Person:

Mueller, Jessica L

OBJECTIVES: Soluble CD163 (sCD163), a marker of Kupffer cell activation detectable in serum, correlates with inflammation and fibrosis in chronic viral hepatitis, but its role in nonalcoholic fatty liver disease is unknown. We hypothesized that sCD163 would correlate with nonalcoholic fatty liver disease activity and fibrosis. METHODS: Liver biopsies and serum were obtained from 145 obese subjects undergoing gastric bypass surgery. Subjects were divided into four groups based on fibrosis stage and nonalcoholic fatty liver disease activity score (NAS); Group 1: F0, NAS=0; Group 2: F<2, 0<NAS<5; Group 3: NAS≥5, F<3; or Group 4: F≥3, any NAS. Serum sCD163 and the monocyte/macrophage marker sCD14 were measured by enzyme-linked immunosorbent assay. Relationships between sCD163, sCD14, fibrosis stage, and NAS were examined. Area under the receiver operating charateristic for the diagnosis of nonalcoholic steatohepatitis based on the Clinical Research Network definition was calculated. RESULTS: sCD163 increased with progressive liver histology, with lowest values in normal histology and highest levels in those with nonalcoholic steatohepatitis and advanced fibrosis (Group 1: 552 ng/ml, Group 2: 721 ng/ml, Group 3: 803 ng/ml, and Group 4:1,031; P=0.001). sCD14 also differed significantly across groups (Group 1: 1,877 ng/ml, Group 2: 1632 ng/ml, Group 3: 1,706 ng/ml, and Group 4: 2111; P=0.008, respectively). sCD163 correlated with steatosis grade (P<0.001), lobular inflammation (P=0.033), and hepatocyte ballooning (P<0.001). In a multivariable ordered logistic regression model, there was a significant association between every 100 ng/ml increase in sCD163 and higher fibrosis stage, with an odds ratio of 1.16 (95% confidence interval 1.02–1.31), P=0.020. The odds ratios of the association between every 100 ng/ml increase in sCD163 and higher NAS was 1.17 (95% confidence interval 1.04–1.32), P=0.010. A sCD163-based predictive score demonstrated an area under the receiver operating charateristic of 0.70 (95% confidence interval: 0.58–0.82) for the diagnosis of nonalcoholic steatohepatitis. Soluble CD14 did not correlate with fibrosis stage or NAS. CONCLUSIONS: In obese subjects, serum sCD163, but not sCD14, correlated with fibrosis stage and NAS. These data support a role for activated Kupffer cells in the pathogenesis of nonalcoholic steatohepatitis and fibrosis, and suggest potential clinical utility for assessment of sCD163 levels.

Purpose: The prognosis of gastric cancer patients is substantially better in Asia than in the West. Genetic, environmental, and treatment factors have all been implicated. We sought to explore the extent to which the place of birth and the place of treatment influences survival outcomes in Korean and US patients with localized gastric cancer.

Patients and Methods: Patients with localized gastric adenocarcinoma undergoing potentially curative gastrectomy from 1989 – 2010 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry and from two single-institution databases from the US and Korea. Patients were categorized into three groups: KK (Koreans born and treated in Korea), KUS (Koreans born in Korea but treated in the US), and W (white Americans born and treated in the US), and overall survival rates were compared.

Results: The final cohort consisted of 16,622 patients: 3,984 (24.0%) KK, 1,046 (6.3%) KUS, and 11,592 (69.7%) W patients. KK patients had longer unadjusted median and 5-year overall survival rates (100.6 months, 72.5%) than KUS (52 months, 47.2%) and W (18 months, 16.4%; p<0.001 for all comparisons) patients. This finding persisted on subset analyses of stage IA patients, patients without cardia/GEJ tumors, patients with >fifteen examined lymph nodes, and patients treated at a US center of excellence. On multivariable analysis, KUS (HR 1.98, 95% CI 1.54-2.55, p<0.001) and W (HR 5.01, 95% CI 4.15-6.06, p<0.001) patients had an increased risk of mortality when compared to KK patients.

Conclusions: Both the place of birth and the place of treatment significantly contribute to the improved prognosis of patients with gastric cancer in Korea relative to those in the US, implicating both nature and nurture in this phenomenon.