Many factors initially considered to be important predictors of disease progression appear, in fact, not to have such a predictive role. These factors include mode of transmission, serum transaminase levels, hepatitis C viral loads, and hepatitis C genotype. The authors of one paper, however, concluded that transfusion- acquired disease was associated with more rapid disease progression than was disease acquisition due to other risk factors.
CLINICAL PRESENTATION
Most patients with hepatitis C are asymptomatic. But if symptoms do occur, the most common complaints are fatigue, abdominal pain, poor appetite, weight loss, and pruntus. The diagnosis of hepatitis C is made following the completion of specific tests requested by the clinician. The primary care physician generally performs this testing if risk factors are identified or abnormal liver chemistries noted. Blood banks and life insurance companies routinely test blood donors and applicants for hepatitis C. Hepatitis C testing, unlike testing for HIV, does not require that consent be obtained.
Hepatitis C can lead to a broad spectrum of liver disease. Patients may develop mild disease as evidenced by mild inflammation and/or fibrosis. Others may develop increasing amounts of inflammation or fibrosis, which can lead to the development of significant fibrosis or cirrhosis.
EXTRAHEPATIC MANIFESTATIONS
In addition to liver disease, hepatitis C is associated with a number of extra hepatic effects, including hematologic, renal, dermatologic, endocrine, and autoimmune disorders.
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-sized 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 biopsies taken from patients with EMC and chronic vasculitis. Interferon therapy has been shown to reduce the cryocrit and allow symptomatic improvement of both rash and joint pains. The response is short-lived, however, because symptoms almost universally reappear upon cessation of therapy.
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 cryoglobutinemia for the presence of lymphoma. Results of bone marrow biopsy were consistent with non-Hodgkin’s lymphoma in 2 patients and suspicious for lymphoma in 7. While 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.
Renal Disorders
Glonierulonephritis has been associated with hepatitis C. These patients are found 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. Interferon therapy may reduce proteinuria, but a sustained response is seldom achieved in these patients. Ribavirin should be avoided in patients with significant renal impairment. Some may benefit from the use of plasmapheresis, although the relief tends to be short-lived.
DERMATOLOGIC DISORDERS
Several dermatologic disorders have been described in association with hepatitis C. These include porphyria cutanea tarda, lichen planus, and cutaneous necrotizing vasculitis.
Porphyria cutanea tarda:
Porphyria cutanea tarda (PCT) is the most common form of porphyria. PCT ha been associated with hepatitis C infection, particularly in those patients with significant alcohol use. Hepatitis C may occur in 58% to 71% of all PCT patients. This dermatologic disorder tends to present at an earlier age in patients with hepatitis C than in those PCT patients without hepatitis C. Despite this association, the clinical changes seen in the setting of PCT do not appear to be a direct consequence of the viral infection.
Lichen planus:
This condition has been associated with hepatitis C, although hepatitis C has not been shown to be the causative agent.
Cutaneous necrotizing vasculitis: This condition has been associated With hepatitis C as well, although hepatitis C has not been shown to be the causative agent.
Endocrine Disorders:
Hepatitis C has also been linked to both diabetes mellitus and an increased incidence of anti-thyroid antibodies.
Diabetes mellitus:
An association between hepatitis C and diabetes mellitus has recently been demonstrated Mason and colleagues retrospectively evaluated patients with chronic hepatitis C and found this infection to be an independent predictor of diabetes.
Additionally, Mehta and associateS58l found that among individuals older than 40 years of age, those with hepatitis C infection were more than 3 times as likely to have type 2 diabetes mellitus than those without hepatitis C infection. The prevalence of type 1 diabetes was not increased. The link between these 2 disorders must be further investigated in an effort to improve available therapies.
Other Extra Hepatic Manifestations
Finally, hepatitis C has been associated with a number of other extrahepatic disorders as well, incluaing sialadenitis, uveitis, corneal ulceration, polyarteritis flodosa, peripheral neuropathy, and the development of autoimmune phenomena.
CLINICAL PRESENTATION
Most patients with hepatitis C are asymptomatic. But if symptoms do occur, the most common complaints are fatigue, abdominal pain, poor appetite, weight loss, and pruntus. The diagnosis of hepatitis C is made following the completion of specific tests requested by the clinician. The primary care physician generally performs this testing if risk factors are identified or abnormal liver chemistries noted. Blood banks and life insurance companies routinely test blood donors and applicants for hepatitis C. Hepatitis C testing, unlike testing for HIV, does not require that consent be obtained.
Hepatitis C can lead to a broad spectrum of liver disease. Patients may develop mild disease as evidenced by mild inflammation and/or fibrosis. Others may develop increasing amounts of inflammation or fibrosis, which can lead to the development of significant fibrosis or cirrhosis.
EXTRAHEPATIC MANIFESTATIONS
In addition to liver disease, hepatitis C is associated with a number of extra hepatic effects, including hematologic, renal, dermatologic, endocrine, and autoimmune disorders.
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-sized 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 biopsies taken from patients with EMC and chronic vasculitis. Interferon therapy has been shown to reduce the cryocrit and allow symptomatic improvement of both rash and joint pains. The response is short-lived, however, because symptoms almost universally reappear upon cessation of therapy.
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 cryoglobutinemia for the presence of lymphoma. Results of bone marrow biopsy were consistent with non-Hodgkin’s lymphoma in 2 patients and suspicious for lymphoma in 7. While 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.
Renal Disorders
Glonierulonephritis has been associated with hepatitis C. These patients are found 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. Interferon therapy may reduce proteinuria, but a sustained response is seldom achieved in these patients. Ribavirin should be avoided in patients with significant renal impairment. Some may benefit from the use of plasmapheresis, although the relief tends to be short-lived.
DERMATOLOGIC DISORDERS
Several dermatologic disorders have been described in association with hepatitis C. These include porphyria cutanea tarda, lichen planus, and cutaneous necrotizing vasculitis.
Porphyria cutanea tarda:
Porphyria cutanea tarda (PCT) is the most common form of porphyria. PCT ha been associated with hepatitis C infection, particularly in those patients with significant alcohol use. Hepatitis C may occur in 58% to 71% of all PCT patients. This dermatologic disorder tends to present at an earlier age in patients with hepatitis C than in those PCT patients without hepatitis C. Despite this association, the clinical changes seen in the setting of PCT do not appear to be a direct consequence of the viral infection.
Lichen planus:
This condition has been associated with hepatitis C, although hepatitis C has not been shown to be the causative agent.
Cutaneous necrotizing vasculitis: This condition has been associated With hepatitis C as well, although hepatitis C has not been shown to be the causative agent.
Endocrine Disorders:
Hepatitis C has also been linked to both diabetes mellitus and an increased incidence of anti-thyroid antibodies.
Diabetes mellitus:
An association between hepatitis C and diabetes mellitus has recently been demonstrated Mason and colleagues retrospectively evaluated patients with chronic hepatitis C and found this infection to be an independent predictor of diabetes.
Additionally, Mehta and associateS58l found that among individuals older than 40 years of age, those with hepatitis C infection were more than 3 times as likely to have type 2 diabetes mellitus than those without hepatitis C infection. The prevalence of type 1 diabetes was not increased. The link between these 2 disorders must be further investigated in an effort to improve available therapies.
Other Extra Hepatic Manifestations
Finally, hepatitis C has been associated with a number of other extrahepatic disorders as well, incluaing sialadenitis, uveitis, corneal ulceration, polyarteritis flodosa, peripheral neuropathy, and the development of autoimmune phenomena.
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