Microsomal Antibodies Research Articles

Frequency and Presentation of Autoimmune Hepatitis and Type of Autoantibodies among Yemeni Patients Attending Private Medical Clinic in Aden Yemen

AbstractBackground: Autoimmune hepatitis is a complex disease that represents a challenge in diagnosis and management due to the diversity of the clinical presentation, now recognized as a relatively rare disease predominantly affecting females.Aim of Study: This study aimed to describe the frequency and presentation of autoimmune hepatitis and type of autoan-tibodies among patients who attend a private clinic in Aden Yemen.Patient and Methods: A prospective study carried out in a private clinic over a period of two years, from June 2016 to June 2018, all of 60 patients had raised liver enzymes and Antinuclear Antibodies (ANA), Anti-Smooth-Muscle Anti-bodies (ASMA) titers 1:80 or above upper limit, Anti Liver Kidney Microsomal (LKM-1). Titer 1:40 or above upper limit, and IgG more than 10 times of normal have been included in this study, all patients rejected liver biopsy.Results: 60 subjects were recruited into study. The sex distribution showed a prominence of female gender (63%) versus (36%) being male. Residency distribution revealed that, the majority of our patients came from shabwa governorate (53.3%). The frequency of chronic hepatitis is 40% while each of acute hepatitis and liver cirrhosis constituted 30% of patients, antinuclear antibodies was elevated in 73.3% anti-smooth-muscle antibodies in 25% while anti liver kidney microsomal antibody was elevated only in 1.6%.Conclusion: Autoimmune hepatitis frequency, presentation and type of autoantibodies among Yemeni patients do not remarkably differ from studies carried out world wide.

Autoimmune hepatitis in 847 childhood-onset systemic lupus erythematosus population: a multicentric cohort study

ObjectiveTo evaluate autoimmune hepatitis (AIH) in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients.MethodsThis retrospective multicenter study included 847 patients with cSLE, performed in 10 Pediatric Rheumatology services of São Paulo state, Brazil. AIH was defined according to the International Autoimmune Hepatitis Group criteria (IAHGC). The statistical analysis was performed using the Bonferroni’s correction (p < 0.0033).ResultsAIH in cSLE patients confirmed by biopsy was observed in 7/847 (0.8%) and all were diagnosed during adolescence. The majority occurred before or at cSLE diagnosis [5/7 (71%)]. Antinuclear antibodies were a universal finding, 43% had concomitantly anti-smooth muscle antibodies and all were seronegative for anti-liver kidney microsomal antibodies. All patients with follow-up ≥18 months (4/7) had complete response to therapy according to IAHGC. None had severe hepatic manifestations such as hepatic failure, portal hypertension and cirrhosis at presentation or follow-up. Further comparison of 7 cSLE patients with AIH and 28 without this complication with same disease duration [0 (0–8.5) vs. 0.12 (0–8.5) years, p = 0.06] revealed that the frequency of hepatomegaly was significantly higher in cSLE patients in the former group (71% vs. 11%, p = 0.003) with a similar median SLEDAI-2 K score [6 (0–26) vs. 7 (0–41), p = 0.755]. No differences were evidenced regarding constitutional involvement, splenomegaly, serositis, musculoskeletal, neuropsychiatric and renal involvements, and treatments in cSLE patients with and without AIH (p > 0.0033).ConclusionsOverlap of AIH and cSLE was rarely observed in this large multicenter study and hepatomegaly was the distinctive clinical feature of these patients. AIH occurred during adolescence, mainly at the first years of lupus and it was associated with mild liver manifestations.

Painless thyroiditis induced by the cessation of a dipeptidyl peptidase-4 inhibitor

We describe the first reported case of painless thyroiditis induced by an abrupt cessation of a dipeptidyl peptidase-4 (DPP-4) inhibitor. A 38-year-old man who had type 2 diabetes mellitus, hypertension, hyperuricemia, and pruritus, was treated with metformin, glimepiride, dapagliflozin, sitagliptin, azelnidipine, trichlormethiazide, febuxostat, and fexofenadine. One year previously, his thyroid-stimulating hormone (TSH) was 1.59 (reference range, 0.34–4.94 U/mL). As his HbA1c value reached to 13%, sitagliptin was switched to dulaglutide. One month later, the HbA1c was 12.3%, TSH was <0.05, FT4 was 3.16 (0.7–1.48 ng/dL), FT3 was 7.79 (1.71–3.71 pg/mL), anti-TSH receptor antibody was 0.7 (0–1.99 IU/L), and thyroglobulin was 159.5 (0–32.6 ng/mL). Additionally, his anti-thyroglobulin and anti-thyroid microsomal antibodies were negative. Thyroid ultrasonography revealed a heterogeneous, hypoechogenic, normal-sized thyroid gland with decreased doppler flow. He was diagnosed with painless thyroiditis and was kept under observation without any change in current medication. One month later, the HbA1c was 12.4%, TSH was 9.06, FT4 was 0.81, FT3 was 2.26, and thyroglobulin was 86.7. Additionally, 2 months later, the HbA1c was 9.8%, TSH was 4.2, FT4 was 1, FT3 was 2.55, and thyroglobulin was 21.92. He continued taking dulaglutide once a week. His thyrotoxicosis disappeared within 3 months without specific drug therapy. Anti-TSH receptor antibody was negative throughout his clinical course. We speculate that the cessation of a DPP-4 inhibitor maybe one of the triggers of painless thyroiditis. However, glucagon-like peptide-1 is not likely a cause for painless thyroiditis because he continues taking dulaglutide once a week to date. Our findings indicate that it is important to examine thyroid function after termination of a DPP-4 inhibitor.

Clarithromycin-Induced Acute Liver Failure (ALF)

Clarithromycin is a macrolide antibiotic widely used to treat respiratory, skin, and soft tissue infections. Although elevated liver enzymes and cholestatic hepatitis have been infrequently reported, comprehensive literature review reveals only 6 cases of clarithromycin-induced ALF (fig 2). 60-year-old male with history of hypertension and hypothyroidism presented to the hospital with acute asthma exacerbation secondary to respiratory tract infection. Complete blood picture, and liver and kidney function tests were within normal limits. Clarithromycin, prednisone and albuterol inhaler were prescribed, and he was discharged. 10 days later, he represented and physical examination revealed stable vital data but soft, diffusely tender abdomen with hypoactive bowel sounds and no peritoneal signs. Laboratory analysis revealed WBC=12.2bil/L, hemoglobin(hb)=14.5 g/dL and platelets=129bil/L, lipase=33 U/L, lactic acid=0.6 mmol/L, ammonia=22 mcmol/L and normal coagulation profile. Figure 1 highlights the trend of liver function tests (LFTs) during hospitalization. CT of the abdomen with contrast, abdominal ultrasound with doppler and echocardiography were all normal. Viral hepatitis panel (anti-HAV, anti-HBs, anti-HBc, HBs antigen, anti-HCV, HCV-RNA, & anti-HEV), autoimmune hepatitis panel (ANA, AMA, smooth muscle antibody, liver-kidney microsomal antibody, and total immunoglobulin) and atypical viruses (HIV, CMV, and HSV) were insignificant. On third day, he developed altered mental status; Hb dropped to 5.5 g/dL, platelets dropped to 35 bil/L and LFTs worsened. Liver biopsy was canceled due to hemodynamic instability and coagulopathy. Massive transfusion was initiated, but despite aggressive resuscitation, the patient had cardiac arrest and expired. On autopsy, histopathologic analysis of the liver revealed diffuse hepatocellular necrosis with occasional sparing of periportal hepatocytes (fig 3) consistent with the prior reported cases and the pattern of idiosyncratic drug induced liver injury (DILI). There was no evident lobular or portal inflammation, fibrosis, viral cytopathic effect, thromboemboli, or malignancy.2304_A Figure 1. Trend of liver function testsProminent eosinophils in the portal tract or lobules can suggest a drug-induced hypersensitivity reaction but are rarely seen in cases of idiosyncratic drug reactions. There are no defined pathognomonic histopathologic findings of DILI and a high index of clinical suspicion in combination with histopathologic findings are needed for the diagnosis.2304_B Figure 2. Reported cases of acute liver failure from Clarithromycin2304_C Figure 3. A: Low power photomicrograph of H&E section of liver showing geographic areas of necrosis and marked sinusoidal congestion. B: High power photomicrograph of H&E stain of liver showing a central vein (*) with adjacent marked sinusoidal congestion and extensive hepatocyte necrosis.

Autoantibody profile in children with Kawasaki disease on long-term follow-up: A prospective study from North India.

To study the profile of autoantibodies on long-term follow-up of children with Kawasaki disease (KD). In this single-center observational cohort study, 50 children who had been diagnosed and treated for KD with a minimum follow-up period of 3years were enrolled. The organ-specific autoantibodies that were assessed in the study included anti-thyroid microsomal antibody (TMA), anti-parietal cell antibody (PCA) and anti-liver kidney microsomal (LKM) antibody. The organ-nonspecific autoantibodies that were studied included anti-endothelial cell antibody (AECA), anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), anti-mitochondrial antibody (AMA) and anti-smooth muscle antibody (SMA). The sample for assessment of serology was taken at a mean follow-up period of 6.41years (±1.95 SD) after diagnosis. Autoantibodies were detected in 11/50 (22%) patients. ANA was detected in three patients, TMA was positive in seven and ANCA was positive in one. These autoantibodies likely develop in children with KD during the acute stage and may persist for many years. There is no concrete evidence to suggest that these children are at increased risk of developing an autoimmune disease in the future. However, there is some justification for prolonged surveillance for development of autoimmune manifestations.

An exploration on the influence of positive simple thyroid peroxidase antibody on female infertility.

The aim of the present study was to explore the influence of positive simple thyroid peroxidase antibody (TPO-Ab) on female infertility. Venous blood was collected on an empty stomach from infertile female patients (all of whom were in line with the World Health Organization's diagnostic criteria for infertility) receiving treatments at The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University from 2014 to 2017 to detect thyroid function and thyroid antibodies [thyroglobulin antibody (TG-Ab), TPO-Ab and thyroid microsome antibody (TM-Ab)]. A total of 529 patients with normal thyroid function, TG-Ab and TM-Ab were included in the present study; they were divided into the positive group (121 cases with positive TPO-Ab) and the negative group (408 cases with negative TPO-Ab). Comparisons of age, body mass index (BMI), basal hormone levels, irregular menstruation, tubal obstruction, premature ovarian failure (POF), endometriosis (EMT) and polycystic ovary syndrome (PCOS) between the two groups of patients were conducted in order to determine whether the differences were statistically significant. The incidence rate of EMT was 39.6% in the positive group and 17.1% in the negative group (P<0.05). The incidence rate of PCOS in the observation group was 43.9%, which was significantly higher than that of the control group (21.3%; P<0.01). The results revealed that the differences in age, BMI, basal hormone levels, irregular menstruation and POF between the two groups were not statistically significant (P>0.05). Finally, the factors that had statistical significance (EMT and PCOS) were stratified by different age groups to compare the incidence rate of positive results among the different age groups, thus concluding which age group was influenced to a greater extent by TPO-Ab. The results indicated that positive TPO-Ab may be associated with PCOS and EMT, though particularly with PCOS. Infertile PCOS patients aged 28–35 years old were influenced more by TPO-Ab than those in other age groups. Thus, it is recommended that thyroid autoantibodies are detected in infertile PCOS females aged 28–35 years old, and treatment should be administered as soon thereafter.

Serum thyroid autoantibodies are not associated with anemia, hematinic deficiencies, and hyperhomocysteinemia in patients with Behcet's disease

Background/purposeOur previous study found that 13 of 63 recurrent aphthous stomatitis (RAS)/Behcet's disease (BD) patients have thyroglobulin antibody (TGA) positivity and/or thyroid microsomal antibody (TMA) positivity (TGA/TMA positivity) but without gastric parietal cell antibody positivity. This study mainly assessed whether the serum TGA/TMA positivity was significantly associated with anemia, hematinic deficiencies, and hyperhomocysteinemia in TGA/TMA-positive RAS/BD patients. Materials and methodsThe mean blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine levels were measured and compared between 13 TGA/TMA-positive RAS/BD patients and 41 gastric and thyroid antibodies-negative RAS/BD patients (Abs־RAS/BD patients) or 126 healthy control subjects. ResultsWe found no significant differences in the mean blood Hb, iron, vitamin B12, folic acid, and homocysteine leve1s as well as no significant differences in the frequencies of blood Hb and folic acid deficiencies and of hyperhomocysteinemia between 13 TGA/TMA-positive RAS/BD patients and 41 Abs־RAS/BD patients. The 41 Abs־RAS/BD patients even had a significantly greater frequency of serum iron deficiency than the 13 TGA/TMA-positive RAS/BD patients. Moreover, although a significant greater frequency of anemia was demonstrated in 13 TGA/TMA-positive RAS/BD patients than in 126 healthy control subjects, there were no significant differences in the mean serum iron, vitamin B12, folic acid, and homocysteine levels as well as no significant differences in the frequencies of serum iron and folic acid deficiencies and of hyperhomocysteinemia between 13 TGA/TMA-positive RAS/BD patients and 126 healthy control subjects. ConclusionThe serum TGA/TMA-positivity is not significantly associated with anemia, hematinic deficiencies, and hyperhomocysteinemia in TGA/TMA-positive RAS/BD patients.

Gastric parietal cell and thyroid autoantibodies in recurrent aphthous stomatitis patients with concomitant oral lichen planus.

Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) have not yet been reported in recurrent aphthous stomatitis (RAS) patients with concomitant oral lichen planus (OLP/RAS patients). This study mainly assessed the frequencies of serum GPCA, TGA, and TMA (GPCA/TGA/TMA) positivities in 44 OLP/RAS patients. The frequencies of serum GPCA/TGA/TMA positivities in 44 OLP/RAS patients, OLP/RAS patients of four different subgroups, 520 RAS patients, and 352 healthy control subjects were calculated and compared. We found that 20.5%, 27.3%, and 31.8% of 44 OLP/RAS patients, 75.0%, 100.0%, and 100.0% of 4 OLP/major-typed RAS (OLP/major RAS) patients, 15.0%, 20.0%, and 25.0% of 40 OLP/minor-typed RAS (OLP/minor RAS) patients, 45.5%, 72.7%, and 54.5% of 11 atrophic glossitis-positive OLP/RAS (AG+OLP/RAS) patients, and 12.1%, 12.1%, and 24.2% of 33 AG-negative OLP/RAS (AG־OLP/RAS) patients had the presence of GPCA, TGA, and TMA in their sera, respectively. OLP/RAS patients and OLP/RAS patients of four different subgroups all had significantly higher frequencies of GPCA/TGA/TMA positivities than healthy control subjects. Moreover, OLP/RAS patients had a significantly higher frequency of TMA positivity than RAS patients, and OLP/major RAS and AG+OLP/RAS patients had significantly higher frequencies of GPCA/TGA/TMA positivities than RAS patients. Furthermore, OLP/major RAS patients had significantly higher frequencies of GPCA/TGA/TMA positivities than OLP/minor RAS patients. For OLP/RAS patients, the concomitant OLP may play a role in causing an increased frequency of TMA positivity, and major RAS and the concomitant AG are contributory factors causing the elevated frequencies of GPCA/TGA/TMA positivities.

Potential triggering factors of acute liver failure as a first manifestation of autoimmune hepatitis-a single center experience of 52 adult patients.

AIMTo investigate potential triggering factors leading to acute liver failure (ALF) as the initial presentation of autoimmune hepatitis (AIH).METHODSA total of 565 patients treated at our Department between 2005 and 2017 for histologically-proven AIH were retrospectively analyzed. However, 52 patients (9.2%) fulfilled the criteria for ALF defined by the “American Association for the Study of the Liver (AASLD)”. According to this definition, patients with “acute-on-chronic” or “acute-on-cirrhosis” liver failure were excluded. Following parameters with focus on potential triggering factors were evaluated: Patients’ demographics, causation of liver failure, laboratory data (liver enzymes, MELD-score, autoimmune markers, virus serology), liver histology, immunosuppressive regime, and finally, outcome of our patients.RESULTSThe majority of patients with ALF were female (84.6%) and mean age was 43.6 ± 14.9 years. Interestingly, none of the patients with ALF was positive for anti-liver kidney microsomal antibody (LKM). We could identify potential triggering factors in 26/52 (50.0%) of previously healthy patients presenting ALF as their first manifestation of AIH. These were drug-induced ALF (57.7%), virus-induced ALF (30.8%), and preceding surgery in general anesthesia (11.5%), respectively. Unfortunately, 6 out of 52 patients (11.5%) did not survive ALF and 3 patients (5.7%) underwent liver transplantation (LT). Comparing data of survivors and patients with non-recovery following treatment, MELD-score (P < 0.001), age (P < 0.05), creatinine (P < 0.01), and finally, ALT-values (P < 0.05) reached statistical significance.CONCLUSIONDrugs, viral infections, and previous surgery may trigger ALF as the initial presentation of AIH. Advanced age and high MELD-score were associated with lethal outcome.

Assessment of thyroid function in children, adults and pregnant and lactating women after long-term salt iodisation measurements.

Universal salt iodisation (USI) has been successfully implemented in China for more than 15 years. Recent evidence suggests that the definition of 'adequate iodine' (100-199 µg/l) be revised to 'sufficient iodine' (100-299 µg/l) based on the median urinary iodine concentration (MUI) in school-age children. The objective of this study was to determine the prevalence of thyroid dysfunction in populations after long-term salt iodisation and examine whether the definition of adequate iodine can be broadened to sufficient iodine based on the thyroid function in four population groups. A cross-sectional survey was conducted in six provinces in the northern, central and southern regions of China. Four population groups consisting of 657 children, 755 adults, 347 pregnant women and 348 lactating women were recruited. Three spot urinary samples were collected over a 10-d period and blood samples were collected on the 1st day. In the study, among the adults, pregnant women and lactating women, the prevalence rates of elevated thyroglobulin antibody and thyroid microsomal antibody levels were 12·4, 8·5 and 7·8 %, and 12·1, 9·1 and 9·1 %, respectively. Abnormally high thyroid dysfunction prevalence was not observed after more than 15 years of USI in China because the thyroid dysfunction rates were all <5 %. The recommended range should be cautiously broadened from adequate iodine to sufficient iodine according to the MUI of school-age children considering the high levels of hormones and antibodies in the other populations. Adults, particularly pregnant women positive for thyroid antibodies, should be closely monitored.

Gastric parietal cell and thyroid autoantibodies in patients with Behcet's disease.

Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) were rarely examined in Behcet's disease (BD) patients. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in 63 BD patients. The frequencies of serum GPCA, TGA, and TMA positivities in 63 BD patients, 19 major-typed recurrent aphthous stomatitis (RAS)/BD (major RAS/BD) patients, 44 minor-typed RAS/BD (minor RAS/BD) patients, 520 RAS patients, and 126 healthy control subjects were calculated and compared. We found that 14.3%, 20.6%, and 20.6% of 63 BD patients, 21.1%, 21.1%, and 26.3% of 19 major RAS/BD patients, 11.4%, 20.5%, and 18.2% of 44 minor RAS/BD patients, 11.5%, 18.5%, and 18.3% of 520 RAS patients, and 1.6%, 2.4%, and 2.4% of 126 healthy control subjects had serum GPCA, TGA, and TMA positivities, respectively. BD, major RAS/BD, minor RAS/BD, and RAS patients all had significantly higher frequencies of serum GPCA, TGA, and TMA positivities than healthy control subjects (all P-values<0.05). However, there were no significant differences in different serum autoantibody frequencies between BD, major RAS/BD, or minor RAS/BD patients and RAS patients. Of 16 TGA/TMA-positive BD patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 87.5%, 6.3%, and 6.3% of these TGA/TMA-positive BD patients had normal, lower, and higher serum TSH levels, respectively. Approximately 35% BD patients have serum GPCA/TGA/TMA positivity. However, BD patients do not have significantly higher frequencies of serum GPCA, TGA, and TMA positivities than RAS patients.

Rheumatic Manifestations in Autoimmune Liver Disease.

Autoimmune liver diseases coexist with rheumatic disorders in approximately 30% of cases and may also share pathogenic mechanisms. Autoimmune liver diseases result from an immune-mediated injury of different tissues, with autoimmune hepatitis (AIH) targeting hepatocytes, and primary biliary cholangitis (PBC) and primary sclerosing cholangitis targeting cholangiocytes. Sjogren syndrome is diagnosed in 7% of AIH cases and serologic autoimmunity profiles are a common laboratory abnormality, particularly in the case of serum antimitochondrial (PBC) or anti-liver kidney microsomal antibodies (AIH). Therapeutic strategies may overlap between rheumatic and autoimmune liver diseases and practitioners should be vigilant in managing bone loss.

Characteristics of autoimmune hepatitis in a sample of Egyptian children

BackgroundAutoimmune hepatitis is a rare liver disease that can be presented aggressively in children. Early treatment can control the hyper immune state and save the liver. The aim of the workTo assess clinical manifestations, biochemical features, and response to immunosuppressive drugs in children with AIH. Methods25 children with AIH, based on the International Scoring Criteria of Autoimmune Hepatitis (IAIHG score system), recruited from Pediatric Hepatology clinic, Benha University Hospitals have been analyzed for their clinical, biochemical features, histological profile and their response to treatment. Results25 children were 15 female (60%) and 10 male (40%) their ages ranged from 3 to 15 years old. The main clinical presentation were jaundice (68.0%), abdominal pain (48.0%), acute hepatic-like illness was the first presentation in (32.0%), hepatomegaly (80.0%), splenomegaly (40.0%) lower limb edema (12.0%), and ascites (12.0%). All patients at first presentations had high serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum immunoglobulin G (IgG). According to the autoantibody profile, all children were classified as AIH type 1 as no patient was seropositive for anti-liver kidney microsome antibody (anti-LKM). Prednisone with or without azathioprine was started and complete remission noticed in 13 (52.0%) while 12 (48.0%) had relapses. ConclusionAIH type 1 was the main type of autoimmune hepatitis in children referred to Benha University Hospitals. Females more affected than boys. The combination of prednisone and azathioprine are effective in abating the inflammatory process in most of the cases. Early diagnosis and treatment of AIH had apparently good outcome in children.

Prognostic factor analysis in 325 patients with Graves' disease treated with radioiodine therapy.

Introduction131I therapy is a choice for Graves’ hyperthyroidism. Several factors that affect the success of 131I treatment in Graves’ disease (GD) patients have been put forward. The aim of this retrospective study was to evaluate the factors influencing the success of 131I therapy and the occurrence of hypothyroidism after 131I therapy.Patients and methodsWe reviewed 325 GD patients, who were well documented out of 779 cases, treated with 131I in the First Affiliated Hospital of Xi’an Jiaotong University between 2010 and 2016. We collected the potential influencing factors, including demographic data (age, sex, family history), iodine intake state, antithyroid drugs (ATD) taking, thyroid texture, complications of hyperthyroidism, physical and laboratory examinations [thyroid weight, effective 131I half-life time (Teff), 24-h iodine uptake rate, tri-iodothyronine, thyroxine, free tri-iodothyronine (FT3), free thyroxine, thyroid-stimulating hormone, thyroglobulin antibody, thyroid microsome antibody, thyrotropin receptor antibody], and final administered dosages according to Quimby formula. The correlations between the prognosis of GD patients and these factors were analyzed by logistic regression analysis.ResultsOut of 325 patients, 247 (76.00%) were treated successfully with radioiodine. GD patients who were cured by 131I therapy were more likely to have smaller thyroid [odds ratio (OR)=0.988, 95% confidence interval (CI)=0.980–0.996, P=0.002], lower FT4 levels (OR=0.993, 95% CI=0.988–0.997, P=0.002), and shorter time of ATD withdrawal before 131I treatment (OR=0.985, 95% CI=0.975–0.996, P=0.002). Hypothyroidism occurred in 132 (41.00%) out of 325 patients. There was an increased risk of early hypothyroidism in patients with lower 24-h iodine uptake (OR=0.964, 95% CI=0.941–0.988, P=0.004), and treated with a lower total dose of iodine (OR=0.892, 95% CI=0.824–0.965, P=0.005) and a higher iodine dose per garm of thyroid tissue (OR=5.414E+14, 95% CI=45.495–6.444E+27, P=0.027).ConclusionOur results showed that 131I treatment was more successful in patients with lower weight of the thyroid, lower free thyroxine level, and shorter ATD taking period. Furthermore, early hypothyroidism after radioiodine treatment was more likely to occur in patients with lower 24-h iodine uptake, lower total dose of iodine, and higher iodine dose per garm of thyroid tissue.

Mauriac Syndrome: A Rare Cause of Lactic Acidosis in the ICU

SESSION TITLE: Student/Resident Critical Care SESSION TYPE: Student/Resident Case Report Slide PRESENTED ON: Tuesday, October 31, 2017 at 04:30 PM - 05:30 PM INTRODUCTION: Tissue hypoperfusion is the most common cause of lactic acidosis in critically ill patients. We present a rare case of persistent lactic acidosis in the absence of tissue hypoperfusion after resolution of diabetic ketoacidosis (DKA) in a patient with long standing uncontrolled diabetes mellitus type-1 (DM-1) due to glycogenic hepatopathy (Mauriac syndrome). CASE PRESENTATION: A 19-year-old male with uncontrolled DM-1 and recurrent DKA presented with abdominal pain, nausea and vomiting. Physical exam was normal except for mildly tender hepatomegaly. He was in DKA and was started on intravenous insulin in the intensive care unit. Lactic acid on presentation was 2.5 mmol/L, but increased to 7.5 mmol/L after resolution of DKA. Insulin drip was restarted and he was managed empirically for suspected sepsis. Abdominal ultrasonography demonstrated hepatomegaly with a liver span of 20 cm. Antibiotics were discontinued after a negative infectious work-up. However, the patient had persistent lactic acidosis. Liver enzymes, bilirubin, albumin and coagulation studies were normal. The patient was transitioned to subcutaneous insulin. He had documented hepatomegaly for 3 years. Hepatitis profile, thiamine level, alpha 1 antitrypsin, ceruloplasmin, Anti Nuclear Antibody, Extractable Nuclear Antigen antibody screen, anti-smooth muscle antibody, anti Liver Kidney Microsomal antibody, rheumatoid factor, anti-CCP antibody, anti-tissue transglutaminase were all negative. Liver biopsy showed edematous hepatocytes with glycogenated nuclei. Periodic Acid Schiff stain showed intense staining of glycogen in the hepatocytes with diastase pretreatment showing disappearance of glycogen. There was no steatosis, inflammation, fibrosis, necrosis or Mallory bodies. A diagnosis of glycogenic hepatopathy was made and the patient was sent home on insulin. DISCUSSION: Glycogenic hepatopathy is an under-recognized reversible cause of infiltrative hepatomegaly and lactic acidosis in patients with poorly controlled diabetes. The concomitant presence of persistent hyperglycemia and insulin leads to hepatic glycogen storage. Clinical features in adults include abdominal pain, nausea, vomiting, hepatomegaly, and lactic acidosis. Lactic acidosis is due to decrease in gluconeogenesis and failure to convert pyruvate into glucose and can be acutely worsened by high dose insulin. Liver biopsy is the definitive method of diagnosis. Rigorous glucose control reverses this condition. CONCLUSIONS: Awareness of glycogenic hepatopathy should help the clinician to not treat lactic acidosis based on numbers and expose patients to unnecessary sepsis treatment in the right clinical setting. Reference #1: Ross, J. J., et al. (2011). “Interactive medical case. A sweet source of abdominal pain.” N Engl J Med 364(15): e30 Reference #2: Deemer, K. S. and G. F. Alvarez (2016). “A Rare Case of Persistent Lactic Acidosis in the ICU: Glycogenic Hepatopathy and Mauriac Syndrome.” Case Rep Crit Care 2016: 6072909. DISCLOSURE: The following authors have nothing to disclose: Aditya Kotecha, Dongping Shi, Mohamed Siddique, Saraschandra Vallabhajosyula, Vivek Iyer, Geetha Krishnamoorthy No Product/Research Disclosure Information

The Dangers of Herbal Supplements: A Case of Acute Liver Injury From Fenugreek

Fenugreek (Trigonella foenum-graecum) is a long established medicinal plant traditionally recommended for increasing milk production in lactating women. However, research has discovered antioxidant and anti-inflammatory properties, among others. Despite an abundance of benefits, the toxic profile of Fenugreek continues to increase as more studies uncover unintended toxicological effects. Hepatotoxicity has been noted, including necrosis of liver hepatocytes, acute hepatitis and early liver degeneration. A 34 year old healthy female three months after uncomplicated vaginal delivery presented with acute onset right upper quadrant abdominal pain beginning hours prior to arrival and associated with emesis. Prior to presentation, patient reported mild difficulty with lactation for which she had been taking Fenugreek to enhance her milk production for the past 8 weeks. Patient denied alcohol use and was not taking any other medications. During her hospital course, AST/ALT levels peaked at 5720/2164. Her physical exam revealed tenderness to palpation of right upper quadrant with no organomegaly, no signs of peritonitis, and no jaundice or icterus. A CT abdomen and pelvis with contrast revealed subhepatic fluid consistent with acute liver injury without significant dilatation of common bile duct or stones visualized; findings from right upper quadrant ultrasound were similar. All viral causes of hepatitis were excluded; viral serologies were normal, as well as iron studies, ceruloplasmin and quantitative immunoglobulin levels, kappa/lambda ratios, microsomal antibody assays, mitochondrial antibody, smooth muscle antibody, and ANA. Patient was monitored over several days and treated conservatively with pain control; Fenugreek was discontinued on presentation to emergency room. Liver enzymes continued to downtrend without further intervention. Patient was discharged home and told to avoid any herbal supplements indefinitely. This case illustrates the potential hepatotoxic effects seen with Fenugreek use as well as the necessity to consider this supplement as an etiology of liver injury. In a patient with acute liver injury in the absence of common causes of acute hepatitis, it behooves clinicians to take a thorough history, including over-the-counter remedies since no such supplements are currently federally regulated. Additionally, there is no monitoring system to track side effects, requiring clinicians to broaden their understanding of commonly used supplements.Figure: Subhepatic fluid consistent with acute liver injury.Figure: Trend of LFT's and transaminases over hospital course.

Acute Hepatitis Due To Garcinia Cambogia, An Herbal Weight Loss Supplement

Introduction: Garcinia Cambogia(GC) is a tropical fruit and its extract is sold as a weight loss supplement. The most important ingredient is hydroxycitric acid(HCA) which blocks adenosine triphosphatase citrate lyase, a catalyst important in fatty acid and cholesterol synthesis. HCA was one of the main components of hydroxycut products recalled after Food and Drug Administration received report of 23 cases of hepatotoxicity. Currently sold as GC, hepatotoxicity has again been reported, including cases of fulminant hepatic failure. We present a case of acute hepatitis due to GC. Case presentation: A 57-year-old female with no previous history of liver disease presented to the hospital due to abdominal pain and vomiting. Physical examination was significant for diffuse abdominal tenderness without any rigidity or guarding. Laboratory evaluation revealed an alanine aminotransferase (ALT) of 738 U/L, aspartate aminotransferase (AST) of 856 U/L and an alkaline phosphatase of 80 U/L, with normal bilirubin and prothrombin time. She had been taking vitamins A and D and GC for weight loss, and she was on no prescription medications. She had normal Vitamin A and D levels ruling out hypervitaminosis as the cause of hepatitis. Further testing revealed the following negative results: alcohol and acetaminophen levels, iron profile, anti nuclear antibody, acute viral hepatitis panel, smooth muscle antibody, and liver kidney microsomal antibody. Abdominal ultrasound showed a normal liver. She was asked to stop taking GC. Her liver enzymes decreased significantly with an ALT of 396 U/L and AST of 138 U/L within three days with resolution of her abdominal symptoms. Discussion: GC, is a culinary agent in South East Asia, and its extract is sold for weight loss and lipid lowering. A meta analysis of 9 randomized controlled trials of GC for weight loss found that it causes modest short term weight loss with gastrointestinal side effects. Cases of acute hepatitis including fulminant hepatic failure requiring liver transplantation have been reported due to GC. There is a misconception that herbal supplements are safe, but the Drug Induced Liver Disease Network reports dietary supplements as one of the important causes of drug induced hepatotoxicity. Acute hepatitis is a reversible side effect of GC, which if not identified in a timely fashion, can lead to fulminant hepatitis. Obtaining history of herbal supplement use is important in the evaluation of acute hepatitis.

Evolution of correlation between Helicobacter pylori infection and autoimmune liver disease.

The present study was planned to evaluate correlation between Helicobacter pylori (HP) infection and autoimmune liver disease (AILD). A total of 60 patients diagnosed with AILD in Affiliated Hospital of Binzhou Medical College were continuously enrolled in the present study. HP infection was detected by 13C-urea breath test. The levels of anti-myeloperoxidase were tested by ELISA. The positive rate of anti-nuclear antibody (ANA), anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (SMA) and anti-neutrophil cytoplasm antibody (ANCA) were tested by indirect immunofluorescence. The positive rates of anti-mitochondrial antibody (AMA-M2), anti-liver-kidney microsomal antibody (LKM-1), anti-liver cytoplasm antibody I (LC-1) and anti-soluble liver antigen/liver-pancreas antigen (SLA/LP) were tested by immunoblotting. Liver function indexes including alanine transaminase, aspartate transaminase, alkaline phosphatase and glutamyltransferase, were analyzed with a fully automatic biochemical analyzer. The levels of serum cytokine IFN-γ, interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) were tested by ELISA. A total of 37 patients (61.67%) were observed to be HP-positive. MPO-positive rate, positive rate of ANA, AMA, SMA and ANCA and positive rate of AMA-M2, LKM-1, LC-1 and SLA/LP in patients with positive HP infection were significantly higher than those of patients with negative HP infection. On the other hand, the levels of liver function indices did not showed any significant differences among HP-positive cases or HP-negative cases. However, the levels of IFN-γ, IL-6, IL-10 and TNF-α in patients with positive HP infection were significantly higher than those of patients with negative HP infection. In conclusion, the positive infection rate of HP infection in patients with AILD is high and is closely associated with various positive immune antibodies as well as cytokine levels.

Repairing effects of ICAM-1-expressing mesenchymal stem cells in mice with autoimmune thyroiditis.

The aim of the present study was to determine the repairing effects of intercellular adhesion molecule (ICAM)-1-expressing mesenchymal stem cells (MSCs) in mice with autoimmune thyroiditis. Following induction of an experimental autoimmune thyroiditis (EAT) model, mice were randomly divided into the following groups (n=10 each): i) Normal control; and experimental groups that were subject to EAT induction, including ii) EAT model; and iii) primary MSC; iv) C3H10T1/2/MSC; v) C3H10T1/2-MIGR1/MSC; and vi) C3H10T1/2-MIGR1-ICAM-1/MSC, which were all administered the relevant cells. MSCs were administered via the caudal vein. A blood sample was harvested from the angular vein of each animal 28 days post-treatment and ELISA was used to determine the serum total triiodothyronine, total thyroxine (T4), thyroid-stimulating hormone (TSH), anti-thyroid peroxidase (TPOAb), anti-thyroid microsomal (TMAb) and anti-thyroglobulin (TGAb) antibodies. Hematoxylin and eosin staining was performed to evaluate injury of the thyroid gland by determining the size of the follicle, inflammatory infiltration, colloidal substance retention and epithelial injury. Reverse transcription-quantitative polymerase chain reaction was performed to determine the mRNA expression of interleukin (IL)-4, IL-10, IL-17 and interferon (INF)-γ. Western blot analysis was performed to determine the expression of p38 mitogen-activated protein kinase (p38) and extracellular signal-regulated kinase (ERK). To observe cellular migration in vivo, mice were divided into the following groups, (n=10 each), which were subject to EAT induction: i) CM-DiI-labeled primary MSC; ii) CM-DiI-labeled C3H10T1/2/MSC; iii) CM-DiI-labeled C3H10T1/2-MIGR1/MSC; and iv) CM-DiI-labeled C3H10T1/2-ICAM-1/MSC, which were all administered the relevant cells via the caudal vein. C3H10T1/2-ICAM-1/MSCs were able to ameliorate the expression of T4, TSH, TPOAb, TMAb and TGAb in vivo, attenuate thyroid follicle injury and decrease the splenic index in mice. They were also able to ameliorate the mRNA expression of IL-4, IL-10, IL-17 and INF-γ, and the modulation of the P38 and ERK-signaling pathways in the mouse spleen. Furthermore, ICAM-1 overexpression was able to modulate the nesting of MSCs in the thyroid gland and lung. These findings suggest that C3H10T1/2-ICAM-1/MSC may affect the differentiation, proliferation and migration of immunocytes through modulating the p38 and ERK signaling pathways, and that ICAM-1 may modulate the immunoregulatory effects of MSCs by affecting the migration of MSCs in vivo.

Prevalence and Significance of Autoantibodies in Children With Acute Liver Failure.

The purpose of the present study is to estimate autoantibody (auto-AB) frequency, clinical characteristics, and 21-day outcome of participants in the Pediatric Acute Liver Failure Study Group (PALFSG) by antinuclear antibody, smooth muscle antibody, and liver-kidney microsomal (LKM) antibody status. Auto-ABs were determined at local and/or central laboratories. Subjects were assigned to autoimmune hepatitis (AIH), indeterminate, and other diagnoses groups. Between 1999 and 2010, 986 subjects were enrolled in the PALFSG. At least 1 auto-AB result was available for 722 (73.2%). At least 1 auto-AB was positive for 202 (28.0%). Diagnoses for auto-AB+ subjects were AIH (63), indeterminate (75), and other (64). Auto-ABs were more common in Wilson disease (12/32, 37.5%) compared with other known diagnoses (52/253, 20.6%, P = 0.03). LKM+ subjects were younger (median 2.4 vs 9.1 years, P < 0.001) and more likely to undergo liver transplantation (53.3% vs 31.4% P = 0.02) than other auto-AB+/LKM- subjects. Steroid treatment of subjects who were auto-AB+ was not significantly associated with survival and the subgroup with known diagnoses other than AIH had a higher risk of death. Auto-ABs are common in children with acute liver failure, occurring in 28%. Auto-AB+ subjects have similar outcomes to auto-AB negative subjects. LKM+ children are younger and more likely to undergo liver transplantation compared with other auto-AB+ subjects. Although auto-AB may indicate a treatable condition, positivity does not eliminate the need for a complete diagnostic evaluation because auto-ABs are present in other conditions. The significance of auto-AB in pediatric acute liver failure remains uncertain, but LKM+ appears to identify a unique population of children who merit further study.