Adult nonalcoholic fatty liver disease (NAFLD) is characterized by absent or mild portal chronic inflammation (CI); in children, portal CI may be predominant. This study correlated clinical features with portal CI. Centrally-graded biopsies and temporally-related clinical parameters from 728 adults and 205 children. From the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) were evaluated. Mild, more than mild and no portal CI were found in 60%, 23% and 16% of adult biopsies and 76%, 14% and 10% of pediatric biopsies. Autoantibodies, and elevated alanine aminotransferase were not associated with portal CI. Clinical features associated with "more than mild" in adults were older age (P < 0.0001), female gender (P ‫؍‬ 0.001), higher body mass index (P < 0.0001), elevated insulin levels (P ‫؍‬ 0.001), higher homeostasis model assessment of insulin resistance score (HOMA-IR) (P < 0.0001), and medications used for NAFLD (P ‫؍‬ 0.0004), diabetes (P < 0.0001), and hypertension (P < 0.0001). "More than mild" in the pediatric biopsies correlated with younger age (P ‫؍‬ 0.01), but not with body mass index, insulin or HOMA-IR. In both groups, lobular and portal inflammation scores had no association, but there was an association with definite steatohepatitis (P < 0.0001). Features associated in the adult biopsies with "more than mild" were steatosis amount (P ‫؍‬ 0.01) and location (P < 0.0001), ballooning (P < 0.0001), and advanced fibrosis (P < 0.0001). In the pediatric biopsies, "more than mild" was associated with steatosis location (P ‫؍‬ 0.0008) and fibrosis score (P < 0.0001), specifically, the portal/periportal fibrosis or greater fibrosis) (P < 0.01). Conclusion: Increased portal CI is associated with many clinical and pathologic features of progressive NAFLD in both adults and children, but not with ALT, autoantibodies, or lobular inflammation. More than mild portal CI in liver biopsies of untreated NAFLD may be considered a marker of advanced disease. (HEPATOLOGY 2009;49:809-820.)

Review of the medical records of 43 patients with common variable immunodeficiency (CVID) and 23 patients with X-linked agammaglobulinemia (XLAG) revealed a high incidence of chronic gastrointestinal complaints, most commonly diarrhea. Thirty-eight biopsies, four small-bowel resection specimens, and one autopsy from 10 patients with CVID and one patient with XLAG showed a wide range of abnormalities. A pattern resembling acute graft-versus-host disease, with apoptotic bodies and lymphocytes in crypts, was seen in the stomach (four patients), small bowel (three patients), and colon (three patients). Small-bowel specimens from three CVID patients with malabsorption showed mild to severe villous atrophy. Three CVID patients had Giardia in biopsies. Two cases of small bowel lymphoma associated with nodular lymphoid hyperplasia were identified in CVID patients. One patient's small bowel contained foamy histiocytes in the lamina propria, resembling Whipple's disease or chronic granulomatous disease, with numerous apoptotic bodies in crypts. Ultrastructurally, the histiocytes contained cellular debris. The patient with XLAG had recurrent fissuring necrosis of small bowel resembling Crohn's disease; a patient with CVID had colitis with features similar to ulcerative colitis. Poorly formed granulomas were seen in the stomach (one CVID patient) and the colon (two CVID patients). Lymphocyte populations were dominated by T cells; B cells were scarce except in lymphoid follicles in CVID patients with nodular lymphoid hyperplasia. Patients with CVID and XLAG manifest a spectrum of abnormalities in the gastrointestinal tract, with patterns superficially resembling graft-versus-host disease, inflammatory bowel disease, and Whipple's disease, but often lacking some of the diagnostic features of the diseases. Many of the CVID patients with chronic gastrointestinal complaints (62%) also had evidence of autoimmune phenomena, suggesting that in some patients the inflammatory process in the gastrointestinal tract has an autoimmune component.

Histological response to neoadjuvant CRT--as measured by residual tumor load--may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.