Spontaneous Clearance of Chronic HCV: The Key Ending Left in the Dark

BACKGROUND: Hepatitis C is the second leading cause of liver cirrhosis and hepatocellular carcinoma. Although the discovery of direct-acting agents made the disease curable, HCV elimination can be achieved solely by the host’s immunologic arsenal. CASE REPORT: We report the case of a 29-year-old woman with chronic hepatitis C infection - elevated transaminases, positive serology. HCV was detectable on two occasions, and histology showed mild disease - A1F1. Upon follow up and without any treatment, the patient achieved spontaneous clearance confirmed by two consecutive undetectable HCV RNA tests. Spontaneous HCV clearance rarely occurs – 0.5% per person-year. This is sometimes accompanied by special circumstances like additional disease or medical interventions. Host factors like gender and interleukin-28B polymorphisms have been known to contribute to clearance. Viral factors like HCV RNA levels are also a factor. The characteristics of host-viral interplay – age of acquisition and fibrosis stage – cannot be overlooked. CONCLUSION: All of the abovementioned factors contribute to the complex immunological interaction between virus and host and the result, although rarely can be spontaneous clearance.

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Risk Factors Contributing to the Occurrence and Recurrence of Hepatocellular Carcinoma in Hepatitis C Virus Patients Treated with Direct-Acting Antivirals

Biomedicines ◽

10.3390/biomedicines8060175 ◽

2020 ◽

Vol 8 (6) ◽

pp. 175

Author(s):

Sara Kishta ◽

Ashraf Tabll ◽

Tea Omanovic Kolaric ◽

Robert Smolic ◽

Martina Smolic

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Hepatitis C ◽

Dna Ploidy ◽

Hcv Rna ◽

Direct Acting Antivirals ◽

Hepatic Cells ◽

Chronic Hcv ◽

Direct Acting

Although hepatitis C virus (HCV) RNA may be eliminated from blood circulation by direct-acting antivirals (DAA) therapy as assessed by real-time polymerase chain reaction (PCR), HCV RNA can still be present in liver tissue, and this is known as occult HCV. There has been a lot of controversy surrounding the recurrence of hepatocellular carcinoma (HCC) after DAA treatment of hepatic cells infected with chronic HCV. One of the main risk factors that leads to de novo HCC is the chronicity of HCV in hepatic cells. There are many studies regarding the progression of HCV-infected hepatic cells to HCC. However, there is a lack of research on the different molecular mechanisms that lead to the progression of chronic HCV infection to HCC, as well as on the effect of HCV on the alteration of DNA ploidy, which eventually leads to a recurrence of HCC after DAA treatment. In this review article, we will address some risk factors that could lead to the development/recurrence of HCC after treatment of HCV with DAA therapy, such as the role of liver cirrhosis, the alteration of DNA ploidy, the reactivation of hepatitis B virus (HBV), the role of cytokines and the alteration of the immune system, concomitant non- alcoholic fatty liver disease (NAFLD), obesity, alcohol consumption and also occult HCV infection/co-infection. Clinicians should be cautious considering that full eradication of hepatocarcinogenesis cannot be successfully accomplished by anti-HCV treatment alone.

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Interferon treatment for chronic hepatitis C infection in hemophiliacs-- influence of virus load, genotype, and liver pathology on response

Blood ◽

10.1182/blood.v87.5.1704.bloodjournal8751704 ◽

1996 ◽

Vol 87 (5) ◽

pp. 1704-1709 ◽

Cited By ~ 1

Author(s):

JP Hanley ◽

LM Jarvis ◽

J Andrew ◽

R Dennis ◽

PC Hayes ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Early Stage ◽

Hcv Infection ◽

Hcv Rna ◽

Interferon Treatment ◽

Hepatitis C Infection ◽

Virus Load ◽

Chronic Hcv

In this study, we assessed the effectiveness of interferon treatment in 31 hemophiliacs with chronic hepatitis C virus (HCV) infection. Interferon alfa-2a (3 MU three times weekly) was administered for 6 months. Response was assessed by both serial alanine transaminase (ALT) and HCV RNA levels measured by a sensitive semiquantitative polymerase chain reaction (PCR) method. HCV genotype was determined by restriction fragment length polymorphism (RFLP), and evidence of changing genotypes during interferon therapy was sought. Severity of liver disease was assessed by both noninvasive and invasive methods, including laparoscopic liver inspection and biopsy. Sustained normalization of ALT levels occurred in eight patients (28%), and seven (24%) became nonviremic as assessed by PCR (<80 HCV/mL). Responders universally cleared HCV RNA within 2 months of starting interferon. Genotype 3a was associated with a favorable response to interferon. No evidence was found for a change in circulating genotype in patients who failed to respond to interferon or who relapsed. This study confirms that response rates to interferon are low in hemophiliacs as compared with other groups with chronic HCV infection. We have also demonstrated that virus load measurement over the first 8 to 12 weeks of treatment is an extremely useful method to identify responders at an early stage.

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Hepatitis C virus screening of high-risk patients in a community hospital emergency department: Retrospective review of patient characteristics and future implications

PLoS ONE ◽

10.1371/journal.pone.0252976 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252976

Author(s):

Ji Seok Park ◽

Judy Wong ◽

Hillary Cohen

Keyword(s):

Hepatitis C ◽

Tobacco Use ◽

Screening Test ◽

Linkage To Care ◽

Hcv Infection ◽

Hcv Rna ◽

Spontaneous Clearance ◽

History Of ◽

Chronic Hcv Infection ◽

Chronic Hcv

Background Chronic hepatitis C virus infection (HCV) is a common infectious disease that affects more than 2.7 million people in the US. Because the emergency department (ED) can present an ideal opportunity to screen patients who may not otherwise get routine screening, we implemented a risk-based screening program for ED patients and established a system to facilitate linkage to care. Methods and findings A risk-based screening algorithm for HCV was programmed to trigger an alert in Epic electronic medical record system. Patients identified between August 2018 and April 2020 in the ED were tested for HCV antibody reflex to HCV RNA. Patients with a positive screening test were contacted for the confirmatory test result and to establish medical care for HCV treatment. Patient characteristics including age, sex, self-awareness of HCV infection, history of previous HCV treatment, history of opioids use, history of tobacco use, and types of insurance were obtained. A total of 4,525 patients underwent a screening test, of whom 131 patients (2.90%) were HCV antibody positive and 43 patients (0.95%) were HCV RNA positive, indicating that only 33% of patients with positive screening test had chronic HCV infection. The rate of chronic infection was higher in males as compared to females (1.34% vs 0.60%, p = 0.01). Patients with history of opioid use or history of tobacco use were found to have a lower rate of spontaneous clearance than patients without each history (opioids: 48.6% vs 72.0%, p = 0.02; tobacco: 56.6% vs 80.5%, p = 0.01). Among 43 patients who were diagnosed with chronic hepatitis C, 26 were linked to a clinical setting that can address chronic HCV infection, with linkage to care rate of 60.5%. The most common barrier to this was inability to contact patients after discharge from the ED. Conclusions A streamlined EMR system for HCV screening and subsequent linkage to care from the ED can be successfully implemented. A retrospective review suggests that male sex is related to chronic HCV infection, and history of opioid use or history of tobacco use is related to lower HCV spontaneous clearance.

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Interferon treatment for chronic hepatitis C infection in hemophiliacs-- influence of virus load, genotype, and liver pathology on response

Blood ◽

10.1182/blood.v87.5.1704.1704 ◽

1996 ◽

Vol 87 (5) ◽

pp. 1704-1709 ◽

Cited By ~ 28

Author(s):

JP Hanley ◽

LM Jarvis ◽

J Andrew ◽

R Dennis ◽

PC Hayes ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Early Stage ◽

Hcv Infection ◽

Hcv Rna ◽

Interferon Treatment ◽

Hepatitis C Infection ◽

Virus Load ◽

Chronic Hcv

Abstract In this study, we assessed the effectiveness of interferon treatment in 31 hemophiliacs with chronic hepatitis C virus (HCV) infection. Interferon alfa-2a (3 MU three times weekly) was administered for 6 months. Response was assessed by both serial alanine transaminase (ALT) and HCV RNA levels measured by a sensitive semiquantitative polymerase chain reaction (PCR) method. HCV genotype was determined by restriction fragment length polymorphism (RFLP), and evidence of changing genotypes during interferon therapy was sought. Severity of liver disease was assessed by both noninvasive and invasive methods, including laparoscopic liver inspection and biopsy. Sustained normalization of ALT levels occurred in eight patients (28%), and seven (24%) became nonviremic as assessed by PCR (<80 HCV/mL). Responders universally cleared HCV RNA within 2 months of starting interferon. Genotype 3a was associated with a favorable response to interferon. No evidence was found for a change in circulating genotype in patients who failed to respond to interferon or who relapsed. This study confirms that response rates to interferon are low in hemophiliacs as compared with other groups with chronic HCV infection. We have also demonstrated that virus load measurement over the first 8 to 12 weeks of treatment is an extremely useful method to identify responders at an early stage.

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Adherence to a Fish-Rich Dietary Pattern Is Associated with Chronic Hepatitis C Patients Showing Low Viral Load: Implications for Nutritional Management

Nutrients ◽

10.3390/nu13103337 ◽

2021 ◽

Vol 13 (10) ◽

pp. 3337

Author(s):

Claudia Ojeda-Granados ◽

Arturo Panduro ◽

Karina Gonzalez-Aldaco ◽

Ingrid Rivera-Iñiguez ◽

Liliana Campos-Medina ◽

...

Keyword(s):

Viral Load ◽

Hepatitis C ◽

High Viral Load ◽

Hcv Infection ◽

Hcv Rna ◽

Spontaneous Clearance ◽

Nutritional Management ◽

Chronic Hcv ◽

Few Data

Hepatitis C virus (HCV) infection is influenced by genetic (e.g., APOE polymorphisms) and environmental factors between the virus and the host. HCV modulates the host’s lipid metabolism but dietary components influence lipids and in vitro HCV RNA replication. Few data exist on the role of dietary features or patterns (DPs) in HCV infection. Herein, we aimed to evaluate the nutritional profiles of chronic HCV (CHC) and spontaneous clearance (SC) Mexican patients in the context of APOE alleles and their correlation with HCV-related variables. The fibrosis-related APOEε3 allele prevailed in CHC and SC patients, who had four DPs (“meat and soft drinks”, DP1; “processed animal and fried foods”, DP2; “Mexican-healthy”, DP3; and “fish-rich”, DP4). In CHC subjects, polyunsaturated fatty acid intake (PUFA ≥ 4.9%) was negatively associated, and fiber intake (≥21.5 g/d) was positively associated with a high viral load (p < 0.036). High adherence to fish-rich DP4 was associated with a higher frequency of CHC individuals consuming PUFA ≥ 4.9% (p = 0.004) and low viral load (p = 0.036), but a lower frequency of CHC individuals consuming fiber ≥ 21.5 g/d (p = 0.038). In SC and CHC individuals, modifying unhealthy DPs and targeting HCV-interacting nutrients, respectively, could be part of a nutritional management strategy to prevent further liver damage.

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Inflammatory cytokines and S-100b protein in patients with hepatitis C infection and cryoglobulinemias

Clinical & Investigative Medicine ◽

10.25011/cim.v30i5.2892 ◽

2007 ◽

Vol 30 (5) ◽

pp. 167 ◽

Cited By ~ 12

Author(s):

Katia Falasca ◽

Paola Mancino ◽

Claudio Ucciferri ◽

Margherita Dalessandro ◽

Pompea Zingariello ◽

...

Keyword(s):

Hepatitis C ◽

Protein S ◽

Serum Levels ◽

Mixed Cryoglobulinemia ◽

Control Group ◽

Hcv Rna ◽

Hepatitis C Infection ◽

Predictive Role ◽

Chronic Hcv ◽

Sensitive Marker

Objective: To investigate a predictive role for the protein S-100b and serum circulating levels of Th1/Th2 cytokines in patients with chronic hepatitis C virus (HCV) infection with and without mixed cryoglobulinemia (MC). Methods: Sixty chronically HCV-infected patients were divided into two groups: 30 with and 30 without MC. Patients with MC presented detectable mixed cryoglobulins and clinical weakness, purpura and arthralgias. HCV-RNA and genotype, serum levels of cryoglobulins, principal hepatic indexes and levels of IL-6, IL-18 and S-100b protein were evaluated. Twenty uninfected healthy subjects were a control group to evaluate serum levels of S-100b protein. Results: IL-6 and IL-18 serum levels were higher in the MC+ group than the MC- group (8.7 ± 4.5 pg/mL versus 4.6 ± 2.3 pg/mL P < 0.0001 and 743.5 ± 128.2 pg/mL versus 578.5 ± 296.5 pg/mL P < 0.001 respectively). S-100b serum levels were higher in HCV+ with MC (0.23 ± 0.07 microg/L) respect to HCV+ patients without MC (0.17 ± 0.05 microg/L, P < 0.0001) and were statistically higher than in the control group (0.08 ± 0.03 microg/L, P < 0.0001 and P < 0.0001, respectively). A positive correlation was shown between serum levels of S-100b protein and levels of cryoglobulins in the group of HCV+ patients MC+ (r=0.72 and P < 0.0001). Conclusion: HCV patients with MC have a worse inflammatory condition than those without MC. Moreover, S-100b protein seems to be a sensitive marker of endothelial and tissue damage in chronic HCV hepatitis with cryoglobulinemia.

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Hepatitis C core antigen: a simple predictive marker for treatment response to the new direct-acting antiviral drugs in chronic HCV Egyptian patients

Egyptian Liver Journal ◽

10.1186/s43066-021-00092-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Asmaa M. Elbrolosy ◽

Moamena S. Elhamouly ◽

Emad M. Eed ◽

Gamalat A. El Gedawy ◽

Mai Abozeid ◽

...

Keyword(s):

Hepatitis C ◽

Treatment Response ◽

Antiviral Drugs ◽

Core Antigen ◽

Hcv Rna ◽

Promising Alternative ◽

Direct Acting Antiviral ◽

Significant Difference ◽

Chronic Hcv ◽

Direct Acting

Abstract Background Successful eradication of hepatitis C virus (HCV) has great impact on the prognosis of HCV-related complications and the associated mortality. The development of the new direct-acting antiviral drugs (DAAs) has revolutionized the treatment of HCV infection. HCV core antigen (HCVcAg) is a recently developed marker that displayed a good correlation with HCV RNA assays. Our main objectives were to correlate between serum levels of HCVcAg and HCV RNA loads in chronic HCV patients as well as to explore the potential value of HCVcAg assay in predicting treatment response to the new DAAs. The study enrolled a total of 280 chronic HCV-infected patients scheduled to start the new regimen for treatment of chronic HCV by all-oral, interferon-free DAAs. According to the viral load, the studied individuals were arranged into three groups corresponding to mild, moderate, and sever viremia. Serum level of HCVcAg was determined by ELISA technique and HCV RNA viral loads were quantified using the real-time PCR system. The assays were performed three times for all participants: prior to initiation of treatment, at the end of treatment (week 12), and 3 months post-treatment cessation (week 24). Results A statistically significant difference between HCV RNA and HCVcAg baseline levels among different viremia groups was detected (P < 0.001). There was a significant positive correlation between HCV RNA and HCVcAg baseline values among all the studied cases (P < 0.05) with a correlation coefficient of 0.752, 0.976, and 1.00 respectively for mild, moderate, and severe viremia groups. 92.9% (260/280) of the studied patients achieved sustained virologic response, 3.6% (10/280) were non-responders, and 3.6% (10/280) had recurrent viremia/relapse as regards RT-PCR results. Conclusion HCVcAg is a promising alternative to HCV RNA assay. The ELISAs for HCVcAg proved excellent correlations with HCV RNA levels. Moreover, HCVcAg can be introduced as a simple and highly specific tool for monitoring the new DAA regimens particularly in low-resource settings.

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Retrospective study of hepatitis C outcomes and treatment in HIV co-infected persons from the Australian HIV Observational Database

Sexual Health ◽

10.1071/sh16151 ◽

2017 ◽

Vol 14 (4) ◽

pp. 345 ◽

Cited By ~ 4

Author(s):

Rainer Puhr ◽

Stephen T. Wright ◽

Jennifer F. Hoy ◽

David J. Templeton ◽

Nicolas Durier ◽

...

Keyword(s):

Hepatitis C ◽

Hcv Rna ◽

Hcv Treatment ◽

Logistic Regression Models ◽

Factors Associated ◽

Treatment Uptake ◽

Observational Database ◽

Treatment Data ◽

Chronic Hcv ◽

Direct Acting

Background: The widespread availability of direct-acting antivirals (DAAs) is expected to drastically improve the treatment uptake and cure rate of hepatitis C virus (HCV). In this paper, rates of and factors associated with HCV treatment uptake and cure in the HIV co-infected population in Australia were assessed before access to DAAs. Methods: The medical records of patients in the Australian HIV Observational Database who were reported to be HCV antibody positive from 1999 to 2014 were reviewed for HCV treatment data. Patients with detectable HCV RNA were included in this analysis. Logistic regression models were applied to identify factors associated with treatment uptake and HCV sustained virological response (SVR) 24 weeks’ post treatment. Results: The median follow-up time of those with chronic HCV/HIV co-infection was 103 months (interquartile range 51–166 months). Of 179 HCV viraemic patients, 79 (44.1%) began treatment. In the adjusted model, a higher METAVIR score was the only significant factor associated with treatment uptake (odds ratio (OR) 8.87, 95% confidence interval (CI) 2.00–39.3, P = 0.004). SVR was achieved in 37 (50%) of 74 treated patients. HCV genotypes 2/3 compared with 1/4 remained the only significant factor for SVR in an adjusted multivariable setting (OR 5.44, 95% CI 1.53–19.4, P = 0.009). Conclusions: HCV treatment uptake and SVR have been relatively low in the era of interferon-containing regimens, in Australian HIV/HCV coinfected patients. With new and better tolerated DAAs, treatment of HCV is likely to become more accessible, and identification and treatment of HCV in co-infected patients should become a priority.

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Relationship between Duffy Antigen Receptor for Chemokines and Clinical Characteristics in Han People with Chronic Hepatitis C Infection in Dalian, China

10.32592/ircmj.2020.22.10.146 ◽

2020 ◽

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Hepatic Fibrosis ◽

Protective Factor ◽

Hcv Infection ◽

Hcv Rna ◽

Hepatitis C Infection ◽

Duffy Antigen ◽

Chronic Hcv

Background and Objectives: Most patients with untreated chronic hepatitis C virus (HCV) infection develop hepatic fibrosis. Hepatic disease progression is monitored with hematological markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin and platelet [PLT] count, AST/ALT ratio, AST/PLT ratio index [APRI], and fibrosis 4 score [FIB-4]) and FibroScan. The present study aimed to investigate the association between Duffy antigen/chemokines receptor (DARC) polymorphisms and clinical parameters in the Han people with chronic hepatitis C infection in Dalian, China. Materials and Methods: This cohort study was performed on 245 Han people with chronic HCV at Dalian infectious hospital during April-December 2015. The participants of the research were selected using the consecutive sampling method. The DARC genotyping was performed using the TaqMan probe method and transient elastography was measured by FibroScan. Results: Based on the findings, DARC polymorphisms correlated with ALT concentrations (FY*A/FY*A vs. FY*A/FY*B, P=0.025). However, the DARC polymorphism did not have an association with HCV RNA titers (FY*A/FY*A vs. FY*A/FY*B, P=0.241) or hepatic fibrosis (FY*A/FY*A vs. FY*A/FY*B, P=0.325). Moreover, correlation analyses showed that APRI (P<0.001, rho=0.603) and FIB-4 (P<0.001, rho=0.698) were useful predictors of hepatic fibrosis in chronic HCV infection. Besides, HCV RNA titers (P=0.327) and hepatic injury markers (P=0.814, 0.198, 0.767, and 0.171 for ALT, AST, ALB, and AST/ALT, respectively) were not useful for the estimation of the fibrosis stage in patients with chronic hepatitis C. Conclusion: The FY*A allele is a potentially valuable protective factor against hepatocyte damage in chronic HCV-infected patients.

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Mental health outcomes for individuals with chronic hepatitis C infection.

Online Journal of Public Health Informatics ◽

10.5210/ojphi.v11i1.9800 ◽

2019 ◽

Vol 11 (1) ◽

Author(s):

William W. Thompson ◽

Mohammed A. Khan ◽

Jay Soh ◽

Lauren Canary ◽

Michael Blank ◽

...

Keyword(s):

Mental Illness ◽

Hepatitis C ◽

Hcv Infection ◽

Hcv Rna ◽

Fee For Service ◽

Hepatitis C Infection ◽

Hcv Antibody ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Test Result

ObjectiveUsing data from the 2011–2015 IBM MarketScan® Commercial Claims and Encounters, we sought to assess the relationship between mental health outcomes and chronic hepatitis C infection after adjusting for important confounders. Persons with HCV antibody and RNA test results between 2011 and 2015 and continuous enrollment in fee-for-service plans were included in the analysisIntroductionHepatitis C virus (HCV) infection is a leading cause of liver disease-related morbidity and mortality in the United States and HCV incidence has been increasing. Mental illness may impact the likelihood of initial HCV infection, progress and adherence to treatment along the hepatitis C care cascade, and risk of subsequent reinfection for those cured of hepatitis C. The relationship between HCV infection and mental illness is not well understood and many studies have lacked sufficient sample size to adjust for important confounders. We sought to explore the association between chronic HCV infection and mental illness after adjusting for important confounders.MethodsWe obtained data from the 2011–2015 IBM MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases. These data consist of inpatient and outpatient service claims for persons with employer-sponsored health insurance coverage and their dependents. Persons with HCV antibody and RNA test results between 2011 and 2015 and continuous enrollment in a fee-for-service plan were included in the analysis. Chronic HCV infection was defined by a positive HCV RNA test result. Controls without chronic HCV infection had a negative HCV antibody test result and no positive HCV antibody or RNA test result in the preceding or following year. The index date was defined by the date of the earliest positive HCV RNA or negative HCV antibody test. Demographic characteristics were obtained from the MarketScan® enrollment tables. All enrollees in the study population were at least 18 years old during the year of the index date. The analysis sample was restricted to persons who were identified as receiving outpatient prescription drug claims data feeds. We estimated adjusted odds ratios (OR) for the association between mental illness (ICD-9 code 295 or 296) and HCV RNA status. Multivariate models included age (18-44, 45-64, 65+ years), sex, region, and an adjusted Charlson Comorbidity Index which excluded liver disease and hepatocellular carcinoma.ResultsWe identified 2,847 individuals with chronic HCV infection (HCV RNA+) and 57,418 controls who were HCV antibody negative. With respect to age, 83% of HCV RNA+ individuals were aged 45-64 years while only 43% of the HCV antibody negative individuals were in the same age range. Similarly, for sex, 62% and 40% of HCV RNA+ individuals and controls, respectively, were male. For unadjusted analyses, age, sex, region, comorbid conditions, and mental illness (OR= 2.25 [95% CI; 1.52 - 3.34]) were all statistically associated with HCV RNA+. For the multivariate adjusted models, these same variables remained statistically significant. For the multivariate model, individuals with a mental illness were more likely to be HCV RNA+ relative to HCV antibody negative controls. (OR= 1.95 [95% CI; 1.30 - 2.93]).ConclusionsThis study demonstrated a strong association between mental illness and HCV chronic infection after adjusting for important confounders including other comorbid conditions. A growing body of research suggests that persons with mental illness are at increased risk for contracting and transmitting HCV due to high rates of substance use and high-risk sexual behavior among infected persons as well as high rates of sexual victimization. HCV prevention efforts should be directed toward individuals with mental illness or seeking treatment for mental illness.

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