Percutaneous Liver Biopsy Specimens Research Articles

Yield and Safety of Transjugular Versus Percutaneous Liver Biopsies in Suspected Cases of Diffuse Liver Disease and Correlation of Yield of Transjugular Liver Biopsy with Hepatic Venous Pressure Gradient

Abstract Background Liver biopsy is indicated in both diagnosis and prognosis of diffuse liver diseases. Conventionally, percutaneous liver biopsy (PLB) is used, as it is easily available, affordable and has a shorter procedure time, whereas transjugular liver biopsy (TJLB) is used in the setting of ascites and coagulopathy. Our aim is to evaluate the diagnostic yield of TJLB in comparison to PLB with tract embolization. Our secondary aims were to evaluate whether there is any difference in rate of major and minor complications between the two procedures and evaluate whether there is any correlation between diagnostic yield of TJLB and hepatic venous pressure gradient (HVPG). Methods In this retrospective study, we included a total of consecutive 123 patients who underwent liver biopsy through percutaneous (n = 97) and transjugular route (n = 26). We compared the yield of the specimen based on the number of complete portal tracts (CPT). Results There was no significant difference between mean CPT in TJLB and PLB specimens (mean CPT of TJLB and PLB were 10.9 ± 2.7 and 11.6 ±2.5, respectively [p = 0.566]). There was a moderate but significant negative correlation between the total number of CPT and HVPG in the TJLB group (Spearman’s rho − 0.58) (p = 0.002). There was no statistically significant difference in minor complication between the two procedures. Only one patient who underwent PLB developed major complication and none of TLJB procedure had any major complication. Conclusion Yield of tissue and complication rates are comparable in TJLB and PLB groups. Yield of tissue in TJLB have intermediate but significant negative correlation with HVPG.

Predictors of adequate percutaneous liver biopsy specimens: a single-center experience

BackgroundPercutaneous liver biopsy is one of the widely accepted procedures to find any disorder, infection, and disease. Understanding the correlation between biopsy factors and adequacy rate will improvize efficacy and safety of biopsy.ObjectivesThis study was carried out to find the effect of needle size on the adequacy rate of biopsy and also to establish the association of factors such as BMI, cumulative length, and the number of cores to adequacy rate of biopsy.Materials and methodsThis retrospective review study was carried out at King Abdul-Aziz Medical City, MNGHA, Jeddah, Saudi Arabia. The data were acquired on adult patients who underwent percutaneous liver biopsy for 2010–2016 time periods. The data were analyzed by using the statistical package for social sciences, version 23.ResultsNo significant difference was observed in the adequacy rate of biopsy among samples of different needles (P=0.998). Similarly, BMI and guidance did not significantly (P=0.860 and 0.873) affect the adequacy rate. However, the number of cores (P<0.001) and cumulative length (P<0.001) had a significant effect on adequacy rate. Finally, only cumulative length (2.4 cm) was significantly correlated (P<0.05) to the adequacy rate of Percutaneous liver biopsy (PLB).ConclusionThe adequacy rate significantly depends on cumulative length and the number of cores. However, further studies are required to establish a conclusive relationship between factors and adequacy rate.

Baseline Values and Changes in Liver Stiffness Measured by Transient Elastography Are Associated With Severity of Fibrosis and Outcomes of Patients With Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that leads to extensive liver fibrosis and cirrhosis, which are associated with poor outcome. However, there are no validated noninvasive markers of liver fibrosis in patients with PSC. We assessed the diagnostic performance, reproducibility, longitudinal changes, and prognostic value of liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE). In a prospective study, we analyzed percutaneous liver biopsy specimens from 73 consecutive patients with PSC from January 2005 to December 2010. Patients underwent VCTE no more than 6 months after the biopsy specimens were collected. The biopsy specimens were analyzed by a pathologist blinded to the results of VCTE for the stage of fibrosis, and LSM was associated with the stage of fibrosis and other variables using the Kruskal-Wallis and Spearman correlation tests. The cutoff values of LSM were selected based on the accuracy with which they identified the stage of fibrosis on receiver-operating characteristic analysis. The rates of LSM progression were assessed using a linear mixed model, and the association between LSM values and clinical outcomes were evaluated using Cox regression analysis in 168 patients with PSC treated with ursodeoxycholic acid and followed up from November 2004 to July 2013 (mean follow-up period, 4 years). LSM was independently linked to the stage of fibrosis. Cutoff values for fibrosis stages ≥F1, ≥F2, ≥F3, and F4 were 7.4 kPa, 8.6 kPa, 9.6 kPa, and 14.4 kPa, respectively. The adjusted diagnostic accuracy values for severe fibrosis and cirrhosis were 0.83 and 0.88, respectively. The diagnostic performance of LSM was comparable to that of hyaluronic acid measurement but superior to the aspartate aminotransferase/platelet ratio index, FIB-4 score, and Mayo risk score in differentiating patients with significant or severe fibrosis from those without. LSM had a high level of reproducibility between operators for the same measurement site and for the same operator between 2 adjacent sites. LSM increased significantly and exponentially over time. Baseline measurements and rate of LSM progression were strongly and independently linked with patients' outcomes. VCTE is able to differentiate severe from nonsevere liver fibrosis with high levels of confidence in patients with PSC. Baseline measurements of LSM and longitudinal changes are prognostic factors for PSC.

Nasobiliary Drainage in an Episode of Intrahepatic Cholestasis in a Child With Mild ABCB11 Disease

Nasobiliary Drainage in an Episode of Intrahepatic Cholestasis in a Child With Mild <i>ABCB11</i> Disease

Preactivation of the interferon signalling in liver is correlated with nonresponse to interferon alpha therapy in patients chronically infected with hepatitis B virus

Interferon alpha (IFN-α) therapy is widely used to treat patients with chronic hepatitis B (CHB) but the sustained response rate is low, and the molecular mechanisms for the ineffectiveness of IFN-α treatments are not known. We screened differentially expressed genes between responders (Rs) and nonresponders (NRs) in patients with CHB treated with IFN-α to explore the molecular basis for treatment failure. Expression profiling was performed on percutaneous needle liver biopsy specimens taken before therapy. Gene expression levels were compared between seven patients who did not respond to therapy (NR) and six who did respond (R). Gene ontology category and KEGG pathway were analysed for differentially expressed genes, and the selected differentially expressed genes were confirmed using real-time polymerase chain reaction. We identified 3592 genes whose expression levels differed significantly between all Rs and NRs (P < 0.05); many of these genes are IFN-stimulated genes (ISGs) and immune-related genes. The ISGs were more highly expressed, while immune-related genes were inhibited in NRs before IFN-α treatment. Two ISGs (CEB1 and USP18) that are linked in an IFN inhibitory pathway are highly expressed in NRs, and a potential antiviral gene ISG20 was inhibited in NRs, suggesting a possible rationale for treatment nonresponse. Patients who do or do not respond to IFN have different liver gene expression profiles before IFN-α treatment. Preactivation of the IFN signalling pathway leading to the increased expression of inhibitory ISGs and inhibition of immune response in the pretreatment livers was associated with treatment failure.

Fibrinogen Storage Disease Caused by Aguadilla Mutation Presenting With Hypobeta‐lipoproteinemia and Considerable Liver Disease

Fibrinogen Storage Disease Caused by Aguadilla Mutation Presenting With Hypobeta‐lipoproteinemia and Considerable Liver Disease

Cyclooxygenase‐2 expression in chronic hepatitis C and the effect of interferon α treatment

Cyclooxygenase-2 (COX-2), a target of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), is upregulated in chronic hepatitis B and may have a role in hepatocellular carcinoma. Little is known about the expression of COX-2 in chronic hepatitis C (HCV) infection. The aim the present study was to evaluate the extent of COX-2 expression in liver biopsies in patients with HCV infection and to determine the effect of treatment with interferon alpha (IFN). Percutaneous liver biopsy specimens were retrieved. Following formalin fixation and paraffin embedding, the biopsies were histologically evaluated for inflammation and fibrosis. The extent of COX-2 expression was measured by the avidin biotin immunohistochemical technique using a monoclonal COX-2 antibody. The extent of COX-2 expression was graded according to the number of hepatocytes expressing COX-2. Data were analyzed using Student's t-test. Liver biopsies from 10 patients before and after treatment with IFN were obtained and compared with nine normal liver biopsies. All of the liver biopsies showed some COX-2 expression. COX-2 expression was confined to hepatocytes and bile duct epithelium and was not detected in vascular endothelium or inflammatory cells. The extent of COX-2 expression was greater in hepatitis C infected liver biopsies than in normal biopsies. Following treatment with IFN, there was a greater than threefold reduction in COX-2 expression (P < 0.01). This result was independent of the sustained virological response. In this small pilot study we have shown that COX-2 is overexpressed in liver biopsies infected with HCV and COX-2 expression is reduced following treatment with IFN.

Hepatic Gene Expression Discriminates Responders and Nonresponders in Treatment of Chronic Hepatitis C Viral Infection

Pegylated interferon (IFN)-alpha plus ribavirin is the most effective treatment of chronic hepatitis C but has unpleasant side effects and high costs. A large proportion of patients do not respond to therapy for reasons that are unclear. We used gene expression profiling to investigate the molecular basis for treatment failure. Expression profiling was performed on percutaneous needle liver biopsy specimens taken before therapy. Gene expression levels were compared among 15 nonresponder, 16 responder, and 20 normal liver biopsy specimens. Differential gene expression was confirmed using real-time polymerase chain reaction. We identified 18 genes whose expression differed significantly between all responders and all nonresponders (P < .005). Many of these 18 genes are IFN sensitive and 2 (ISG15/USP18) are linked in a novel IFN-regulatory pathway, suggesting a possible rationale for treatment resistance. Using a number of independent classifier analyses, an 8-gene subset accurately predicted treatment response for 30 of 31 patients. The classifier analyses were applicable to patients with genotype 1 infection and were not correlated with viral load, disease activity, or fibrosis. Hepatic gene expression profiling identified consistent differences in patients who subsequently fail treatment with pegylated IFN-alpha plus ribavirin: up-regulation of a specific set of IFN-responsive genes predicts nonresponse to exogenous therapy. These data may be of use in predicting clinical responses to treatment.

Correlation of percutaneous liver biopsy fragmentation with the degree of fibrosis.

Although fragmentation of a liver biopsy specimen has been considered to be suggestive of cirrhosis, the evidence for this is difficult to find in the published literature. To determine whether fragmentation of percutaneous liver biopsy specimens correlates with the degree of fibrosis. One hundred and eighty-six patients underwent percutaneous liver biopsy prospectively. The specimens were measured for the length and number of fragments. The extent of fibrosis was scored by a pathologist blind to the clinical data. Length and fragmentation data were compared between the different stages. The overall median fragment length was 1.85 cm and the median fragment number was four. Specimens with advanced fibrosis (stages III-IV) had more fragments than those with no or mild fibrosis (stages 0-II) (P < 0.0001). The aggregate fragment length decreased with increasing stage of fibrosis (P < 0.0001). Specimens with greater than 12 fragments were seen only with advanced fibrosis. Fragmentation of percutaneous liver biopsy specimens is common and increases with progression from early to advanced fibrosis. Fibrotic specimens fragment more often and more extensively.

587 Retrospective study correlating the prometheus liver fibrosis panel with findings of fibrosis on percutaneous liver biopsy specimens in Alaska natives with hepatitis C

587 Retrospective study correlating the prometheus liver fibrosis panel with findings of fibrosis on percutaneous liver biopsy specimens in Alaska natives with hepatitis C

Intravascular lymphomatosis of the lung and liver following eyelid lymphoma in a Chinese man and review of primary pulmonary intravascular lymphomatosis

Intravascular lymphomatosis (IVL) is characterised by an almost exclusive intravascular proliferation of malignant lymphoid cells, with the diagnosis often made only when the illness is in its terminal phase or at autopsy. We detail a case of IVL affecting the lung and liver of a 49-year-old Chinese man presenting primarily with lung symptoms and incidental findings of abnormal serum transaminase levels, the ante-mortem diagnosis being established on transbronchial lung biopsy and percutaneous liver biopsy specimens, respectively. Histology disclosed CD20 + CD5 - CD10 [corrected] - malignant large mononuclear B cells within the lumina of the blood vessels of the affected organs as well as sinusoids of the liver. Significantly, the patient had a history of large B cell lymphoma affecting the eyelid 18 months prior to the angiotropic disease, suggesting a possible link between the more common types of non-Hodgkin's lymphoma and IVL. A brief review of all cases of primary pulmonary intravascular lymphomatosis is also presented.

UTILITY OF LIVER BIOPSY CULTURE IN PEDIATRIC LIVER TRANSPLANT RECIPIENTS

77 The purpose of our study was to determine the utility of the practice of culturing percutaneous liver biopsy specimens obtained from pediatric liver transplant recipients for evaluation of fever and/or elevated serum aminotransferases. Accordingly, a retrospective analysis was done of the 101 liver biopsies obtained during an 8-year period which had been submitted for bacterial, fungal, and/or viral culture, (out of a total of 174 biopsies in 38 patients). The purpose of the analysis was to ask 3 questions :1)What organisms were cultured? 2)Were there clinical profiles that were characteristic of the type of organism? 3) Was the practice cost-effective? 34/86 biopsy cultures were positive for bacteria, 4/75 for fungus and 2/81 for virus. Clinical and laboratory data for children with cultures positive for enteric flora (n = 9) were compared to those with cultures positive for gram positive organisms(n = 17), laboratory contaminants(n = 8), and those with negative cultures(n = 52). Children with biopsies positive for enteric flora had a "cholestasis profile:" mean direct bilirubin 7mg/dl, alanine aminotransferase (ALT) 78 IU/L, direct bilirubin/ ALT 0.09, in comparison to children with biopsies positive for gram positive flora. These children had a "hepatocellular profile:" mean direct bilirubin 4 mg/dl, ALT 332 IU/L, direct bilirubin/ALT 0.02, p = 0.04 and a high percentage of polymorphonuclear leukocytes (mean 69% vs. 38% for those with negative cultures, p = 0.001.) A total of $15,848 was spent for 32 positive cultures. Given the high cost of liver transplantation, this information suggests that discretion should be used in submission of liver biopsy samples for culture in pediatric transplant patients. We recommend that bacterial liver culture of biopsy specimens from pediatric liver transplant recipients should be restricted to subjects with a "cholestasis profile:" direct bilirubin/ALT >0.08 or a "hepatocellular profile:" direct bilirubin/ ALT <0.02 and polymorphonuclear leukocytes >70%. Fungal and viral cultures are seldom indicated. Following these guidelines could provide valuable information pertinent to patient management while reducing costs.

The relationship of hepatotoxic risk factors and liver histology in methotrexate therapy for juvenile rheumatoid arthritis

Objective: To examine the relationship between hepatotoxic risk factors and liver histopathology in patients with juvenile rheumatoid arthritis (JRA) treated with methotrexate (MTX). Study design: We graded the histology of 33 percutaneous liver biopsy specimens from 25 patients with JRA treated at Children’s Hospital Medical Center, Cincinnati, Ohio, using the Roenigk Classification Scale. Stepwise linear and logistic regression analyses were performed to examine the relationship of the Roenigk grade and presence of liver fibrosis of biopsy specimens with potential risk factors. Results: Twenty-seven biopsy specimens (82%) were classified as grade I, 4 (12%) as grade II, and 2 (6%) as grade IIIA; none demonstrated significant fibrosis. The frequency of biochemical abnormalities ( P < .001) and body mass index ( P = .05) were the only risk factors found to significantly relate to the Roenigk grade. The following factors were not significantly associated with the Roenigk grade: age, gender, disease duration, JRA subtype and course, duration of MTX administration, weekly MTX dose, cumulative dose of MTX, route of MTX administration, use of folic acid supplementation, concurrent use of other medications, and potential hepatotoxic comorbidities. Conclusions: Serial biochemical abnormalities are significantly associated with Roenigk grade and the presence of liver fibrosis. These findings concur with studies of patients with rheumatoid arthritis, suggesting that guidelines for monitoring MTX hepatotoxicity in rheumatoid arthritis may be applicable to patients with JRA. (J Pediatr 1999;134:47-52)

Ultrasonographic "triangular cord": the most definitive finding for noninvasive diagnosis of extrahepatic biliary atresia.

Early diagnosis of extrahepatic biliary atresia (EHBA) is very important for a successful bile drainage procedure. An urgent and extensive investigation is warranted to make a differential diagnosis of EHBA from other cholestatic disease, especially neonatal hepatitis (NH). The diagnosis may be made by laparotomy with cholangiogram and liver biopsy but these procedure are invasive. Because a cone-shaped fibrous tissue was always found at the porta hepatis during Kasai's procedure and that type of fibrous tissue has never been seen in other types of cholestatic jaundice, the authors have used ultrasonography (US) to detect fibrous remnants at the porta hepatis in infants clinically suspected of having EHBA and identified a triangular- or tubular-shaped echogenic density in the bifurcation of the portal vein at the porta hepatis in EHBA and called it an ultrasonographic "triangular cord (TC)". The authors determined that the presence of TC denoted the EHBA. On the other hand, nonvisualization of TC was interpreted as consistent with NH. In the present study, the authors reviewed ultrasonographic examination and hepatobiliary scintigraphy in a series of 41 infants suspected of having EHBA or NH. The TC was identified in thirteen infants. In twelve of thirteen infants with TC found by US, the diagnosis of EHBA was confirmed at the time of Kasai's Roux-en-Y hepatoportojejunostomy operation. The remaining one died at 15 months of age without having treatment. TC was not visualized in 28 infants. Twenty-seven of 28 infants with absent TC improved clinically through medical treatment for NH. The other, diagnosed to have NH by needle and wedge liver biopsies, eventually showed a TC on follow-up US examination performed 40 days after the initial examinations. Moreover, follow-up percutaneous liver biopsy specimen showed typical findings of biliary atresia with bile duct proliferation and portal fibrosis. The patient underwent a Kasai hepatoportoenterostomy. On review of the hepatobiliary scintigraphy, all 13 infants with TC had no intestinal excretion of isotope. Thirteen of 28 infants (46%) without TC also had no intestinal excretion of isotope in the 24hour follow-up but all of them were confirmed to have NH by percutaneous liver biopsy and their subsequent clinical course confirmed NH with the detection of bile in their stool except one. On the basis of these results, the authors conclude that ultrasonographic TC is a very specific finding representing the fibrous cone at the porta hepatis and is a quick, simple, and definitive tool in the noninvasive diagnosis of EHBA. If TC is visualized, no further studies are necessary and exploratory-laparotomy can be done. If TC is not visualized, hepatobiliary scintigraphy is recommended to demonstrate bile duct patency. Percutaneous liver biopsy is only required if neither TC nor intestinal excretion of isotope is seen. However, early exploration or close US follow-up study is recommended in any patient suspected of having EHBA clinically, even if liver biopsy confirms the presence of NH.

‘Triangular cord’: A sonographic finding applicable in the diagnosis of biliary atresia

Biliary atresia (BA) is characterized by luminal obstruction of the extrahepatic bile duct with fibrous remnants. The authors reviewed ultrasonographic examinations of the fibrous tissue in the bifurcation of the portal vein at the porta hepatis and identified the triangular- or tubular-shaped echogenic density, the so-called “triangular cord” (TC), in the vicinity of the portal vein on a transverse or longitudinal scan. In this prospective study, the authors investigated whether TC was useful in the noninvasive diagnosis of biliary atresia in 18 infants who had persistent neonatal jaundice. This was done by comparing the ultrasonographic examination with the histopathologic examination (HPE) of liver specimens obtained from a needle biopsy. The TC was identified in nine patients, all of whom were confirmed to have BA by HPE. The TC was not observed in the other nine patients, who had neonatal hepatitis (NH). The mean size of the TC was 13 mm (wide) × 6 mm (thick) (width range, 5 to 21 mm; thickness range, 4 to 12 mm). The diagnosis of BA was confirmed at the time of Kasai hepatoportojejunostomy in eight of the nine patients whose TC was noted by ultrasonography (US). The other patient was discharged because his parents refused the operation; he died of liver failure at 15 months of age. The nine patients with absent TC were treated medically for NH. Eight of them improved clinically. The other, diagnosed to have NH by needle and wedge liver biopsies, was reexamined 40 days after the initial examination because of worsening jaundice. A 18 × 12-mm TC was visualized ultrasonographically. Additionally, a percutaneous liver biopsy specimen showed BA with severe portal fibrosis and ductal proliferation. The patient underwent a Kasai hepatoportoenterostomy. On the basis of these results, the authors conclude that TC is a very specific ultrasonographic finding, representing the fibrous cone at the porta hepatis, and is a useful tool in the noninvasive diagnosis of BA. However, early exploration or close US follow-up is recommended for any patient suspected of having BA clinically, even if a liver biopsy confirms the NH.

Expression of transforming growth factor alpha in the liver before and after interferon alfa therapy for chronic hepatitis B

The effect of interferon alfa (IFN-α) therapy on the expression of transforming growth factor alpha (TGF-α) in the liver during chronic hepatitis B was investigated. Serial liver biopsy specimens were evaluated from 35 patients who had participated in a randomized, controlled trial of recombinant human IFN-α for the treatment of chronic hepatitis B. Percutaneous liver biopsy specimens obtained before and 1 year after entry in the trial were sectioned and stained with a monoclonal antibody to TGF-α in an avidin-biotin-peroxidase-complex system. The expression of TGF-α in each section was evaluated blindly (with respect to treatment group and order of biopsies) and was numerically scored. There was no significant difference in TGF-α expression before or after therapy between 13 patients receiving daily IFN-α, 13 receiving alternate-day IFN-α, and 9 receiving no therapy. Sustained clearance of HBV-DNA and DNA polymerase activity occurred in 8 of 26 treated patients (“responders”); the 18 other patients were “nonresponders”. Expression of TGF-α before IFN-α therapy was significantly higher in responders than in nonresponders; after IFN-α therapy, TGF-α expression decreased significantly among responders compared with nonresponders and untreated controls. Thus, the level of expression of TGF-α in the liver, which was correlated with the severity of inflammation in the liver in this study, appeared to be predictive of the response to IFN-α therapy in chronic hepatitis B, with a higher level of expression indicating a greater likelihood that the patient would respond.

Expression of transforming growth factor alpha in the liver before and after interferon alfa therapy for chronic hepatitis B

The effect of interferon alfa (IFN-α) therapy on the expression of transforming growth factor alpha (TGF-α) in the liver during chronic hepatitis B was investigated. Serial liver biopsy specimens were evaluated from 35 patients who had participated in a randomized, controlled trial of recombinant human IFN-α for the treatment of chronic hepatitis B. Percutaneous liver biopsy specimens obtained before and 1 year after entry in the trial were sectioned and stained with a monoclonal antibody to TGF-α in an avidin-biotin-peroxidase-complex system. The expression of TGF-α in each section was evaluated blindly (with respect to treatment group and order of biopsies) and was numerically scored. There was no significant difference in TGF-α expression before or after therapy between 13 patients receiving daily IFN-α, 13 receiving alternate-day IFN-α, and 9 receiving no therapy. Sustained clearance of HBV-DNA and DNA polymerase activity occurred in 8 of 26 treated patients (“responders”); the 18 other patients were “nonresponders.” Expression of TGF-α before IFN-α therapy was significantly higher in responders than in nonresponders; after IFN-α therapy, TGF-α expression decreased significantly among responders compared with nonresponders and untreated controls. Thus, the level of expression of TGF-α in the liver, which was correlated with the severity of inflammation in the liver in this study, appeared to be predictive of the response to IFN-α therapy in chronic hepatitis B, with a higher level of expression indicating a greater likelihood that the patient would respond. (Hepatology 1995; 22:1021-1026.).

Subcellular pathologic features of glucocorticoid-induced hepatopathy in dogs

SUMMARY Dogs are particularly susceptible to development of glucocorticoid-induced hepatopathy, but the mechanisms are not well understood. We investigated the pathogenesis of glucocorticoid hepatopathy by examining sequential morphologic and biochemical changes in the liver of dogs during steroid administration. Six adult Beagles were given prednisolone acetate (4 mg/kg of body weight, once daily for 24 days, im). Serum samples and percutaneous liver biopsy specimens were obtained before the start of the study (treatment day [td] 0) and at td 5, 10, 15, and 25. There were significant (P &lt; 0.05) and progressive increases in serum activities of alkaline phosphatase, γ-glutamyltransferase, and alanine transaminase. Light microscopic changes in liver biopsy specimens included progressive hepatocellular swelling and vacuolation. Electron microscopy revealed glycogen accumulation, peripheral displacement of organelles, and prominent dilatation of bile canaliculi, compared with findings at td 0. Liver biopsy specimens taken at td 25 had significantly (P &lt; 0.05) increased activities of the plasma membrane enzymes, alkaline phosphatase and γ-glutamyltransferase, and 5'-nucleotidase was significantly (P &lt; 0.01) decreased. Subcellular fractionation on reorientating sucrose density gradients revealed high-density peaks of alkaline phosphatase and γ-glutamyltransferase, compatible with a specific increase in the biliary canalicular component of the enzyme activities. Neutral α-glucosidase activity was shifted to the denser fractions, indicative of an increase in the proportion of rough to smooth endoplasmic reticulum and consistent with enhanced synthesis of plasma membrane proteins. There also was evidence for progressive increase in fragility of intracellular organelles, particularly lysosomes. These findings indicate that glucocorticoid hepatopathy in dogs is associated with progressive alterations not only to the plasma membrane, but also to other subcellular organelles.

Histopathological heterogeneity in fulminant hepatic failure

The clinicopathological features of 38 patients admitted consecutively for fulminant hepatic failure were studied. Histopathological material was reviewed in all patients. Both percutaneous and whole livers (either explanted or autopsy specimens) were available in 16 patients: whole livers only in 12 patients and biopsy specimens only in 10 patients. All patients were negative for antibodies to hepatitis C, whereas 24% had hepatitis B infection and 10% had adverse drug reactions. Livers from 75% of patients showed confluent hepatic necrosis. However, there was considerable variability in the extent of necrosis, and biopsy specimens from about 50% of the most severely affected livers showed only minimal bridging necrosis. In patients with massive hepatic necrosis, percutaneous liver biopsy specimens were frequently misleading because of regional inhomogeneities. Interestingly, five patients (13%) had established cirrhosis at the time of diagnosis. The best clinical predictors of survival were age and the maximal grade of encephalopathy. By contrast, neither the severity of confluent hepatic necrosis nor the etiology predicted the decision to transplant or the outcome. There were no differences in the histopathology corresponding to different etiologies. In summary, the approach to the patient with fulminant hepatic failure should be guided principally on clinical grounds, and further classification should be based on pathological and etiologic considerations. However, histological classification and prognosis based on percutaneous biopsy specimens alone may be misleading.

Histopathological heterogeneity in fulminant hepatic failure

The clinicopathological features of 38 patients admitted consecutively for fulminant hepatic failure were studied. Histopathological material was reviewed in all patients. Both percutaneous and whole livers (either explanted or autopsy specimens) were available in 16 patients: whole livers only in 12 patients and biopsy specimens only in 10 patients. All patients were negative for antibodies to hepatitis C, whereas 24% had hepatitis B infection and 10% had adverse drug reactions. Livers from 75% of patients showed confluent hepatic necrosis. However, there was considerable variability in the extent of necrosis, and biopsy specimens from about 50% of the most severely affected livers showed only minimal bridging necrosis. In patients with massive hepatic necrosis, percutaneous liver biopsy specimens were frequently misleading because of regional inhomogeneities. Interestingly, five patients (13%) had established cirrhosis at the time of diagnosis. The best clinical predictors of survival were age and the maximal grade of encephalopathy. By contrast, neither the severity of confluent hepatic necrosis nor the etiology predicted the decision to transplant or the outcome. There were no differences in the histopathology corresponding to different etiologies. In summary, the approach to the patient with fulminant hepatic failure should be guided principally on clinical grounds, and further classification should be based on pathological and etiologic considerations. However, histological classification and prognosis based on percutaneous biopsy specimens alone may be misleading.