History Of Chronic Hepatitis C Virus Infection Research Articles

Prevalence and Outcome of Serum Autoantibodies in Chronic Hepatitis C Patients Undergoing Direct-Acting Antiviral Treatment.

BackgroundChronic immune stimulation by hepatitis C virus (HCV) may cause occurrence of several autoantibodies in infected patients, with or without features of clinically overt autoimmune diseases. The recent introduction of direct-acting antivirals (DAAs) has dramatically changed the natural history of chronic HCV infection. The aim of this study was to assess the effects of DAA therapy on serum autoantibodies in chronic hepatitis C (CHC) patients.MethodsThe medical records of 113 CHC patients were reviewed to assess autoantibody behavior following DAA-directed HCV eradication. Statistical analysis was performed to assess correlations between DAA treatment and autoantibody titers, HCV genotypes, and viral loads.ResultsAnti-nuclear (ANA), anti-smooth muscle cell (ASMA) and anti-mitochondrial (AMA) antibody testing was available in 77 patients; 31 out of 77 patients (40%) had one or more serum autoantibodies prior to treatment. Measurement of autoantibody titers before and after HCV eradication was performed in 20 of 31 patients. DAA treatment significantly affected ANA and ASMA titers, leading to disappearance or reduction of autoantibody titers; conversely, AMA were not influenced by DAA treatment. No correlations were observed between autoantibody specificity and both HCV genotypes and viral loads at baseline. Likewise, serum autoantibody titers were independent of HCV genotypes.ConclusionsDAA-directed HCV clearance may interrupt chronic immune stimulation by removing the drive for autoantibody induction. The isolated persistence of autoantibodies in the small fraction of patients who did not show clearance following DAA treatment may require long-term vigilance.

Perceptions of Alcohol Risk Among HIV/Hepatitis C Coinfected Patients.

We examined how patient perceptions of alcohol risk, provider discussions about alcohol, and treatment of hepatitis C virus (HCV) differed among HIV-HCV coinfected patients in primary care. Between April, 2016 and April, 2017, we conducted a screening survey with patients in an HIV primary care clinic in Seattle, Washington, who had chronic HCV coinfection or a history of chronic HCV infection who had successfully cleared their infection with treatment. Of 225 participants, 84 (37%) were active drinkers (drank ≥2-4 times/mo in past 3 months). Of those with little to no use for ≥3 months, 65 (29%) were former drinkers with a history of alcohol use and 76 were abstainers with no such history. Former drinkers and abstainers were more likely than active drinkers to perceive that any drinking was unsafe (69% vs 58% vs 31%; P < 0.001). Former drinkers were more likely to report a physician's recommendation to stop drinking than active drinkers (63% vs 47%; P = 0.05). The great majority (87%) of former drinkers decided to stop or reduce drinking on their own (most often in response to a nonhealth life event) and only 13% acknowledged doing so on their doctor's prompting. HCV treatment was not associated with former or active drinking status. Our findings underscore the importance of educating not only HIV-HCV patients about the effects of alcohol use but also HIV clinicians about delivering consistent counseling about alcohol avoidance. Understanding the reasons that HIV-HCV coinfected persons make changes in their alcohol use could drive novel interventions that reduce the negative consequences of drinking.

Epidemiology and natural history of hepatitis C virus infection.

Hepatitis C virus (HCV) affects 130-210 million people worldwide and is one of the major risk factors for hepatocellular carcinoma. Globally, at least one third of hepatocellular carcinoma cases are attributed to HCV infection, and 350000 people died from HCV related diseases per year. There is a great geographical variation of HCV infection globally, with risk factors for the HCV infection differing in various countries. The progression of chronic hepatitis C to end-stage liver disease also varies in different study populations. A long-term follow-up cohort enrolling participants with asymptomatic HCV infection is essential for elucidating the natural history of HCV-caused hepatocellular carcinoma, and for exploring potential seromarkers that have high predictability for risk of hepatocellular carcinoma. However, prospective cohorts comprising individuals with HCV infection are still uncommon. The risk evaluation of viral load elevation and associated liver disease/cancer in HCV (REVEAL-HCV) study has followed a cohort of 1095 residents seropositive for antibodies against hepatitis C virus living in seven townships in Taiwan for more than fifteen years. Most of them have acquired HCV infection through iatrogenic transmission routes. As the participants in the REVEAL-HCV study rarely receive antiviral therapies, it provides a unique opportunity to study the natural history of chronic HCV infection. In this review, the prevalence, risk factors and natural history of HCV infection are comprehensively reviewed. The study cohort, data collection, and findings on liver disease progression of the REVEAL-HCV study are described.

Long-term health outcomes of chronic hepatitis C patients: A review of findings from REVEAL-HCV cohort study

Chronic hepatitis C affects more than 180 million people worldwide. As one of the most important infectious diseases, it causes around 250,000 deaths per year. A long-term follow-up cohort study is essential for evaluating health outcomes associated with virus infection, and for exploring potential seromarkers that have high predictability for risk of developing various diseases. However, the prospective cohorts consisted of individuals with chronic hepatitis C virus (HCV) infection are still rare. The Risk Elevation of Viral Load Elevation and Associated Liver Disease/Cancer in HCV (REVEAL-HCV) study has followed a cohort of 1095 residents seropositive for anti-HCV antibodies lived in seven townships in Taiwan for 15 years. These anti-HCV seropositives were asymptomatic and relatively more healthy than chronic hepatitis C patients cared in clinics and hospitals. Most of them acquired HCV infection through iatrogenic transmission routes in study townships. The epidemiological characteristics of HCV infection were very similar to those in countries with high prevalence such as Japan, Korea, Italy, and India. As the participants in the REVEAL-HCV study rarely received antiviral therapies, it provided an exceptional opportunity to study the natural history of chronic HCV infection. In this review article, we describe the details of participant enrollment, laboratory tests, follow-up procedures, and major recent findings. Anti-HCV seropositives with elevated serum HCV RNA levels were found to have an increasing risk of developing hepatocellular carcinoma in a dose-response relationship. In addition to the serum HCV RNA level, serum alanine aminotransferase levels and HCV genotype also had long-term predictability for the risk of hepatocellular carcinoma. Moreover, anti-HCV seropositives with detectable serum HCV RNA levels had an increased mortality from extrahepatic diseases such as cerebrovascular and renal diseases. Our study revealed that anti-HCV seropositives with detectable serum HCV RNA levels had an increased risk of hepatic and extrahepatic diseases.

NASPGHAN Practice Guidelines

Hepatitis C virus (HCV) is an RNA virus that affects >180 million individuals worldwide with a high propensity for chronic infection. Children with HCV infection differ from adults in several ways including some modes of transmission, rates of clearance, progression of fibrosis, and the duration of potential chronic infection when acquired at birth. Since the discovery of HCV in 1989, there have been significant advances in the understanding of the virology and natural history of chronic HCV infection in children. In addition, there are now several treatment options for children with chronic hepatitis C infection and many new therapies on the horizon. As a consequence, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition brought together experts in pediatric hepatology to review the available data in children and provide clinicians with approaches to the diagnosis, management, and prevention of HCV infection in children and adolescents. The guideline details the epidemiology and natural history of HCV infection in children, the diagnostic workup, monitoring and treatment of disease, and provides an update on future treatment options and areas of research.

Gangrene Associated with Cryoglobulinemia (CR) in Hepatitis C Virus (HCV) Infection with a Fatal Outcome

Purpose: Cryoglobulins are characterized by cold perceptible immunoglobulins in the serum. Chronic HCV infection is well-known to be associated with CR, especially mixed CR. This condition typically manifests as vasculitis involving the skin. However, it is very unusual to have distal gangrene caused by HCV-induced CR alone. There have been case reports of gangrene caused by CR in multiple myeloma. This is a unique report of a patient who developed gangrene secondary to HCV associated CR. A 75-year-old female with past medical history of chronic HCV infection and splenomegaly was evaluated in the hematology clinic in 2008 for thrombocytopenia and palpable purpura on bilateral lower extremities. During the work-up, the patient was found to have an elevated cryoglobulin level of 2.6%, complement C3 level of 78 mg/dL, low C4 level (7mg/dL) and low C1q level (<3.6 mg/dL). Skin biopsy showed leukocytoclastic vasculitis. The patient failed HCV therapy and was managed conservatively for CR-induced vasculitic purpura, initially with good results, but was subsequently lost to follow up. In early 2011, the patient presented to the ER after a suicide attempt with oxycontin and Lantus® secondary to unbearable pain from vasculitis. On physical exam, she was unresponsive to any stimuli, with a decreased pulse on the right side and bilateral lower extremity purpura. Labaratory studies revealed elevated BUN and Creatinine with mild anemia. After initial resuscitation, she was admitted to MICU and on day 2, she was noted to have swelling and dusky discoloration of the left hand with palpable radial and brachial pulses. Doppler compression studies of the left hand showed thrombi in the superficial veins and IV heparin therapy was started. The arterial doppler showed good blood flow in the radial and ulnar arteries. From day 3 to day 5, the swelling and cyanosis worsened with development of gangrene. Cryoglobulin level was not detectable but C3, C4 and CH50 levels were low. Plasmapheresis was started with improvement of clinical condition. On day 10, the patient started to develop gastrointestinal bleeding with melena prompting stoppage of IV heparin therapy while octreotide and Nexium® therapy was started. The patient started to develop leukocytosis on day 10 with stool for Clostridium difficile antigen being positive. Broad-spectrum antibiotics and antibiotics for C. diff colitis were given. In spite of vigorous management, the patient's condition worsened and the patient expired on day 13. This is the first reported case of HCV induced CR leading to gangrene and ultimately death. Clinicians must be vigilant in diagnosing and treating severe manifestations of CR in patients with untreatable HCV.

Genetic variation in the interleukin -28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection

Polymorphisms in the interleukin-28B (IL28B) region are associated with spontaneous and treatment-induced viral clearance in hepatitis C virus (HCV) infection. Nevertheless, it is unknown whether genetic variation at the IL28B locus influences the natural history of chronic HCV infection. Thus, we asked whether an association between IL28B polymorphisms and liver fibrosis progression existed. We studied 247 consecutive patients with chronic HCV, an accurate estimate of the date of infection, and a liver biopsy performed before any treatment. No patient had a history of alcohol abuse or coinfection with other viruses. We assessed the role of rs8099917 and rs12979860 polymorphisms and the effect of host and environmental factors on fibrosis progression. Blood transfusion (75%) was the main modality of infection. Median age at infection was 21 years, and median interval between infection and liver biopsy was 25 years. One hundred twenty-nine patients (52%) were infected by HCV-1, 74 (30%) by HCV-2, 34 (14%) by HCV-3, and 10 (4%) by HCV-4. Bridging fibrosis/cirrhosis (Ishak ≥ 4) was detected in 24% of patients. Age at infection had a marked effect on fibrosis progression by both a linear model and Cox proportional-hazard regression (P < 2E-16). A 12.1% increase in the hazard of advanced fibrosis was estimated for each additional year at infection, suggesting that this was the major explanatory variable in this cohort. Male gender (P < 0.05), HCV genotype 3 (P < 0.001) and steatosis (P < 0.05) were also associated with faster fibrosis progression. Conversely, the two IL28B polymorphisms had no impact on fibrosis progression. In HCV patients with a known date of infection, IL28B genotype was not associated with fibrosis progression rate or with the risk of developing advanced liver fibrosis.

Role of genetic polymorphisms in the progression of liver fibrosis in chronic hepatitis C virus infection

Role of genetic polymorphisms in the progression of liver fibrosis in chronic hepatitis C virus infection

Resolution of chronic hepatitis C following parasitosis

An inefficient cellular immune response likely leads to chronic hepatitis C virus (HCV) infection. Resolution of chronic HCV infection in the absence of treatment is a rare occurrence. We report the case of a 39-year old white male with a 17-year history of chronic HCV infection, who eradicated HCV following a serious illness due to co-infection with Babesia (babesiosis), Borriela Borgdorferi (Lyme disease) and Ehrlichia (human granulocytic ehrlichiosis). We hypothesize that the cellular immune response mounted by this patient in response to his infection with all three agents but in particular Babesia was sufficient to eradicate HCV.

Guest Editor's Editorial: Advances in Managing Hepatitis C Virus (HCV) Infection (A Special Issue)

Editorial Chronic infection of hepatitis C virus (HCV) affects approximately 170 million people worldwide and 4-5 million people in the Unites States. Studies have projected a substantial burden from HCV disease and related complications, including liver failure and hepatocellular carcinoma (HCC), over the next 10 to 20 years. Since the identification of HCV in 1989, significant advances have been made in our understanding of HCV virology, diagnosis, natural history, and treatment of chronic HCV infection. The goal of this special issue of International Journal of Medical Sciences is to report and update our current knowledge in the selected areas. The issue is started with a thorough review of the advances in HCV molecular virology by Drs. Brass, Moradpour, and Blum. Understanding HCV life cycle and the novel in vitro HCV replicating system will facilitate discovery of new anti-HCV drugs. Drs. Chevaliez and Pawlotsky describe the currently available serologic and molecular assays and their application in diagnosing HCV infection and monitoring HCV treatment. Understanding natural history of chronic HCV infection is essential for evidence-based management of HCV-infected patients. Drs. Sy and Jamal present a systematical overview on the epidemiology of chronic HCV infection, and Drs. Chen and Morgan provide a detailed update of our current understanding of natural history of HCV-related disease. Hepatic steatosis is a common presentation in HCV-infected individuals. Drs. Yoon and Hu review the incidence, pathogenesis, and clinical impact of steatosis on natural history of chronic HCV infection. Co-infection of hepatitis B virus (HBV) with HCV represents another challenge that is especially common in areas where HBV is prevalent. Drs. Liu and Hou give us an update on this important topic. Perhaps, the most noteworthy advances with chronic HCV infection over the past decade have been the improved response rate to anti-HCV therapy. Drs. Huang and Hu review our practical approach to managing chronic hepatitis C from diagnosing and staging HCV disease to assessing candidacy, selecting, administering, and monitoring standard HCV treatments. It is well known that the sustained virological response (SVR) rate depends on a variety of virological and host factors, and the HCV treatment should be individualized. Management of chronic hepatitis C in special population is reviewed by Drs. Aulakh and Hoefs. HCV-related end-stage liver disease represents the leading cause of liver transplantation in the Unites States. Recurrent hepatitis C has been associated with graft failure. Drs. Herrine and Navarro update pre-liver transplant treatment of patient with decompensated liver disease. Drs. Schiano and Martin review post-liver transplant treatment of recurrent hepatitis C. I would like to thank all the contributors of this special issue for their time, experience, and insights to these important topics. Also, I wish that this special issue will be a valuable resource for your clinical practice.

Effects of immunosuppression and organ transplantation on the natural history and immunopathogenesis of hepatitis C virus infection

The hepatitis C virus (HCV) is recognized as the leading cause for parenterally transmitted hepatitis. It is characterized by a high propensity to chronicity. Several efforts have been directed towards understanding the natural history of chronic HCV infection and the immunopathogenic pathways involved in mediating liver injury in the non-immunosuppressed and immunosuppressed states. In the non-immunosuppressed setting, liver damage seems to be largely immune mediated. In contrast, in the non-immunosuppressed state, there are several other factors that may modify the natural course of the infection and play a role in mediating liver injury. In this review we will address the natural history, virological and immunological aspects of HCV infection. Also, the role played by immunosuppression and organ transplantation in modifying the course of the infection and the pathogenesis of liver injury will be discussed.

Treatment of hepatitis C virus infection in children.

Hepatitis C virus (HCV) infection is the most common cause of chronic liver disease in the western world. Despite extensive epidemiological data in adults, the exact number of children infected is still unknown, and little is known about the natural history of chronic HCV infection in childhood. The authors review studies focusing on HCV infection in children, and summarize the results, including the efficacy of interferon, and interferon plus ribavirin combination treatment of HCV hepatitis in childhood.

Structure of replicating hepatitis C virus (HCV) quasispecies in the liver may not be reflected by analysis of circulating HCV virions.

We have analyzed the population of hepatitis C virus (HCV) sequences in paired liver and serum samples from four patients with chronic hepatitis C. Sequences from three different biopsy specimens from a liver explant from one patient were compared with each other and with the circulating sequences. Our results demonstrate that the circulating quasispecies does not necessarily reflect the viral population replicating in the liver and that this is not due to a macroscopic anatomic compartmentalization of HCV replication. This finding has important implications for the pathogenesis and natural history of chronic HCV infection.

The natural history of chronic hepatitis C in haemophiliacs.

Most haemophiliacs treated with non-virally-inactivated clotting factor concentrates have been infected with hepatitis C virus (HCV). We have studied the natural history of chronic HCV infection by following all 138 HCV-positive patients from our centre for periods of up to 28 years. As well as the clinical and biochemical characteristics, we studied 116 liver samples from 63 patients obtained at elective biopsy (n = 103) or autopsy (n = 13). 36 (26%) of the patients were HIV positive, and three were chronic carriers of hepatitis B. Evidence of previous exposure to hepatitis A and B was found in 37.2% and 48.1% respectively. Raised transaminase levels were found in 82.6% of patients. 11 of 15 patients with normal transaminases tested by PCR for HCV RNA were positive, indicating that most patients, even in this group, have chronic hepatitis C infection. Cirrhosis was diagnosed by liver histology in 19 patients, and nine patients developed liver failure. The incidence of cirrhosis rose rapidly 15 years after HCV infection to 15.6 per 1000 person-years. Multivariate analysis showed that HIV status, length of time since HCV infection and age at HCV infection were independently associated with both the development of cirrhosis and liver failure. Two patients developed hepatocellular carcinoma: one of these was exposed only to a single batch of FVIII concentrate 11 years earlier. Chronic hepatitis C is increasingly recognized as a major cause for morbidity and mortality in haemophiliacs, especially those who are HIV positive and who were infected at an older age.