Status of Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection and Remaining Challenges

Baumert, Thomas F.; Berg, Thomas; Lim, Joseph K.; Nelson, David R.

doi:10.1053/j.gastro.2018.10.024

Cited by 157 publications

(137 citation statements)

References 130 publications

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“…Stratification of patients’ prognosis using the ALBI score in our study could depend on the development of more effective antiviral therapy than non‐pegylated IFN. Patients with smaller ALBI scores should have longer follow‐up periods until HCC develops and more chances to undergo next‐generation antiviral therapies, such as pegylated IFN therapy, combination therapy with pegylated IFN and telaprevir or simeprevir, and then IFN‐free oral treatments …”

Section: Discussionmentioning

confidence: 99%

Albumin–bilirubin score indicates liver fibrosis staging and prognosis in patients with chronic hepatitis C

Fujita

Oura

Yoneyama

et al. 2019

Hepatology Research

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Aim Albumin–bilirubin (ALBI) grade was investigated to predict prognosis of patients with cirrhosis. It was defined using the ALBI score calculated based on serum total bilirubin and albumin, which represent liver function. The diagnostic accuracy for liver fibrosis staging in patients with chronic hepatitis using the ALBI score has not been investigated well. This study aimed to evaluate the diagnostic abilities of the ALBI score for liver fibrosis staging in chronic hepatitis and cirrhosis in Japanese patients with hepatitis C virus (HCV) infection. Methods Japanese patients with HCV infection who underwent liver biopsy examinations were enrolled in a retrospective study. Fibrosis staging and activity grading were assessed using the modified METAVIR score. The ALBI score was calculated according to the following equation: Log10 total bilirubin (μmol/L) × 0.66 + albumin (g/L) × (−0.085). Results A total of 382 patients were enrolled in this study. The ALBI score differentiated fibrosis stage 4 from 3 and stage 3 from 2 (P < 0.05). When an ALBI score of −2.125 was adopted as a cut‐off value, the sensitivity and specificity were 73.2% and 87.1%, respectively, with a positive likelihood ratio of 5.67 to differentiate stage 4 from stages 1–3. Kaplan–Meier analysis showed that smaller ALBI scores at baseline correlated with better hepatocellular carcinoma (HCC)‐free and overall survival (P < 0.05). Conclusions The ALBI score indicates liver fibrosis staging in Japanese patients with HCV infection. Furthermore, smaller ALBI scores predict better HCC‐free survival and overall survival. The ALBI score has the potential to expand its application from cirrhosis to chronic hepatitis.

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Section: Discussionmentioning

confidence: 99%

Albumin–bilirubin score indicates liver fibrosis staging and prognosis in patients with chronic hepatitis C

Fujita

Oura

Yoneyama

et al. 2019

Hepatology Research

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“…Thus, approximately 80% of infected patients become chronic carriers and 20-30% develop liver cirrhosis within 25-30 years [171]. Chronic hepatitis C can now efficiently be cured by direct acting antivirals (for review see [172]). Chronic HCV infection induces hepatocyte cell death, that leads to release of DAMPs that can directly activate HSCs [31,35,77].…”

Section: Chronic Hepatitis Cmentioning

confidence: 99%

Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives

Roehlen

Crouchet

Baumert

2020

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440

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Liver fibrosis due to viral or metabolic chronic liver diseases is a major challenge of global health. Correlating with liver disease progression, fibrosis is a key factor for liver disease outcome and risk of hepatocellular carcinoma (HCC). Despite different mechanism of primary liver injury and disease-specific cell responses, the progression of fibrotic liver disease follows shared patterns across the main liver disease etiologies. Scientific discoveries within the last decade have transformed the understanding of the mechanisms of liver fibrosis. Removal or elimination of the causative agent such as control or cure of viral infection has shown that liver fibrosis is reversible. However, reversal often occurs too slowly or too infrequent to avoid life-threatening complications particularly in advanced fibrosis. Thus, there is a huge unmet medical need for anti-fibrotic therapies to prevent liver disease progression and HCC development. However, while many anti-fibrotic candidate agents have shown robust effects in experimental animal models, their anti-fibrotic effects in clinical trials have been limited or absent. Thus, no approved therapy exists for liver fibrosis. In this review we summarize cellular drivers and molecular mechanisms of fibrogenesis in chronic liver diseases and discuss their impact for the development of urgently needed anti-fibrotic therapies.

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“…Modern directly acting antiviral (DAA) therapy for HCV facilitates virological cure at a favorable safety and drug tolerability profile in nearly all patients [3][4][5][6][7][8]. The latest pangenotypic treatment regimens induce excellent SVR (sustained virologic response) rates independent of HCV-genotype (GT), even in former difficult-to-treat populations including patients with cirrhosis, pretreated subjects and HIV-coinfected patients [9].…”

Section: Introductionmentioning

confidence: 99%

Directly observed therapy for HCV with glecaprevir/pibrentasvir alongside opioid substitution in people who inject drugs—First real world data from Austria

Schmidbauer

Schubert²,

Schütz³

et al. 2020

PLoS ONE

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Background Directly acting antivirals (DAA) against hepatitis C virus (HCV) infection have facilitated sustained virologic response (SVR) rates >90% in clinical studies. Yet, real life data regarding DAA treatment in people who inject drugs (PWIDs) are scarce. We evaluated the effectiveness of glecaprevir/pibrentasvir (G/P) in difficult-to-treat PWIDs with presumed high risk of non-adherence to DAA therapy using the concept of directly observed therapy involving their opioid substitution therapy (OST) facility. Methods N = 145 patients (m/f: 91/54; median age: 41.1 (IQR 19.5) years; HCV-genotype (GT) 1/2/3/ 4: 82/1/56/5, GT3: 38.6%; cirrhosis: n = 6; 4.1%) treated with G/P were included. PWIDs at high risk for non-adherence to DAA therapy received HCV treatment together with their OST under the supervision of medical staff ("directly observed therapy", DOT). The effectiveness of G/P given as DOT in PWIDs with presumed high risk of non-adherence to DAA therapy was compared to patients with suspected "excellent compliance" in the "standard setting" (SS) of G/P prescription at a tertiary care center and self-managed G/P intake at home. Treatment duration was 8-16 weeks according to the G/P drug label. Results DOT-patients (n = 74/145; 51.0%) were younger than SS-patients (median 38.7, IQR 12.5 vs. median 50.6, IQR 20.3 years), all had psychiatric co-morbidities and most had a poor socioeconomic status. 50/74 (67.6%) reported ongoing intravenous drug use (IDU). SVR was achieved in n = 70/74 (94.6%) patients with n = 3 being lost to follow-up (FU) and n = 1 showing nonresponse to therapy.

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Status of Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection and Remaining Challenges

Cited by 157 publications

References 130 publications

Albumin–bilirubin score indicates liver fibrosis staging and prognosis in patients with chronic hepatitis C

Albumin–bilirubin score indicates liver fibrosis staging and prognosis in patients with chronic hepatitis C

Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives

Directly observed therapy for HCV with glecaprevir/pibrentasvir alongside opioid substitution in people who inject drugs—First real world data from Austria

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