Most patients infected with hepatitis C virus (HCV)Chronic hepatitis develops in 60% or more of individdevelop chronic hepatitis. Unfortunately, the pathologi-uals after acute hepatitis C virus (HCV) infection. 1-4 cal evolution of this disease over time is not completely Based on clinical and biochemical follow-up, an estiunderstood. We studied 70 HCV-positive patients, from mated 50% of cases of chronic hepatitis C have nonprowhom 2 to 10 liver biopsy specimens (mean, 3.9) had gressive disease, with the other half insidiously probeen obtained during an interval of 1 to 26 years (mean, gressing to cirrhosis. 5 The rate of progression and 8.8 years). Each biopsy specimen was evaluated indepen-histopathological pathways to cirrhosis have not been dently by four pathologists who each provided a numeri-clearly delineated, in part because of the short periods patients (50%) developed cirrhosis. Cirrhosis developedIn contrast to a recent multicenter study in the in all patients with a high final grade (¢5) of necroin-United States 6 that failed to show increased long-term flammation on initial biopsy who were followed for 10 mortality among patients with transfusion-associated years and in 96% of patients with an intermediate final non-A, non-B hepatitis, there has been a marked ingrade (3.5-4.9) who were followed for 17 years. Only crease in mortality in Japanese patients with transfu-30.4% of patients with low final grade (°3.4) on initial sion-acquired chronic hepatitis C and cirrhosis, chiefly biopsy developed cirrhosis after 13 years. All patients from hepatocellular carcinoma. 7-10 Therefore, in Japan, with evidence of septal fibrosis with incomplete nodu-as in other regions where HCV infection is prevalent, larity (stage 3.0-3.4) in the initial biopsy progressed to it is desirable to understand the natural pathological unequivocal cirrhosis by 10 years. The rate of progreshistory of chronic HCV infection. Accordingly, we sesion to cirrhosis was accelerated in patients whose inilected for review a group of patients with chronic hepatial biopsies showed high-grade and -stage lesions. This study demonstrates the importance of grading and stag-titis C who had undergone multiple liver biopsies over ing liver biopsy lesions in chronic hepatitis C, particu-a long period of follow-up (as long as 26 years). The larly for patients with high-grade necroinflammation, biopsies were assessed to determine the changes of septal fibrosis, and regions of nodularity on initial bi-chronic hepatitis during its progression to cirrhosis, opsy who are at high risk of developing advanced cirrho-the speed (time frame) of progression to cirrhosis, and sis in the ensuing decade. (HEPATOLOGY 1996;23:1334-histological features 11-14 that may be predictive of prog- 1340.)nosis. PATIENTS AND METHODSPatients. The initial study group comprised 80 patients with HCV infection who had been continuously followed (durAbbreviation: HCV, hepatitis C virus.ing the period 1967-1993) for more than 5 and up to 26 years. pital, Ohmura, and Toranomon Hosp...

Objective: To evaluate the diagnostic accuracy of liver cirrhosis by imaging modalities, including CT, MRI and US, compared to results obtained from histopathological diagnoses of resected specimens. Materials and Methods: CT, MRI and US examinations of 142 patients with chronic liver disease who underwent surgery for complicated hepatocellular carcinoma (<3 cm in diameter) in 10 institutions were blindly reviewed in a multicenter study by three radiologists experienced in CT, MRI and US. The images were evaluated for five imaging parameters (irregular or nodular liver surface, blunt liver edge, liver parenchymal abnormalities, liver morphological changes and manifestations of portal hypertension) using a severity scale. The diagnostic imaging impression score was also calculated. Patients were histologically classified into chronic hepatitis (CH; n = 54), liver cirrhosis (LC; n = 71) and pre-cirrhosis (P-LC; n = 17) by three pathologists, independently, who reviewed the resected liver specimens. The results of the three imaging methods were compared to those from histological diagnoses, and a multivariate analysis (stepwise forward logistic regression analysis) was performed to identify independent predictive signs of cirrhosis. The diagnostic efficacies for LC and early cirrhosis were also compared among CT, MRI and US using a receiver-operating characteristic (ROC) curve analysis. Results: The differences in the five imaging parameters evaluated by CT, MRI and US between LC and CH were statistically significant (p < 0.001) except for the manifestations of portal hypertension on US. Irregular or nodular surface, blunt edge or morphological changes in the liver were selected as the best predictive signs for cirrhosis on US whereas liver parenchymal abnormalities, manifestations of portal hypertension and morphological changes in the liver were the best predictive signs on MRI and CT by multivariate analysis. The predictive diagnostic accuracy, sensitivity and specificity in discriminating LC from CH based on the best predictive signs were 71.9, 77.1 and 67.6% by CT; 67.9, 67.5 and 68.3% by MRI, and 66.0, 38.4 (lower than CT and MRI, p =0.001) and 88.8% (higher than CT and MRI, p =0.001)by US. According to the imaging impression scoring system, diagnostic accuracy, sensitivity and specificity were 67.0, 84.3 and 52.9% by CT; 70.3, 86.7 and 53.9% by MRI, and 64.0, 52.4 (lower than CT and MRI, p =0.0001) and 73.5% (higher than CT and MRI, p < 0.003) by US. ROC analysis showed that MRI and CT were slightly superior to US in the diagnosis of LC but no statistically significant difference was found between them. For the pathological diagnosis of P-LC, cirrhosis was diagnosed in 59.5, 46.7 and 41.7% of the P-LC cases by US, CT and MRI, respectively, with no significant difference among these methods. Conclusion: US, CT and MRI had different independent predictive signs for the diagnosis of LC. MRI and CT were slightly superior to US in predicting cirrhosis, especially regarding sensitivity. Noninvasive imaging techniqu...

Biliary lining epithelia of the bile ducts in biliary diseases are known to have intraepithelial atypical/proliferative lesions related to the development of cholangiocarcinoma. The purpose of the present study was to determine the histological criteria for these lesions based on interobserver agreement. Digital images of 30 intraepithelial atypical/proliferative lesions in the stone-containing intrahepatic bile ducts of hepatolithiasis (30 cases) were sent to 10 pathologists. At first, 10 pathologists made a diagnosis (either of reactive/regenerative change, low-grade or high-grade biliary intraepithelial neoplasia (BilIN-1 and BilIN-2), or in situ carcinoma (BilIN-3)) based on their own criteria. The histological criteria for these four lesions were then determined, and the digital images of the same lesions with proposed criteria were re-distributed. Interobserver agreement on these four lesions was slightly improved (kappa = 0.44, first diagnosis; 0.49, second diagnosis) and intraobserver agreement was 'almost perfect' (kappa = 0.82 at both first and second diagnosis). Interobserver agreement between BilIN-1 and BilIN-2 and that between BilIN-2 and BilIN-3 were 'moderate', although the agreement between regenerative/reactive change and BilIN-1 was 'fair'. In this report, we propose histological criteria for reactive/regenerative change, BilIN-1, BilIN-2 and BilIN-3. Improvement of interobserver agreement suggests their applicability in diagnostic and research fields.

of apoptosis such as portal vein thrombosis (PVT). Portal Ischemia is known to be a cause of hepatocellular apoptosis vein ligation is well-known to cause apoptosis in an experiand atrophy in experimental animals, but the effect of vascular mental model, 1,2 but the association of ischemia and obstruction on such lesions in the normal or cirrhotic human apoptosis has not been reported in human livers.3 liver has not been studied. ity, and acute and healed portal vein thrombosis (PVT). LargeThe effect of portal vein obstruction on the cirrhotic liver numbers of apoptotic cells were found in livers with acute has not been studied. PVT (17.2/medium-power field [MPF]) and in infarcts of ZahnThe aim of the present study was to examine the role of caused by obstruction of portal veins (PVs) by tumor (16.4/ ischemia in the pathogenesis of apoptosis and atrophy in the MPF). Smaller numbers of apoptotic cells were found in cirhuman liver. Explants, segmental resections, and autopsies rhosis of various etiologies (3.8-10.0/MPF) and rarely in norwere reviewed to establish the prevalence and histological mal livers (0.16/MPF). Evidence of healed PVT was found features of apoptosis, atrophy, and nodular hyperplasia, and in 47% of cirrhotic livers and was associated with nodular to correlate these features with portal vein disease, disease hyperplasia (58% vs. 32%, P õ .01) and focal atrophy (79% activity, and cirrhosis. vs. 49%, P õ .002). Apoptotic cells were found equally in those with and without healed PVT (40% vs. 38%, not signifi- MATERIALS AND METHODS cant). These observations suggest that apoptosis is a transient response to acute ischemia and that atrophy and nodularTwo sets of liver specimens were studied. The first was a series hyperplasia are chronic responses to ischemia. Vascular ob-of 100 large specimens selected to include a range of diagnoses, struction may be an important cause of the apoptosis and with or without cirrhosis, to be correlated with apoptotic cells and atrophy. The second set was composed of 118 consecutive explants atrophy, which are found in nodular regenerative hyperplasia with cirrhosis, for correlation of healed PVT with apoptosis, atro-(NRH), infarct of Zahn, chronic hepatitis, and cirrhosis. (HEPphy, and nodular hyperplasia.

tion. The patients all had hepatic and systemic sarcoidosis. The Sarcoidosis often involves the liver with mild elevation of main clinical and morphological features are summarized in Table serum enzymes and granulomas histologically. Rarely, chronic 1. Tissue blocks were obtained from the peripheral parenchyma of cholestasis, portal hypertension, cirrhosis, or nodular hyper-both lobes, as well as from all major vessels and ducts. Sections plasia may be found. The pathogenesis of the portal hyperten-were stained with hematoxylin-eosin and elastic trichrome stains. sion and of the cirrhosis are not understood, in part because Selected blocks were stained with orcein, periodic acid-Schiff-dialarge samples of tissue have seldom been described. We de-stase, iron, and reticulin. Portal and hepatic veins were classified scribe the clinical and anatomic findings of four patients with as large if the outside diameter was larger than 3 mm, medium if sarcoid liver disease in whom the whole livers were available it was between 0.2 and 3 mm, and small if it was smaller than 0.2 mm. Granulomatous involvement was graded 0 through 3. Grade for examination. One patient had cirrhosis, one had diffuse and focal fibrosis were caused by ischemia secondary to pri-before death. A lung biopsy revealed sarcoid-type granulomas, and mary granulomatous phlebitis of portal and hepatic veins. The steroid therapy was begun. She died suddenly at home. portal hypertension in two patients was likely secondary to At autopsy, granulomas were found in many organs, including portal vein thrombosis, because cirrhosis was absent at the liver, spleen, lungs, heart, and lymph nodes. The liver parenchyma onset of variceal bleeding. (HEPATOLOGY 1997;26:554-560.) was grossly normal except for several localized regions of parenchymal extinction (Fig. 1). In grossly normal regions, granulomas were rarely seen, and most portal and hepatic veins were normal. In did not allow analysis of the form or histogenesis of sarcoid-involved, the medium portal or hepatic veins usually had lumina related liver disease. In the present study of four whole livers, that were compromised by intimal fibrosis, and small veins usually we show that granulomatous phlebitis of portal and hepatic had lumina that were obliterated by granuloma(s) or by fibrous veins may cause multifocal ischemia, leading to parenchymal tissue (Fig. 1). The granulomas in the large and medium hepatic extinction and cirrhosis.veins could be seen to involve intima, media, and adventitia. DuctsIt has been speculated that portal hypertension occurs as of all sizes were usually normal.Case 2. A 35-year-old black man with a 1-year history of congesa complication of cirrhosis or as a result of portal granulomas tive heart failure and dilated cardiomyopathy died suddenly.compressing and restricting blood flow through small portal At autopsy the liver showed moderate widespread chronic passive veins. [1][2][3][4][5][9][10][11][12] In our study, clinical portal hypertension was congestion with patchy sinusoidal...