Autoantibodies in chronic hepatitis C virus infection: impact on clinical outcomes and extrahepatic manifestations

Gilman, Andrew J.; Le, An K.; Zhao, Changqing; Hoang, Joseph; Yasukawa, Lee Ann; Weber, Susan C.; Vierling, John M.; Nguyen, Mindie H.

doi:10.1136/bmjgast-2018-000203

Cited by 29 publications

(29 citation statements)

References 33 publications

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“…In contrast to our study, however, they only tested patients with acute hepatitis E, and not with chronic or asymptomatic HEV infection. In line with our data, Gilman et al reported a rate of ANA positivity of 22% in a cohort of 1556 chronic HCV patients [35], whereas, in the German general population, the rate of ANA positivity was reported to be 33% (defined as a titer ≥1:80) [38].…”

Section: Discussionsupporting

confidence: 91%

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Significance of Anti-Nuclear Antibodies and Cryoglobulins in Patients with Acute and Chronic HEV Infection

et al. 2020

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Background: Hepatitis E virus (HEV) has been associated with immunological phenomena. Their clinical significance, however, still needs to be clarified, that is, whether cryoglobulins or autoantibodies impact overt disease in HEV-infected individuals. To better understand, we analyzed these different immune phenomena in three cohorts, each representing different types of HEV infection. Methods: The cohorts included: (i) immunocompetent patients with acute hepatitis E, (ii) immunosuppressed patients with chronic hepatitis E, and (iii) individuals with asymptomatic HEV infection. Together, they consisted of 57 individuals and were studied retrospectively for the presence of anti-nuclear antibodies (ANAs), cryoglobulins, and serum total IgG. They were then compared with a control cohort of 17 untreated patients with chronic hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection. Results: Thirteen (23%) were immunocompetent patients with acute hepatitis E (median alanine aminotransferase (ALT) = 872 U/L), 15 (26%) were immunosuppressed patients with chronic hepatitis E (median ALT = 137 U/L), and 29 (51%) were blood donors with asymptomatic HEV infection (median ALT = 35 U/L). Overall, 24% tested positive for elevated ANA titers of >1:160, and 11% presented with a specific ANA pattern. ANA detection was not associated with the type of HEV infection, IgG levels, sex, or age. All individuals tested negative for anti-mitochondrial antibodies, anti-neutrophil cytoplasmic antibodies, liver-kidney microsomal antibodies, anti-myeloperoxidase-, and anti-proteinase-3 antibodies. Five patients (9%) tested positive for cryoglobulins. Notably, cryoglobulinemia was present in overt hepatitis E (Groups (i) and (ii); one acute and four chronic HEV infections), but was not present in any of the asymptomatic blood donors (p = 0.02). The frequency of cryoglobulins and elevated ANAs did not differ significantly between HEV and HBV/HCV patients. Conclusion: In line with findings on HBV and HCV infections, we frequently observed detection of ANAs (24%) and cryoglobulins (9%) in association with HEV infections. The presence of cryoglobulins was limited to patients with overt hepatitis E. We add to the findings on the immune phenomena of hepatitis E.

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Section: Discussionsupporting

confidence: 91%

“…In line with these data, the presence of autoantibodies has also been associated with HEV infection. This was very much like other forms of viral hepatitis [13,30,33,35,36]. However, it has not yet been clarified whether cryoglobulins or autoantibodies have a pathogenetic impact and contribute to overt disease in HEV-infected individuals.…”

Section: Introductionmentioning

confidence: 85%

Significance of Anti-Nuclear Antibodies and Cryoglobulins in Patients with Acute and Chronic HEV Infection

et al. 2020

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“…Infections would play a central role in triggering autoimmunity and autoantibody production in patients with PIDs. In fact, the presence of autoantibodies such as ANA, RF, ACPA, aPL, ANCA and ASMA has been described as an epiphenomenon in several bacterial and viral infections (ex., Staphylococcus aureus , Mycobacterium tuberculosis and HCV ) ( 30 – 34 ).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and Predictive Contribution of Autoantibodies Screening in a Large Series of Patients With Primary Immunodeficiencies

Tahiat¹,

Yagoubi

Ladj³

et al. 2021

Front. Immunol.

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ObjectivesTo evaluate the diagnostic and predictive contribution of autoantibodies screening in patients with primary immunodeficiencies (PIDs).MethodsIn the present study, PID patients and healthy controls have been screened for 54 different autoantibodies. The results of autoantibodies screening in PID patients were correlated to the presence of autoimmune diseases.ResultsA total of 299 PID patients were included in this study with a predominance of antibody deficiencies (27.8%) followed by immunodeficiencies affecting cellular and humoral immunity (26.1%) and complement deficiencies (22.7%). Autoimmune manifestations were present in 82 (27.4%) patients. Autoimmune cytopenia (10.4%) was the most common autoimmune disease followed by gastrointestinal disorders (10.0%), rheumatologic diseases (3.7%), and endocrine disorders (3.3%). Autoantibodies were found in 32.4% of PID patients and 15.8% of healthy controls (P < 0.0005). Anti-nuclear antibodies (ANA) (10.0%), transglutaminase antibody (TGA) (8.4%), RBC antibodies (6.7%), anti-smooth muscle antibody (ASMA) (5.4%), and ASCA (5.0%) were the most common autoantibodies in our series. Sixty-seven out of the 82 patients with autoimmune manifestations (81.7%) were positive for one or more autoantibodies. Eleven out of the 14 patients (78.6%) with immune thrombocytopenia had positive platelet-bound IgM. The frequencies of ASCA and ANCA among patients with IBD were 47.4% and 21.0% respectively. All patients with celiac disease had TGA-IgA, while six out of the 11 patients with rheumatologic diseases had ANA (54.5%). Almost one third of patients (30/97) with positive autoantibodies had no autoimmune manifestations. ANA, rheumatoid factor, ASMA, anti-phospholipid antibodies and ANCA were often detected while specific AID was absent. Despite the low positive predictive value of TGA-IgA and ASCA for celiac disease and inflammatory bowel disease respectively, screening for these antibodies identified undiagnosed disease in four patients with positive TGA-IgA and two others with positive ASCA.ConclusionThe present study provides valuable information about the frequency and the diagnostic/predictive value of a large panel of autoantibodies in PIDs. Given the frequent association of some AIDs with certain PIDs, screening for corresponding autoantibodies would be recommended. However, positivity for autoantibodies should be interpreted with caution in patients with PIDs due to their low positive predictive value.

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“…Early studies showed that HCV could induce transient autoimmune responses leading to development of autoantibodies classically associated with AIH, and it has been reported that chronic HCV infections that were autoantibody positive were more common in women, exhibited more severe transaminase elevation, and had histologic evidence of liver injury . A study by Gilman et al also showed that autoantibody positivity in HCV infection was more common in women; their presence predicted a lower rate of achieving SVR when using IFN‐based regimens, but their presence did not otherwise affect the natural history of chronic HCV or presence of extrahepatic manifestations. In the current study, the majority of patients who were HCV+ that had serum markers of AIH were female patients (12/21, 57.1%), and liver biopsies from these patients showed significantly more inflammatory activity and slightly increased fibrosis compared to controls.…”

Section: Discussionmentioning

confidence: 99%

Direct‐Acting Antiviral Treatment of Patients with Hepatitis C Resolves Serologic and Histopathologic Features of Autoimmune Hepatitis

et al. 2019

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Patients with hepatitis C virus (HCV) often have elevated serum markers and histologic features of autoimmune hepatitis (AIH). We evaluated an HCV‐positive (HCV+) study group that had elevated serum markers of AIH before starting direct‐acting antiviral (DAA) therapy (n = 21) and compared them to an HCV+ control group that did not have laboratory studies suggesting AIH (n = 21). Several patients in the study (17/21) and control (11/21) groups had liver biopsies before DAA treatment, and many were biopsied due to elevated serum markers of AIH. Evaluation of pre‐DAA treatment liver biopsies showed histologic features suggestive of AIH in 64.7% (11/17) of the study group and 45.5% (5/11) of the control group. Patients who were HCV+ with elevated serum markers of AIH had significantly increased hepatitis activity (P < 0.001) and slightly increased fibrosis stages (P = 0.039) in their pretreatment liver biopsies compared to controls. We hypothesized that the elevated serum markers and histologic features of AIH would resolve following DAA treatment. Serum markers of AIH in the study group began decreasing by 6 months posttreatment, and 52.4% (11/21) had complete resolution. Alanine aminotransferase levels significantly decreased into the normal range for all patients (21/21). Even patients that had persistence of serum markers of AIH after DAA treatment had normal transaminases. Six patients from the study patient group and 4 patients from the control group had follow‐up liver biopsies after DAA treatment, and all biopsies showed resolution of the histologic features of AIH. Conclusion: The majority of HCV+ patients that have serum markers and/or histopathologic features of AIH should initially be treated with DAA.

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Autoantibodies in chronic hepatitis C virus infection: impact on clinical outcomes and extrahepatic manifestations

Cited by 29 publications

References 33 publications

Significance of Anti-Nuclear Antibodies and Cryoglobulins in Patients with Acute and Chronic HEV Infection

Significance of Anti-Nuclear Antibodies and Cryoglobulins in Patients with Acute and Chronic HEV Infection

Diagnostic and Predictive Contribution of Autoantibodies Screening in a Large Series of Patients With Primary Immunodeficiencies

Direct‐Acting Antiviral Treatment of Patients with Hepatitis C Resolves Serologic and Histopathologic Features of Autoimmune Hepatitis

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