Hepatic abnormalities in patients with chronic granulomatous disease

Abstract

Chronic granulomatous disease (CGD) is a rare congenital disorder characterized by repeated bacterial and fungal infections. Aside from a high incidence of liver abscess, little is known about hepatic involvement in CGD. The aim of this study was to describe the spectrum of liver abnormalities seen in CGD. The charts of 194 patients with CGD followed at the NIH were reviewed, with a focus on liver abnormalities. Liver enzyme elevations occurred on at least one occasion in 73% of patients during a mean of 8.9 years of follow-up. ALT elevations were generally transient. Although transient alkaline phosphatase (ALP) elevations were also common, persistent ALP elevations lasting up to 17.6 years were seen in 25% of patients. Liver abscess occurred in 35% of patients. Drug-induced hepatotoxicity was documented in 15% of patients but likely occurred more frequently. Hepatomegaly was found in 34% and splenomegaly in 56% of patients. Liver histology showed granulomata in 75% and lobular hepatitis in 90% of specimens. Venopathy of the portal vein was common (80%) and associated with splenomegaly. Venopathy of the central vein was also common (63%) and was associated with the number of abscess episodes. Nodular regenerative hyperplasia (NRH) was seen in 9 patients, including 6 of 12 autopsy specimens. C hronic granulomatous disease (CGD) is a rare inherited disorder occurring in 1 in 250,000 individuals. 1 The underlying defect is a loss or inactivation of a component of the reduced NADPH complex, resulting in a defective oxygen metabolic burst with inadequate production of superoxide and peroxide and, perhaps most importantly, an inability of phagocytic cells to kill certain bacteria and fungi. 2 These defects predispose affected individuals to recurrent infectious complications and significantly reduced long-term survival. 3 Four principal CGD genotypes have been described, with important differences in phenotypic expression. Because the gp91 phox genotype is X-linked and accounts for 70% of patients in large cohort studies, CGD has a significant male predominance. 4 The other described genotypes, p22 phox , p47 phox , and p67 phox , are autosomal recessive. 4 In addition to being more common, X-linked CGD (gp91 phox ) portends a worse prognosis with a higher annual mortality compared with the other genotypes. 1 The reduced NADPH is composed of cell membrane (p22 phox , gp91 phox ) or cytoplasmic moieties (p47 phox , p67 phox ). 1 Although pulmonary infections predominate in CGD, with 79% of a 368-patient registry reporting a history of pneumonia, other sites are also commonly affected, including suppurative adenitis (53%), subcutaneous abscess From the

Identification of high-risk group and therapeutic options in children with liver abscess

“…CGD is an important cause of LA, and LA is observed in nearly a third of patients with this condition [14]. Although most cases have a history of recurrent infections and multisystem disease, a small percentage of patients may present for the first time with LA [25].…”

Abnormal liver function in common variable immunodeficiency disorders due to nodular regenerative hyperplasia

“…The presence of CD8 + T cells in the liver sinusoids in some (14 of 44) patients with NRH has led to the suggestion that NRH may be the result of chronic cytotoxic T cell infiltration of the sinusoidal epithelium [19]. Association with granuloma is interesting, as NRH has been reported in 4·6% of patients with chronic granulomatous disease, another primary immunodeficiency, but no mechanism was suggested [20].…”

Granulomatous liver disease

“…Other rheumatologic diseases, such as Churg-Strauss syndrome, are rarely associated with granulomas in the liver, but there are sporadic case reports of complications (eg, Budd-Chiari syndrome) occurring in such patients [37]. Chronic granulomatous disease (CGD) is a rare inherited disorder caused by a defect of the reduced NADPH complex and resultant loss of a macrophage's capacity to kill phagocytized bacteria and fungi [38,39]. The disease is characterized by repeated infections.…”

“…The disease is characterized by repeated infections. Although it is rare, CGD should be considered in the differential diagnosis of patients with recurrent infections, as hepatic granulomas are observed in about 75% of patients, especially those with portal or lobular chronic hepatitis [39].…”