Clinical Characteristics and Outcome of Hepatic Sarcoidosis: A Population-Based Study 1976–2013

Abstract

Objectives Data on clinical manifestations and outcome of hepatic sarcoidosis are scarce. This study aimed to use a population-based cohort of patients with incident sarcoidosis to better describe the characteristics of hepatic sarcoidosis. Methods A cohort of incident cases of sarcoidosis in Olmsted County, Minnesota, United States from 1976 to 2013 was identified from the database. Diagnosis was verified by individual medical record review. Confirmed cases of sarcoidosis were then reviewed for liver involvement. Data on clinical manifestations, imaging study, liver biochemical tests, treatment and outcome were collected. Cumulative incidence of cirrhosis adjusted for the competing risk of death was estimated. Results A total of 345 cases of incident sarcoidosis were identified. Of these, 19 cases (6%) had liver involvement (mean age 46.1 years, 53% female and 79% Caucasian). Most patients had asymptomatic liver disease and were discovered in pursuit of abnormal biochemical tests and imaging studies. Alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) were elevated in the majority of patients (88% and 90%, respectively). Elevated transaminases were less common and less severe. About half of patients had abnormal imaging study with hypodense nodular lesions being the most common abnormality (6 patients) followed by hepatomegaly (3 patients). Liver biopsy revealed non-caseating granuloma in 88% (14 of 16 patients). A total of 4 patients developed cirrhosis. Conclusions Involvement of the liver by sarcoidosis was seen in 6% of patients with sarcoidosis. The majority of patients were asymptomatic. Elevated ALP and GGT were the most common abnormal biochemical tests. Liver biopsy revealed non-caseating granuloma in almost all cases. Cirrhosis was seen in a significant number of patients. Generalizability of the observations to other populations may be limited as the studied population was predominantly Caucasian. The prevalence of liver disease may be higher in more diverse populations.

Hepatic Sarcoidosis: Current Concepts and Treatments

“…14 Actually, most patients with hepatic sarcoidosis remain asymptomatic (up to 79% in clinical series). 8 Hepatomegaly and splenomegaly were previously reported in 50 to 70% of cases in historical series, 17,18 but appear to be lower in most recent series. 8 Thus, diagnosis of a hepatic manifestation is fortuitous in numerous cases diagnosed by liver function test (LFT) abnormalities or liver biopsy in case of sarcoidosis with extrahepatic manifestations.…”

“…8 Hepatomegaly and splenomegaly were previously reported in 50 to 70% of cases in historical series, 17,18 but appear to be lower in most recent series. 8 Thus, diagnosis of a hepatic manifestation is fortuitous in numerous cases diagnosed by liver function test (LFT) abnormalities or liver biopsy in case of sarcoidosis with extrahepatic manifestations. Other symptoms include weight loss, fever, and abdominal pain, 8-10 similar to hepatitis manifestations.…”

“…Autopsy series have shown hepatic involvement in 50 to 70% of patients with sarcoidosis, [5][6][7] but clinically significant hepatic sarcoidosis has been reported in only 11.5 to 30% of cases. [8][9][10][11] Thus, the incidence of hepatic involvement seems to be underestimated. Although this is considered as a common extrapulmonary manifestation, the lack of specificity of symptoms or biomarkers and frequency of asymptomatic patients could lead to misdiagnosis.…”

“…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.…”

“…28 Noncaseating granulomas are the cornerstone of sarcoidosis diagnosis and have been found on liver biopsy in 71 to 100% of sarcoidosis patients. [8][9][10][11]18,31 Mononuclear cells, mainly macrophages, that can sometimes form multinucleated giant cells, surrounded by a rim of CD4þ T lymphocytes and fibroblasts, represent typical granulomas (►Figs. 1 and 2).…”