E M Brunt

..While largely focused on adult NAFLD, the manuscript also summarizes what has been reported to date for NAFLD in the pediatric population...

..Diabetes and the metabolic syndrome are also associated with HCC. However, it is not clear whether NAFLD predisposes patients to HCC in the absence of cirrhosis...

..Histologic markers to predict hepatocellular carcinoma (HCC) include small cell change and dysplastic nodules. Hepatocyte senescence is noted in chronic liver disease and may or may not be important in progression to HCC...

..In this review, these concepts as well as the pathophysiologic bases for them are discussed...

..A histological "grading and staging" system has been developed to reflect the unique features of steatohepatitis, gradations of severity and fibrosis, and to promote uniform reporting of the histopathology...

..When pertinent, pathophysiology of this metabolic liver disease and recent treatment considerations have been mentioned as well...

..In this article, histopathologic findings in conditions of iron overload and in several forms of liver disease are discussed...

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..Clinical characteristics and clues to the diagnosis are discussed as well as the importance of histologic confirmation and the controversy surrounding liver biopsy...

..In many instances, however, the microscopic lesions of these two processes are similar, likely as a reflection of common pathogenetic pathways, and the distinction between the two is ultimately clinically derived...

..Analysis of mice from crosses between C57BL/6 and AKR mice should allow the mapping and subsequent identification of genes modifying the severity of iron loading in this murine model of HH...

..Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain...

..This however did not reach statistical significance. CONCLUSIONS: Hepatic alpha-smooth muscle actin expression, as a marker of hepatic stellate cell activation appears reversible and tends to correlate with necroinflammatory activity...

..These data support the model for HH in which HFE mutations lead to inappropriately low crypt cell iron, with resultant stabilization of DMT1(IRE) mRNA, up-regulation of DMT1, and increased absorption of dietary iron...

..This study suggests that the combination of IFN and ribavirin is a useful modality of therapy in patients with chronic hepatitis C who did not respond to IFN alone...

..Hereditary hemochromatosis is a common inherited disorder of iron metabolism. The gene HFE, which contains two missense mutations (C282Y and H63D), was recently identified...

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..These findings identify myeloperoxidase as a component of human Kupffer cells. Oxidative damage resulting from the action of myeloperoxidase may contribute to acute liver injury and hepatic fibrogenesis...

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..The delay in ulcer healing, compared with the gross changes reported during follow-up endoscopic examinations, may be related to the severity of the underlying illness and the compromised immune status of patients in the present series...

..The knockout mouse model of HH will facilitate investigation into the pathogenesis of increased iron accumulation in HH and provide opportunities to evaluate therapeutic strategies for prevention or correction of iron overload...

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..The product of HIC and age is highly sensitive and specific for diagnosis of high-grade fibrosis and can be obtained using MRI...

..NAS of > or =5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH."..

..In hepatitis C, an increased number of CD14-positive cells are associated with high inflammatory activity...

..The relationship between severity and zonal location of steatosis and the presence of steatohepatitis and various histological features that define NASH has not been formally studied...

..We propose that activation of this pathway, with increased cell injury in NASH, also induces a periportal ductular reaction (DR) that could produce a profibrogenic stimulus...

..Transcripts from adjacent genes encoding snoRNAs and microRNAs were overexpressed in tumors. Our findings implicate this locus in the development of HCC and raise concerns over the clinical use of AAV vectors...

..Whether these are adaptive or pathological remains unknown, and further studies are warranted to assess hepatic mitochondrial function during thiazolidinedione therapy for NASH...

..Detection and classification of MDBs using MDB-marker-selective staining may offer unique links to specific histological features of DDC-induced liver injury...

..Finally, other aspects for consideration by practicing pathologists, such as sampling issues, histopathologic findings after therapeutic interventions, and recurrence after liver transplantation, are addressed...

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..Because of the inherent limitations of autopsy studies, prospective assessment of iron stores in healthy blacks is needed to determine more accurately the prevalence and clinical significance of iron overload in this population...

..In conclusion, increased expression of GP73 in hepatocytes appears to be a general feature of advanced liver disease, and may be regulated via distinct pathways that involve hepatotropic viruses or cytokines...

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..Among those patients with severe recurrent hepatitis C, HCV appeared to be under greater immune pressure. The greatest change in viral amino acid sequences occurred in the first 36 months after OLT...

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..This chapter will elucidate the constellation of microscopic findings, the issues of concern for pathological evaluation and the knowledge to date of their significance in various forms of fatty liver disease...

..Refinements of all of these may lead to better HCC detection, earlier intervention, and successful treatment. Randomized controlled trials are necessary to evaluate the most efficacious and cost-effective approach to screening...

..However, EBER-positive cells can be sparse and easily overlooked. Immunohistochemistry for EBV latent membrane proteins apparently has no utility in the diagnosis of EBV hepatitis...

..IFN monotherapy nonresponder patients tended to have a higher HIC. With IFN plus ribavirin, the sustained virologic response rate was not affected by the HIC...

..Ballooning degeneration is considered a hallmark of steatohepatitis, but enlarged hepatocytes may also be observed in a variety of other acute and chronic liver diseases...

..We sought direct evidence for a keratin mutation-related predisposition to liver fibrosis using transgenic mouse models because the relationship between keratin mutations and cirrhosis is based primarily on human association studies...

..These findings support the concept that the combination of HH-induced iron overload and HCV has a potentiating effect on hepatic fibrogenesis...

..This report is, to our knowledge, the first such case of a tumor of this cell type reported in the gallbladder. In addition, we present a review of the literature...

..This case is unusual in two aspects: the patient survived 30 yr after shunt surgery with undiagnosed Budd-Chiari syndrome; and the association of Budd-Chiari syndrome with subsequent hepatocellular carcinoma is uncommon...

..In control human liver, Kupffer cells had a very low expression of CD14. These findings suggest that CD14-positive monocytes/macrophages may contribute to the process of hepatic fibrogenesis in HH...

..These observations suggest that HSP47 is constitutively expressed in human HSC and that HSP47 may be a target for antifibrotic therapy...

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..A control group (group 2) of 231 CHC patients was identified by using a 2-year database (January 2000-June 2001) of patients without evidence of greater than 33% steatosis or SH...

..The aim of this study was to determine the effects of dietary fat of varying PUFA content on iron-induced oxidative stress and fibrosis...

..Further studies are needed to precisely characterize diabetic hepatosclerosis and to understand mechanisms of pathogenesis and the clinical significance...

..Obtaining material for both cytologic and histologic examination at biopsy maximizes the diagnostic yield...

..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...