Extrahepatic Manifestations of Hepatitis C

1. Essential mixed cryogiobulinemia
2. Lymphoma
3. Glomerulonephritis
4. Porphyria cutanea tarda
5. Diabetes mellitus
6. Corneal ulceration
7. Autoimmune phenomena
8. Uveitis
9. Sialadenitis
10. Peripheral neuropathy

The mechanism by which alcohol effects a more rapid progression of disease is not known. The amplification of cytokine signals is believed to play a role in this process by stimulating stellate cells and increasing fibrosis. Alcohol consumption also increases the risk of developing HCC.
Age and gender. Acquisition of hepatitis C after age 40 is associated with a more rapid disease progression. The reasons for this effect are uncertain but may be related to an aging immune system. Male sex is also associated with more rapid disease progression.

Coinfection. Hepatitis C and HIV coinfection appears to lead to rapid progression of liver disease. Progression to cirrhosis or liver failure may occur within 10-15 years after infection with HCV, and this progression occurs at approximately twice the rate as what occurs with hepatitis C infection alone. Hepatitis C and related liver disease are now the leading cause of non-AIDS-associated death in patients with HIV.

NATURAL HISTORY OF HEPATITIS C

The precise natural history of hepatitis C remains unknown because of the lack of prospective data, the inability to determine time of initial onset of disease, and the variable influences of multiple cofactors leading to disease progression. What has been determined, however, is that a subset of hepatitis C patients will progress to cirrhosis and its associated complications. Chronicity is the hallmark of hepatitis C infection. Approximately 15% to 30% of patients exposed to HCV recover spontaneously, while the remaining 70% to 85% develop chronic infectioni. Most patients with chronic hepatitis C infection appear to have mild to moderate histologic disease. Cirrhosis may develop in as many as 15% to 30% of infected patients. Although fulminant disease is rare in hepatitis C, its occurrence has been reported. Several studies have attempted to determine the rate of histologic disease progression in transfusion-acquired disease. Tong and colleagues found a mean interval of 20.6 years from time of infection to development of cirrhosis, and a mean interval of 28.3 years from time of diagnosis to development of hepatocellular carcinoma (HCC).

The infusion of hepatitis C-contaminated anti-D immune globulin in 1977 and 1978 in Ireland has allowed the prospective evaluation of 376 women, 17 years after exposure. Most of the hepatitis C-infected women had evidence of moderate hepatic inflammation on liver biopsy, while 51% had fibrosis, and only 2% had cirrhosis. The results of a similar German study of 152 women infected with hepatitis C-contaminated Rh0 immune globulin showed no evidence of cirrhosis 15 years after exposure.

In a recent study published in the Annals of Internal Medicine, coworkers conducted a 45-year follow-up of hepatitis C infection in healthy young adults. In this retrospective study, stored sera from 8568 US Air Force recruits in Wyoming dating from 1948-1955 were evaluated for hepatitis C. Ten patients were found to be positive for HCV.

FACTORS INFLUENCING DISEASE PROGRAM

Several factors appear to influence the rate of progression of hepatitis C to cirrhosis. These factors include alcohol use, age at time of exposure, sex, and coinfection with either hepatitis B or HIV.

Alcohol. Alcohol ingestion and chronic hepatitis C infection appear to be synergistic in accelerating the progression of liver disease. An increased risk of cirrhosis and decompensated liver disease is associated with sustained alcohol consumption of greater than 40 g/day. Other effects of concomitant alcohol use in the setting of hepatitis C include increased transaminase levels, higher hepatitis C viral loads and increased number of hepatitis C quasispecies. These elevations have been shown to be significantly reduced with a decrease in daily alcohol intake.

HEPATITIS - SEXUAL TRANSMISSION

SEXUAL TRANSMISSION:
Sexual Transmission of hepatitis C remains controversial and probably accounts for less than 5% of cases. Risk factors for sexual transmission include multiple sex partners, prostitute use, rectal intercourse, and traumatic sex. Sexual intercourse during menstruation or without adequate vaginal lubrication may increase the transmission rate. Studies in married couples have indicated a great risk of spousal transmission with increasing duration of married. Whether this risk is secondary to Sexual Transmission, the potential role of more frequent sharing of household (razors, toothbrushes, etc) items or other factors remains to be determined.

Perinatal transmission
Perinatal transmission of hepatitis C occurs in approximately 3% to 5% of infants born to women infected with HCV. Perinatal transmission is associated with 2 independent risk factors: high viral load at time of delivery and having a mother who is HIV – positive.

Italian investigators recently reported the decreased risk of perinatal transmission of hepatitis C with cesarean section when compared with vaginal delivery. The risk of perinatal transmission of hepatitis C in a woman who is HIV-positive is estimated to be 15% to 35%. Infants born to hepatitis C- infected mothers may initially be hepatitis C antibody –positive due to passive transfer of this antibody across the placenta. This antibody may be present throughout thee first year of an uninfected newborn’s life before Disappearing. Therefore, the determination of hepatitis C infection in the newborn requires the demonstration of positive HCV RNA in the serum. Breastfeeding by mothers with hepatitis C appears to be safe, with no reported cases of viral transmission to newborns.

OTHER FACTORS:
Other groups at high risk for Hepatitis C infections include persons who received clothing factor concentrates prior to 1987, persons on hemodialysis, hemophiliacs and individuals who received either a solid organ or bone marrow transplant prior to 1992. Contamination of the ultrafiltrate dialysis membrane may help explain the high rate of hepatitis C infection seen in dialysis units.

Hepatitis Risk Factors:

RISK FACTOR:

BACKGROUND:

Hepatitis C is transmitted parenterally the most common risk factor for Hepatitis C is intravenous drug use. Prior to 1992- before the introduction of blood donor screening and surrogate Hepatitis Tests- transmit ion of blood plasma- derived product was associated with significant risk of transmission of Hepatitis C. Other potential risk factor of hepatitis C include: internal cocaine use, tattooing, body piercing, accidental middle stick injury and the sharing if house hold items, such as nail clipper, razor, blades and tooth brushes.


Common
Intervenes Drug Use
Blood transmission period to 1992
Accidental middle injury
Sexual Transmission
Perinatal Transmission
Kidney Dialysis
Transplant prior to 1992
Hemophilia
Uncommon
Internsal cocaine
Body piercing
Tattooing
Sharing of house hold items
Fistfights involving blood contact

Case reports have also documented transmission of hepatitis C between patients who underwent colon scope with an inadequately disinfected colon scope, between 2 family members who had engaged in a fistfight during which there was blood exposure and during cardio thoracic surgery.