Ultrasonographic assessment of liver fibrosis with computer-assisted analysis of liver surface irregularities.

PURPOSE: The goal of this study was to evaluate the diagnostic accuracy of a software program that automatically analyzes the liver surface to diagnose significant fibrosis, by comparing it to the subjective analysis of a radiologist and to transient elastography (Fibroscan(®)). PATIENTS AND METHODS: One hundred fourteen patients with chronic liver disease were included in the study. They underwent liver biopsy, FibroScan(®) and ultrasonographic examination of the liver surface. The liver surface was analyzed by a software program that gave a score of surface irregularities. This evaluation was compared to subjective analysis by a radiologist expert in liver imaging and by two general radiologists. RESULTS: Fifty percent of the patients had significant fibrosis according to the METAVIR score. The AUROC for the diagnosis of significant fibrosis by the software program was 0.80 (95%CI: 0.71-0.87), which was equivalent (P=0.86) to that of FibroScan(®) (0.81; 95%CI: 0.71-0.89). Results of the subjective analysis by the expert radiologist were poorer than those of the software analysis (P=0.02) (AUROC=0.66; 95%CI: 0.56-0.75). Interobserver agreement among radiologists was poor (0.25

[Assessment of functional activity of phagocytic system in patients suffered from Dupuytren's contracture with hepatic fibrosis].

Dupuytren's contracture--a pathology that should not be seen as an isolated lesion tendon-aponeurotic structures of the palmar surface of the hand, but as a disease that requires careful research and a comprehensive, differentiated approach to treatment. The aim of the study was to investigate the functional activity of the phagocytic system of Dupuytren's contracture patients with chronic hepatitis and liver fibrosis in liquidators of the CHNPP accident consequences. The resulting study 188 patients aged 45-65 years showed the correlation of the data of the functional activity of phagocytic system with degree of liver fibrosis, thus objectively assess the patient's condition and make the appropriate correction in the diagnostic criteria as well as in medical and rehabilitative programs.

Liver function assessment with three (13)C breath tests by two-point measurements.

In this study, we performed three breath tests - l-[1-(13)C ]phenylalanine breath test (PBT), l-[1-(13)C ] methionine breath test, and [(13)C]methacetin breath test (MethaBT) - in patients with chronic liver disease to determine the optimal timing of expired air collection for diagnosing chronic liver disease and evaluating the grade of fibrosis. The subjects were 61 adults with normal livers, 98 chronic hepatitis patients, and 91 liver cirrhosis patients. We investigated the relationships of breath test results with routine biochemical tests and the Child-Pugh score, as well as the diagnostic capacities of the breath tests for liver dysfunction/cirrhosis and grade of liver fibrosis. For the diagnosis of liver cirrhosis and correlations with liver fibrosis, the accuracy of the PBT at 30 min (PBT30) was similar to that of the MethaBT at 15 min (Metha15). For liver function assessment by two-point measurement with (13)C breath tests, we recommend the PBT30 and the Metha15.

Assessment of chronic hepatitis and fibrosis: comparison of MR elastography and diffusion-weighted imaging.

OBJECTIVE: The purpose of our study was to compare the utility of MR elastography (MRE) and diffusion-weighted imaging (DWI) in characterizing fibrosis and chronic hepatitis in patients with chronic liver diseases. SUBJECTS AND METHODS: Seventy-six patients with chronic liver disease underwent abdominal MRI, MRE, and DWI. Severities of liver fibrosis and chronic hepatitis were graded by histopathologic analysis according to standard disease-specific classifications. The overall predictive ability of MRE and DWI in assessment of fibrosis was compared by constructing a receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC) on the basis of histopathologic analysis. RESULTS: Using ROC analysis, MRE showed greater capability than DWI in discriminating stage 2 or greater (≥ F2), stage 3 or greater (≥ F3), and cirrhosis (≥ F4), shown as significant differences in AUC (p = 0.003, p = 0.001, and p = 0.001, respectively). Higher sensitivity and specificity were shown by MRE in predicting fibrosis scores ≥ F2 (91% and 97%), scores ≥ F3 (92% and 95%), and scores F4 (95% and 87%) compared with DWI (84% and 82%, 88% and 76%, and 85% and 68%, respectively). Although MRE had higher ability in identification of liver with fibrosis scores ≥ F1 than DWI, a significant difference was not seen (p = 0.398). Stiffness values on MRE increased in relation to increasing severity of fibrosis confirmed by histopathology scores; however, a consistent relationship between apparent diffusion coefficient (ADC) values and stage of fibrosis was not shown. In addition, liver tissue with chronic hepatitis preceding fibrosis may account for mild elevation of liver stiffness. CONCLUSION: MRE had greater predictive ability in distinguishing the stages of liver fibrosis than DWI.

Assessment of fibrosis in chronic liver diseases.

The assessment of liver fibrosis provides useful information not only for diagnosis but also for therapeutic decisions. Although liver biopsy is the current gold standard for fibrosis assessment, it has some risks and limitations, including intra-observer and inter-observer variation, sampling error and variability. In recent years, many studies and great interest have been dedicated to the development of non-invasive tests to substitute a liver biopsy for fibrosis assessment and follow up. Advances in serological and radiological tests such as serum marker panels, transient elastography and their combinations can assess fibrosis accurately and reduce the need for a liver biopsy. But at present, all have failed to completely replace a liver biopsy because of their respective limitations and an imperfect gold standard used in current researches. The searching for an ideal surrogate is still in progress.

Liver biopsy assessment in chronic hepatitis.

Liver biopsy has been a major diagnostic tool in the evaluation of individuals with chronic hepatitis for many decades and remains the most direct way of visualizing hepatic necroinflammation and fibrosis. In chronic viral hepatitis B and C, immune attack on hepatocytes bearing viral antigens results in the entry of lymphocytes and other effector cells through the portal tracts from which other lesions may evolve, including interface and lobular hepatitis as well as fibrosis or cirrhosis. Classification systems have been developed in order to provide semiquantitative grading of necroinflammation and staging of fibrosis and include the Scheuer, Batts and Ludwig, Ishak, and METAVIR systems. This review provides an historical perspective on histopathological methods of analyzing chronic hepatitis, describes the essential criteria of each of the major scoring systems and discusses problems related to sampling error, observer variation, and specimen size.

[Assessment of hepatocyte AgNORs expression in chronic hepatopathy]. / Valutazione della espressione di AgNORs epatocitarie in corso di epatopatie croniche.

The high incidence of liver chronic diseases has aroused strong interest in researching and trying to discover the biomolecular basis. In this context the study of nucleolar organizing regions could be interesting as a prognostic factor for chronic hepatitis and for liver neoplastic disease. The Authors report on the results of their study performed on 39 selected samples from 4 different inflammatory hepatic disorders.

Assessment of nucleolar organizer regions (NORs) in proliferative conditions of the liver.

To overcome the diagnostic dilemma in proliferative conditions of the liver which sometimes pose a problem to the working pathologist especially when the material is inadequate, a special staining technique (AgNOR) has been applied. By using this technique, nucleolar organizer regions were counted which determine the proliferative status of the cells. This prospective study included 65 cases of randomly selected liver core and fine needle aspiration biopsies. AgNOR staining was performed on formalin-fixed, paraffin-embedded tissue sections NOR dots were counted in 100 randomly selected hepatocytes at x100 oil immersion objective, and the mean count per cell was calculated for each case. Statistical analysis was done by using the Mann Whitney U test. AgNOR count results were later compared with the histologic diagnosis. The study revealed a gradual increase in mean AgNOR counts from normal liver through cirrhosis to hepatocellular carcinoma. The difference in NOR counts was significant in these three groups. The hepatocellular carcinomas were graded according to the Edmondson-Steiner histological grading system. The Grade I hepatocellular carcinomas show AgNOR counts ranging between 5-6/cell, a score which is much higher than in the normal liver, where it ranges between 1.2-2.0/cell. This technique can be used to assess the lesions where the distinction between normal liver and Grade I hepatocellular carcinoma is difficult with the use of routine methods. AgNOR counts in normal liver and chronic hepatitis cases were insignificant, but there was an appreciable difference between cases of chronic hepatitis, cirrhosis and hepatocellular carcinoma. In view of the results of this study, the AgNOR staining method is found to be a useful diagnostic tool to differentiate between normal liver, cirrhosis and hepatocellular carcinoma and also to precisely discriminate between cases of normal liver and Grade I hepatocellular carcinoma.

Broadsheet number 47: Chronic hepatitis: an update with guidelines for histopathological assessment of liver biopsies. Board of Education of The Royal College of Pathologists of Australasia.

The liver biopsy remains the 'gold standard' for the diagnosis of chronic hepatitis, particularly since it is the only investigation that permits assessment of the severity (grade of histological activity and stage of fibrosis) of liver injury. As outlined below, the liver biopsy is invaluable for both diagnosis and the monitoring of therapy. To optimise the value of the liver biopsy, a standardised approach for assessment and reporting of chronic hepatitis is recommended.

[Compared efficiency of three strategies of management of chronic hepatitis C. Effect on the risk of cirrhosis 8 years after diagnosis]. / Efficience comparée de trois stratégies de prise en charge de l'hépatite chronique C. Influence sur le risque de cirrhose à 8 ans.

OBJECTIVES AND METHODS: The goal of treating chronic hepatitis C with alfa interferon is to eradicate HCV infection. The actual influence of this treatment on the development of cirrhosis is unknown. Moreover, the poor results and the high cost of this treatment have caused a public health problem. Three strategies were evaluated by decision analysis: no treatment (S1), treatment of chronic active hepatitis only (S2), treatment of all chronic hepatitis (S3). For each strategy, we estimated the probability of the occurrence of the following events based on data in the literature: presence of chronic active hepatitis, chronic persistent hepatitis or cirrhosis at the time of diagnosis; discontinuation of interferon because of adverse events; biological response to treatment; incidence of cirrhosis 8 years after diagnosis without treatment or in case of response to treatment. RESULTS: The risk of cirrhosis was 28.5% with S1, 25.4% with S2, and 25.2% with S3, 8 years after diagnosis. If HCV infection was detected early before cirrhosis, the number of cases of cirrhosis occurring in an 8 year-followup period would be 45,600 with S1, 40,640 with S2, and 40,320 with S3 and the cost of S2 and S3 would be 1.23 10(9) French Francs (FF), and 2.57 10(9) FF, respectively. The mean cost to prevent one case of cirrhosis would vary from 248,000 FF with S2 to 487,000 FF with S3. CONCLUSION: This decision analysis study suggests that the S3 strategy is not suitable for a population of HCV infected patients, because of its low efficiency and high cost.

Morphometric assessment of nucleolar activity in liver cells during the evolutive pathway of chronic hepatitis C to cirrhosis.

Using a computer-assisted image analysis system, we performed a morphometric study of silver-stained nucleoli of hepatocytes in liver biopsy specimens from hepatitis C virus-positive patients with chronic persistent hepatitis (3 cases), chronic active hepatitis (4 cases), and cirrhosis (4 cases). The number and the total area of nucleoli, the average area of each nucleolus and the nuclear area were determined for each of 100 hepatocytes per case. A continuing increase in the area of both nucleoli and nuclei paralleled a progressive decrease in the number of nucleoli during the evolution of chronic hepatitis C to liver cirrhosis. These findings would indicate that the hepatitis C virus-induced liver damage causes reactive changes in surviving hepatocytes resulting in an increased nucleolar biosynthetic activity rather than in an increment of cell proliferation rate. Therefore, the liver response to hepatitis C virus injury seems to be mainly based on a condition of cell "hypertrophy", whereas we previously showed that a process also of compensatory hyperplasia occurs in chronic hepatitis B, possibly resulting from a different pathogenesis of the viral damage.

Laboratory assessment of chronic hepatitis in Syrian hamsters.

Clinical chemistry studies in the diagnosis of hamster diseases have received little attention. Although normal values exist for serum constituents, the effects of disease on these values are not well documented. Chronic hepatitis is endemic in several Syrian hamster (Mesocricetus auratus) colonies and is reported mainly through routine histologic examination. We investigated whether any differences in serum clinical chemistries were present in animals with hepatobiliary disease versus unaffected hamsters. Only serum alanine aminotransferase (ALT) and bile acids were significantly elevated in hamsters with chronic hepatitis only. In hamsters that had both chronic hepatitis and biliary disease, the serum ALT, alkaline phosphatase, cholesterol, and bile acids were significantly elevated. The results of this study indicated that serum clinical chemistries may be a useful antemortem diagnostic test for chronic hepatobiliary disease in hamsters.

Application of a numerical scoring system for assessment of histological outcome in patients with chronic posttransfusion non-A, non-B hepatitis with or without antibodies to hepatitis C.

A numerical scoring system was applied and compared to the conventional histological classification to assess the histological status of liver specimens from 37 patients with chronic posttransfusion non-A, non-B hepatitis followed for 7 to 105 months (mean 35 months). Four histological categories of alterations were assessed and scored: piecemeal necrosis (PMN), fibrosis and cirrhosis, lobular necrosis and portal inflammation. Sequential liver biopsies were obtained from 19 patients. PMN was generally mild but still predictive of progressing fibrosis. Thus, in none of the biopsies from four patients with initial PMN score 0 was there any increase in the fibrosis score in the follow-up biopsy, while in 10/15 (67%) patients with an initial PMN score of greater than or equal to 1 the fibrosis score increased with time (p = 0.033). Lobular necrosis and portal inflammation were not predictive of progressing fibrosis. Judging from the scoring method, 22% of all the 37 patients displayed cirrhosis and 27% bridging fibrosis in the latest liver biopsy performed. Patients with antibodies to hepatitis C did not differ in histological status or outcome from those without antibodies to hepatitis C. It is concluded that the scoring system can be used to monitor the histological long-term follow-up in patients with chronic posttransfusion non-A, non-B hepatitis, and offers a means of predicting the histological outcome.

Variation in serum type III procollagen peptide with age in healthy subjects and its comparative value in the assessment of disease activity in children and adults with chronic active hepatitis.

To determine the comparative value of serum Type III procollagen peptide (PIIIP) in paediatric and adult liver disease we have measured PIIIP in 201 healthy subjects (aged 1 day-77 years) and twenty-one children and five adults with chronic active hepatitis (CAH). Healthy children had significantly higher PIIIP levels than adults (P less than 0.001), with highest values of 298 +/- 88 ng ml-1 (s.d.) in the neonatal period. PIIIP fell to 30.9 +/- 7.0 by 1 year, 19.1 +/- 4.5 by 3 years and rose significantly (P less than 0.01) at puberty. Adult levels (8.3 +/- 3.2) occurred by 16 years of age. Serum PIIIP levels were significantly elevated (P less than 0.001) in adults when they had biochemical and histological evidence of active liver disease but were consistently within the normal range for age in 70% of children with similar hepatic pathology. The minor elevations in PIIIP in the other children were unrelated to clinical, biochemical or histological evidence of active liver disease. While raised PIIIP may be a non-invasive marker of liver disease activity in adults, its value in childrens' disorders appears to be limited by the high levels of PIIIP which occur during growth.