even better if the role of inflammation is higher.
In addition, during the last years, a noninvasive technique, transient elastography (TE), has been shown to identify fibrosis stage accurately. Liver stiffness measurement through TE is reproducible and independent of the operator and explores a volume of liver parenchyma, which can be approximated to a cylinder of 1 cm in diameter and 4 cm in length. This volume is 100 times larger than the biopsy specimen volume and is thus much more representative of the entire hepatic parenchyma. Therefore, this technique could permit to repeat fibrosis evaluation in treated and untreated patients, evaluating changes along the time in liver fibrosis, without the biopsy-associated risk of morbidity.
Thus, the aim of this study was to determine the effect of achieving an SVR on long-term histological outcomes, specifically in terms of progressive fibrosis improvement, and the usefulness of TE in the follow-up of HIV-/HCV-coinfected patients.
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