THE NATIONAL
HEPATITIS C INSTITUTE
The Hepatitis C Awareness & Prevention Campaign


Serving the Hepatitis C Community

 

 Disease Symptoms
Most people infected with hepatitis C have no symptoms for years. When symptoms are present, they can range from mild to severe. The most common early symptoms are mild fever, headache, muscle aches, fatigue, loss of appetite, nausea, vomiting and diarrhea. Later symptoms may include dark coffee-colored rather than dark yellow urine, clay-colored stools, abdominal pain, and yellowing of the skin and/or whites of the eyes (jaundice).

This is a list in progress of other diseases associated with Hepatitis C. These diseases are referred to as "Extrahepatic Manifestations." One or Additional diseases are usually present in patients before getting the diagnoses of Hepatitis C. Be sure to check back for updates.

Extrahepatic Manifestations of Hepatitis C

In addition to liver disease, hepatitis C is associated with several other diseases caused by the Virus and referred to as "Extrahepatic Manifestations"

Click on the links to learn Additional Info:

Autoimmune Disorders Non-Hodgkin's Lymphoma 
Thyroid Disorders Additional NHL Info
Fulminant Hepatic Failure Skin Disease
Bone Marrow Function Porphyria cutanea tarda   Additional Info
Asthma Hemochromatosis
Diabetes mellitus  Additional Info Arthritis   Additional Info
Cryoglobulinemia Additional Info Sjögren's syndrome
Renal Disease HCV and the Eyes
Glomerulonephritis  Additional Info   The HCV Heart
Membranoproliferative GN Serum Cholesterol
Opportunistic Infections HCV and the CNS
Peripheral neuropathy    Additional Info HCV and the Brain   Additional Info
Fibromyaliga Cirrhosis/ Carcinoma
Steatosis Liver Transplantation
Fibrosis Sexual dysfunctions
Menopause & Fibrosis HIV/Hepatitis C Coinfection
Treatment Impact HIV Co-Infection & HAART
Neutropenia Depression: Options for Treatment


Clinical & Scientific Research

  • Prevalence of clinical and biologic extrahepatic manifestations of hepatitis C virus (HCV) infection
    Extrahepatic clinical manifestations are frequently observed in HCV patients and involve primarily the joints, muscles, and skin. The most frequent immunologic abnormalities include mixed cryoglobulins, antinuclear antibodies, and anti-smooth muscle antibodies. The most frequent risk factors for the presence of clinical and biologic extrahepatic manifestations are advanced age, female sex, and extensive liver fibrosis.
     

  • Extrahepatic manifestations of hepatitis C among United States male veterans
    In conclusion, we found a significant association between HCV infection and PCT, lichen planus, vitiligo, cryoglobulinemia, membranoproliferative GN, and NHL. Patients presenting with these disorders should be tested for HCV infection.

    HCV and Brain Dysfunction

  • Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease
    The HCV-infected patients were impaired on Additional Info cognitive tasks than the HCV-cleared group (mean [SD]: HCV-infected, 2.15 [1.56]; HCV-cleared, 1.06 [1.24]; P = .02). A factor analysis showed impairments in power of concentration and speed of working memory, independent of a history of intravenous drug usage (IVDU), depression, fatigue, or symptom severity.
     
  • Cognitive Brain Function Is Subclinically Impaired In Patients With Chronic Hepatitis C -
    Does Hepatitis C Affect The Brain?
    The percentage of people with hepatitis C that complain about fatigue and quality of life is much higher than in other liver diseases.....Non-cirrhotic hepatitis C patients were found to have some subclinical impairment of cerebral function prior to combination therapy with interferon and ribavirin.
     
  • HCV Found in Autopsy Brain Tissue- we found HCV RNA in the cellular fraction of CSF (eight out of 13 patients), but viral sequences were rarely present in supernatants (two out of 13 patients). Importantly, in half of the patients in whom viral sequences were amplified, the CSF-derived virus was closer to that found in PBMC, than to that circulating in serum, which suggested that it was of lymphoid origin. In two of the latter patients sequences recovered from CSF and serum were classified as belonging to different genotypes. However, they were compatible with the genotype present in PBMC. These findings strongly suggest that the virus found in CSF was derived from peripheral blood leukocytes, and not serum. The presence of differing viral genotypes in serum and lymphoid compartments was also reported by others [23].
     
  • Hepatitis C and the Brain
    Hepatitis C: Pathogenesis, Virology, and Immunology
    These investigators found an association with HCV-RNA positivity in the cerebrospinal fluid of HCV-infected persons, particularly in association with the cellular compartment. The presence of the negative strand of HCV suggested active HCV replication rather than contamination from the peripheral blood.
     
  • Psychiatric Disorders Common Among HCV-Infected Veterans
    A total of 22,341 veterans were infected with HCV and 43,267 veterans were not infected. Several psychiatric disorders were found to be Additional Info common among HCV-infected than non-infected veterans, including depressive disorders, posttraumatic stress disorder, psychosis, bipolar disorder, and anxiety disorders.

    • Mania associated with interferon
    We report a case of mania with psychotic symptoms in a 21-year-old female...receiving interferon. The report supports the view that dose reductions or pauses during interferon treatment can cause mania.

    Hematologic Disorders

    Essential mixed cryoglobulinemia. Essential mixed cryoglobulinemia (EMC) is a condition that results in the deposition of circulating immune complexes in small-to-medium blood vessels. Patients with EMC usually present with rash, arthralgias, and weakness. A review of the literature reveals that hepatitis C can be found in 95% of all patients with EMC.

    Several investigators have suggested that hepatitis C may have a causative role in EMC. Anti-HCV antibodies can be detected in the vessel walls of skin biopsy specimens taken from patients with EMC and chronic vasculitis. Interferon (IFN) therapy has been shown to reduce the cryocrit and lead to symptomatic improvement of both rash and joint pains. The response is short-lived, however, because symptoms almost universally reappear on cessation of therapy.

    Mixed cryoglobulinaemia & Rheumatic Manifestations

    Arthritis & Rheumatism

    Renal Disorders

    Glomerulonephritis has been associated with hepatitis C.[59,60] Patients are noted to have proteinuria, which can be significant and in the nephrotic range. Most cases of glomerulonephritis are associated with cryoglobulinemia. The most common histologic lesion seen is membranoproliferative glomerulonephritis. IFN therapy may reduce proteinuria, but a sustained response is seldom achieved in these patients.[61,62] Ribavirin should be avoided in patients with significant renal impairment. Some patients may benefit from the use of plasmapheresis, although the relief tends to be short-lived.

    Spectrum of HCV-Related Glomerular Disease
    It is now regarded that HCV infection is the pathogenetic basis for the great majority of cases of what were previously thought to be idiopathic MPGN and essential mixed cryoglobulinemia

    Kidney Manifestations The kidneys are also affected in some patients with hepatitis C. The most common kidney disease related to hepatitis C infection is membranoproliferative glomerulonephritis (MPGN) (6). The prevalence of MPGN varies with geographical location. It is Additional Info common in Japan and is less frequently seen in France. Patients with MPGN usually complain of weakness, edema and have systemic arterial hypertension. Urine of such patients contains a lot of protein (>3.5 g/day), a condition called nephritic syndrome. Other abnormalities include low serum albumin (due to losses in the urine), decreased complement levels, and the presence of rheumatoid factor and cryoglobulins. MPGN may sometimes occur in the absence of cryoglobulinemia.

    Another kidney disease called membranous nephropathy (MN) is less common in HCV infected patients and is not associated with cryoglobulinemia or rheumatoid factor but is associated with heavy proteinuria (7). The mechanism of the disease is still unclear, but some studies suggest that it is caused by circulating complexes of antibodies and HCV particles directly causing damage to the kidneys as they are deposited in the glomerulus and tubules of the kidneys. Some authors recommend treatment of patients with HCV-related kidney disease even in the absence of active liver disease. The current treatment of choice for HCV infection is interferon and ribavirin. However, in patients with severe renal failure, only interferon monotherapy is recommended because ribavirin cannot be removed by dialysis. Thus, it accumulates and causes severe breakdown of red blood cells (hemolysis) and anemia.

    Dermatologic Disorders

    Several dermatologic disorders have been described in association with hepatitis C. These include porphyria cutanea tarda (PCT) and lichen planus.

    Porphyria Cutanea Tarda, also know as PCT is the most common form of porphyria. PCT has been associated with hepatitis C infection, particularly in those patients with significant alcohol use.[47,64,65] Hepatitis C may be found in 58% to 71% of PCT patients. PCT tends to present at an earlier age in patients with hepatitis C than in those without HCV infection. Despite this association, the clinical changes seen in PCT do not appear to be a direct consequence of viral infection.

    Lichen planus. Lichen planus lesions may be associated with prolonged hepatitis C infection. These lesions are most commonly seen in the oral mucocutaneous area, but can occur anywhere on the skin. This condition, which is immunologically mediated, may be worsened by interferon therapies.

    The Skin and Hepatitis C Additional Info rmation on different skin disorders related to the hepatitis C virus infection.

    Endocrine Disorders

    According to  studies by the Dept. of Veterans Affairs Extrahepatic Manifestations and nonHodgkin's  lymphoma appeared Additional Info often in HCV infected VA patients hospitalized between 1992 to 1999 than the general public. 

    Lymphoma. Several reports have described an increased incidence of B-cell lymphoma in patients with hepatitis C. Rasul and colleagues studied 16 patients with chronic hepatitis C and cryoglobulinemia for the presence of lymphoma. Bone marrow biopsy results were consistent with non-Hodgkin's lymphoma in 2 patients and suspicious for lymphoma in 7. Although this finding needs to be evaluated further in larger studies, the development of lymphadenopathy or unexplained chronic anemia in a patient with hepatitis C infection should raise concern about the possibility of underlying lymphoma.

    Quality of life in patients with low-grade non-Hodgkin's lymphoma. Low-grade non-Hodgkin's lymphoma (NHL) is an indolent form of the disease with a generally slow course of progression.

    Primary hepatic high-grade non-Hodgkin's lymphoma and chronic ... Little is known about the coincidence of hepatitis C virus infection (HCV) and non-Hodgkin's lymphoma, although there is an increased incidence

    Non-Hodgkin lymphoma in chronic hepatitis C
    Rasul et al. (1999): Hepatology 29: 543-547.

      In some countries - in particular in Italy - there is an increased prevalence of Non-Hodgkin lymphoma and patients with hepatitis C, in particular in those with cryoglobulinemia.

    • 16 patients with CHH and mixed cryoglobulinemia underwent bone marrow biopsy.

    • Characterized by morphology, flow cytometry and molecular analysis.

    • 25 % had morphology and evidence of monoclonal B-cell NHL

    The epidemiology of non-Hodgkin's lymphoma The incidence of non-Hodgkin's lymphoma (NHL) has doubled over the past two ... The disease occurs Additional Info often in whites than in blacks, and it is about 50% ...

    Thyroid Dysfunction in Chronic Hepatitis C Patients Treated with Interferon/Ribavirin
    14.7%) patients developed thyroid dysfunction by the end of treatment or the six-month post-treatment measurement.

    Diabetes
    Hepatitis C has been associated with both diabetes mellitus and an increased incidence of antithyroid antibodies.

    Diabetes mellitus. An association between hepatitis C and diabetes mellitus has recently been demonstrated. Mason and colleagues retrospectively evaluated 1117 patients with chronic hepatitis C and found this infection to be an independent predictor of diabetes. Mehta and associates found that among individuals older than 40 years, those with hepatitis C infection were Additional Info than 3 times as likely to have type 2 diabetes mellitus as those without hepatitis C infection. The prevalence of type 1 diabetes was not increased. The link between these 2 disorders needs to be investigated further, because this may lead to an improvement in available therapies.

    Diabetes mellitus and hepatitis C
    Mason et al. (1999): Hepatology 29: 328-333.
    These studies provide epidemiological and virological data to link HCV infection and diabetes. In the liver disease cohort, diabetes was observed in 21% of patients with HCV infection, as compared with only 12% of HBV-infected patients. In the diabetes cohort, Additional Info than 20% of patients with consistently elevated serum aminotransferases had evidence of HCV infection.

  • Retrospective analysis of 1117 patients with chronic hepatitis

  • Case-control study comparing hepatitis C with 594 diabetic patients and 377 clinic controls

  • HCV infection and age were independent predictors of diabetes

    • Diabetes and HCV -Insulin resistance is associated with chronic hepatitis C and virus infection fibrosis progression. "HCV patients were Additional Info than 11 times as likely as those without infection to develop diabetes"

    Association of Diabetes Mellitus and Chronic Hepatitis C Virus Infection While patients with liver disease are known to have a higher prevalence of glucose intolerance, preliminary studies suggest that Hepatitis C virus (HCV) infection may be an additional risk factor for the development of diabetes mellitus.

    Our findings are in concordance with similar epidemiological studies from Europe and the Middle East. A striking observation from all the studies with chronic viral hepatitis cohorts of Additional Info than 300 patients, including our own, is the consistent finding that diabetes was observed in 24% to 26% of patients with HCV infection compared with 9% to 13% of patients with HBV infection and other liver disease controls.6,7,21

    Insulin resistance and HCV These data support the concept that viral-induced IR may facilitate fibrogenesis in chronic HCV infection.

    Do You Have Insulin Resistance?. Silvia Hinojosa-Price, RN, poses  questions related to insulin resistance in advanced liver disease, as well as lower response to antiviral therapy, to Zobair Younossi, M.D., M.P.H. Director, Center for Liver Diseases, Medical Director, Liver Transplant Program,

    HCV functions as an opportunistic infection in HIV-positive patients
    Lesens O. et al. (1999) J. Inf. Dis. 179: 1254-1258

    • 124 hemophiliacs were studied
    • Progressive liver disease (PLD) defined as hyperbilirubinemia ± signs of decompensation
    • Risk of PLD in HIV+ was 7.6 and higher in patients with AIDS-defining symptoms (RR 3)

    Neutropenia and Infections in People with Hepatitis C
    T    he authors concluded that neutrophil count “is not correlated with infection rate in recipients of interferon-based therapy for hepatitis C,” and suggested that patients who develop neutropenia during hepatitis C treatment may not require interferon dose reduction or adjunct therapy with G-CSF.