Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease

BACKGROUND/AIMS: The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH. METHODS: One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8+/-13.5 years, mean+/-SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea. RESULTS: According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis > or =2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH. CONCLUSIONS: Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.

Nonalcoholic fatty liver disease: histopathological evaluation and interobserver agreement

BACKGROUND: Nonalcoholic fatty liver disease comprises a spectrum of lesions ranging from steatosis to cirrhosis, with nonalcoholic steatohepatitis being the progressive form of the disease. Alcohol intake, viral hepatitis and other liver diseases must be excluded. Liver biopsy is the gold standard for diagnosis of the disease and is the only method able to differentiate nonalcoholic steatohepatitis from simple steatosis, to grade inflammation and to stage fibrosis. AIMS: To analyze the histopathological findings and evaluate interobserver agreement in biopsies previously diagnosed as steatosis or steatohepatitis. METHODS: Seventy needle biopsies were analyzed according to Brunt et al.(4), with modifications in the grading and staging components. Clinical data of patients were collected. Interobserver agreement was calculated based on histopathological findings. RESULTS: Mild nonalcoholic steatohepatitis (grade 1) was the most common form. If fibrosis was detected, stage 1 was the most frequent. Interobserver agreement was very good for macrovesicular steatosis (K W = 0,82) and good for lobular inflammation (K W = 0,68) and fibrosis (K W = 0,73). CONCLUSIONS: The classification of Brunt et al., with modifications, can be applied to diagnosis not only of nonalcoholic steatohepatitis but also of nonalcoholic fatty liver disease, representing a reliable method for use in the daily practice of pathologists.

INTRODUÇÃO: A doença hepática gordurosa não-alcoólica compreende um espectro de lesões que variam da esteatose à cirrose, sendo a esteatoepatite não-alcoólica a forma progressiva da doença. Uso de álcool, hepatites virais e outras doenças hepáticas devem ser excluídos. A biópsia hepática é o padrão-ouro para o diagnóstico da doença, sendo o único método capaz de diferenciar a esteatoepatite da esteatose, graduar a inflamação e estadiar a fibrose. OBJETIVOS: Analisar os achados histopatológicos e avaliar a concordância interobservador em biópsias previamente diagnosticadas como esteatose ou esteatoepatite. MATERIAIS E MÉTODOS: Setenta biópsias por agulha foram analisadas segundo Brunt et al.(4), com modificações nos componentes determinantes da atividade e no estadiamento. Os informes clínicos dos pacientes foram coletados. A concordância interobservador foi calculada com base nos achados histopatológicos. RESULTADOS: Esteatoepatite não-alcoólica discreta (grau 1) foi a forma mais comum. Se havia fibrose, o estágio 1 foi o mais freqüente. Concordância interobservador foi muito boa para esteatose macrovacuolar (KW = 0,82) e boa para inflamação lobular (KW = 0,68) e fibrose (KW = 0,73). CONCLUSÕES: A classificação de Brunt et al., com modificações, pode ser usada para o diagnóstico não somente da esteatoepatite não-alcoólica, mas também da doença hepática gordurosa não-alcoólica, representando método confiável para uso na rotina diária dos patologistas.

Demographic and clinicopathological characteristics of nonalcoholic fatty Liver disease in the East-Southeastern Anatolia regions in Turkey

To identify the demographic and Clinicopathological characteristics of patients diagnosed with nonalcoholic fatty liver disease [NAFLD] and the risk factors for fibrosis based on histopathological findings in East-Southeastern Anatolia regions in Turkey. The study included a total of 93 patients diagnosed with NAFLD from 5 different centers. Histopathological findings were evaluated by dividing them into four categories using Matteoni classifications. Cases with fibrosis were further evaluated using Brunt classifications. The patients with a nonalcoholic fatty liver were in the 3rd and 4th decade age groups. The mean age was 38 years, 76% of the patients were male, 85% were overweight, 37% were obese, 18% had type 2 diabetes mellitus, and 80.6% had hyperlipidemia. A multiple regression analysis showed that age, type 2 diabetes mellitus, and aspartate aminotransferase [AST] levels were linked with the severity of the disease. Of the 93 patients, 55 [59.1%] had fibrosis, of which 10.8% were classified as severe. The severity of fibrosis was significantly higher in obese patients. The risk factors for severity of NAFLD included advanced age, type 2 diabetes mellitus and serum AST level, while the risk factor for the severity of fibrosis was obesity