Preperitoneal fat as a non-invasive marker of increased risk of severe non-alcoholic fatty liver disease in patients with type 2 diabetes.

BACKGROUND AND AIM: Fat distribution may have prognostic value in the evaluation of non-alcoholic fatty liver disease. This study was conducted to evaluate associations of magnetic resonance imaging-measured abdominal fat areas with steatosis, steatohepatitis, and fibrosis, assessed histopathologically, in patients with type 2 diabetes. METHODS: This prospective study included 66 patients with type 2 diabetes (12 males, 54 females, age 26-68 years), without chronic liver disease of other causes. Axial dual-echo magnetic resonance images were acquired. Visceral, subcutaneous, and preperitoneal fat areas were measured using Osirix software. Liver biopsy specimens were obtained from all patients and examined histopathologically to evaluate steatosis, steatohepatitis, and fibrosis. Linear (for steatosis) and logistic (for steatohepatitis and fibrosis) regression models were fitted for the outcomes. R2 was used as a measure of how much model variance the predictors explained and to compare different predictors of the same outcome. RESULTS: Visceral and preperitoneal fat areas correlated well with histopathologically determined liver steatosis grade (both P = 0.004) and liver fibrosis (P = 0.008 and P = 0.037, respectively). All fat areas correlated well with steatohepatitis (P ≤ 0.002). Preperitoneal and visceral fat areas were the best predictors of steatohepatitis (R2 = 0.379) and fibrosis (R2 = 0.181), respectively. CONCLUSIONS: Visceral fat area was the best predictor of fibrosis in patients with type 2 diabetes. Preperitoneal fat area was the best predictor of steatohepatitis and is a potential new non-invasive marker for use in the screening of these patients to detect more aggressive forms of non-alcoholic fatty liver disease.

Practical Considerations of Real Life of Hepatocellular Carcinoma in a Tertiary Center of Brazil.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignancy that develops in cirrhotic livers. Its clinical and epidemiological characteristics and mortality rates vary according to geographical region. The objective of this study was to evaluate the clinical profile, epidemiological characteristics, laboratory parameters, treatment and survival of patients with HCC. MATERIAL AND METHODS: Patients with HCC seen between 2000 and 2012 were studied. The Kaplan-Meier method was used for survival analysis according to variables in question. RESULTS: The study included 247 patients with a mean age of 60 ± 10 years. There was a predominance of males (74%). The main etiologies of HCC were HCV infection (55%), excessive alcohol consumption (12%), and HBV infection (8%). Liver cirrhosis was present in 92% of cases. The mean tumor number and diameter were 2 and 5 cm, respectively. Patients meeting the Milan criteria corresponded to 43% of the sample. Liver transplantation was performed in 22.4% of patients of the Milan subset and in 10% of the whole sample. The overall mean survival was 60 months, with a 1-, 3- and 5-year survival probability of 74%, 40% and 29%, respectively. Lower survival was observed among patients with alcoholic etiology. Survival was higher among patients submitted to liver transplantation (P < 0.001), TACE (P < 0.001), or any kind of treatment (P < 0.001). However, no difference was found for surgical resection (P = 0.1) or sorafenib (P = 0.1). CONCLUSION: Patients with HCC were mainly older men diagnosed at an advanced stage. Treatment was associated with better overall survival, but few patients survived to be treated.

Clinical Characteristics of Genuine Acute Autoimmune Hepatitis.

Introduction: Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH. Methods: This cross-sectional observational study evaluated patients with acute AIH presentation, defined as total bilirubin >5 times the upper limit of normality (xULN) and/or alanine aminotransferase >10 xULN, and no prior history of liver disease. Histology findings of acute disease defined GAAIH. Bivariate analyses were performed to identify factors associated with the GAAIH, when compared with acute exacerbation of chronic AIH. Results: Seventy-two patients with acute presentation of AIH were included and six (8.3%) of them presented GAAIH. Comparative analysis between patients with GAAIH and patients with acute exacerbation of chronic AIH revealed that prothrombin activity (96% [74-100] vs. 61% [10-100]; p = 0.003) and albumin levels (3.9 ± 0.2 g/dL vs. 3.4 ± 0.5 g/dL; p < 0.001) were higher in patients with GAAIH. The International Autoimmune Hepatitis Group score was higher in patients with acute exacerbation of chronic AIH (18.5 [8-23] vs. 16.5 [15-17]; p = 0.010). Compared to 15.2% of acute exacerbation of chronic AIH, complete therapeutic response to treatment was achieved in 67.7% of cases with GAAIH (p = 0.018). Conclusions: GAAIH was rare (8.3%), and patients with this presentation exhibited more preserved liver function tests, suggesting that most cases presenting with loss of function are acute exacerbation of chronic AIH. Additionally, patients with GAAIH had a better complete therapeutic response, suggesting a more preserved liver function at presentation, and early diagnosis has a positive therapeutic implication.

Introdução: A hepatite autoimune (HAI) apresenta um espectro de sintomas que varia de doença assintomática a hepatite aguda grave, hepatite crónica e cirrose descompensada. A apresentação aguda não é rara e pode representar hepatite autoimune aguda genuína (HAIAG) ou exacerbação aguda de hepatite autoimune crónica (EAHAIC). O nosso objetivo foi identificar a prevalência, caraterísticas clínicas e fatores prognósticos associados à HAIAG, e comparar esses casos com EAHAIC. Métodos: Estudo observacional, transversal, incluindo doentes com apresentação aguda de HAI, definida como bilirrubina total > 5 vezes o limite superior da normalidade (xLSN) e/ou ALT > 10 xLSN, e sem história prévia de doença hepática. HAIAG foi definida pela presença de achados histológicos de doença aguda. Análises bivariadas foram realizadas para identificar fatores associados à HAIAG, quando comparado com o EAHAIC. Resultados: Foram incluídos setenta e dois doentes com apresentação aguda de HAI, dos quais seis (8.3%) com HAIAG. A análise comparativa entre doentes com HAIAG e doentes com EAHAIC mostrou que a atividade de protrombina (96% (74-100) versus 61% (10-100; p=0.003) e os níveis de albumina (3,9 ± 0,2 g/dL vs. 3,4 ± 0,5 g/dL; p < 0,001) foram significativamente mais elevados em pacientes com HAIAG. O score do Grupo Internacional de Hepatite Autoimune foi mais elevado em doentes com EAHAIC (18.5 (8-23) versus 16.5 (15-17); p=0.010). A resposta terapêutica completa ao tratamento foi alcançada em 66.7% dos casos de HAIAG (vs. 15,2% na EAHAIC, p=0,018). Conclusões: A HAIAG é rara (8.3%), e os doentes com esta apresentação mostraram testes de função hepática mais preservados, sugerindo que a maioria dos casos com perda de função são EAHAIC. Além disso, os doentes com HAIAG tiveram maior taxa de resposta terapêutica completa, sugerindo que uma função hepática mais preservada na apresentação e o diagnóstico precoce tem uma implicação terapêutica positiva.

Histological evolution of hepatitis C virus infection after renal transplantation.

BACKGROUND: information regarding histological progression of hepatitis C after renal transplant (RTx) is scarce. AIMS: To analyze clinical and laboratory evolution and histological progression of hepatitis C in patients evaluated before and after RTx. METHODS: Twenty-two HCV-infected patients submitted to liver biopsy pre- and post-RTx were included. A semiquantitative analysis of necroinflammatory activity and fibrosis staging was performed and the two biopsies were compared. RESULTS: Patients were mostly men (73%) with mean age of 36±9 yr. Time post-transplant was 4±2 yr and time between biopsies was 5±2 yr. An elevation of alanine aminotransferase (p=0.041) and aspartate aminotransferase (p=0.004) levels was observed in the post-transplant period. Fibrosis progression after renal transplantation was observed in 11 (50%) of the patients, and necroinflammatory activity worsening was observed in 7 (32%) of the patients. The histological progression occurred even among those without significant histological lesions in pre-transplant biopsy. CONCLUSION: The findings of this study suggest that the practice of indicating treatment in the pre-transplant phase based mainly on histological disease should be revised, because a high proportion of patients present disease progression. Because interferon cannot be used safely after RTx, treatment should be indicated for all ESRD patients with hepatitis C.

Late-onset systemic lupus erythematosus-associated liver disease.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease, which predominantly affects women under 50 years old. Although liver disease is not included in the diagnostic criteria, abnormal liver tests are common among patients with SLE and, in a significant proportion of those patients, no other underlying condition can be identified. We described a case of liver involvement in late-onset SLE presenting with a predominantly cholestatic pattern. Other conditions associated with abnormal liver tests were excluded, and the patient showed a prompt response to steroid therapy. The spectrum of the liver involvement in SLE is discussed, with emphasis on the differential diagnosis with autoimmune hepatitis.

YKL-40 and hyaluronic acid (HA) as noninvasive markers of liver fibrosis in kidney transplant patients with HCV chronic infection.

OBJECTIVE: Hepatitis C is highly prevalent among kidney transplant (KT) recipients. In this population, the natural history of hepatitis C virus (HCV) infection and its proper management remains controversial. The invasiveness of the procedure and the interpretation variability of liver biopsy limit its use in these patients. We sought to evaluate the performance of YKL-40 and HA as markers of liver fibrosis in KT patients with HCV infection. MATERIAL AND METHODS: This cross-sectional study included HCV infected KT individuals. Univariate analysis was used to identify variables associated with significant fibrosis (METAVIR >or= F2). The diagnostic values of the YKL-40 and HA were compared using receiver operating characteristic (ROC) curves. RESULTS: Eighty-five patients were included (60% males, mean age 44.9 +/- 9.4 years). Significant fibrosis was observed in 14 patients (17%). When compared to F0/F1 individuals, patients with significant fibrosis were older, showed a higher time since transplantation, and higher prevalence of diabetes. No difference was observed in YKL-40 levels between the groups. Significantly higher levels of HA were noted in METAVIR >or= F2 subjects (108 vs. 37 ng/ml, p = 0.002). The AUROCs of YKL-40 and HA for predicting significant fibrosis were 0.615 and 0.765, respectively (p = 0.144). Levels of YKL-40 or= 418 ng/ml and HA >or= 120 ng/ml exhibited a PPV of 31% and 39%, respectively. CONCLUSIONS: Increased serum levels of HA but not of YKL-40 were associated with more advanced stages of liver fibrosis in KT HCV-infected patients.

Paternal exercise protects against liver steatosis in the male offspring of mice submitted to high fat diet.

Parental lifestyle has been related to alterations in the phenotype of their offspring. Obese sires can induce offspring insulin resistance as well as increase susceptibility to obesity. On the other hand, obese sires submitted to voluntary exercise ameliorate the deleterious metabolic effects on their offspring. However, there are no studies reporting the effect of programmed exercise training of lean sires on offspring metabolism. AIMS: This study aimed to investigate the role of swimming training of sires for 6 weeks on the offspring metabolic phenotype. MAIN METHODS: Male C57BL/6 mice fed a control diet were divided into sedentary and swimming groups. After the exercise, they were mated with sedentary females, and body weight and molecular parameters of the offspring were subsequently monitored. KEY FINDINGS: Swimming decreased the gene expression of Fasn and Acaca in the testes and increased the AMPK protein content in the testes and epididymis of the sires. The progeny presented a low weight at P1, which reached a normal level at P60 and at P90 the animals were challenged with HFD for 16 weeks. The male offspring of trained sires presented less body weight gain than the control group. The level of steatosis decreased in the male offspring from trained sires. The gene expression of Prkaa2, Ppar-1α and Cpt-1 was also increased in the liver of male offspring from trained sires. SIGNIFICANCE: Taken together, these findings suggest that paternal exercise training can improve the metabolic profile in the liver of the progeny, thereby ameliorating the effects of obesity.

Observational Study Evaluating the Outcome of Cirrhotic Hepatitis C Patients Submitted to Renal Transplantation.

BACKGROUND: After renal transplantation (RTx) hepatitis C virus (HCV) is associated with higher morbidity and mortality resulting in lower patient and graft survival. Few studies have investigated the evolution of renal transplant patients with cirrhosis owing to HCV. The objectives were to evaluate the post-transplant evolution of cirrhotic patients and to compare them with noncirrhotic patients considering the outcomes, including hepatic decompensation, graft loss, and death. METHODS: The retrospective-cohort study analyzed the data of patients undergoing RTx between 1993 and 2014, positive anti-HCV, HCV-RNA before RTx, and availability of data for assessment of cirrhosis. Demographic, clinical, and laboratory variables were compared between the groups according to the outcomes. The same were made between cirrhotic patients with and without portal hypertension (PH). Survival curves were constructed by the Kaplan-Meier test and compared by the log-rank test. Variables associated with the outcomes were analyzed using Cox regression. RESULTS: This study included noncirrhotic (n = 201) and cirrhotic patients (n = 23). In cirrhotic patients, they were significantly older (49 vs 41.6 years) and mostly male (87% vs 65%), with a greater number of previous RTx (48% vs 18%), less frequent use of azathioprine (26% vs 54%), cyclosporine (13% vs 46.5%), more frequent use of tacrolimus (87% vs 55%), lower count of platelets × 1000 cells/mm3(110 vs 187), and higher pre-RTx international normalized ratio (1.20 vs 1.1).The Kaplan-Meier survival differed in cirrhotic vs noncirrhotic patients only in hepatic decompensation. Cox regression analysis identified pretransplant cirrhosis (hazard ratio 6.64, 95% confidence interval, 2.59-17.06) and tacrolimus (hazard ratio 3.17,95% confidence interval, 1.05-9.58) as variables independently associated with decompensation. CONCLUSIONS: Patients with HCV and cirrhosis exhibit higher morbidity when submitted to RTx than noncirrhotic patients, with a higher risk of hepatic decompensation. However, no difference was observed in liver-related mortality, suggesting that RTx is a feasible option in cirrhotic patients without decompensation, even if they have PH.

Clinical and histological impact of previous hepatitis B virus infection in patients with chronic hepatitis C.

BACKGROUND: Recent reports suggest that hepatitis C virus (HCV) carriers with serological markers of prior hepatitis B virus (HBV) infection have more advanced liver fibrosis, irrespective of HBV-DNA detection. AIMS: We sought to assess the prevalence and impact of previous HBV infection in patients with HCV chronic infection. METHODS: This cross-sectional study included hepatitis B surface antigen- and human immunodeficiency virus-negative subjects with positive HCV-RNA. All patients had prior parenteral exposure as the probable source of HCV infection. Serum samples were tested for HBV-DNA using a commercial assay. The METAVIR system was used for histological analysis. RESULTS: One-hundred and eleven patients were evaluated. Thirty-one out of 111 patients (28%) tested positive for antihepatitis B core antigen (anti-HBc). HBV-DNA was not detected in any sample. Anti-HBc-positive patients showed higher histological grading, staging and a higher fibrosis progression rate. By multivariate analysis, anti-HBc-positivity was predictive of moderate to severe activity [odds ratio (OR)=3.532; P=0.032] and significant hepatic fibrosis (OR=3.364; P=0.017). After approximately 20 years of infection, advanced liver fibrosis (F3/F4) can be expected in 13% of anti-HBc-negative subjects who acquired HCV before the age of 30 and in 57% of those anti-HBc-positive patients who were infected by HCV after 30 years of age (P<0.001). CONCLUSION: Previous HBV infection is common among HCV carriers and may exert a negative impact on the natural history of HCV infection, independently of the presence of significant HBV replication.

Underlying mechanism of portal hypertensive gastropathy in cirrhosis: a hemodynamic and morphological approach.

BACKGROUND AND AIM: Portal hypertensive gastropathy (PHG) is an important cause of bleeding in patients with cirrhosis associated with portal hypertension. Histologically, the condition is characterized by dilation of the mucosal and submucosal vessels of the stomach; however, its mechanisms remain unclear. The aim of the present cross-sectional study was to evaluate the role of portal and systemic hemodynamic features, humoral factors and hepatocellular function in the development and severity of PHG in patients with cirrhosis. METHODS: Forty-six patients with cirrhosis of different etiologies underwent endoscopy. Portal hypertension was evaluated by hepatic venous pressure gradient (HVPG). The gastric mucosa was analyzed using two diagnostic methods: endoscopy according to the McCormack criteria and histological by histomorphometric analysis. RESULTS: The prevalence of PHG according to the endoscopic and histomorphometric methods was 93.4% and 76.1%, respectively. There were no statistically significant differences in HVPG measurements between the patients with mild (16.0 +/- 5.9 mmHg) and severe PHG (16.9 +/- 6.5 mmHg; P = 0.80) or between patients who did not have (15.2 +/- 8.0 mmHg) and those who had PHG (16.3 +/- 5.7 mmHg). No correlation was found between the presence or severity of PHG and systemic vascular resistance index (P = 0.53 and 0.34, respectively), Child-Pugh classification (P = 0.73 and 0.78, respectively) or glucagon levels (P = 0.59 and 0.62, respectively). CONCLUSIONS: The present data show no correlation between the presence or the severity of PHG and portal pressure, Child-Pugh classification or systemic hemodynamics, suggesting that other factors may be involved in the physiopathology of PHG, such as local gastric mucosal factors or other underlying factors.

Changing pattern of chronic hepatitis C in renal transplant patients over 20 years.

BACKGROUND: The prevalence and clinical epidemiological profile of hepatitis C virus (HCV) infection have changed over time. AIM: This study aimed to evaluate these changes in renal transplant recipients (RTx) comparing two different decades. MATERIALS AND METHODS: RTx with HCV referred to RTx from 1993 to 2003 (A) and from 2004 to 2014 (B) were studied retrospectively. The demographic and clinical characteristics and different outcomes were compared between groups A and B. Variables that were statistically different were tested for inclusion in a multivariate Cox proportional hazard model predicting patient survival within the group. RESULTS: Among 11 715 RTx, the prevalence of HCV was 7% in A and 4.9% in B. In the more recent period (B), the mean age was older (46.2 vs. 39.5 years), with more males (72 vs. 60.7%), larger number of deceased donors (74 vs. 55%), higher percentage of previous RTx (27 vs. 13.7%), less frequent history of blood transfusion (81 vs. 89.4%), lower prevalence of hepatitis B virus coinfection (4.7 vs. 21.4%), and higher percentage of cirrhotic patients (13 vs. 5%). Patients of group B more frequently underwent treatment of HCV (29 vs. 9%), less frequently used azathioprine (38.6 vs. 60.7%) and cyclosporine (11.8 vs. 74.7%), and more frequently used tacrolimus (91 vs. 27.3%). In the outcomes, graft loss showed no difference between periods; however, decompensation was more frequent (P = 0.007) and patients' survival was lower in the more recent period (P = 0.032) compared with the earlier one. CONCLUSION: The profile of RTx with HCV has changed over the last 20 years. Despite a decrease in the prevalence of HCV, new clinical challenges have emerged, such as more advanced age and a higher prevalence of cirrhosis.

Optimized cutoffs improve performance of the aspartate aminotransferase to platelet ratio index for predicting significant liver fibrosis in human immunodeficiency virus/hepatitis C virus co-infection.

AIM: To assess the diagnostic value of modified cutoffs for aspartate aminotransferase to platelet ratio index (APRI) to predict significant liver fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) patients. PATIENTS AND METHODS: This retrospective cross-sectional study included consecutive patients with HIV/HCV co-infection who underwent percutaneous liver biopsy. The accuracy of APRI for the diagnosis of significant fibrosis (F2/F3/F4 METAVIR) was evaluated by estimating the positive and negative predictive values (PPV and NPV respectively) and by measuring the area under the receiver operating characteristics curve (AUROC). RESULTS: One hundred and eleven patients were included (73% men, mean age 40.2+/-7.8 years). Significant fibrosis was observed in 45 patients (41%). To discriminate these subjects, the AUROC of APRI was 0.774+/-0.045. An APRI > or = 1.8 showed a PPV of 75% for the presence of significant fibrosis, and an index < 0.6 excluded significant fibrosis with an NPV of 87%. If biopsy indication was based only on APRI and restricted to scores in the intermediate range (> or = 0.6 and < 1.8), 46% of liver biopsies could have been avoided as compared with 40% using the classical cutoffs. CONCLUSION: APRI with adjusted cutoffs can predict significant liver fibrosis in patients with HIV/HCV co-infection and might obviate the need to perform a biopsy in a considerable percentage of those subjects.

Hepatitis C in chronic kidney disease: predialysis patients present more severe histological liver injury than hemodialysis patients?

BACKGROUND: The characteristics of hepatitis C virus (HCV) infection in predialysis patients are poorly understood and they could be different from hemodialysis patients. AIMS: To evaluate the demographics, laboratory and histological characteristics of chronic HCV infection in predialysis patients and to compare them with those observed in hemodialysis patients. METHODS: Thirty-nine predialysis patients with chronic HCV infection were compared to HCV-infected hemodialysis patients (ratio of 1:3) in terms of demographics, laboratory and histological characteristics. The fibrosis progression rate (FPR) was calculated as the ratio between fibrosis stage and duration of infection. RESULTS: Predialysis patients were older (57 +/- 10 vs. 45 +/- 12 years; p < 0.001), presented a higher proportion of elevated alanine aminotransferase (71.8 vs. 41.0%; p = 0.001) and aspartate aminotransferase (64.1 vs. 26.5%; p < 0.001), a higher proportion of interface hepatitis (66.7 vs. 47%; p = 0.033) and more advanced fibrosis (71.8 vs. 16.2%; p = 0.001). Among patients with estimated duration of infection, predialysis patients presented a longer duration of infection (22 vs. 6 years; p < 0.001) and no difference in FPR was observed between groups (p = 0.692). CONCLUSION: Although predialysis patients with HCV infection present more severe histological injury than hemodialysis patients, this finding probably reflects a longer duration of infection with no evidence supporting that hepatitis C presents a more aggressive course in this group.

Cutaneous amyloidosis associated with primary biliary cirrhosis.

Primary cutaneous amyloidosis is defined as the deposition of amyloid in the skin in the absence of systemic involvement. The association between primary cutaneous amyloidosis and other diseases, although rare, has been documented for connective tissue disorders such as systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis. We report the case of a 41-year-old woman who developed primary biliary cirrhosis in association with primary cutaneous amyloidosis. This association has not been reported before in the literature.

Factors associated with the intensity of liver fibrosis in renal transplant patients with hepatitis B virus infection.

BACKGROUND: Hepatitis B may show a more aggressive course after kidney transplantation, but the factors associated with the progression of fibrosis in this group have not been identified. OBJECTIVES: To determine the influence of hepatitis B virus (HBV) viral load and host-related factors on the progression of hepatic fibrosis in hepatitis B virus-infected renal transplant recipients. PATIENTS AND METHODS: Renal transplant patients positive for HBV surface antigen (HBsAg) and submitted to a liver biopsy because of evidence of viral replication were included. Patients with advanced fibrosis (METAVIR F3-F4) were compared with patients with mild fibrosis (F0-F2) regarding sex, age, estimated time since infection, post-transplant time, donor type, history of renal transplantation, alanine aminotransferase, anti-hepatitis C virus, HBeAg and quantitative hepatitis B virus-DNA. Logistic regression analysis was applied to identify variables independently associated with more advanced fibrosis. RESULTS: Fifty-five patients (75% men, 41+/-11 years) with a mean post-transplant time of 5+/-4 years were included. HBeAg was detected in 67% of the patients and anti-hepatitis C virus in 35%. The median hepatitis B virus-DNA level was 2.8 x 10(8) copies/ml. Seventeen (31%) patients had advanced fibrosis. Using logistic regression analysis, the only variable that showed an independent association with more advanced stages of fibrosis was post-transplant time (P=0.03, odds ratio: 1.2, 95% confidence interval: 1.02-1.45). CONCLUSION: Hepatitis B virus viral load, although very high, and hepatitis B virus/hepatitis C virus coinfection are not related to the intensity of liver fibrosis in renal transplant patients infected with hepatitis B virus. Post-transplant time was the only factor independently associated with more advanced liver fibrosis, suggesting the influence of immunosuppression on the progression of liver disease in these patients.

Primary mucinous adenocarcinoma of the bladder with signet-ring cells: case report.

CONTEXT: Primary adenocarcinomas of the bladder are uncommon and usually occur by contiguity with or hematogenic dissemination of other adenocarcinomas such as colorectal, prostate and gynecological tract carcinomas. Mucinous and signet-ring cell histological patterns are even rarer and it is often difficult to morphologically distinguish them from metastatic colorectal adenocarcinoma. CASE REPORT: We present and discuss a rare case of primary mucinous adenocarcinoma of the bladder with signet-ring cells in a 57-year-old male patient. Other primary sites for the tumor had been excluded and, in the absence of digestive tract tumor and for confirmation that it was a primary bladder tumor, an immunohistochemistry study was performed.

Does mesenchymal stem cell improve the liver regeneration after the 70% hepatectomy?

PURPOSE:: To evaluate the effects of mesenchymal stem cells on liver regeneration in rats following a 70% hepatectomy. METHODS:: Forty rats were subjected to 70% hepatectomy and then ~106 mesenchymal stem cells (test group), or saline solution (control group), were infused into their livers via the portal vein. Each treatment group was divided into early and late subgroups (euthanized 3 d and 5 d following the operation, respectively). Group comparisons of Albumin, aminotransaminases (AST, ALT), and Alcaline Phosphatase (AP) levels, proliferative index (ki-67+ straining), and mitotic cell counts were conducted. RESULTS:: No significant differences in liver regeneration rate, number of mitoses, proliferative index, or serum levels of albumin, AST, or AP were observed. ALT levels were higher in the test group than in the control group (p<.05). CONCLUSIONS:: Mesenchymal stem-cell therapy did not improve liver regeneration rate 3 d or 5 d after 70% hepatectomy in rats. Likewise, the therapy appeared not to affect liver function, proliferative index, or number of mitoses significantly.

[13C-methacetin breath test in chronic hepatitis C liver disease]. / Teste respiratório da 13C-metacetina na doença hepática crônica pelo vírus C.

BACKGROUND: The 13C-methacetin breath test is a non-invasive method to evaluate hepatic microsomal function that allows a quantitative assessment of the functional hepatic mass. AIM: To evaluate the clinical usefulness of the 13C-methacetin breath test in patients with hepatitis C chronic liver disease. PATIENTS AND METHODS: Seventy eight patients with chronic hepatitis C and 13 matched healthy controls were studied. HCV patients were classified as having chronic hepatitis (n = 51), cirrhosis (n = 27), being seven with decompensated disease (presence of ascite, jaundice and/or encephalopathy). HbsAg/HIV co-infected patients, chronic alcohol drinker, having other chronic diseases and those using drugs that could interfere with hepatic cytochrome P450, were excluded. The disease stage and activity in biopsy fragments were determined according the Brazilian Society of Hepatology criteria. Breath test was performed with 75 mg of 13C-methacetin, and the 13CO2 in the expired air was measured through a nondispersive infra red spectrometry. The delta over baseline, and the cumulative recovery of 13CO2 at 40 (13C-methacetin breath test 40 min) and 120 minutes (13C-methacetin breath test 120 min) were calculated. RESULTS: 13C-methacetin breath test parameters correlate only with hepatic staging but not with necroinflammatory (activity) parameters, being the best correlation found between hepatic staging and the 13C-methacetin breath test 120 minutes. The mean values for 13C-methacetin breath test 120 min was significantly reduced in the cirrhotic groups (19.2 +/- 7.1% for compensated and 14.7 +/- 4.0% for decompensated cirrhotics) than in control (29.9 +/- 4.5%) and chronic hepatitis (27.8 +/- 6.1%) groups. The best diagnostic accuracy for the diagnosis of cirrhosis among HCV patients was found for 13C-methacetin breath test 120 min with 81% of sensibility and 77% of specificity. CONCLUSION: 13C-methacetin breath test is correlated with structural changes in HCV-related chronic hepatic diseases and the cumulative recovery at 120 minutes is a sensitive parameter to identify the presence of hepatic cirrhosis in these patients.

Evaluating the best time to intervene acute liver failure in rat models induced by d-galactosamine.

PURPOSE:: To describe an animal model for acute liver failure by intraperitoneal d-galactosamine injections in rats and to define when is the best time to intervene through King's College and Clichy´s criteria evaluation. METHODS:: Sixty-one Wistar female rats were distributed into three groups: group 1 (11 rats received 1.4 g/kg of d-galactosamine intraperitoneally and were observed until they died); group 2 (44 rats received a dose of 1.4 g/kg of d-galactosamine and blood and histological samples were collected for analysis at 12 , 24, 48 , 72 and 120 hours after the injection); and the control group as well (6 rats) . RESULTS:: Twelve hours after applying d-galactosamine, AST/ALT, bilirubin, factor V, PT and INR were already altered. The peak was reached at 48 hours. INR > 6.5 was found 12 hours after the injection and factor V < 30% after 24 hours. All the laboratory variables presented statistical differences, except urea (p = 0.758). There were statistical differences among all the histological variables analyzed. CONCLUSION:: King's College and Clichy´s criteria were fulfilled 12 hours after the d-galactosamine injection and this time may represent the best time to intervene in this acute liver failure animal model.

DISSEMINATED FUNGAL INFECTION WITH ADRENAL INVOLVEMENT: REPORT OF TWO HIV NEGATIVE BRAZILIAN PATIENTS.

Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic in Brazil. Disseminated clinical forms are uncommon in immunocompetent individuals. We describe two HIV-negative patients with disseminated fungal infections, paracoccidioidomycosis and histoplasmosis, who were diagnosed by biopsies of suprarenal lesions. Both were treated for a prolonged period with oral antifungal agents, and both showed favorable outcomes.