Spontaneous elimination of serum hepatitis C virus (HCV) RNA in chronic HCV carriers: A population-based cohort study

ABSTRACTDanoprevir is a hepatitis C virus (HCV) NS3/4A protease inhibitor that promotes multi-log10reductions in HCV RNA when administered as a 14-day monotherapy to patients with genotype 1 chronic HCV. Of these patients, 14/37 experienced a continuous decline in HCV RNA, 13/37 a plateau, and 10/37 a rebound. The rebound and continuous-decline groups experienced similar median declines in HCV RNA through day 7, but their results diverged notably at day 14. Plateau group patients experienced a lesser, but sustained, median HCV RNA decline. Baseline danoprevir susceptibility was similar across response groups but was reduced significantly at day 14 in the rebound group. Viral rebound in genotype 1b was uncommon (found in 2/23 patients). Population-based sequence analysis of NS3 and NS4A identified treatment-emergent substitutions at four amino acid positions in the protease domain of NS3 (positions 71, 155, 168, and 170), but only two (155 and 168) were in close proximity to the danoprevir binding site and carried substitutions that impacted danoprevir potency. R155K was the predominant route to reduced danoprevir susceptibility and was observed in virus isolated from all 10 rebound, 2/13 plateau, and 1/14 continuous-decline patients. Virus in one rebound patient additionally carried partial R155Q and D168E substitutions. Treatment-emergent substitutions in plateau patients were less frequently observed and more variable. Single-rebound patients carried virus with R155Q, D168V, or D168T. Clonal sequence analysis and drug susceptibility testing indicated that only a single patient displayed multiple resistance pathways. These data indicate the ascendant importance of R155K for viral escape during danoprevir treatment and may have implications for the clinical use of this agent.

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Hepatitis C Virus Prevalence and Risk Factors in a Village in Northeastern Romania—A Population-Based Screening—The First Step to Viral Micro-Elimination

Healthcare ◽

10.3390/healthcare9060651 ◽

2021 ◽

Vol 9 (6) ◽

pp. 651

Author(s):

Laura Huiban ◽

Carol Stanciu ◽

Cristina Maria Muzica ◽

Tudor Cuciureanu ◽

Stefan Chiriac ◽

...

Keyword(s):

Risk Factors ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Treatment ◽

Population Based ◽

Hcv Infection ◽

World Health ◽

Hcv Rna ◽

Virus Eradication ◽

Tertiary Center

(1) Background: The World Health Organization adopted a strategy for the Global Health Sector on Viral Hepatitis in 2016, with the main objective of eliminating hepatitis C virus (HCV) by 2030. In this work, we aimed to evaluate the prevalence of HCV infection and risk factors in a Romanian village using population-based screening as part of the global C virus eradication program. (2) Methods: We conducted a prospective study from March 2019 to February 2020, based on a strategy as part of a project designed to educate, screen, treat and eliminate HCV infection in all adults in a village located in Northeastern Romania. (3) Results: In total, 3507 subjects were invited to be screened by rapid diagnostic orientation tests (RDOT). Overall, 2945 (84%) subjects were tested, out of whom 78 (2.64%) were found to have positive HCV antibodies and were scheduled for further evaluation in a tertiary center of gastroenterology/hepatology in order to be linked to care. In total, 66 (85%) subjects presented for evaluation and 55 (83%) had detectable HCV RNA. Of these, 54 (98%) completed antiviral treatment and 53 (99%) obtained a sustained virological response. (4) Conclusions: The elimination of hepatitis C worldwide has a higher chance of success if micro-elimination strategies based on mass screening are adopted.

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Clinical application of the Quantiplex HCV RNA 2.0 and Amplicor HCV Monitor assays for quantifying serum hepatitis C virus RNA

Journal of Clinical Pathology ◽

10.1136/jcp.52.11.807 ◽

1999 ◽

Vol 52 (11) ◽

pp. 807-811 ◽

Cited By ~ 10

Author(s):

M. L. Yu ◽

W. L. Chuang ◽

S. C. Chen ◽

Z. Y. Lin ◽

M. Y. Hsieh ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Clinical Application ◽

Hcv Rna ◽

Serum Hepatitis ◽

Hepatitis C Virus Rna ◽

Virus Rna

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A Treatment-as-Prevention Trial to Eliminate Hepatitis C Among Men Who Have Sex With Men Living With Human Immunodeficiency Virus (HIV) in the Swiss HIV Cohort Study

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1124 ◽

2020 ◽

Cited By ~ 2

Author(s):

Dominique L Braun ◽

Benjamin Hampel ◽

Bruno Ledergerber ◽

Christina Grube ◽

Huyen Nguyen ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Cohort Study ◽

Hepatitis C ◽

Population Based ◽

Hcv Infection ◽

World Health ◽

Treatment As Prevention ◽

Hcv Rna ◽

Immunodeficiency Virus ◽

Sex With Men

Abstract Background In 2016, the World Health Organization (WHO) introduced global targets for the elimination of hepatitis C virus (HCV) by 2030. We conducted a nationwide HCV micro-elimination program among men who have sex with men (MSM) living with human immunodeficiency virus (HIV) from the Swiss HIV Cohort Study (SHCS) to test whether the WHO goals are achievable in this population. Methods During phase A (10/2015–06/2016), we performed a population-based and systematic screening for HCV-RNA among MSM from the SHCS. During phase B (06/2016–02/2017) we offered treatment with HCV direct-acting antiviral (DAA) agents to MSM identified with a replicating HCV infection. During phase C (03/2017–11/2017), we offered rescreening to all MSM for HCV-RNA and initiated DAA treatment in MSM with replicating infections. Results We screened 3715/4640 (80%) MSM and identified 177 with replicating HCV infections (4.8%); 150 (85%) of whom started DAA treatment and 149 (99.3%) were cured. We rescreened 2930/3538 (83%) MSM with a prior negative HCV-RNA and identified 13 (0.4%) with a new HCV infection. At the end of the micro-elimination program, 176/190 MSM (93%) were cured, and the HCV incidence rate declined from .53 per 100 patient-years (95% CI, .35–.83) prior to the intervention to .12 (95% CI, .03–.49) by the end of 2019. Conclusions A systematic, population-based HCV micro-elimination program among MSM living with HIV was feasible and resulted in a strong decline in HCV incidence and prevalence. Our study can serve as a model for other countries aiming to achieve the WHO HCV elimination targets. Clinical Trials Registration NCT02785666.

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Maternal Hepatitis B Virus or Hepatitis C Virus Carrier Status and Long-Term Endocrine Morbidity of the Offspring—A Population-Based Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm9030796 ◽

2020 ◽

Vol 9 (3) ◽

pp. 796 ◽

Cited By ~ 1

Author(s):

Naim Abu Freha ◽

Tamar Wainstock ◽

Tzvi Najman Menachem ◽

Eyal Sheiner

Keyword(s):

Cohort Study ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Cox Regression ◽

Population Based ◽

Carrier Status ◽

B Virus

This study aimed to investigate the long-term effect of maternal hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier status on offspring endocrine morbidity. A population-based cohort study included all singleton deliveries between the years 1991–2014 at the Soroka University Medical Center, Beer-Sheva, Southern Israel. The mothers were subdivided into three groups, HBV carriers, HCV carriers and non-carriers. Data regarding the long-term endocrine morbidity of their offspring were compared between the groups. The study included 242,905 (99.7%) non-carrying mothers, 591 (0.2%) mothers who were carriers for HBV and 186 (0.1%) mothers who were carriers for HCV. The Kaplan–Meier’s survival curve demonstrated a significantly higher cumulative endocrine morbidity in children born to mothers with HCV (log-rank test, p = 0.002). Specifically, higher rates of hypoglycemia were noted among the offspring born to mothers who were carriers of HCV (1.1%; p = 0.001) compared with the offspring of mothers who were either carriers of HBV (0.2%) or non-carriers (0.1%). A Cox regression model controlled for maternal age, gestational age, maternal diabetes, hypertensive disorders of pregnancy, found maternal HCV carrier status to be independently associated with pediatric endocrine morbidity in the offspring (adjusted hazard ratio = 5.05, 95% CI: 1.625–15.695, p = 0.005). Maternal HCV carrier status is an independent risk factor for long-term endocrine morbidity.

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