Smooth Muscle Antibodies Research Articles

An Unusual Presentation of Auto-immune Hepatitis

Purpose: A 26-year-old Caucasian male with no significant history presented with new onset jaundice for 3 weeks. Two weeks prior to admission, he developed daily nausea and vomiting. One week prior to admission, he developed night sweats, anorexia, constipation, and generalized pruritis. In addition, he began to experience a post-prandial right upper quadrant abdominal pain with no radiation, and a 16-pound weight loss, which prompted presentation to the hospital. His medications included occasional acetaminophen/ diphenydramine PRN for insomnia. Family history was significant for cholelithiasis in his mother and lung cancer in multiple family members. The patient's social history included consumption of approximately 5 oz of spirits per week, a remote tobacco history, experimentation with intravenous heroin, as well as multiple professionally-obtained tattoos. Pertinent physical exam findings included stable vital signs, icterus, a soft and non-tender abdomen with liver edge palpated two cm below the costal margin, and percussed splenomegaly. No lymphadenopathy or asterixis were appreciated. Laboratory findings were significant for AST of 825 U/L, ALT of 596 U/L, total bilirubin of 26 mg/dL with a direct bilirubin of 20 mg/DL, and alkaline phosphatase of 118 U/L. His INR was 1.46 with a PT of 17.4, albumin of 3.1 g/dl, and total protein of 6.8 g/dl. Abdominal ultrasound revealed a nodular liver surface, hepatosplenomegaly, marked gallbladder thickening, and enlarged peripancreatic lymph nodes consistent with acute hepatitis. Hepatitis A, B, and C serologies were negative. His ferritin was 423 ng/mL with a percent saturation of 38. Anti-mitochondrial antibody, anti-LKM and alpha 1 anti-trypsin titers were within normal limits. His total IgG was 2,657 (reference range 650-1,600.) Anti smooth muscle antibody titers were measured at 36 U (reference range <20.) Given his clinical picture, along with an international autoimmune hepatitis group scoring of 10, treatment was started for autoimmune hepatitis with corticosteroids. His clinical picture improved soon thereafter. Discussion: This case represents an unusual presentation of autoimmune hepatitis. Autoimmune hepatitis is typically diagnosed in the fourth or fifth decade of life, and more commonly affects females. It typically presents with markedly elevated ASTs, compared to bilirubin and alkaline phosphatase, as was seen in this case. This presentation demonstrates, however, that this condition can present at any age, and can also affect males. Autoimmune hepatitis should, therefore, remain high on the differential in young males with hepatitis.

Radiologic and Histologic Heterogeneity in a Case of Autoimmune Acute Liver Failure

Apreviously healthy 31-year-old woman taking no medications was admitted to an outside hospital with a 10-day history of epigastric discomfort, followed by jaundice. Laboratory tests revealed aspartate aminotransaminase 1123 U/L, alanine aminotransaminase (ALT) 620 U/L, gamma-glutamyl transpeptidase 151 U/L, total bilirubin (T-BIL) 24.3 mg/dL, prothrombin time (PT) activity 22% of control, and ammonia 69 mg/dL. Abdominal computed tomography (CT) showed no evidence of chronic disease or hepatic heterogeneity, and viral hepatitis serologies were negative. Conservative treatment was undertaken, but hepatic function deteriorated, and encephalopathy developed during a period of 2 weeks. A positive antinuclear antibody was found. The patient was transferred to our hospital. On admission to our unit, the patient had grade II encephalopathy, and laboratory tests revealed aspartate aminotransaminase 1381 U/L, alanine aminotransaminase 498 IU/L, total bilirubin 31.0 mg/ dL, prothrombin activity 16% of control, platelets 12.3 10/mL, and ammonia 187 mg/dL. Hepatotropic viruses were all negative. Antinuclear antibody was 1:1280, and immunoglobulin G was 1968 mg/dL. Anti–smooth muscle antibody, anti-mitochondrial antibody, and liver kidney microsomal antibody-1 were negative. Her HLA-DR was DR4 and 15. Repeat noncontrast abdominal CT scan showed hepatic atrophy with heterogeneous hypoattenuating regions. Her revised international autoimmune hepatitis (AIH) score was 14, consistent with probable AIH. Medical therapy including corticosteroids, anticoagulation, plasma exchange, and hemodiafiltration were initiated, but hepatic function did not improve (Figure A). A living donor liver transplantation was

Characteristics and Outcome of three forms of Autoimmune Hepatitis in Iranian Children

Introduction To define the clinical features, biochemical and histological findings and outcome of three forms of autoimmune hepatitis. Materials and Methods In a cross sectional study between November 2001 to January 2008 in Tehran and Mashhad university of medical sciences, 61 children who diagnosed as AIH (40 girls and 21 boys) have been analyzed for their clinical, serological, and histological data. Variables analyzed included age, sex, clinical presentation, hepatic function, immunoglobulins, autoimmunity markers, histology and clinical evolution. According to the auto-antibodies profile, AIH patients were classified as type I AIH (ANA or smooth-muscle antibodies or both positive), type II (anti-LKM-1 positive) and type III (antibody negative). Results We analyzed data of 61 children with AIH. 51 patients (median age: 10 (0.7-14) years had anti-nuclear and/or smooth muscle antibody (ANA/ASMA or both), 5 (median age: 7 (2-8) years) had liver/kidney microsomal antibody (LKM-1). 5 patients had no detectable autoantibody. At presentation: 60% had jaundice or symptoms of acute hepatitis; LKM-1 positive were younger. Interface hepatitis was seen in 100% and fibrosis+/- cirrhosis were found in 70%. Frequency of AIH was 2:1 in girls. Type 1 was the most frequent diagnosis (83%) and was more frequent in older children. Relapse and treatment failure were common in type II. Conclusion AIH may have different clinical presentation in children. Althout most of cases may have high inflammatory activity or cirrhosis, good response to treatment and remission may accur.

Prevalence of Non Organ-Specific Auto Antibodies and its Effect on Response to Antiviral Therapy in Patients with Chronic Hepatitis C Virus Genotype 4

Background and study aim:: Immunological disorders have been frequently described in the course of hepatitis C virus (HCV)–related chronic hepatitis. Our aim was to determine the prevalence of non-organ-specific autoantibodies (NOSAs) and evaluate its impact on the response to combined antiviral therapy in patients with chronic HCV genotype-4 Patients and methods: A total of 134 adult patients with chronic HCV genotype-4 were investigated for the presence of serum Antinuclear antibody (ANA), anti–smooth muscle antibody (SMA), and anti liver/kidney microsomal antibody type 1 (LKM1). 109 out of 134 HCV patients were treated naive and received combined antiviral therapy (pegylated interferon–ribavirin). The presence of these autoantibodies was studied in relation to the patient’s characteristics and the outcome of antiviral therapy. Results :Thirty-six (26.9%) patients were positive for at least one autoantibody. Various autoantibodies were presented as follows: ANA in 29 (21.6%) patients, SMA in 9 (6.7%) and anti-LKM-1 in 2 (1.5%). In two patients, both ANA and anti-SMA were positive, and in other two cases both ANA anti-LKM-1 were positive. Female patients had a higher prevalence of positive autoantibodies (P=0.005). Chronic hepatitis C (CHC) patients with positive autoantibodies had higher serum ALT, AST and GGT levels. The rate of sustained virological response to combined antiviral therapy was similar between autoantibody-positive and -negative groups (46.9% vs. 53.2%). Conclusion : Autoantibodies can be induced in the course of CHC. Autoantibody-positive CHC patients are older and have higher disease activity and severity. However, the presence of these autoantibodies did not influence the response to combination antiviral therapy.

Modulation of serum smooth muscle antibody levels by levamisole treatment in patients with oral lichen planus

Serum autoantibodies have been found in patients with oral lichen planus (OLP). This study evaluated whether OLP patients had significantly higher frequencies of serum smooth muscle antibody (SMA) than healthy control individuals, and assessed whether levamisole treatment could modulate the serum SMA levels in OLP patients. This study used an indirect immunofluorescence technique to measure the baseline serum SMA levels in a group of 647 OLP patients and 53 controls. Ninety-five SMA-positive OLP patients were treated with levamisole under a regular follow-up schedule, and their serum SMA levels were measured after treatment. The frequencies of serum SMA in patients with OLP (21.9%), erosive OLP (EOLP, 21.6%), major EOLP (17.9%), minor EOLP (24.2%), and nonerosive OLP (24.4%) were all significantly higher than that (0%) in healthy controls (all p<0.001). Of 142 SMA-positive OLP patients, 95 were treated with levamisole under a regular follow-up schedule. Treatment with levamisole for a period of 2-29 months (mean, 9.4±6.0 months) effectively reduced the high mean serum SMA titer (71.0±7.2) at baseline to an undetectable level (0) in all SMA-positive OLP patients, regardless of different initial serum SMA titers. There was a significantly higher frequency of serum SMA (21.9%) in OLP patients than in healthy controls. Treatment with levamisole for 2-29 months significantly reduced the high serum SMA to an undetectable level, and significantly improved the signs and symptoms in all treated OLP patients.

Clinical and histological features of autoantibody‐negative autoimmune hepatitis in Chinese patients: A single center experience

This study aimed to define the clinical features of Chinese patients with autoantibody-negative autoimmune hepatitis (AIH) and to refine the diagnosis and management of these atypical patients in a single Chinese center. A retrospective evaluation of 167 Chinese patients with AIH was performed. Patients meeting comprehensive criteria with the absence of antinuclear antibodies, smooth muscle antibodies, liver-kidney microsomal-1 antibodies and antimitochondrial antibodies were defined as autoantibody-negative patients. In total, 17 (10.2%) of the 167 patients with AIH were autoantibody-negative. The general status and biochemical tests between the classical and autoantibody-negative patients were not significantly different (P > 0.05). Serum immunoglobulin G levels of the autoantibody-negative AIH patients were lower than those of the classical AIH ones (P = 0.004). There was no significant difference in the histological inflammatory grades between the two groups; however, advanced histological stages were more common in the autoantibody-negative AIH group (P < 0.001). In the autoantibody-negative AIH patients, 11 (64.7%) had a possible diagnosis and 6 (35.3%) had a definite diagnosis according to the comprehensive criteria. While with the simplified criteria only 3 patients (17.6%) had a possible diagnosis, and none had a definite diagnosis of AIH. The complete biochemical remission rate was 86% within 24 months of immunosuppressive therapy, which was comparable to classical AIH (P = 0.658). Autoantibody-negative AIH is not uncommon in Chinese AIH patients, and has a good response to immunosuppressive treatment comparable to classical patients.

Liver Injury From Tumor Necrosis Factor-α Antagonists: Analysis of Thirty-four Cases

Tumor necrosis factor (TNF)-α antagonists have been associated with drug-induced liver injury (DILI). We reviewed cases of DILI in the United States to identify those associated with use of TNF-α antagonists. We searched the U.S. DILI Network (DILIN) database, from 2003 to 2011, for cases associated with TNF-α antagonists. Mean Roussel-Uclaf Causality Assessment Method scores were calculated. A DILIN severity score was assigned according to a previously published scale, and we identified 6 subjects likely to have DILI associated with use of TNF-α antagonists. We also searched PubMed for articles that reported hepatotoxicity from TNF-α antagonists, identifying 28 additional cases suitable for analysis. The drugs presumed to have caused DILI were infliximab (n = 26), etanercept (n = 4), and adalimumab (n = 4). The anti-TNF-α agent was the probable cause of 12 cases of DILI (35%), a very likely cause for 21 (62%), and a definite cause for 1 (3%). Median latency was 13 weeks (range, 2-104); however, 7 cases (20%) had latency periods longer than 24 weeks. Twenty-two of 33 subjects who underwent serologic analysis (67%) tested positive for anti-nuclear and/or smooth muscle antibodies. Of these 22, 17 underwent liver biopsy; 15 subjects had clear features of autoimmunity. The 22 subjects with autoimmune features had longer median latency (16 vs 10 weeks) and higher peak levels of alanine aminotransferase (784 vs 528 U/L) than the 12 without such features. There was 1 case of severe cholestasis. All but one subject improved after discontinuation of the implicated drug; 12 subjects received corticosteroid therapy. No deaths were attributed to liver injury, although one patient with preexistent cirrhosis required liver transplantation. Acute liver injury caused by TNF-α antagonists may be a class effect because multiple agents in this category have been implicated. The most common presentation is an autoimmune phenotype with marked hepatocellular injury, but a mixed non-autoimmune pattern or predominant cholestasis also occurs. The prognosis is usually good after drug discontinuation, although some patients may benefit from a course of corticosteroids. ClinicalTrials.gov: Number, NCT00345930.

Angioleiomyoma of the Auricle

Angioleiomyoma of the Auricle

Hepatoportal Sclerosis in Childhood: Descriptive Analysis of 12 Patients

Hepatoportal sclerosis (HPS) is defined as sclerosis of portal areas in the absence of cirrhosis. There is little information about HPS in children in the literature. The aim of this study was to describe the clinical presentation, associated disorders, laboratory characteristics and outcome of children who were diagnosed as HPS. This study included 12 children diagnosed as HPS by the Pathology Department between 2005 and 2011. Data were collected from the gastroenterology clinic charts retrospectively, including demographics, presentation characteristics, laboratory data and recent status of patients. Twelve patients were enrolled (6 girls, 6 boys). The median age of patients was 13.5 yr. Median age at the time of biopsy was 11 yr. Four patients had splenomegaly, 3 had esophageal varices, one had hepatopulmonary syndrome and had been transplanted. Smooth muscle antibody was found positive in 4 patients, without autoimmune hepatitis findings in liver biopsy. One patient had celiac disease and another patient had positive celiac disease serology but pathology findings. Another patient had Turner's syndrome. Mean follow-up time was 39 months (3.3 yr) after biopsy. Hepatoportal sclerosis does not necessarily present with portal hypertension in children.

Sporadic Porphyria Cutanea Tarda in a Patient with Multiple Sclerosis Treated with Interferon Beta 1-a Therapy: A Case Report

Dear Editor, Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system, and interferon beta-1a (IFN-β1a) is a valuable medication in the treatment of the relapsing-remitting form of MS (RR MS). Porphyria cutanea tarda (PCT), which is the most frequent type of porphyria, is the result of a catalytic deficiency of uroporphyrinogen decarboxylase. In sporadic PCT (sPCT), which represents 75% of cases, the deficiency is limited to the liver.1 Accumulated uroporphyrin and other highly carboxylated porphyrins, which are soluble, diffuse from the plasma into the upper dermis. The clinical picture reflects the phototoxic reaction that subsequently occurs in the upper dermis, in that lesions occur almost exclusively in light-exposed areas.2 The cutaneous findings include increased photosensitivity, skin fragility, blistering, erosions, and crusts.1 In this letter we describe new onset of sPCT in a patient with RR MS who was treated with IFN-β1a. In brief, a 33-year-old man without a family history of PCT was admitted to our department complaining of dizziness and diplopia of 3 weeks duration. Neuroimaging revealed several demyelinating lesions in the subcortical white matter and the periventricular regions. Within 4 months he presented with paresthesia and hyposthenia of the left arm, and repeat MRI revealed additional demyelinating lesions (Fig. 1A). The patient was diagnosed with MS according to McDonald criteria3 and was started on treatment with IFN-β1a, which was administered subcutaneously three times weekly. Fig. 1 A: MRI showing several demyelinating lesions. B: Skin lesions on the back of the patient's hands. In the course of his treatment, the patient exhibited no relevant neurological alterations; however, after 5 years he observed the development of skin lesions that were localized to the back of his hands, appearing as bullae up to 1 cm wide, and sometimes larger. There were also crusts, atrophic scars, and areas of hypopigmentation (Fig. 1B). He was diagnosed with dermatitis bullosa, for which he was prescribed prednisone at 25 mg/day, which had no effect. His levels of transaminases were elevated as follows: glutamic-oxaloacetic transaminase, 47 U/L [normal value (NV), <38 U/L]; and glutamic-pyruvate transaminase, 138 U/L (NV, <41U/L). However, testing for hepatitis, including viral markers, antinuclear antibodies, smooth muscle antibodies, and antibodies to liver and kidney microsomes, alcoholic liver disease, and hemochromatosis yielded negative findings. PCT was suspected because of the blistering skin lesions on the back of his hands and other sun-exposed areas of his skin. Laboratory testing for porphyrin levels yielded the following results: total urine porphyrins, 1.838 mg/24 h (NV, <0.150 mg/24 h);4 total serum porphyrins, 0.069 mg/L (NV, <0.004 mg/L);5 plasmatic fluorimetric peak, 620 nm; and erythrocyte porphyrins, within the normal range. A skin biopsy procedure was performed on the patient's thigh, and a final diagnosis of PCT was confirmed by a dermatologist. Repeated phlebotomy resulted in the almost complete disappearance of the skin lesions. The patient suspended the IFN-β1a, and after 3 months commenced glatiramer acetate therapy. Follow-up examinations demonstrated that this medication switch resulted in the patient not experiencing any recurrence of the skin lesions, and porphyrin and transaminase levels within the normal ranges. Cassiman et al.6 showed that there is a significant association between sPCT and liver disorders, and described the occurrence of sPCT after medication intake in three patients. However, to our knowledge the present case is the first report of sPCT probably induced by IFN-β1a. We speculate that the possible hepatotoxic effect of IFN-β1a can trigger the development of sPCT in certain predisposed patients. Furthermore, this case highlights the importance of monitoring liver function in all patients treated with IFN-β1a.

Autoimmune hepatitis in childhood: The role of genetic and immune factors

Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hypergammaglobulinemia, elevated liver enzymes, presence of autoantibodies and histological changes. Although being rare in children, it represents a serious cause of chronic hepatic disease that can lead to cirrhosis and hepatic failure. Clinical findings, exclusion of more common liver disorders and the detection of antibodies antinuclear antibodies, smooth muscle antibodies and anti-LKM1 are usually enough for diagnosis on clinical practice. The pathogenic mechanisms that lead to AIH remain obscure, but some research findings suggest the participation of immunologic and genetic factors. It is not yet knew the triggering factor or factors that stimulate inflammatory response. Several mechanisms proposed partially explain the immunologic findings of AIH. The knowledge of immune factors evolved might result in better markers of prognosis and response to treatment. In this review, we aim to evaluate the findings of research about genetic and immune markers and their perspectives of application in clinical practice especially in pediatric population.

A Case of Q Fever that may Mimic Systemic Lupus Erythematosus

Q fever is a zoonosis caused by a Coxiella burnetii. Q fever is clinically variable, presenting as asymptomatic infection, pneumonia, hepatitis and endocarditis. Treatment of acute Q fever with doxycycline is usually successful. Autoantibodies, such as anti-mitochondrial antibodies, smooth muscle antibodies (SMA), anti-cardiolipin and lupus anticoagulant, often rise in acute Q fever infection. Some cases may occasionally meet the criteria for autoimmune disease like systemic lupus erythematosus. We report a first case of Q fever that may mimic systemic lupus erythematosus in Korea

Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome developed in a patient with vitiligo and Hashimoto thyroiditis

Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are main autoimmune liver diseases. The term overlap syndrome describes the coexistence of two autoimmune liver diseases in the same patient, and AIH/PBC overlap is the most common form 1–3. Patients with AIH/PBC overlap also have other organ and nonorgan specific autoimmune diseases. In the may issue of the European Journal of Gastroenterology & Hepatology, Efe et al. 4 described this association in a large group of AIH/PBC patients. In this study, they found a 43.6% (31/71) prevalence of extrahepatic autoimmune diseases in patients with AIH/PBC overlap. Autoimmune thyroid diseases, Sjögren syndrome, celiac disease, psoriasis, and rheumatoid arthritis were the most commonly associated autoimmune diseases. To contribute additional information in this area of active investigation, we would like to present a case of AIH/PBC overlap that developed in a patient with Hashimoto thyroiditis and vitiligo. A 52-year-old man with a known history of both Hashimoto thyroiditis and vitiligo first presented to our clinic with fatigue, pruritus, and yellowish discoloration of the sclera and skin. Laboratory examinations yielded the following results: alanine aminotransferase 278 IU/l (0–54 IU/l), aspartate aminotransferase 228 IU/l (0–34 IU/l), alkaline phosphatase 512 IU/l (64–160 IU/l), γ-glutamyl transpeptidase 1315 IU/l (20–64 IU/l), total bilirubin 6.5 mg/dl (0.6–1.2 mg/dl), IgG 36.6 g/l (7–16 g/l), and IgM 3.5 g/l (0.4–2.3 g/l). Antinuclear antibody was positive at the titer of 1/320, smooth-muscle antibody was 1/320, antimitochondrial antibody (AMA-M2) was 1/160, and anti-double-stranded DNA (ds-DNA) was 3.4 (0.1–1.1). Findings on a subsequent liver biopsy were consistent with both AIH and PBC, with moderate interface hepatitis along with proliferation of the bile ducts. With a diagnosis of AIH/PBC overlap syndrome, the patient was started on a daily regimen of 30 mg prednisolone, 50 mg azathiopyrine, and 1250 mg ursodeoxycholic acid (UDCA). After remission was achieved, prednisolone was tapered slowly to a maintenance dose of 5 mg/day whereas azathioprine and UDCA were continued at the same doses. The overlap of AIH and PBC is a very rarely encountered clinical entity in clinical practice. Although still there is no consensus on diagnosis and therapy regimes, the Paris criteria suggested by Chazouillères et al.2 are widely used for the diagnosis of these patients. Our patient fulfilled the criteria of overlap syndrome and also showed concomitant AMA and ds-DNA seropositivity, which was found to be a highly specific serological marker of AIH/PBC overlap 5,6. Therapy of these patients includes UDCA combination with immunosuppressive or UDCA alone 1,7. For our patient, we preferred the combination therapy regime and this led to complete biochemical remission 3 months after the initiation of therapy. The coexistence of AIH and PBC with other autoimmune disorders has been well described in large population-based studies 8,9. However, until recently, this association has been described in only small case-based studies for patients with overlap syndromes 10–12. However, in the study by Efe et al.4, a high prevalence of concurrent autoimmune diseases have been reported in a large population of AIH/PBC overlap patients. This study highlighted the importance of considering the association of AIH/PBC overlap syndrome in patients with other known autoimmune disorders presenting with liver dysfunction or extended screening for existing autoimmune diseases during the routine assessment of patients with overlap syndrome. Acknowledgements Conflicts of interest There are no conflicts of interest.

Tamoxifen decreases the myofibroblast count in the healing bile duct tissue of pigs

OBJECTIVE:The aim of this study was to evaluate the effect of oral tamoxifen treatment on the number of myofibroblasts present during the healing process after experimental bile duct injury.METHODS:The sample consisted of 16 pigs that were divided into two groups (the control and study groups). Incisions and suturing of the bile ducts were performed in the two groups. Tamoxifen (20 mg/day) was administered only to the study group. The animals were sacrificed after 30 days. Quantification of myofibroblasts in the biliary ducts was made through immunohistochemistry analysis using anti-alpha smooth muscle actin of the smooth muscle antibody. Immunohistochemical quantification was performed using a digital image system.RESULTS:In the animals treated with tamoxifen (20 mg/day), there was a significant reduction in immunostaining for alpha smooth muscle actin compared with the control group (0.1155 vs. 0.2021, p = 0.046).CONCLUSION:Tamoxifen reduced the expression of alpha smooth muscle actin in the healing tissue after bile duct injury, suggesting a decrease in myofibroblasts in the scarred area of the pig biliary tract. These data suggest that tamoxifen could be used in the prevention of biliary tract stenosis after bile duct surgeries.

Clinical features of autoimmune hepatitis and comparison of two diagnostic criteria in Korea: A nationwide, multicenter study

As a rare liver disease, little is known about autoimmune hepatitis (AIH). This study investigated the clinical features and compared two diagnostic criteria of AIH in Korea. A nationwide, multicenter, retrospective analysis was done of data of adult patients diagnosed with AIH from January 2005 to December 2009. The enrolled patients (n = 343; mean age, 52.8 years; range, 19-87 years; 12% male, 88% female) met diagnostic criteria of AIH according to the revised original criteria (n = 311) or the simplified criteria (n = 250). At diagnosis, 30.6% were asymptomatic, 22.7% were cirrhotic, and 4.3% displayed hepatic decompensation. The positive results for anti-nuclear antibody, smooth muscle antibody, and anti-liver/kidney microsomal antibody were 94.2%, 23.0%, and 2.9%, respectively. Definite AIH and probable AIH according to the revised original criteria were 24.8% and 65.3%, respectively, while those according to the simplified criteria were 34.4% and 38.5%, respectively. The diagnostic sensitivity and positive predictive value of simplified criteria in comparison with the revised original criteria were 69.9% and 86.4%, respectively. As an initial therapy, corticosteroid (37.7%) or corticosteroid with azathioprine (36.8%) was administered. Remission, incomplete response, and treatment failure were noted with 85.7%, 10.5%, and 3.9% of patients, respectively. Autoimmune hepatitis in Korea is mostly type I, showing a mean age of 53 years with comparable clinical features to other countries. The concordant rate of the two diagnostic criteria was rather low with modest sensitivity of the simplified criteria. Further studies on the validation of the diagnostic criteria are warranted.

Autoimmune Hepatitis Induced by Nitrofurantoin. The Importance of the Autoantibodies for an Early Diagnosis of Immune Disease

Nitrofurantoin has been in use since 1953 as an effective agent for the prevention of recurrent urinary tract infection. It is associated with a wide range of adverse drug reactions. Chronic active hepatitis has increasingly been observed and many cases have been reported with case fatalities. We present a case of nitrofurantoin induced chronic active hepatitis and briefly review the serology and clinico pathological features of 57 similar cases reported in English literature. The consistent presence of antinuclear antibody, anti smooth muscle antibody, elevated immunoglobulin and pathological feature suggests an immunologic mechanism. Complete recovery is possible in most cases if medication is discontinued in time. Steroids may play a role in management if no improvement occurs despite discontinuation of medication. We suggest all patients who are on prolonged nitrofurantoin therapy be followed up with anti nuclear antibody, anti smooth muscle antibody, serum immunoglobulin and hepatic panel every three months.

Screening for autoantibodies in chronic hepatitis C patients has no effect on treatment initiation or outcome

Autoantibodies in hepatitis C virus-infected patients may indicate autoimmune hepatitis or other immune-mediated diseases. This may impact safety and efficacy of interferon-based therapy of chronic hepatitis C. We investigated the association between a positive test result for a variety of autoantibodies and the initiation and efficacy of therapy for chronic hepatitis C. We analysed an observational cohort of 24 306 patients for an association between autoantibodies and treatment outcome. 8241 patients were tested simultaneously for antinuclear antibodies (ANA), liver kidney microsomal antibodies (LKM), smooth muscle antibodies (SMA) and antimitochondrial antibodies (AMA). Matched-pair analysis was performed matching one autoantibody-positive patient to three controls. Control patients had negative tests for all four antibodies. Analyses were performed for patients with a single positive autoantibody test and for patients with multiple positive autoantibody tests. A positive test result for ANA, LKM, SMA or AMA did not affect the physician's decision to initiate therapy with pegylated interferon and ribavirin. In addition, a positive test for one or multiple autoantibodies did not adversely affect sustained virologic response. There was no difference in fibrosis stage or alanine transaminase at baseline or during therapy irrespective of antibody status. Thyroid dysfunction was more frequent in patients with positive LKM antibodies (P = 0.004). Initiation of therapy for chronic hepatitis C and outcome were not affected by the presence of ANA, LKM, SMA or AMA. Routine testing of these autoantibodies seems not warranted. Determination of autoantibodies should be guided by individualized clinical decisions.

Unusual Presentation of Autoimmune Hepatitis in Pre-Existing Ulcerative Colitis

Purpose: About 16% of patients with Autoimmune hepatitis (AIH) have ulcerative colitis (UC). Conventionally, AIH is characterized by antinuclear antibodies (ANA), anti smooth muscle antibodies (ASMA), and/or anti liverkidney microsmal antibodies (anti-LKM-1). We present three cases from a single institution of newly diagnosed AIH in UC patients with negative ANA, ASMA, and anti-LKM-1. Case 1: A 56-year-old Chinese male with a 22 year history of UC well controlled on mesalamine presents with three weeks of dark urine accompanied by lethargy and two weeks of jaundice. His AST and ALT were both over 2000, with an elevated gamma globulin fraction. His additional liver workup was negative. His ANA, ASMA, and Anti-LKM-1 were negative. The MRCP was negative for PSC. The liver biopsy showed markedly active chronic hepatitis with confluent necrosis and a predominance of plasma cells. pANCA was strongly positive. His liver function normalized with initiation of prednisone and 6-mercaptopurine (6-MP). Case 2: A 20-year-old Hispanic male with an eight year history of UC well controlled on mesalamine was admitted to the hospital with jaundice and right upper quadrant pain. His AST and ALT were over 700, with an elevated gamma globulin fraction. His additional liver workup was negative. His ANA, ASMA, and Anti-LKM-1 were negative. His pANCA was strongly positive. The MRCP was negative for PSC. His liver biopsy showed markedly active chronic hepatitis with confluent necrosis, and plasma cell predominance. His liver function normalized with initiation of prednisone and 6-MP. Case 3: A 17-year-old African-American male with a two month history of UC in remission on mesalamine presented with AST and ALT over 400, and an elevated gamma globulin fraction. His additional liver workup was negative. His ANA, ASMA, and Anti-LKM-1 were negative. His anti-actin antibodies were strongly positive. The MRCP was negative for PSC. The liver biopsy showed markedly active chronic hepatitis with interface hepatitis, confluent necrosis, and plasma cell predominance. Furthermore, there was focal bile duct paucity possibly consistent with possible incipient or small duct PSC. Prednisone and 6-MP was started concomitantly and his liver function normalized. The patient is being followed closely with serial labs and cholagiographies. Discussion: We presented three cases of AIH with preexisting well controlled UC with negative ANA, ASMA, and anti-LKM1. All three of these patients responded to prednisone, and are being maintained with 6-MP. Since up to 42% of patients with UC and AIH may develop abnormal cholangiography, close follow up with labs and imaging is required.

Miopatías inflamatorias idiopática: su asociación a hepatopatías

The aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) are sensitive indicators of liver damage. While the TSGOT is also found in other organs, the SGPT is considered an enzyme specific liver. However, some authors state that the TGP can rise also in cases of muscle injury. Furthermore, there are reports in the literature suggesting the association of idiopathic inflammatory myopathies (IIM) with viral hepatitis.Objective: To determine the frequency of abnormal liver function tests in patients with idiopathic inflammatory myopathies, evaluate possible associationsto liver diseases, determine its relationship with elevation of muscle enzymes and whether these patients have particular clinical and / or serological characteristics.Material and Methods: Consecutive patients older than 16 years diagnosed with DM / PM according to Bohan and Peter criteria during 1999-2000 were included. Patients with other connective tissue disease (CTD) were excluded. Demographic data were recorded, characteristics of the disease, laboratory data and elevated liver enzymes and muscle during the course of the disease. Serologic tests were performed for viral hepatitis B and C and confirmatory tests (HBV-DNA and HCV-RNA by PCR). Autoantibodies were determined: ANA (antinuclear antibody) by Hep II, ASMA (anti smooth muscle antibody), AMA (anti-mitochondrial antibodies) and LKM (Liver Kidney Microsomal) by mouse wound, MSA (myositis-specific antibodies) by ELISA. Patients who had abnormal liver tests underwent hepatic ultrasonography. For statistical analysis, descriptive statistics, categorical variables were compared by Fisher's exact test.Results: We included 27 patients, of whom 22 had sufficient data for analysis. Mean age 47.95 years ± 16, 18 female (81.8%) and mean disease duration 8.09 ± 5.6 years. With regard to liver enzymes, 14/22 patients (63.3%) had elevated SGPT and 11/22 (50%) elevated SGOT, 10 of these patients also had elevated SGPT concomitantly. In the 10/15 (66.7%) abdominal ultrasonography showed abnormalities, 8 patients had liver hyperechogenicity, 4 cholelithiasis and 1 patient hepatomegaly. No patient bearing of HBV or HCV. The 8 patients with liver hyperechogenicity matched the 8 patients with isolated elevation of SGPT/SGOT. As for the 10 patients who had both elevated liver enzymes (SGPT and SGOT), only one case could be explained by liver disease (patient ASMA +). However in the 15 cases studied, elevations of SGPT and / or SGOT coincided with outbreaks of myositis,findingconcomitant apparent liver disease in only 9 of them. Conclusions: In this study, elevated transaminases, including the TGP, was observed concomitantly with the activity of myositis. Approximately half of these cases could not be associated with coexisting liver disease, which could be attributed to injury to muscle secondary to inflammatory myopathy.

Small duct autoimmune sclerosing cholangitis and Crohn colitis in a 10-year-old child. A case report and review of the literature

Autoimmune sclerosing cholangitis is an overlap syndrome characterized by features of both autoimmune hepatitis and primary sclerosing cholangitis, the latter usually involving the large bile ducts. Autoimmune sclerosing cholangitis occurs more often in children than in adults and is frequently associated with inflammatory bowel disease, predominantly ulcerative colitis. We report a unique case of a 10-year-old Danish boy with severe small duct autoimmune sclerosing cholangitis and synchronic Crohn colitis. He was referred with a history of weight loss, abdominal pain, vomiting and diarrhea. Biochemical anomalies included elevated alanine aminotransferase, γ-glutamyl transferase and immunoglobulin G levels and the presence of smooth muscle antibodies and perinuclear antineutrophil cytoplasmic antibodies but normal alkaline phosphatase. Liver biopsy specimen revealed features of both autoimmune hepatitis and sclerosing cholangitis, the latter characterized by acute, hyperplastic and destructive inflammation – granulocytic epithelial lesion – of the small ducts. Magnetic resonance cholangiography was normal. Colonoscopic biopsies showed chronic inflammatory changes of the caecum and the ascending and transverse colon compatible with Crohn disease. Ursodeoxycholic acid and immunosuppressive treatment was initiated and within four weeks of treatment the general condition improved. Normalization of aminotransferase was seen at 21 weeks and γ-glutamyl transferase at 72 weeks after first admittance, while immunoglobulin G remained slightly increased.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1418596609736470