Results :
Of the 8 patients with a diagnosis of LCH, active disease was present in 6, and 2 patients were referred after completion of chemotherapy with cirrhosis and portal hypertension. (Table 1). The median age of onset of symptoms of LCH was 13.5 months (3 to 26 months). The median age of diagnosis was 25 months and the median interval between the onset of symptoms of LCH and its diagnosis was 10 months (1 to 15 months).
The common clinical presentations of LCH included hepatomegaly (100%), scaly lesions of the scalp (75%), skin rash (75%), splenomegaly (75%) and lytic bone lesions (50%). Liver biopsy revealed features of large duct obstructive cholangiopathy with portal fibrous expansion, and bile ductular proliferation without active infiltration by Langerhans cells One patient had Langerhans cells which were positive for CD1a . The median PELD score of patients with active disease was 21 (4 – 31.4) and those with burnt-out disease was 2.2.
The flow of patients is depicted in Figure1. 4 patients each were fitting into Category 1(Patients 1,2,3 and 4) and Category 2 (Patients 5,6,7 and 8) (Table 1) as per the previously mentioned classification. In category 1, patient 1 and 2 who had completed chemotherapy 95 and 183 months prior, presented with compensated cirrhosis and portal hypertension. They underwent FDG-PET screening to make sure there is no active disease and were offered LT. Patient 3 and 4 with active LCH and compensated cirrhosis were started on standard Vinblastine based chemotherapy. They tolerated the chemotherapy and underwent LT after completion course of drug regimen.
All patients in Category 2, i.e Patients 5,6,7 and 8 had active disease. Patient 5 was started on standard Vinblastine based protocol and child had deterioration of his liver function and died of gram negative sepsis. We changed our policy to use low dose Cytarabine instead of Vinblastine, which is less hepatotoxic for category 2 patients. The modified regimen was subsequently started in 3 patients.18 Of the three patients, one (patient 8) defaulted therapy and was lost to followup. Patient number 6 achieved remission after 1 cycle of induction and patient number 7 achieved remission after 3 cycles of induction therapy. Both underwent liver LT and then completed one year maintenance phase of chemotherapy (Table 1). Hence 2 out of 6 patients underwent chemotherapy in the post LT period.
The median time of LT from time of diagnosis was 28 months (2 – 195 months) for the whole cohort. Median Duration of ICU stay and hospital stay were 4 & 12 days respectively. There were no episodes of vascular, biliary or immunological complications.
The liver explants showed greenish discolouration macroscopically (Figure 3E, 3F) Light microscopy revealed biliary pattern cirrhosis with ulceration in large ducts, biliary sludge and duct loss (Figure 3G, 3H). No significant CD1a or CD 207 positive Langerhans cells were identified in the explants – indicating LCH in remission
Post-LT patient and graft survival was 100% at a median follow-up of 36 months (18 to 80 months). None of the patients had recurrence of LCH in the graft or extrahepatic sites.