Virologic, Clinical, and Immune Response Outcomes of Patients With Hepatitis C Virus–Associated Cryoglobulinemia Treated With Direct-Acting Antivirals

AbstractClinical trials showed pangenotypic direct-acting antivirals’ (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.

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Enhanced immune responses, PI3K/AKT and JAK/STAT signaling pathways following hepatitis C virus eradication by direct-acting antiviral therapy among Egyptian patients: a case control study

Pathogens and Disease ◽

10.1093/femspd/ftab008 ◽

2021 ◽

Author(s):

Haidi Karam-Allah Ramadan ◽

Gamal Badr ◽

Nancy K Ramadan ◽

Aml Sayed

Keyword(s):

Immune Response ◽

Liver Cirrhosis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Immune Responses ◽

Signaling Pathways ◽

Liver Diseases ◽

Stat Signaling ◽

Chronic Hcv ◽

Direct Acting

Abstract The use of direct-acting antivirals (DAAs) therapy for the treatment of hepatitis C virus (HCV) results in a high sustained virological response (SVR) and subsequently alters liver immunologic environment. However, hepatocellular carcinoma (HCC) may occur after DAAs treatment. We aimed to clarify changes of immune responses, PI3K/AKT and JAK/STAT signaling pathways in HCV-induced liver diseases and HCC following DAAs treatment. Four cohorts are classified as chronic HCV patients, HCV-related cirrhosis without HCC, HCV-related cirrhosis and HCC, and healthy control group. The patient groups were further divided into treated or untreated with DAAs with SVR12. Increased percentages of CD3, CD8 and CD4, decreased CD4/FoxP3/CD25, CD8/PD-1 and CD19/PDL-1 were found in DAAs-treated patients in the three HCV groups. Following DAAs therapy, the levels of ROS, IL-1β, IL-6, IL-8 and TNF-α were significantly decreased in the three HCV groups. Treated HCV patients showed up regulation of p-AKT and p-STAT5 and down regulation of p-STAT3, HIF-1α and COX-2. In conclusion, DAAs enhance the immune response in chronic HCV and liver cirrhosis, hence our study is the first to show change in PI3K/AKT and JAK/STAT signaling pathways in different HCV-induced liver diseases after DAAs. In chronic HCV, DAAs have better impact on the immune response while in liver cirrhosis not all immune changes were prominent.

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The challenges of administering a new treatment: the case of direct-acting antivirals for hepatitis C virus

Public Health ◽

10.1016/j.puhe.2020.02.009 ◽

2021 ◽

Vol 190 ◽

pp. 116-122

Author(s):

S. Mondschein ◽

N. Yankovic ◽

O. Matus

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Direct Acting Antivirals ◽

New Treatment ◽

Direct Acting

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Risk of extrahepatic cancer in a nationwide cohort of hepatitis C virus infected persons treated with direct acting antivirals

GastroHep ◽

10.1002/ygh2.456 ◽

2021 ◽

Author(s):

Charlotte Lybeck ◽

Daniel Bruce ◽

Scott M Montgomery ◽

Soo Aleman ◽

Ann‐Sofi Duberg

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Direct Acting Antivirals ◽

Direct Acting

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Direct, indirect and total effect of HIV coinfection on the risk of non‐liver‐related cancer in hepatitis C virus‐infected patients treated by direct‐acting antivirals: a mediation analysis

HIV Medicine ◽

10.1111/hiv.13153 ◽

2021 ◽

Author(s):

Mathieu Chalouni ◽

Stanislas Pol ◽

Philippe Sogni ◽

Helene Fontaine ◽

Karine Lacombe ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Mediation Analysis ◽

Total Effect ◽

Direct Acting Antivirals ◽

Hiv Coinfection ◽

Direct Acting

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Improvement of Gut Diversity and Composition After Direct-Acting Antivirals in Hepatitis C Virus–Infected Patients With or Without Human Immunodeficiency Virus Coinfection

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab094 ◽

2021 ◽

Author(s):

Natthaya Chuaypen ◽

Thananya Jinato ◽

Anchalee Avihingsanon ◽

Sakkarin Chirapongsathorn ◽

Supapon Cheevadhanarak ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Gut Microbiota ◽

Alpha Diversity ◽

Healthy Controls ◽

Direct Acting Antivirals ◽

Microbial Dysbiosis ◽

Immunodeficiency Virus ◽

Direct Acting

Abstract Background The influence of direct-acting antivirals (DAAs) on the composition of gut microbiota in hepatitis C virus (HCV)–infected patients with or without human immunodeficiency virus (HIV) is unclear. Methods We enrolled 62 patients with HCV monoinfection and 24 patients with HCV/HIV coinfection receiving elbasvir-grazoprevir from a clinical trial. Fecal specimens collected before treatment and 12 weeks after treatment were analyzed using amplicon-based 16S ribosomal RNA sequencing. Results Sustained virological response rates in the monoinfection and coinfection groups were similar (98.4% vs 95.8%). Pretreatment bacterial communities in the patient groups were less diverse and distinct from those of healthy controls. Compared with HCV-monoinfected patients, HCV/HIV-coinfected individuals showed comparable microbial alpha diversity but decreased Firmicutes-Bacteroidetes ratios. The improvement of microbial dysbiosis was observed in responders achieving sustained virological response across fibrosis stages but was not found in nonresponders. Responders with a low degree of fibrosis exhibited a recovery in alpha diversity to levels comparable to those in healthy controls. Reciprocal alterations of increased beneficial bacteria and reduced pathogenic bacteria were also observed in responders. Conclusions This study indicates a short-term effect of direct-acting antivirals in restoration of microbial dysbiosis. The favorable changes in gut microbiota profiles after viral eradication might contribute toward the reduction of HCV-related complications among infected individuals.

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