What situations can arise in PBC treatment with obeticholic acid? Answers provided by case studies from real practice at CKTCH

OCA is a hope for PBC if UDCA is not sufficient

PBC is known as a disease predominantly affecting women over 40. In older women, it progresses more slowly and mildly, while in younger women and men, it progresses rapidly, tends to be aggressive, and can eventually lead to liver cirrhosis with all its possible consequences. The average survival time for untreated patients is 9–10 years.

The first line of treatment for PBC patients is ursodeoxycholic acid (UDCA), and if they respond well, their life expectancy can be similar to that of the general population. Without an adequate response to UDCA, however, the risk of developing liver complications (ascites, variceal bleeding, and encephalopathy) increases, and if they reach severity, the risk of needing a liver transplant (LTx) or death rises soon after inadequate response to UDCA is confirmed. Therefore, second-line treatment – obeticholic acid (OCA) – is required for these patients as it has been proven to improve prognosis by reducing mortality and the inevitability of LTx.

The author then presented case studies highlighting potential pitfalls associated with using OCA in PBC treatment.

Case Study 1

The first case was of a patient where Dr. Husová said she would never indict OCA again. It involved a woman who had slightly elevated liver tests in 1995 as a 40-year-old. In 1996, she was diagnosed with PBC based on liver biopsy and the presence of antimitochondrial antibodies (AMA). The patient also had hypertension and depressive syndrome and underwent a hysterectomy in 1995.

PBC treatment began with UDCA at a dose of 1000 mg, about 15 mg/kg (she weighed 50 kg at a height of 158 cm). Subjectively, she had no issues, and objectively, there were no pathological findings. However, the condition progressed despite the therapy. In 2015, the first decompensation with esophageal variceal bleeding was detected, indicating the development of liver cirrhosis. Her bilirubin concentration was 47 μmol/l, albumin levels were still normal, and ALP was 6.41 μkat/l. Symptomatic therapy continued.

In January 2019, further progression and decompensation of liver cirrhosis occurred, along with a small ascites. The patient had higher bilirubin levels and lower albumin levels by then. She stabilized and started second-line treatment, OCA, in October 2019 at a dose of 5 mg twice a week. However, after three months, a slight increase in bilirubin and ALP concentrations was noted, so OCA was discontinued (reimbursement conditions not met – no 10% decrease in ALP). Rapid decompensation occurred, ascites progressed, and variceal bleeding recurred. In January 2020, the patient was placed on the waiting list for LTx, which she underwent on July 1, 2021.

In January 2023, her liver functions were completely normal with no signs of cholestasis, no recurrence of the underlying disease, and she was doing very well.

The presenter added that current data suggest treatment benefits for patients with advanced compensated liver disease, but the risks of treatment significantly increase in case of decompensation, which was not known at the time of OCA administration for this patient. In 2021, the American Association for the Study of Liver Diseases (AASLD) issued a new recommendation not to administer OCA to patients with current or previous decompensated liver cirrhosis.

Case Study 2

Dr. Husová demonstrated a case of a patient who responded well to OCA but did not meet reimbursement conditions with a woman born in 1963. In 2010, she was referred to CKTCH for a cholestatic liver lesion. Based on AMA positivity and liver biopsy, a diagnosis of PBC was made, and the patient began taking UDCA at a dose of 1000 mg, i.e., 15 mg/kg at a body weight of 63 kg. She also had hypertension and hypothyroidism, with an ultrasound in 2010 showing a small liver hemangioma and hepatomegaly. She only felt fatigue subjectively and had no significant pathological findings objectively.

In 2019, under CKTCH treatment, she had compensated liver disease with ALP 8.88 μkat/l and severe fibrosis (F3), which did not progress until 2022. After three months of OCA treatment, ALP levels dropped by 43%, so she could continue using it. However, after a year, despite further ALP reduction, the therapy had to be discontinued as she did not achieve ALP levels below 1.67 times the upper limit of normal. A year after OCA discontinuation, while taking UDCA, progression was noted (increase in ALP levels), and on January 26, 2023, Fibroscan indicated cirrhosis (F4). After discontinuing OCA, progression in liver elasticity and ALP values occurred over about 1.5 years.

According to the presenter, the next steps for this patient are uncertain. She is taking UDCA and awaiting LTx.

Case Study 3

As the third case, Dr. Husová presented a patient with an ideal response to OCA. A woman born in 1965 has been monitored since 2003 for PBC diagnosed based on the presence of AMA and biopsy. She had no comorbidities and took UDCA 1500 mg (20 mg/kg).

In November 2019, she was indicated for OCA due to inadequate UDCA response. After three months of therapy, a 13% ALP decrease was confirmed, and the patient continued the treatment. After one and two years, ALP values were below 1.67 times the upper limit of normal, allowing her to continue this treatment.

Conclusion

OCA, which is tied to specialized centers for administration, positively affects important prognostic markers of PBC, such as alkaline phosphatase (ALP) and bilirubin levels. However, it is unsuitable for patients with decompensated liver cirrhosis or previous decompensation. It is the only drug that must be discontinued if insurance reimbursement conditions are not met, even if liver test values decrease and liver elasticity stabilizes. Meeting reimbursement conditions is necessary not only when starting treatment but also during it, after three months and then every six months.

Eva Srbová
proLékaře.cz editorial team

Source: Husová L. Primary biliary cholangitis: a serious diagnosis – case studies. Hradec Gastroenterology Days, March 24, 2023.