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.)
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the UnitedStates. The association between NAFLD and quality of life (QOL) remains unclear. These data are important to estimate the burden of illness in NAFLD. The aim was to report QOL scores of adults with NAFLD and examine the association between NAFLD severity and QOL. QOL data were collected from adults with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network using the Short Form 36 (SF-36) survey, and scores were compared with normative U.S. population scores. Liver biopsy histology was reviewed by a central pathology committee. A total of 713 subjects with NAFLD (male ؍ 269, female ؍ 444) were included. Mean age of subjects was 48.3 years; 61% had definite nonalcoholic steatohepatitis (NASH), and 28% had bridging fibrosis or cirrhosis. Diabetes was present in 27% of subjects. Subjects with NAFLD had worse physical (mean, 45.2) and mental health scores (mean, 47.6) compared with the U.S. population with (mean, 50) and without (physical, 55.8; mental, 52.5) chronic illness. Subjects with NASH reported lower physical health compared with subjects with fatty liver disease without NASH (44.5 versus 47.1, P ؍ 0.02). Subjects with cirrhosis had significantly (P < 0.001) poorer physical health scores (38.4) than subjects with no (47.6), mild (46.2), moderate (44.6), or bridging fibrosis (44.6). Cirrhosis was associated with poorer physical health after adjusting for potential confounders. Mental health scores did not differ between participants with and without NASH or by degree of fibrosis. Conclusion: Adults with NAFLD have a significant decrement in QOL. Treatment of NAFLD should incorporate strategies to improve QOL, especially physical health. (HEPATOLOGY 2009;49:1904-1912
Background-Although many predictors of disease severity of nonalcoholic fatty liver disease (NAFLD) have been proposed, studies of the potential effects of specific environmental exposures on human NAFLD are lacking. Smoking increases insulin resistance. Given the pathophysiological role of insulin resistance in NAFLD, characterization of the influence of smoking in NAFLD is warranted.
Reported are the clinical and pathologic features of glycogenic hepatopathy, a pathologic overloading of hepatocytes with glycogen that is associated with poorly controlled diabetes mellitus. Fourteen cases were studied by stains, including hematoxylin and eosin, trichrome, periodic acid-Schiff, and periodic acid-Schiff with diastase. Ultrastructural analysis was performed in 2 cases. Medical records were reviewed for clinical presentations, laboratory findings, and clinical outcomes. The individuals ranged from 8 to 25 years of age. All had type I diabetes mellitus with poor glycemic control. The clinical presentations included hepatomegaly, abdominal pain, and elevated transaminases (range, 50-1600 IU/L). The transaminases were dramatically elevated in 3 cases to greater than 10 times the upper limit of normal. All biopsies showed diffusely pale staining hepatocytes on hematoxylin and eosin stains, with excessive glycogen accumulation demonstrated by periodic acid-Schiff stains. Ultrastructural examination revealed marked glycogen accumulation in the cytoplasm and nuclei. Most cases showed no evidence for fatty liver disease: steatosis was absent in 12 of 14 cases, simple steatosis was seen in 1 of 14 cases, and mild steatohepatitis was present in 1 of 14 cases. Mallory hyaline was absent in all cases, acidophil bodies were only rarely seen, and inflammation was absent or minimally present. Fibrosis was typically absent, with only 2 cases demonstrating focal mild fibrosis. Three patients had adequate follow-up and demonstrated improvement of liver enzyme levels with control of blood glucose. We conclude that glycogenic hepatopathy can cause hepatomegaly and significant transaminase elevations in individuals with type I diabetes mellitus. The pathology is distinct from steatohepatitis.
An insulinoma is a rare pancreatic endocrine tumor that is typically sporadic, solitary, and less than 2 cm in diameter. Fewer than 5% of insulinomas are larger than 3 cm. Ninety percent or more of all insulinomas are benign. Larger tumors are more likely to be malignant. We report a case of a giant pedunculated insulinoma, measuring 9 cm in diameter and weighing 100 g, with amyloid deposits accounting for 70% of the tumor volume. At the time of operation, no local invasion or metastatic disease was identified. On pathological evaluation, the tumor was classified as an insulinoma of uncertain biological behavior. In addition to describing the clinical presentation and operative findings, criteria for determining malignancy are outlined, a detailed pathological description is presented, and the 2000 World Health Organization Classification for Pancreatic Endocrine Neoplasms is reviewed.
Diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) phenotype is believed to confer a better prognosis than DLBCL with an activated B-cell (ABC) phenotype. Previous studies have suggested that nuclear factor-κB (NF-κB) activation plays an important role in the ABC subtype of DLBCL, whereas c-REL amplification is associated with the GCB subtype. Using immunohistochemical techniques, we examined 68 newly diagnosed de novo DLBCL cases (median follow-up 44 months, range 1 to 142 months) for the expression of c-REL, BCL-6, CD10, and MUM1/IRF4. Forty-four (65%) cases demonstrated positive c-REL nuclear expression. In this cohort of patients, the GCB phenotype was associated with a better overall survival (OS) than the non-GCB phenotype (Kaplan–Meier survival (KMS) analysis, p = 0.016, Breslow–Gehan–Wilcoxon test). In general, c-REL nuclear expression did not correlate with GCB vs. non-GCB phenotype, International Prognostic Index score, or OS. However, cases with a GCB phenotype and negative nuclear c-REL demonstrated better OS than cases with a GCB phenotype and positive nuclear c-REL (KMS analysis, p = 0.045, Breslow–Gehan–Wilcoxon test), whereas in cases with non-GCB phenotype, the expression of c-REL did not significantly impact the prognosis. These results suggest that c-REL nuclear expression may be a prognostic factor in DLBCL and it may improve patient risk stratification in combination with GCB/non-GCB phenotyping.
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