Paeoniflorin mitigates PBC-induced liver fibrosis by repressing NLRP3 formation

ABSTRACT Purpose: To delve into the influence of paeoniflorin (PA) on abating primary biliary cholangitis (PBC)-induced liver fibrosis and its causative role. Methods: Our team allocated the mice to control group, PA group, PBC group and PBC+PA group. We recorded the weight change of mice in each group. We used Masson staining for determining liver fibrosis, immunofluorescence staining for measuring tumor necrosis factor-α (TNF-α) expression, quantitative real-time polymerase chain reaction (qRT-PCR) for assaying related gene expression, as well as Western blot for testing related protein expression. Results: The weight of PBC model mice declined. Twenty-four weeks after modeling, the positive rate of anti-mitochondrial antibody-M2 (AMA-M2) in PBC mice reached 100%. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), hydroxyproline (HYP), laminin (LN), procollagen type III (PC III), and malondialdehyde (MDA) contents saliently waxed (p<0.01). Meanwhile, superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity patently waned (p<0.01). Liver fibrosis levels were flagrantly higher (p<0.01), and TNF-α, NOD-like receptor protein 3 (NLRP3), caspase-1, interleukin-18 (IL-18), and interleukin-1β (IL-1β) protein or gene expression were manifestly up-regulated (p<0.01). PA could restore the weight of PBC mice, strikingly restrain the positive expression of AMA-M2, and down-regulate serum ALP, ALT, AST, HYP, LN, PC III, MDA in PBC mice (p<0.01). PA could also significantly up-regulate SOD and GSH-px levels (p<0.01), down-regulate IL-1β, IL-18, caspase-1, NLRP3, and TNF-α protein or gene expression in PBC mice (p<0.01) and inhibit liver fibrosis levels (p<0.01). Conclusions: PA can reduce PBC-induced liver fibrosis in mice and may function by curbing the formation of NLRP3.

Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways

BACKGROUND: Non-canonical Wnt pathways play important roles in liver fibrosis. Notum is a newly discovered inhibitor to Wnt proteins. This study was to investigate anti-fibrotic effects of Notum. METHODS: 53 patients with hepatitis B virus (HBV) infection as well as a cell co-culture system of LX-2 and Hep AD38 cells were engaged in this study. Clinical, biological and virological data of each patient were analyzed. Cell viability was detected at different time points. mRNA and protein levels of NFATc1 (Nuclear factor of activated T-cells), Jnk, α-SMA, Col1A1 and TIMP-1 were detected both in LX-2 and liver tissue. Protein levels of NFATc1 and Jnk in liver tissue and their correlations with fibrosis score were analyzed. RESULTS: Hepatitis B virus replication up-regulated Wnt5a induced NFATc1 and Jnk activity in Hep AD38. Notum suppressed NFATc1, Jnk and fibrosis genes expression, reduced cell viability in co-cultured LX-2 cells induced by HBV. Interestingly, Patients with HBV DNA > 5log copies/ml had higher mRNA levels of NFATc1 and fibrosis genes than patients with HBV DNA < 5log copies/ml. Most importantly, protein expressions of NFATc1 and pJnk have positive correlations with liver fibrosis scores in HBV-infected patients. CONCLUSIONS: Our data showed that Notum inhibited HBV-induced liver fibrosis through down-regulating Wnt 5a mediated non-canonical pathways. This study shed light on anti-fibrotic treatment.

Long-term effects of human amniotic membrane in a rat model of biliary fibrosis

Liver fibrosis is the most common outcome of chronic liver diseases, and its progression to cirrhosis can only be effectively treated with liver transplantation. The amniotic membrane (AM) has been studied as an alternative therapy for fibrosis diseases mainly for its favorable properties, including anti-inflammatory, anti-scaring and immunomodulatory properties. It was recently demonstrated that the AM reduces the progression of biliary fibrosis to its advanced stage, cirrhosis, when applied on the liver for 6 weeks after fibrosis induction. Here, we investigated the effects of AM on rat fibrotic liver, during a prolonged period of time. Fibrosis was induced by bile duct ligation (BDL), and at the same time, a fragment of AM was applied around the liver. After 1, 3, 6, and 9 weeks, the degree of fibrosis was assessed by qualitative Knodell scoring, and by quantitative image analysis to quantify the area of collagen deposition in hepatic tissue. While fibrosis progressed rapidly in untreated BDL animals, leading to cirrhosis within 6 weeks, AM-treated livers showed confined fibrosis at the periportal area with few and thin fibrotic septa, but without cirrhosis. In addition, collagen deposition was reduced to about 36 and 55% of levels observed in BDL at 6 and 9 weeks after BDL, respectively, which shows that the longer the period of AM application, the lower the collagen deposition. These results suggested that AM applied as a patch onto the liver surface for longer periods attenuated the severity of biliary fibrosis and protected against liver degeneration caused by excessive collagen deposition.

Nuevas estrategias farmacológicas para el tratamiento del hígado graso no alcohólico / New pharmacological strategies for the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) represents an increasing health problem in Chile and worldwide. In some cases NAFLD presents with a progressive form that can lead to liver fibrosis, cirrhosis and hepatocellular carcinoma. Current pharmacological therapies (pioglitazone and vitamin E) show limited response and are associated to significant adverse effects. During recent years several novel and promising pharmacological therapies have been developed to prevent fibrosis, liver cirrhosis and reduce liver related deaths. The present article summarizes some of these promising strategies, including reported efficacy in clinical trials and associated adverse effects. Hopefully in the near future these new therapies will help to improve NAFLD management and reduce liver related complications.

El hígado graso no alcohólico (HGNA) es un creciente problema de salud pública en Chile y el mundo. En un subgrupo de sujetos, el HGNA puede presentarse con un fenotipo de daño hepático progresivo que puede evolucionar a fibrosis progresiva, cirrosis y carcinoma hepatocelular. Las estrategias farmacológicas actuales (pioglitazona y vitamina E) presentan eficacia limitada y no están exentas de efectos adversos. Durante los últimos años se han desarrollado múltiples estrategias farmacológicas novedosas y promisorias que buscan evitar la progresión hacia cirrosis y reducir la mortalidad de causa hepática. El presente artículo resume los principales nuevos fármacos, los efectos beneficiosos reportados y sus efectos adversos. Es de esperar que en un futuro próximo estas terapias permitan cambiar el pronóstico de nuestros pacientes con HGNA.

Participação da via do Hedgehog na fibrose hepática da esquistossomose mansoni humana e murina experimental / Participation via the Hedgehog in liver fibrosis of human schistosomiasis and experimental murine

INTRODUÇÃO/OBJETIVO: A esquistossomose mansonica é causa importante de fibrose hepática e hipertensão porta em regiões tropicais, e a patogênese da fibrose não está bem esclarecida. Como a via do hedgehog e um dos seus genes alvos, a osteopontina, estão envolvidos em fibroses hepáticas de outras etiologias o objetivo foi investigar a ativação destas vias na esquIsitossomose humana e murina experimental, no intuito de verificar o seu envolvimento no desenvolvimento da forma hepatoesplênica da esquistossomose mansonica (FHE). MATERIAL E MÉTODOS: 87 biópsias em cunha de fígados de pacientes com FHE submetidos a cirurgia e fragmentos de fígado de camundongos suiços infectados com Schistosoma mansoni foram submetidos a métodos imunohistoquímicos e de biologia molecular para avaliar a expressão de ligantes hedgehog (Ihh, Shh), receptor Patched, fatores de transcrição Gli 1 e 2...

inglês: BACKGROUND AND AIMS: Schistosomiasis is a major cause of liver fibrosis and portal hypertension in tropical regions, and the pathogenesis of fibrosis is not well established. As hedgehog pathway and one of its target genes, osteopontin, are involved in liver fibrosis of other etiologies our aims were to investigate the activation of these pathways in human and experimental murine schistosomiasis, in an attempt to verify their involvement in the development of hepatosplenic schistosomiasis mansoni (HS). METHODS: 87 wedge liver biopsies of patients with HS submitted to surgery and liver fragments Swiss mice infected with Schistosoma mansoni were submitted to immunohistochemistry and molecular biology methods to evaluate the expression of hedgehog ligands (Ihh, Shh), patched receptor , Gli transcription factors and osteopontin...

Participação da via do Hedgehog na fibrose hepática da esquistossomose mansoni humana e murina experimental / Participation via the Hedgehog in liver fibrosis of human schistosomiasis and experimental murine

INTRODUÇÃO/OBJETIVO: A esquistossomose mansonica é causa importante de fibrose hepática e hipertensão porta em regiões tropicais, e a patogênese da fibrose não está bem esclarecida. Como a via do hedgehog e um dos seus genes alvos,a osteopontina, estão envolvidos em fibroses hepáticas de outras etiologias o objetivo foi investigar a ativação destas vias na esquIsitossomose humana e murina experimental, no intuito de verificar o seu envolvimento no desenvolvimento da forma hepatoesplênica da esquistossomose mansonica (FHE). MATERIAL E MÉTODOS: 87 biópsias em cunha de fígados de pacientes com FHE submetidos a cirurgia e fragmentos de fígado de camundongos suiços infectados com Schistosoma mansoni foram submetidos a métodos imunohistoquímicos e de biologia molecular para avaliar a expressão de ligantes hedgehog (Ihh, Shh), receptor Patched, fatores de transcrição Gli 1 e 2 e osteopontina. Osteopontina sérica e ligante Shh do hedgehog foram avaliados em camundongos suíços infectados e os de osteopontina em camundongos CBA/J infectados e em pacientes com FHE e forma hepatointestinal da esquistossomose. In vitro foi avaliado o efeito de antígeno solúvel do ovo (SEA) em células de Kuppfer, células estreladas, macrófagos, colangiócitos e células endoteliais sinusoidais hepáticas. A relação com a via da IL-13 foi avaliada em camundongos geneticamente deficientes ou hiperexpressando a citocina. Foi avaliado in vitro se a IL-13 induz ligantes hedghog ou ativação da via em células de Kuppfer. RESULTADOS: Os resultados mostraram: (a) aumento expressão de ligantes Ihh, de fatores de transcrição Gli2 e de osteopontina no fígado de camundongos suíços infectados com Schistosoma mansoni, aumento de shh e osteopontina no plasma de camundongos suíços e de osteopontina no plasma de camundongos CBA/J infectados com S. mansoni; (b) aumento na expressão de Ihh, Shh, Gli1 e 2, receptor Patched e de osteopontina no fígado de pacientes com esquistossomose e aumento da osteopontina sérica em pacientes com a FHE; (c) A expressão de ligantes hedgehog e de Gli2 foi observada em macrófagos, células estreladas, ductos biliares e células endoteliais, e a de osteoponina em ductos biliares,macrófagos e células estreladas/miofibroblastos; (d) correlação positiva entre ativação do hedgehog (Gli2 e osteopontina) e fibrose, no modelo murino experimental e nos pacientes; nestes a correlação também foi observada com o grau de fibrose classificada pelo ultrassom e com a hipertensão porta; (e) Inibição in vitro do hedgehog com ciclopamina e vismodegib ou por nocauteamento condicional de receptor Smoothened bloqueou a ativação alternativa de macrófagos e inibiu a angiogênese a partir de células endoteliais sinusoidais hepáticas; (f) que o bloqueio da via da IL-13 reduziu e a hiperexpressão aumentou a ativação da via do hedgehog e IL-13 diretamente induziu, in vitro,produção de ihh em células de Kupffer de camundongos e de humanos, demonstrando a inter-relação das duas vias...

BACKGROUND AND AIMS: Schistosomiasis is a major cause of liver fibrosis and portal hypertension in tropical regions, and the pathogenesis of fibrosis is not well established. As hedgehog pathway and one of its target genes, osteopontin, are involved in liver fibrosis of other etiologies our aims were to investigate the activation of these pathways in human and experimental murine schistosomiasis, in an attempt to verify their involvement in the development of hepatosplenic schistosomiasis mansoni (HS). METHODS: 87 wedge liver biopsies of patients with HS submitted to surgery and liver fragments Swiss mice infected with Schistosoma mansoni were submitted to immunohistochemistry and molecular biology methods to evaluate the expression of hedgehog ligands (Ihh, Shh), patched receptor , Gli transcription factors and osteopontin. Serum osteopontin and Shh were evaluated in infected Swiss mice and osteopontin was evaluated in serum of infected CBA/J mice and plasma from patients with hepatointestinal and HS forms of schistosomiasis. The effect of soluble egg antigen (SEA) on Kuppfer cells, stellate cells, macrophages, cholangiocytes and liver sinusoidal endothelial cells was evaluated in vitro. Relationship with IL-13 pathway was evaluated in mice genetically deficient or with hyperexpression of this cytokine. Whether IL-13 induces production of ligands and/or activation of the hedgehog pathway in Kuppfer cells was evaluated in vitro. RESULTS: Results demonstrated: (a) increased expression of Ihh, transcription factor Gli2 and osteopontin in the livers of Swiss mice infected with S. mansoni, increased plasma levels of shh and osteopontin in infected Swiss mice and increased osteopontin in plasma of S. mansoni infected CBA/J mice; (b) increased expression of ihh, shh, Gli1 and 2, patched and osteopontin receptor in the liver of patients with schistosomiasis and increased serum osteopontin in patients with HS; (c) expression of hedgehog ligands and Gli2 was observed in macrophages, stellate cells, endothelial cells and bile duct and expression of osteopontin was detected in macrophages and stellate/myofibroblast cells; (d) positive correlation between activation of the hedgehog (Gli2 and osteopontin) and fibrosis in experimental murine model and in patients; these correlation was also observed with the degree of fibrosis classified by ultrasound and with portal hypertension; (e) in vitro inhibition of hedgehog pathway with cyclopamine or vismogedib or by conditional knockout of Smoothened co-receptor blocked the alternative activation of macrophage and inhibited angiogenesis in liver sinusoidal endothelial cells; (f) reduction of IL-13 pathway or IL-13 over-expression respectively reduced or increased the activation of the hedgehog pathway and IL-13 directly induced in vitro ihh production in Kupffer cells from mice and human, demonstrating a cross-talk between the two pathways...

Coffee has hepatoprotective benefits in Brazilian patients with chronic hepatitis C even in lower daily consumption than in American and European populations

The potential role of coffee as a hepatoprotective substance for chronic liver diseases has been widely discussed. Our main aim was to evaluate the effect of coffee intake regarding clinical, biochemical tests and liver biopsy data in treatment naïve patients with chronic hepatitis C. One hundred and thirty-six patients with chronic hepatitis C, diagnosed through liver biopsy, or by means of clinical, ultrasound or endoscopic signs of cirrhosis, were assessed by determination of biochemical tests, metabolic and morphological alterations. Food frequency was scrutinized by using a structured questionnaire. Coffee intake represented more than 90% of the total daily caffeine, and the 75th percentile was 4-Brazilian coffee-cup/day (>255mL/day or >123mg caffeine/day). According to caffeine intake, patients were divided into two groups (< or >123mg caffeine/day). Patients with higher ingestion of caffeine had lower serum levels of aspartate aminotransferase (× upper limit of normal) (1.8±1.5 vs 2.3±1.5, p=0.04), lower frequencies of advanced (F3, F4) fibrosis (23.5% vs 54.5%, p<0.001) and of histological activity grade (A3, A4) observed in liver biopsies (13.8% vs 36.9%, p<0.001). By multivariate logistic regression, fibrosis was independently associated with caffeine intake (OR- 0.16; 95%CI - 0.03-0.80; p=0.026), γ-glutamil transferase serum levels and morphological activity. But only fibrosis was associated with histological activity. In conclusion caffeine consumption greater than 123mg/day was associated with reduced hepatic fibrosis. In addition, this study supports the assumption that coffee intake has hepatoprotective benefits for Brazilian patients with chronic hepatitis C, even in lower doses than that of American and European population intake.

¿Pensar en hepatitis autoinmune precozmente evita la cirrosis? / Does early autoimmune hepatitis diagnose prevent from cirrhosis?

La hepatitis autoinmune (HAI) es una hepatopatía inflamatoria crónica y progresiva, que afecta predominantemente al sexo femenino y se caracteriza por la presencia de autoanticuerpos, elevación de aminotransferasas e hipergammaglobulinemia. Evoluciona rápidamente a cirrosis en pacientes no tratados, por lo que su diagnóstico precoz es indispensable. El propósito de este estudio es evaluar el tiempo promedio entre el inicio de los síntomas y el diagnóstico, así como su correlación con la presencia de cirrosis. Se realizó un estudio analítico, retrospectivo, no experimental. Se revisaron las historias clínicas de 51 pacientes que acudieron a la consulta de gastroenterología del hospital de niños J.M. de los Ríos desde abril de 1996 hasta septiembre de 2010 diagnosticados de HAI según criterios clínicos, serológicos e histológicos. Se excluyeron 3 pacientes por presentar patologías asociadas o estar recibiendo tratamiento inmunosupresor previo. La edad varió entre 2 y 15 años (media 8,3±3,2 DE); prevaleciendo el sexo femenino (72,9%). La clínica predominante fue ictericia (81,3%), coluria (47,9%) y dolor abdominal (39,5%). El diagnóstico se realizó en promedio 8,4 ± 7,3 meses luego del inicio de los síntomas. 50% se diagnosticó en los primeros 6 meses, de éstos 54,2% presentó cirrosis y 33,3% fibrosis. La HAI debe considerarse en pacientes pediátricos con clínica de hepatopatía inflamatoria a fin de realizar un diagnóstico oportuno y precoz debido a su rápida evolución a cirrosis

Autoimmune hepatitis (HAI) is a progressive chronic inflammatory hepatopathy with higher prevalence in females characterized by autoantibodies presence, elevation of aminotransferases and hipergammaglobulinemia. Another important characteristic is that it can develop into a rapid cirrhosis, so early diagnosis is vital. The purpose of our study is to evaluate the time spent between initial symptoms and final diagnosis, and it relation with the presence of cirrhosis. An analytic, retrospective non experimental study was performed. We reviewed the clinical records of 51 patients from April 1996 to September 2010 who attended the consultation of gastroenterology in the J. M. de los Ríos Children's Hospital with the diagnose of HAI according to clinical criteria, serological and histological. We excluded 3 patients for two reasons. 1. They were presenting associated pathologies 2. They were receiving immunosuppressive treatment. The ages vary from 2 to 15 years old (mean 8.3±3.2 ED); female prevail with (72.9%). The predominant symptoms were jaundice (81.3%), coluria (47.9%) and abdominal pain (39.5%). The diagnosis was made on average 8.4 ± 7.3 months after the beginning of the symptoms. 50% were diagnosed in the first 6 months, from these 54.2% presented with cirrhosis and 33,3% with fibrosis. HAI must be considered in pediatric patients with inflammatory hepatopathy clinical history in order to make an early and opportune diagnosis due to its rapid evolution to cirrhosis

Trasplante hepático en cirrosis por virus B: profilaxis con gammaglobulina antiHBs en dosis a "demanda" / Hepatitis B virus immunoglobulin on demand to prevent infection recurrence among liver allograft recipients: Report of three cases

Infection recurrence rates among hepatitis B virus infected liver allograft recipients, may be as high as 80%. Immunoprophylaxis with anti HBVgammaglobulin may reduce these rates and improve survival. The dose of anti HBV gammaglobulin that must be used is not clearly defined. The most commonly accepted protocol uses 10,000 units during the anhepatic phase and 10,000 units daily during one week, followed by weekly doses of 10,000 units during one month and maintenance with 10,000 units monthly, without measuring anti hepatitis B surface antigen antibodies (antiHBs). Some reports recommend the use of immunoglobulin on demand, to maintain antiHBs titers between 100 and 250 U/l. The infection recurrence rates among patients treated with immunoglobulin and Lamivudine fluctuates between 0 and 10%, during follow up periods of 13 to 30 months. We report three liver allograft recipients that received immunoglobulin on demand, using a mean of41,000 units, maintaining adequate antiHBs titers.

Contagem de plaquetas na avaliação de fibrose hepática / Platelet count in assessment of liver fibrous

Verificar a contagem de plaquetas como teste não invasivo indireto de fibrosehepática, em pacientes com hepatite C crônica. Método: estudo analítico, descritivo,desenvolvido no Ambulatório do Fígado da Fundação Santa Casa de Misericórdia do Pará, noqual foram incluídos 98 pacientes com diagnóstico de hepatite C crônica, todos com avaliaçãohistológica usando a classificação METAVIR e contagem de plaquetas no período em que foirealizada a biopsia hepática. Resultados: a curva ROC para contagem de plaquetas na prediçãode fibrose, encontrou AUROC (área abaixo da curva) de 0,70, com acurácia de 71,4% ecoeficiente de correlação de Spearman -0,45. Considerações finais: o valor absoluto dasplaquetas em sangue periférico pode ser útil como índice preditor do estágio de fibrosehepática, sendo bom parâmetro de acompanhamento ambulatorial

To evaluate the platelet count as indirect non-invasive test of liver fibrosis in patientswith hepatitis C. Methods: this is a retrospective, descriptive of the liver developed in the clinicof Santa Casa de Misericordia do Para, which included 98 patients with chronic hepatitis C, allwith histological grading using the METAVIR score and score platelets in the period in whichliver biopsy was performed. Results: ROC curve for platelet count in the prediction of fibrosisfound AUROC (area under the curve) of 0.70 with an accuracy of 71.4% and the Spearmancorrelation coefficient -0.45. Conclusion: absolute value of platelets in peripheral blood may beuseful as a predictive index of liver fibrosis stage

Cirrhosis; frequency of HCV and mean age

To know the frequency of HCV in patients with cirrhosis and to know the mean age of patients with cirrhosis A descriptive study. Medical Unit Khyber Teaching Hospital Peshawar. From Jan 2007 to Jan 2008. 100 consecutive cirrhotic patients or those with signs and symptoms of cirrhosis, admitted to the medical units. They were either known cirrhotic or having signs and symptoms of chronic liver disease and diagnosed as cirrhotic during their stay in the hospital on the basis of ultrasound findings. The routine investigations including liver function test [LFTs], prothrombin time [PT], activated partial thromboplastin time [APTT], serum albumin were carried out in all patients. Ultrasound was the main tool for the diagnosis of cirrhosis liver. The hepatitis C virus [HCV] status was diagnosed by detecting Anti HCV antibodies by enzyme linked immunosorbent assay [ELISA]. Polymerase chain reaction [PCR] for HCV RNA was done only in affording patients. The overall frequency of HCV was 52 in 100 patients. Out of these 52 HCV positive patients, PCR for HCV RNA was positive in 20 patients [38.15%] and the rest of the patients were not able to afford the test. Out of 52 HCV positive patients the number of male were more [1.8:1] as compared to female. The age of the patients ranged from 45-65 years, the majority being from 45 to 65 years with the mean age of 52 years. The stratification of risk factors was not the objective of this study. However, a note was made of exposure to various risk factors. Most of the patients had the history of receiving injections in the past from quacks. It is concluded that chronic HCV infection is the commonest cause of cirrhosis leading to chronic ill health, great economic burden on family and health care system and mortality. As there is no treatment for cirrhosis so prevention, early detection of HCV infection and prompt treatment of HCV infected patients will undoubtedly lead to a decrease in morbidity and mortality from this silent epidemic

Changes in adrenal steroidogenesis in spontaneous bacterial peritonitis and sterile ascites

Adrenal androgens, particularly dehydroepiandrosterone [DHEA], may have important regulatory effects on the immune system in humans. This study measured the changes in adrenal steroidogenesis in 13 non-infected cirrhosis patients with sterile ascites and 13 patients with spontaneous bacterial peritonitis and the relation with circulating interleukin-6 [IL-6] levels. Comparisons were made with 10 healthy age-matched control subjects. The severity of bacterial peritonitis in liver cirrhosis was significantly associated with enhanced serum IL-6 and cortisol levels, and a decrease in serum DHEA sulfate in relation to serum IL-6 concentrations. Careful, long-term studies on DHEA administered to cirrhosis patients are needed to assess its safety in improving a number of pathological conditions that complicate liver cirrhosis

Thalidomide failed to inhibit angiogenesis and fibrosis in hepatic schistosomiasis of the mouse

The relationship between angiogenesis and fibrosis has been demonstrated in several pathological conditions, one of them being schistosomiasis. To observe whether suppression of angiogenesis would interfere with fibrosis, Thalidomide, an anti-angiogenesis drug, was administered during 30 consecutive days to mice with experimental schistosomiasis. Computerized morphometric measurements of fibrosis, and the counting of blood vessels from hepatic schistosomal lesions did not significantly differ when treated animals and their controls were compared at the end of the experiments. These rather unexpected results are presented under the understanding that they may be of interest during further studies on the anti-angiogenesis properties of thalidomide, and the relationship between angiogenesis and fibrosis.

Chronic liver disease prevention strategies and liver transplantation / Estratégias de prevenção da doença hepática crônica e transplante de fígado

Chronic liver disease is a considerable burden on society, being one of the three main causes of death in certain regions of Africa and Asia. Liver transplant is the only treatment option for cirrhosis, which is the end stage of many chronic liver diseases. This article reviews the preventable causes of cirrhosis and the preventive strategies which could be implemented in order to avoid the catastrophic consequences of cirrhosis. With small variations around the world, 70 to 80 percent of the end stage liver diseases are caused by excessive alcohol consumption and by viral hepatitis, both of which are potentially preventable. Excessive alcohol consumption has important public health consequences because of its involvement not only with cirrhosis, but also with motor vehicle accidents, unemployment, domestic violence etc. Among the viral causes, Hepatitis Virus B and C have the greatest impact on public health. Effective vaccine is available for Hepatitis Virus B and must be put in use. While a vaccine for Hepatitis Virus C is awaited, effective preventive strategies should be undertaken to avoid the preventable cases of end stage liver disease.

As doenças hepáticas crônicas estão entre as três principais causas de morte na Africa e Asia.O transplante de fígado é o único tratamento curativo para esta doença hepática de caráter terminal.O presente artigo tem como objetivo apresentar as causas passíveis de prevenção de cirrose e as estratégias que podem ser utilizadas no sentido de preveni-las. Com pequenas variações ao redor do mundo, 70 a 80 por cento das doenças hepáticas terminais são causadas por consumo excessivo de álcool e por hepatites virais que são doenças passíveis de prevenção.O consumo excessivo de álcool é importante problema de saúde pública, pois envolve violência doméstica, acidentes de trânsito, além da possível evolução para cirrose e suas conseqüências. Entre as causas virais as hepatites pelo vírus B e C têm o maior impacto na saúde pública. Para a hepatite B já há vacinas disponíveis. Enquanto a vacina para a hepatite C é ainda aguardada, estratégias efetivas de prevenção devem ser efetuadas com o objetivo precípuo de se evitar, por conseqüência, casos de hepatopatias crônicas desta natureza.

Biopsy or biochemistry? the monitoring of hepatic fibrosis from methotrexate

Hepatic fibrosis is an important consequence of inflammatory disorders affecting the liver, and ultimately progresses to cirrhosis. Here we explore methods for the detection and monitoring of hepatic fibrosis, particularly during methotrexate therapy, in which progressive fibrosis can develop over a number of years in a minority of patients. Liver biopsy remains currently the gold standard to assess fibrosis. However, it has several limitations, including manpower issues, cost, risk of patient injury, including mortality and morbidity, observer variability and sampling variation. Several non-invasive diagnostic tests for fibrosis and cirrhosis have therefore been evaluated. The usefulness of a laboratory test for screening for a pathological abnormality such as fibrosis is critically dependent on the prevalence of the pathology in the population under investigation. When the prevalence is expected to be low, screening tests should have a high negative predictive value, so that large numbers of patients can be spared the next diagnostic step, namely liver biopsy. For the moment, clinicians should use the aspartate aminotransferase [AST] / alanine aminotransferase [ALT] ratio and the AST/platelet [APRI] ratio for monitoring the development of hepatic fibrosis

efficancy of herbal medicine khar maryam [silybum marianum[L.] Gaertn] on liver cirrhosis in chronic hepatitis B patients

Cirrhosis is the irreversible sequel of various disorders that damage liver cells permanently over time. Presently, the use of herbal medicines for prevention and control of chronic liver diseases is in the focus of attention for both the physicians and the patients; the reasons for such shift toward the use of herbals include the expensive cost of conventional drugs adverse drug reactions, and their inefficacy The present study was undertaken to evaluate the efficacy of herbal medicine Khar maryam or silymarin on liver cirrhosis in chronic hepatitis patients compare to placebo therapy 60 chronic hepatitis B cirrhotic patients were selected out of 500 patients to Tehran Hepatic center The patients were randomly divided in two groups of 30 patients One group received silymarin l50mg/kg three times a day and the other group placebo received for twelve months. The outcome measures included child-pugh score,ascitis, serum aspartate aminotransferase [AST], alanine aminotransferase [ALT] total billirubin, albumin, prothrombin time, platelet and white blood cells counts. The indices were recorded in all patients before and after 12 months of drug or placebo treatment The results demonstrated that the patients treatment with silymarin for 12 months had significantly better child-pugh score, decreased ascitis, decreased serum AST and ALT. In placebo administered patients all the clinical parameters recorded before and after 12 months were not significantly different. We conclude that silymarin treatment for 12 months in cirrhotic patients has hepatoprotective effect. To investigate the effects of this herbal remedy on the mortality rate of cirrhotic ratients, asimilar study, over an extended period has to be carried out

[Passive and active immunization in prevention of vertical transmission of HBV infection in infants of HBsAg positive mothers]

In order to prevent liver cirrhosis and hepatocellular carcinoma in later life, it is essential to prevent Hepatitis B virus [HBV] infection in infants. Despite the availability of an effective vaccine, hepatitis B still continues to be a significant health problem. The aim of this study is to reveal the efficacy of passive and active immunoprophylaxis for preventing perinatal transmission of the hepatitis B virus in Iran. In this cohort study with historical controls, 823 children of the HBsAg positive mothers were evaluated. There were 637 cases who had received neither Hepatitis B [HB] vaccine nor hepatitis B immunoglobulin [HBIG], 125 persons received only HB vaccine and 60 neonates that we administered them HB vaccine and HBIG together. The prevalence of HBsAg in cases who have received neither vaccine nor HBIG and aged > 16 years [group1] or <= 16 years [group 2], cases who have received vaccine alone [group 3], and in cases who have received both vaccine and HBIG [group 4] was 56.1%, 40.3%, 12.6%, and 3.6%, respectively. The prevalence of HBsAb had a significant descending rate in groups 4 [85.7%], 3 [68.8%], 2 [33.3%], and 1 [21.8%] respectively. The addition of HBIG to recombinant vaccine will significantly increase the protection against HBV infection in comparison with HB vaccine without HBIG. After focusing on the vertical route for many years, and implementing strategies such as vaccination and HBIG injection to neonates of HBsAg positive mothers, nowadays it seems that we should pay more attention to horizontal way of HBV transmission in Iran

[Impact of immunosuppressive treatment on liver fibrosis in autoimmune hepatitis]

Impact of treatment on progression of fibrosis in autoimmune hepatitis [AIH] is unknown. We assessed the changes in liver fibrosis before and after treatment among these patients. Nineteen AIH patients who had paired liver biopsies were studied. Of these, seven had been treated with 6 months of Cyclosporine-A and the rest with 6 months of prednisolone for induction of remission. Thereafter all had been maintained on azathioprine. Biopsy specimens before and after treatment, were reviewed by one pathologist and scored by the Ishak method. Mean fibrosis stage before and after treatment were compared. Also, factors predicting significant fibrosis [stage >/= 3] and cirrhosis [stage >/= 5] at presentation were assessed. Mean interval between biopsies was 3.38 years. Mean fibrosis stage decreased from 4.53 to 2.16 following treatment [p< 0.001]. Mean decrement in inflammatory grade was 8 scores [range: 4-10] in patients in whom fibrosis improved, and 2 scores [range: 0-4] in patients in whom fibrosis did not decrease after treatment [p< 0.001]. ALT to platelet ratio was the best predictor of significant fibrosis and also cirrhosis. Fibrosis commonly improves after immunosuppressive treatment in AIH. ALT to Platelet ratio can predict accurately the presence of significant fibrosis and cirrhosis in AIH

Role of pentoxifylline and anti-transforming growth factor-B in controlling hepatic fibrosis in murine Schistosomiasis

On the basis of fibroblast and myofibroblast-like cells, the inhibitory effect of pentoxifylline [PTX] and anti-transforming growth factor-beta [anti-TGF-beta] and their role in controlling hepatic fibrosis were investigated. Sixty albino mice were infected with schistosomiasis by subcutaneous [s.c.] injection of 60 cercariae/mouse. They were divided into two groups: The first group [30 mice] was sacrificed at seventh week and the other [30 mice] at fifteenth week after infection. Groups of infected mice were treated with PTX or anti-TGF-beta for three weeks before sacrifice at the acute [7 weeks] and chronic [15 weeks] phases of infection. Three weeks before sacrifice, ten mice from each group were treated by PTX. In parallel, another ten mice from each group received s.c. Injection with anti-TGF-beta three weeks before sacrifice. The remaining ten mice of each group served as controls. Human fibroblasts were incubated with supernatants derived from splenic or hepatic cell cultures and the cell proliferation was measured by the XTT assay