Histopathological changes of parotid and larynx in hypothyroid rats: experimental study.

OBJECTIVES: In this study, we aimed to investigate the laryngeal and parotid histopathological alterations in rats with experimentally induced postnatal hypothyroidism. MATERIALS AND METHODS: 200-300 g weighed Wistar albino rats were included in this study. The rats were randomly divided into four groups: group 1 is control and the other groups are experimental groups. Food and water were supplied ad libitum in group 1, no medication was administered. Propylthiouracil (PTU) was administered intraperitoneally for 15 days in group 2; for 30 days in group 3, for 45 days in group 4. The larynx and parotid glands of the rats were removed and intracardiac blood samples were collected for thyroid-stimulating hormone (TSH) analysis under anesthesia (ketamine hydrochloride, 100 mg/kg) 24 h after the last PTU injection. The same procedures were done for the control group at day 46. Histopathological evaluation was done for all the specimens. RESULTS: While submucosal vascular dilatation was significantly higher in the experiment groups (p < 0.05), there was not a significant difference in lamina propria edema, inflammation, goblet cell loss, cilia loss between the groups in larynx specimens. In parotid gland specimens, serous asinus atrophy, stromal connective tissue increase were significantly higher in experiment groups (p < 0.05). In addition, there was a significant difference in nuclear morphology between control and experimental groups (p < 0.05). CONCLUSION: The results of the study showed that hypothyroidism may have effect on inflammatory procedure by causing vascular dilation in larynx and serous asinus atrophy nucleus changes, connective tissue increase in stroma in parotid gland.

Adjuvant Rituximab-Exploratory Trial in Young People With Graves Disease.

CONTEXT: Remission rates in young people with Graves hyperthyroidism are less than 25% after 2 years of thionamide antithyroid drug (ATD). OBJECTIVE: We explored whether rituximab (RTX), a B-lymphocyte-depleting agent, would increase remission rates when administered with a short course of ATD. METHODS: This was an open-label, multicenter, single-arm, phase 2 trial in young people (ages, 12-20 years) with Graves hyperthyroidism. An A'Hern design was used to distinguish an encouraging remission rate (40%) from an unacceptable rate (20%). Participants presenting with Graves hyperthyroidism received 500 mg RTX and 12 months of ATD titrated according to thyroid function. ATDs were stopped after 12 months and primary outcome assessed at 24 months. Participants had relapsed at 24 months if thyrotropin was suppressed and free 3,5,3'-triiodothyronine was raised; they had received ATD between months 12 and 24; or they had thyroid surgery/radioiodine. RESULTS: A total of 27 participants were recruited and completed the trial with no serious side effects linked to treatment. Daily carbimazole dose at 12 months was less than 5 mg in 21 of 27 participants. Thirteen of 27 participants were in remission at 24 months (48%, 90% one-sided CI, 35%-100%); this exceeded the critical value (9) for the A'Hern design and provided evidence of a promising remission rate. B-lymphocyte count at 28 weeks, expressed as a percentage of baseline, was related to likelihood of remission. CONCLUSION: Adjuvant RTX, administered with a 12-month course of ATD, may increase the likelihood of remission in young people with Graves hyperthyroidism. A randomized trial of adjuvant RTX in young people with Graves hyperthyroidism is warranted.

Adhesion molecules before and after propylthiouracil in patients with subclinical hyperthyroidism.

OBJECTIVE: This study aimed to investigate the effect of propylthiouracil treatment on adhesion molecules in patients with subclinical hyperthyroidism. METHODS: In this study, a total of 168 patients diagnosed with subclinical hyperthyroidism were treated with propylthiouracil for one year. The levels of adhesion molecules, consisting of sICAM-1, sVCAM-1, and sE-Selectin, before and after the treatment were measured and compared. These results were compared with the levels of 148 healthy controls who received a placebo. RESULTS: sICAM-1 levels were significantly higher in subclinical hyperthyroidism patients than in healthy controls (*pa=0.000). sICAM-1 levels were significantly decreased after the treatment (**pb=0.000). Despite this decrease in patients with subclinical hyperthyroidism, it did not decrease to the level of the control group. sVCAM-1 did not change before and after propylthiouracil treatment. The level of sE-selectin was similar to that of the pretreatment control group, but it did not have statistical significance, although it increased after the treatment (**pb=0.004). CONCLUSION: The sICAM level was significantly higher than the pretreatment values and decreased after the propylthiouracil treatment. However, further studies are needed to reduce the risk of atherosclerosis and cancer in patients with subclinical hyperthyroidism.

Adhesion molecules before and after propylthiouracil in patients with subclinical hyperthyroidism

SUMMARY OBJECTIVE This study aimed to investigate the effect of propylthiouracil treatment on adhesion molecules in patients with subclinical hyperthyroidism. METHODS In this study, a total of 168 patients diagnosed with subclinical hyperthyroidism were treated with propylthiouracil for one year. The levels of adhesion molecules, consisting of sICAM-1, sVCAM-1, and sE-Selectin, before and after the treatment were measured and compared. These results were compared with the levels of 148 healthy controls who received a placebo. RESULTS sICAM-1 levels were significantly higher in subclinical hyperthyroidism patients than in healthy controls (*pa=0.000). sICAM-1 levels were significantly decreased after the treatment (**pb=0.000). Despite this decrease in patients with subclinical hyperthyroidism, it did not decrease to the level of the control group. sVCAM-1 did not change before and after propylthiouracil treatment. The level of sE-selectin was similar to that of the pretreatment control group, but it did not have statistical significance, although it increased after the treatment (**pb=0.004). CONCLUSION The sICAM level was significantly higher than the pretreatment values and decreased after the propylthiouracil treatment. However, further studies are needed to reduce the risk of atherosclerosis and cancer in patients with subclinical hyperthyroidism.

RESUMO ANTECEDENTES O objetivo deste estudo foi investigar o efeito do tratamento com propiltiouracil nas moléculas de adesão em pacientes com hipertireoidismo subclínico. MÉTODOS Neste estudo, 168 pacientes diagnosticados com hipertireoidismo subclínico foram tratados com propiltiouracil por um ano. Os níveis de moléculas de adesão, especificamente sICAM-1, sVCAM-1 e sE-Selectina, antes e após o tratamento foram medidos e comparados. Esses resultados foram comparados com os níveis de 148 indivíduos saudáveis no grupo de controle que receberam um placebo. RESULTADOS Os níveis de sICAM-1 foram significativamente maiores em pacientes com hipertireoidismo subclínico do que nos controles saudáveis (*pa=0,000). Os níveis de sICAM-1 diminuíram significativamente após o tratamento (**pb=0,000). Apesar dessa diminuição em pacientes com hipertireoidismo subclínico, ela não diminuiu para o nível do grupo controle. O sVCAM-1 não se alterou antes e após o tratamento com propiltiouracil. O nível de sE-Selectina foi semelhante ao do grupo de controle pré-tratamento, mas não apresentou significância estatística, embora tenha aumentado após o tratamento (** pb = 0,004). CONCLUSÃO O nível de sICAM foi significativamente superior aos valores pré-tratamento e diminuiu após o tratamento com propilciliouracil. No entanto, mais estudos são necessários para reduzir o risco de aterosclerose e câncer em pacientes com hipertireoidismo subclínico.

SIDE EFFECTS OF PTU AND MMI IN THE TREATMENT OF HYPERTHYROIDISM: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Objective: The present study aimed to investigate the adverse effects of the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating hyperthyroidism. Methods: Qualitative analysis was performed for studies identified in a literature search up to April 20, 2019, and 30 studies were selected for meta-analysis. The study designs included case-control, randomized controlled, and retrospective cohort. Patients were in four age groups: childhood, gestating mothers, older adults, and other ages, and all were receiving PTU or MMI/CMZ. Adverse reactions to MMI/CMZ and PTU were evaluated and compared. Results: Odds of liver function injury were higher in the PTU group than in the MMI/CMZ group (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.16 to 4.96; P = .02). Odds of elevated transaminase were much higher in the PTU group than in the MMI/CMZ group (OR, 3.96; 95% CI, 2.49 to 6.28; P<.00001). No significant between-group differences were found in odds of elevated bilirubin, agranulocytosis, rash, or urticaria; incidence of other adverse events; or in children. Odds of birth defects during the first trimester of pregnancy were higher in the MMI/CMZ group than in the PTU group (OR, 1.29; 95% CI, 1.09 to 1.53; P = .003). Conclusion: The impact of PTU on liver injury and transaminase levels is greater than that of MMI/CMZ, but no significant between-group differences are found in the drugs' effects on bilirubin, agranulocytosis and rash, urticaria, or in children. In treating pregnancy-related hyperthyroidism, PTU should be used in the first trimester and MMI reserved for use in late pregnancy. Abbreviations: ALT = alanine aminotransferase; ATD = antithyroid drug; CI = confidence interval; CMZ = carbimazole; GD = Graves disease; MMI = methimazole; MTU = methylthiouracil; NOS = Newcastle-Ottawa Scale; OR = odds ratio; PTU = propylthiouracil; RAI = radioactive iodine.

Propylthiouracil-induced organizing pneumonia: A case report.

RATIONALE: Propylthiouracil (PTU) is a common antithyroid drug which can treat hyperthyroidism effectively. PTU is, however, associated to multiple adverse effects. In rare case, PTU can cause interstitial pneumonia. PATIENT CONCERNS: A 40-year-old woman presented with dyspnea and was diagnosed with pulmonary infection at the first time. After the treatment with moxifloxacin, her symptoms still got worse. DIAGNOSIS: The lung tissues biopsy confirmed the diagnosis of organizing pneumonia (OP) and the administration of PTU suggested the diagnosis of PTU-induced OP. INTERVENTION: Withdrawal of PTU and the administration of methylprednisolone. OUTCOMES: The patient's symptoms relieved significantly 1 month later and lung computed tomography (CT) scan also demonstrated significant reduction of lung lesions. LESSONS: Here we report the first case of histologically confirmed OP induced by PTU and conduct a literature review of the cases of PTU-induced interstitial pneumonia. The awareness of PTU-induced OP can help physicians reduce the possibility of misdiagnosis.

Neutropenia severa inducida por propiltiuracilo / (Severe neutropenia induced by propylthiuracil)

Resumen Los pacientes con hipertiroidismo tienen varias opciones de tratamiento. El tratamiento de la enfermedad de Graves consiste en bloquear el exceso de hormonas tiroideas empleando tionamidas, tiroidectomía o terapia con I131. Los agentes antitiroideos como el metimazol, carbimazole, propiltiuracilo, son efectivos para controlar el hipertirodismo en pacientes con enfermedad de Graves, pero tienen efectos adversos incluyendo, alergias, gastritis, hepatitis y agranulocitosis. Se presenta un paciente hipertiroideo con neutropenia severa durante tratamiento con propiltiuracilo.

Abstract Patients with hyperthyroidism have several treatment options. The treatment of Graves' disease consists of blocking the excess of thyroid hormones using thionamides, thyroidectomy or I131 therapy. Antithyroid agents such as methimazole, carbimazole, propylthiuracil are effective in controlling hyperthyroidism in patients with Graves' disease, but they have adverse effects including, allergies, gastritis, hepatitis and agranulocytosis. We present a hyperthyroid patient with severe neutropenia during treatment with propylthiuracil.

Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases After Treatment: A Follow-Up Study.

BACKGROUND: Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions. METHODS: A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3+ T and CD19+ B cells were separated by flow cytometry for total DNA and RNA extraction. Global DNA methylation levels were determined by absorptiometry using a methylation quantification kit. DNA methyltransferase (DNMT) expression levels were detected by real-time polymerase chain reaction. RESULTS: Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases. CONCLUSIONS: Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes. The results provide the first demonstration that antithyroid drugs or radioiodine treatment restore global DNA methylation and DNMT1 expression with concurrent relief of hyperthyroidism.

Management of thyroid disorders in pregnancy: Recommendations made simple.

This review covers the current American Thyroid Association recommendations on diagnosis and management of thyroid disease during pregnancy and the postpartum period. It lists the recommendations in a reader-friendly way, and facilitates rational therapy of thyroid disorders, in relation to obstetric health, at the primary care level.

Thyrotoxicosis Presenting as Unilateral Drop Foot.

Neuromuscular disorders associated with hyperthyroidism have several variations in their clinical phenotype, such as ophthalmopathy, periodic paralysis, and thyrotoxic myopathy. We herein report an unusual case of thyrotoxic myopathy presenting as unilateral drop foot. Histopathological examinations of the left tibialis anterior muscle showed marked variation in the fiber size, mild inflammatory cell infiltration, and necrotic and regenerated muscle fibers with predominantly type 1 fiber atrophy. Medical treatment with propylthiouracil resulted in complete improvement of the left drop foot. This case expands the phenotype of thyrotoxicosis and suggests that thyrotoxicosis be considered as a possible cause of unilateral drop foot.

Long-Term Antithyroid Drug Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: Several studies have reported inconsistent findings on the advantages and disadvantages of long-term treatment with antithyroid drugs (ATD). A systematic review and meta-analysis was undertaken to clarify the numerous aspects of long-term treatment with ATD. METHODS: Medline and the Cochrane Library for trials published between 1950 and May 2016 were systematically searched. Studies containing data for long-term (>24 months) ATD treatment were included. Summary estimates of pooled prevalence, odds ratio, and weighted mean difference were calculated with a random effects model. RESULTS: Of 587 related articles found, six fulfilled the inclusion criteria. Long-term ATD treatment induced a remission rate of 57% [confidence interval (CI) 45-68%], a rate that was higher in adults than in non-adults (61% vs. 53%). The rate of complications was 19.1% [CI 9.6-30.9%], of which only 1.5% were major complications. The annual remission rate for each year of treatment was 16% [CI 10-27%], which was higher in adults than non-adults (19% vs. 14%). However, it should be noted that this is not a true linear correlation, but a positive relationship can be suggested between time and remission rate. Meta-regression revealed that smoking had a significant lowering effect on remission rate. CONCLUSIONS: Long-term ATD treatment is effective and safe, especially in adults, indicating that it should be considered as an alternative treatment for Graves' disease.

DRUG UTILIZATION IN TREATMENT OF THYROID DISORDERS DURING PREGNANCY IN SERBIA.

INTRODUCTION: Depleted uranium radiation and pollution with polychlorinated biphenyls resulting from bombings the territories of Serbia as well as the additional long-term stress may have affected the function of thyroid gland. The objective of this study was to determine the trend of drug utilization in the treatment of thyroid dysfunction during pregnancy in Novi Sad. MATERIAL AND METHODS: Women who had given birth at the Department of Gynecology in 1989, 1999, 2007 and 2011 were interviewed during a one-month period about thyroid diseases in the pregnancy as well as the drugs they had taken. RESULTS: Not a single pregnant woman was reported to have a thyroid disorder in 1989 and 1999, while in 2007 four women were reported to have a thyroid dysfunction. In 2011, fourteen out of 18 women with thyroid dysfunction were using levothyroxine and in most cases hypothyroidism was diagnosed as autoimmune Hashimoto thyroiditis. CONCLUSION: The study results suggest the necessity of performing more detailed analyses of the correlation between the frequency of the thyroid gland dysfunction and the effects of environmental pollution in Serbia.

Thyrotropin Receptor Antibody Levels at Diagnosis and After Thionamide Course Predict Graves' Disease Relapse.

BACKGROUND: Thionamides are associated with a high risk of recurrence following cessation. Thyrotropin receptor-stimulating antibody (TRAb) levels at diagnosis and/or after thionamides may be biomarkers of this risk. This study assesses the natural history of Graves' thyrotoxicosis following thionamide withdrawal and factors that predict recurrence, particularly TRAb levels at diagnosis and cessation. METHODS: An observational study was conducted of patients with a first presentation of Graves' disease, who were prescribed (and completed) a course of primary thionamide treatment (n = 266) in a university teaching hospital endocrine clinic. Recurrence rates over four years and factors predictive of recurrent thyrotoxicosis were assessed. RESULTS: The relapse rate was 31% at one year and 70% at four years. Younger age (39 years [range 30-49 years] vs. 47 years [range 37-53 years]; p = 0.011), higher TRAb levels at diagnosis (8.8 IU/L [range 5.3-17.0 IU/L] vs. 5.7 IU/L [range 4.1-9.1 IU/L]; p = 0.003), and higher TRAb levels at cessation of therapy (1.2 IU/L [range 0-2.3 IU/L] vs. <0.9 IU/L [range 0-1.3 IU/L]; p = 0.003) were associated with a higher risk of relapse. By four years, cessation TRAb <0.9 IU/L was associated with a 58% risk of recurrence compared with 82% with TRAb >1.5 IU/L (p = 0.001). TRAb at diagnosis >12 IU/L was associated with an 84% risk of recurrence over four years compared with 57% with TRAbs <5 IU/L (p = 0.002). CONCLUSION: High TRAb at diagnosis and/or positive TRAb at cessation of therapy suggest a high likelihood of relapse, mostly within the first two years. They stratify patients likely to need definitive therapy (radioiodine or surgery).

The preliminary clinical observation and analysis of childbearingage women with a history of iodine-131 treatment for Graves' disease.

Whether radioactive iodine treatment of Graves' disease (GD) during pregnancy will increase pregnancy loss and affect fetal development is still a matter of concern. From May 2005 to December 2015, 2,276 childbearing-age women with GD received iodine-131 treatment in our departments and were retrospectively enrolled in our study. When some of them were found to have been pregnant, their thyroid functions were measured every 4 weeks, in addition, thyroid-stimulating hormone (TSH) was measured 6 weeks after delivery. When necessary, levothyroxine or propylthiouracil (PTU) was given in order to control their TSH levels during pregnancy. Finally, 69 pregnant women (29 ± 3.5 years old) and 1346 women who were not pregnant during the follow-up period were enrolled into this study. They were all hyperthyroid before or during pregnancy. Among 69 pregnant women, the administrated amount of iodine-131 was 254.9 ± 99.9 MBq. Fifty patients became subclinically hypothyroid after treatment and were administrated levothyroxine (55 ± 25 µg/d). Seven patients were diagnosed with subclinical hyperthyroidism during pregnancy and they received PTU (25 ± 12.5 mg/d). Twelve patients with normal thyroid function were also clinically followed. Among 69 women, 63 had a single birth, 3 had dizygotic twins, 2 had two pregnancies and 1 had a single twin birth. Sixty five babies were born full-term, while 9 were premature (4 ± 1 weeks early) with birth weight 3.2 ± 0.5 kg. Six new born babies were considered to be low birth weight infants (< 2.5 kg) while 5 were high birth weight (> 4 kg), but the weights of all the infants were within the normal range. During the period of observation to December 2015, all the infants were found to grow and develop normally. Among 1346 women who were not pregnant were in the further follow-up. Our study found no detrimental effects of the iodine-131 treatment in the pregnant women or their offspring so far.

[Management of hypothyroidism and hyperthyroidism]. / Lécba hypotyreózy a hypertyreózy.

Functional thyropathies present significant health risks for patients. Advanced functional thyropathies are always treated while indications for therapy of subclinical thyropathies are individual and often controversial. It is widely agreed that these disorders should be diagnosed and individuals should be followed. The drug of choice in substitution therapy of hypothyroidism is levothyroxine, in the treatment of hyperthyroidism it is methimazole. Administration of propylthiouracil should be limited to the first trimester of pregnancy, because its serious hepatotoxicity has been described. Hyperthyroidism based on thyroid nodules and immunogenic hyperthyroidism not reaching long-term remission, need to be treated radically: by surgery or radioiodine treatment. When radiation protection requirements are met, radioiodine can also be administered on an outpatient basis. Exceptionally, small doses of methimazole can be administered over an extended period of time in individual cases.

Propylthiouracil-Induced Vasculitis With Antineutrophil Cytoplasmic Antibody.

Propylthiouracil (PTU)-associated vasculitis is a potentially life-threatening disease with a recent increase in the reported cases in the medical literature. This increase may suggest that some earlier cases have been unrecognized or assigned to an alternative nosology category. Although the skin can be the only organ affected by PTU-associated vasculitis, there are many reports with multiple-system involvement. Classically, the symptoms appear under a tetrad of fever, sore throat, arthralgia, and skin lesions. Cutaneous lesions in reported cases of PTU vasculitis have most commonly consisted of retiform acral, purpuric plaques, or nodules. We report a case of perinuclear antineutrophil cytoplasmic antibody-associated vasculitis developed during treatment with PTU for Grave's disease.

[ANALYSIS OF ULTRASONIC, CYTOLOGICAL AND MORPHOLOGIC RESEARCHES RESULTS OF PATIENTS WITH GRAVES' DISEASE (TOXIC GOITER) DEPENDING ON DISEASE DURATION].

The aim of research is to arrange the results of ultrasonic and cytological researches during long-term drug treatment (more than 1 year) of patients with Graves' disease. From 2008 to 2013 the detailed examination of 220 patients was carried out in Kyiv City Centre for Endocrine Surgery which operates on the basis of the 3d Clinical Hospital. There were established three kinds of echographic patterns which pointed out the ultrasonic changes of the thyroid gland tissue, occurred during the drug treatment. Among 63 (28.6%) patients with long-term drug treatment the development of space-occupying lesions, occurred due to long duration of disease with long-term usage of tyreostatics, was recorded. After the surgical treatment the extracted thyroid gland tissue was subjected to histological study. The papillary carcinoma of thyroid gland was verified in 4 (6,3 %) of 63 patients with space-occupying lesions. The ultrasonic research of thyroid gland in combination with aspiration puncture biopsy and cytological research are the highly informative methods of examination of patients with Graves' disease which allow to objectify the organ structural condition while the disease duration.

Tubulointerstitial nephritis and uveitis syndrome complicated by IgA nephropathy and Graves' disease: a case report.

INTRODUCTION: Tubulointerstitial nephritis and uveitis syndrome is a disorder characterized by a combination of acute tubulointerstitial nephritis and uveitis. Immunoglobulin A nephropathy is defined by the presence of immunoglobulin A deposits in glomerular mesangial areas. In this report, we describe a rare case of tubulointerstitial nephritis and uveitis syndrome complicated by immunoglobulin A nephropathy and Graves' disease, which was successfully treated with corticosteroids. To the best of our knowledge, this is the first time such a case has been documented since tubulointerstitial nephritis and uveitis syndrome was first described. CASE PRESENTATION: A 64-year-old Japanese woman presented with tubulointerstitial nephritis and uveitis syndrome accompanied by immunoglobulin A nephropathy and Graves' disease. She had renal dysfunction, proteinuria, and hematuria. Two weeks after her admission, she developed anterior chamber uveitis. She received corticosteroids, resulting in significant clinical improvement. CONCLUSION: Tubulointerstitial nephritis and uveitis syndrome is a relatively uncommon cause of tubulointerstitial nephritis. Clinicians should recognize that tubulointerstitial nephritis and uveitis syndrome with immunoglobulin A nephropathy can occur in the presence of Graves' disease. Additionally, this report may provide important clues in terms of the management of a concomitant case of these diseases.

Alcoholic hepatitis: a comprehensive review of pathogenesis and treatment.

Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with significant morbidity and mortality. Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol metabolism, inflammation and innate immunity. Several clinical scoring systems have been derived to predict the clinical outcomes of patients with AH; such as Child-Turcotte-Pugh score, the Maddrey discriminant function, the Lille Model, the model for end stage liver disease scores, and the Glasgow alcoholic hepatitis score. At present, Corticosteroids or pentoxifylline are the current pharmacologic treatment options; though the outcomes from the therapies are poor. Liver transplantation as the treatment of alcoholic hepatitis remains controversial, and in an era of organ shortage current guidelines do not recommend transplantation as the treatment option. Because of the limitations in the therapeutic options, it is no doubt that there is a critical need for the newer and more effective pharmacological agents to treat AH.