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PRIMARY BILIARY CIRRHOSIS

Primary biliary cirrhosis is about 10 times more common in women than men. The explanation is unknown, but autoimmune conditions are known to be more common in women primary biliary cirrhosis, primary biliary cirhosis, bile cirrhosis. All races are affected. The changing prevalence reflects increasing physician awareness, better diagnosis (especially with the availability of the serum mitochondrial antibody test), and the recognition of more asymptomatic patients. There is family clustering; usually, mothers and daughters are affected, and the presentation is earlier in the second generation. Prevalence of circulating mitochondrial antibodies is increased in the relatives of patients. Histocompatibility antigen studies give highly variable results, often depending on the geographic location of the patients studied. It is difficult to make a coherent study from these observations primary biliary cirrhosis, primary biliary cirhosis, bile cirrhosis. They suggest a strong immunogenetic background for PBC that runs in families. Environmental factors presumably act on a 

Presentation

In the 1950s and 1960s, the typical patient was an itching, deeply jaundiced and pigmented middle-aged or elderly woman. Her skin was covered with xanthomas, and she was kyphotic. It was soon realized that this was the presentation of end-stage disease that now is rarely attained. In 1958, presymptomatic disease was described. Now the diagnosis is likely to be based on 

Course

Eventually, all patients will develop symptoms. Fatigue is very common, affecting 68% of patients. It is associated with depression and poor sleep quality. (Cholestatic rats show behavior consistent with that seen in depression. With time, pruritus increases, bones become thin, jaundice deepens, and, finally, the picture is that of chronic hepatocellular failure. Hepatocellular carcinoma is rare in cirrhotic patients but is a relatively common cause of death in male PBC patients with

Associated Conditions

Primary biliary cirrhosis is associated with almost every known or postulated autoimmune condition. Collagen diseases, especially Sjogren's syndrome, rheumatoid arthritis, and thyroid disorders are particularly common. Primary biliary cirrhosis may be associated with scleroderma and with calcinosis cutis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and

Pulmonary abnormalities include lymphocytic interstitial pneumonitis. Gas-transfer studies may be abnormal. Chest radiograms may show nodules and interstitial fibrosis. Mediastinal lymphadenopathy is common.

Prognosis

The course of PBC is variable and unpredictable. Some patients never become symptomatic, and others run a progressively downhill course. At present, the patient with end-stage PBC faces not death but possible liver transplantation.

Indications for Transplantation for Primary Biliary Cirrhosis

 
Quality of life
 
Bone thinning
 
Pruritus
 
Child class B or C
 
1-year survival rate, 90%

 

A rise in serum bilirubin level is a bad prognostic sign. The development of hepatocellular failure (edema, ascites, and encephalopathy) or significant portal hypertension (bleeding varices) is also very serious.

Prognostic models have been developed. The Mayo model depends on age, serum bilirubin, and albumin levels, prothrombin time, and edema. Serum bilirubin level and the Mayo model are very good predictors of survival. The Mayo model can yield a precise estimate of survival in an individual patient. Such models do not take into account time-dependent factors. They cannot predict a life-threatening episode such as bleeding varices.

Treatment

General measures, including maintenance of nutrition and replacement of fat-soluble vitamins, apply to all patients with cholestasis.

The pathogenesis of pruritus in cholestatic patients is unknown, but recent evidence suggests increased neurotransmission and neuromodulation by endogenous opioids in the central nervous system. Pruritus is usually controlled by cholestyramine, but oral nalmefene and opiate antagonists have given promising results in an

Osteomalacia is rare and can be corrected by vitamin D and calcium supplements. The major problem is osteoporosis, which is of low-turnover type. The osteoporosis may be related to the accumulation of toxins that impair osteoblast function. Calcitonin is of no value. Biphosphonates may be useful, and cyclical etidronate can be tried. Estrogens stimulate bone formation, and postmenopausal women with PBC should receive

The recognition that PBC is probably an autoimmune disease led to trials of immunosuppressive drugs. The trials tended to be poorly controlled, with small numbers enrolled and short follow-up of participants. Drugs tested included azathioprine, D-penicillamine, chlorambucil, cyclosporin A, and

Results in terms of survival, biochemical tests, and hepatic histology tended to be inconclusive. Methotrexate is the drug most recently tried, but after 6 years, the Mayo score and bilirubin were higher in those receiving the drug than those receiving placebo. Colchicine is of little, if any, benefit. Combination therapy may be more helpful, in particular, ursodeoxycholic acid plus azathioprine or cortisone or methotrexate plus other drugs, but no significant benefit has

Ursodeoxycholic Acid

Ursodeoxycholic acid (URSO) is a nonhepatotoxic, hydrophilic bile acid that protects cell membranes against the detergent effect of hydrophobic bile acids, stimulates the excretion of toxic bile acids, and increases anion exchange in the liver. It reduces

Original studies from France showed that administration of URSO improved liver function and slowed the progression of disease, thus reducing probability of death or the need for transplantation. Results were less satisfactory if, on entry to the trial, the patient had a high serum bilirubin level and cirrhosis was present. Symptoms such as pruritus and fatigue are unaffected. A multinational controlled trial confirmed that URSO reduces the time to death or transplantation. It does not cure the disease. A 6-year

Liver Transplantation

Indications for liver transplantation are a poor quality of life, so that the patient is house-bound, has intractable pruritus, hepatocellular failure (deepening jaundice, encephalopathy, ascites), or bleeding varices. Results are better if referral is early. A model using age, renal failure, Child's class, and United Network for Organ Sharing (UNOS) criteria can be used to predict the

The 1-year survival rate after transplantation is about 85% to 90%, and a 5-year survival rate of 60% to 70% is reported. Twenty-five percent of patients will need a retransplant, usually because of the development of the vanishing bile duct syndrome. The disease almost certainly recurs in the transplanted liver. Mitochondrial antibody levels increase, and the patient may