Short-term therapeutic response to obeticholic acid in patients with primary biliary cholangitis: A case series from the University General Hospital of Patras

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ACHAIKI IATRIKI | 2025; 44(3):151–154

Case Report

Konstantinos Papantoniou, Evangelia Bourdalou, Georgios Geramoutsos, Christos Triantos

Division of Gastroenterology, Department of Internal Medicine, University General Hospital of Patras, Patras, Greece

Received: 06 Feb 2025; Accepted: 10 Jun 2025

Corresponding author: Christos Triantos, Associate Professor of Internal Medicine and Gastroenterology, Tel.: +30 6972 89 46 51, e-mail: chtriantos@hotmail.com

Keywords: Obeticholic acid, ursodeoxycholic acid, primary biliary cholangitis, clinical benefits

 

Abstract

Introduction: Obeticholic acid (OCA) is a synthetic derivative of chenodeoxycholic acid that has been approved for the treatment of patients with primary biliary cholangitis (PBC), particularly those with an inadequate response to ursodeoxycholic acid (UDCA). This case series presents the early biochemical response and tolerability of OCA in two patients with PBC followed at our hospital.

Materials and Methods: A prospective observational follow-up was conducted on two female patients with PBC receiving treatment with OCA in addition to UDCA at the University Hospital of Patras. Data was recorded and analyzed regarding patients’ status before treatment, any previous treatment received, as well as patients’ therapeutic response in the first six months of treatment.

Results: The patients had no findings of advanced liver disease on liver elastography and were asymptomatic at treatment initiation. Both patients had elevated alkaline phosphatase (ALP) levels, while one patient also exhibited increased aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (γ-GT). Patients were re-evaluated within six months of the onset of treatment. Biochemical response with reduced ALP and γ-GT levels was observed in both patients. One patient reported mild nocturnal pruritus after OCA initiation; however, treatment was not discontinued.

Conclusions: The combination therapy of UDCA and OCA in these patients with PBC contributed to the improvement of liver biochemical markers while no significant complications occurred within six months of treatment onset.

Introduction

Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is a chronic cholestatic liver condition characterized by autoimmune destruction of intrahepatic bile duct epithelial cells, prompting the onset of cholestasis which may ultimately result in hepatic fibrosis, cirrhosis, and decompensated liver disease. Typical symptoms include pruritus and fatigue, with jaundice and abdominal pain being less common. Several patients may remain asymptomatic for years before symptoms arise [1]. Serological positivity for antimitochondrial antibodies (AMA) is a hallmark for PBC diagnosis when combined with abnormal serum liver tests. In AMA negative patients, the diagnosis of PBC can be made based on positive PBC specific antinuclear antibodies (ANA) detected by immunofluorescence (nuclear dots or perinuclear rims) or ELISA (sp100, gp210) results. Liver biopsy is not required for the diagnosis of PBC and is reserved for patients without PBC-specific antibodies or when comorbidities, such as autoimmune hepatitis (AIH) or metabolic dysfunction-associated steatohepatitis (MASH), are suspected [2].

First-line treatment for PBC is ursodeoxycholic acid (UDCA), regardless of the disease stage. UDCA treatment has been reliably shown to improve biochemical markers, slow histologic progression, delay the appearance of esophageal varices, and enhance transplant-free survival in patients with PBC, while also being well tolerated [3]. However, many patients show an incomplete response to UDCA monotherapy and require combined therapy with second-line medications. Obeticholic acid (OCA) is a synthetic derivative of chenodeoxycholic acid which was approved for the treatment of patients with PBC in 2016. Although OCA is generally well tolerated, patients may experience side effects such as pruritus. Contraindications of OCA use include advanced cirrhosis, portal hypertension and a history of liver decompensation [4]. However, clinician experience with OCA prescription for PBC remains limited.

Case series

This case series includes a prospective follow-up of patients with PBC receiving treatment with OCA at the University Hospital of Patras. Patient data were collected and analyzed, including baseline status, prior treatments, and therapeutic response within the first six months of OCA therapy. OCA treatment was initiated in two patients with PBC. Both were females, aged 48 and 58 years respectively, and were receiving treatment with UDCA after being diagnosed with PBC. Results from liver elastography showed no evidence of advanced liver disease in either patient. Both were under treatment with statins due to dyslipidemia and calcium due to osteoporosis, with no other serious comorbidities. Both patients were asymptomatic, with elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (γ-GT) levels. Additionally, one patient also had elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels (Table 1).  ALP ≥ 1.67 × upper normal limit (ULN) is a threshold commonly used for the definition of inadequate response to UDCA, and patients who do not achieve this target after 12 months of therapy can be considered for second-line treatments of PBC [5]. Both patients exhibited ALP>1.67 ULN after treatment with 750mg UDCA for six years and 1000mg for 1.5 year, respectively. Both patients were prescribed OCA treatment 5mg once a day along with UDCA and were re-evaluated six months after OCA onset.

Biochemical response was observed in both patients after six months of treatment, with a reduction in both ALP and γGT levels. ALP was reduced to <1.67 ULN in both patients. One patient reported mild nocturnal pruritus two months after treatment initiation, but the side effect was not severe enough to require treatment discontinuation. No other clinical or laboratory side effects were observed during patient follow-up.

Discussion

This prospective observational study evaluated the therapeutic response of two patients with PBC who received OCA. Over a six-month period, both patients demonstrated significant improvements in liver biochemical markers, especially the cholestatic enzymes. These findings support the growing body of evidence suggesting that OCA is an effective treatment option for PBC, particularly in patients with an incomplete response to UDCA, which remains the first-line therapy for PBC.

The efficacy of OCA in treating PBC has been well-established through multiple studies. Reduction of ALP levels is important, as it is a key marker of cholestasis and disease progression in PBC. Nevens et al. found that OCA significantly reduced ALP levels compared to placebo in patients with PBC, including those who had an inadequate response to UDCA [6]. Results from the phase 2 trial by Kowdley et al. showed improved ALP levels in patients who received long term OCA monotherapy, as well as reduction of other liver enzymes, bilirubin and immunoglobulin M (IgM) [7]. Reduction of cholestatic enzymes with OCA treatment could be attributed to improved transport of bile acids from the bloodstream into the bile. Kjærgaard et al. tested the effect of OCA treatment on the bile acid transport capacity of the liver, using PET scan. OCA treatment reduced the duration that potentially harmful bile acids remained in the liver by 30% [8]. In this case series, patients similarly showed a reduction in ALP levels after six months of OCA therapy, along with improvements in other liver biochemistry markers, including AST, ALT and γ-GT.

Bowlus et al. evaluated both biochemistry and liver biopsy reports in PBC patients receiving OCA over a three-year follow up period. They observed sustained reductions in ALP, ductal injury, liver fibrosis, and hepatic inflammation with long-term OCA therapy. These results further reinforced OCA’s role in improving both biochemical and histological endpoints in PBC patients [9]. Although the present case series did not evaluate histological changes, the biochemical improvements observed in the patients after six months of OCA therapy support its potential for long-term benefits in slowing disease progression and improving liver health.

While OCA is generally well-tolerated, some patients experience side effects, most notably pruritus. In the Nevens et al. trial, pruritus was a common side effect in patients receiving OCA, though it was usually mild to moderate in severity and manageable in most cases [6]. The safety profile of OCA was also evaluated by Bowlus et al., who found that OCA was well-tolerated over extended periods, with no new safety concern identified [9]. This suggests that treatment with OCA is suitable for prolonged use, making it an option for long-term management of PBC. The present case series reported mild nocturnal pruritus in one of the patients, with no other significant complications. Notably, pruritus did not lead to treatment discontinuation, indicating that it is often a manageable adverse event.

UDCA remains the standard of treatment for PBC; however, many patients do not achieve adequate disease control with UDCA alone. This has led to the investigation of combination therapies, including UDCA and OCA. This combination was studied by D’Amato et al., who observed significant reduction in ALP, ALT and bilirubin levels in one third of patients after 12 months of UDCA and OCA combination therapy, especially in those not diagnosed with cirrhosis before OCA initiation [10]. Similarly, the present case series showed a biochemical response in both patients who were receiving UDCA before starting OCA, underlining the added benefit of OCA for those patients not fully controlled with UDCA alone.

Results from the recent randomized, placebo-controlled COBALT trial demonstrated that OCA added to UDCA led to a higher rate of biochemical response in PBC patients, particularly those with incomplete responses to UDCA, thus confirming the synergistic effect over UDCA monotherapy. However, failure of the study to provide clear long-term clinical benefits of OCA treatment compared to placebo has raised concerns that these benefits might not outweigh potential risks [11]. In the recent HEROES trial, patients who received OCA treatment showed a significantly reduced incidence of decompensated liver disease, need for liver transplantation and mortality; however, the mean follow-up period was less than two years [12]. Other studies examining long-term effects of OCA treatment in PBC patients are currently lacking. Despite the limitations of the COBALT trial and real-world data supporting the use of OCA in patients unresponsive or intolerant to UDCA, the EMA recommended revoking market authorization of OCA for patients with PBC [13]. At that time, OCA was the only available second-line therapy for PBC patients, and its unavailability in the EU posed a concern for both clinicians and UDCA non-responders, especially those who improved with OCA treatment or awaited treatment initiation. However, the recent conditional approval of two new agents, Seladelpar and Elafibranor, as second-line treatment for PBC patients, has provided new alternatives for these patients [14, 15].

Conclusions

The results of this case series support the growing real-world body of evidence indicating that OCA is an effective treatment for improving liver biochemistry in PBC patients, particularly when combined with UDCA. The observed reductions in ALP and liver enzymes, six months after the onset of treatment, are consistent with findings from larger clinical trials. Although the study’s small sample size and short follow-up period limit the conclusions that can be drawn, the findings suggest that OCA offers significant clinical benefit in managing PBC, especially in patients who are not fully responsive to UDCA monotherapy. Recent data from clinical trials have not confirmed long term clinical benefits of OCA therapy in PBC. Larger, long-term real-world follow-up studies are needed in order to determine whether the biochemical improvements seen with OCA treatment translate into meaningful clinical outcomes, as well as which patients might mostly benefit from UDCA and OCA combination therapy, and who might require different treatment options.

Conflict of interest disclosure

None to declare.

Declaration of funding sources

None to declare.

Author contributions

K. Papantoniou, C. Triantos conception and design; K. Papantoniou, E. Bourdalou, G. Geramoutsos, drafting of the article; C. Triantos critical revision of the article for important intellectual content; C. Triantos final approval of the article.

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