Mo1001 Nodular Regenerative Hyperplasia: Many Ways to Get There

Introduction: Nodular Regenerative Hyperplasia (NRH) is a rare noncirrhotic portal hypertensive liver disease characterized by the diffuse transformation of hepatic parenchyma into regenerative nodules without fibrosis. Although the specific etiology has yet to be elucidated, NRH has been associated with various diseases, conditions and medications. Thus, whether NRH occurs from a single unifying pathophysiologic process or multiple different processes is still uncertain. Aims: To characterize biochemical, radiological, and histologic markers of liver disease in patients (pts) with and without NRH in multiple disease cohorts. Methods: Pts with chronic granulomatous disease (CGD), sickle cell disease (SCD), systemic mast cell disease (SMCD), common variable immunodeficiency disease (CVID) and sporadic cases of NRH underwent hepatologic evaluation and liver biopsy for clinical care purposes were evaluated with biomarkers of liver disease, radiologic imaging and histopathologic analysis. Results: 137 pts were evaluated and 56 (41%) were diagnosed with NRH histologically. Of those with NRH, 11 (20%) had CGD, 22 (39%) SCD, 7 (13%) SMCD, 12 (21%) CVID and 4 (7%) sporadic disease. Age at biopsy across all NRH cohorts was significantly older compared to the non-NRH population (mean 40 vs. 33 years, p=0.0128). Patients with NRH had significantly higher alkaline phosphatase (197 vs. 190 U/L, p=0.01), increased liver volumes (2152 vs. 1166 cm3, p=0.01) and increased spleen volumes (after excluding SCD) (1071 vs. 410 cm3, p=0.01), which negatively correlated with platelets ( ρ -0.58, p= 0.002). In the SCD cohort, pts with NRH had increased gamma-glutamyltransferase (128 vs. 67 U/L, p=0.03) and increased lactate dehydrogenase (432 vs. 322 U/L, p=0.01). On histologic evaluation, SCD-NRH pts had increased lobular inflammation (p=0.04). SMCDNRH pts had increased portal and peri-portal inflammation (p=0.005 and p=0.01, respectively), veno-occlusive changes (p=0.04), portal venopathy (p=0.001) and sinusoidal dilation (p=0.03). Conclusions: Despite parallels in clinical disease presentation, histopathologic examination of NRH in separate disease cohorts suggests different mechanistic pathways. Given the potential for multiple etiologies, NRH may be more common than previously thought. Further investigation should focus on the underlying disease process as it may provide a window into biology.