In pediatric patients, primary sclerosing cholangitis (PSC)-autoimmune hepatitis overlap is the primary phenotype linked to poor long-term outcomes, according to research published in Hepatology Research.

Researchers conducted a retrospective cohort study to determine the clinical features of pediatric patients with PSC in a Japanese cohort to evaluate long-term outcomes. Patients were diagnosed between April 1986 and March 2017 at a single center in Yokohama, Japan.

PSC diagnoses were made using a combination of cholangiography, liver histology, and biochemical findings. The study included 39 patients (22 boys and 17 girls; median age at diagnosis 9 years [interquartile range 6-13.5]) diagnosed with PSC.

In the cohort, twenty-six patients (67%) were asymptomatic at presentation. Nine patients had fever, 2 had pruritus, and 1 had jaundice. Phenotype diagnoses included PSC-autoimmune hepatitis, PSC-inflammatory bowel disease, and small-duct PSC, present in 33.3%, 94.8%, and 7.7% of patients, respectively.

At diagnosis, all 39 patients began ursodeoxycholic acid (UDCA) treatment, with no significant differences between phenotype; 11 patients underwent extreme high-dose treatment. Salazosulfapyridine treatment was undertaken in 37 patients, with 6 switched to mesalazine due to diarrhea. UDCA+5-aminosalicylic acid therapy with methylprednisolone pulse therapy protocol was started in all 9 patients with PSC-autoimmune hepatitis overlap. Three of these patients required additional treatment (cyclosporine A and cyclophosphamide).

At 1 year, the rate of achievement of normal alanine aminotransferase levels was “significantly lower” in patients with PSC-autoimmune hepatitis overlap compared with those with pure-PSC (23.1% vs 64%; P =.04). The achievement rate of median alanine aminotransferase levels was also significantly lower. The gamma-glutamyltransferase biochemical response was also lower in patients with PSC-autoimmune hepatitis overlap.

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Nine of the 39 patients underwent a liver transplant. Four patients died, and the 5-year liver transplant-free survival rate was 93.5%.

Univariate analyses using a Cox proportional hazard model were performed to determine the factors associated with liver transplant or death. Investigators found that PSC-autoimmune hepatitis overlap and total bilirubin >3 mg/dL at diagnosis were independently associated with poor prognosis. PSC-autoimmune hepatitis overlap was identified as the “single independent risk factor for [liver transplant] or death.”

Study limitations include the retrospective nature of the analysis, the small number of total patients included, and the inability of investigators to assess autoantibodies like antibodies to liver cytosol antigen type 1 and antisoluble liver antigen.

The researchers concluded that “the overall outcome of pediatric PSC in Japan is comparable to the outcomes in Western countries.” However, “PSC-[autoimmune hepatitis] overlap was associated with poor prognosis in our Japanese pediatric PSC patients, possibly due to resistance to immunosuppressive therapy. Geoepidemiological analyses are warranted for the evaluation of the phenotypes of pediatric-onset PSC and their long-term outcomes.”  

Reference

Umetsu S, Notohara K, Nakazawa T, et al. The long-term outcomes of pediatric-onset primary sclerosing cholangitis: a single center experience in Japan [published online August 13, 2019]. Hepatol Res. doi: 10.1111/hepr.13421