High-dose ursodeoxycholic acid successfully treats overlap syndrome

Abstract

The first-line treatment regimen of overlap syndrome includes both ursodeoxycholic acid (UDCA) and corticosteroids, with or without azathioprine (AZA).^{1, 2} Herein, we present a high-dose ursodeoxycholic acid successful treatment in a patient with overlap syndrome (primary biliary cholangitis [PBC] with or without autoimmune hepatitis [AIH]).

This is a 45-year-old female, weighing ~60 kg, with a lengthy history of dyslipidemia and liver cirrhosis, presenting with abnormal transaminase levels managed by an endocrinologist. She was referred to a gastroenterologist due to elevated levels of gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), and anti-mitochondria antibody (AMA), measuring 2243 U/L, 854 U/L, 153 U/L, 330 U/L, and positive; 1:160, respectively. However, its antinuclear antibody (ANA), and anti-smooth muscle antibody (ASMA) were all negative, which could not significantly prove the diagnosis of AIH. And the client refused to undergo liver biopsy. However, an ultrasound scan of the patient's liver, gallbladder, pancreas, and spleen revealed mild parenchymal liver disease (acoustic radiation force impulse: 1.61 m/s [F1]). Therefore we diagnosed her with PBC with or without AIH.

The initial therapeutic approach involved UDCA at 200 mg thrice daily (10 mg/kg), and prednisolone at 20 mg thrice daily, leading to a reduction in GGT and ALP to 972 and 296 U/L, respectively. Attempts to discontinue medications resulted in a rebound effect, with GGT and ALP peaking at 1993 and 707 U/L. Subsequently, UDCA was reintroduced at 300 mg thrice daily, omitting prednisolone or immune compression, as the patient declined such interventions due to concerns regarding drug adverse reactions and concurrent polypharmacy. Therefore, we continue to treat patients with UDCA.

Within a month, her GGT and ALP decreased by around half to 783 and 325 U/L, maintaining stability over the subsequent 3 months. Progressing the therapeutic strategy, the UDCA dose was increased to 400 mg thrice daily, leading to a further decrease in GGT and ALP to 399 and 206 U/L in 2 months. To achieve sustained disease control, a consistent upward titration of UDCA was implemented, reaching 600 mg thrice daily, resulting in a GGT and ALP reduction to 148 and 108 U/L (Figure 1). Although her ALP and GGT had significantly decreased, these levels remained abnormal, and her HRF1 was 1.05. As a result, subsequent UDCA titration to 35 mg/kg divided into 700 mg thrice daily produced a rapid decline in GGT and ALP to 130 and 94 U/L within 2 weeks, marking the lowest levels observed in recent years. However, the patient did not complain of any side effects.

Treatment of PBC with UDCA has been shown to have a beneficial effect and highly safe effect on the disease progression. Regarding the dose of UDCA in patients with PBC, 14–16 mg/kg/day of UDCA for at least 2 years has demonstrated significant biochemical and histological improvement.³ Another randomized trial conducted demonstrated that UDCA doses of 13–15 mg/kg/day showed the highest rates of biochemical improvements compared with higher levels (23–25 mg/kg/day) and lower (5–7 mg/kg/day) doses.⁴ However, this patient had to take 35 mg/kg/day (700 mg thrice daily) to significantly improve the biochemical values. Therefore, UDCA can be administered at a dose that “at least does no harm”,⁵ and if this therapy fails to elicit an adequate biochemical response, a corticosteroid (e.g., prednisone 10–15 mg/kg/day) is added. However, in this case, because the patient refused to take steroids, high doses of UDCA were administered to achieve a therapeutic biochemical response. To our knowledge, administration of such high doses of UDCA to treat PBC is the first to be reported.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The authors declare no conflicts of interest.

We received written consent from the patient for publication.