Journal of Pathology and Translational Medicine

Original Articles

A scoring system for the diagnosis of non-alcoholic steatohepatitis from liver biopsy: Kyoungbun Lee, Eun Sun Jung, Eunsil Yu, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Woo Sung Moon, Jin Sook Jeong, Cheol Keun Park, Jae-Bok Park, Dae Young Kang, Jin Hee Sohn, So-Young Jin; J Pathol Transl Med. 2020;54(3):228-236. Published online April 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.03.07

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Background
Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis.
Methods
Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses (‘not-NASH,’ ‘borderline,’ and ‘NASH’) of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system.
Results
Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52–0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH.
Conclusions
A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.

Citations

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Marlone Cunha-Silva, Luíza D. Torres, Mariana F. Fernandes, Tirzah de M. Lopes Secundo, Marina C.G. Moreira, Ademar Yamanaka, Leonardo T. Monici, Larissa B. Eloy da Costa, Daniel F. Mazo, Tiago Sevá-Pereira
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Interobserver Agreement on Pathologic Features of Liver Biopsy Tissue in Patients with Nonalcoholic Fatty Liver Disease: Eun Sun Jung, Kyoungbun Lee, Eunsil Yu, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Woo Sung Moon, Jin Sook Jeong, Cheol Keun Park, Jae-Bok Park, Dae Young Kang, Jin Hee Sohn, So-Young Jin; J Pathol Transl Med. 2016;50(3):190-196. Published online April 18, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.01

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Abstract PDF

Background
The histomorphologic criteria for the pathological features of liver tissue from patients with non-alcoholic fatty liver disease (NAFLD) remain subjective, causing confusion among pathologists and clinicians. In this report, we studied interobserver agreement of NAFLD pathologic features and analyzed causes of disagreement.
Methods
Thirty-one cases of clinicopathologically diagnosed NAFLD from 10 hospitals were selected. One hematoxylin and eosin and one Masson’s trichrome-stained virtual slide from each case were blindly reviewed with regard to 12 histological parameters by 13 pathologists in a gastrointestinal study group of the Korean Society of Pathologists. After the first review, we analyzed the causes of disagreement and defined detailed morphological criteria. The glass slides from each case were reviewed a second time after a consensus meeting. The degree of interobserver agreement was determined by multi-rater kappa statistics.
Results
Kappa values of the first review ranged from 0.0091–0.7618. Acidophilic bodies (k = 0.7618) and portal inflammation (k = 0.5914) showed high levels of agreement, whereas microgranuloma (k = 0.0984) and microvesicular fatty change (k = 0.0091) showed low levels of agreement. After the second review, the kappa values of the four major pathological features increased from 0.3830 to 0.5638 for steatosis grade, from 0.1398 to 0.2815 for lobular inflammation, from 0.1923 to 0.3362 for ballooning degeneration, and from 0.3303 to 0.4664 for fibrosis.
Conclusions
More detailed histomorphological criteria must be defined for correct diagnosis and high interobserver agreement of NAFLD.

Citations

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Ultrastructural Study of Alcohol-Induced Gastric Mucosal Change of Rat.: Kam Rae Cho, Kun Young Kwon, Eun Sook Chang; Korean J Pathol. 1993;27(4):362-370.

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Abstract PDF: In an attempt ultrastructural study of alcohol-induced gastric mucosal change, we selected sixty Sprague-Dawley rats. The rats were administrated with 4 ml of 10% and 40% ethanol enterically and examined by light and electron microscopy. Light microscopically, the thickness of the mucus layer of both 10% and 40% ethanol groups was decreased. The antral mucosa revealed focal inflammatory infiltrates, disturbed glandular arrangements, and significant decrease of mucosal thichness and proper glands. On scanning electron microscopy, flattened or swollen mucosal epithelium and irregularly distributed gastric pits were seen in both experimental groups, and these changes were more severe in the groups of higher concentration and longer duration. On transmission electron microscopy, mitochondrial abnormalities with myelin-like materials and dilatation of endoplasmic reticulum and cytoplasmic blebs were observed. Also the mucus cells show significantly decreased mucus globules, increased fat vacuoles, and large autophagic vacuoles. These alterations were similar to those produced by ethanol in the liver and small intestine. This study indicates that, prolonged administration of ethanol induced chronic gastritis, especially chronic atrophic gastritis.

Liver Cirrhosis: Etiological diagnosis and morphological characteristics of 369 biopsy-proven cases.: Eun Kyung Han, Chanil Park, Sang In Lee; Korean J Pathol. 1990;24(4):412-422.

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Abstract PDF: To pursue a desirable format for the pathological diagnosis of liver cirrhosis, the authors attempted to classify 369 biopsy-proven cirrhosis on the basis of etiology and made effort to find out the morphological characteristics of each category. About 735 of total cases were HBsAg seropositive postnecrotic cirrhosis. Alcholic cirrhosis ws the second most frequent type, although accounted only 6.8%. In about 15%, the etiology was not known. Excluding the congenital biliary atresia, chronic biliary obstruction appeared to be a rare cause of cirrhosis among these biopsied cases. Of the HBsAg positive postnecrotic cirrhosis, the eAg seropositive cases tended to be micronodular and to show a higher necroinflammatory activity, in contrast to eAg seronegative cases and those complicated by hepatocellular carcinoma (HCC), suggesting that the loss of eAg is followed by a decrease of the destructive activity, active regeneration of hepatocytes and finally the development of HCC. alcoholic cirrhosis was micronodular in 64% and revealed histologic evidences of alcoholic liver disease in most cases. The results indicate that etiological diagnosis can be made in most cases of cirrhosis by the morphological characteristics and the precise clinical informations, including those on the NANB virus and the inborn error of metabolism, and that the pathological diagnosis should be more comprehensive, implicating the etiology, the nodular size and the necroinflammatory activity.

Alcoholic Type Cirrhosis Following Side to Side Ileo-Transverse Colon Anastomosis.: Kwang Hwa Park, Kwang Hyup Han, Chan Il Park; Korean J Pathol. 1990;24(2):148-152.

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Abstract PDF: A case of micronodular cirrhosis of the alcoholic type developed following an intestianl bypass surgery in a 47 year-old nonalcoholic male patient is presented. The patient denied any drug use of a long duration and had no diabetes mellitus. Five years before, a side to side ileo-transverse colon anastomosis had been performed for perforated intestinal tuberculosis at 1 m proximal to the ileocecal valve, bypassing a short segment of ileum (about 1.5 m) and transverse colon. The ileum distal to the perforated site had been found completely stenosed. He was severely lean with evidences of nutritional deficiency such as low serum levels of the albumin and vitamin B12. The liver biopsy showed a fatty change, Mallory bodies and perihepatocellular collagenosis within the cirrhotic nodules. The present case suggests that, when there are blind loop formation and nutritional deficiency, hepatic changes identical to those following jejunoileal bypass could develop even by reduction of a shore segment of the small intestine.

Histologic Pattern of Alcoholic Liver Disease in Korea.: Chan Il Park, Ho Guen Kim, So Young Jin, Mi Kyung Lee, Yoo Bock Lee; Korean J Pathol. 1989;23(3):292-304.

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Abstract PDF: To elucidate the histologic pattern of alcoholic liver disease (ALD) in Korea, liver biopsies from 173 chronic alcoholics with clinical liver diseases were classified according to the pathologic parameters. One hundred and seventeen cases, the sum of 91 of 116 serum HBsAg negative and 26 of 57 HBsAg positive patients, had the histologic evidence of ALD. Fatty change(23.9%), alcoholic fibrosis (AF)(23.1%) and cirrhosis (23.1%), comprised the three major ALDs, and only 8.5% of cases fit the criteria of alcoholic hepatitis. Chronic sclerosing hyaline disease (CSHD), chronic active alcoholic hepatitis (CAAH) and AF, where non-cirrhotic fibrosis is the predominant change, comprised 44.5% of ALD. Both features of ALD and HBV liver disease (HBV-LD) were found in 17 cases that included 8 AF and 7 cirrhosis. These 17 patients tended to consume less alcohol than patients with other types of pure ALD except alcoholic heaptitis. Patients with the serum HBsAg positive ALD (37.4years) were about 8 years younger than those with the serum HBsAg negative ALD (45.1years). More or less fatty change and foamy degeneration were seen in 77.4% and 31.6% of ALD respectively. Mallory bodies, megamitochondria, iron deposition and perihepatocellular fibrosis were found in 20.5%, 29.9%, 42.7% and 77.8%, respectively. These findings indicate that non-cirrhotic chronic ALD such as CSHD, CAAH and AF are the important histologic patterns of ALD in Korea, and that chronic alcohol consumption and HBV may act synergistically in developing liver disease.

A Clinicopathologic Study on Chronic Alcoholic Hepatitis.: Gi Yeong Huh, Sun Kyung Lee; Korean J Pathol. 1988;22(4):393-403.

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Abstract PDF: This study was undertaken to evaluate the significant diagnostic points of chronic alcoholic hepatitis (CALH) among clinicopathologic findings observed. The specimens used in this study were 20 cases of CALH and 28 cases of chronic active viral hepatitis (CAVH), which were diagnosed at our University Hospital during 9 years period from 1978 to 1987. In these cases, comparative analysis of age and sex distribution, major clinical manifestations, and laboratory and histopathologic findings was performed. The results obained were summarized as follows: Among 20 cases of CALH, the sex distribution was 15 in male and 15 in female with a ratio of 3:1. The range of age distribution was wide from third to seventh decade. There was no recognizable special point about the age and sex distribution of CALH, compared with cases of CAVH. Major clinical manifestations of CALH were hepatomegaly (85%), jaundice (75%) and abdominal pain (50%). Also there was no recognizable special point about the major clinical manifestations of CALH, compared with cases of CAVH. Abnormal values of major laboratory items in CALH were observed in activities of serum r-GTP (100%), SGOT (95%), SGPT (75%) and serum alkaline phosphatase (60%), and total serum bilirubin (60%). Compared with CAVH in major laboratory findings, the significant diagnostic items of CALH were the activities of serum r-GTP and alkaline phosphatase. The characteristic histopathologic findings of CALH, which were compared with CAVH and observed in liver parenchyma, were fatty change (100%), cytoplasmic ballooning and coagulation (100%), delicate fibrosis (85%), bile stagnation (35%), and Mallory bodies (20%), and that observed blurring of limiting plate (60%) in portal and periportal areas.

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