Liver involvement with Langerhans cell histiocytosis in adults

Abstract

Background and aims: Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement.

Methods: We conducted a retrospective analysis of all adults with LCH (≥ 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022.

Results: Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18-66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAFN486_P490 (29.6%), BRAFV600E (18.5%), and MAP2K1 (14.8%).

Outcomes: After a median 40 months' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550-7.388, P = .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, P = .010) correlated with superior PFS versus chemotherapy.

Conclusions: In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy.

Keywords: Langerhans cell histiocytosis; live; prognosis; survival.

Figure 1.

Representative magnetic resonance imaging (MRI) features of liver Langerhans cell histiocytosis. Each column represents an individual patient. T1-weighted (A-D), T2-weighted (E-H), and diffusion weighted (I-K) images (DWI). (A, E, I) Heterogenous parenchymal changes with diffuse small lesions (long/slightly long T1, long/slightly long T2, hyperintense DWI). (B, F, J) Hepatomegaly with diffuse patchy/nodular lesions (slightly long T1, slightly long T2, and hyperintense DWI). (C, G, K) Atrophic left lobe, widened porta hepatis, and irregular liver edge. Patchy lesions along portal tracts/bile ducts (slightly short T1, short T2, and hypointense DWI). Dilated intrahepatic bile ducts. (D, H) Round lesion (long T1, long T2) and other isointense T1/long T2 lesions.

Figure 2.

Mutational profiles identified by targeted sequencing of 183 genes with FFPE biopsies from 54 patients with Langerhans cell histiocytosis.

Figure 3.

Treatments and outcomes of adults with patients with LCH with liver involvement. Abbreviations: AraC, cytarabine; CA, cladribine and cytarabine; Cda, cladribine; CS, corticosteroid; IMIDs, immunomodulatory drugs; LCH, Langerhans cell histiocytosis; LH, local hospital; MA, methotrexate/cytarabine; MEKi, MEK inhibitors; MTX, methotrexate; PD, progression disease; RD, lenalidomide and dexamethasone; TCD, thalidomide, cyclophosphamide and dexamethasone; VP, vindesine and prednisone.

Figure 4.

Overall survival (OS) and progression-free survival (PFS) (A), PFS according to different levels of hsCRP (B), PFS according to numbers of abnormal liver function tests at baseline (C), and PFS according to first-line treatment (D). Abbreviation: IMIDs, immunomodulatory drugs.