Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance

doi:10.1016/S0016-5085(03)00668-1

Gastroenterology

Volume 125, Issue 1, July 2003, Pages 80-88

https://doi.org/10.1016/S0016-5085(03)00668-1 Get rights and content

Abstract

Background & Aims:

Acute hepatitis C virus infection accounts for approximately 20% of cases of acute hepatitis today. The aim of this study was to define the natural course of the disease and to contribute to the development of treatment strategies for acute hepatitis C virus.

Methods:

The diagnosis of acute hepatitis C virus in 60 patients was based on seroconversion to anti-hepatitis C virus antibodies or clinical and biochemical criteria and on the presence of hepatitis C virus RNA in the first serum sample.

Results:

Fifty-one of 60 (85%) patients presented with symptomatic acute hepatitis C virus. In the natural (untreated) course of acute symptomatic hepatitis C (n = 46), spontaneous clearance was observed in 24 patients (52%), usually within 12 weeks after the onset of symptoms, whereas all asymptomatic patients (n = 9) developed chronic hepatitis C. The start of antiviral therapy (interferon-α with or without ribavirin) beyond 3 months after the onset of acute hepatitis induced sustained viral clearance in 80% of treated patients.

Conclusions:

The management of acute hepatitis C has to take into account the high rate of spontaneous viral clearance within 12 weeks after the onset of symptomatic disease. Treatment of only those patients who remain hepatitis C virus RNA positive for more than 3 months after the onset of disease led to an overall viral clearance (self-limited and treatment induced) in 91% of patients, and unnecessary treatment was avoided in those with spontaneous viral clearance. Patients with asymptomatic acute hepatitis C virus infection are unlikely to clear the infection spontaneously and should be treated as early as possible.

Section snippets

Patients

Sixty consecutive patients (35 women and 25 men) with aHCV were diagnosed in 2 large referral centers for infectious diseases and hepatology (Medical Department II, Klinikum Großhadern, Munich, Germany, and General Hospital München Schwabing, Munich, Germany) from January 1, 1993, to July 31, 2000, and received antiviral treatment after informed consent was obtained. Most patients (51 of 60) presented with symptomatic acute hepatitis. The most likely source of HCV infection was determined in an

Patient characteristics

In this study, 60 patients (35 women and 25 men) with aHCV were enrolled (Table 1 and Figure 2). In most infected individuals, ALT and bilirubin peaked at the time of presentation; an initial increase of ALT and bilirubin at the beginning of the disease was followed by a rapid decline of ALT in the first weeks of follow-up. Although 9 patients were diagnosed with asymptomatic aHCV, most (85%) patients presented with symptomatic disease. Symptoms included jaundice (68%); nausea (34%); dark

Discussion

In this study we showed that in symptomatic aHCV, more than 50% of patients spontaneously and permanently clear HCV infection within the first 3–4 months after the onset of symptoms. If patients with persistent viremia beyond that time period were treated with IFN-α monotherapy or in combination with ribavirin, 80% achieved a sustained biochemical and virological response, leading to a possible cure of 91% of patients with symptomatic aHCV infection.

Acute HCV may be asymptomatic in up to 80% of

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2020 Taiwan consensus statement on the management of hepatitis C: Part (II) special populations
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Hepatitis C virus (HCV) infection is a silent killer that leads to rapid progression of liver cirrhosis and hepatocellular carcinoma (HCC). High prevalence of HCV infection has been reported in Taiwan, especially in high-risk populations including people who inject drugs (PWID) and patients requiring dialysis. Besides, certain populations merit special considerations due to suboptimal outcome, potential drug–drug interaction, or possible side effect. Therefore, in the second part of this 2-part consensus, the Taiwan Association for the Study of the Liver (TASL) proposes the treatment recommendations for the special population in order to serve as guidance to optimizing the outcome in the direct-acting antiviral (DAA) era. Special populations include patients with acute or recent HCV infection, previous DAA failure, chronic kidney disease, decompensated cirrhosis, HCC, liver and other solid organ transplantations, receiving an HCV viremic organ, hepatitis B virus (HBV) and HCV dual infection, HCV and human immunodeficiency virus (HIV) coinfection, active tuberculosis infection, PWID, bleeding disorders and hemoglobinopathies, children and adolescents, and pregnancy. Moreover, future perspectives regarding the management of hepatitis C are also discussed and summarized in this consensus statement.
ERAP1 allotypes shape the epitope repertoire of virus-specific CD8<sup>+</sup> T cell responses in acute hepatitis C virus infection
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Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms are linked with human leukocyte antigen (HLA) class I-associated autoinflammatory disorders, including ankylosing spondylitis and Behçet’s disease. Disease-associated ERAP1 allotypes exhibit distinct functional properties, but it remains unclear how differential peptide trimming in vivo affects the repertoire of epitopes presented to CD8⁺ T cells. The aim of this study was to determine the impact of ERAP1 allotypes on the virus-specific CD8⁺ T cell epitope repertoire in an HLA-B*27:05⁺ individual with acute hepatitis C virus (HCV) infection.
We performed genetic and functional analyses of ERAP1 allotypes and characterized the HCV-specific CD8⁺ T cell repertoire at the level of fine epitope specificity and HLA class I restriction, in a patient who had acquired an HCV genotype 1a infection through a needle-stick injury.
Two hypoactive allotypic variants of ERAP1 were identified in an individual with acute HCV infection. The associated repertoire of virus-derived epitopes recognized by CD8⁺ T cells was uncommon in a couple of respects. Firstly, reactivity was directed away from classically immunodominant epitopes, preferentially targeting either novel or subdominant epitopes. Secondly, reactivity was biased towards longer epitopes (10–11-mers). Despite the patient exhibiting favorable prognostic indicators, these atypical immune responses failed to clear the virus and the patient developed persistent low-level infection with HCV.
ERAP1 allotypes modify the virus-specific CD8⁺ T cell epitope repertoire in vivo, leading to altered immunodominance patterns that may contribute to the failure of antiviral immunity after infection with HCV.
Endoplasmic reticulum aminopeptidase 1 (ERAP1) plays a key role in antigen presentation. Genetic variants of ERAP1 (leading to distinct allotypes) are linked with specific autoinflammatory disorders, such as ankylosing spondylitis and Behçet’s disease. We found that ERAP1 allotypes modified the repertoire of virus-specific CD8⁺ T cell epitopes in a patient with hepatitis C virus, leading to an altered pattern of immunodominance that may have contributed to the failure of antiviral immunity in this patient.
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Hepatitis C virus (HCV) infection is common among maintenance dialysis patients. Few studies have examined both dialysis survival and transplantation outcomes for HCV-seropositive patients because registry data sets lack information for HCV serostatus.
Retrospective cohort study.
Adult long-term dialysis patients treated by a US national dialysis provider between January 1, 2004, and December 31, 2014.
HCV antibody serostatus obtained as part of clinical data from a national dialysis provider.
Mortality on dialysis therapy, entry onto the kidney transplant waiting list, kidney transplantation, and estimated survival benefit from kidney transplantation versus remaining on the waitlist.
After linking clinical data with data from the Organ Procurement and Transplantation Network, Cox and cause-specific hazards regression were implemented to estimate the associations between HCV seropositivity and mortality, as well as entry onto the kidney transplant waitlist. Cox regression was also used to estimate the survival benefit from transplantation versus dialysis among HCV-seropositive individuals.
Among 442,171 dialysis patients, 31,624 (7.2%) were HCV seropositive. HCV seropositivity was associated with a small elevation in the rate of death (adjusted HR [aHR], 1.09; 95% CI, 1.07-1.11) and a substantially lower rate of entry onto the kidney transplant waitlist (subdistribution HR [sHR], 0.67; 95% CI, 0.61-0.74). Once wait-listed, the kidney transplantation rate was not different for HCV-seropositive (sHR 1.10; 95% CI, 0.96-1.27) versus HCV-seronegative patients. HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63). Receiving an HCV-seropositive donor kidney provided a survival advantage at the 2-year posttransplantation time point compared to remaining on dialysis therapy waiting for an HCV-negative kidney.
No data for HCV viral load or liver biopsy.
HCV-seropositive patients experience reduced access to the kidney transplantation waitlist despite deriving a substantial survival benefit from transplantation. HCV-seropositive patients should consider foregoing HCV treatment while accepting kidneys from HCV-infected donors to facilitate transplantation and prolong survival.
Cytokine profile and viral diversity in the early seronegative stage of community-acquired hepatitis C virus (HCV) infection
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Controlled Human Infection Model for Hepatitis C Virus Vaccine Development: Trial Design Considerations
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^☆: This work was funded by the Bundesministerium für Bildung und Forschung, the Wilhelm-Sander-Stiftung (1997.092.02), and a grant of the European Union (QLK2-CT-1999-00356).

¹: The Bundesministerium für Bildung und Forschung and the European Union, as sponsors of the study, had no role in study design, data collection, analysis, or interpretation or in the writing and the decision to submit the report for publication.

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Clinical-liver pancreas and biliary tractAcute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance1 ☆,

Abstract

Background & Aims:

Methods:

Results:

Conclusions:

Section snippets

Patients

Patient characteristics

Discussion

The declining risk of post-transfusion hepatitis C virus infection

N Engl J Med

The prevalence of hepatitis C virus infection in the United States, 1988 through 1994

N Engl J Med

Epidemiology of hepatitis C in the United States

Am J Med

Resolution of acute hepatitis C after therapy with natural beta interferon

Lancet

Recombinant human interferon alfa-2b treatment for acute non-A, non-B hepatitis

Gut

A randomized controlled trial of recombinant interferon alpha-2b in the treatment of Chinese patients with acute post-transfusion hepatitis C

J Hepatol

A multicenter randomized controlled trial of recombinant interferon-alpha 2b in patients with acute transfusion-associated hepatitis C

Hepatology

Interferon-alpha in acute posttransfusion hepatitis Ca randomized, controlled trial

Hepatology

Interferon therapy for acute posttransfusion non-A, non-B hepatitisresponse with respect to anti-hepatitis C virus antibody status

Am J Gastroenterol

Effects of interferon beta on non-A, non-B acute hepatitisa prospective, randomized, controlled-dose study

Gastroenterology

Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening

N Engl J Med

Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin

N Engl J Med

Recovery, persistence, and sequelae in hepatitis C virus infectiona perspective on long-term outcome

Semin Liver Dis

Methods for the differentiation of microorganisms

J Chromatogr B Biomed Sci Appl

HCV RNA in blood donors with isolated reactivities by third-generation RIBA

Transfusion

Peginterferon alfa-2a in patients with chronic hepatitis C

N Engl J Med

Clinical-liver pancreas and biliary tract
Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance¹ ☆,