The clinical management of hepatic sarcoidosis: A systematic review

Abstract

Background: Hepatic sarcoidosis is an uncommon clinical condition in which clear recommendations are lacking in its treatment. We aimed to review systematically the literature on hepatic sarcoidosis treatment to guide clinicians.

Methods: Using MEDLINE, PubMed, CINAHL, Cochrane Library, and Google Scholar databases, we searched original articles on clinical studies reporting the outcome of adult hepatic sarcoidosis patients following treatment with various pharmacological agents. The primary end point was focused on assessing symptomatic relief and biochemical improvement posttreatment.

Results: Out of 614 retrieved references, 34 published studies were eligible, providing data for a total of 268 patients with hepatic sarcoidosis. First-line therapy with corticosteroids alone was reported in 187 patients, whilst ursodeoxycholic acid (UDCA) was used in 40 patients. Symptomatic and biochemical responses were reported among 113(60.4%) and 80(42.8%) cases of corticosteroids respectively, whereas UDCA showed a complete response in 23(57.5%) patients. Second-line therapy was used in steroid-refractory cases, with most cases being reported for azathioprine (n = 32) and methotrexate (n = 28). Notably, 15(46.9%) and 11(39.2%) patients showed both clinical and biochemical responses respectively. Biological therapy including anti-tumor necrosis factor (anti-TNF) was used as third line therapy in twelve cases with a 72.7% symptomatic and biochemical response rate each.

Conclusion: The quality of evidence for the treatment of hepatic sarcoidosis was poor. Nevertheless, it appears that corticosteroid or UDCA may be utilized as first-line therapy. For cases that are refractory to corticosteroids, steroid-sparing immunosuppressive agents and anti-TNF have shown some promising results, but further high-quality studies are required.

Keywords: anti‐TNF, Ursodeoxycholic acid; azathioprine; corticosteroids; hepatic sarcoidosis; methotrexate.

Figure 1

PRISMA flow diagram for the literature search in this study. From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. doi: 10.1136/bmj.n71. For more information, visit: http://www.prisma‐statement.org/.

Figure 2

Graphical summary of treatment efficacy for various drugs in hepatic sarcoidosis. *Cases on Mycophenolate mofetil, cyclophosphamide, chlorambucil, and adalimumab not shown due to small numbers. (a) biochemical improvement, symptomatic improvement. Abbreviations: CS, corticosteroids; UDCA, ursodeoxycholic acid. (b) symptomatic improvement, biochemical improvement. Abbreviations: AZA, azathioprine; IFX, infliximab; MTX, methotrexate.

Figure 3

Proposed treatment algorithm for hepatic sarcoidosis, based on available data from the current literature.