Are Total Prostate-specific Antigen Serum Levels in Cirrhotic Men Different From Those in Normal Men?

OBJECTIVES To determine the serum total prostate-specific antigen (tPSA) levels in cirrhotic men and compare them with those in noncirrhotic men. METHODS We prospectively evaluated 113 cirrhotic patients listed for liver transplantation using the serum tPSA, total testosterone level, and Child-Pugh liver function score according to age and severity of liver disease. The tPSA levels were compared with those of 661 healthy men. The Mann-Whitney U test was used for statistical analysis, with a significance level of .05. RESULTS The median age of the cirrhotic and noncirrhotic patients was 55 years (range 28-70) and 58 years (range 46-70), respectively (P <.01). However, when stratified by age group (<49, 50-59, and >60 years), this difference was not significant. The median serum tPSA level was 0.3 ng/mL (range 0.04-9-9) and 1.3 ng/mL (range 0.04-65.8) in the cirrhotic and noncirrhotic group, respectively (P <.0001). Stratifying both groups according to age, the cirrhotic patients had significantly lower tPSA levels than did the noncirrhotic patients. According to the Child-Pugh score (A,B, and C), Child-Pugh class C patients had significantly lower tPSA levels than did Child-Pugh class A patients and also had lower testosterone levels than did Child-Pugh class A and B patients. The tPSA levels correlated significantly with the testosterone levels in the cirrhotic patients (P =.028). CONCLUSIONS The results of our study have shown that cirrhotic patients have approximately 4 times lower serum tPSA levels than noncirrhotic men. Patients with more severe liver disease have lower tPSA and testosterone levels than patients less affected. The tPSA levels in cirrhotic men are affected by the total testosterone levels. UROLOGY 73: 1032-1035, 2009. (C) 2009 Elsevier Inc.

Follow-up of Pregnant Women With Autoimmune Hepatitis The Disease Behavior Along With Maternal and Fetal Outcomes

Goals: To assess maternal and fetal outcomes and clinical management of pregnancy in patients with autoimmune hepatitis (AIH). Background: There is a paucity of information about maternal and fetal outcomes, and AIH activity during pregnancy and in the postpartum period. There is no consensus about the administration of azathioprine during pregnancy and breastfeeding. Study: Retrospective analysis of 54 pregnancies (3 still in progress) in 39 AIH patients. Results: The median age at conception was 24 years, and 68.4% of women had liver cirrhosis. Before conception and in early pregnancy, azathioprine and prednisone were administered in 48.1%, but treatment regimen vas usually changed further to 20 mg/d prednisone and 20.4%, were off treatment. There were 36 livebirths, and fetal loss rates were 29.4% (13 miscarriages, 1 stillbirth, and 1 ectopic pregnancy). Preterm birth rate was 11.8%. In 2 cases, there was acute fetal distress; and in 2 others congenital malformations (3.9%). The rate of serious maternal complication was 7.8%, with no deaths. There were no flares in 41.2% pregnancies, but aminotransferase elevations occurred in 54.9%, 31.4% of which were true AIH relapses, only registered in the postpartum period. Conclusions: Despite the high fetal miscarriage rate, pregnancy in AIH was safe. Patients needed careful monitoring, especially in the postpartum period because of relapses. There was no evidence of a cause and effect relationship among azathioprine administration and premature births and congenital abnormalities, but more studies are necessary. Higher doses of prednisone may be an alternative option for those who prefer azathioprine withdrawal during pregnancy.

CFTR Polymorphisms in Patients with Alcoholic Chronic Pancreatitis

Introduction: Pancreas susceptibility to alcohol is variable and only 5-10% of chronic alcohol abusers develop chronic pancreatitis; the role of genetic factors in this process is unknown. The CFTR gene encodes a protein that acts on epithelial cells and plays a key role in normal exocrine pancreatic function. Methods: This study investigated the frequency of polymorphisms in intron 8 of the CFTR gene in patients with alcoholic chronic pancreatitis. Three groups of patients were studied: group A-68 adult alcoholics with a diagnosis of chronic pancreatitis; group B-68 adult alcoholics without pancreatic disease or liver cirrhosis and group C-104 healthy nonalcoholic adults. Results: T5/T7 genotype was more frequent in group A (11.8%) than in group B (2.9%) (p = 0.0481), and there was no statistical difference when groups A and C (5.8%) were compared (p = 0.1317). The haplotype combination (TG) 10-T7/(TG) 11-T7 was more frequent in groups B (23.5%) and C (20.2%) than in group A (7.3%) (p = 0.0080 and 0.0162). Conclusion: There are differences when these three groups are compared and individuals with T5/T7 genotype might have a greater risk of developing chronic pancreatitis when they become chronic alcoholics. Copyright (C) 2008 S. Karger AG, Basel and IAP

Management of Uncommon Hernias in Cirrhotic Patients

Background. Abdominal hernias are a common disease among cirrhotic patients, because of malnutrition and persistently high intra-abdominal pressure due to ascites. When tense ascites is present, life-threatening complications are likely to occur. In such cases, the morbidity and mortality rates are high. Objective. We describe 3 cirrhotic patients with rare complicated hernias that needed surgical repair. We discuss optimal timing for surgical approaches and the necessity of ascites control before surgery, as well as the technical details of the procedures. Method. Review of hospital charts of selected rare cases of herniae in cirrhotic patients. Conclusion. Elective surgical approaches can treat even uncommon hernias in cirrhotic patients with good results.

Evaluation of the respiratory muscle strength of cirrhotic patients: Relationship with Child-Turcotte-Pugh scoring system

Pulmonary abnormalities are observed in chronic hepatopathy. The measurement of the maximum inspiratory and expiratory pressure may evaluate lung function and the risks associated with hepatic transplantation. Thus, the present work sought to evaluate the respiratory muscle strength of 29 patients between 17 and 63 years old who were enrolled for liver transplantation. The patients were classified according to Child-Turcotte-Pugh score as A, B, or C, and also according to a physiotherapeutic evaluation, which included measurement of respiratory muscle strength by means of a digital manovactrometer, which determines the maximum inspiratory pressure (MaxIP) and the maximum expiratory pressure (MaxEP). The tests were performed with seated individuals having their nostrils obstructed by a nasal clip. The MaxIP was measured during the effort initiated in the residual volume, whereas the MaxEP was measured during the effort initiated in the total pulmonary capacity, keeping pressures stable for at least 1 second. The statistical analysis was performed through using the Mann-Whitney test with a 5% level of significance. The MaxIP values of Child A 95.5 +/- 40.507 cm H2O (average +/- DP) and Child B 87.2 +/- 35.02 patients were higher than those for Child C patients (34.83 +/- 3.68; P <.05). Similar results were observed for the MaxEP of Child A and B groups (116.25 +/- 31.98 and 97.28 +/- 31.08, respectively; P <.05), versus the Child C group (48.16 +/- 22.60). Between groups A and B, the MaxEP were similar (P >.05). We concluded that Child C patients display muscle weakness significantly greater than that of subjects classified as Child A or B.

Slight activation of nuclear factor kappa-B is associated with increased hepatic stellate cell apoptosis in human schistosomal fibrosis

To investigate the relationship between NF-kappa B activation and hepatic stellate cell (HSC) apoptosis in hepatosplenic schistosomiasis, hepatic biopsies from patients with Schistosoma mansoni-induced periportal fibrosis, hepatitis C virus-induced cirrhosis, and normal liver were submitted to alpha-smooth muscle actin (alpha-SMA) and NF-kappa B p65 immunohistochemistry, as well as to NF-kappa B Southwestern histochemistry and TUNEL assay. The numbers of alpha-SMA-positive cells and NF-kappa B- and NF-kappa B p65-positive HSC nuclei were reduced in schistosomal fibrosis relative to liver cirrhosis. In addition, increased HSC NF-kappa B p65 and TUNEL labeling was observed in schistosomiasis when compared to cirrhosis. These results suggest a possible relationship between the slight activation of the NF-kappa B complex and the increase of apoptotic HSC number in schistosome-induced fibrosis, taking place to a reduced HSC number in schistosomiasis in relation to liver cirrhosis. Therefore, the NF-kappa B pathway may constitute an important down-regulatory mechanism in the pathogenesis of human schistosomiasis mansoni, although further studies are needed to refine the understanding of this process. (C) 2009 Elsevier B.V. All rights reserved.

Morphological and Molecular Pathology of CCl(4)-Induced Hepatic Fibrosis in Connexin43-Deficient Mice

Gap junction channels, formed by connexins (Cx), are involved in the maintenance of tissue homeostasis, cell growth, differentiation, and development. Several studies have shown that Cx43 is involved in the control of wound healing in dermal tissue. However, it remains unknown whether Cx43 plays a role in the control of liver fibrogenesis. Our study investigated the roles of Cx43 heterologous deletion on carbon tetrachloride (CCl(4))-induced hepatic fibrosis in mice. We administered CCl(4) to both Cx43-deficient (Cx43(+/-)) and wild-type mice and examined hepatocellular injury and collagen deposition by histological and ultrastructural analyses. Serum biochemical analysis was performed to quantify liver injury. Hepatocyte proliferation was analyzed immunohistochemically. Protein and messenger RNA (mRNA) expression of liver connexins were evaluated using immunohistochemistry as well as immunoblotting analysis and quantitative real-time PCR. We demonstrated that Cx43(+/-) mice developed excessive liver fibrosis compared with wild-type mice after CCl(4)-induced chronic hepatic injury, with thick and irregular collagen fibers. Histopathological evaluation showed that Cx43(+/-) mice present less necroinflammatory lesions in liver parenchyma and consequent reduction of serum aminotransferase activity. Hepatocyte cell proliferation was reduced in Cx43(+/-) mice. There was no difference in Cx32 and Cx26 protein or mRNA expression in fibrotic mice. Protein expression of Cx43 increased in CCl(4)-treated mice, although with aberrant protein location on cytoplasm of perisinusoidal cells. Our results demonstrate that Cx43 plays an important role in the control and regulation of hepatic fibrogenesis. Microsc. Res. Tech. 74:421-429, 2011. (C) 2010 Wiley-Liss, Inc.

Hepatocellular carcinoma in Brazil: report of a national survey (Florianópolis, SC, 1995)

In order to investigate epidemiological aspects of hepatocellular carcinoma (HCC) in Brazil, basic informations about cases diagnosed from January 1992 to December 1994 were requested to several medical centers of different Brazilian States. A simple questionnaire included age, sex, alcohol abuse (over 80g/day), associated liver cirrhosis, persistent HBV infection (HBsAg), HCV infection (anti-HCV) and serum levels of alpha fetoprotein. 287 cases, over 16 years old, from 19 medical centers of 8 States (Pará, Bahia, Minas Gerais, Espirito Santo, Rio de Janeiro, São Paulo, Paraná and Rio Grande do Sul) were analysed. The results showed: (a) Mean age was 56.3 ± 14.4 for men and 54.7 ± 16.8 yr for women and the male/female ratio was 3.4:1. (b) 69.6% were caucasians, 21.8% mullatoes, 4.8% orientals and 3.7% blacks. (c) HBsAg (+) in 77/236 cases (41.6%) without differences between males and females. (d) Anti-HCV (+) in 52/193 cases (26.9%). (e) 7/180 cases were positive both for HBsAg and anti-HCV (3.8%). (f) There was chronic alcoholism in 88/235 cases (37%). (g) HCC was found in cirrhotic livers in 71.2% of 202 cases in which the presence or absence of cirrhosis was reported. (h) Alpha-fetoprotein above 20 ng/ml was found in 124/172 cases (72%) and above 500 ng/ml only in 40 cases (23.2%). These results showed that the HCC in Brazil has an intermediate epidemiological pattern as compared to those from areas of low and high incidence of the tumor. In spite of the high frequency of the association of HCC with the HBV and/or HCV infections, 42% of 180 cases were negative both for HBsAg and anti-HCV, indicating the possible role of other etiological factors. The comparison of data from different States showed some regional differences: higher frequency of associated HBsAg in Pará, Bahia, Minas Gerais and Espírito Santo, higher frequency of associated HCV infection in Rio de Janeiro, São Paulo and States of the Southern region and low frequency of associated liver cirrhosis in Salvador and Rio de Janeiro (55.5 and 50% respectively). Further investigation will be necessary to study the presence of other possible etiological factors as aflatoxins, suggested by the favourable climatic conditions for food contamination by fungi in the majority Brazilian regions

HEPATOCELLULAR CARCINOMA IN A NON-CIRRHOTIC PATIENT WITH SUSTAINED VIROLOGICAL RESPONSE AFTER HEPATITIS C TREATMENT

Chronic infection by hepatitis C virus (HCV) is one of the main risk factors for the development of liver cirrhosis and hepatocellular carcinoma. However, the emergence of hepatocellular carcinoma (HCC) in non-cirrhotic HCV patients, especially after sustained virological response (SVR) is an unusual event. Recently, it has been suggested that HCV genotype 3 may have a particular oncogenic mechanism, but the factors involved in these cases as well as the profile of these patients are still not fully understood. Thus, we present the case of a non-cirrhotic fifty-year-old male with HCV infection, genotype 3a, who developed HCC two years after treatment with pegylated-interferon and ribavirin, with SVR, in Brazil.

Case histories of infectious disease management in developing countries: Phnom Penh and Kabul

Healthcare in developing countries is affected by severe poverty, political instability and diseases that may be of lesser importance in industrialized countries. The aim of this paper was to present two cases and histories of physicians working in hospitals in developing countries and to discuss the opportunities for clinical investigation and collaboration. Cases of patients in Phnom Penh, Cambodia, with histoplasmosis, cryptococcal meningitis, crusted scabies, cerebral lesions and human immunodeficiency virus and of patients in Kabul, Afghanistan, with liver cirrhosis, nephrotic syndrome and facial ulcer are discussed. Greater developmental support is required from industrialized nations, and mutually beneficial cooperation is possible since similar clinical problems exist on both sides (e.g. opportunistic cardiovascular infections). Examples for possible support of hospital medicine include physician interchange visits with defined objectives (e.g. infection control or echocardiography training) and collaboration with clinical investigations and projects developed locally (e.g. epidemiology of cardiovascular diseases or nosocomial bloodborne infections).

Hepatitis virus and hepatocellular carcinoma in Brazil: a report from the State of Espírito Santo

IntroductionFew studies have examined hepatocellular carcinoma (HCC) in Brazil, and the incidence and risk factors for this type of malignancy vary greatly geographically. In this paper, we report several risk factors associated with HCC diagnosed at the University Hospital in Vitória, ES, Brazil.MethodsWe reviewed 274 cases of HCC (January 1993 to December 2011) in which hepatitis B (HBV) and C (HCV) virus infection and chronic alcoholism were investigated. A diagnosis of hepatocellular carcinoma was confirmed by histology or by the presence of a characteristic pattern on imaging.ResultsHCC with associated liver cirrhosis was noted in 85.4% of cases. The mean ages of men and women were 56.6 years and 57.5 years, respectively. The male-to-female ratio was 5.8:1. Associated risk factors included the following: HBV, 37.6% (alone, 23.4%; associated with chronic alcoholism, 14.2%); HCV, 22.6% (alone, 13.5%; associated with chronic alcoholism, 9.1%), chronic alcoholism, 17.1%, non-alcoholic steatohepatitis, 2.6% and cryptogenic, 19.3%. The male-to-female ratio was higher in cases associated with HBV or chronic alcoholism compared with HCV-associated or cryptogenic cases. In 40 cases without associated cirrhosis, the male-to-female ratio and mean age were lower than those in cirrhosis-associated cases.ConclusionsThese results demonstrate that the main risk factor associated with HCC in the State of Espírito Santo is HBV. Chronic alcoholism is an important etiological factor, alone or in association with HBV or HCV infection.

Tendències temporals de la mortalitat per càncer de fetge a Catalunya: periode 1983-2002 i projeccions pel 2005

Estudi elaborat a partir d’una estada al Finnish Cancer Registry a Helsinki, Finlandia entre setembre i novembre del 2006. Davant l’increment dels tumors hepàtics en països industrialitzats, s’avaluen les tendències temporals de la malaltia hepàtica a Catalunya durant el període 1983-2002 i s’estima la tendència futura a partir de l’any 2005. L’estudi s’ha basat en dades del Registre de Mortalitat de Catalunya i de l’Institut d’Estadística de Catalunya. La malaltia hepàtica inclou diverses tipologies de tumors hepàtics i la cirrosi hepàtica. Els models edad-període-cohort s’han emprat per estimar els efectes període de mortalitat i cohort de naixement. Els resultats han mostrat que les taxes de mortalitat per cirrosi han disminuït en ambdós sexes, exceptuant els homes d’entre els 35-50 anys, pels quals la mortalitat es mantingué estable. S’han observat increments en la mortalitat per carcinoma hepatocel•lular i en els tumors de vies biliars intrahepàtiques, mentre que les projeccions mostren estabilitat en la tendència d’aquestes malalties durant el període 2005-2009. Les tendències de la mortalitat per malaltia hepàtica constatades poden ser degudes a la implementació de teràpies noves, nous mètodes de diagnòstic, infecció pel virus de l’hepatitis C d’altres factors desconeguts.

Hepatitis C Virus Infection and Kidney Transplantation in 2014: What's New?

Chronic hepatitis C virus (HCV) infection remains an important health problem, which is associated with deleterious consequences in kidney transplant recipients. Besides hepatic complications, several extrahepatic complications contribute to reduced patient and allograft survival in HCV-infected kidney recipients. However, HCV infection should not be considered as a contraindication for kidney transplantation because patient survival is better with transplantation than on dialysis. Treatment of HCV infection is currently interferon-alpha (IFN-α) based, which has been associated with higher renal allograft rejection rates. Therefore, antiviral treatment before transplantation is preferable. As in the nontransplant setting, IFN-free treatment regimens, because of their greater efficacy and reduced toxicity, currently represent promising and attractive therapeutic options after kidney transplantation as well. However, clinical trials will be required to closely evaluate these regimens in kidney recipients. There is also a need for prospective controlled studies to determine the optimal immunosuppressive regimens after transplantation in HCV-infected recipients. Combined kidney and liver transplantation is required in patients with advanced liver cirrhosis. However, in patients with cleared HCV infection and early cirrhosis without portal hypertension, kidney transplantation alone may be considered. There is some agreement about the use of HCV-positive donors in HCV-infected recipients, although data regarding posttransplant survival rates are controversial.

Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C.

BACKGROUND/AIM: Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. Connective tissue growth factor (CTGF) plays a major role in extracellular matrix production in fibrotic disorders including cirrhosis, and its expression is stimulated in vitro by insulin and glucose. We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis. METHODS: We included 153 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study and for whom a liver biopsy and plasma samples were available. CTGF expression was assessed quantitatively by immunohistochemistry. In 94 patients (57 with genotypes non-3), plasma levels of glucose, insulin and leptin were also measured. CTGF synthesis was investigated by immunoblotting on LX-2 stellate cells. RESULTS: Connective tissue growth factor expression was higher in patients with steatosis (P=0.039) and in patients with fibrosis (P=0.008) than those without these features. CTGF levels were neither associated with insulinaemia or with glycaemia, nor with inflammation. By multiple regression analysis, CTGF levels were independently associated with steatosis, a past history of alcohol abuse, plasma leptin and HCV RNA levels; when only patients with genotypes non-3 were considered, CTGF levels were independently associated with a past history of alcohol abuse, plasma leptin levels and steatosis. Leptin stimulated CTGF synthesis in LX-2 cells. CONCLUSIONS: In patients with chronic hepatitis C and steatosis, CTGF may promote fibrosis independently of inflammation. CTGF may link steatosis and fibrosis via increased leptin levels.