Shunt portosistémico, una causa poco frecuente de hepatitis colestásica en neonatología. A propósito de un caso / Portosystemic shunt, a rare cause of neonatal cholestatic hepatitis. A case report

El shunt portosistémico congénito es una anomalía vascular venosa que comunica circulación portal y sistémica, por la que se deriva el flujo sanguíneo, salteando el paso hepático. Es una entidad poco frecuente, cuya incidencia varía entre 1/30 000 y 1/50 000 recién nacidos. Puede cursar de forma asintomática o presentarse con complicaciones en la edad pediátrica o, menos frecuente, en la edad neonatal. Ante el diagnóstico, se deberá definir la necesidad de intervención quirúrgica o intravascular para el cierre. Esta decisión depende de las características anatómicas de la malformación, de las manifestaciones clínicas y complicaciones presentes. Se presenta el caso de un paciente de un mes de vida derivado a nuestro centro para estudio de hepatitis colestásica neonatal, con diagnóstico de shunt portosistémico extrahepático. Se realizó cierre intravascular de la lesión con mejoría significativa posterior.

Congenital portosystemic shunt is a venous vascular abnormality that connects portal and systemic circulation, resulting in diversion of the blood flow, bypassing the hepatic passage. It is a rare malformation; its incidence varies from 1:30 000 to 1:50 000 newborns. It may be asymptomatic or present with complications in the pediatric age or, less frequently, in the neonatal age. Upon diagnosis, the need for a surgical or an intravascular intervention for closure should be defined. This decision depends on the malformation anatomical characteristics, clinical manifestations, and complications. We present the case of a 1-month-old patient referred to our center for the study of neonatal cholestatic hepatitis, with a diagnosis of extrahepatic portosystemic shunt. Intravascular closure of the defect was performed with significant subsequent improvement.

Hypoxic hepatitis in an extensive aortic disecction: case report / Hepatitis hipóxica en una disección aórtica extensa: reporte de caso

Hypoxic hepatitis is an uncommon cause of hepatic damage characterized by a centrolobular necrosis. Its pathophysiology remains unclear. Aortic dissection is a rare but frequently catastrophic event. It is caused by an aortic intimal tear with propagation of a false channel in the media. Depending on the site and extension, it can cause hypoperfusion of any organ leading to cellular ischemia and necrosis. We are presenting a case of hypoxic hepatitis in a patient with an extensive aortic dissection who present to the emergency department.

La hepatitis hipóxica es una causa poco frecuente de daño hepático caracterizada por una necrosis centrolobular. Su fisiopatología sigue siendo poco clara. La disección aórtica es un evento raro pero con frecuencia catastrófico. Dependiendo del sitio y la extensión, puede causar hipoperfusión de cualquier órgano lo que conduce a una isquemia celular y necrosis. Nosotros presentamos un caso de hepatitis hipóxica en un paciente con disección aórtica extensa que se presenta al servicio de emergencia.

Hepatitis isquémica fulminante inducida por disfunción cardiaca severa: reporte de caso / Fulminating ischemic hepatitis induced by severe cardiac dysfunction: case report

La hepatitis isquémica es una entidad infrecuente en la práctica clínica diaria con una prevalencia de 0,16 a 0,5% entre los pacientes admitidos en unidad de cuidados críticos, asociado a una mortalidad aproximada en el 60% de los casos. Esta hepatopatía se caracteriza por un incremento rápido y marcado (más de 20 veces el valor normal) del nivel de transaminasas secundario a una hipoperfusión hepática severa y persistente ocasionada por múltiples etiologías, que puede ser transitoria de identificarse y tratar la causa desencadenante oportunamente. A continuación presentamos el caso de un paciente adulto mayor con un cuadro clínico, epidemiológico y bioquímico compatible con hepatitis isquémica secundario a disfunción cardiaca severa.

Ischemic Hepatitis is an uncommon entity in daily clinical practice with a prevalence of 0.16 to 0.5% among patients admitted to a critical care unit, associated with an approximate 60% mortality rate. This liver disease is characterized by a rapid and marked increase (more than 20 times the normal value) of the level of transaminases secondary to a severe and persistent hepatic hypoperfusion caused by multiple etiologies, which may be transient when the triggering cause is timely identified and appropiately treated. The case of an elderly adult patient with a clinical, epidemiological and biochemical profile compatible with ischemic hepatitis secondary to severe cardiac dysfunction is presented below.

Low Hepatic Toxicity in Primary and Metastatic Liver Cancers after Stereotactic Ablative Radiotherapy Using 3 Fractions

This study evaluated the incidence of hepatic toxicity after stereotactic ablative radiotherapy (SABR) using 3 fractions to the liver, and identified the predictors for hepatic toxicity. We retrospectively reviewed 78 patients with primary and metastatic liver cancers, who underwent SABR using 3 fractions between 2003 and 2011. To examine the incidence of hepatic toxicity, we defined newly developed hepatic toxicity> or =grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 within 3 months after the end of SABR as a significant adverse event. To identify the predictors for hepatic toxicity, we analyzed several clinical and dosimetric parameters (rV(5Gy)-rV(35Gy): normal liver volume receiving or =grade 2 occurred in 10 patients (13%): grade 2 in 9 patients and grade 3 in 1 patient. On univariate analysis, baseline Child-Pugh (CP) score (5 vs. 6-8), normal liver volume, and planning target volume were the significant clinical predictors. All dosimetric parameters were significant: rV(20Gy) was the most significant predictor. On multivariate analysis, baseline CP score (hazard ratio, 0.026; P=0.001) was the only significant predictor. In conclusion, SABR using 3 fractions in primary and metastatic liver cancers produces low hepatic toxicity, especially in patients with a baseline CP score of 5. However, further studies are needed to minimize hepatic toxicity in patients with baseline CP scores> or =6.

Manifestaciones sistémicas del dengue / Systemic manifestations of dengue

Introducción: el dengue es una infección que puede afectar múltiples órganos.Objetivo: determinar la afectación multisistémica por dengue. Metodología: estudio observacional, descriptivo, prospectivo realizado en sujetos adultos con dengue grave con signos de alarma internados en el Hospital Nacional entre diciembre 2012 y mayo 2013. La infección debía estar confirmada con antígeno NS1 y/o serología IgM (+). Resultados: se encontró 10,1% de hepatitis, 85,6% de transaminitis, 48% con relación CPKmb/CPK total >5%, 22,5% de alteraciones electrocardiográficas, 70,4% con proteinuria de 24 hs elevada y 9,3% con proteinuria en rango nefrótico. Conclusiones: la afectación multisistémica es frecuente, generalmente pasa desapercibida y en general es autolimitada aunque se requieren más estudios para evaluar la evolución a largo plazo en estos casos.

Introduction: dengue is an infection that could affect multiple organs. Objective: to determine the multisystem involvement of dengue. Methodology: observational, descriptive, prospective study conducted in adult subjects with severe and warning signs of dengue admitted to the National Hospital between December 2012 and May 2013. Infection should be confirmed with NS1 antigen and / or IgM serology (+). Results: we found 10.1% of hepatitis, 85.6% of transaminitis the relation CPKmb / total CPK > 5% in 48%, electrocardiographic alterations in 22.5%, elevated proteinuria in 70.4% and nephrotic proteinuria in 9.3%. Conclusions: multisystemic involvement is frecuent, usually asymptomatic and generally self-limited although more studies are needed to evaluate the long-term outcome in these cases.

Acute Hepatitis Like Presentation of Budd Chiari Syndrome in a Child.

The patient presented with progressively increasing ascites and pain abdomen but without any bleeding tendency, or encephalopathy. The initial diagnosis of acute hepatitis was proved wrong by contrast enhanced CT scan of abdomen which showed atretic hepatic veins. Atretic hepatic veins causing Budd Chiari Syndroem (BCS) is a rarity in literature.

Prevalência das infecções pelos vírus das hepatites em localidade rural sob influência de um projeto de mineração / Prevalence of infections by the hepatitis virus in a rural locality under influence of a mining project

Definir a frequência de marcadores das infecções pelos vírus das hepatites A-D na Comunidade Café Torrado, Juruti, Oeste do estado do Pará, Brasil, atualmente sob a influência de um projeto de mineração. Método: estudo de campo, transversal de prevalência, onde amostras de soro coletadas em novembro de 2009, na Comunidade Café Torrado, foram examinadas por técnica imunoenzimática para as hepatites A, B e C. Resultados: incluídos no estudo 232 indivíduos, sendo 53% do sexo feminino. A análise mostrou prevalência global de 78% para o anti-VHA total, com 75% de suscetíveis na faixa etária de 1 a 4 anos. Com relação à hepatite B, o estudo mostrou prevalência total de 2,2% para algum marcador do VHB; não foram detectados portadores do vírus da hepatite B; 1,3% apresentaram indicadores de infecção pregressa; 0,9% anti-HBc+ isolado; 37,1% com perfil compatível de proteção vacinal; 60,8% eram susceptíveis ao VHB e o perfil sorológico vacinal até os 19 anos se mostrou em 44,4%. Não foram detectadas pessoas infectadas pelo VHC. A ausência de portadores do VHB tornou desnecessária a realização dos testes HBeAg, anti-HBe e anti-HD total. Conclusões: a comunidade Café Torrado apresentou alta endemicidade para o VHA; moderada endemicidade para o VHB, onde a detecção de susceptíveis reitera a importância da vacinação e a necessidade em ampliá-la no município. Para o VHC e VHD foi demonstrada baixa endemicidade.

To define the frequency of markers of infections by the Hepatitis A-D viruses in the Café Torrado Community, Juruti, West of Pará, Brazil, currently under influence of a mining project. Methods: study, transversal; serum samples were collected in November 2009 in Café Torrado Community. These samples were analyzed by immunoenzymatic technique for Hepatitis A, B and C. Results: 232 individuals were included in this study; 53% were female. The analysis showed a global prevalence of 78% for anti- HAV, with 75% of susceptible in the age group of 1-4 years old. This study showed total prevalence of 2.2% for any marker of HBV; virus carriers were not detected; 1,3% had markers of previous infection; 0.9% had isolated anti-HBc+.37.1% had a compatible profile with vaccine protection; 60.8% were susceptible to HBV and the vaccine serum profile up to 19 years of age was 44.4%. HCV-infected people were not detected. The absence of HBV carriers made the HBeAg, anti-HBe and anti-HD tests unnecessary. Conclusions: the Café Torrado Community showed high endemicity for HAV; mild endemicity for HBV, but the detection of susceptible strengths the importance of the vaccine and the need of amplifying it in the city. HCV and HDV had low endemicity.

Doença de Wilson: apresentação clínica, diagnóstico e tratamento / Wilson's disease: clinical presentation, diagnosis and treatment

A doença de Wilson é um erro inato do metabolismo do cobre causado por uma mutação no gene ATP7B, responsável por seu transporte. É uma doença de herança autossômica recessiva, caracterizada pela deposição excessiva de cobre principalmente no fígado e no cérebro. Clinicamente, os pacientes apresentam manifestações hepáticas, neurológicas e psiquiátricas. O diagnóstico pode ser feito quando as seguintes características estiverem presentes: anéis de Kayser-Fleischer na córnea, diminuição dos níveis plasmáticos de ceruloplasmina e sintomas neurológicos típicos. A prevenção de danos permanentemente severos depende do reconhecimento e diagnóstico precoces pelo médico, seguidos de tratamento apropriado. A doença de Wilson pode ter prognóstico excelente, desqe que o tratamento seja feito durante toda a vida.

Wilson's disease is an inborn error of copper metabolismo caused by a mutation to the cooper-transporting gene ATP7B. This disease has an autosomal recessive mode of inheritance, and is characterized by excessive cooper deposition, predominantly in the liver and brain. Clinically, patients usually present hepatic, neurologic or psychiatric manifestations. The diagnosis can be done when these symptoms are present: Kayser-Fleischer rings, low serum ceruloplasmin levels and typical neurological symptoms. The prevention of severe permanente damage depends upon early recognition and diagnosis by the physician, followed by appropriate anticopper treatment. Wilson's disease it can have an excellent prognosis since that treatment either for all the life.

Infectious Mononucleosis Hepatitis in Young Adults: Two Case Reports

Infectious mononucleosis due to Epstein-Barr virus (EBV) infection sometimes causes acute hepatitis, which is usually self-limiting with mildly elevated transaminases, but rarely with jaundice. Primary EBV infection in children is usually asymptomatic, but in a small number of healthy individuals, typically young adults, EBV infection results in a clinical syndrome of infectious mononucleosis with hepatitis, with typical symptoms of fever, pharyngitis, lymphadenopathy, and hepatosplenomegaly. EBV is rather uncommonly confirmed as an etiologic agent of acute hepatitis in adults. Here, we report two cases: the first case with acute hepatitis secondary to infectious mononucleosis and a second case, with acute hepatitis secondary to infectious mononucleosis concomitantly infected with hepatitis A. Both cases involved young adults presenting with fever, pharyngitis, lymphadenopathy, hepatosplenomegaly, and atypical lymphocytosis confirmed by serologic tests, liver biopsy and electron microscopic study.

Bone marrow transplantation in thalassemia [Part 1]

During the last two decades conventional therapy has improved the prognosis of thalassemia. However, despite such improvement it still remains a progressive disease with treatment-related complications such as hepatitis, liver fibrosis, and cardiac disease. Bone marrow transplantation [BMT] can prevent or delay progression of the aforementioned complications. The importance of clinical research in the field of BMT was recognized with the award of the 1990 Nobel Prize in Physiology and Medicine to E. Donnall Thomas, one of the pioneers of BMT in humans. George Mathe' was a pioneer in the early development of clinical BMT. Mathe' et al. were the first to describe graft-versus-host-disease [GVHD] and its treatment, and the graft-versus- leukemia [GVL] effect in human. The first BMT for beta-thalassemia major was performed successfully by Thomas et al. in Seattle, in 1981. In the same year another patient with beta-thalassemia major underwent BMT in Pesaro, Italy, by Lucarelli et al. Since then, several hundred transplantations have been performed worldwide, the majority of these in Italy. From 1991 through 2007 BMT have been performed on 497 [Tehran=342, Shiraz=155] blood transfusion dependent patients with thalassemia major in Iran, with disease-free survival of 71-77% respectively. Due to high graft failure and GVHD rates, BMT from alternative donors should be restricted to patients who have poor life expectancies because they cannot receive adequate conventional treatment or because of alloimmunization to minor blood antigens. Beginning in the early 1980s, it was shown that umbilical cord blood contained high levels of hematopoietic progenitor cells

Granulomatous hepatitis following open heart surgery with cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) initiates an inflammatory cascade, predisposing the patient to a number of infections. The stress of surgery and anaesthesia further expose the patient to a variety of non-infectious complications. We report a group of patients who developed granulomatous disease after open heart surgery. METHODS: We retrospectively analysed a subset of patients who developed a syndrome of fever, jaundice and hepatomegaly after open heart surgery. We recruited age- and sex-matched controls who underwent open heart surgery during the same period (July 2002-July 2004). Details of demographic profiles, diagnostic evaluation and drug treatment were noted and compared between the two groups using the SPSS software. RESULTS: Five patients were identified to have the specific syndrome of high grade intermittent fever with jaundice and hepatomegaly with investigations revealing an intrahepatic cholestasis. A detailed evaluation revealed granulomas in tissue specimens of the bone marrow and/or liver in these patients. An extensive evaluation for an alternative aetiological agent was non-contributory. CONCLUSION: We found granulomatous hepatitis in 5 patients following open heart surgery and they were given conventional antituberculous therapy to which they responded. It is possible that in these patients, tuberculosis was re-activated from a dormant focus due to a period of transient immunodeficiency caused by an extracorporeal circulation.

Incidence and risk factors of nevirapine-associated severe hepatitis among HIV-infected patients with CD4 cell counts less than 250 cells/microL.

OBJECTIVES: To determine incidence and risk factors of nevirapine (NVP)-associated severe hepatitis that led to NVP discontinuation among HIV-infected patients with CD4 < 250 cells/microL. MATERIAL AND METHOD: A retrospective cohort study was conducted among antiretroviral-naïve HIV-infected patients who had baseline CD4 < 250 cells/microL and were initiated NVP-based antiretroviral therapy (ART) between January 2003 and October 2005. All patients were categorized to group A: occurred clinical hepatitis and group B: did not occur clinical hepatitis. All were followed until 6 months after ART. RESULTS: There were 910 patients with a mean age of 35.4 years, 57% were males and median (IQR) CD4 cell count was 27 (9-80) cells/microL; contributing 5,006 person-months of observations. Ten (1.1%) patients were in group A and 900 (98.9%) patients were in group B. Incidence of clinical hepatitis was 2 per 1,000 person-months. Probabilities of clinical hepatitis at 0.5, 1, 2, 3 and 6 months after ART were 0.2%, 0.5%, 0.7%, 0.8% and 1.1%, respectively. By Cox regression analysis, baseline AST > or = 1.5 times of upper limit was associated with higher incidence of clinical hepatitis (p = 0.019, HR = 5.83, 95% CI = 1.33-25.51). CONCLUSION: Incidence of NVP-associated severe hepatitis that lead to NVP discontinuation among HIV-infected patients with baseline CD4 < 250 cells/microL is low. The higher baseline AST is also associated with a higher risk of severe hepatitis.

Nonalcoholic steatohepatitis: Pathogenesis and treatment / 대한간학회지

Nonalcoholic fatty liver disease (NAFLD) is characterized by a wide spectrum of liver damage spanning steatosis, nonalcoholic steatohepatitis (NASH), cryptogenic liver cirrhosis, and even to hepatocellular carcinoma. Investigations in the last few years have focused on NASH, a relatively aggressive form of liver disease, due largely to the explosion of information provided by clinical and basic science studies related to the widespread presence of risk factors, such as obesity, type II diabetes mellitus, and dyslipidemia. This is especially important given that obesity and type II diabetes mellitus have recently reached epidemic proportions in Korea. The pathogenesis of NASH is multifactorial, with insulin resistance and increased fatty acid possibly being important factors in the accumulation of hepatocellular fat, and oxidant stress, lipid peroxidation, mitochondrial dysfunction, and dysregulation of variable cytokines possibly being important causes of hepatocellular injury in steatotic liver. Because not all steatotic livers progress to NASH, some other environmental factors or a combination of genetic factors are thought to be required for progression to NASH and fibrosis. Lifestyle modifications continue to be the cornerstone therapy in NAFLD, but some insulin-sensitizing drugs might be more effective in treating NASH. Many pilot trials for antioxidants and lipid-lowering and hepatic protective agents have yielded promising initial results in improving liver enzymes or features of liver histology. However, the efficacy of these agents remains questionable. Despite recent gains in understanding NASH, several issues related to its natural history, pathogenesis, and treatment remain unresolved.

[ case report of acute hemolytic crisis as the initial manifestation of Wilson disease]

Wilson disease is a hereditary disorder of copper metabolism which can present with hepatic, neurologic or psychiatric symptoms and in rare cases as a hemolytic disturbance. Free copper can result in red blood cell damage and hemolysis which is a rare feature of the disease affecting less than 10% of patients. In this condition the liver is usually involved and liver transplantation can be life saving. This article is a case report of acute hemolytic crisis as the initial manifestation of Wilson disease. An 8 years old girl was admitted in pediatric ward of Golestan hospital because of abdominal pain, icterus, anemia and tea color urine. Hepatitis or Glucose 6 Phosphate Dehydrogenase deficiency was the first diagnosis. Because of unresponsiveness to transfusion, Wilson disease was considered and the diagnosis was established with the presence of Kayser Fleischer ring. Chronic or acute hemolytic anemia is a rare or unusually presentation of Wilson disease. In any child especially older than 5 years with liver disease or hemolytic anemia, Wilson disease should be considered and appropriate diagnostic tests performed

study on knowledge of diseases causation among adults of an urban slum of Multan

A cross-sectional study with descriptive and analytical components was carried out at Basti Oddan, an urban slum of Multan city. The concept of disease causation regarding tuberculosis, hepatitis B and malaria among 320 adults was assessed utilising a pre-tested questionnaire. Data was entered and analysed using SPSS software, 11[th] version. Running and tabulation of all the variable frequencies were done as part of data management. Tables were used to present the data. Chi -square test was used as the test of significance. Level of significance was set at 0.05. The overall knowledge of disease, causation was poor i.e. less than 50%. Respondents with better educational status had better concept of causation regarding three common communicable diseases. The association between economic status and concept of disease causation was variable i.e. no significant association between economic status and awareness of tuberculosis causation. However a positive association between economic status and awareness regarding hepatitis B and malaria was noted. It is concluded that there is great need to improve the educational status of the people otherwise any health improvement program is unlikely to succeed

Hepatitis isquemica / Ischemic hepatitis

La hepatitis isquémica es una complicación sumamente infrecuente de cirugía cardiovascular. Las biopsias muestran necrosis centrolobulillar. El término de “hepatitis” fue propuesto debido al aumento de transaminasas similar a aquellas de origen infeccioso, e “isquémica” por falla en la perfusión hepática. Posteriormente se definió el término de hepatitis isquémica como cuadro de elevación aguda y reversible(dentro de las 72 horas) de transaminasas de hasta 20 veces el valor normal, asociado a trastornos en la perfusión hepática, luego de haber excluido otras causas de hepatitis aguda o daño hepatocelular. Se describe elcaso de un paciente de 53 años que consulta por dolor epigástrico de 12 h de evolución sin fiebre, náuseas nivómitos, resistente a la medicación. Tenía antecedentes inmediatos de reemplazo de válvula aórtica, y estabaanticoagulado. Evolucionó con shock y fallo multiorgánico. El examen evidenció marcada ictericia y signos detaponamiento pericárdico, asociado a un aumento considerable de enzimas hepáticas. Un ecocardiograma informósignos de taponamiento cardíaco y ausencia de disección aórtica. Se decidió pericardiocentesis, extrayéndose 970 cc. de líquido sanguinolento, y hemodiálisis, con notable mejoría de su estado hemodinámico. Los valores enzimáticos disminuyeron. Los marcadores virales fueron negativos

Ischemic hepatitis is an uncommon cardiovascular surgery complication. Hepatic biopsies show centrolobulillar necrosis. The term “hepatitis” was proposed because of a raise in hepaticenzymes similar with infectious disease, and “ischemic” because of failure in hepatic perfusion. Ischemic hepatitis was then defined as an acute and reversible elevation of hepatic enzymes (within 72 h), associated with disturbance in hepatic perfusion after excluding other causes of acute hepatitis. A 53 year-old male presentedcomplaining of a 12 h epigastric pain, without nausea or vomiting, resistant to medication. He underwent an aortic valve replacement and was under anticoagulation. He suddenly developed shock and multiorgan failure. Jaundice and cardiac tamponade signs were present, associated with elevated hepatic enzymes. A transthoracicechocardiography accounted for cardiac tamponade signs. A pericardiocentesis was performed, removing 970 cc of hemorrhagic fluid, and hemodialysis, with improvement of his hemodynamic status. Hepatic enzymes improved. Viral markers were negative

Investigation of changes in levels of liver trans-aminases in measles affected patients hospitalized in Be'sat hospital in 1379

One of measles manifestations -especially in adolescents- is liver malfunction which can vary from just changes in liver enzymes to hepatitis with prominent jaundice. It is important to screen hepatitis patients in order to special medical treatment and avoidance of prescribing hapatotoxic drugs and some pain relief medications. In addition, patients of such complications are high risk for long duration of hospitalization and secondary complications and long duration of the disease. This was a cross-sectional study of 172 patients selected from 180 patients with clinical measles admitted in Be'sat hospital of NAHAJA. CBC and liver enzymes were checked. Patients aged between 18 to 24 years. Mean of hospitalization time was 6.48 +/- 2.37days and ranged from 2 to 14. Mean of white blood count was 4153.85 +/- 1706.08 and ranged from 1700 to 13000. PMNs percentage was 61.01 +/- 16.27 in mean and ranged from 26% to 89%. Mean of total PMN count was 2591.38 +/- 1409.42 [from 513 to 10270]. ALT [SGPT] was 40.86 +/- 33.68 in mean [from 10 to 280]. Mean of AST [SGOT] was 53.23+7- 35.76 ranged from 15 to 250. Total bilirobin was 0.9 +/- 0.31 [from 0.2 to 2.1] in mean. Mean of direct bilirobin was 0.2 +/- 0.8 ranged from 0.1 to 0.8. ALKP was 195.19+7-88.6 [from 41 to 590]. 9.5%of patients [16 patients] had liver malfunction [2 times increase of enzymes levels]. No one had jaundice at the time of admit. Comparison of evaluation of lab values of the patients with duration of hospitalization with Pearson test, only in two cases PMN percentage and total PMN had significant relation [P<0.05]. When measles patients had no complications such as secondary bacterial infections and had no history of hepatotoxic drugs, increase in liver enzymes levels is mild and had no significant clinical interest