Fulminant hepatitis with microvesicular steatosis (a histologic comparison of cases occurring in Brazil - Labrea hepatitis - and in central Africa - Bangui hepatitis)

A similar histopathologic picture of fatal hepatitis associated with widespread acute fatty changes in hepatocytes and single-cell necrosis was seen in epidemic cases occurring in two distinct equatorial areas having high prevalences of HBV and HDV infections. The cases were previously considered to be two different entities; Labrea hepatitis in Brazil, and Bangui hepatitis in the Central African Republic. However, the histopathologic findings suggest that they are pathogenetically and etiologically related to HBVand HDV infections, probably modified by some as yet unknown factor (s) present in equatorial forest zones.

Labrea-like hepatitis in Vitoria, Espirito Santo state, Brazil: report of a case

A case of fulminat hepatitis with microvesicular steatosis resembling Labrea 's fever, diagnosed in Vitoria (ES) is reported. The 16 year old bcy presented with severe epistaxis, agitation, jaundice and hemorrhagic vomiting and died two days after admission to the emergency unit of the Vnivesity Hospital. The disease started five days before with fever, myalgias, dark urine and jaundice andprogressed withpsychic agitation, torpor and coma. The liver andspleen were notpalpable. HBsAg was negative in the serum. The autopsy showed acute hepatitis with tylic necrosis confluent in the midizonal and periportal areas with massive microvesicular steatosis in the remaining hepatocytes. Mononuclear cellspredominated in the exudate. The reticulum showed condensation in the necrotic areas without typical bands of collapse. The portal tracts were edematous with mononuclear infiltration and mild bile duct proliferation. Absence of cholestasis. Exceptfor the confluent midzonalandperiportal necrosis this case showed several clinical and morphological aspects of the Labreafever describedfrom the East Amazon, demonstrating that the anatomical picture of this disease probabty is not in related to afactor peculiar to the Amazon region.

In vivo growth-inhibition of Sarcoma 180 by piplartine and piperine, two alkaloid amides from Piper

Piplartine {5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)pyridinone} and piperine {1-5-(1,3)-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]piperidine} are alkaloid amides isolated from Piper. Both have been reported to show cytotoxic activity towards several tumor cell lines. In the present study, the in vivo antitumor activity of these compounds was evaluated in 60 female Swiss mice (N = 10 per group) transplanted with Sarcoma 180. Histopathological and morphological analyses of the tumor and the organs, including liver, spleen, and kidney, were performed in order to evaluate the toxicological aspects of the treatment with these amides. Administration of piplartine or piperine (50 or 100 mg kg-1 day-1 intraperitoneally for 7 days starting 1 day after inoculation) inhibited solid tumor development in mice transplanted with Sarcoma 180 cells. The inhibition rates were 28.7 and 52.3% for piplartine and 55.1 and 56.8% for piperine, after 7 days of treatment, at the lower and higher doses, respectively. The antitumor activity of piplartine was related to inhibition of the tumor proliferation rate, as observed by reduction of Ki67 staining, a nuclear antigen associated with G1, S, G2, and M cell cycle phases, in tumors from treated animals. However, piperine did not inhibit cell proliferation as observed in Ki67 immunohistochemical analysis. Histopathological analysis of liver and kidney showed that both organs were reversibly affected by piplartine and piperine treatment, but in a different way. Piperine was more toxic to the liver, leading to ballooning degeneration of hepatocytes, accompanied by microvesicular steatosis in some areas, than piplartine which, in turn, was more toxic to the kidney, leading to discrete hydropic changes of the proximal tubular and glomerular epithelium and tubular hemorrhage in treated animals.

Serum lipid profile and hepatic evaluation in mice fed diet containing pequi nut or pulp (Caryocar brasiliense Camb.)

Caryocar brasiliense (popular name pequi) is widely consumed by the population of Brazilian Savannah. This fruit has a high concentration of monounsaturated fatty acids that can influence positively the lipid profile. In addition, pequi also has an important concentration of saturated fatty acids which, in turn, is associated with atherosclerosis risk. This study aimed to investigate the effect of a pequi-supplemented diet on blood lipid and glucose levels and hepatic histology. Female Albino swiss mice were divided into three groups and fed a standard chow diet (control group), chow diet supplemented with 33% pequi nut (nut group), and chow diet supplemented with 33% pequi pulp (pulp group). After 6 weeks, following an overnight fast, blood and liver were collected for posterior analyses. Serum total cholesterol and HDL-cholesterol were significantly higher in mice fed pequi-rich diets compared to the control group. Nevertheless, there was no modification in blood triglycerides, atherogenic fraction, and glucose levels. In addition, there was development of liver microvesicular steatosis related to pequi intake. In conclusion, the diets supplemented with pequi nut or pulp reduced the atherogenic risk by increasing the anti-atherogenic lipoproteins without changing the pro-atherogenic fraction in mice.

Clinical and laboratory characteristics associated with dyslipidemia and liver steatosis in chronic HBV carriers

Introduction Chronic hepatitis B virus (HBV) infection and liver steatosis (LS) are the most common causes of chronic liver disease, and their coexistence is frequently observed in clinical practice. Although metabolic syndrome is the main cause of LS, it has not been associated with HBV infection. The aims of this study were to describe the lipid profile and prevalence of LS among HBV carriers and to identify the characteristics associated with LS in this group. Methods This retrospective cross-sectional study included hepatitis B surface antigen (HBsAg)-positive patients evaluated during 2011 and 2012. Results Of the 83 patients included, the mean age was 46.4±12.5 years, 53% were men, and 9.1% were hepatitis B e antigen (HBeAg) -positive. These patients exhibited the following lipid profile: total cholesterol = 175.4±38.8mg/dL, low-density lipoprotein (LDL) = 113.0±32.7mg/dL, and triglycerides = 91.1±45.2mg/dL. Their fasting glucose was 95.3±14.5g/dL, and fasting insulin was 6.1±5.9µIU/mL. Liver steatosis was observed on abdominal ultrasound in 11.3% of individuals. Factors associated with the presence of LS included higher levels of total cholesterol, prothrombin activity, fasting insulin, and body mass index (BMI) as well as lower levels of aspartate aminotransferase (AST). Conclusions These findings suggest that LS in patients with chronic HBV appears to be a consequence of metabolic alterations and insulin action rather than of viral factors.

Diagnosis of hepatic steatosis by contrast-enhanced abdominal computed tomography

Objective To evaluate the diagnostic capacity of abdominal computed tomography in the assessment of hepatic steatosis using the portal phase with a simplified calculation method as compared with the non-contrast-enhanced phase. Materials and Methods In the present study, 150 patients were retrospectively evaluated by means of non-contrast-enhanced and contrast-enhanced computed tomography. One hundred patients had hepatic steatosis and 50 were control subjects. For the diagnosis of hepatic steatosis in the portal phase, the authors considered a result of < 104 HU calculated by the formula [L - 0.3 × (0.75 × P + 0.25 × A)] / 0.7, where L, P and A represent the attenuation of the liver, of the main portal vein and abdominal aorta, respectively. Sensitivity, specificity, positive and negative predictive values were calculated, using non-contrast-enhanced computed tomography as the reference standard. Results The simplified calculation method with portal phase for the diagnosis of hepatic steatosis showed 100% sensitivity, 36% specificity, negative predictive value of 100% and positive predictive value of 75.8%. The rate of false positive results was 64%. False negative results were not observed. Conclusion The portal phase presents an excellent sensitivity in the diagnosis of hepatic steatosis, as compared with the non-contrast-enhanced phase of abdominal computed tomography. However, the method has low specificity.

The role of ultrasonography in the measurement of subcutaneous and visceral fat and its correlation with hepatic steatosis

Objective To evaluate the sonographic measurement of subcutaneous and visceral fat in correlation with the grade of hepatic steatosis. Materials and Methods In the period from October 2012 to January 2013, 365 patients were evaluated. The subcutaneous and visceral fat thicknesses were measured with a convex, 3–4 MHz transducer transversely placed 1 cm above the umbilical scar. The distance between the internal aspect of the abdominal rectus muscle and the posterior aortic wall in the abdominal midline was considered for measurement of the visceral fat. Increased liver echogenicity, blurring of vascular margins and increased acoustic attenuation were the parameters considered in the quantification of hepatic steatosis. Results Steatosis was found in 38% of the study sample. In the detection of moderate to severe steatosis, the area under the ROC curve was 0.96 for women and 0.99 for men, indicating cut-off values for visceral fat thickness of 9 cm and 10 cm, respectively. Conclusion The present study evidenced the correlation between steatosis and visceral fat thickness and suggested values for visceral fat thickness to allow the differentiation of normality from risk for steatohepatitis.

MTP -493G/T gene polymorphism is associated with steatosis in hepatitis C-infected patients

The reduction of hepatic microsomal transfer protein (MTP) activity results in fatty liver, worsening hepatic steatosis and fibrosis in chronic hepatitis C (CHC). The G allele of the MTP gene promoter, -493G/T, has been associated with lower transcriptional activity than the T allele. We investigated this association with metabolic and histological variables in patients with CHC. A total of 174 untreated patients with CHC were genotyped for MTP -493G/T by direct sequencing using PCR. All patients were negative for markers of Wilson’s disease, hemochromatosis and autoimmune diseases and had current and past daily alcohol intake lower than 100 g/week. The sample distribution was in Hardy-Weinberg equilibrium. Among subjects with genotype 1, 56.8% of the patients with fibrosis grade 3+4 presented at least one G allele versus 34.3% of the patients with fibrosis grade 1+2 (OR = 1.8; 95%CI = 1.3-2.3). Logistic regression analysis with steatosis as the dependent variable identified genotypes GG+GT as independent protective factors against steatosis (OR = 0.4, 95%CI = 0.2-0.8; P = 0.01). The results suggest that the presence of the G allele of MTP -493G/T associated with lower hepatic MTP expression protects against steatosis in our CHC patients.

A clinical, epidemological, 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 histopathological 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.

Patients with chronic hepatitis C and normal transaminases

Hepatitis C virus infection evolves progressively persisting in the majority of patients (85%). Most patients have high ALT (alanine aminotransferase) levels and approximately 25% normal ALT. The latter are usually female and there is no association between genotype and severity of hepatic lesion. Histologic analysis usually shows small lesion and absence or low amount of fibrosis, despite cirrhosis having been reported. Aiming at assessing prevalence, demographic, genotypical and anatomopathological characteristics in patients with normal ALT levels, we have carried out a study of 68 chronic hepatitis C patients between January 1997 and April 2000. There was a prevalence of 13.8% chronic hepatitis C patients with normal ALT levels, 45.6% of which were male and 54.4% female, the mean age being 38 +/- 13 years. We found a predominance of genotype 1 in 84.7% of the patients, genotype 2 in 6.8% and genotype 3 in 10.7%. In 52.9% of the cases liver biopsies revealed liver reaction, periportal activity score 0-1 was observed in 85.3% of the patients and score 2-4 was seen in 14.7%. Structural activity score 0-1 was seen in 73.5% of the patients and score 2-4 in 26.5% of them. Periportal activity > 2 and structural activity > 1 was seen in 29%, but steatosis was not seen in 73.5%. Our results suggest the need to revisit for liver biopsy practice in patients with Chronic Hepatitis C and normal transaminases.

Do differences exist between chronic hepatitis C genotypes 2 and 3?

Introduction Six genotypes of the hepatitis C virus (HCV) have been identified thus far, and their distribution is well defined. Genotype 1, which is the most prevalent worldwide, is always compared to genotypes 2 and 3, particularly in terms of treatment response. However, little is known about the differences between genotypes 2 and 3 because these genotypes are analyzed together in most studies. Therefore, the aim of this study was to evaluate differences in the clinical, epidemiological, laboratory, and histological parameters between HCV-2 and HCV-3. Methods Patients with chronic hepatitis C infected with genotypes 2 and 3 were studied retrospectively and compared according to clinical, laboratory, and histological aspects. Hepatitis C virus-ribonucleic acid (HCV-RNA) was analyzed quantitatively by TaqMan® real-time PCR, and the HCV genotype was determined by sequencing the 5′-untranslated region. Results A total of 306 patients with chronic HCV-2 (n=50) and HCV-3 (n = 256) were studied. Subtype 2b (n=17/50) and subtype 3a (n=244/256) were the most prevalent among patients infected with HCV-2 and HCV-3, respectively. The mean age was 47 ± 10 years, and there was a predominance of men in the group studied (61%). Comparative analysis between HCV-2 and HCV-3 showed a younger age (p=0.002), less prevalence of arterial hypertension (p=0.03), higher serum albumin levels (p=0.01), more advanced stage of liver fibrosis (p=0.03), and higher frequency of steatosis in patients with HCV-3 (p=0.001). After multivariate regression analysis, all the variables, except serum albumin, remained as variables associated with HCV-3 in the final model. Conclusions Clinical and histological differences exist between HCV-2 and HVC-3, which suggests the need for separate analyses of these genotypes.

Frequency of histopathological changes in Howler monkeys ( Alouatta sp.) naturally infected with yellow fever virus in Brazil

Abstract: INTRODUCTION: Due to the importance that Howler monkeys have on the yellow fever (YF) epidemiological sylvatic cycle in Brazil, more accurate morphological diagnostic criteria needs to be established, especially considering the differences that may exist between the genera of Brazilian non-human primates (NHPs) involved in yellow fever virus (YFV) epizootics. METHODS: Records of YF epizootics in NHPs in Brazil between 2007 and 2009 were obtained from the Brazilian Ministry of Health database to select YF positive (n=98) Howler monkeys (Alouatta sp.) for this study. The changes described in the histopathological reports were categorized by organ and their frequencies calculated. RESULTS: The most frequent lesions observed in the animals with YF were hepatocyte apoptosis (Councilman body formation), midzonal hepatocyte necrosis, steatosis, liver hemorrhage, inflammatory mononuclear cell infiltration of the liver, renal acute tubular necrosis and interstitial nephritis. Midzonal hepatocyte necrosis, steatosis and hemorrhage presented positive correlations with apoptosis of hepatocytes, suggesting strong YFV pathogenic effect association; they were also the main histopathological changes in the Alouatta sp. A pronounced negative correlation between apoptosis of hepatocytes and hepatic mononuclear cell infiltration pointed to significant histopathological differences between YFV infection in Howler monkeys and humans. CONCLUSIONS: The results warn that NHPs may exhibit different response patterns following YFV infection and require a more careful diagnosis. Presumptive diagnosis based on primate histopathological lesions may contribute to public health service control.

Histopathologic and biochemical liver test abnormalities in chronic asymptomatic or oligosymptomatic alcoholics: a review

PURPOSE: To review the medical literature regarding the histopathologic and biochemical liver test abnormalities in chronic asymptomatic or oligosymptomatic alcoholics. METHODS: Review of articles in the MEDLINE and LILACS databases regarding serum levels and prevalence of alterations in aspartate-aminotransferase, alanine-aminotransferase, alkaline phosphatase, and total bilirubin, in relation to liver histopathology, with or without discrimination of types of histopathologic alteration. RESULTS: Global mean prevalence rates of aspartate-aminotransferase and alanine-aminotransferase alterations were 86.3% and 51.1%; in cases with steatosis they were 79.1% and 38.5%; and in cases of hepatitis, 90.1% and 58%. In all studies, prevalence rates of aspartate-aminotransferase alterations were significantly higher with lower variability than those of alanine-aminotransferase. Mean aspartate-aminotransferase levels were higher than 2N (N is the upper normal limit of the method employed) in all cases with hepatitis histopathology, while those of alanine-aminotransferase were 1.48N, in the same cases. Prevalence of alkaline phosphatase and total bilirubin abnormalities were 74.5% and 74.9% globally; in cases of steatosis, they were 70.9% and 67.9%; and in cases of hepatitis, 75.9% and 77.7%. Mean alkaline phosphatase levels were above the upper normal limit in all cases, but those of total bilirubin were above normal in 4 of 7 hepatitis studies. CONCLUSIONS: Prevalence of aspartate-aminotransferase alteration was consistently related to presence of histopathologic abnormalities; an enzyme level higher than 2N suggests the diagnosis of alcoholic hepatitis.

Hepatic stereology of schistosomiasis mansoni infected-mice fed a high-fat diet

High-fat diets induce weight gain and fatty liver in wild-type mice. Schistosomiasis mansoni infection also promotes hepatic injury. This study was designed to quantify hepatic alterations in schistosomiasis mansoni-infected mice fed a high fat-rich chow compared to mice fed a standard rodent chow, using stereology. Female SW mice fed each either high-fat diet (29% lipids) or standard chow (12% lipids) over 8 months, and then were infected with Schistosoma mansoni cercariae. Four experimental groups were studied: infected mice fed a high-fat diet (IHFC) or standard chow (ISC), uninfected mice fed a high-fat diet (HFC) or standard chow (SC). Mice were sacrificed during early infection (9 weeks from exposure). The following hepatic biometry and the stereology parameters were determined: volume density (hepatocytes [h], sinusoids [s], steatosis [st] and hepatic fibrosis [hf]); numerical density (hepatocyte nuclei - Nv[h]); absolute number of total hepatocyte N[h], normal hepatocyte N[nh], and binucleated hepatocyte N[bh], percentage of normal hepatocyte P[nh] and binucleated hepatocyte P[bh]. IHFC and HFC groups exhibited TC, HDL-C, LDL-C, and body mass significantly greater (p < 0.05) than control group. No significant differences were found regards liver volume (p = 0.07). Significant differences were observed regards P[nh] (p = 0.0045), P[bh] (p = 0.0045), Nv[h] (p = 0.0006), N[h] (p = 0.0125), N[bh] (p = 0.0164) and N[nh] (p = 0.0078). IHFC mice group presented 29% of binucleated hepatocytes compared to HFC group (19%), ISC group (17%) and SC (6%). Volume density was significantly different between groups: Vv[h] (p = 0.0052), Vv[s] (p = 0.0025), Vv[st] (p = 0.0004), and Vv[hf] (p = 0.0007). In conclusion, schistosomiasis mansoni infection with concurrent high-fat diet promotes intensive quantitative changes in hepatic structure, contributing to an increasing on hepatic regeneration.