The guidelines of the European Association for the Study of the Liver (EASL) provide recommendations for the treatment of PSC, PBC and AIH. However, these are not always up to date: while PBC received its most recent update in 2022, the guidelines for autoimmune hepatitis are already eight years old. New research findings are therefore expected to lead to a rethink in some areas.
Autoimmune liver diseases such as primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are serious conditions that can develop into cirrhosis. In the end, a liver transplant is often the only option. What updates and new recommendations the guidelines provide for treatment were discussed at Visceral Medicine 2023.
Primary sclerosing cholangitis (PSC)
The old terminology of “dominant strictures” has been replaced by the new definitions “high-grade stricture” (>75% reduction in duct diameter [DHC oder Ductus hepaticus]) and “relevant stricture” (high-grade stricture with signs or symptoms of obstructive cholestasis and/or bacterial cholangitis). Patients with such strictures have a poorer overall survival than those without such strictures. “Behind these terms are the patients who may be suffering from cholangiocarcinoma,” explained Dr. Marcial Sebode, I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf [1].
A central symptom of PSC is pruritus. The new recommendations are based primarily on the multicenter, randomized, double-blind FITCH study, in which bezafibrate (400 mg/d) was used against placebo in various cholestatic liver diseases (PBC, PSC and secondary sclerosing cholangitis). The aim was to improve pruritus using the visual analog scale. The positive results (Fig. 1) have led to bezafibrate being classified by the EASL as a first-line treatment for PSC. Rifampicin is recommended in the second line, which Dr. Sebode believes is a good alternative. “Which medication you choose always depends on the respective accompanying symptoms and risk profiles in each individual case.”
With regard to surveillance of colorectal carcinoma in PSC-associated cholitis, but also cholangiocarcinoma, the recommendations are to perform an MRI/MRCP and/or ultrasound once a year in PSC patients with disease of the large bile ducts, regardless of the stage of the disease. In addition, those patients in whom gallbladder polyps ≥8 mm are detected or those with smaller polyps that grow over time should undergo a cholecystectomy. “However, study data give us a sobering result: this screening for cholangiocarcinoma using MRI/MRCP only ensures long-term survival in a minority of cases,” said Dr. Sebode. There is a great need for biomarkers to further improve early detection.
Primary biliary cholangitis (PBC)
The first-line therapy for PBC is still ursodeoxycholic acid (URSO, 13-15 mg/kgKG/d). “It’s a very simple therapy that is very consistently recommended in national and international guidelines. But how is it implemented in reality?” asked the expert, referring to a study carried out in Germany with the Techniker Krankenkasse health insurance company: Although well tolerated and inexpensive, URSO was only used in 80% of those insured (Fig. 2). “And particularly alarming: it is used even less in older patients.”
PBC treated with URSO can remain a progressive disease. All PBC patients should be screened for risk factors for progressive disease. Please note:
- Young age at the time of manifestation
- male gender
- Stage at the time of manifestation
- biochemical and serological indices/markers before and after the start of URSO therapy.
There are several scores for evaluation. Dr. Sebode advised looking at ALP and bilirubin after six months and taking other risk factors into consideration. “The trend is to start these patients on second-line therapy earlier and earlier.” Complications such as pruritus, fatigue or bone density must also always be taken into account in the further course of treatment.
Autoimmune hepatitis (AIH)
Dr. Sebode began by saying that a lot of the old familiar things about AIH need to be questioned. When diagnosing suspected autoimmune hepatitis, autoantibodies should be measured at the beginning. SLA and IgG are very helpful as markers, “but then a liver biopsy is absolutely necessary”. In histology, interface hepatitis is one of the classic criteria in the context of chronic manifestations, as are markers such as hepatocellular rosette formation or emperipolesis. “Take a close look at the guideline recommendations to see how many pathologists were involved, these were individual cases,” says the expert. In a new study with 17 international experts, a closer look was taken at whether these supposedly specific markers emperipolesis and rosetting are actually specific for AIH. “Hardly any pathologist believes in this,” concluded Dr. Sebode.
With regard to the first-line treatment of AIH, a recent multicenter intervention study from the Netherlands compared MMF + remission induction (prednisolone) vs. classic first-line therapy with azathioprine + prednisolone (n=35 in each case). Both the response rate with MMF was better and the side effect rate lower compared to azathioprine, so that changes can also be expected in future guidelines with regard to the first-line treatment of AIH.
Congress: Viszeralmedizin 2023
Sources:
- Sebose M: Vortrag «Autoimmune Lebererkrankungen»; Sitzung «Die wichtigsten neuen internationalen GI-Leitlinien 2023»; Viszeralmedizin 2023, Hamburg, 15.09.2023.
- De Vries E, Bolier R, Goet J, et al.: Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial. Gastroenterology 2021; 160: 134–743; doi: 10.1053/j.gastro.2020.10.001.
GASTROENTEROLOGIE PRAXIS 2023; 1(2): 33–34
