Primary biliary cholangitis: Epidemiology, prognosis, and treatment

Abstract

Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune liver disease characterized by a destructive, small duct, and lymphocytic cholangitis, and marked by the presence of antimitochondrial antibodies. The incidence and prevalence of PBC vary widely in different regions and time periods, and although disproportionally more common among White non-Hispanic females, contemporary data show a higher prevalence in males and racial minorities than previously described. Outcomes largely depend on early recognition of the disease and prompt institution of treatment, which, in turn, are directly influenced by provider bias and socioeconomic factors. Ursodeoxycholic acid remains the initial treatment of choice for PBC, with obeticholic acid and fibrates (off-label therapy) reserved as add-on therapy for the management of inadequate responders or those with ursodeoxycholic acid intolerance. Novel and repurposed drugs are currently at different stages of clinical development not only for the treatment of PBC but also for its symptomatic management. Here, we summarize the most up-to-date data regarding the epidemiology, prognosis, and treatment of PBC, providing clinically useful information for its holistic management.

FIGURE 1

Approach to the diagnosis of PBC. The assessment of patients with cholestasis whether symptomatic or not should include a liver ultrasound and testing for the AMA in serum. A positive AMA in this setting is sufficient to make the diagnosis of PBC. PBC-specific ANAs, ie, anti-sp100 and anti-gp210, can aid in the diagnosis of PBC in individuals with cholestasis and negative AMA serology. Liver biopsy is reserved for those with unclear diagnosis after serologic workup, or when a coexisting process is suspected, including fatty liver disease and autoimmune hepatitis. Abbreviations: AMA, antimitochondrial antibody; AMS, altered mental status; ANAs, antinuclear antibodies; MRCP, magnetic resonance cholangiopancreatography; PBC, primary biliary cholangitis; US, ultrasound.

FIGURE 2

Natural history in primary biliary cholangitis (PBC). Most patients with PBC are diagnosed while asymptomatic. Liver disease progression is inevitable in most untreated individuals, with fibrosis and cirrhosis ensuing as a consequence of the inflammatory and cholestatic processes. The cumulative incidence of major non-neoplastic hepatic complications has been reported as 15% after 15 years of follow-up. Liver transplantation is the only curative treatment option for those with decompensated disease and declining liver function. PBC will recur in 20%–40% of post-transplant patients. Symptoms do not correlate with the degree of cholestasis or fibrosis although patients with more severe disease tend to experience more symptoms in general. Fatigue may not completely resolve post-transplantation even in the absence of recurrent disease. ¹Symptoms do not correlate with the disease stage and can occur at any point. ²Fatigue may persist after liver transplant. ³The frequency of post-transplant PBC is highly variable among studies (9%–61%).

FIGURE 3

Geographical variations of PBC incidence and prevalence. (A) Global variations in PBC incidence. (B) Global variations in PBC prevalence. Lower to higher rates are qualitatively represented by lighter to darker blue, respectively. Countries with no population-based epidemiologic studies available at the time of this review are represented in gray. Abbreviation: PBC, primary biliary cholangitis.

FIGURE 4

PBC management flow chart. A holistic approach for the management of patients with PBC is recommended and should be based on: (1) PBC treatment; (2) disease staging and monitoring; (3) symptomatic treatment; and (4) extrahepatic complications of cholestasis management. Currently recommended strategy supports assessing response to UDCA after 1 year of treatment although ongoing studies indicate that this may be evaluated at earlier timepoints as well. In addition, while existing guidelines still associate “response to UDCA” with achieving specific cutoff values for ALP and TB, it is likely that the field will evolve in the direction of aiming to normalize liver chemistries. ¹Per guidelines published for the general population. AHA/ACC guidelines, ACE guidelines. Abbreviations: PBC, primary biliary cholangitis; pHTN, pulmonary hypertension; PLTs, platelets; UDCA, ursodeoxycholic acid.

FIGURE 5

Approach to patients with primary biliary cholangitis (PBC) in the outpatient clinic. PBC is a relatively rare disease, and managing affected patients in the office can be challenging for providers not familiarized with the disorder. Although PBC treatment should be tailored to the patient’s individual needs, we propose a structured approach for its management in the outpatient setting. This should include symptomatic and disease assessment and treatment during each clinic visit, periodic fibrosis staging, and screening for extrahepatic complications of cholestasis when appropriate. For those with advanced disease stages, screening for complications derived from portal hypertension is also necessary. ¹Recommend comanagment with ophthalmologist. ²Contraindicated in cirrhosis with portal hypertension and decompensated disease. ³Patients with LSM>10 kPa and/or nonreponders to UDCA. ⁴Patients with LSM<10 kPa or with appropriate UDCA response. ⁵Avoid in patients with esophageal varices. ⁶In the absence of cardiovascular risk factors, hyperlipidemia associated with PBC does not increase the risk of cardiac events. Screening should be performed at baseline and the according to guidelines published for the general population. Abbreviations: AFP, alpha fetoprotein; BMP, basic metabolic panel; CBC, complete blood count; EV, esophageal varices; INR, international normalized ratio; LSM, liver stiffness measurement; pHTN, pulmonary hypertension; PLTs, platelets; TG, triglycerides; TSH, thyroid-stimulating hormone; UDCA, ursodeoxycholic acid.