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- PBC facts
- What treatments are used in patients with PBC?
- Ursodeoxycholic acid (UDCA)
- Immunosuppressive medications
- Elevated serum cholesterol and xanthomas
- Malabsorption of fat and fat-soluble vitamins (A, D, E and K)
- Edema and ascites
- Bleeding from varices
- Hepatic encephalopathy
- Sicca Syndrome
- Raynaud's Phenomenon
- What is the role of liver transplantation in PBC?
- What is the future for PBC?
What treatments are used in patients with PBC?
The treatments used in patients with PBC can be subdivided into:
- Medications to treat PBC itself
- Treatments for the symptoms of PBC
- Treatments for the complications of PBC
- Treatments for the diseases associated with PBC
- Liver transplantation
Ursodeoxycholic acid (UDCA)
The destruction of bile ducts in PBC leads to the retention of certain toxic bile acids in the liver cells (hepatocytes). These toxic bile acids are believed to cause death of the hepatocytes and a gradual loss of liver function. Ursodeoxycholic acid (UDCA is an abbreviation for this chemical name) is a naturally occurring bile acid that is produced in small quantities by normal hepatocytes. UDCA is available to prescribe as ursodiol (Urso-250, Actigal, and generic preparations). When taken orally, UCDA is absorbed from the gut, taken up and processed by hepatocytes, and transported in bile back to the intestine. UDCA has at least four beneficial effects in PBC:
- First, it increases the rate of bile flow from the hepatocytes, thereby combating cholestasis and diluting toxic bile acids in bile.
- Second, it inhibits the body's production of toxic bile acids, thereby preventing further injury to the hepatocytes.
- Third, it inhibits apoptosis (genetically programmed cell death), thereby preventing hepatocytes from dying.
- Fourth, it mildly inhibits the immune response in the liver, thereby possibly reducing immunological injury to the bile ducts and liver.
Four large-scale, clinical trials have compared the effectiveness and safety of UDCA to that of an inactive drug (a placebo). These controlled trials were done in both symptomatic and asymptomatic patients with a spectrum of tissue abnormalities (pathology) on their liver biopsies, ranging from early disease to cirrhosis. UDCA treatment led to improvement in liver blood test abnormalities, significantly reducing elevated levels of bilirubin, alkaline phosphatase, ggt, and cholesterol. UDCA, however, did not improve fatigue or prevent or improve osteoporosis, and had a variable effect on itching. Three of the four trials used a similar dose of UDCA (13-15 mg per kg body weight per day) and were combined for an analysis of a total of 548 patients.
The results of the combined analysis showed that UDCA significantly increased survival after up to 4 years of therapy, without the need for liver transplantation. The fourth large-scale study used a lower dose of UDCA (10 to 12 mg per kg per day). The results of this study differed somewhat from those of the other three studies. This one showed a benefit of UDCA treatment primarily in patients with bilirubin levels of less than 2 mg/dL. The three other studies, analyzed alone or combined, however, did not confirm this observation about the bilirubin. In fact, each of those studies actually demonstrated a benefit for patients with advanced disease and elevated bilirubin levels. Furthermore, the development of portal hypertension was reduced by the UDCA. It is important to note that despite producing clear benefits, UDCA treatment primarily retards progression and does not cure PBC.
All patients with PBC who have abnormal liver tests, regardless of the stage of the liver biopsy or the phase of natural progression of the disease, probably should be treated with UDCA. The dose usually should be between 13 and 15 mg per kg body weight per day. Patients can take UDCA as either a single dose or a divided dose without affecting its clinical benefits. UDCA is very safe for long-term use. The primary side effect is diarrhea, which is due to failure to absorb all of the UDCA from the gut. Patients who experience diarrhea can take smaller doses more frequently, trying to maintain the recommended total daily dose. On the other hand, patients who do not have diarrhea can try taking larger amounts per dose, with the goal of taking only one dose (again, the recommended total dose) per day at bedtime.