Hepatic disease in CVID is characterized by a combination of sinusoidal fibrosis and nodular regenerative hyperplasia

Background: Common variable immunodeficiency (CVID) is an immunodeficiency syndrome of heterogeneous etiology, characterized by failure of B-cell maturation and deficient immunoglobulin production. CVID can be associated with distinct histologic patterns of organ involvement. CVID involving the liver is a known phenomenon, but the histologic characteristics are not well described in the literature. Design: We identified six liver biopsies taken between 2013 and 2018 at our institution. These biopsies came from five patients with known CVID. Histologic slides were reviewed, and pathologic and clinical features were evaluated for each case. Results: ALT, AST, and alkaline phosphatase levels were elevated in one, five, and five of six cases, respectively, with median values of 37 U/L (normal 10-55 U/L), 54 U/L (10-40 U/L), and 193 U/L (45-115 U/L). Three of the five patients had biopsies demonstrating CVID involvement of other organs, of which two were granulomatous-lymphocytic interstitial lung disease and one was CVID enteritis. All liver biopsies of CVID demonstrated a distinct pattern of predominantly centrizonal sinusoidal fibrosis, with panlobular involvement in four of six cases (67%). A nodular regenerative hyperplasia (NRH)-like pattern of nodularity was present in all cases. Bridging fibrosis and cirrhosis were not identified in any case. Portal hepatitis was present in all six cases (5 with mild inflammation, and 1 with moderate inflammation). Lobular hepatitis was also identified in all cases (5 mild, 1 moderate). Lymphocyte trafficking was identified in five of six cases (83%). Plasma cells were not identified in any biopsy. Additional findings included granulomatous or giant cell inflammation, identified in four biopsies (67%). Two of six cases also demonstrated focal copper deposition. Conclusions: Hepatic disease in CVID is commonly associated with mild elevations in AST and alkaline phosphatase and histologically demonstrates a distinctive pattern of involvement on liver biopsies, characterized by a combination of sinusoidal fibrosis, NRH-like changes, lymphocyte trafficking, absence of plasma cells, and mild lobular lymphocytic infiltrates.