Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis

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• 作者：Graham R. Foster¹ ; ^&dagger ; ; ^{g.r.foster@qmul.ac.uk" class="auth_mail" title="E-mail the corresponding author} ; William L. Irving² ; ^&dagger ; ; ^{Will.irving@nottingham.ac.uk" class="auth_mail" title="E-mail the corresponding author} ; Michelle C.M. Cheung³ ; Alex J. Walker⁴ ; Benjamin E. Hudson⁵ ; Suman Verma⁶ ; John McLauchlan⁷ ; David J. Mutimer⁸ ; Ashley Brown⁹ ; William T.H. Gelson¹⁰ ; Douglas C. MacDonald¹¹ ; Kosh Agarwal⁶ ; on behalf of HCV Research ; UK
• 关键词：DAA ; direct acting antiviral ; HCV ; hepatitis C virus ; EAP ; Expanded access programme ; SVR ; sustained virological response ; MELD ; model for end-stage liver disease ; ALT ; alanine aminotransferase ; RNA ; ribonucleic acid ; HIV ; human immunodeficiency virus ; SAE ; serious adverse event ; BMI ; body mass index ; LLQ ; lower limit of quantification ; ROC ; receiver-operating characteristic ; AUC ; area under the curve ; SOF ; sofosbuvir ; DCV ; daclatasvir ; LDV ; ledipasvir ; RBV ; ribavirin ; OR ; odds ratio ; CI ; confid
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：64
• 期：6
• 页码：1224-1231
• 全文大小：752 K

文摘

All oral direct acting antivirals (DAAs) effectively treat chronic hepatitis C virus (HCV) infection, but the benefits in advanced liver disease are unclear. We compared outcomes in treated and untreated patients with decompensated cirrhosis.

Methods

Patients with HCV and decompensated cirrhosis or at risk of irreversible disease were treated in an expanded access programme (EAP) in 2014. Treatment, by clinician choice, was with sofosbuvir, ledipasvir or daclatasvir, with or without ribavirin. For functional outcome comparison, untreated patients with HCV and decompensated cirrhosis who were registered on a database 6 months before treatment was available were retrospectively studied. Primary endpoint was sustained virological response 12 weeks post antiviral treatment (treated cohort) and the secondary endpoint (both cohorts) was adverse outcomes (worsening in MELD score or serious adverse event) within 6 months.

Results

467 patients received treatment (409 decompensated cirrhosis). Viral clearance was achieved in 381 patients (81.6%) – 209 from 231 (90.5%) with genotype 1 and 132 from 192 (68.8%) with genotype 3. MELD scores improved in treated patients (mean change −0.85) but worsened in untreated patients (mean + 0.75) (p <0.0001). Patients with initial serum albumin <35 g/L, aged >65 or with low (<135 mmol/L) baseline serum sodium concentrations were least likely to benefit from therapy.

Conclusions

All oral DAAs effectively cured HCV in patients with advanced liver disease. Viral clearance was associated with improvement in liver function within 6 months compared to untreated patients. The longer term impact of HCV treatment in patients with decompensated cirrhosis remains to be determined.