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The Connection
Between Hepatitis C Infection with the hepatitis C virus (HCV) can lead to
autoimmune hepatitis in a minority of patients. This means that the liver
cells are damaged not only by the virus but also by the body's own immune
system. IMMUNOLOGICAL
DISORDERS IN C-VIRUS CHRONIC HEPATITIS
Author: COSSERAT J, CTR MEDICOCHIRURG
FOCH, DEPT INTERNAL MED, 40 RUE WORTH, F-92151 SURESNES, FRANCE Hepatitis C virus infection can be
accompanied by a number of systemic, non-specific or autoimmune disorders
and by extra-hepatic biological abnormalities. Their exact prevalence
remains to be determined, together with their association with certain
pathologies such as non-Hodgkin lymphoma. The most frequent biological
peculiarity is cryoglobulinaemia, found in more than 50% of patients. It
is only symptomatic in less than one-third of cases (as purpura, Raynaud's
syndrome, neuropathy or renal failure), and could be the origin of benign
lymphoproliferative haematological pathology, then of a malignant one
(non-Hodgkin lymphoma). Rheumatoid arthritis may develop in 20-25% of
cases. Periarteritis nodosa is a rare but possible occurrence. Autoimmune
disorders proper include hepatitis with anti-LKM1 antibodies, thyroiditis,
kin manifestations, complex connectivitis and Gougerot-Sjogren's syndrome.
This syndrome is histologically detected in 15-50% of patients. It affects
women preferentially and is usually not accompanied by anti-SSA or anti-SSB
antibodies. Thyroidites are different from those occurring under
Interferon-rx. therapy, and should be systematically investigated before
initiating that therapy. Lichen planus can be associated to HCV infection.
The proven induction of autoimmune disorders by Interferon therapy
requires that immune disorders be fully assessed before treatment
initiation, and close monitoring for their occurrence is necessary
throughout the treatment course. TSH and thyroid hormone in particular
should be closely monitored.
and Autoimmune Disorders
Autoimmune hepatitis triggers the body to attack its liver cells, as if
the liver cells were harmful foreign bodies. Patients with a combination
of HCV and autoimmune hepatitis generally suffer from more debilitating
symptoms than patients with HCV alone. Autoimmune hepatitis is associated
with other autoimmune illnesses, including thyroiditis (inflammation of
the thyroid), diabetes mellitus, and ulcerative colitis (inflammation of
the intestines). Although only a few patients with HCV develop autoimmune
hepatitis, these patients appear to have a genetic predisposition that
makes them more likely to develop autoimmune hepatitis, compared to
HCV-infected individuals without that predisposition.
Below are some frequently asked questions about the complex relationship
between HCV and autoimmune hepatitis.
Q. What are the Symptoms of Autoimmune Hepatitis?
A. The most common symptom is fatigue. Recurrent jaundice frequently
develops in severe cases.
Extrahepatic features (those that involve organs and tissue other than the
liver) result from the immune system harming] other organs of the body.
These symptoms can include amenorrhea (absence of menstrual period),
bloody diarrhea (due to ulcerative colitis), abdominal pain, arthritis,
rashes, anemia, glomerulonephritis (a form of kidney disease), dry eyes,
and dry mouth.
Symptoms of autoimmune hepatitis tend to develop slowly over a period of
several weeks or months.
Q. What Causes These Symptoms?
A. When the immune system becomes activated, as in the case of an
autoimmune disease, there is increased production of inflammatory cells
(T-cells), antibodies, and other inflammatory mediators (chemicals). The
overactivated immune system can lead to systemic symptoms of fatigue and
low grade fever. Some of the extrahepatic symptoms, such as
glomerulonephritis and arthritis, are due to deposits of antibodies that
accumulate in the kidney or joints, leading to damage in those tissues.
Q. What is the Process by Which HCV Triggers Autoimmune Conditions?
A. Although the mechanism is still poorly understood, it is theorized that
proteins appear on the surface of infected liver cells. This leads to an
autoimmune response, in which cells of the immune system (including T and
B cells) recognize these new proteins as foreign bodies. These cells then
attack the liver, causing inflammation of the liver cells and eventual
destruction of liver tissue.
Q. How is Autoimmune Hepatitis Diagnosed?
A. Autoimmune hepatitis requires laboratory tests to distinguish it from
uncomplicated hepatitis C infections. Hypergammaglobulinemia, an excess of
antibodies in the blood, is a common finding in autoimmune hepatitis.
Blood tests for certain autoantibodies may also provide diagnostic clues.
The diagnosis may, however, require a liver biopsy.
Q. How is Treatment for Patients with Autoimmunity Determined?
A. Interferon is the only approved treatment for HCV, but its use in
people with autoimmune hepatitis has been shown to exacerbate symptoms. In
general, steroids are used for people with autoimmune hepatitis due to
non-viral causes, but in patients with hepatitis C, steroids can increase
viral replication.
A liver biopsy is usually recommended to determine which disease process
is causing the greatest damage to the liver: the HCV infection or the
autoimmune hepatitis. In general, if the HCV infection were predominant
and the autoimmune hepatitis mild, alfa interferon treatment would be
considered. However, if the autoimmune hepatitis were severe, leading to
such complications as kidney damage, rashes, or rapid liver failure,
steroids or other immunosuppressant drugs would more likely be
recommended.
The choice between these treatment options boils down to the immune
system. Alfa interferon, which activates the immune system to reduce viral
replication, could be problematic for those whose immune system was
already over-activated due to severe autoimmune hepatitis. Steroids, which
suppress the immune system, could be problematic for those with severe
HCV-infection, leading to a compromise the body's ability to fight the
infection.
Source
Harrison's Principles of Internal Medicine, Thirteenth Edition, 1994,
McGraw-Hill, Inc.
Source: NEPHROLOGY DIALYSIS TRANSPLANTATION 1996 ;11:31-35
From autoimmune hepatitis (AIH) classification which recognizes three types of AIH, we discuss the main relations between hepatitis C virus (HCV) infection and AIH. Type I AIH is associated with antinuclear and antismooth muscle antibodies, and with other autoimmune diseases. There is no relation between type I AIH and HCV. Type I anti-liver kidney microsome and anti-liver cytosol I antibodies represent the hallmark of type II AIH. Among type II AIH, two subgroups emerged: type IIa AIH (10-40%) are true AIH (sensitive to steroids but worsens with interferon alpha), whereas type IIb AIH (60-90%) appear as a particular form of HCV hepatitis. Type IIb AIH have a moderate activity, a low titer of autoantibodies, anti-GOR antibodies but never anti-liver cytosol I, no sensitivity to steroids but are sensitive to interferon alpha. The hallmark of type III AIH are anti-cytosol antibodies, but these AIH have the same characteristics as type I AIH. The classification between true AIH (I, IIa, III) or "pseudo-AIH" due to HCV infection has major therapeutic implications. Steroids or immunosuppressive treatments are effective in type I, IIa and III AIH but have no efficacy in type IIb AIH. Alpha interferon has an efficacy in type IIb AIH, but it has no efficacy and may even worsen hepatitis in type I, IIa and III AIH.
Hepatitis C virus infection and autoimmunity
Author: McMurray RW, Elbourne K, Department of Medicine, University of Mississippi Medical Center, Jackson 39216, USA. SOURCE: Semin Arthritis Rheum 26 (4): 689-701 (1997)
Hepatitis C virus (HCV) infection has been associated with a plethora of immune and autoimmune perturbations. We review serological and clinical autoimmune manifestations associated with HCV infection, discuss treatment regimens for HCV-related autoimmune diseases, and present a framework for understanding HCV-associated autoimmune disease by performing a computerized literature search from which representative articles were used and referenced. The immune response to HCV may include the development of cryoglobulins, rheumatoid factor, antinuclear antibodies (ANA), anticardiolipin, antithyroid, anti-liver/kidney/microsomal antibodies (anti-LKM), as well as HCV/anti-HCV immune complex formation and deposition. HCV infection is a significant cause of mixed essential cryoglobulinemia, which may then be complicated by cryoglobulinemic glomerulonephritis, vasculitis, or neuropathy. It has also been associated with membranous and membranoproliferative glomerulonephritis. Subsets of autoimmune hepatitis patients are infected with HCV and evidence suggests that HCV is a causative agent of antithyroid antibodies and autoimmune thyroid disease. Although cause-and-effect remain to be proved, there are reports of HCV infection preceding or coincident with polyarthritis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and polymyositis/dermatomyositis (PM/DM). HCV-infected patients also have a high incidence of sialoadenitis, and reports of low-grade lymphoproliferative malignancies have emerged. However, HCV is not a major causative factor for most autoimmune diseases. Optimal treatment for HCV-related autoimmune disease remains to be determined. Interferon alpha (IFN alpha) has successfully reduced viremia/transaminitis, cryoglobulins, proteinuria, and nephritis, but recurrent disease manifestations are frequent after discontinuation of therapy. Moreover, IFN alpha may precipitate or exacerbate autoimmune disease symptoms. HCV-related autoimmune disease also has been treated successfully with corticosteroids, azathioprine, and cyclophosphamide, although HCV viremia persists and may worsen.
Author: MANNS MP, HANNOVER MED SCH, DEPT GASTROENTEROL & HEPATOL, CARL NEUBERGSTR 1, D-3000 HANNOVER, GERMANY Source: JOURNAL OF VIRAL HEPATITIS 1997 ;4:7-10
Autoimune hepatitis is a disease of unknown cause. Apart from genetic markers such as HLA DR3 and HLA DR4, female predominance, hypergammaglobulinaemia and characteristic autoantibodies are diagnostic hallmarks, Several viruses have been discussed to induce autoimmune hepatitis, among them all major hepatotropic viruses, Epstein-Barr virus and herpes simplex virus, It seems that herpes viruses may be responsible in at least some cases of patients with autoimmune hepatitis type 2, Furthermore, hepatotropic viruses like hepatitis C and hepatitis D virus may cause autoimmune phenomena which are similar to those in idiopathic autoimmune hepatitis. LKM-1 antibodies in hepatitis C and LKM-3 antibodies in hepatitis D map cause diagnostic problems. LKM-1 antibodies in hepatitis C are directed either against cytochrome P450 2D6 or other yet unidentified microsomal antigens. As in hepatitis C the antimicrosomal autoantibody response in hepatitis D is more heterogeneous. These LKM-3 antibodies react with several epitopes on proteins of family 1 and 2 UDP-glucuronosyltransferases (UGT). Additional autoantibodies are seen in hepatitis D virus infection, Liver diseases are models to study autoimmune disease, drug-induced and virus-induced autoimmunity in humans.
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