Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in both developed and developing countries. A noninvasive method of detecting early stage NAFLD and distinguishing non-alcoholic steatohepatitis (NASH) from simple steatosis (SS) would be useful. The over-accumulation of fat in hepatocytes alters the physical microstructure and chemical contents of the liver tissue. This study included dynamic mechanical analysis (DMA) testing on liver samples from a rat model of NAFLD to determine whether the tissue shows any significant changes in viscoelasticity due to the histological changes. Liver steatosis was induced in 57 rats by gavage feeding of a high fat emulsion; 12 rats received a standard diet only and served as controls. Each rat provided 2 or 3 samples for DMA tests. The shear modulus and loss modulus were measured at 9 frequency points evenly-spaced in the range from 1Hz to 41Hz. The phase velocity of shear wave was calculated from the measured modulus. Multivariate T² test was used to assess the significance of intra-group difference. The results showed significant changes (p < 0.05) in storage modulus in livers with moderate to severe (S2 to S4) steatosis in comparison with livers without steatosis (S0), while the loss modulus demonstrated significant changes earlier in stage S1, indicating that fat accumulation affects the mechanical properties of liver, particularly viscosity. However, no significant differences were observed between the steatosis grades. These results also suggest that mild inflammation may affect the mechanical properties, which requires further verification. These findings provide new information about the mechanical properties of livers with NAFLD in low frequency range and suggest that it is possible to distinguish normal livers from livers with NAFLD.

The etiology of the chronic liver disease (CLD) in patients with acute on chronic liver failure (ACLF) may vary from region to region. The major cause of underlying CLD is viral (hepatitis B and C) in the East, while it is alcohol related in the West and in some parts of the Indian subcontinent. Autoimmune liver disease and Wilson's disease are the major underlying etiologies in the pediatric age group. The patients with CLD without cirrhosis should be included when defining ACLF. Non-alcoholic fatty liver disease related chronic liver insult in patients with known risk factors for progressive disease should be taken as a chronic liver disease in the setting of ACLF, whereas fatty liver with normal aminotransferases in low risk patients should not. The patients with CLD and previous decompensation should be excluded. Diagnosis of chronic liver disease in the setting of ACLF is made by history, physical examination and previously available or recent laboratory, endoscopic or radiological investigations. A liver biopsy through the transjugular route may help in cases where the presence of underlying CLD or its cause is not clear. The need of liver biopsy in ACLF should, however, be individualized. Standardization of liver biopsy assessment is essential for a uniform approach to the diagnosis and treatment of CLD and acute insult. Tools to measure liver stiffness may aid in identifying patients with advanced fibrosis. Studies are needed to validate the performance of these tests in the setting of ACLF.

Pathologic evaluation of liver allograft biopsies plays an integral role in the management of patients after liver transplantation. This review summarizes the clinical context and classical histology of different types of allograft rejection and also the common entities that enter the differential diagnosis of allograft rejection, and provides practical approaches to liver allograft biopsy interpretation. In addition, some of the new developments in the field of liver transplant pathology are updated. The purpose of this review is to provide guidance for pathologists interpreting liver allograft biopsies, particularly those interested in developing expertise in the field of liver transplant pathology.

S It remains unknown whether the normal adult liver contains bipotent stem/progenitor cells, and if it does, then what are the circumstances under which they proliferate. The aim of this study was to clarify whether the normal adult liver contains hepatic stem/progenitor cells, and if it does, will they be activated by extensive hepatectomy? Adult rat liver cells were isolated and cultured at a low-density, and the colony-forming assay was performed to evaluate the cell proliferative capacity. Immunocytochemistry and reverse transcription-polymerase chain reaction were used to investigate the multilineage differentiation capability. The rate of colony formation by cells from the normal liver and those from the regenerating liver after partial hepatectomy (PH) were compared to determine whether progenitor cell proliferation might be activated by PH. Only a few epithelial colonies (0.043+/-0.009% of nonparenchymal cells) continued to proliferate for more than 1 month. Reverse transcription-polymerase chain reaction and immnocytochemistry showed that these progenitor colonies expressed both hepatocyte and cholangiocyte markers. The proportion of progenitor cells that formed bipotential colonies did not differ significantly between the cells obtained from the normal and PH livers. Adult normal liver contains bipotent hepatic progenitor cells, but they are scarcely activated even after extensive hepatectomy.

To provide the accurate alternative metrical means of monitoring the effects of new antiviral drugs on the reversal of newly formed collagen.

Digitized histological biopsy sections taken from 209 patients with chronic C virus hepatitis with different grade of fibrosis or cirrhosis, were measured by means of a new, rapid, user-friendly, fully computer-aided method based on the international system meter rectified using fractal principles.

The following were described: geometric perimeter, area and wrinkledness of fibrosis; the collation of the Knodell, Sheuer, Ishak and METAVIR scores with fractal-rectified metric measurements; the meaning of the physical composition of fibrosis in relation to the magnitude of collagen islets; the intra- and inter-biopsy sample variability of these parameters; the"staging" of biopsy sections indicating the pathway covered by fibrosis formation towards its maximum known value; the quantitative liver tissue architectural changes with the Hurst exponent.

Our model provides the first metrical evaluations of the geometric properties of fibrosis and the quantitative architectural changes of the liver tissue. The representativeness of histological sections of the whole liver is also discussed in the light of the results obtained with the Hurst coefficient.

To introduce a computer-aided morphometric method for quantifying the necro-inflammatory phase in liver biopsy specimens using fractal geometry and Delaunay's triangulation.

Two-micrometer thick biopsy sections taken from 78 chronic hepatitis C virus-infected patients were immunohistochemically treated to identify the inflammatory cells. An automatic computer-aided image analysis system was used to define the inflammatory cell network defined on the basis of Delaunay's triangulation, and the inflammatory cells were geometrically classified as forming a cluster (an aggregation of a minimum of three cells) or as being irregularly distributed within the tissue. The phase of inflammatory activity was estimated using Hurst's exponent.

The proposed automatic method was rapid and objective. It could not only provide rigorous results expressed by scalar numbers, but also allow the state of the whole organ to be represented by Hurst's exponent with an error of no more than 12%.

The availability of rigorous metrical measures and the reasonable representativeness of the status of the organ as a whole raise the question as to whether the indication for hepatic biopsy should be revised by establishing clear rules concerning the contraindications suggested by its invasiveness and subjective interpretation.

Numerous medical, surgical, psychiatric, gynecologic, and obstetric disorders can cause abdominal pain during pregnancy. The patient history, physical examination, laboratory data, and radiologic findings usually provide the diagnosis. The pregnant woman has physiologic alterations that affect the clinical presentation, including atypical normative laboratory values. Abdominal ultrasound is generally the recommended radiologic imaging modality; roentgenograms are generally contraindicated during pregnancy because of radiation teratogenicity. Concerns about the fetus limit the pharmacotherapy. Maternal and fetal survival have recently increased in many life-threatening conditions, such as ectopic pregnancy, appendicitis, and eclampsia, because of improved diagnostic technology, better maternal and fetal monitoring, improved laparoscopic technology, and earlier therapy.

Steatohepatitis, of either alcoholic or nonalcoholic etiologies, is ultimately diagnosed by clinical-pathologic correlation and is characterized histologically by lesions that differ from the portal-based chronic inflammation and fibrosis of most other forms of chronic liver disease. With the increasing prevalence of steatohepatitis in our society, it is likely that some patients will have coexistent clinical and/or histopathologic findings of steatohepatitis concurrently with another form of liver disease. The aim of this study was to document clinical and histologic findings in biopsies in an academic referral center. Ninety-three non-allograft liver biopsies with lesions of both steatohepatitis and another liver disease were retrospectively identified in 85 patients. The finding of coexisting disease represented 5.5% of all hepatitis C biopsies and 4.0% of other forms of chronic liver disease in the 34 month time period. Clinical chart review of patients with concurrent disease showed the following: Group 1, patients with hepatitis C (n = 54); Group 2, patients with hepatitis C and prior or current history of more than 80 g/d alcohol consumption (n = 20); Group 3, patients with other forms of chronic liver disease (n = 11). Groups 1 and 3 had <10 g/d alcohol use. Obesity (body mass index >30) was noted in 75%, 60%, and 33% respectively, while 94%, 87% and 100% of patients were considered overweight (body mass index > or = 25). Diabetes was reported in 35%, 25%, and 9%. The concurrence of clinical and histologic features of steatohepatitis with another chronic liver disease may be a reflection of the frequency of steatohepatitis in the population at large.

Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a relatively prevalent disorder (ie, occurring in 3% of adults) that may progress to cirrhosis in 15% to 40% of those who are afflicted. NASH is a subset of a broader diagnostic category, nonalcoholic fatty liver disease, a term applied to a condition involving the presence of excess fat in the liver with or without inflammation and cellular injury. A diagnosis of NASH is established by the presence of morphologic changes on liver biopsy similar to those seen in alcoholic hepatitis, including hepatocellular fat accumulation, evidence of lobular inflammation and cell injury, and in some cases, progressive fibrosis. Obesity and type 2 diabetes, two conditions associated with insulin resistance, are major risk factors for the development of NASH. Accumulating evidence suggests that the hyperinsulinemia associated with insulin resistance may be important in the pathogenesis of NASH. Clinical trials will now determine whether treatment of insulin resistance is an effective therapy for NASH.