APPROXIMATELY 70% OF ALL CASES OF CHRONIC viral hepatitis are caused by the hepatitis C virus (HCV), and approximately 100 million persons worldwide are infected. Although the liver is the primary target of the virus, HCV infections are associated with disorders of various organs, essentially through immunologic mechanisms Currently, there is only little information about the ocular manifestations of this common infectious disease, and the mode of transmission is not completely understood. The proof of HCV virus in tears of HCV-infected patients may be important as a possible mode of transmission and for the understanding of ocular surface manifestations. There are several case reports suggesting that HCV infection can be associated with keratitis, Sjogren syndrome, and retinohathy.
HEPATITIS C VIRUS IS A PRINCIPAL CAUSE OF CHRONIC hepatitis worldwide. In addition to hepatic disease, there are important extrahepatic manifestations of HCV infection." They often are associated with autoimmun lymphoproliferative states which may be related to the observation that HCV is able to replicate in lymphoid cells. Systemic diseases such as Sjogren syndrome often have been linked to HCV infection. There are also several reports in the current ophthalmic literature describing ocular involvement in chronic HCV infection. An important site of manifestation is the ocular surface. Cornea, conjunctiva, and accessory lacrimal glands together with the meibomian glands, main lacrimal gland, and interconnecting neural reflex loops constitute a functional unit. A possible pathogenetic association between Mooren ulcer, recurrent ketatitis, and chronic hepatitis C infection has been proposed. This idea is based on the fact that immunologic mechanisms in central and peripheral cornea are different. The peripheral cornea has distinct morphologic and immunologic characteristics that predispose one to inflammatory reactions. Major differences exist regarding humoral and cellular components of the immune system. The peripheral cornea has a higher concentration of high molecular immunoglobulin M, Langerhans cells, and initial complement component C1 in comparison with the central cornea, and this may predispose one to immune complex formation. Cl is the recognition unit of the classic pathway of complement, so that antigen-antibody complexes, whether formed in the cornea or derived from the tears, aqueous humor, or limbal vessels, may activate complement more effectively in the peripheral than central cornea. Circulating immune complexes may lodge in the limbal vasculature, causing an immune vasculitis or deposit in the peripheral cornea, setting off the complement cascade. Langerhans cells and macrophages as important antigen presenting and processing cells also are present in higher numbers in the peripheral cornea.
Other forms of ocular involvement in patients with chronic hepatitis C include episcleritis, retinopathy, and retinal vasculitis. Besides saliva and bile, HCV RNA also has been detected in aqueous humor and teats. Involvement of salivary and lacrimal glands often is seen in patients with chronic HCV infection. Siagris and associates, Guisset and associates, mariette, as well as Gordon have described an association, between HCV infection and keratoconjunctivitis sicca. In one study, 25 of 50 patients with chronic HCV infection showed a remarkable reduction of tear secretion. Cacoub and associates described sicca syndrome in 10% of more than 1,600 patients with chronic.
hepatitis C. Verbaan and associates found in northern European patients with HCV infection a common involvement of salivary and lacrimal glands. The pathogenetic mechanism responsible for glandular inflammation investigated by immunohistochemistry seemed to be different from that in primary Sjogren syndrome. Because HCV antigen could not be detected in affected lacrimal glands, it was concluded that the chronic inflammation of salivary and lacrimal glands is caused by immunologic mechanisms. Roy and Bagg, Zegans and associates, Cacoub and associates, and I,auer and associate? all observed xerophthalmia and keratoconjunctivitis sicca in patients with chronic hepatitis C, but were also not able to find an association with primary Sjogren syndrome. The results of our ophthalmologic examinations, especially corneal and conjunctival findings such as, for example, papillary or follicular conjunctivitis, conjunctival injection, and pannus cornea, can also be explained by immunologic mechanisms. 32 The conjunctival epithelium contains a dense intra-epithelial network of langerhans cells and macrophages that are potent antigen presenting and processing cells. The estimated density of Langerhans cells in the human limbal conjunctiva is 250 to 300/mm. If surface inflammation occurs, Iangerhans cell density increases considerably, and they migrate to the area of inflammation. We observed significantly fewer goblet cells at baseline compared with normal specimens. V The median was 74 goblet cells/mm. 2 in the conjunctival epithelium. Our goblet cell counts revealed a decrease of goblet cell densities of up to 33% to 50% in the conjunctival epithelium of patients with chronic hepatitis C. In concordance with our data, several groups previously observed a decrease in the numbers of goblet cells in patients with chronic HCV infection. 27 Goblet cell densities are thought to be very sensitive indicators of ocular surface disease.
In eyes with keratoconjunctivitis sicca, the first evidence of ocular surface injury is a decrease in conjunctival goblet cells. As the disease progresses in severity, goblet cell numbers decrease further, resulting in squamous metaplasia, enlargement of the epithelial area, and occasional keratinization of the ocular surface. Moreover, goblet cells are sensitive to local electrolyte concentrations. Dry eye
syndrome seems to facilitate tear hyperosmolarity through a rise in the sodium concentration and, in this 'respect, contributes to a reduction in goblet cell density or the loss of goblet cells. We observed that younger patients with chronic hepatitis C infection (21 to 60 years; Figure) had a significantly lower tear secretion estimated by the ]ones test compared with the controls. This decrease in tear production may be the result of an inflammation of the lacrimal gland as an extrahepatic manifestation of hepatitis C. The lacrimal gland normally contains small populations of plasma cells and T lymphocytes (CD8+/CD4+ cells) as well as a limited array of dendritic cells, macrophages, and B cells. In patients with hepatitis C, focal lymphocytic infiltration of the lacrimal gland has been demonstrated. The periductal and perivascular infiltrates primarily consist of CD4+ T cells and B cells. The activated immune cells in the inflammatory infiltrate seem to release proinflammatory cytokines, such as interleukin (IL)-1(3, IL-2, interferon-y, and tumor necrosis factor a. These cytokines can cause apoptosis of the glandular epithelial cells and may expose epitopes that activate autoreactive lymphocytes. These mechanisms can result in a progressive destruction of the parenchyma and in decreased secretion of tears. Inflammatory mediators contribute to the ocular surface modifications because of tear insufficiency. Their presence leads to a rise in the corresponding markers (HLA-DR,.ICAM-1, and 1L-b). This inflammatory process affects all components of the functional unit of the ocular surface. This leads to the concept that immunologic circuits are an integrated part of the system.
Dry eye syndrome is a common ocular manifestation in patients with chronic hepatitis C infection, especially in younger patients. Therefore, hepatitis C should be included in the differential diagnosis of patients with keratoconjunctivitis sicca. Also, our data show the proof of I-ICV RNA in the tear fluid of 10% of the examined patients. Although HCV RNA levels in tear samples were considerably lower than in blood samples, the tear concentration may be relevant for infection. The presence of HCV RNA in 10% of tear samples emphasizes the potential risk of viral transmission through tears.
ok that's good information