Key for Patients with PBC are Timely Diagnosis and Assessment of Therapy Effectiveness
Primary biliary cholangitis (PBC) cannot be cured. It progresses slowly and over several decades leads to liver cirrhosis with all its potential consequences, including possible transplantation and the risk of premature death. The foundation of PBC pharmacotherapy is ursodeoxycholic acid (UDCA) and in recent years, obeticholic acid (OCA) has also been available, which European and Czech guidelines recommend as the second-line treatment. One of the symposiums at this year's XLVIII May Hepatology Days also focused on PBC and its therapy, including experiences from Czech practice.
Introduction
Primary biliary cholangitis (PBC) is one of those diseases that accompany a person from onset for the rest of their life. Although classified as a rare disease, it is one of the most common autoimmune liver diseases. It is estimated that the prevalence in the Czech Republic is 12–15/100,000 inhabitants. PBC progresses in several stages and remains preclinical for a long time. Levels of alkaline phosphatase (ALP) and bilirubin correlate with transplantation and death risk. Predicting its course is difficult as the disease is very heterogeneous, but it appears that reducing biochemical activity is crucial for improving prognosis. Early and effective therapy is key for PBC.
How to Recognize PBC?
Diagnosis of PBC requires meeting 2 out of the following 3 criteria:
- Elevated ALP level > 1.5 times the norm for > 24 weeks
- Positive antimitochondrial antibodies (AMA) at a titer higher than 1:40
- Or a biopsy finding of nonsuppurative, non-purulent cholangitis and interlobular bile duct involvement
Liver biopsy should now only be used when diagnostic uncertainty exists.
A typical PBC patient is a woman (9 times more often than men) over 45 years old (in the population of women > 40 years old prevalence reaches 1/1000), with positive AMA (> 95% of cases), hyperimmunoglobulinemia, elevated IgM. MRCP usually shows normal findings (despite cholestasis), and if performed, liver biopsy reveals lymphocytic infiltrate. The occurrence of idiopathic inflammatory bowel disease is uncommon. Clinically, PBC primarily manifests as increased fatigue (78%), especially daytime sleepiness, pruritus may be present at diagnosis (20–70%), and sicca syndrome is typical. A third of patients have bone disease, and hyperlipidemia (elevation of HDL cholesterol levels) also occurs.
Prognosis and Development Scenarios
The natural prognosis of the disease can be determined using the Mayo risk score. It includes bilirubin levels, albumin, patient age, presence of edema, and the need for diuretics. However, PBC is a heterogeneous disease, and the risk of progression varies significantly among individuals. There are two main progression scenarios:
- Mild: Usually in older women (age > 70 years), who respond well to ursodeoxycholic acid, associated with a very low risk of death from liver disease, and transplantation is rarely needed. Significant pruritus and fatigue can still occur.
- Rapid Progression: Diagnosed in younger women, men, with poor response to UDCA, or presence of fatigue or pruritus at the time of diagnosis.
Criteria for Assessing UDCA Effectiveness in PBC Treatment
UDCA is a hydrophilic bile acid used to treat PBC since the end of the 20th century. Its administration improves bilirubin, ALP, GGT, AST, ALT values, reduces cholesterol and IgM levels, significantly slows histological disease progression, cirrhosis progression, including related complications, and improves survival without the need for transplantation.
Two criteria exist for UDCA response evaluation – Barcelona and Paris. They are based on two studies (Pares et al., 2006; Corpechot et al., 2008) which demonstrated that response to UDCA administration improves transplant-free survival. According to the Barcelona criteria, the goal is a reduction in ALP to normal or by ≥ 40% from baseline values after one year of standard recommended dose UDCA therapy, associated with a 95% chance of transplant-free survival after 14 years of follow-up. The Paris criteria include achieving a bilirubin level of 17 µmol/l, ALP reduction to ≤ 3 times the norm, and AST to ≤ 2 times the norm, associated with a 90% chance of transplant-free survival after 10 years. The fundamental marker of long-term prognosis is ALP level.
Summary and Conclusion
PBC remains incurable, but early initiation of treatment can significantly improve patient prognosis. If a physician finds that a patient does not respond to ursodeoxycholic acid after one year of therapy, it is recommended to initiate second-line treatment, i.e., obeticholic acid (OCA), as soon as possible.
Eva Srbová
editorial staff proLékaře.cz
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