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Liver Biopsy Specimens (liver + biopsy_specimen)
Selected AbstractsPhysiological hepatic nuclear vacuolation,how long does it persist?HISTOPATHOLOGY, Issue 4 2010Adam P Levene Levene A P & Goldin R D (2010) Histopathology56, 426,429 Physiological hepatic nuclear vacuolation,how long does it persist? Aims:, Nuclear vacuolation\glycogenation is a characteristic histological feature of non-alcoholic fatty liver disease (NAFLD) that can help distinguish it from alcohol-induced liver disease. There are, however, other associations of nuclear vacuolation of which the commonest is as a normal feature of childhood. The aim of this study was to identify how long this physiological nuclear vacuolation persists. Methods and results:, Liver biopsy specimens from 872 patients with chronic hepatitis B virus infection (a condition known not to be associated with nuclear vacuolation) were studied to assess the frequency of nuclear vacuolation at different ages. All the patients studied had a body mass index of <25 kg/m2 and an alcohol intake of <15 units/week, as well as no other risk factors for liver disease. It was found that the frequency of nuclear vacuolation, in the absence of NAFLD, fell from 13% at age 20,24 years to 4% in the early 30s and to 0% at age 60,64 years. Conclusions:, Physiological hepatic nuclear vacuolation is common in the 20s and persists into the 30s. This knowledge can help in the assessment of liver biopsy specimens in which nuclear vacuolation is a feature. [source] Hepatitis C virus induces oxidative stress, DNA damage and modulates the DNA repair enzyme NEIL1JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2010Sampa Pal Abstract Background and Aims:, Hepatitis C virus (HCV)-induced chronic inflammation may induce oxidative stress which could compromise the repair of damaged DNA, rendering cells more susceptible to spontaneous or mutagen-induced alterations, the underlying cause of liver cirrhosis and hepatocellular carcinoma. In the current study we examined the induction of reactive oxygen species (ROS) resulting from HCV infection and evaluated its effect on the host DNA damage and repair machinery. Methods:, HCV infected human hepatoma cells were analyzed to determine (i) ROS, (ii) 8-oxoG and (iii) DNA glycosylases NEIL1, NEIL2, OGG1. Liver biopsies were analyzed for NEIL1. Results:, Human hepatoma cells infected with HCV JFH-1 showed 30,60-fold increases in ROS levels compared to uninfected cells. Levels of the oxidatively modified guanosine base 8-oxoguanine (8-oxoG) were significantly increased sixfold in the HCV-infected cells. Because DNA glycosylases are the enzymes that remove oxidized nucleotides, their expression in HCV-infected cells was analyzed. NEIL1 but not OGG1 or NEIL2 gene expression was impaired in HCV-infected cells. In accordance, we found reduced glycosylase (NEIL1-specific) activity in HCV-infected cells. The antioxidant N-acetyl cystein (NAC) efficiently reversed the NEIL1 repression by inhibiting ROS induction by HCV. NEIL1 expression was also partly restored when virus-infected cells were treated with interferon (IFN). HCV core and to a lesser extent NS3-4a and NS5A induced ROS, and downregulated NEIL1 expression. Liver biopsy specimens showed significant impairment of NEIL1 levels in HCV-infected patients with advanced liver disease compared to patients with no disease. Conclusion:, Collectively, the data indicate that HCV induction of ROS and perturbation of NEIL1 expression may be mechanistically involved in progression of liver disease and suggest that antioxidant and antiviral therapies can reverse these deleterious effects of HCV in part by restoring function of the DNA repair enzyme/s. [source] Prognostic analysis in chronic hepatitis B patients: a retrospective study of 216 cases about Scheuer scores, in situ expression of viral antigens and tissue hepatitis B virus DNA levelsLIVER INTERNATIONAL, Issue 1 2006Rong Zhu Abstract: Background: Most of the previous studies of patients with chronic hepatitis B virus (HBV) infection concentrated on serum samples. Liver biopsy specimens for HBV have not been systematically analyzed. This study was performed to analyze some histopathological indicators (Scheuer scores, the expression of HBV antigens in situ, HBV DNA quantification) in the biopsy samples and showed the relationship among them and the prognosis of chronic hepatitis. Methods: A total of 216 consecutive chronic HBV-infected patients were followed up by clinical and laboratory data and classified into two groups at first: carcinogenesis and non-carcinogenesis. The non-carcinogenesis also included two groups: cirrhosis and non-cirrhosis. The non-cirrhosis was still divided into fluctuation and normalization at last. Histological activity index was described by Scheuer scores. Two-step immunohistochemical staining showed the expression of viral antigens in situ. Tissue HBV DNA levels were determined by fluorescence quantitative real-time PCR. Results: Regression analysis revealed significant positive correlations between the expression of hepatitis B e antigen (HBeAg) and grading, as well as between hepatitis Bx (HBx) protein and grading or staging of Scheuer scores. Positive correlations between grading or staging and prognosis were statistically significant. The expressions of HBeAg and HBx protein were higher in patients with cirrhosis than those without cirrhosis. Scheuer score was the most important indicator of prognosis. Conclusions: HBeAg and HBx protein can be used as indicators of hepatitis activity and their positive expressions increase the risk for cirrhosis remarkably. In addition to be a marker of liver damage, Scheuer score is the most reliable indicator of the prognosis. [source] Liver histology after current intensified therapy for childhood acute lymphoblastic leukemia: microvesicular fatty change and siderosis are the main findingsPEDIATRIC BLOOD & CANCER, Issue 3 2003Päivi Halonen MD Abstract Background During modern intensified therapy for childhood acute lymphoblastic leukemia (ALL) serum liver enzymes reach fairly high levels. Since no recent data on liver histopathology after therapy are available, we conducted a study of the subject. Procedure Liver biopsy specimens were evaluated and serum liver function tests and lipid profiles measured from 27 consecutive children, aged 3.5,17.6 years, treated according to the regimens for standard (SR) and intermediate risk (IR) ALL. Results None of the patients had entirely normal liver histology. Fatty infiltration was detected in 25 out of 27 (93%) and siderosis in 19 out of 27 patients (70%). Fourteen (52%) had both. Three (11%) also had mild portal and/or periportal fibrosis in addition to fatty change and siderosis. Fatty change was mainly microvesicular. Siderosis was in most cases grade II/IV to III/IV (in 16/19 or 84%). No hepatitis or cirrhosis was found. Serum total and LDL-cholesterol levels were higher in the patients with fibrosis than in the patients with fatty change (P,=,0.036, P,=,0.042) or with siderosis,±,fatty change (P,=,0.036, P,=,0.042). In serial ALT measurements a value of 300 U/L or more was oftener reached in the fibrosis than in the fatty change or siderosis groups (in 33 vs. in 12 or in 4% of the measurements, respectively, P,=,0.014, in Kruskall,Wallis test). Conclusions Microvesicular fatty change and siderosis are the main liver findings after current therapy for childhood ALL. Fibrosis occurs rarely. High values in serial serum ALT measurements repeatedly or a disturbed serum lipid profile may facilitate decisions about the need for a liver biopsy. Med Pediatr Oncol 2003;40:148,154. © 2003 Wiley-Liss, Inc. [source] Association of non-alcoholic steatohepatitis (NASH) with chronic neutrophilic leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2004Chikashi Yoshida Abstract: A 54-yr-old female having chronic neutrophilic leukemia (CNL) associated with severe liver injury is presented. Physical examination on admission showed severe jaundice, hepatosplenomegaly, massive ascites, and pretibial edema. Complete blood count showed a hemoglobin level of 9.1 g/dL, platelet count of 25.8 × 104/,L, and white blood cell count of 36.6 × 103/,L with 89.7% neutrophils. Blood chemistry showed hyperbilirubinemia (21.9 mg/dL) with normal transaminase levels. There was no abnormality in serum cholesterol, triglyceride, or glucose levels. Neutrophil alkaline phosphatase activity was significantly elevated. Bone marrow aspiration showed myeloid hyperplasia with normal karyotype. Rearrangement of the bcr/abl was not detected by either polymerase chain reaction or fluorescence in situ hybridization. Human androgen receptor gene assay (HUMARA) of the bone marrow cells showed clonal proliferation of neutrophils. The patient was diagnosed as having CNL. To evaluate the pathogenesis of the liver injury, a needle biopsy was performed, which showed steatohepatitis with infiltration of neutrophils. As the patient had no history of alcohol abuse, a diagnosis of non-alcoholic steatohepatitis (NASH) was made. Assuming that the infiltration of abnormal neutrophils into the liver contributed to the development of NASH, she was treated with cytoreductive chemotherapy (cytosine arabinoside: 100 mg/d, 1,3 doses/wk). With decreases in white blood cell counts, serum bilirubin levels decreased gradually to 1.5 mg/mL. A postchemotherapy liver biopsy specimen showed marked improvement of the fatty degenerative change. To our knowledge, this is the first report describing the development of NASH in a myeloproliferative disorder. We believe that the infiltration of leukemic cells contributed to the development of NASH in this patient. [source] Successful clearance of hepatitis B virus after allogeneic stem cell transplantation: beneficial combination of adoptive immunity transfer and lamivudineEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2003Tetsuhiro Chiba Abstract: We report a 38-yr-old male with acute lymphocytic leukemia (ALL), whose serological tests for the hepatitis B virus (HBV) before transplantation showed a chronic carrier status, and a liver biopsy specimen revealed chronic liver injury because of HBV. The patient underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his sibling who was hepatitis B surface antibody (HBsAb) positive. He had received lamivudine treatment for the prophylaxis of HBV reactivation during cytotoxic chemotherapy, and lamivudine administration continued after transplantation. Successful engraftment was documented 3 wk after PBSCT, and clearance of the hepatitis B surface antigen (HBsAg) was observed 2 months after PBSCT. Liver function tests transiently showed a mild elevation of aminotransferases on day 25, although this returned to normal after the dose escalation of the immunosuppressive agent. We presume that the combination of adoptive immunity transfer by bone marrow transplantation (BMT) from an HBsAb-positive donor and antiviral drugs such as lamivudine is beneficial in clearing HBV in chronic carriers. [source] Sampling variability of liver fibrosis in chronic hepatitis CHEPATOLOGY, Issue 6 2003Pierre Bedossa M.D. Fibrosis is a common endpoint of clinical trials in chronic hepatitis C, and liver biopsy remains the gold standard for fibrosis evaluation. However, variability in the distribution of fibrosis within the liver is a potential limitation. Our aim was to assess the heterogeneity of liver fibrosis and its influence on the accuracy of assessment of fibrosis with liver biopsy. Surgical samples of livers from patients with chronic hepatitis C were studied. Measurement of fibrosis was performed on the whole section by using both image analysis and METAVIR score (reference value). From the digitized image of the whole section, virtual biopsy specimens of increasing length were produced. Fibrosis was assessed independently on each individual virtual biopsy specimen. Results were compared with the reference value according to the length of the biopsy specimen. By using image analysis, the coefficient of variation of fibrosis measurement with 15-mm long biopsy specimens was 55%; and for biopsy specimens of 25-mm length it was 45%. By using the METAVIR scoring system, 65% of biopsies 15 mm in length were categorized correctly according to the reference value. This increased to 75% for a 25-mm liver biopsy specimen without any substantial benefit for longer biopsy specimens. Sampling variability of fibrosis is a significant limitation in the assessment of fibrosis with liver biopsy. In conclusion, this study suggests that a length of at least 25 mm is necessary to evaluate fibrosis accurately with a semiquantitative score. Sampling variability becomes a major limitation when using more accurate methods such as automated image analysis. [source] Risk factors for fibrosis progression in HIV/HCV coinfected patients from a retrospective analysis of liver biopsies in 1985,2002HIV MEDICINE, Issue 5 2006M Schiavini Objectives To identify predictive factors for moderate/severe liver fibrosis and to analyse fibrosis progression in paired liver biopsies from HIV-positive patients with chronic hepatitis C virus (HCV) infection. Methods HIV/HCV coinfected patients followed at the 2nd Department of Infectious Diseases of L. Sacco Hospital in Milan, Italy, with at least one liver biopsy specimen were retrospectively evaluated. Results A total of 110 patients were enrolled in the study. In a univariate analysis, predictive factors of Ishak,Knodell stage ,3 were a history of alcohol abuse [odds ratio (OR) 3.6, P=0.004], alanine aminotransferase level >100 IU/L at biopsy (OR 2.4, P=0.05), necro-inflammatory grade ,9 (OR 37.14, P<0.0001) and CD4 count <350 cells/,L at nadir (OR 5.3, P=0.05). In a multivariate analysis, age >35 years (OR 3.19, P=0.04) and alcohol abuse (OR 4.36, P=0.002) remained independently associated with Ishak,Knodell stage. Paired liver biopsies were available in 36 patients; 18 showed an increase of at least one stage in the subsequent liver biopsy. Either in a univariate or in a multivariate analysis, a decrease of CD4 cell count of more than 10% between two biopsies (OR 6.85, P=0.002) was significantly associated with liver fibrosis progression. Conclusion Our findings highlight the relevance of encouraging a withdrawal of alcohol consumption in people with chronic HCV infection and of carrying out close follow-up of patients, especially if they are more than 35 years old. It is therefore mandatory to evaluate HIV/HCV coinfected patients for anti-HCV treatment and to increase CD4 cell count through antiretroviral therapy in order to reduce the risk of fibrosis progression and to slow the evolution of liver disease. [source] Hepatic graft-versus-host disease resembling acute hepatitis: additional treatment with ursodeoxycholic acidLIVER INTERNATIONAL, Issue 6 2002Tetsuhiro Chiba Abstract: Hepatic graft-versus-host disease (GVHD) is a frequent complication after bone-marrow transplantation (BMT). The disease is often refractory to immunosuppressive therapy. We present a 30-year-old Japanese male, who developed an abrupt elevation of aminotransferases, on day 135 after allogeneic BMT. A liver biopsy specimen revealed degeneration of the small bile ducts and portal fibrosis, and the diagnosis of chronic hepatic GVHD was confirmed. No manifestation of chronic GVHD was observed except liver dysfunction. The administration of prednisolone (PSL) and cyclosporin (CsA) ameliorated laboratory data to a degree, but they did not return to normal. Treatment with ursodeoxycholic acid (UDCA), subsequently added to the immunosuppressive therapy, apparently normalized the levels of biliary tract enzyme and total bilirubin. His liver function test completely returned to normal on day 260. We believe that it is worthwhile to administer UDCA as an additional treatment for not only common hepatic GVHD but also atypical cases presenting as acute hepatitis. [source] Correlation of percutaneous liver biopsy fragmentation with the degree of fibrosisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2004A. H. Malik Summary Background :,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. Aim :,To determine whether fragmentation of percutaneous liver biopsy specimens correlates with the degree of fibrosis. Methods :,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. Results :,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. Conclusions :,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. [source] Detection of Helicobacter ganmani -Like 16S rDNA in Pediatric Liver TissueHELICOBACTER, Issue 5 2004Vasundhara Tolia ABSTRACT Background., To determine the presence of Helicobacter species in the liver biopsy specimens from children with various chronic liver diseases as data in adult literature suggests a possible role of these bacteria in their pathogenesis. Materials and methods., Paraffin sections of 61 liver biopsies of pediatric patients with miscellaneous diseases and autopsy liver tissue from 10 control subjects with no evidence of preexisting liver disease were examined for the presence of Helicobacter species by a genus-specific seminested polymerase chain reaction (PCR) assay. PCR,products of positive samples were further characterized by denaturing gradient gel electrophoresis (DGGE) and DNA-sequence analysis. Based on those results, a seminested PCR assay for H. ganmani was developed and applied to the samples. Results., On analysis, 40/61 patient samples were positive in the genus-specific Helicobacter PCR and 4/10 from the control group. The nucleotide sequences of 16S rDNA fragments were 99,100% similar to mainly Helicobacter sp. ,liver' and H. ganmani. PCR-products similar to H. canis and H. bilis were also found. The 16S rDNAs of control specimens showed similarity to Helicobacter sp. ,liver'. In the H. ganmani -specific PCR analysis 19 patients, but none of the controls, were positive. Conclusions., Amplified Helicobacter 16S rDNAs were related to Helicobacter sp. ,liver' or H. ganmani in liver biopsy specimens of pediatric patients. The possible significance of Helicobacter species in pediatric liver diseases needs to be evaluated further in prospective studies. [source] The interleukin-17 pathway is involved in human alcoholic liver disease,,HEPATOLOGY, Issue 2 2009Arnaud Lemmers Immune dysregulations in alcoholic liver diseases are still unclear, especially regarding alcoholic hepatitis inflammatory burst. Interleukin-17 (IL-17) is known to enhance neutrophil recruitment. We studied the IL-17 pathway in alcoholic cirrhosis and alcoholic hepatitis. Patients with alcoholic liver disease were compared with patients with chronic hepatitis C virus (HCV) infection or autoimmune liver disease and with healthy controls. IL-17 plasma levels and peripheral blood mononuclear cell secretion were assessed by enzyme-linked immunosorbent assay (ELISA) and T cell phenotype by flow cytometry. IL-17 staining and co-staining with CD3 and myeloperoxidase were performed on liver biopsy specimens. IL-17 receptor expression was studied on liver biopsies and in human hepatic stellate cells as well as their response to recombinant IL-17 by chemotaxis assays. IL-17 plasma levels were dramatically increased in alcoholic liver disease patients. Peripheral blood mononuclear cells of patients with alcoholic liver disease produced higher amounts of IL-17, and their CD4+ T lymphocytes disclosed an IL-17,secreting phenotype. In the liver, IL-17,secreting cells contributed to inflammatory infiltrates in alcoholic cirrhosis, and alcoholic hepatitis foci disclosed many IL-17+ cells, including T lymphocytes and neutrophils. In alcoholic liver disease, liver IL-17+ cells infiltrates correlated to model for end-stage liver disease score, and in alcoholic hepatitis to modified discriminant function. IL-17 receptor was expressed in alcoholic liver disease by hepatic stellate cells, and these cells recruited neutrophils after IL-17 stimulation in a dose-dependent manner through IL-8 and growth related oncogen , (GRO-,) secretion in vitro. Conclusion: Human alcoholic liver disease is characterized by the activation of the IL-17 pathway. In alcoholic hepatitis, liver infiltration with IL-17,secreting cell infiltrates is a key feature that might contribute to liver neutrophil recruitment. (Clinical trials number NCT00610597). (HEPATOLOGY 2009;49:646,657.) [source] High frequency of chimerism in transplanted liversHEPATOLOGY, Issue 4 2003Irene Oi-Lin Ng M.D. Recent studies have shown that primitive stem cells can mobilize and differentiate into hepatocytes. We investigated the time and extent in which cells of recipient origins could differentiate into hepatocytes and other cells in human liver allografts. Microsatellite analysis, which can assess quantitatively the proportions of recipient and donor DNA, was performed in posttransplantation liver biopsy specimens from 17 patients at various times. Combined fluorescence in situ hybridization (FISH) for Y chromosome and immunofluorescence for different cell types was also performed in 10 of these cases with sex mismatch. Organ chimerism in the transplanted livers was found to be of variable extent, and the recipients' DNA in the posttransplantation liver biopsy specimens (excluding portal tracts) amounted up to 50%. The recipient DNA in the posttransplantation liver biopsy specimens increased after liver transplantation by as early as 1 week, peaked at around 30 to 40 weeks, and could be shown 63 weeks after transplantation. Most (64%,75%) of the recipientderived cells showed macrophage/Kupffer cell differentiation. Only up to 1.6% of the recipient-derived cells in the liver grafts showed hepatocytic differentiation in the liver grafts and made up 0.62% of all hepatocytes of both donor and recipient origins. These livers had mild or minimal injury histologically. In conclusion, our results show that most of the recipient-derived cells in the liver allografts were macrophages/Kupffer cells and only a small proportion of hepatocytes was recipient derived. However, with regard to recipient-derived hepatocytes, our data cannot distinguish between transdifferentiation and cell fusion. (Hepatology 2003;38:989,998). [source] A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis CHEPATOLOGY, Issue 2 2003Chun-Tao Wai Information on the stage of liver fibrosis is essential in managing chronic hepatitis C (CHC) patients. However, most models for predicting liver fibrosis are complicated and separate formulas are needed to predict significant fibrosis and cirrhosis. The aim of our study was to construct one simple model consisting of routine laboratory data to predict both significant fibrosis and cirrhosis among patients with CHC. Consecutive treatment-naive CHC patients who underwent liver biopsy over a 25-month period were divided into 2 sequential cohorts: training set (n = 192) and validation set (n = 78). The best model for predicting both significant fibrosis (Ishak score , 3) and cirrhosis in the training set included platelets, aspartate aminotransferase (AST), and alkaline phosphatase with an area under ROC curves (AUC) of 0.82 and 0.92, respectively. A novel index, AST to platelet ratio index (APRI), was developed to amplify the opposing effects of liver fibrosis on AST and platelet count. The AUC of APRI for predicting significant fibrosis and cirrhosis were 0.80 and 0.89, respectively, in the training set. Using optimized cut-off values, significant fibrosis could be predicted accurately in 51% and cirrhosis in 81% of patients. The AUC of APRI for predicting significant fibrosis and cirrhosis in the validation set were 0.88 and 0.94, respectively. In conclusion, our study showed that a simple index using readily available laboratory results can identify CHC patients with significant fibrosis and cirrhosis with a high degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among CHC patients. [source] Caspase activation correlates with the degree of inflammatory liver injury in chronic hepatitis C virus infectionHEPATOLOGY, Issue 4 2001Heike Bantel Hepatitis C virus (HCV) infection is a major cause of liver disease characterized by inflammation, cell damage, and fibrotic reactions of hepatocytes. Apoptosis has been implicated in the pathogenesis, although it is unclear whether proteases of the caspase family as the central executioners of apoptosis are involved and how caspase activation contributes to liver injury. In the present study, we measured the activation of effector caspases in liver biopsy specimens of patients with chronic HCV infection. The activation of caspase-3, caspase-7, and cleavage of poly(ADP-ribose)polymerase (PARP), a specific caspase substrate, were measured by immunohistochemistry and Western blot analysis by using antibodies that selectively detect the active truncated, but not the inactive precursor forms of the caspases and PARP. We found that caspase activation was considerably elevated in liver lobules of HCV patients in comparison to normal controls. Interestingly, the immunoreactive cells did yet not reveal an overt apoptotic morphology. The extent of caspase activation correlated significantly with the disease grade, i.e., necroinflammatory activity. In contrast, no correlation was observed with other surrogate markers such as serum transaminases and viral load. In biopsy specimens with low activity (grade 0) 7.7% of the hepatocytes revealed caspase-3 activation, whereas 20.9% of the cells stained positively in grade 3. Thus, our results suggest that caspase activation is involved in HCV-associated liver injury. Moreover, measurement of caspase activity may represent a reliable marker for the early detection of liver damage, which may open up new diagnostic and therapeutic strategies in HCV infection. [source] Physiological hepatic nuclear vacuolation,how long does it persist?HISTOPATHOLOGY, Issue 4 2010Adam P Levene Levene A P & Goldin R D (2010) Histopathology56, 426,429 Physiological hepatic nuclear vacuolation,how long does it persist? Aims:, Nuclear vacuolation\glycogenation is a characteristic histological feature of non-alcoholic fatty liver disease (NAFLD) that can help distinguish it from alcohol-induced liver disease. There are, however, other associations of nuclear vacuolation of which the commonest is as a normal feature of childhood. The aim of this study was to identify how long this physiological nuclear vacuolation persists. Methods and results:, Liver biopsy specimens from 872 patients with chronic hepatitis B virus infection (a condition known not to be associated with nuclear vacuolation) were studied to assess the frequency of nuclear vacuolation at different ages. All the patients studied had a body mass index of <25 kg/m2 and an alcohol intake of <15 units/week, as well as no other risk factors for liver disease. It was found that the frequency of nuclear vacuolation, in the absence of NAFLD, fell from 13% at age 20,24 years to 4% in the early 30s and to 0% at age 60,64 years. Conclusions:, Physiological hepatic nuclear vacuolation is common in the 20s and persists into the 30s. This knowledge can help in the assessment of liver biopsy specimens in which nuclear vacuolation is a feature. [source] Expression of tumour necrosis factor-related apoptosis-inducing ligand and caspase-3 in relation to grade of inflammation and stage of fibrosis in chronic hepatitis CHISTOPATHOLOGY, Issue 5 2007A Piekarska Aim:, To assess whether the distribution of the recently described proapoptotic ligand, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), and the apoptosis effector, caspase-3 alters with the degree of inflammation and fibrosis present in liver biopsy specimens from patients with chronic hepatitis C virus infection. Methods and results:, Expression of TRAIL and caspase-3 was assessed immunohistochemically in liver biopsy specimens obtained from 89 adults with chronic hepatitis C. Expression of TRAIL in hepatocytes correlated inversely with stage of fibrosis (P = 0.001), classified according to the Scheuer score; expression of caspase-3 in hepatocytes correlated with grade of inflammation (P = 0.012). Expression of TRAIL in hepatocytes was not correlated with grade of inflammation (P > 0.05); expression of caspase-3 was not correlated with stage of fibrosis (P > 0.05). Maximum expression of proapoptotic TRAIL protein was observed in cases with low grade inflammation (G0) and low stage fibrosis (S1). Maximum expression of caspase-3 in hepatocytes was observed in cases with high grade inflammation (G3,4) and high stage fibrosis (S3), but not with liver cirrhosis (S4). Conclusions:, There is a significant decrease in TRAIL expression with increasing grade of inflammation, whereas caspase-3 expression is significantly increased with advanced fibrosis, short of cirrhosis. [source] Immunohistochemical staining of liver grafts with a monoclonal antibody against HCV-Envelope 2 for recurrent hepatitis C after living donor liver transplantationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2009Hiroshi Sadamori Abstract Aim:, We evaluated the expression of hepatitis C virus (HCV) antigen on liver grafts by immunohistochemical staining (IHS) using IG222 monoclonal antibody (mAb) against HCV-envelope 2 (E2). Methods:, The study material was 84 liver biopsy specimens obtained from 28 patients who underwent living donor liver transplantation (LDLT) for HCV infection. The biopsy samples were examined histopathologically, and by IHS using IG222 mAb against HCV-E2. Serum HCV-RNA level was measured in all patients. The IHS grades were compared among the three groups classified according to the time elapsed from LDLT (at 1,30, 31,179 and ,180 days post-LDLT) and among four post-transplant conditions, including acute cellular rejection (ACR). Results:, Immunoreactivity to IG222 was detected in 78.6% of the specimens obtained during the first month after LDLT, and there were no significant differences on the IHS grades between the three groups classified according to the time elapsed from LDLT. The IHS grades were significantly stronger in definite recurrent HCV (n = 12) and probable recurrent HCV (n = 7) than in definite ACR (n = 7) and other complications (n = 8). There were no significant differences in serum HCV-RNA levels among the four post-transplant conditions. There was no significant correlation between the IHS grades using IG222 mAb and serum HCV-RNA levels when data of 84 liver biopsy specimens were analyzed. Conclusions:, Constant HCV-E2 expression was observed in liver biopsy specimens obtained 1 month or longer. The strong HCV-E2 expression on liver grafts were associated with recurrent hepatitis C after LDLT, but the serum HCV-RNA levels were not. [source] Long-term outcome of chronic hepatitis B based on histological grade and stageJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2007Byung Kyu Park Abstract Background and Aim:, This study evaluated the long-term outcome and prognostic factors of chronic hepatitis B, based on histological grade and stage. Methods:, A total of 188 patients with chronic hepatitis B were followed for a mean 119.8 months. Ultrasonography and clinical assessment were performed regularly. In addition, liver biopsy specimens were re-evaluated based on histological grade and stage. Results:, During follow-up, cirrhosis developed in 62 patients, decompensation in 20 patients, and hepatocellular carcinoma (HCC) in 21 patients. The serum alanine aminotransferase (ALT) level at the time of liver biopsy was significantly correlated with the grades of lobular and porto-periportal activity. The development of cirrhosis correlated well with the grade of porto-periportal activity and stage of fibrosis. The probabilities of developing cirrhosis, decompensation and HCC were significantly higher in patients whose ALT levels were persistently elevated without flares or flared-up without normalization than in patients whose ALT levels flared-up then normalized or were normally sustained. By multivariate analysis, age and biochemical profile during follow-up were independent prognostic factors for chronic hepatitis B. Conclusions:, The results demonstrate that histological grade and stage, and biochemical profile during follow-up in patients with chronic hepatitis B are important prognostic factors. Therefore, effective control of hepatitis activity might improve the long-term outcome of chronic hepatitis B patients. [source] Serum amino-terminal propeptide of type III procollagen and 7S domain of type IV collagen correlate with hepatic iron concentration in patients with chronic hepatitis C following ,-interferon therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2001Ichiro Shimizu Abstract Background: It has been reported that chronic infection with hepatitis C virus is associated with excess iron deposits in the liver of subjects who are neither alcoholics nor recipients of blood transfusions. However, little is known about the relationship between hepatic iron concentration (HIC) and the serum levels of hepatic fibrogenesis markers, which were caused by interferon therapy for chronic hepatitis C. Therefore, changes in the serum amino-terminal propeptide of type III procollagen (P-III-P) and the 7S domain of type IV collagen (7S-IV) in 16 patients treated with ,-interferon (IFN-,) were studied, and their HIC and histological assessment evaluated. Hepatic iron concentrations were measured by using liver biopsy specimens obtained before and 6 months after the cessation of treatment. Methods and Results: Eight subjects (50%) who had normal alanine transaminase levels at 6 months after therapy showed significantly lowered HIC, and attenuated hepatic iron staining with decreased serum levels of P-III-P and 7S-IV compared to the remaining subjects. The HIC was significantly correlated with the serum levels of P-III-P and 7S-IV in all subjects. Conclusions: These findings suggest that IFN-, treatment may decrease stimuli for fibrogenesis, at least in part, by reducing the hepatic iron deposition in patients with chronic hepatitis C. [source] The correlation of hepatocyte nuclear factor 4 alpha and 3 beta with hepatitis B virus replication in the liver of chronic hepatitis B patientsJOURNAL OF VIRAL HEPATITIS, Issue 8 2009Y. Long Summary., Hepatocyte nuclear factors 4 alpha (HNF4,) and 3 beta (HNF3,) are members of a group of liver-enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV). Using cell culture and animal models, we showed that HNF4, supports HBV replication in nonhepatic cells and HNF3, inhibits HBV replication. However, the expression of HNF4, and HNF3, in the liver tissue of chronic HBV-infected patients and the relationship between the levels of HNF4, and HNF3, and HBV replication are unclear. In this study, liver biopsy specimens from 86 chronic HBV-infected patients were collected. The expression levels of HNF4,, HNF3,, hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) were detected by an immunohistochemical technique and the level of HBV DNA was checked by in situ hybridization with serial sections from liver biopsy tissue samples. We show here that samples with higher levels of HNF4, expression also have higher levels of HBsAg, HBcAg and HBV DNA. In contrast, in samples with higher levels of HNF3, expression, levels of HBsAg, HBcAg and HBV DNA were lower. There was a positive correlation between HNF4, expression and HBV replication, and a negative correlation between HNF3, expression and HBV replication, in the liver of chronic HBV-infected patients. This suggests that HNF4, and HNF3, likely participate in HBV replication in patients with HBV infection, or that HBV replication may somehow influence the expression of HNF4, and HNF3, in the liver. [source] Predicting progressive hepatic fibrosis stage on subsequent liver biopsy in chronic hepatitis C virus infection,JOURNAL OF VIRAL HEPATITIS, Issue 1 2005J. D. Collier Summary., Retrospective cross-sectional studies indicate that 20% with chronic hepatitis C virus (HCV) infection become cirrhotic within 20 years. Known risk factors for advanced hepatic fibrosis include age at time of infection, male sex, excess alcohol consumption and cytokine polymorphisms. Prospective study to assess and identify factors predictive of change in hepatic fibrosis stage in chronic HCV infection by interval protocol liver biopsy was performed. One hundred and five patients with paired liver biopsy specimens separated by a mean 41 months were recruited from a cohort of 823 HCV carriers. Five per cent developed worsening hepatic fibrosis by more than two stages. In 43% there was no change in fibrosis stage. Excessive alcohol intake currently (P = 0.037) or previously (P = 0.07) predicted progression. In contrast, always having a normal alanine transaminase (P = 0.038) and always being negative in serum for HCV RNA (P =0.067) predicted no progression. Three models were developed to predict outcome. Progressive fibrosis was predicted by baseline fibrosis (P = 0.018), steatosis (P = 0.02) and age (P = 0.017). The rate of progressive fibrosis was predicted by baseline fibrosis (P = 0.0002), steatosis (P =0.039) and lobular inflammation (P = 0.09). Fibrosis stage on the second biopsy was predicted by baseline fibrosis alone (P = 0.01). The rate of progression varies widely. Alcohol misuse is an important co-factor. Progressive fibrosis can be predicted at first liver biopsy, where baseline fibrosis is most critical, allowing targeted therapy for those with early disease and a significant risk of progression. [source] Correlation of percutaneous liver biopsy fragmentation with the degree of fibrosisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2004A. H. Malik Summary Background :,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. Aim :,To determine whether fragmentation of percutaneous liver biopsy specimens correlates with the degree of fibrosis. Methods :,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. Results :,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. Conclusions :,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. [source] Recurrence of primary sclerosing cholangitis after liver transplantationLIVER TRANSPLANTATION, Issue 7 2002Ivo W. Graziadei MD Orthotopic liver transplantation (OLT) has become the only effective therapeutic option for patients with end-stage liver disease caused by primary sclerosing cholangitis (PSC). Excellent long-term outcome has been reported, with 5-year patient survival rates of approximately 80%. In the last few years, increasing evidence has emerged that PSC recurs after OLT. The diagnosis of PSC is based on well-defined cholangiographic features combined with biochemical and histological findings. However, none of these features is specific for PSC, particularly after OLT, because biliary strictures in the liver allograft can occur from a variety of causes other than recurrence. Therefore, PSC recurrence remains a controversial issue, especially because of a lack of a gold standard for diagnosis and well-established diagnostic criteria. Some reports provided cholangiographic evidence that post-OLT biliary strictures occurred more frequently in patients with PSC than in those who underwent OLT for other liver diseases (including patients with a Roux-en-Y biliary reconstruction). Because no other possible cause of biliary strictures could be invoked to explain the greater prevalence of these strictures, recurrent disease has been implicated. There also is histological evidence suggesting that PSC recurs after OLT. Histological findings suggestive of PSC were found more often in PSC allografts compared with a control group. Furthermore, histological features typical for PSC (fibro-obliterative lesions) were seen exclusively in liver biopsy specimens from patients with PSC. Recurrence of PSC was defined in a recent study from the Mayo Clinic by means of strict cholangiographic and histological criteria in a large cohort of patients with PSC in whom other causes of biliary strictures were excluded. PSC recurrence was found in 20% of patients. No risk factor for PSC recurrence could be found, and recurrent disease did not influence patient or graft survival after a mean follow-up of 4.5 years. In conclusion, several studies provided convincing evidence that PSC recurs after OLT, with an incidence of 5% to 20% and an interval to diagnosis of at least 1 year after OLT. To date, patient and graft survival do not appear to be negatively affected by disease recurrence in the intermediate term of follow-up. (Liver Transpl 2002;8:575-581.) [source] Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver diseaseLIVER TRANSPLANTATION, Issue 9 2001Janus Ong Some patients diagnosed with cryptogenic cirrhosis may have "burned-out" nonalcoholic fatty liver disease (NAFL). To test this hypothesis, we used our liver transplant database (November 1984 to November 1998) to assess the incidence of NAFL in patients with cryptogenic cirrhosis after orthotopic liver transplantation (OLT). We also examined the clinicodemographic features associated with post-OLT NAFL, obtained by chart review and telephone interviews. When available, post-OLT liver biopsy specimens were reviewed blindly by a hepatopathologist according to the NAFL pathology protocol. We identified 51 patients with cryptogenic cirrhosis (mean age, 51 ± 12 years); 60% were women, 94% were white, and 34% had type 2 diabetes mellitus (DM). Mean pre-OLT body mass index (BMI) was 27.33 ± 5.54 kg/m2. Twenty-five patients underwent at least 1 post-OLT liver biopsy. Post-OLT NAFL was identified in 13 patients (25.4%), whereas post-OLT nonalcoholic steatohepatitis (NASH) was seen in 8 patients (15.7%). Features associated with post-OLT NASH were pre- and post-OLT type 2 DM (P , .05) and an elevated fasting triglyceride level (P < .05). BMI tended to be greater in patients with post-OLT NAFL or NASH. Those who did not develop post-OLT NAFL showed a decrease in BMI. Patients with cryptogenic cirrhosis undergoing OLT resemble patients with NAFL. Post-OLT NAFL and NASH can be seen in a number of patients with cryptogenic cirrhosis. This supports the notion that some cases of cryptogenic cirrhosis represent burned-out NAFL. [source] Impairment of Hepatic Microcirculation in Fatty LiverMICROCIRCULATION, Issue 6 2003SAMIA IJAZ ABSTRACT Fatty liver or hepatic steatosis, which is the result of the abnormal accumulation of triacylglycerol within the cytoplasm of hepatocytes, is a common histological finding in human liver biopsy specimens that is attributed to the effects of alcohol excess, obesity, diabetes, or drugs. There is a general consensus that fatty liver compromises hepatic microcirculation, the common exchange network upon which hepatic arterial and portal inflows converge, regardless of underlying etiology. A significant reduction in hepatic microcirculation has been observed in human fatty donor livers and in experimental models of hepatic steatosis. There is an inverse correlation between the degree of fat infiltration and both total hepatic blood flow and flow in microcirculation. Fatty accumulation in the cytoplasm of the hepatocytes is associated with an increase in the cell volume that reduces the size of the hepatic sinusoid space by 50% compared with a normal liver and may result in partial or complete obstruction of the hepatic sinusoid space. As a result of impaired hepatic microcirculation, the hepatocytes of the fatty liver have reduced tolerance against ischemia-reperfusion injury, which affects about 25% of the donors for liver transplantation because severe steatosis is associated with a high risk of primary nonfunction after liver transplantation. [source] Liver biopsy results in patients with sickle cell disease on chronic transfusions: Poor correlation with ferritin levelsPEDIATRIC BLOOD & CANCER, Issue 1 2008Lina B. Karam MD Abstract Background: Chronic transfusions are effective in preventing stroke and other complications of sickle cell disease. The aim of this study was to determine whether serum ferritin levels correlated with liver iron content in sickle cell patients on chronic transfusion. Procedure: Forty-four liver biopsy specimens from 38 patients with homozygous sickle cell anemia (HbSS) and one patient with sickle thalassemia receiving chronic transfusions were studied. Five patients underwent a second liver biopsy for follow up. Three ferritin measurements were used to calculate a mean for each patient. The association between serum ferritin levels and liver iron quantitation was measured using the Spearman rank correlation, and sensitivity and specificity were determined for selected threshold values of serum ferritin. Results: Serum ferritin levels ranged from 515 to 6076 ng/ml, liver iron concentration ranged from 1.8 to 67.97 mg/g dry weight. The amount of iron per gram liver dry weight was moderately correlated with serum ferritin values (r,=,0.46). The correlation of duration of transfusion with serum ferritin (r,=,0.40) and with liver iron content (r,=,0.41) also indicated moderate correlation. Liver biopsy results led to changes in the management after 29/44 (66%) of the biopsies. Serum ferritin ,2500 ng/ml predicted high liver iron content (,7 mg/g), with a sensitivity of 62.5% and a specificity of 77.8%. Conclusion: We found a poor correlation between serum ferritin levels and liver iron content (LIC). Despite being on chelation therapy, many patients on chronic transfusion had high levels of liver iron. Measurement of LIC is highly recommended in these patients. Pediatr Blood Cancer 2008;50:62,65. © 2007 Wiley-Liss, Inc. [source] Patterns of hepatic iron distribution in patients with chronically transfused thalassemia and sickle cell disease,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009Nilesh R. Ghugre Patients with sickle cell disease (SCD) appear to be at lower risk of endocrinopathies and cardiac dysfunction than those with thalassemia major (TM). Circulating redox active iron is lower in these patients, possibly due to increased systemic inflammation and circulating cytokines. Hepcidin synthesis is upregulated during chronic inflammation, reducing intestinal iron absorption and promoting retention of iron in the reticuloendothelial cells. Hence, we hypothesized that livers of patients with SCD would exhibit greater iron deposition in sinusoidal spaces relative to hepatocytes and less in portal tracts when compared to patients with TM. To test this hypothesis, iron scoring analysis was performed on 70 clinically indicated liver biopsy specimens from children and young adults with the two syndromes. Sinusoidal scores were lower in around 1 of 4 patients with TM but the relative iron loading in hepatocytes, and portal tracts was identical in both diseases. Sinusoidal iron burdens saturated at low hepatic iron concentration (HIC) while hepatocyte and portal iron depots increased proportionally to HIC. Liver fibrosis was increased in patients with TM regardless of their chronic hepatitis status. Overall, liver iron distribution was relatively insensitive to differences in disease type and to the presence or absence of hepatitis. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Significance of CT Attenuation Value in Liver Grafts Following Right Lobe Living-Donor Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2005Taku Iida In adult living-donor liver transplantation (LDLT), the assessment of the allograft functional reserve is important for adequate graft regeneration. From March 2002 to December 2003, 30 adult recipients underwent right lobe LDLT. Mean CT attenuation values (CT-AVs) in the graft were measured on unenhanced CT for 6 months after LDLT. The histological features of the graft parenchyma were evaluated with post-operative liver biopsy specimens. Mean CT-AVs after LDLT were decreased significantly from the pre-operative values, recovered to over 60 HU within 6 months. There was a positive linear correlation between the CT-AVs and the receptor index (LHL15) in technetium-99m-diethylenetriaminepenta-acetic acid-galactosyl-human serum albumin (99mTc-GSA) liver scintigraphy (r = 0.803, p = 0.005). The recipients were divided into two groups according to the CT-AV at one post-operative week (group H; ,55HU, group L; <55HU). The low CT-AVs, under 55 HU, in group L were prolonged for 3 months compared with those in group H (p < 0.05). The 1-year cumulative survival rate was 94.7% and 45.5% in groups H and L, respectively (p = 0.014). Histological findings revealed that the parenchymal damage was severe in the grafts with low CT-AVs. The CT-AVs in the grafts may be a useful parameter for assessing the allograft functional reserve. [source] | ||||||||||||||||||||||||||||