Treatment options for sclerosing cholangitis and macrophage activation

Seventy-five percent of children with sclerosing cholangitis will not respond to chemotherapy because the LCH is no longer active, but the fibrosis and sclerosis remain. Despite the limitations, liver biopsy may be the only way to distinguish active LCH from end-stage fibrosis. Liver transplant is the only alternate treatment when hepatic function worsens. A review of 60 patients with LCH (55 children) who underwent hepatic transplant for LCH-associated liver failure reported a 5-year survival rate of 82%. Posttransplant rejection occurred in 55% of patients, 22% of whom received a second transplant. The 5-year overall graft survival rate was 62% for patients who underwent deceased-donor liver transplant and 81% for patients who underwent living-donor liver transplant (not statistically significant). Nine patients died (15%). There was one case of posttransplant lymphoproliferative disease (PTLD), and no data on LCH recurrences. The authors conducted a literature review to identify an additional 50 patients with LCH who underwent a liver transplant. Of these patients, 47% experienced rejection, 11% had PTLD, and 8% had recurrent LCH. Seven patients (14%) with graft loss were treated with retransplant.[159][Level of evidence C2]

Case reports and case series have documented the efficacy of MAPK inhibitors for the treatment of progressive hepatic LCH.[148,160]

Some patients develop a macrophage activation of their marrow. This could be confusing to clinicians, who may think the patient has hemophagocytic lymphohistiocytosis (HLH) and LCH. The best therapy for this life-threatening manifestation is not clear because it tends not to respond well to standard HLH therapy. Clofarabine, anti-CD52 antibody alemtuzumab, or reduced-intensity allogeneic stem cell transplant could be considered.[161][Level of evidence C3] It is unknown whether newer HLH therapies, such as the antibody to interferon-gamma or the JAK-STAT inhibitor ruxolitinib, will be more effective in the LCH-macrophage activation than the above options.