Steatosis Of Indeterminate Cause In A Pediatric Group: Is It A Primary Mitochondrial Hepatopathy? [esteatose De Causa Não Determinada Em Grupo Pediátrico: Hepatopatia Mitocondrial Primária?]

CONTEXT AND OBJECTIVE: In children, hepatic steatosis may be related to inborn errors of metabolism (IEMs) or to non-alcoholic fatty liver disease (NAFLD). The aim of this study was to assess and characterize steatosis of indeterminate cause through morphological and morphometric analysis of liver tissue. DESIGN AND SETTING: Cross-sectional study at the Departments of Pathology of Faculdade de Ciências Médicas, Universidade Estadual de Campinas (FCM-Unicamp) and Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (FMB-Unesp). METHODS: Eighteen consecutive liver biopsies obtained from 16 patients of ages ranging from 3 months to 12 years and nine months that were inserted in a database in the study period were analyzed using optical microscopy and transmission electron microscopy. Through electron microscopy, the mitochondrial density and mean mitochondrial surface area were determined in hepatocytes. Ten patients ranging in age from 1 to 14 years were used as a control group. RESULTS: "Pure" steatosis was detected, unaccompanied by fbrosis or any other histological alteration. Microvesicular steatosis predominated, with a signifcant increase in mean mitochondrial surface area. CONCLUSION: Microvesicular steatosis may be related to primary mitochondrial hepatopathy, especially due to reduction of β-oxidation or partial stagnation of oxidative phosphorylation. For these reasons, this form of steatosis (which should not be called "pure") is likely to represent an initial stage in the broad spectrum of NAFLD. We have drawn attention to cases of steatosis in the pediatric group, in which the microvesicular form predominates, since this may be associated with mitochondrial disorders.1294217223Browning, J.D., Horton, J.D., Molecular mediators of hepatic steatosis and liver injury (2004) J Clin Invest, 114 (2), pp. 147-152Zafrani, E.S., Non-alcoholic fatty liver disease: An emerging pathological spectrum (2004) Virchows Arch, 444 (1), pp. 3-12Nobili, V., Marcellini, M., Devito, R., NAFLD in children: A prospective clinical-pathological study and efect of lifestyle advice (2006) Hepatology, 44 (2), pp. 458-465da Silva, G.H., Coelho, K.I., Coelho, C.A., Escanhoela, C.A., Mitochondrial alterations in nonalcoholic fatty liver disease. Pediatric case description of three submitted sequential biopsies (2009) J Gastrointest Liver Dis, 18 (2), pp. 215-219Zhou, Y.J., Li, Y.Y., Nie, Y.Q., Prevalence of fatty liver disease and its risk factors in the population of South China (2007) World J Gastroenterol, 13 (47), pp. 6419-6424Imhof, A., Kratzer, W., Boehm, B., Prevalence of non-alcoholic fatty liver and characteristics in overweight adolescents in the general population (2007) Eur J Epidemiol, 22 (12), pp. 889-897Sagi, R., Reif, S., Neuman, G., Nonalcoholic fatty liver disease in overweight children and adolescents (2007) Acta Paediatr, 96 (8), pp. 1209-1213Ciba, I., Widhalm, K., The association between non-alcoholic fatty liver disease and insulin resistance in 20 obese children and adolescents (2007) Acta Paediatr, 96 (1), pp. 109-112Radetti, G., Kleon, W., Stuefer, J., Pittschieler, K., Non-alcoholic fatty liver disease in obese children evaluated by magnetic resonance imaging (2006) Acta Paediatr, 95 (7), pp. 833-837Zou, C.C., Liang, L., Hong, F., Fu, J.F., Zhao, Z.Y., Serum adiponectin, resistin levels and non-alcoholic fatty liver disease in obese children (2005) Endocr J, 52 (5), pp. 519-524Louthan, M.V., Theriot, J.A., Zimmerman, E., Stutts, J.T., McClain, C.J., Decreased prevalence of nonalcoholic fatty liver disease in black obese children (2005) J Pediatr Gastroenterol Nutr, 41 (4), pp. 426-429Fishbein, M., Mogren, J., Mogren, C., Cox, S., Jennings, R., Undetected hepatomegaly in obese children by primary care physicians: A pitfall in the diagnosis of pediatric nonalcoholic fatty liver disease (2005) Clin Pediatr (Phila), 44 (2), pp. 135-141Schwimmer, J.B., Behling, C., Newbury, R., Histopathology of pediatric nonalcoholic fatty liver disease (2005) Hepatology, 42 (3), pp. 641-649Marion, A.W., Baker, A.J., Dhawan, A., Fatty liver disease in children (2004) Arch Dis Child, 89 (7), pp. 648-652Rashid, M., Roberts, E.A., Nonalcoholic steatohepatitis in children (2000) J Pediatr Gastroenterol Nutr, 30 (1), pp. 48-53Molleston, J.P., White, F., Teckman, J., Fitzgerald, J.F., Obese children with steatohepatitis can develop cirrhosis in childhood (2002) Am J Gastroenterol, 97 (9), pp. 2460-2462Mandel, H., Hartman, C., Berkowitz, D., The hepatic mitochondrial DNA depletion syndrome: Ultrastructural changes in liver biopsies (2001) Hepatology, 34 (4 PART 1), pp. 776-784Bioulac-Sage, P., Parrot-Roulaud, F., Mazat, J.P., Fatal neonatal liver failure and mitochondrial cytopathy (oxidative phosphorylation defciency): A light and electron microscopic study of the liver (1993) Hepatology, 18 (4), pp. 839-846Ghadially, F.N., (1997) Ultrastuctural Pathology of the Cell and Matrix, , 4 th ed. Boston: Butterworth-HeinemannPérez-Carreras, M., del Hoyo, P., Martín, M.A., Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis (2003) Hepatology, 38 (4), pp. 999-1007Morris, A.A., Mitochondrial respiratory chain disorders and the liver (1999) Liver, 19 (5), pp. 357-368Hensley, K., Kotake, Y., Sang, H., Dietary choline restriction causes complex I dysfunction and increased H(2)O(2) generation in liver mitochondria (2000) Carcinogenesis, 21 (5), pp. 983-989Pessayre, D., Mansouri, A., Haouzi, D., Fromenty, B., Hepatotoxicity due to mitochondrial dysfunction (1999) Cell Biol Toxicol, 15 (6), pp. 367-373Oleszczuk, A., Spannbauer, M., Tannapfel, A., Regenerative capacity difers between micro- and macrovesicular hepatic steatosis (2007) Exp Toxicol Pathol, 59 (3-4), pp. 205-213Reid, A.E., Nonalcoholic steatohepatitis (2001) Gastroenterology, 121 (3), pp. 710-723Sanyal, A.J., AGA technical review on nonalcoholic fatty liver disease (2002) Gastroenterology, 123 (5), pp. 1705-1725. , Sanyal AJAmerican Gastroenterological AssociationSokol, R.J., Treem, W.R., Mitochondria and childhood liver diseases (1999) J Pediat Gastroenterol Nut, 28 (1), pp. 4-16Natarajan, S.K., Eapen, C.E., Pullimood, A.B., Balasubramanian, K.A., Oxidative stress in experimental liver microvesicular steatosis: Role of mitochondria and peroxisomes (2006) J Gastroenterol Hepatol, 21 (8), pp. 1240-1249Fromenty, B., Pessayre, D., Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity (1995) Pharmacol Ther, 67 (1), pp. 101-154Sherlock, S., Dooley, J., Nutritional and metabolic liver diseases (2002) Diseases of the Liver and Biliary System, pp. 423-452. , In: Sherlock S, Dooley J eds., 11 th ed. 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(1998) Gastroenterology, 114 (4), pp. 842-845Gentile, C.L., Pagliassotti, M.J., The role of fatty acids in the development and progression of nonalcoholic fatty liver disease (2008) J Nutr Biochem, 19 (9), pp. 567-57

Clinical and pathological challenges in the diagnosis of late-onset biliary atresia: four case studies

Biliary atresia (BA) is classically described at the neonatal age. However, rare cases of BA in older infants have also been reported. We report four cases of late-onset BA in infants older than 4 weeks (3 males, 1 female), and describe the diagnostic and management difficulties. One of the cases had a late-onset (29 weeks) presentation with a successful surgical procedure. We highlight the importance of this unusual differential diagnosis in infants with cholestatic syndrome, who may benefit from Kasai surgery, regardless of age.Biliary atresia (BA) is classically described at the neonatal age. However, rare cases of BA in older infants have also been reported. We report four cases of late-onset BA in infants older than 4 weeks (3 males, 1 female), and describe the diagnostic and management difficulties. One of the cases had a late-onset (29 weeks) presentation with a successful surgical procedure. We highlight the importance of this unusual differential diagnosis in infants with cholestatic syndrome, who may benefit from Kasai surgery, regardless of age49

Diagnosis Of Alpha-1-antitrypsin Deficiency By Dna Analysis Of Children With Liver Disease

Background - Alpha-1-antitrypsin deficiency is a genetic disorder which is transmitted in a co-dominant, autosomal form. Alpha-1-antitrypsin deficiency affects mainly the lungs and the liver leading, in the latter case, to neonatal cholestasis, chronic hepatitis or cirrhosis. A precise diagnosis of Alpha-1-antitrypsin deficiency may be obtained by biochemical or molecular analysis. Objective - The purpose of this study was to use DNA analysis to examine the presence of an alpha-1-antitrypsin deficiency in 12 children suspected of having this deficiency and who showed laboratory and clinical characteristics of the disease. Patients and Methods - Twelve patients, aged 3 months to 19 years, who had serum alpha-1-antitrypsin levels lower than normal and/or had hepatic disease of undefined etiology were studied. The mutant alleles S and Z of the alpha-1-antitrypsin gene were investigated in the 12 children. Alpha-1-antitrypsin gene organization was analyzed by amplification of genoma through the polymerase chain reaction and digestion with the restriction enzymes Xmnl (S allele) and Taq 1 (Z allele). Results - Seven of the 12 patients had chronic liver disease of undefined etiology and the other five patients had low serum levels of alpha-1-antitrypsin as well as a diagnosis of neonatal cholestasis and/or chronic liver disease of undefined etiology. Five of the 12 patients were homozygous for the Z allele (ZZ) and two had the S allele with another allele (*S) different from Z. Conclusion - These results show that alpha-1-antitrypsin deficiency is relatively frequent in children with chronic hepatic disease of undefined etiology and/or low alpha-1-antitrypsin levels (41.6%). A correct diagnosis is important for effective clinical follow-up and for genetic counseling.3816368Alagille, D., Cholestasis in the first three months of life (1979) Prog Liver Dis, 6, pp. 471-485Andresen, B.S., Knudsen, I., Jensen, P.K.A., Gregersen, N., Two novel nonradioactive polymerase chain reaction-based assays of dried blood spots, genomic DNA, or whole cells for fast, reliable detection of Z and S mutations in the alpha-1-antitrypsin gene (1992) Clin Chem, 38, pp. 2100-2107Balistreri, W.F., Schubert, W.K., Liver disease in infancy and childhood (1993) Diseases of the Liver. 7.ed., pp. 1099-1203. , Schiff L, Schiff ER, editors. Philadelphia: LippincottBillingsley, G.D., Cox, D.W., Functional assessment of genetic variants of alpha 1-antitrypsin (1982) Hum Genet, 61, pp. 118-122Brantly, M., Nukiwa, T., Crystal, R.G., Molecular basis of alpha-1-antitrypsin deficiency (1988) Am J Med, 84, pp. 13-31Carlson, J.A., Rogers, R.B., Sifers, R., Acumulation of PiZ alpha 1-antitrypsin causes liver damage in transgenic mice (1989) J Clin Invest, 83, pp. 1183-1190Carrel, R.W., Alpha 1-antitrypsin: Molecular pathology, leukocytes and tissue damage (1986) J Clin Invest, 78, pp. 1427-1431Cox, D.W., Woo, S.L., Mansfield, T., DNA restriction fragments associated with alpha 1-antitrypsin indicate a single origin for deficiency allele PI Z (1985) Nature, 316, pp. 79-81Crystal, R.G., Brantly, M.L., Hubbard, R.C., Curiel, D.T., States, D.J., Holmes, M.D., The alpha 1-antitrypsin gene and its mutations. Clinical consequences and strategies for therapy (1989) Chest, 95, pp. 196-208Crystal, R.G., Ferrans, V.J., Basset, F., Biologic basis of pulmonary fibrosis (1991) The Lung: Scientific Foundations, pp. 2031-2046. , Crystal RG, West JB, Barnes PJ, Cherniack S, editors. New YorkRaven PressCuriel, D., Brantly, M., Curiel, E., Crystal, R.G., Alpha-1-antitrypsin deficiency caused by the alpha-1-antitrypsin Nullmattawa gene. An insertion mutation rendering the alpha-1-antitrypsin gene incapable of producing alpha-1-antitrypsin (1989) J Clin Invest, 83, pp. 1144-1152Dermer, S.J., Johnson, E.M., Rapid DNA analysis of alpha 1-antitrypsin deficiency: Application of an improved method for amplifying mutated gene sequence (1988) Lab Invest, 59, pp. 403-408Deutsch, J., Becker, H., Auböck, L., Histopathological features of liver disease in alpha 1-antitrypsin deficiency (1994) Acta Paediatr, 393 (SUPPL.), pp. 8-12Dubel, J.R., Finwick, R., Hejtmancik, J.F., Denaturing gradient gel electrophoresis of the alpha 1-antitrypsin gene: Application to prenatal diagnosis (1991) Am J Med Genet, 41, pp. 39-43Evans, H.E., Levi, M., Mandl, I., Serum enzyme inhibitor concentrations in the respiratory distress syndrome (1970) Am Rev Resp Dis, 101, pp. 359-363Fagerhol, M.K., Cox, D.W., The PI polimorphism: Genetic, biochemical and clinical aspects of human alpha-1-antitrypsin (1981) Human Genetic, pp. 1-62. , Harris H, Hirchorn, K, editors. New York: PlenumGartner, J.C., Zitelli, B.J., Malatak, J.J., Shaw, B.W., Iwatsuki, S., Starzl, T.E., Orthotopic liver transplantation in children: Two-year experience with 47 patients (1984) Pediatrics, 74, pp. 140-145Ishak, K.G., Hepatic morphology in inherited metabolic diseases (1986) Sem Liver Dis, 6, pp. 246-258Jeppsson, J.O., Laurell, C.B., Fagerhol, M.K., Properties of isolated alpha-1-antitrypsin of Pi types M, S and Z (1978) Eur J Biochem, 83, pp. 143-153Lai, E.C., Kao, F.T., Law, M.L., Woo, S.L., Assignment of the alpha 1-antitrypsin gene and a sequence-related gene to human chromossome 14 by molecular hybridization (1983) Am J Hum Genet, 35, pp. 385-392Laurell, C.B., Eriksson, S., The electrophoretic alpha-1-globulin pattern of serum in alpha-1-antitrypsin deficiency (1963) Scand J Clin Lab Invest, 15, pp. 132-140Laurell, C.B., Kullander, S., Thorell, J., Effect of administration of a combined strogen-progestin contraceptive on the level of individual plasma proteins (1968) Scand J Clin Lab Invest, 21, pp. 337-343Massi, G., Chiarelli, C., Alpha 1-antitrypsin: Molecular and the Pi system (1994) Acta Paediatr, 393 (SUPPL.), pp. 1-4Mowat, A.P., Avaliação laboratorial das afecções hepatobiliares (1991) Doenças Hepáticas Em Pediatria. 2.ed., pp. 410-430. , Mowat AP. Rio de Janeiro: RevinterNukiwa, T., Brantly, M., Ogushi, F., Crystal, R.G., Characterization of the M1(ala 213) type of alpha-1-antitrypsin, a newly recognized common "normal" alpha-1-antitrypsin haplotype (1987) Biochemistry, 26, pp. 5259-5267Okayama, H., Curiel, D.T., Brantly, M.L., Holmes, M.D., Crystal, R.G., Rapid nonradioactive detection of mutations in the human genome by allele-specific amplification (1989) J Lab Clin Med, 114, pp. 105-113Perlmutter, D.H., The cellular basis for liver injury in alpha-1-antitrypsin deficiency (1991) Hepatology, 13, pp. 172-185Perlmutter, D.H., Clinical manifestations of alpha 1-antitrypsin deficiency (1995) Gastroenterol Clin North Am, 24, pp. 27-43Schroeder, W.T., Miller, M.F., Woo, S.L., Saunders, G.F., Chromosomal localization of the human alpha 1-antitrypsin gene (PI) to 14q31-32 (1985) Am J Hum Genet, 37, pp. 868-872Serra, H.G., (1998) Identificação Molecular Dos Alelos S e Z Do Gene Da Alfa-1-antitripsina Em Um Grupo de Pacientes Portadores de Doença Pulmonar Crônica [tese de Doutorado], , Campinas, SP: Instituto de Biologia da Universidade Estadual de CampinasSilverman, E.K., Miletich, J.P., Pierce, J.A., Sherman, L.A., Endicott, S.K., Broze, G.J., Campbell, E.J., Alpha-1-antitrypsin deficiency. High prevalence in the St. Louis area determined by direct population screening (1989) Am Rev Respir Dis, 140, pp. 961-966Sveger, T., Liver disease in alpha 1-antitrypsin deficiency detected by screening of 200,000 infants (1976) N Engl J Med, 294, pp. 1316-1321Sveger, T., The natural history of liver disease in alpha 1-antitrypsin deficient children (1988) Acta Paediatr Scand, 77, pp. 847-851Sveger, T., Ericksson, S., The liver in adolescents with alpha 1-antitrypsin deficiency (1995) Hepatology, 22, pp. 514-517Talbot, I.C., Mowat, A.P., Liver disease in infancy. Histological features and relationship to alpha 1-antitrypsin phenotype (1975) J Clin Pathol, 28, pp. 559-563Travis, J., Salvesen, G.S., Human plasma proteinase inhibitors (1983) Annu Rev Biochem, 52, pp. 655-709Van Steenbergen, W., Alpha 1-antitrypsin deficiency: An overview (1993) Acta Clin Belg, 48 (3), pp. 171-189Wewers, M.D., Casolaro, M.A., Sellers, S.E., Swayze, S.C., McPhaul, K.M., Wittes, J.T., Crystal, R.G., Replacement therapy deficiency associated with emphysema (1987) N Engl J Med, 316, pp. 1055-1062Woodhead, J.L., Fallon, R., Figuered, H., Longdale, J., Malcom, A.D.B., Alternative methodology of gene diagnosis (1986) Human Genetic Diseases - a Pratical Approach, pp. 51-64. , Davies KE, editor. Oxford: IRL Pres

No Protective Function Found in Wistar Rats Submitted to Long Ischemia Time and Reperfusion After Intermittent Clamping of the Total Hepatic Pedicle

AbstractBackgroundAlthough the intermittent Pringle maneuver is used for major transplant surgery, traumas, and hepatic protection, long ischemia time and reperfusion may limit some protection in Wistar rats. The aim of the study was to evaluate the protection effects of intermittent clamping in the total hepatic pedicle after a long period of ischemia and reperfusion in Wistar rats.MethodsForty-two male Wistar rats, weighing ±327.7 g, were anesthetized intravenously with sodium thiopental and given a U-shaped incision in the abdomen. The total hepatic pedicle was isolated and subjected to clamping with a microvascular clamp. Groups included were the continuous group (CG, n = 14, 40 minutes of ischemia/40 minutes of reperfusion); the intermittent group (IG, n = 14, 4 cycles a 10 minute ischemia/reperfusion 10 minutes); and the sham group (SG, n = 14, 80 minutes of observation time). Blood collection for transaminase dosage was carried out, and hepatic biopsy specimens were taken for mitochondrial respiration and histological evaluation.ResultsIn groups CG and IG, aspartate aminotransferase and alanine aminotransferase enzymes were elevated in comparison to group SG (P < .008); mitochondrias, when stimulated by use of adenosine diphosphate or carbonylcyanide p-trifluoromethoxyphenylhydrazone, had a significant decrease in mitochondrial respiration (P < .05), and the respiratory control ratio in the ischemic groups was lower (P < .03) when compared with the GS. On histological examination, 100% of the GC had lesions: 33% focal hemorrhagic necrosis, 17% sinuzoidal congestion and/or vacuolization, and 50% venous congestion; in the IG, 100% had lesions: 43% sinusoidal congestion and/or vacuolization and 57% venous congestion.ConclusionsThe intermittent total hepatic pedicle clamping for a long period of time in the Wistar rats had no efficacy in protection of liver injury

A Clinical, Epidemiological, Laboratorial, Histological And Ultrasonographical Evaluation Of Anti-hcv Eia-2 Positive Blood Donors

Between 1992 and 1997, 790 blood donors with anti-HCV EIA-2 strongly reagent (relationship between the sample optical density/cut-off > 3) detected at the blood bank serological screening, were evaluated in ambulatory environment. They were all negative for Chagas disease, syphilis, hepatitis B (HBsAg) and AIDS. Blood samples were collected at the first ambulatorial evaluation, for hemogram, biochemical tests and new serological tests for HCV (anti-HCV EIA-2). In blood samples of 226 repeatedly reagent anti-HCV EIA-2 blood donors, supplementary "immunoblot" test for HCV (RIBA-2) was used. In 209 donors, the presence of HCV-RNA was investigated by the PCR test. The abdominal ultrasonography was realized in 366 donors. In 269 patients liver biopsy was performed for the histopathological study. The follow-up of blood donors showed that 95.6% were repeatedly EIA-2 reagent, 94% were symptomless and denied any hepatitis history, with only 2% mentioning previous jaundice. In 47% of this population at least one risk factor has been detected for the HCV transmission, the use of intravenous drugs being the main one (27.8%). Blood transfusion was the second factor for HCV transmission (27.2%). Hepatomegaly was detected in 54% of the cases. Splenomegaly and signs of portal hypertension have seldom been found in the physical examination, indicating a low degree of hepatic compromising in HCV. Abdominal ultrasound showed alterations in 65% of the subjects, being the steatosis the most frequent (50%). In 83.5% of the donors submitted to the liver biopsy, the histopathological exam showed the presence of chronic hepatitis, usually classified as active (89%) with mild or moderate grade in most of the cases (99.5%). The histopathological exam of the liver was normal in 1.5% of blood donors. The RIBA-2 test and the HCV-RNA investigation by PCR were positive in respectively 91.6 and 75% of the anti-HCV EIA-2 reagent donors. The HCV-RNA research was positive in 82% of the RIBA-2 positive subjects, in 37.5% of the indeterminate RIBA-2 donors and in 9% of the negative RIBA-2 donors. Chronic hepatitis has also been observed in 50% of the histopathologieal exams of the anti-HCV EIA-2 reagent donors which were, indeterminate RIBA-2. Among 18 blood donors with minimal changes histopathological exam 11 (61%) were HCV-RNA positive. Our blood donors anti-HCV reagent generally had clinical, laboratorial and histopathological features observed in patients with chronic HCV hepatitis and a high proportion could be identified in interviews and medical evaluation realized in blood blanks. Generally, these HCV infected donors are identified and discharged only by the serological tests results.423147152Alter, H.J., To C or not to C: These are the questions (1995) Blood, 85, pp. 1631-1695Alter, H.J., Conry-Cantilena, C., Melpolder, J., Hepatitis C in asymptomatic blood donors (1997) Hepatology, 26 (1 SUPPL.), pp. 29S-33SAlter, H.J., Purcell, R.H., Shih, J.W., Detection of antibodies to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis (1989) New Engl. J. Med., 321, pp. 1494-1500Alter, H.J., Tegtmeier, G., Jett, B., The use of a recombinant immunoblot assay in the interpretation of anti-hepatitis C virus reactivity among prospectively followed patients, implicated donors, and random donors (1991) Transfusion, 31, pp. 771-776Alter, M.J., Epidemiology of hepatitis C in the West (1995) Semin. Liver Dis., 15, pp. 5-14Areias, J., Pedroto, I., Freitas, T., Hepatitis C virus carriers with normal ALT activity: Viraemia, genotype and effect of interferon therapy (1996) Gastroenterology, 110, pp. A1143Choo, Q.L., Kuo, G., Weiner, A.J., Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome (1989) Science, 244, pp. 359-362Conry-Cantilena, C., Van Raden, M., Gibble, J., Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C infection (1996) New Engl. J. Med., 334, pp. 1691-1696Esteban, J.I., Esteban, R., Viladomiu, L., Hepatitis C virus antibodies among risk groups in Spain (1989) Lancet, 2, pp. 294-297Esteban, J.I., Gonzales, A., Hernandez, J.M., Evaluation of antibodies to hepatitis C virus in a contemporary study of transfusion-associated hepatitis (1990) New Engl. J. Med., 323, pp. 1107-1112Garcia-Samaniego, J., Enriquez, A., Soriano, V., Third-generation recombinant immunoblot assay to confirm hepatitis C virus-indeterminate serological samples (1993) Vox Sang., 64, pp. 191-192. , BaselHoofnagle, J.H., Hepatitis C: The clinical spectrum of disease (1997) Hepatology, 26 (1 SUPPL.), pp. 15S-20SKleinman, S., Alter, H., Busch, M., Increased detection of hepatitis C virus (HCV)-infected blood donors by a multiple-antigen HCV enzyme immunoassay (1992) Transfusion, 32, pp. 805-813Kuo, G., Choo, Q.L., Alter, H.J., An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis (1989) Science, 244, pp. 362-364Lok, A.S.F., Gunaratnam, N.T., Diagnosis of hepatitis C (1997) Hepatology, 26 (1 SUPPL.), pp. 48S-56SPrati, D., Capelli, C., Zanella, A., Influence of different hepatitis C virus genotypes on the course of asymptomatic hepatitis C virus infection (1996) Gastroenterology, 100, pp. 178-183Prieto, M., Olaso, V., Verdu, C., Does the healthy hepatitis C virus carrier state really exist? An analysis using polymerase chain reaction (1995) Hepatology, 22, pp. 413-417Prince, A.M., Brotman, B., Inchauspe, G., Patterns and prevalence of hepatitis C virus infection in posttransfusion non-A, non-B hepatitis (1993) J. Infect.Dis, 167, pp. 1296-1301Rossini, A., Gazzola, G.B., Ravaggi, A., Long-term follow-up and infectivity in blood donors with hepatitis C antibodies and persistently normal alanine aminotransferase levels (1995) Transfusion, 35, pp. 108-111Salmeron, F.J., Palacios, A., Perez-Ruiz, M., Epidemiology, serological markers, and hepatic disease of anti-HCV ELISA-2 positive blood donors (1996) Dig. Dis. Sci., 41, pp. 1933-1938Schiff, E.R., Hepatitis C and alcohol (1997) Hepatology, 26 (1 SUPPL.), pp. 39S-42SSerfaty, L., Nousbaum, J.R., Elghouzzi, M.H., Prevalence, severity, and risk factors of liver disease in blood donors positive in a second-generation anti-hepatitis C virus screening test (1995) Hepatology, 21, pp. 725-729Shakil, A.O., Conry-Cantilena, C., Alter, H.J., Volunteer blood donors with antibody to hepatitis C virus: Clinical, biochemical, virologic and histologic features (1995) Ann. Intern. Med., 123, pp. 330-337Sharara, A.I., Hunt, C.M., Hamilton, J.D., Hepatitis C (1996) Ann. Intern. Med., 125, pp. 658-668Ulrich, P., Romeo, J., Lane, P., Detection, semiquantitation, and genetic variation in hepatitis C virus sequences amplified from the plasma of blood donors with elevated alanine aminotransferase (1990) J. Clin. Invest., 86, pp. 1609-161

Long-time choledochal clamping in wistar rats causes biliary obstruction progressing to hepatic fibrosis

Biliary complications are important causes of morbidity and mortality in patients undergoing hepatic surgery. The aim of the study was to evaluate late liver alterations after a long period of choledochal clamping in Wistar rats. Methods. Ten male Wistar rats, weighing 304 grams, anesthetized with sodium thiopental (25 mg/kg) and xylazine (10 mg/kg) intravenously, were distributed into 2 groups: the choledochal clamping group (CCG) and the operation sham group (OSG), with 5 animals each submitted to an abdominal incision. In the CCG, the choledochal was isolated, dissected, and clamped with a microvascular clamp for 40 minutes. After this occlusion time, the clamp was removed and the incision was closed. In the OSG the animals, under normal conditions, were submitted only to anesthesia and laparotomy for choledochal manipulation. In all animals, after the 31st day, a hepatic biopsy was carried out for histology and blood biochemical tests: total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase. The animals were euthanized under anesthesia. This research was approved by the Ethics Committee on Animal Use (CEUA, Unicamp, No. 2511-1). Results. In the CCG, 100% of the animals showed bile duct dilatation, ductular proliferation, and portal inflammatory infiltrate; 60% showed regenerative nodule formation; and 80% had porta-porta septa and foci of necrosis, all of which were not found in the OSG. All CCG group biochemical tests had significant increases (P <.05) compared with OSG. Conclusions. Long-time choledochal clamping in Wistar rats caused hepatic dysfunction and biochemical and histological injuries with degrees of distortion to the hepatic architecture.Biliary complications are important causes of morbidity and mortality in patients undergoing hepatic surgery. The aim of the study was to evaluate late liver alterations after a long period of choledochal clamping in Wistar rats. Methods. Ten male Wistar4872375237814th Brazilian Transplantation Association (ABTO) and 14th Luso-Brazilian Transplantation Congress together with the 13th Transplantation Nursing Meeting and Histocompatibility Forumde 24 a 27 de outubroGramado, Brasi

Liver Transplantation For Budd-chiari Syndrome [transplante De Fígado Na Síndrome De Budd-chiari]

A case of acute Budd-Chiari syndrome in a 21-year-old man is reported. The transplanted liver was from a patient with the same blood. No veno-venous bypass was necessary during operation. The patient presented two major complications after liver transplantation: a) stenosis of the anastomosis of the supra hepatic inferior cava vein, treated with percutaneous angioplasty; b) biliary leak, treated with sphincterotomy. The patient is assymptomatic thirty one month after transplantation.531010541060Berenhauser-Leite, G., Souza, V., Boni, I.F.S.F., Leonardi, L.S., Percutaneous angioplasty in orthotopic liver transplantation (1995) European IHPBA Congress, pp. 807-808. , Papastamatiou, L. ed. Monduzzi, BolognaLeonardi, L.S., Callejas-Neto, F., Berenhauser-Leite, G., Boin, I.F.S.F., Endoscopy sphincterotomy in patients with biliary leak after orthotoptc liver transplantation (1995) European IHPBA Congress, pp. 269-272. , Papastamatiou, L. ed. Monduzzi, BolognaLeonardi, L.S., Berenhauser-Leite, G., Boin, I.F., Santos, M.C., Udo, E.Y., Avaliação psicossocial de um grupo de doentes submetidos a transplante hepático (1994) Resumo dos Trabalhos Científicos da I Semana Brasileira do Aparelho Digestivo, p. 148. , Porto AlegreShill, M., Henderson, J.M., Tavill, A.S., The Budd-Chiari syndrome revised (1994) Gastroenterologist, 2, pp. 27-38Sanchez-Bueno, F., Parrilha, P., Ramirez, P., Robles, R., Pons, J.A., Acosta, F., Nuñez, R., Sanchez-Ortega, J.L., Transplante ortotópico de higado en el síndrome de Budd-Chiari. Presentación de un caso (1992) Rev. Esp. Enf. Digest, 81, pp. 52-56Rodes, J., Prieto, J., Rapado, A., Dotor abdominal y ascitis (1995) Gastroenterología y Hepatología, pp. 169-173. , Panéz, J. ed. Masson-Salvat, BarcelonaHalft, G., Todo, S., Tzakis, A., Gordon, R., Starzl, T.E., Liver transplantation for the Budd-Chiari Syndrome (1990) Ann. Surg., 211, pp. 43-49Berenhauser-Leite, G., Complicações da cirrose hepática (1995) Ped. Mod., 31, pp. 366-374Kane, R., Eustace, S., Diagnosis of Budd-Chiari syndrome: Comparison between sonography and MR angiography (1995) Radiology, 195, pp. 117-121Berenhauser-Leite, G., Anatomia cirúrgica do fígado (1995) Arq. Cat. Med., 24, pp. 33-37Mahmoud, A.E.A., Gakis, D., Oliffe, S., West, R., Buckels, J., Elias, E., Mesocaval shunt versus radiological intervention in the treatment of Budd-Chiari syndrome (1995) HPBSE, 9 S, p. 63Baulieux, J., De La Roche, E., Genin, G., Ducerf, C., Pignal, C., Petipas, E., Adham, M., Pouyet, M., Interest of transjugular intrahepatic porto-systemic shunt before orthotopic liver transplantation (1995) HPBSE, 9 S, p. 117Rogopoulos, A., Gavelli, A., Sakai, H., McNamara, M., Huguet, C., Transjugular intrahepatic portosystemic shunt for Budd-Chiari syndrome after failure of surgical shunting (1995) Arch. Surg., 130, pp. 227-228Jamieson, N.V., Williams, R., Calne, R.Y., Liver transplantation for Budd-Chiari syndrome, 1976-1990 (1991) Ann. Chir, 45, pp. 362-365Moreno-Gonzalez, E., Landa-Garcia, I., Calleja-Kempin, J., Gomez-Gutierrez, M., Jover-Navalon, J.M., Anas-Dtaz, J., Berenhauser-Leite, G., Comparação dos resultados do transplante hepático em duas fases de um programa (1988) Rev. Col. Bras. Cirurg., 15, p. 94Zajko, A.B., Claus, D., Clapuyt, P., Esquivel, C., Moulin, D., Starzl, T.E., Goyet, J.V.G., Otte, J.B., Obstruction to hepatic venous drainage after liver transplantation: Treatment with ballon angioplasty (1989) Radiology, 170, pp. 763-765Donovan, J., Nosurgical management of biliary tract dease after liver transplantation. Gastroenterol (1993) Clin. N. Am., 22, pp. 317-33

Evaluation And Comparison Of Microvessel Density Using The Markers Cd34 And Cd105 In Regenerative Nodules, Dysplastic Nodules And Hepatocellular Carcinoma

Purpose: The progression of hepatocellular carcinoma (HCC) is multifactorial and angiogenesis plays a fundamental role, mainly because HCC is a highly vascularized tumor. Methods: In this study, we determined microvessel density (MVD) using the immunohistochemical markers, CD34 and CD105 (Endoglin), in 44 hepatectomy specimens, encompassing 44 malignant nodules (HCC), 44 regenerative nodules (RN), and 15 dysplastic nodules (DN). The evaluation included the determination of MVD in all nodules. For statistical analysis, a descriptive analysis was carried out using measurements of position and dispersion for continuous variables; ANOVA was used to compare between groups, considering p < 0.05 as statistically significant. Results: We observed a significant difference when comparing CD34 and CD105 immunoexpression in HCC, DN, and RN. CD105 was predominantly expressed in the peripheral regions in HCC, with mean MVD scores of 6.2 ± 4.1 and 10.7 ± 4.4 at the center and periphery of the nodules, respectively, with significant differences between groups (p < 0.0001). CD34 had higher mean MVD scores than CD105 in HCC, with a more uniform positivity pattern. CD105 immunoexpression in DN exhibited a pattern similar to HCC. However, in RN, CD105 exhibited a higher MVD score in the central portion of the nodules. CD105 was expressed in a subset of newly formed microvessels in HCC and demonstrated an elevated mean MVD in cirrhotic or regenerative nodules. Conclusions: MVD determined by CD34 and CD105 expression may be used as an additional parameter to distinguish benign from malignant liver nodules. © 2014 Asian Pacific Association for the Study of the Liver.82260265Tsukuma, H., Hiyama, T., Tanaka, S., Nakao, M., Yabuuchi, T., Kitamura, T., Nakanishi, K., Kawashima, T., Risk factors for hepatocellular carcinoma among patients with chronic liver disease (1993) New England Journal of Medicine, 328 (25), pp. 1797-1801. , DOI 10.1056/NEJM199306243282501El-Serag, H.B., Rudolph, K.L., Hepatocellular Carcinoma: Epidemiology and Molecular Carcinogenesis (2007) Gastroenterology, 132 (7), pp. 2557-2576. , DOI 10.1053/j.gastro.2007.04.061, PII S0016508507007998Theise, N.D., Park, Y.N., Curado, M.P., Hepatocellular carcinoma (2010) WHO Classification of Tumours of the Digestive System, pp. 205-216. , Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. Lyon: IARC PressTheise, N.D., Park, Y.N., Kojiro, M., Dysplastic nodules and hepatocarcinogenesis (2002) Clinics in Liver Disease, 6 (2), pp. 497-512. , DOI 10.1016/S1089-3261(02)00006-5, PII S1089326102000065Villanueva, A., Newell, P., Chiang, D.Y., Friedman, S.L., Llovet, J.M., Genomics and signaling pathways in hepatocellular carcinoma (2007) Semin Liver Dis, 27 (1), pp. 55-76Pang, R.W., Joh, J.W., Johnson, P.J., Monden, M., Pawlik, T.M., Poon, R.T., Biology of hepatocellular carcinoma (2008) Ann Surg Oncol, 15 (4), pp. 962-971Hytiroglou, P., Morphological Changes of Early Human Hepatocarcinogenesis (2004) Seminars in Liver Disease, 24 (1), pp. 65-75. , DOI 10.1055/s-2004-823097Park, Y.N., Yang, C.-P., Fernandez, G.J., Cubukcu, O., Thung, S.N., Theise, N.D., Neoangiogenesis and sinusoidal 'capillarization' in dysplastic nodules of the liver (1998) American Journal of Surgical Pathology, 22 (6), pp. 656-662. , DOI 10.1097/00000478-199806000-00002Semela, D., Dufour, J.-F., Angiogenesis and hepatocellular carcinoma (2004) Journal of Hepatology, 41 (5), pp. 864-880. , DOI 10.1016/j.jhep.2004.09.006, PII S0168827804003940Deli, G., Jin, C.-H., Mu, R., Yang, S., Liang, Y., Chen, D., Makuuchi, M., Immunohistochemical assessment of angiogenesis in hepatocellular carcinoma and surrounding cirrhotic liver tissues (2005) World Journal of Gastroenterology, 11 (7), pp. 960-963Terminology of nodular hepatocellular lesions (1995) Hepatology, 22 (3), pp. 983-993. , International Working PartyHytiroglou, P., Park, Y.N., Krinsky, G., Theise, N.D., Hepatic Precancerous Lesions and Small Hepatocellular Carcinoma (2007) Gastroenterology Clinics of North America, 36 (4), pp. 867-887. , DOI 10.1016/j.gtc.2007.08.010, PII S0889855307000817, Pathology and Clinical Relevance of Neoplastic Precursor Lesions of the Gastrointestinal Tract, Liver, and Pancreaticobiliary SystemPathologic diagnosis of early hepatocellular carcinoma: A report of the international consensus group for hepatocellular neoplasia (2009) Hepatology, 49 (2), pp. 658-664. , International Consensus Group for Hepatocellular NeoplasiaRoncalli, M., Borzio, M., Di Tommaso, L., Hepatocellular dysplastic nodules (2008) Ann Ital Chir, 79 (2), pp. 81-89Sakamoto, M., Effendi, K., Masugi, Y., Molecular diagnosis of multistage hepatocarcinogenesis (2010) Jpn J Clin Oncol, 40 (9), pp. 891-896Shiraha, H., Yamamoto, K., Namba, M., Human hepatocyte carcinogenesis (2013) Int J Oncol, 42 (4), pp. 1133-1138. , reviewFolkman, J., Tumor angiogenesis: Therapeutic implications (1971) N Engl J Med, 285 (21), pp. 1182-1186Folkman, J., Tumor angiogenesis (1985) Adv Cancer Res, 43, pp. 175-203Folkman, J., Shing, Y., Angiogenesis (1992) J Biol Chem, 267 (16), pp. 10931-10934Frachon, S., Gouysse, G., Dumortier, J., Couvelard, A., Nejjari, M., Mion, F., Berger, F., Scoazec, J.-Y., Endothelial cell marker expression in dysplastic lesions of the liver: An immunohistochemical study (2001) Journal of Hepatology, 34 (6), pp. 850-857. , DOI 10.1016/S0168-8278(01)00049-6, PII S0168827801000496Di, C.I., Fraggetta, F., Lombardo, R., Azzarello, G., Vasquez, E., Puleo, S., CD 34 expression in chronic and neoplastic liver diseases (2002) Panminerva Medica, 44 (4), pp. 365-367Yang, L., Lu, W., Huang, G., Wang, W., Correlation between CD105 expression and postoperative recurrence and metastasis of hepatocellular carcinoma (2006) BMC Cancer, 6, p. 110Nakamura, T., Changes in expression of bile canalicular CD10 and sinusoidal CD105 (endoglina) in peri-tumoral hepatic tissue (2009) Tumori, 95 (4), pp. 495-500Wang, Y., Zhang, X.H., Guo, P., Yan, L.N., He, D., Tumor microvascular density detected by anti-CD105 and anti-CD34 in hepatocellular carcinoma patients and its predictive value of tumor recurrence after liver transplantation (2010) Sichuan Da Xue Xue Bao Yi Xue Ban, 41 (5), pp. 818-882Ho, J.W., Poon, R.T., Sun, C.K., Xue, W.-C., Fan, S.-T., Clinicopathological and prognostic implications of endoglin (CD105) expression in hepatocellular carcinoma and its adjacent non-tumorous liver (2005) World Journal of Gastroenterology, 11 (2), pp. 176-181Yu, D., Zhuang, L., Sun, X., Chen, J., Yao, Y., Meng, K., Particular distribution and expression pattern of endoglin (CD105) in the liver of patients with hepatocellular carcinoma (2007) BMC Cancer, 7, p. 122Wang, Z.S., Wu, L.Q., Yi, X., Geng, C., Li, Y.J., Yao, R.Y., Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-feto-protein after radical hepatectomy (2013) BMC Cancer, 13 (1), p. 30

Hepatic Involvement In Paediatric Patients With Paracoccidioidomycosis: A Histological Study

Aim: Paracoccidioidomycosis is a systemic mycosis that is endemic to certain countries in Latin America. This study aimed to describe the histological features of liver involvement in patients with paracoccidioidomycosis aged <16 years of age who were treated between 1980 and 2010, with a diagnosis that was confirmed by detection of the fungus by pathological examination. Methods and results: Liver tissue was obtained from one necropsy and 12 biopsies. Throughout 2007, biopsies were taken from patients with persistent jaundice or portal hypertension, after which biopsies became indicated due to elevated aminotransferase and low albumin levels. Using haematoxylin and eosin (H&E), Masson's trichrome and immunohistochemical (CK7 and CK19) staining, we noted degenerative alterations in bile duct cells and inflammatory injury to the bile ducts in 10 biopsies. Using immunohistochemistry for CK7 and CK19, we observed ductal proliferation in all 12 samples. Conclusions: Bile duct injuries by inflammatory cells might explain the predominant increase in canalicular enzymes; immunohistochemistry is more sensitive in demonstrating ductular reactions and might show changes that are not apparent on H&E staining. © 2013 John Wiley & Sons Ltd.642256262Brummer, E., Castaneda, E., Restrepo, A., Paracoccidioidomycosis: an update (1993) Clin. Microbiol. Rev., 6, pp. 89-117Londero, A.T., Epidemiologia (1982) Paracoccidioidomicose (Blastomicose sul-americana). Paracoccidioidomycosis (South american blastomycosis), pp. 85-90. , In Del Negro G, Lacaz CS, Fiorillo A eds. São Paulo: Sarvier-EduspCoutinho, Z.F., Silva, D., Lazera, M., Paracoccidioidomycosis mortality in Brazil (1980-1995) (2002) Cad. Saude Publica, 18, pp. 1441-1454Fiorillo, A.M., Martinez, R., Moraes, C.R., Lesões do aparelho digestivo (1982) Paracoccidioidomicose (Blastomicose sul-americana). Paracoccidioidomycosis (South american blastomycosis), pp. 179-193. , In Del-Negro G, Lacaz CS, Fiorillo AM eds. São Paulo: Sarvier - Editora da Universidade de São PauloFranco, M.F., Montenegro, M.R.G., Anatomia patológica (1982) Paracoccidioidomicose (Blastomicosesul-americana). Paracoccidioidomycosis (South american blastomycosis), pp. 97-117. , In Del-Negro G, Lacaz CS, Fiorillo AM eds. São Paulo: Sarvier-EduspTeixeira, F., Gayotto, L.C., Brito, T., Morphological patterns of the liver in South American blastomycosis (1978) Histopathology, 2, pp. 231-237Boccalandro, I., Albuquerque, F.J.M., Icterícia e comprometimento hepático na blastomicose sul-americana. A propósito de 10 casos. Jaundice and hepatic involvement in South American blastomycosis. Description of 10 cases (1960) Rev. Paul. Med., 56, pp. 350-366Daher, R.R., Vasconcelos, W.M.P., Cardoso, V.M., Fígado e a blastomicose sul-americana. Liver and the South American blastomycosis (1973) J. Bras. Med., 25, pp. 83-90Brito, T., Castro, R.M., Shiroma, M., Biópsia hepática na blastomicose sul-americana. Liver biopsy in South American blastomycosis (1968) Rev. Inst. Med. Trop. SãoPaulo, 10, pp. 188-191Barbosa, G.L., Paracoccidioidomicose na criança. Paracoccidioidomycosis in children (1992) Rev. Pat. Trop., 21, pp. 269-383Mowat, A.P., (1991) Doenças hepáticas em pediatria, pp. 367-370. , Liver disorders in childhood. 2nd edn. Rio de Janeiro: RevinterBateman, A.C., Hübscher, S.G., Cytokeratin expression as an aid to diagnosis in medical liver biopsies (2010) Histopathology, 56, pp. 415-425Zimmerman, H.J., (1999) Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver, pp. 589-637. , 2nd edn. Philadelphia, PA: Lippincott Williams & WilkinsMarques Mello, L., Silva-Vergara, M.L., Rodrigues Jr, V., Patients with active infection with Paracoccidioidesbrasiliensis present a Th2 immune response characterized by high interleukin-4 and interleukin-5 production (2002) Hum. Immunol., 63, pp. 149-154Benard, G., An overview of the immunopathology of human paracoccidioidomycosis (2008) Mycopathology, 165, pp. 209-221Shikanai-Yasuda, M.A., Higaki, Y., Uip, D.E., Bone marrow involvement and eosinophilia in paracoccidioidomycosis (1992) Rev. Inst. Med. Trop. SãoPaulo, 34, pp. 85-90Gonçalves, A.J.R., Terra, G.M.F., Rozenbaum, R., A eosinofilia na paracoccidioidomicose infantil. The eosinophilia in infantile paracoccidioidomycosis (1999) Arq. Bras. Med., 73, pp. 13-21Nogueira, M.G.S., Andrade, G.M.Q., Tonelli, E., Aspectos laboratoriais evolutivos de crianças em tratamento da paracoccidioidomicose. Laboratory evolutive aspects of children under paracoccidioidomycosis treatment (2006) Rev. Soc. Bras. Med. Trop., 39, pp. 478-483Wagner, J.M., Franco, M., Kephart, G.M., Localization of eosinophil granule major basic protein in paracoccidioidomycosis lesions (1998) Am. J. Trop. Med. Hyg., 59, pp. 66-72Rammaert, B., Desjardins, A., Lortholary, O., New insights intohepatospleniccandidosis, a manifestation of chronic disseminatedcandidosis (2012) Mycoses, 55, pp. 74-84Matheus, T., Muñoz, S., Granulomatousliver diseaseandcholestasis (2004) Clin. Liver Dis., 8, pp. 229-246Lagana, S.M., Moreira, R.K., Lefkowitch, J.H., Hepatic granulomas: pathogenesis and differential diagnosis (2010) Clin. Liver Dis., 14, pp. 605-617Andrade, Z.A., Schistosomiasis and liver fibrosis (2009) Parasite Immunol., 31, pp. 656-66