Previous hepatitis E virus infection, cirrhosis and insulin resistance in patients with chronic hepatitis C

ABSTRACT Background: Hepatitis E virus (HEV) infection in patients with pre-existing liver disease has shown high morbidity and lethality. The consequences of HEV superinfection in patients with chronic hepatitis C virus (HCV) infection are not fully understood. This study aimed to evaluate the association between the presence of anti-HEV antibodies, liver cirrhosis, and insulin resistance. Methods: A total of 618 patients chronically infected with HCV were included from three reference centers for viral hepatitis in São Paulo, Brazil. Presence of anti-HEV IgG was assessed by enzyme-linked immunosorbent assay (WANTAI HEV-IgG ELISA). Results: The seroprevalence of anti-HEV in patients with cirrhosis was significantly higher than in patients without cirrhosis (13.2% vs 8%, OR = 1.74, p = 0.04). Seropositivity for anti-HEV, adjusted for sex, age, and HCV genotype showed an association trend with hepatic cirrhosis (aOR = 1.75, p = 0.059). Presence of HEV antibodies, adjusted for age, body mass index and cirrhosis, was shown to be independently associated with insulin resistance (aOR: 4.39; p = 0.045). Conclusion: Patients with chronic hepatitis C are under risk of hepatitis E virus superinfection in Brazil. The trend toward association between cirrhosis and previous HEV infection suggests that it may accelerate liver fibrosis in patients with chronic hepatitis C. In addition, previous infection by HEV is independently associated with insulin resistance in the studied population, which may be an extra-hepatic manifestation of hepatitis E that persists after resolution of the active infection, and may contribute to fibrosis progression.

IL-6, TNF-α, IL-10, and nutritional status in pediatric patients with biliary atresia / IL-6, TNF-α, IL-10 e estado nutricional em pacientes pediátricos com atresia biliar

Abstract Objectives: The objective of the present study is to evaluate whether IL-6, TNF-α, IL-10 are associated with nutritional status in patients with cirrhosis secondary to biliary atresia and compare to healthy controls. Methods: The parameters used for nutritional assessment were the standard deviation scores of height-for-age and of triceps skinfold thickness-for-age. The severity of cirrhosis was evaluated using the Child-Pugh score and PELD/MELD. Serum cytokines were measured using Cytometric Bead Array flow cytometry. Results: IL-6, TNF-α, and IL-10 were significantly higher in the cirrhosis group when compared with the control group (2.4 vs. 0.24 (p < 0.001), 0.21 vs. 0.14 (p = 0.007), and 0.65 vs. 0.36 (p = 0.004), respectively. IL-6 and IL-10 were positively correlated with disease severity (0.450 [p = 0.001] and 0.410; [p = 0.002], respectively). TNF-α did not show a significant correlation with disease severity (0.100; p = 0.478). Regarding nutritional evaluation, IL-6 was negatively correlated with the standard deviation score of height-for-age (−0.493; p < 0.001) and of triceps skinfold thickness-for-age (−0.503; p < 0.001), respectively. IL-10 exhibited a negative correlation with the standard deviation score of height-for-age (−0.476; p < 0.001) and the standard deviation score of triceps skinfold thickness-for-age (−0.388; p = 0.004). TNF-α did not show any significance in both anthropometric parameters (−0.083 (p = 0.555) and −0.161 (p = 0.253). Conclusion: The authors suggest that, in patients with cirrhosis secondary to biliary atresia, IL-6 could be used as a possible supporting biomarker of deficient nutritional status and elevated IL-10 levels could be used as a possible early-stage supporting biomarker of deteriorating nutritional status.

Resumo Objetivos: Avaliar se há associações entre a IL-6, o TNF-α, a IL-10 e a estado nutricional em pacientes com cirrose secundária a atresia biliar e comparar com controles saudáveis. Métodos: Os parâmetros usados na avaliação nutricional foram desvio padrão de estatura para a idade e espessura da prega cutânea do tríceps para a idade. A gravidade da cirrose foi avaliada por meio da classificação de Child-Pugh e do PELD/MELD. As citocinas no soro foram medidas por citometria de fluxo - técnica de Cytometric Bead Array. Resultados: A IL-6, o TNF-α e a IL-10 foram significativamente maiores no grupo de cirrose em comparação com o grupo de controle [2,4 em comparação com 0,24 (p < 0,001)], [0,21 em comparação com 0,14 (p = 0,007)] e [0,65 em comparação com 0,36 (p = 0,004)], respectivamente. A IL-6 e a IL-10 demonstraram correlação positiva com a gravidade da doença (0,450; p = 0,001) e (0,410; p = 0,002), respectivamente. O TNF-α não mostrou relevância na gravidade da doença (0,100; p = 0,478). Com relação à avaliação nutricional, a IL-6 demonstrou correlação negativa com o desvio padrão de estatura para a idade (−0,493; p < 0,001) e o desvio padrão de espessura da prega cutânea do tríceps para a idade (−0,503; p < 0,001), respectivamente. A IL-10 demonstrou correlação negativa com o desvio padrão de estatura para a idade (−0,476; p < 0,001) e o desvio padrão de espessura da prega cutânea do tríceps para a idade (−0,388; p = 0,004), respectivamente. O TNF-α não mostrou relevância em ambos os parâmetros antropométricos [(−0,083; p = 0,555); (−0,161; p = 0,253)]. Conclusão: Assim, sugerimos que, em pacientes com cirrose secundária a atresia biliar, IL-6 pode ser usado como um possível biomarcador de suporte do estado nutricional deficiente e níveis aumentados de IL-10 podem ser usados como um possível biomarcador de suporte, em fase inicial, de deterioração do estado nutricional.

Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection

Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants.

Characteristics of an outpatient chronic hepatitis B virus infection cohort / Caracterização de uma coorte ambulatorial de pacientes com infecção por vírus da hepatite B crônica

ABSTRACT Objective: To characterize a chronic hepatitis B cohort based on initial and follow-up clinical evaluations. Methods: A retrospective and descriptive analysis of clinical and laboratory data from chronic HBsAg adult carriers, without HIV, unexposed to treatment, with at least two outpatient visits, between February 2006 and November 2012. Fisher´s exact test, χ², Wilcoxon, Spearman, multiple comparisons and Kappa tests were applied, the level of significance adopted was 5%, with a 95% confidence interval. Results: 175 patients with mean age of 42.95±12.53 years were included: 93 (53.1%) were men, 152 (86.9%) were negative for hepatitis B e-antigen (HBeAg), 3 (1.7%) had hepatitis C coinfection, 15 (8.6%) had cirrhosis, and 2 (1.1%) had hepatocellular carcinoma. Genotype A predominated. Sixty-six patients (37.7%) had active hepatitis, 6 (3.4%) presented immune tolerance, and 38 (21.7%) were inactive carriers. Exacerbations and/or viral breakthrough were detected in 16 patients (9.1%). In 32 patients (18.3%), hepatitis B virus DNA remained persistently elevated and alanine aminotransferase levels were normal, whereas in 17 (9.7%), there was low hepatitis B virus DNA and alterated alanine aminotransferase. If only initial alanine aminotransferase and hepatitis B virus DNA values were considered, 15 cases of active hepatitis would not have been detected. Advanced fibrosis was more common in HBeAg-positive patients, and it was significantly associated with transaminases, hepatitis B virus DNA, and age. Conclusion: Many patients had active hepatitis, but almost 25%, who were HBeAg non-reactive, were only identified because of combined analyses of the hepatitis B virus DNA and transaminases levels, sometimes associated with histological data, after clinical follow-up. .

RESUMO Objetivo: Caracterizar uma coorte de pacientes com hepatite B crônica, segundo parâmetros iniciais e evolutivos. Métodos: Análise retrospectiva e descritiva dos dados clínicos e laboratoriais de portadores crônicos adultos do HBsAg, sem HIV, virgens de tratamento, com ao menos duas consultas ambulatoriais entre fevereiro de 2006 a novembro de 2012. Empregaram-se os testes exato de Fisher, χ², Wilcoxon, Spearman, Kappa e comparações múltiplas, o nível de significância estatística adotado foi de 5% e intervalo de confiança de 95%. Resultados: Foram incluídos 175 pacientes com média de idade de 42,95±12,53 anos, 93 (53,1%) do sexo masculino, 152 (86,9%) não reagentes para o antígeno e (HBeAg), 3 (1,7%) coinfectados com hepatite C, 15 (8,6%) cirróticos e 2 (1,1%) com carcinoma hepatocelular. Predominou o genótipo A. Constataram-se hepatite ativa em 66 pacientes (37,7%), imunotolerância em 6 (3,4%), estado de portador inativo em 38 (21,7%), exacerbações e/ou escapes virais em 16 (9,1%). Em 32 (18,3%), havia DNA viral persistentemente elevado e alanina aminotransferase normal; em 17 (9,7%), carga viral constantemente baixa e alanina aminotransferase alterada. Se fossem considerados apenas transaminases e DNA viral iniciais, 15 casos de hepatite ativa não teriam sido evidenciados. Fibrose avançada foi mais prevalente em HBeAg reagentes e associou-se direta e significativamente ao DNA do vírus da hepatite, idade e transaminases. Conclusão: Grande parte dos pacientes apresentou hepatite ativa. Porém, aproximadamente um quarto (todos pertencentes ao grupo HBeAg não reagente) foram identificados somente em função da análise conjunta das mensurações sequenciais de DNA do vírus da hepatite e transaminases, por vezes aliada a dados histológicos, após seguimento. .

Esquistossomose mansônica humana: avaliação do receptor antagonista de IL-13 (IL-13Ra2) e da resposta imune celular / Human schistosomiasis: evaluation of receptor antagonist IL-13 (IL-13ra2) and cellular immune responses

Estudos indicam que citocinas Th1 (IL-2, TNF-alfa e IFN-gama) reduzem a fibrose na esquistossomose mansônica, enquanto que as Th2 (IL-4, IL-5, IL-6, IL-10 e IL-13) tem papel crítico na patogênese da doença. O desenvolvimento da resposta Th2 é dependente de IL-4, mas estudos revelaram a IL-13 como a mediadora da fibrose. Os mecanismos de controle da IL-13 estão ligados aos receptores desta citocina. O receptor IL-13Ra2, conhecida como receptor antagonista se liga com alta afinidade a IL-13, e estudos identificaram a sua participação na diminuição da fibrose e tamanho do granuloma. O principal objetivo desse projeto é avaliar o papel do IL-13Ra2 e da resposta imune celular nos diferentes graus de fibrose hepática e nas formas clínicas da esquistossomose mansônica humana. Os pacientes com diversas formas clínicas foram selecionados no Ambulatório de Gastroenterologia do HC- UFPE e avaliados através da ultrassonografia. As citocinas Th1 e Th2 foram dosadas através de citometria de fluxo e ELISA (IL-13 e IFN-gama), para a análise estatística foram utilizados testes de Mann-Whitney e Kruskal-Wallis e o teste de correlação de Spearman considerando um p 0,05 como significativo. Foi encontrado uma correlação negativa (p 0,05) entre o IL-13Ra2 e a IL-13, sugerindo um aumento da citocina no início da fibrose. Foi encontrada correlação inicialmente negativa nos pacientes sem fibrose e posteriormente positiva, nos pacientes com fibrose grave, entre IFN-gama e IL-13, salientando um novo mecanismo de regulação no processo de fibrose periportal na doença. Houve correlação positiva entre as citocinas do perfil Th1 e entre as citocinas do perfil Th2, sugerindo falta de supressão imunológica e presença de ambas às respostas, regulando a doença, com diferentes graus de fibrose periportal. Os resultados contribuirão para um melhor entendimento sobre os mecanismos imunes que controlam o processo de fibrogênese hepática em humanos e poderão ainda permitir um melhor entendimento da relação entre resposta imune celular e esquistossomose mansônica.

Seroprevalence of hepatitis A immunity among brazilian adult patients with liver cirrhosis: is HAV vaccination necessary?

BACKGROUND: Patients with chronic liver disease have a higher risk of fulminant hepatitis when infected with hepatitis A virus, and vaccination of these patients against such infection is recommended. In Brazil, mainly in the South and Southeast regions, the epidemiology of hepatitis A (HA) has shifted from high to intermediate endemicity, which would have implication on policy of HA vaccination for these populations. OBJECTIVE: To verify the prevalence of HA immunity in adult patients with liver cirrhosis (LC), in Uberlândia MG, a city of Southeastern Brazil. METHODS: Between December 2005 and December 2006, 106 patients with LC were consecutively evaluated. In addition, 75 individuals without LC or alcoholism were evaluated (control group - CG). RESULTS: Total anti-HAV (ELISA methods) was positive in 104 (98.1 percent) patients with LC (82 men, 24 women; mean age, 53.3 ± 11.9 years) and in 74 (98.7 percent) individuals of the CG (55 men, 20 women; mean age, 47 ± 11.6 years), p > 0.05. CONCLUSIONS: For patients with chronic liver disease, in the geographic regions and age groups evaluated, routine vaccination against hepatitis A is not recommended. Moreover, the serum determination of total anti-HAV, used to assess immunity, is five times cheaper than vaccination against hepatitis A and, for this reason, should precede vaccination.

Smooth muscle antibodies and cryoglobulinemia are associated with advanced liver fibrosis in Brazilian hepatitis C virus carriers

Cryoglobulinemia and non-organ-specific-autoantibody are biomarkers of autoimmunity of the chronic infection caused by hepatitis C virus (HCV). In this work, we report the association between the presence of smooth muscle antibodies (SMA) and cryoglobulinemia and chronic liver disease in HCV carriers. Sixty-five untreated HCV patients, 38 women and 27 men were included in this study. Cryoglobulinemia was tested by cryoprecipitation, SMA by indirect fluorescent antibody test, and liver fibrosis and hepatocellular inflammation activity was investigated by histology of liver biopsy using the METAVIR score. The prevalence of SMA in the patients was 33.8 percent and cryoglobulinemia was demonstrated in 36.9 percent patients. Cryoglobulinemia and SMA seropositivity was associated with advanced fibrosis (p < 0.05). The presence of SMA and cryoglobulinemia was not associated with hepatocellular inflammation activity, age, carrier gender or HCV genotype. We concluded that liver biopsy should be recommended for HCV carriers that are seropositive for SMA or cryoglobulinemia.

Infecciones bacterianas en el paciente cirrótico / Bacterial infections in patients with cirrhosis

Las infecciones bacterianas constituyen una complicación frecuente y severa en pacientes cirróticos debido a la existencia de alteraciones inmunológicas diversas, traslocación bacteriana y una mayor respuesta inflamatoria. La producción aumentada de citoquinas proinflamatorias, óxido nítrico y otros mediadores favorece el desarrollo de otras complicaciones, tales como deterioro hemodinámico, insuficiencia renal y encefalopatía hepática. Los efectos hemodinámicos de los mediadores inflamatorios son capaces de acentuar las alteraciones de la circulación sistémica y renal propias de la cirrosis. La insuficiencia renal en pacientes con sepsis no relacionada a peritonitis bacteriana espontánea tiene mal pronóstico incluso en casos reversibles y el índice MELD pareciera ser un buen predictor en este sentido. Estudio recientes sobre encefalopatía hepática sugieren que la respuesta inflamatoria y sus mediadores pueden ser importantes en la modulación de los efectos del amonio sobre el cerebro en los pacientes con cirrosis. El diagnóstico y tratamiento oportuno de la infección permiten mejorar el pronóstico en estos pacientes. La relación entre infección y hemorragia digestiva es estrecha, fundamentando el uso de antibióticos profilácticos. El uso de albúmina en cirróticos con infecciones diferentes a peritonitis bacteriana espontánea no ha demostrado reducir la incidencia de insuficiencia renal ni la mortalidad.

Bacterial infections are a frequent and severe complication in cirrhotic patients due to the existence of multiple immune alterations, bacterial translocation and increased inflammatory response. Increased production of proinflammatory cytokines, nitric oxide and other mediators promotes the development of other complications such as hemodynamic deterioration, renal failure and hepatic encephalopathy. Hemodynamic effects of inflammatory mediators are able to increase changes of systemic and renal circulation, typical of cirrhosis. Renal failure in patients with sepsis unrelated to spontaneous bacterial peritonitis has a poor prognosis, even in reversible cases; MELD score might be a good predictor in this regard. Recent studies about hepatic encephalophaty suggest that inflammatory response and its mediators may be important in modulating the effect of ammonia on the brain of the cirrhotic patient. Early diagnosis and treatment of the infection can improve the prognosis in these patients. The relationship between infection and gastrointestinal bleeding is narrow, justifying the use of prophylactic antibiotics. The administration of albumin to patients with cirrhosis and infections other than spontaneous bacterial peritonitis has not shown to reduce the incidence of renal failure or mortality.

Prognostic value of TNF alpha mRNA and VEGF mRNA expression in patients with chronic hepatitis C geno-type-4, with and without cirrhosis and hepatocellular carcinoma to predict disease outcome

The study aimed to clarify whether vascular endothelial growth factor mRNA [VEGF mRNA] and TNF alpha mRNA in the HCC tissues on top of HCV with and without cirrhosis obtained from specimens after curative hepatic resection has a prognostic value and recurrence predictive value compared to other tumor criteria. A total of 160 patients were studied. The preoperative laboratory, radiological and staging to patients was done. Using in situ hybridization technique, VEGF mRNA and TNF alpha mRNA were determined in liver tissues of, 10 controls, 50 with HCC, 50 with HCV without cirrhosis and 50 HCV with cirrhosis. The results showed that in HCC cases there was positive correlation between increasing age, loss of weight, INR and AFP but not in other cases of CHC with or without cirrhosis. AFP, vascular invasion, encapsulation, tumor size and grade and platelet count were related to patients outcome and recurrence of tumor after follow up of most cases for 3 years. The expression of VEGF in liver tissues was proportional to progress of viral hepatitis to cirrhosis with more expression in cases progressed to malignant changes. More expression of VEGF in HCC was more evident with intense expression in cases with Vascular and capsular invasion and higher level of AFP. Expression of TNF alpha mRNA and VEGF mRNA shows increasing expression with positive correlation to progression of viral hepatitis to cirrhosis with more positive with cases developed HCC

Double-dose hepatitis B vaccination in cirrhotic patients on a liver transplant waiting list

Development of immunity to hepatitis B virus in cirrhotic patients waiting for liver transplantation is highly desirable. Though a double-dose regimen is available, little is know about its effectiveness. We examined the efficacy of double-dose hepatitis B virus vaccination in cirrhotic patients waiting for liver transplantation. We studied 43 patients who were waiting for liver transplantation. They were vaccinated with three doses of 40 mg hepatitis B vaccine at 0, 1 and 6 months; the normal dose is 20 mg. Efficacy was measured based on seroconversion of anti-HBs. Global response to the primary vaccination scheme was 67.5 percent (29 patients). Forty-one per cent of responders had anti-HBs titers above 1,000 IU/mL. No factors were associated with response, based on multivariate analysis. The vaccination scheme of 40 mg at 0, 1 and 6 months was superior to conventional vaccination doses (20 mg) for cirrhotic patients on a waiting list for liver transplantation.

Hepatic local micro-environmental immune status in hepatocellular carcinoma and cirrhotic tissues / Estatus inmune microambiental local hepático en el carcinoma hepatocelular y los Tejidos Cirróticos

Hepatocellular carcinoma (HCC) is one of the most common malignant tumours in the world, especially in Guangxi, China. The causes and mechanism of its tumourigenesis and development have not been completely clarified Some studies revealed that the hepatic local cellular immune function was one of the factors. In the present study, the local micro-environmental immune status was explored by investigating the number, distribution and function of CD3, CD57, CD20, CD68, and granzyme B (GrB) positive cells in 60 patients with HCC and 62 patients with liver cirrhosis (LC) and its relationship with the prognosis of the patients. The results showed that the number of T and B lymphocytes and natural killer (NK) cells in the liver of HCC patients was significantly higher than that in the LC and normal controls; while the number of macrophages (Mphi) was significantly lower The number of Mphi in the tissues decreased successively with the decrease of HCC differentiation; GrB-expressing cells in the liver predominantly consisted of CD57 positive cells. The number of NK cells, B lymphocytes and GrB-expressing cells in the cancerous tissues of stage I and II was significantly higher than that of stages III and IV. The number of T lymphocytes, NK cells, Mphi, and GrB-expressing lymphocytes in HCC cases without metastasis in 15 months was significantly higher than in the metastatic counterparts. The number of T and B lymphocytes, NK cells, and GrB-expressing cells decreased in patients with the progression of the HCC. These results suggest that the number of T and B lymphocytes, NK cells, Mphi and GrB-positive lymphocytes might be important markers in the estimation of hepatic local immune status and be useful factors for predicting the prognosis of HCC patients.

Preliminar evaluation of cytokines in the hepatitis C-schistosomiasis co-infection

Evaluation of hepatic fibrosis is usually performed by histopathological examination of biopsies. However, this is an invasive and potentially dangerous procedure. Several studies have proposed serum biological markers of hepatic fibrosis. This communication evaluates the use of serum cytokines as markers of hepatic fibrosis in hepatitis C, schistosomiasis, and co-infection.

Apoptosis and progression of hepatic fibrosis in hepatitis C patients

Hepatitis C is a worldwide endemic disease, affecting roughly 200 million people. It has a variable prognosis, depending on the progression to fibrosis. During the last five years, the importance of apoptosis for the pathogenesis of various diseases, including hepatitis, has been recognized. It has been suggested that an increase in T cell-apoptosis during a hepatitis C virus infection is the cause of impaired regulation of the immune cellular response, helping to maintain infection. Thus, the interest in discovering the probable mechanisms by which the hepatitis C virus perpetuates in the liver, and to determine the conditions that predispose for progression of this disease, makes investigation of apoptosis in hepatic injury of great interest. We have made an overview of the various mechanisms by which the cell, more specifically the hepatic cell, is affected by apoptosis, and how it interacts with the hepatitis C virus and the immune system.

Diagnóstico, manejo y prevención de infecciones en pacientes con cirrosis hepática / Diagnosis, management and prevention of infections in cirrhotic patients

Las infecciones en pacientes afectados por cirrosis hepática son frecuentes, recurrentes y de pronóstico desfavorable. Su génesis está facilitada por defectos adquiridos y progresivos de la inmunidad innata y del sistema retículo-endotelial, siendo agravados por el consumo de alcohol. Estas infecciones son habitualmente bacterianas o virales y tienen habitualmente una presentación clínica estereotipada, aunque en ocasiones el diagnóstico puede ser difícil. Las neumonías, infecciones del tracto urinario, bacteriemias y peritonitis bacteriana espontánea (PBE) abarcan más del 90% de los casos; esta última exige de una alta sospecha clínica y de un protocolo de diagnóstico estandarizado. Las medidas preventivas son importantes en el manejo de estos pacientes e incluyen quimioprofilaxis contra la PBE en casos seleccionados, vacunas contra infecciones neumocóccicas e influenza en general, y hepatitis A y B en pacientes susceptibles. Debido a que la seroconversión con estas vacunas es deficiente, la inmunización activa debiera ser aplicada tan precozmente como sea posible, antes que se establezca un deterioro clínico.

Dysregulation of blood lymphocyte subsets and natural killer cells in schistosomal liver cirrhosis and hepatocellular carcinoma

Immunological factors are important in the pathogenesis of a wide spectrum of hepatobiliary diseases. Using flow cytometry, we determined the changes in lymphocyte subsets and natural killer cells in 123 individuals [81 patients with liver disease and 42 healthy volunteers]. The liver diseases included periportal fibrosis [PPF, 10 patients]. liver cirrhosis [LC, 31 patients], and hepatocellular carcinoma [HCC, 40 patients]. Schistosomiasis and viral hepatitis B and C were the putative etiological agents of liver diseases. Immunophenotyping by indirect immunofluorescence was conducted using monoclonal antibodies to CD3 [T-lymphocytes], CD4 [helper/inducer T-cells], CD8 [suppressor/cytotoxic T-cells] and CD 57 [natural killer cells] cell surface markers. Immunophenotyping of PPF patients showed no significant changes in all markers compared with the healthy controls. However, there was a significant decrease [P<0.01] in CD3 and CD4 T-cells, and a highly significant increase [P<0.001] in CD 57 T-cells in patients with LC or HCC. In addition, LC and HCC patients showed no significant change in CD8 T-cells compared with controls. The progression of liver diseases is associated with a dysregulation of cellular immune responses. T-lymphocytes and natural killer cells may play a role in the immunopathogenesis of LC and HCC

High CA-125 level in cirrhosis of the liver

This patient was 64 years old female who presented with abdominal swelling of 6 weeks duration. She had history of non-insulin dependent diabetes mellitus and hypertension and was taking Dibenclamide, Metformin and Amlodipin. Her physical examination showed distended abdomen with fluid thrill. Her vital signs were normal. Peripheral edema was present and she was moderately obese. Laboratory findings showed hemoglobin 16.5 g/dl, hematocrit 46.9% WBC count was 6500/ul, platelet 224000/ul, Fasting Blood Suger 119 mg/dl, total bilirubin 0.6 mg/dl, direct bilirubin 0.4 mg/dl, AST 46 U/l, ALT 26 U/l, alkaline phosphatase 221 [Normal 39 - 117 U/l] Serum albumin was 3.3 g/dl [Normal 3.5 - 5.0 g/dl], creatinine 0.6mg/dl. Hepatitis B surface Antigen was negative and so was anti HCV. Thyroid profile was normal. CA-125 level was 484 and after one week, repeat level was more than 500 U/ml [Normal 1.7 - 32 U/ ml]. Chest X-Ray was normal and abdominal sonography showed massive ascites and cholelithasis. CT scan of the abdomen and pelvis showed massive ascites and no abnormal masses were noted and pancreas and ovaries were found to be normal. Ascitic fluid was sent for examination and total leucocyte count was 200 cells/ul with 50% of lymphocytes and total protein of 2.4 g/dl. Ascitic fluid cytology was negative for malignant cells. She underwent exploratory laparotomy at which time no malignancy of the ovary or any other organs of the abdomen was found. Liver was noted to be small and shrunken and a biopsy was taken which was reported as cirrhosis of the liver. There were no changes of steatosis. On re-evaluation, her total core antibody [HB core total 1gG] was positive. She was treated with Diuretics and continued on other medical treatment

Anti-HVC en niños con hepatitis crónica activa y cirrosis. Estudio de 25 casos / Anti HCV in children with chronic active hepatitis and liver disease. Study of 25 cases

Se hizo determinación de anti-HVC con la técnica de inmunoanálisis enzimatico de tercera generación en 53 niños. Un grupo (I) fue de 25 niños con hepatopatía, 14 con cirrosis y 11 hepatitis crónica activa (HCA). Otro grupo (II) fue el control, con 28 niños sanos (sin hepatopatia al momento del estudio). En el grupo I hubo seis con anti-HVC positivo. El anti-HVC fue negativo en todos los controles. Hubo una diferencia altamente significativa al comparar el anti-HVC en población enferma con el control p>0.001. La prevalancia del anti-HVC en este estudio es baja en relación a lo señalado en adultos (44 a 86 por ciento); esto puede deberse al tamaño de la muestra, a la alta sensibilidad y especificidad de esta prueba o a ambos hechos

Different T-lymphocyte subset responses dictate organ involvement in schistosomiasis

In this study, 2 color flow cytometric immunophenotyping analysis of lymphocytes and their subsets estimated in fresh peripheral venous blood sample of 15 patients with bilharzial hepatic fibrosis as a result of Schistosoma mansoni infection. 15 patients with active intestinal bilharziasis only without hepatic fibrosis or splenomegaly as well as 15 healthy volunteers. Bilharzial hepatic fibrosis was confirmed by histopathological examination of liver biopsy specimens. HBsAg and HCV Ab positive patients were excluded from the study. Results showed that CD4+% in the group of patients with bilharzial hepatic fibrosis was significantly higher than that of the group with active intestinal bilharziasis. While no significant difference was observed between the two groups of patients with bilharziasis when compared with the control group. CD8+% decreased significantly in patients with bilharzial hepatic fibrosis compared with both control and patients with active intestinal bilharziasis. While CD8+% increased significantly in the group of active intestinal bilharziasis compared with control. CD4/CD8 ratio increased significantly in patients with bilharzial hepatic fibrosis compared with the group of active intestinal bilharziasis and control group. NK% decreased significantly in patients with bilharziasis while NK% increased significantly in the group of active intestinal bilharziasis compared to control. No significant difference was present among the studied groups as regards total leucocytic count, absolute lymphocytic count, CD3%, CD19% and activated T-lymphocyte percentages

Hepatic histology in chronic liver disease in hepatitis B surface antigen positive cases.

The spectrum of histological changes in needle biopsies of the liver tissue was analysed in 43 patients with chronic liver disease who were positive for hepatitis B surface antigen (HBsAg) in their sera. Majority of the patients were around 40 years and there was a male predominance. According to histopathological pattern, there were 18 (41.8%) cases of chronic active hepatitis, 16 (37.2%) cases of inactive cirrhosis, 3 (6.9%) cases of chronic persistent hepatitis and 2 (4.7%) cases of chronic lobular hepatitis and hepatoma each. Two (4.7%) cases could not be exactly categorised into any particular histological entity. The inflammation, hepatic cell necrosis and fibrosis were more marked in cases of chronic active hepatitis without past history of jaundice. Micronodular cirrhosis was the most common histological pattern in the study. Shikata orcein stain for detection of HBsAg in the hepatocytes was positive in 8 (18.6%) cases only.