The presence of anti-M2, anti-M4, anti-M8, and anti-M9 has been associated with the severity of the disease. Patients with profile A (ie, only anti-M9) or profile B (ie, anti-M9 and/or anti-M2-positive by enzyme-linked immunosorbent assay [ELISA]) have a better disease course than patients with profile C (ie, anti-M2, anti-M4, and/or anti-M8-positive by ELISA) and profile D (ie, anti-M2, anti-M4, and/or anti-M8-positive by ELISA and complement-fixation test).
Medical Care: The goals of treatment are to slow the progression rate of the disease and to alleviate the symptoms (eg, pruritus, osteoporosis, sicca syndrome). Liver transplantation appears to be the only life-saving procedure.
" Ursodeoxycholic acid (UDCA) is the major medication used to slow the progression of the disease. Patients with early disease have clinical, biochemical, and histologic improvement. Reports suggest that UDCA delays the need for transplantation or delays death. The efficacy of this medication in late stages (ie, cirrhosis) is questionable. Patients who achieve biochemical response to UDCA after 1 year of treatment reportedly have a similar survival rate to the matched control population, and this observation might be used to identify the population of nonresponders who will require alternative or additional treatments.
" Immunosuppressive agents inhibit immune reactions that mediate the progression of the disease.
" Methotrexate: Results of various trials suggest improvement in biochemical and histological findings after treatment.
" Corticosteroids may alleviate symptoms and improve biochemical and histologic findings. Corticosteroid-induced osteoporosis is of great concern.
" Cyclosporine has some therapeutic potential.
" Colchicine has been used to limited effect.
" Antipruritic treatment
o Pruritus is often refractory to medical therapy and significantly impacts patients' quality of life. Antihistamines are first-line agents to relieve pruritus in early stages and are the first line of medication for patients with mild-to-moderate pruritus. Use caution in patients with cirrhosis and signs of encephalopathy because antihistamines can further depress brain function.
o Cholestyramine and colestipol are effective in sequestering bile salts in the enteric lumen. A 1- to 4-day delay is expected before the itching remits.
o Rifampin can also be used, but the precise mechanism of action is unclear (may involve inhibition of bile acid uptake into hepatocytes and facilitation of excretion of dihydroxy and monohydroxy bile acids and toxic bile acids). Rifampin is used in patients whose conditions are not responding to cholestyramine.
o Some evidence suggests that dronabinol (Marinol) can be used to good effect.
o Plasmapheresis has also been implemented for patients with severe pruritus intractable to medical treatment. Results have been good.
Surgical Care: As the disease progresses to cirrhosis, an elevated bilirubin level, a prolonged prothrombin time, and a decreased albumin level can be found. The increased bilirubin level is an ominous sign of disease progression, and liver transplantation must be considered. Liver transplantation appears to be the only life-saving procedure.
Activity: Increased activity is recommended, especially in postmenopausal women, to prevent osteoporosis.
DRUG TREATMENT : The goals of treatment are to slow the progression rate of the disease and to alleviate the symptoms (eg, pruritus, osteoporosis, sicca syndrome). Liver transplantation appears to be the only life-saving procedure.
Drug Category:
1. Bile acids -- UDCA is the major medication used to slow the progression of the disease. Patients with early disease have clinical, biochemical, and histologic improvement. Reports suggest that UDCA delays the need for transplantation or delays death. The efficacy of this medication in late stages (ie, cirrhosis) is questionable.
- URSODIOL
2. IMMUNOSUPPRESSANTS :
- METHOTREXATE
- PREDNISOLONE
- CYCLOSPORINE
3. ANTIINFLAMMATORY DRUGS :
- COLCHICINE
4. ANTIPRURITICS :
- ANTIHISTAMINES
- CHOLESTYRAMINE
- COLESTIPOL
- RIFAMPICIN : Precise mechanism of action is unclear. May involve inhibition of bile acid uptake into hepatocytes and facilitation of excretion of dihydroxy and monohydroxy bile acids and toxic bile acids. Used in patients who are not responding to cholestyramine.