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Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection.

ABSTRACT: We followed patients with ongoing hepatitis C virus (HCV) exposure following control of an initial HCV infection to determine whether primary control conferred protection against future persistent infections.Twenty-two active injection drug users (IDU) who had cleared a primary hepatitis C viremia for at least 60 days were monitored monthly. Reinfection was defined as the detection of a new HCV infection. Protection was assessed based on the magnitude and duration of viremia following reinfection and generation of T-cell and neutralizing antibody (nAb) responses.Reinfection occurred in 11 IDU (50%) who previously spontaneously controlled primary HCV infection. Although viral clearance occurs in approximately 25% of patients with primary infections, spontaneous viral clearance was observed in 83% of reinfected patients. The duration and maximum level of viremia during subsequent episodes of reinfection were significantly decreased compared with those of the primary infection in the same subjects. In contrast to chronic infection, reinfection was associated with a significant increase in the breadth of T-cell responses. During acute infection, nAbs against heterologous viral pseudoparticles were detected in 60% of reinfected subjects; cross-reactive nAbs are rarely detected in patients who progress to chronic infection.HCV reinfection is associated with a reduction in the magnitude and duration of viremia (compared with the initial infection), broadened cellular immune responses, and generation of cross-reactive humoral responses. These findings are consistent with development of adaptive immunity that is not sterilizing but protects against chronic disease.

SUBMITTER: Osburn WO

PROVIDER: S-EPMC2889495 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection.

Osburn William O WO Fisher Brian E BE Dowd Kimberly A KA Urban Giselle G Liu Lin L Ray Stuart C SC Thomas David L DL Cox Andrea L AL

Gastroenterology 20090924 1

<h4>Background & aims</h4>We followed patients with ongoing hepatitis C virus (HCV) exposure following control of an initial HCV infection to determine whether primary control conferred protection against future persistent infections.<h4>Methods</h4>Twenty-two active injection drug users (IDU) who had cleared a primary hepatitis C viremia for at least 60 days were monitored monthly. Reinfection was defined as the detection of a new HCV infection. Protection was assessed based on the magnitude an ...[more]

PMID: 19782080

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Project description:The nucleic acid polymer REP 2139 inhibits assembly/secretion of hepatitis B virus (HBV) subviral particles. Previously, REP 2139-Ca and pegylated interferon (pegIFN) in HBV/hepatitis delta virus (HDV) coinfection achieved high rates of HDV RNA and hepatitis B surface antigen (HBsAg) loss/seroconversion in the REP 301 study (NCT02233075). The REP 301-LTF study (NCT02876419) examined safety and efficacy during 3.5 years of follow-up. In the current study, participants completing therapy in the REP 301 study were followed for 3.5 years. Primary outcomes were safety and tolerability, and secondary outcomes were HDV functional cure (HDV RNA target not detected [TND], normal alanine aminotransferase [ALT]), HBV virologic control (HBV DNA ≤2,000 IU/mL, normal ALT), HBV functional cure (HBV DNA TND; HBsAg <0.05 IU/mL, normal ALT), and HBsAg seroconversion. Supplemental analysis included high-sensitivity HBsAg (Abbott ARCHITECT HBsAg NEXT), HBV pregenomic RNA (pgRNA), HBsAg/hepatitis B surface antibody (anti-HBs) immune complexes (HBsAg ICs), and hepatitis B core-related antigen (HBcrAg). Asymptomatic grade 1-2 ALT elevations occurred in 2 participants accompanying viral rebound; no other safety or tolerability issues were observed. During therapy and follow-up, HBsAg reductions to <0.05 IU/mL were also <0.005 IU/mL. HBsAg ICs declined in 7 of 11 participants during REP 2139-Ca monotherapy and in 10 of 11 participants during follow-up. HDV functional cure persisted in 7 of 11 participants; HBV virologic control persisted in 3 and functional cure (with HBsAg seroconversion) persisted in 4 of these participants. Functional cure of HBV was accompanied by HBV pgRNA TND and HBcrAg <lower limit of quantitation. Conclusion: REP 2139-Ca + pegIFN is not associated with long-term safety or tolerability issues. The establishment of HDV functional cure and HBV virologic control/functional cure and HBsAg seroconversion are durable over 3.5 years and may reflect removal of integrated HBV DNA from the liver. Further investigation is warranted in larger studies.

Project description:UnlabelledHepatitis C virus reinfection and spontaneous clearance of reinfection were examined in a highly characterised cohort of 188 people who inject drugs over a five-year period. Nine confirmed reinfections and 17 possible reinfections were identified (confirmed reinfections were those genetically distinct from the previous infection and possible reinfections were used to define instances where genetic differences between infections could not be assessed due to lack of availability of hepatitis C virus sequence data). The incidence of confirmed reinfection was 28.8 per 100 person-years (PY), 95%CI: 15.0-55.4; the combined incidence of confirmed and possible reinfection was 24.6 per 100 PY (95%CI: 16.8-36.1). The hazard of hepatitis C reinfection was approximately double that of primary hepatitis C infection; it did not reach statistical significance in confirmed reinfections alone (hazard ratio [HR]: 2.45, 95%CI: 0.87-6.86, p=0.089), but did in confirmed and possible hepatitis C reinfections combined (HR: 1.93, 95%CI: 1.01-3.69, p=0.047) and after adjustment for the number of recent injecting partners and duration of injecting. In multivariable analysis, shorter duration of injection (HR: 0.91; 95%CI: 0.83-0.98; p=0.019) and multiple recent injecting partners (HR: 3.12; 95%CI: 1.08-9.00, p=0.035) were independent predictors of possible and confirmed reinfection. Time to spontaneous clearance was shorter in confirmed reinfection (HR: 5.34, 95%CI: 1.67-17.03, p=0.005) and confirmed and possible reinfection (HR: 3.10, 95%CI: 1.10-8.76, p-value=0.033) than primary infection. Nonetheless, 50% of confirmed reinfections and 41% of confirmed or possible reinfections did not spontaneously clear.ConclusionsHepatitis C reinfection and spontaneous clearance of hepatitis C reinfection were observed at high rates, suggesting partial acquired natural immunity to hepatitis C virus. Public health campaigns about the risks of hepatitis C reinfection are required.

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Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection.

Publications

Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection.

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