Hepatitis C Virus-Related Liver Damage Is Related to Cold Activation of Complement

Nomura, Hideyuki; Ogo, Tomonori; Rikimaru, Nobuki; Ueno, Sachio; Kakuno, Tatsuya; Okamoto, Osamu; Shiraishi, Genji; Kashiwagi, Seizaburo

doi:10.1097/00004836-199710000-00010

Cited by 8 publications

(5 citation statements)

References 26 publications

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“…Significantly, the association between complement activation and HCV-related liver damage has already been previously reported [1,15,18]. Ig light chain deposition was only very rarely found in MAC-positive vessels, and may have been caused by serum leakage as a consequence of the angiopathy, as usually occurs when the blood barrier is damaged.…”

Section: Discussionmentioning

confidence: 57%

“…However, the presence of actual HCV-RNA in our patient's muscle, as demonstrated by PCR, suggests that the virus may be directly involved in the pathway leading to MHC-I expression, T cell recruitment and MAC deposition. In this respect it is of considerable interest to note that a definite association between complement activation and HCV-related liver damage has already been reported [1,15,18].…”

Section: Discussionmentioning

confidence: 95%

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Hepatitis C virus infection and myositis: a polymerase chain reaction study

et al. 2000

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Muscle biopsy tissue from a patient with chronic hepatitis, who was hepatitis C virus (HCV) positive and showed slight weakness of the right arm and leg associated with increased serum creatine kinase levels, was studied using immunocytochemical and polymerase chain reaction (PCR) techniques. Muscle biopsy showed changes compatible with an inflammatory myopathy. Immunohistochemical studies included the use of monoclonal antibodies against human T lymphocytes, macrophages, immunoglobulins, major histocompatibility complex class I molecules (MHC-I), and the neoantigens of the terminal C5b-9 complement membrane attack complex (MAC). In addition to confirming the potential importance of cytotoxic T cells and MHC-I antigen expression in inducing muscle pathology, we demonstrated MAC deposition and the presence of HCV-RNA in the muscle of our patient, suggesting that direct involvement of the virus leading to complement activation might be important in inducing muscle damage.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 95%

Hepatitis C virus infection and myositis: a polymerase chain reaction study

et al. 2000

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“…Cold activation of complement (loss of hemolytic activity in serum during storage at low temperature) was observed in patients with chronic HCV infection, contributed to HCV-associated liver damage, and was useful in monitoring responses to interferon therapy in these patients (2,13,31). HCV core protein has been shown to bind with the gC1q receptor (gC1qR) on activated human peripheral blood T cells, causing inhibition of the T cell response (20,43) by increasing the frequency of gC1qR ϩ CD4 ϩ T cells (14).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Proteins Inhibit C3 Complement Production

Mazumdar

Kim

Meyer

et al. 2012

J Virol

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The third component of human complement (C3) plays a central role in innate immune function as its activation is required to trigger classical as well as alternative complement pathways. In this study, we have observed that sera from patients chronically infected with hepatitis C virus (HCV) displayed significantly lower C3 levels than sera from healthy individuals. Liver biopsy specimens from the same patients also exhibited lower C3 mRNA expression than liver tissues from healthy donors. C3 mRNA level was reduced in hepatocytes upon infection with cell culture-grown HCV genotype 1a or 2a in vitro. Further analysis suggested that HCV core protein displayed a weak repression of C3 promoter activity by downregulating the transcription factor farnesoid X receptor (FXR). On the other hand, HCV NS5A protein strongly downregulated C3 promoter activity at the basal level or in the presence of interleukin-1␤ (IL-1␤) as an inducer. In addition, the expression of the transcription factor CAAT/ enhancer binding protein beta (C/EBP-␤), which binds to the IL-1/IL-6 response element in the C3 promoter, was inhibited in liver biopsy specimens. Furthermore, expression of C/EBP-␤ was reduced in hepatocytes infected with cell culture-grown HCV, as well as in hepatocytes transfected with the NS5A genomic region of HCV. Together, these results underscore the role of HCV NS5A protein in impairing innate immune function.

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“…Although we chose cirrhosis as the definable endpoint of progressive liver disease for our comparisons, it is noteworthy that increased fibrosis scores for CP positive versus CP negative patients has also been reported. 12,13,26,34 Unfortunately, there were insufficient data to adjust fibrosis scores for the effects of other variables.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C, cryoglobulinemia, and cirrhosis: A meta-analysis

et al. 2002

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Approximately 40% of patients with chronic hepatitis C virus (HCV) infection develop detectable serum cryoglobulins or cryoprecipitates (CP), although most do not show clinical or physical signs of syndromic cryoglobulinemia. Although association of HCV with the extrahepatic complications of cryoglobulinemia is widely recognized, the relationship of cryoglobulinemia with liver disease is unclear. We wished to study the relationship between CP and cirrhosis and to determine whether the development of CP is a true covariate for progressive liver disease or a confounding variable that impacts cirrhosis because of patient age, duration of disease, or differences in gender. We undertook a meta-analysis of 19 studies published between 1994 and 2001. The incidence of cirrhosis was compared in patients with and without CP after logistic regression adjustments for accepted risk factors for progressive liver disease, including age, gender, and estimated duration of disease (EDD). A total of 2,323 patients with chronic hepatitis C were identified, with 1,022 (44%) having detectable CP. Cirrhosis was present in 40% of patients with CP but only 17% of patients without CP (total Chi;(2) = 141.69, P <.001). After adjusting for age, gender, and estimated duration of disease by logistic regression, the combined odds ratio for incidence of cirrhosis in patients CP positive versus CP negative was 4.87, (95% CI: 3.32, 7.15), indicating a highly significant association between cirrhosis and cryoglobulinemia. In conclusion, cryoglobulins may be a useful prognostic indicator for increased risk of cirrhosis with chronic hepatitis C.

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Hepatitis C Virus-Related Liver Damage Is Related to Cold Activation of Complement

Cited by 8 publications

References 26 publications

Hepatitis C virus infection and myositis: a polymerase chain reaction study

Hepatitis C virus infection and myositis: a polymerase chain reaction study

Hepatitis C Virus Proteins Inhibit C3 Complement Production

Hepatitis C, cryoglobulinemia, and cirrhosis: A meta-analysis

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