Hepatic Sarcoidosis: Natural History and Management Implications

Abstract

Introduction: Hepatic granulomas are common in patients with sarcoidosis, but clinically significant liver disease is uncommon and poorly studied. We aimed to characterize the frequency and clinical course of hepatic sarcoidosis in an ethnically diverse population.Methods: This is a retrospective study including all cases of hepatic sarcoidosis in a single center. The median follow-up time was 49 months (4–121). Cases were identified based on ICD-9 and ICD-10 codes for granulomatous hepatitis, sarcoidosis, and hepatic sarcoidosis. The Chi-square and Wilcoxon-signed rank tests were used as indicated to assess for differences between groups.Results: Of 286 patients with sarcoidosis, 27 had hepatic involvement; 78% were female and 48% African American. The most common pattern of liver tests abnormalities was cholestatic. Ten patients had clinically significant hepatic involvement: cirrhosis in seven (25.9%), portal hypertension in nine (33%), and portal vein thrombosis in one (3.7%). Sex, race, and ethnicity were not associated with an increased risk of hepatic involvement or symptomatic hepatic sarcoidosis. Most patients received medical treatment, most commonly oral glucocorticoids. At the end of the follow-up period, all patients were alive but two had undergone liver transplantation due to complications of hepatic sarcoidosis. Three patients with hepatic sarcoidosis had initially been classified as AMA-negative PBC.Conclusions: Hepatic sarcoidosis was found in 9.4% of patients with sarcoidosis and was clinically significant in 37% of those. Identifying and monitoring hepatic sarcoidosis is crucial given its potential complications.

Hepatic Sarcoidosis: Current Concepts and Treatments

“…PH may complicate hepatic sarcoidosis and may be inaugural in numerous cases. PH affects 10 to 30% of cases of hepatic sarcoidosis in various studies 8,11,13,17,19,20 and may be revealed by esophageal varices with potential gastrointestinal bleeding. Pathogenesis of PH in sarcoidosis is unknown.…”

“…Histological features suggestive of sarcoidosis can be found in most cases. 19,28,30 It can also help to rule out other diagnoses. Prognostic factors of histological data have not been assessed.…”

“…8 However, among 21 patients with biopsy-proven sarcoid liver disease reported by Sedki et al, ALT and AST normalized in 83 and 67% of patients, respectively, during follow-up but CSs and biological agents were not significantly associated with improvement. 19 Moreover, spontaneous improvement of asymptomatic liver biological abnormalities has been reported in more than half of cases, which suggests treatment is not essential in many patients. 53 Impact of CSs on histological progression and hepatic fibrosis is unknown, as data are limited.…”

“…Azathioprine in association with CS showed its efficacy in reducing symptoms and LFT abnormalities in two retrospective studies. 14,19 Low-dose methotrexate has been associated with improvement in LFTs in patients with refractory sarcoidosis. 53 However, the choice of these drugs must be discussed in cases of significant hepatic fibrosis due to potential drug-induced hepatic toxicity and difficulty in surveillance.…”

Screening Sarcoidosis Patients for Occult Disease

“…[106][107][108] The most common serum liver function test abnormality with hepatic sarcoidosis is an elevated serum alkaline phosphate in isolation or coupled with a relatively smaller increase in transaminases. 109,110 Occasionally, the serum alkaline phosphatase may reach 5 to 10 times the upper limit of normal with hepatic sarcoidosis, and cholestatic symptoms such as pruritus may develop. 109 Although some have suggested that an elevated serum alkaline phosphatase in a sarcoidosis patient without an alternative etiology confirms liver sarcoidosis, 111 this approach is controversial.…”