Representative images of histological findings seen in liver biopsies from patients (P1-1, P2-1, P3-1, and P4-1) with biallelic mutations in GIMAP5. (A) P1-1’s liver biopsy shows lobular parenchyma devoid of any steatosis, hepatocytic ballooning, or acidophil necrosis. Minimal and focal lymphocytic infiltrates (arrow) are seen along with dilated channels at the periphery of the portal tracts, with some of them extending into the sinusoids (left panel; H&E stain). Middle panel reveals nodular architecture due to areas of regeneration consisting of thickened hepatic cell plates next to areas of atrophy without any intervening fibrosis (reticulin stain). Right panel shows few thin septa (in blue) in the left aspect of the picture (arrow) but lack of cirrhosis (trichrome stain). (B) P2-1’s liver biopsy shows largely unremarkable hepatocytes with occasional foci of lobular inflammation (arrow; left panel; H&E stain). Middle panel shows liver nodularity with zones of widened two-cell-thick plates consistent with hepatic regeneration bounded by narrow compressed liver cell plates (reticulin stain). Right panel shows periportal fibrosis (arrow; trichrome stain). (C) P3-1’s liver biopsy shows no significant abnormalities in the hepatocytes (left panel; H&E stain). Middle panel shows areas of regeneration consisting of thickened hepatic cell plates (reticulin stain). Right panel shows an area of hepatocyte loss with parenchymal collapse and fibrosis (arrow) but no evidence of cirrhosis (trichrome stain). (D) P4-1’s liver biopsy shows a portal tract with minimal and focal lymphocytic infiltrates (arrow). The lobular parenchyma is devoid of any steatosis, hepatocytic ballooning, or acidophil necrosis (left panel; H&E stain). Middle panel highlights an area of pericentral hepatocyte loss with parenchymal collapse and thin fibrous septa. The liver shows vague nodularity with areas of hepatic regeneration but no cirrhosis (reticulin stain). Right panel reveals few thin septa (blue) but lacks features of cirrhosis (trichrome stain). (E) Normal-appearing portal tract (oval) and a central venule (asterisk). The portal tract depicts a hepatic arteriole, bile duct, and portal venule. The portal venule is the largest structure with the widest lumen and a thin wall (H&E stain). Middle panel shows hepatic cords in a single thick cord plate. The central vein is seen near the center, and a portal tract is at the periphery (reticulin stain). Right panel shows normal architecture of the liver and no fibrosis (trichrome stain). Scale bars = 50 µm.