Anti-smooth Muscle Antibodies Research Articles

Clinicopathological impact of anti-smooth muscle antibodies in patients with non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a public health burden associated with significant liver-related and unrelated morbidity and mortality [1]. Results of epidemiological studies suggest t...

Autoantibody detection is not recommended for chronic pancreatitis: a cross-sectional Study of 557 patients

BackgroundAutoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a role in non-AIP CP or not was unknown.MethodsHospitalized patients with non-AIP CP from January 2010 to October 2016 were detected for 22 autoantibodies at the time of hospital admission. Autoantibodies with frequency > 0.5% were enrolled to calculate the frequency in historial healthy controls through literature search in PubMed. Differentially expressed autoantibodies were determined between patients and historial healthy controls, and related factors were identified by multivariate logistic regression analysis.ResultsIn a total of 557 patients, 113 cases were detected with 19 kinds of positive autoantibodies, among them anti-β2-glycoprotein I (β2-GPI) antibody was most frequent (9.16%). Compared with historial healthy controls, the frequencies of serum β2-GPI and anti SS-B antibody in patients were significantly higher, while frequencies of anti-smooth muscle antibody and anticardiolipin antibody were significantly lower (all P < 0.05). Multivariate logistic regression analysis result showed that diabetes mellitus (OR = 2.515) and common bile duct stricture (OR = 2.844) were the risk factors of positive β2-GPI antibody in patients while diabetes mellitus in first−/second−/third-degree relatives (OR = 0.266) was the protective factor. There were no related factors for other three differentially expressed autoantibodies.ConclusionsFour autoantibodies were expressed differentially between patients with non-AIP CP and historial healthy controls. Due to limited significance for diagnosis and treatment of chronic pancreatitis, autoantibodies detection is not recommended conventionally unless suspected of AIP.

Permeability of the porcine iris stroma

Current literature has not considered or provided any data on the permeability of the iris stroma. In this study, we aimed to determine the hydraulic permeability of porcine irides from the isolated stroma. Fifteen enucleated porcine eyes were acquired from the local abattoir. The iris pigment epithelium was scraped off using a pair of forceps and the dilator muscles were pinched off using a pair of colibri toothed forceps. We designed an experimental setup, based on Darcy's law, and consisting of a custom 3D-printed pressure column using acrylonitrile butadiene styrene (ABS) plastic. PBS solution was passed through the iris stroma in a 180° arc shape, with a column height of approximately 204 mm (2000 Pa). Measurements of iris stromal thickness were conducted using optical coherence tomography (OCT). To measure flow rate, we measured the mass (volume) of PBS solution using a mass balance in approximately 1 min. Histology was performed using hematoxylin and eosin (H&E) and anti-smooth muscle antibody (anti-α-SMA) for validation. The permeability experiments demonstrated that the iris stroma is a biphasic tissue that allows fluid flow. Our image processing results determined the area of flow to be 7.55 mm2 and the tissue thickness to be between 180 and 430 μm. The hydraulic permeability of the porcine stroma, calculated using Darcy's law, was 5.13 ± 2.39 × 10−5 mm2/Pa•s. Histological and immunochemical studies confirmed that the tissues used for this permeability study were solely iris stroma. Additionally, anti-α-SMA staining revealed staining specific for stromal blood vessels, with the notable absence of dilator and sphincter muscle staining. Our study combined experimental microscopic data with the theory of biphasic materials to investigate the hydraulic permeability of the iris stroma. This work will serve as a basis on which to validate future biomechanical studies of human irides with which may ultimately aid disease diagnosis and inform the design of novel treatments.

High Seroprevalence of Autoantibodies Typical of Autoimmune Liver Disease in Eastern Ethiopia: Is Chewing of Khat (Catha edulis) a Triggering Factor?

Background Recent studies have identified chewing of khat (Catha edulis) as an independent risk factor for liver injury; however, the pathogenetic mechanism remains poorly understood. Case series have found markers of autoimmune hepatitis in patients with khat-related liver disease, suggesting that khat chewing might trigger an autoimmune response. The aims of the present study were (i) to assess the prevalence of autoantibodies typical for autoimmune liver diseases in a healthy population in Ethiopia and (ii) to explore the hypothesis that khat usage triggers autoimmunity. Methods Consenting adults (≥18 years) without known autoimmune disease or manifest liver disease were included. One-hundred-and-sixty-nine individuals with current khat use were compared to 104 individuals who never used khat. Seroprevalence of antinuclear (ANA), antismooth muscle (SMA), and antimitochondrial antibodies (AMA) were determined and compared between the groups using logistic regression models to adjust for age and sex. Results Overall, 2.6% of the study subjects were positive for ANA, 15.4% for SMA, and 25.6% for AMA. When comparing khat users to nonusers, ANA was detected in 4.1% vs. 0% (p=0.047), SMA in 16.0% vs. 14.4% (p=0.730), and AMA in 24.9% vs. 26.9% (p=0.704). ANA was excluded from multivariable analysis since there was no seropositive in the reference group. After adjusting for sex and age, no significant association between khat use and SMA or AMA was found. Conclusions No association between khat usage and the seropresence of SMA or AMA was found, weakening the hypothesis that khat-related liver injury is mediated through autoimmune mechanisms. However, the seroprevalences of AMA and SMA were strikingly high in this Ethiopian population compared to global estimates, suggesting that diagnostic algorithms for autoimmune liver diseases developed in Europe and North America might lead to misdiagnosis of patients on the African continent.

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.

Spatial distribution of smooth muscle tissue in the male pelvic floor with special reference to the lateral extent of the rectourethralis muscle: Application to prostatectomy and proctectomy.

The anatomy of the rectourethralis muscle is essential for performing radical prostatectomy and proctectomy. The rectourethralis muscle is known to continue to the rectal wall posteriorly and to the membranous urethra anteriorly. However, the lateral extent of the rectourethralis muscle remains unclear. This study aimed to verify the hypothesis that the rectourethralis muscle laterally extends and directly adheres to the levator ani. Eight male cadavers were used for macroscopic dissection, and three male cadavers were used for immunohistological analysis using anti-smooth muscle and anti-skeletal muscle antibodies. The rectourethralis muscle laterally extended smooth muscle fibers both superoposteriorly and inferoanteriorly toward the levator ani. The smooth muscle fibers sandwiched the levator ani superoanteriorly and inferoanteriorly. A few smooth muscle fibers of the rectourethralis muscle inserted into the levator ani. This study clarified the spatial distribution of the rectourethralis muscle and its detailed positional relationship with the levator ani. The findings are valuable especially to urologists and anorectal surgeons for dissecting an optimal layer around the urethra and the rectum, and for avoiding rectal or urethral injuries during surgery. Clin. Anat. 31:1167-1176, 2018. © 2018 Wiley Periodicals, Inc.

Investigation of antinuclear antibodies in chronic hepatitis B patients

Antinuclear antibodies (ANA) facilitate the diagnosis and evaluation of patients in many systemic autoimmune conditions. Besides, ANA may also be detected in chronic infectious diseases. Although a number of investigations associated with autoantibody positivity in patients with chronic hepatitis C were reported, autoantibody positivity in patients with chronic hepatitis B remain rarely addressed in the literature. The aim of this study was to evaluate the antinuclear antibody (ANA), antimitocondrial antibody (AMA), anti-smooth muscle antibodies (ASMA) and anti-liver-kidney microsomal antigen (LKM) antibodies in chronic hepatitis B patients. Serum samples were obtained from adult patients with chronic hepatitis B diagnosis according to "European Association for the Study of the Liver (EASL)" criteria. Samples were taken from 47 patients (22 female, 25 male) with treatment-naive, histologically-proven chronic hepatitis B. Cases co-infected with HCV and/or HIV or that also had systemic autoimmune diseases were excluded. As a control group, 30 healthy blood donors were included in the study. Autoantibodies, including ANA, AMA, ASMA and LKM were detected with indirect immunofluorescence (IIF) method (Euroimmune, Lubeck, Germany) and evaluated by fluorescence microscope (Eurostar III plus, Germany). Positive results were graded into 4 levels ( "+", "++","+++" and "++++") from weak to strong Positive samples were studied with a immunoblotting method (ANA Profile 3, Euroimmun, AG) for the detection of extractable nuclear antigen (ENA). The positive results were detected in 8 (17%) of the HBV patients while all the samples were negative in the control group. The difference between the groups was significant (p< 0.05). Among the 47 serum samples tested, none of the patients were positive for AMA, ASMA, LKM. ANA was present in eight of the serum samples in which six were female and two were male patients. Among the IIF patterns of ANA positivity, one mixed pattern (homogeneous and nucleolar) and one cytoplasmic anti-golgi antibody pattern were detected. Positivity grade was ''++''. Other positive patterns were nucleolar (two patients), granular (two patients), ribozomal (one patient) and homogeneous (one patient) and positivity grade was ''+''. ENA was detected in three samples. Two of them was granular pattern positive samples. SS-A was borderline (±) in one and SS-B was borderline (±) in one of the samples. In the mixed pattern positive sample, histon was detected as ''+''. Autoantibody positivity between the patient and control groups were statistically significant (p< 0.05). The difference between autoantibody positivity and gender/age was not statistically significant. In conclusion, autoimmune manifestations may be detected in patients with chronic hepatitis B. Low level titer of antibodies such as ANA, AMA, ASMA or LKM may be present in such patients. An increased frequency of these autoantibodies may be associated with non-autoimmune conditions such as chronic viral infection even in treatment-naive patients.

Strongyloides Infection in Immunocompetent Patient With New Onset Cirrhosis

Infection with Strongyloides is a rarely reported infection in industrialized nations; usually only found in immunocompromised patients. We present a case of a 36 year-old Hispanic male with new onset cirrhosis found to have a Strongyloides infection. He presented with jaundice, abdominal swelling and lower extremity edema. He had moved to Shreveport, LA from Mexico 3 years prior to admission. Patient had no prior medical history. He took no medications, but did drink six beers daily. Patient was found to have a hemoglobin of 4.0 g/dL, WBC of 20,410/uL with eosinophilia, Total Bilirubin 3.3 mg/dL (direct bilirubin 2.1 mg/dL), AST/ALT 66/40 U/L, ALP 402, Iron/TIBC/T-sat 12/243/5%, urine drug screen was cocaine positive, Hepatitis panel, HIV, RPR were negative. Interestingly, ANA and anti-RNP antibodies were positive. IgG was elevated at 1,950 mg/dL. Anti-smooth muscle antibody was elevated at 26 units and anti-mitochondrial antibody was equivocal at 20.4 units. US of the abdomen showed cirrhotic changes of the liver and ascites without biliary dilation. Paracentesis was negative for infection and SAAG >1.1. EGD was performed and showed esophageal and gastric varies. Patient was transfused with packed red blood cells and started on spironolactone, furosemide and propranolol. He clinically improved and was discharged with close follow up for EGD and colonoscopy. After patient was discharged, the result of the serum Strongyloides IgG antibody test returned positive. Strongyloidiasis is more common in tropical regions, but it has an estimated prevalence of up to 1.2-4.9% in the US. Symptoms can range from asymptomatic with mild eosinophilia to disseminated disease in an immunosuppressed host. Most commonly infected individuals live in endemic rural areas and are asymptomatic. Diagnosis can be made either by detecting rhabditiform larvae in the stool or by serologic as in our patient. Treatment includes 2 day course of ivermectin or up to 7 days for disseminated disease. Our patient appears to have an underlying autoimmune disease process, which is unclear. His elevated ALP and elevations in Anti-smooth muscle antibody and Anti-mitochondrial antibody raise concern for autoimmune hepatitis. In literature, AIH shows an inverse relationship with development of Strongyloides infection. However, our patient also consumed alcohol which does correlate with increased incidence of Strongyloides infection.

Fulminant Liver Failure Due to Acute Hepatitis E Infection in an Immunocompetent Male: A Case Report

Hepatitis E Virus (HEV) is a major cause of acute hepatitis and acute liver failure, especially in the developing countries. Hepatitis E virus (HEV) generally causes a self-limited acute infection, although Acute Liver Failure(ALF) can develop in a small proportion of patients (pregnant women and underlying liver disease being at highest risk). We present a case of Fulminant Liver Failure, strictly defined as acute liver injury leading to coagulopathy and altered mentation, due to Acute Hepatitis E infection in an immunocompetent male needing Orthotopic Liver Transplantation (OLT). 58-year-old African American man with past medical history of Diabetes with recent travel to India presented to the hospital with fatigue, nausea and yellowish urine. Initial physical examination showed scleral icterus. Lab investigation revealed elevated liver enzymes (Aspartate transaminase [AST] 13086 U/L and Alanine Aminotransferase [ALT] 6798 U/L), elevated total bilirubin (20.6 mg/dL) and elevated INR (4.5). Hepatitis A, B, C panel were negative, Autoimmune workup ( including Antineutrophil antibody, Anti smooth muscle antibody, Anti mitochondrial antibody) was negative, Toxicology screen was negative. Hepatitis E IgM and IgG were positive, but Hepatitis E RNA Polymerase Chain Reaction (PCR) was negative. He had an acute derangement in mental status overnight with marked confusion and lethargy needing intubation. An Orthotopic Liver Transplant (OLT) was performed on Day 4 of hospitalization. Patient had an initial complicated post-transplant course with eventual full recovery. In the United States, HEV infection is rare, accounting for less than 1% of cases of ALF in adults. Commonly, patients present with acute hepatitis with non specific symptoms. Routine testing for HEV antibodies is usually not performed, especially in the absence of high risk factors like pregnancy or underlying liver disease or immunocompromised status. This poses a risk of delay or even failure to diagnose and appropriately treat cases. Recent reports suggest that acute sporadic HEV infection may account for 5-10% of presumed drug-induced liver injury (DILI) in developed nations. As discussed above, HEV infection can result in a rapidly deteriorating clinical course leading to liver transplantation even in an immunocompetent individual. So it is important to have a high clinical suspicion and a need to take the complete clinical picture into consideration to make a diagnosis of HEV infection.2359_A Figure 1 No Caption available.2359_B Figure 2. Total Bilirubin2359_C Figure 3. INR

A Case of Acute Hepatitis With Co—Infections: Co—Existent Hepatitis E With a Positive Serology for Double Mono

Epstein—Barr virus (EBV), Cytomegalovirus (CMV) and Hepatitis E virus (HEV) are all known to cause mild and usually self—limiting acute viral hepatitis. Acute hepatitis caused by simultaneous presence of two viruses has been reported in literature. However, patients with positive serology for three acute viral infections causing acute hepatitis is very rare. A 23—year—old Caucasian female with an unremarkable past medical history presented with one—week duration of nausea, vomiting, generalized abdominal pain, fever and one day duration of scleral icterus and jaundice. The patient had stable vital signs but elevated liver enzymes on admission with AST 385 IU/L, ALT 290 IU/L, Alkaline phosphatase 461 IU/L, Total bilirubin 9 mg/dL and Direct bilirubin of 5.1 mg/dL. White blood cell (WBC) count was 13500/uL. Work up was unremarkable for acute hepatitis A, B & C viruses, Influenza A & B and infectious mono—spot test along with a negative pregnancy test. When Ultrasound and Computed tomography scan of the abdomen was unrevealing a magnetic resonance cholangiopancreatography was obtained and was unremarkable. Anti—mitochondrial antibody, anti—smooth muscle antibody, anti—nuclear antibody, Alpha—1 antitrypsin level and ceruloplasmin level were all un—remarkable. Infectious disease was consulted when the patient became febrile to 102.0 F despite negative work up. Serologic work up for acute EBV, CMV and HEV infections turned out to be positive; with positive PCR for EBV (Table. 1). The patient was subsequently managed conservatively per infectious disease recommendations and improved. She was discharged on her fourth hospital day with a 6 week follow up showing normalization of liver enzymes. The above patient was diagnosed with Infectious mononucleosis with associated acute hepatitis due to EBV infection. Positive CMV serology was thought to be false positive as the patient's CMV PCR titers were low. HEV PCR wasn't obtained but given the significantly elevated bilirubin in combination with positive serology, it was thought to be a true infection. The patient improved only with conservative management. This lead to two important conclusions: (1) If the patient has positive serology concerning for co—infection of EBV, CMV and/or HEV; it should be confirmed via PCR and (2) if the patient truly is co—infected supportive treatment is one management option in immunocompetent patients.3047.tif Figure 1: No Caption available.

Extrapulmonary Hepatic Histoplasmosis Presenting as Chronic Liver Disease: A Case Report

Introduction: Histoplasma capsulatum is the most common endemic mycosis in the United States. Extrapulmonary hepatic histoplasmosis as a primary manifestation is extremely rare. We report a case of histoplasmosis that presented like chronic liver disease with portal hypertension, splenomegaly, esophageal varices, and thrombocytopenia in an immunocompetent adult. Case Description: A 56 year-old Caucasian man from West Virginia who works in construction presented to the hepatology clinic for work up of chronic liver disease. He was initially evaluated by his primary care doctor for complaints of diarrhea and had an EGD performed that revealed esophageal varices. On examination, he was noted to have splenomegaly but no other stigmata of chronic liver disease. A CBC was only remarkable for a platelet count of 86. A CMP was unremarkable with normal liver enzymes. INR was 1.0. Serological work up for liver disease including ceruloplasmin, remote hepatitis panel, iron studies, anti-nuclear antibody, anti-mitochondrial antibody, anti-smooth muscle antibody, and alpha 1 anti-trypsin were normal. A RUQ ultrasound with elastography showed a normal, homogenous liver, splenomegaly and a liver stiffness of F2-F3 indicating moderate fibrosis. EGD was repeated which showed large (>5mm) esophageal varices that were banded. It also revealed moderate portal hypertensive gastropathy. Transjugular liver biopsy was performed that revealed bridging fibrosis with minimal steatosis, no obvious granulomas but loose clusters of histiocytes, and a gomori methenamine silver stain was performed looking for histoplasmosis that highlighted small yeast with budding typical for Histoplasma capsulatum. Histoplasma antibody in the blood was positive. The patient was seen by infectious disease and he was started on oral itraconazole. Discussion: Hepatic histoplasmosis can present as granulomatous hepatitis, as stigmata of portal hypertension, including ascites or varices, or with elevated liver enzymes. The most common hepatic finding on liver biopsy is portal lymphohistiocytic inflammation; discrete hepatic granulomas are seen in less than 20% of involved livers. There are only a few case reports of disseminated histoplasmosis presenting as primary hepatic histoplasmosis. A high clinical suspicion is warranted in patients who present with stigmata of portal hypertension and chronic liver disease with no evidence of cirrhosis, especially if the person lives in or has visited an endemic area.2252 Figure 1. The normal lobular architecture is distorted by bridging fibrosis. The hepatocytes show minimal steatosis. Although well-developed granulomas are not identified, there are loose clusters of histiocytes.

Bactrim-Induced Liver Injury: It Can Happen!

Trimethoprim-Sulfamethoxazole (TMP- SMX) is an antibiotic commonly used to treat a variety of infections including urinary tract infections, cellulitis, gastrointestinal infections, and prophylaxis for infections in HIV infected individuals. The most common adverse effects are hypersensitivity reactions and gastrointestinal upset, however hepatotoxicity in immunocompetent patients is rare. This case outlines an immunocompetent male with elevated LFTs two weeks after starting TMP-SMX. 56-year-old Caucasian male with past medical history of hypertension, hyperlipidemia, alcohol abuse, colon cancer post hemicolectomy and hepatic steatosis presented with transaminitis and jaundice. Three weeks prior he was started on TMP-SMX at an urgent care for arm cellulitis. Initially he began to experience fever and fatigue followed by pale colored stools and diarrhea. Outpatient Influenza testing was negative. Laboratory data revealed alkaline phosphatase 750 U/L, aspartate aminotransferase 339 U/L, alanine aminotransferase 857 U/L, total bilirubin of 19.2 mg/dl, international normalized ratio 1.2. Hepatitis A IgM antibody, hepatitis B surface antigen and antibody, hepatitis B IgM core antibody, hepatitis C antibody were non-reactive. Antimitochondrial antibody, cytomegalovirus, human immunodeficiency virus, Epstein Barr virus, anti-smooth muscle antibody, ceruloplasmin level, acetaminophen level and antinuclear antibody were all negative. Liver ultrasound demonstrated patent hepatic vasculature with normal waveforms and hepatic steatosis. Due to the timing of TMP-SMX initiation and onset of symptoms it was concluded that this was probable drug induced liver injury from TMP-SMX use in the setting of hepatic steatosis and chronic alcohol intake. During the hospital stay, liver function tests continued to trend down. Patient was discharged with outpatient follow up. TMP-SMX can cause hepatic injury ranging from transaminitis to liver failure. It can cause injury through hepatocellular injury, hepatocellular and cholestatic injury, or bile duct injury. This can occur within days to months of starting TMP-SMX. Although liver injury is rare with TMP-SMX use in an immunocompetent patient, this case illustrates the importance of a detailed history, physical and early identification of agents causing liver injury.

Rare Post-Infectious Autoimmune Hepatitis-Induced Liver Failure: A Consequence of HAV Infection

Autoimmune Hepatitis (AIH) is a chronic liver hepatitis of unclear etiology. Rarely AIH can be triggered by viral hepatitis, especially Hepatitis A virus(HAV), Hepatitis B, Hepatitis C and Hepatitis E virus(HEV). We present a case of AIH which developed in a patient with recent HAV infection. 45-year-old female from Mexico with past history of traumatic brain injury presented with progressive yellowish discoloration of eyes, headache and confusion. She had been diagnosed with acute Hepatitis A in Mexico 1 month prior to her presentation and had full recovery with supportive management. On presentation her vital signs were normal. She was confused, icteric, and had asterixis. Her ALT and AST were 2869 U/L and 1469 U/L respectively. Total bilirubin was 15.1 gm/dL, with a direct bilirubin of 6.2 gm/dL, INR 1.6 and Ammonia 55 μmol/L. Her initial MELD (Model for End-Stage Liver Disease) was 22. Work up for etiologies of chronic liver disease showed a ferritin of 1657 ng/mL and IgG 2580. Her ANA, anti-mitochondrial antibody (AMA), anti-smooth muscle antibody, P-ANCA, C- ANCA, Anti-LKM1 antibody were negative. Ceruloplasmin and Alpha-1 antitrypsin levels were normal. Anti HAV IgM, HEV IgG and IgM were positive, but HEV RNA was undetectable. Abdominal ultrasound and CT scan showed no significant abnormality. Transjugular liver biopsy was performed revealing a portosystemic gradient of 7mmHg and histologic consistent with autoimmune hepatitis (panlobular hepatitis with abundant portal and perivenular lymphoplasmacytic infiltrate). She was started on oral prednisone and azathioprine. Her liver enzymes and liver function improved. After 1-week MELD score improved to 16. She was discharged on a prednisone taper. At 6 months follow-up she had normal liver enzymes and synthetic function, and HEV IgM and IgG remained positive. HAV infection is common but development of post viral hepatitis AIH is unusual. We describe a patient with acute autoimmune hepatitis after HAV infection. HAV infection can rarely act as a trigger for autoimmune hepatitis by initiating a self-perpetuating immune-mediated liver inflammation and can present acutely after resolution of viral hepatitis. Although other viral hepatitis markers were positive(HEV) raising the concern for coinfection, she had no HEV viremia. It is crucial to differentiate between acute viral hepatitis and AIH since their treatment is different and recognize the potential for immune mimicry in acute immunologic flares.

A Case of Isolated Direct Hyperbilirubinemia Associated with High Dose Cytarabine

Cytarabine is one of the chemotherapy agents used to treat myelodysplastic syndrome, and its use can lead to isolated direct hyperbilirubinemia. 54 year old man with MDS s/p AI induction and HIDAC cycle 1 day 10 presented with fever of 102, diffuse abdominal pain, and diarrhea. Physical exam revealed jaundice and mild LUQ and RUQ abdominal tenderness. Labs revealed neutropenia, total bilirubin 7.2, direct bilirubin 5.4, AST 19, ALT 41, alk phos 70. Abdominal US did not show cholelithiasis. Abdominal Doppler US showed patent hepatosplenic vasculature. CT A/P showed diffuse circumferential thickening of multiple mid to distal small bowel loops which may be secondary to infectious enteritis. The patient's bilirubin continued to rise, peaking 6 days after admission at 15.7 and transaminases remained normal to mildly elevated (Figure 1). Other labs including ANA, anti-smooth muscle antibody, mitochondrial antibody, hepatitis A, B, and C, cerulopasmin, immunoglobulins, anti-SLA, and alpha-1 anti-trypsin were negative. Liver biopsy showed benign hepatic parenchyma. Patient was treated with Meropenem for neutropenic enterocolitis. After neutropenia improved, bilirubin trended down (Figure 2), and patient was discharged on day 16. Several case reports have described severe isolated hyperbilirubinemia following the use of high dose cytarabine in the treatment of hematologic malignancies. Aside from isolated direct hyperbilirubinemia, patients present with neutropenia, and can have fever, abdominal pain, and diarrhea during the second week of therapy. Concomitantly, they are diagnosed with neutropenic entercolitis. The mechanism of action for the isolated hyperbilirubinemia is not known but is likely similar to the pathogenesis of neutropenic enterocolitis, where cytarabine has cytotoxic effects on the gastrointestinal mucosa leading to hyperpermeability of the mucosal barrier. Cytarabine may have a similar effect on the gallbladder mucosa, leading to bile leak age and isolated hyperbilirubinemia. Despite the use of percutaneous drainage, the hyperbilirubinemia does not resolve as expected and improves after neutropenic recovery, suggesting the mechanism is not only secondary to cholestasis but related to the integrity of gallbladder mucosa. This case highlights another rare presentation of isolated hyperbilirubinemia with the use of HIDAC and illustrates the timeline of hyperbilirubenima after intiation of HIDAC and its resolution after neutropenia recovery.1354_A.tif Figure 1: Liver enzyme course since treatment with high dose cytarabine. Left Y axis for alkaline phosphatase, ALT, and AST. Right Y axis for total bilirubin and direct bilirubin.1354_B.tif Figure 2: Trend of white blood cells, total bilirubin, and direct bilirubin since treatment with high dose cytarabine. Left Y axis for WBC, and right Y axis for total and direct bilirubin.

Drug-Induced Autoimmune Hepatitis in a Patient Treated With Minocycline: A Rare Adverse Effect

Minocycline is an oral broad-spectrum tetracycline antibiotic that is used to treat moderate to severe acne vulgaris as well as certain sexually transmitted infections. Minocycline-induced autoimmune hepatitis can be differentiated from “classic” autoimmune hepatitis by the patient's swift recovery after discontinuing the offending drug and no relapse of the condition upon discontinuation of treatment with corticosteroids. A 31-year-old Chinese woman, with past medical history of acne vulgaris, presented to the Emergency Department with nausea, vomiting, and abdominal pain for the last 3-4 days. She had experienced three episodes of non-bloody, non-bilious vomiting. She described a persistent dull aching pain in the right upper quadrant of the abdomen that had been increasing in intensity, particularly over the last two days. She denied any recent change in her diet. She reported that no one in her household had experienced similar symptoms. She denied any additional recent symptoms. Upon medication reconciliation, it was discovered that the patient had been taking minocycline, on her own and not under medical supervision, for the past three months. Initial laboratory testing was remarkable for significantly elevated transaminase levels with aspartate aminotransferase (AST) of 718 U/L (10-35 U/L) and alanine aminotransferase (ALT) of 1138 U/L (10-55 U/L). An autoimmune workup revealed an elevated antinuclear antibody (ANA) titer (1:160) (<1:40), positive anti-smooth muscle antibodies (ASMA), and the finding of hypergammaglobulinemia (3.2 g/dL) (0.7-1.6 g/dL) with elevated levels of serum immunoglobulin G (IgG) (3176 mg/dL) (700-1600 mg/dL). The bilirubin levels decreased steadily from Day 1 of the hospital admission, but the transaminase levels continued to rise despite discontinuation of the minocycline (Figure 2). On Day 7, she was started on treatment with prednisolone. Also, an IR-guided liver biopsy was performed for the purpose of confirming the diagnosis as well as to assess the degree of liver injury (Figure 3). After two days of treatment with prednisolone, the patient's transaminase levels began to decrease steadily (Figure 2). Physicians should be informed about and suspect drug-induced hepatitis for any individual taking minocycline who presents with elevated LFTs. Physicians who prescribe it to treat acne vulgaris should be aware of this potentially severe adverse effect and stop it immediately when suspicion is raised.2316_B Figure 2. Changes in total bilirubin and alanine aminotransferase (ALT) before and after treatment with prednisolone *Prednisolone, at an initial dose of 50 mg/day, was started on Day 7 of the hospital admission.2316_C Figure 3. Figure 3 (A, B, C, D; left to right). Histopathologic images of the patient's drug-induced hepatitis from liver biopsy A) Piecemeal necrosis. There is chronic inflammation in the portal tracts. H&E stain. 100x. B) Again, there is chronic inflammation in the portal tracts with many plasma cells, lymphocytes, and occasional eosinophils. H&E stain. 400x. C) and D) Spotty necrosis. There is mild chronic inflammation in the portal tracts, as well as ballooning degeneration of hepatocytes indicative of hepatocellular injury. H&E stain. 100x and 400x, respectively.2316_A Figure 1. Abdominal ultrasound There is mild hepatomegaly with increased liver echogenicity.

Fever and Transaminitis: A Case of Carbamazepine Hypersensitivity Reaction Associated With Human Herpes Virus 6 Reactivation

Introduction: Carbamazepine is an aromatic anticonvulsant commonly used for the treatment of epilepsy and trigeminal neuralgia. Carbamazepine has been associated with hepatotoxicity ranging from mild transaminitis to fatal liver failure. Here, we highlight a rare case of carbamazepine hypersensitivity reaction associated with human herpesvirus 6 (HHV-6) reactivation. Case Description: A 60-year-old woman presented with a 2-week history of fevers, chills, fatigue, and myalgias. Approximately 3 weeks prior, she had been initiated on carbamazepine for left glossopharyngeal neuralgia. In the ED, she was febrile to 39.5 C. Laboratory workup revealed hemoglobin 14.1, leukocytes 5.5, creatinine 0.74, ALT 474, AST 562, alkaline phosphatase 148, total bilirubin 0.8, albumin 3.9, and INR 1.1. Acetaminophen and ethanol levels were unremarkable. An infectious work-up including urinalysis, chest x-ray, and blood cultures was negative. Abdominal ultrasound demonstrated normal hepatic echotexture, no focal masses, and normal gallbladder and biliary tree. After admission, she continued to have high-grade fevers to 39.4 C. Additional laboratory testing including hepatitis virus panel, EBV, CMV, HSV, HIV, tick-borne panel, thyroid function, antinuclear antibody, anti-smooth muscle and antimitochondrial antibodies was unremarkable. HHV-6 PCR was positive. CT chest, abdomen, and pelvis were negative for an infectious, inflammatory, or neoplastic process. Carbamazepine was discontinued and she was initiated on a slow prednisone taper with improvement in her symptoms and liver tests. Discussion: This clinical vignette highlights a case of drug-induced hypersensitivity reaction secondary to carbamazepine. Asymptomatic transaminitis with initiation of carbamazepine is not uncommon and typically resolves with drug discontinuation. Clinically apparent hepatotoxicity is uncommon but can present as drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, which can sometimes progress to acute liver failure and even death. Several case reports have described an association between reactivation of HHV-6 and carbamazepine hypersensitivity syndrome with unclear underlying mechanism. While eosinophilia, lymphadenopathy, and rash are typical features of carbamazepine hypersensitivity reaction that were absent in this case, the time course of symptoms, positive HHV-6, and lack of an alternative diagnosis were consistent with this clinical entity.

Persistent Hepatitis a IgM Antibody: A Clue in the Diagnosis of Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is a condition characterized by persistent inflammation of the liver, associated with a T-cell mediated immune response directed against liver antigens. The presence of underlying genetic predisposition, failure of immune tolerance mechanisms, and the presence of exogenous precipitating stimulus have been linked to its pathophysiology. Hepatitis A (HAV) infection has been described as an environmental trigger associated with AIH development. We describe a patient with previously diagnosed acute HAV, presenting with persistent IgM antibody against Hepatitis A (anti-HAV IgM) who was subsequently diagnosed with AIH. A 56-year-old African-American lady presenting with two-week history of dark urine, pale stools, fatigue, lower extremity edema, and nocturnal pruritus. She had a well-documented prior history of HAV infection two years before, with subsequent resolution of symptoms and laboratory abnormalities. On physical examination, she appeared mildly ill with conjunctival icterus and jaundice. See Table 1 for laboratory results. Her MELD score was 21 upon presentation. Antinuclear antibody and anti-smooth muscle antibody titer were 1/640 and 1/1280, respectively. A liver biopsy demonstrated interface hepatitis with exuberant plasma cell infiltrate, and stage 4/4 fibrosis on trichrome stain, suggestive of AIH. The patient was diagnosed with AIH according to international diagnostic criteria for AIH (Score 17). She received treatment with oral steroids and azathioprine with later normalization of liver function and transaminases after three months of treatment. Anti-HAV IgM could be detected for up to three to six months after acute HAV infection. Our case illustrates the significance of late detection of Anti-HAV IgM more than six months after resolution of acute HAV infection. A study in children aged 6-14 years showed persistent Anti-HAV IgM in more than 20% of patients 12 to 18 months after initial infection. Several case reports (Table 2) have been published of AIH diagnosed seven to sixteen weeks after the initial acute HAV infection. In our case the time interval from initial acute HAV infection to the diagnosis of AIH is much longer, but the sustained anti-HAV IgM response indicates persistent antigenic stimuli, which could play a role in subsequent development of AIH, and facilitate its diagnosis.2265_A Figure 1. Laboratory values before and after treatment of AIH, including prior diagnosis of acute HAV and interval resolution2265_B Figure 2. Prior case reports of AIH diagnosed after documented acute HAV

Autoimmune associations in a Mexican cohort with primary biliary cholangitis

IntroductionSeveral groups have reported associations of primary biliary cholangitis with other autoimmune entities, particularly Sjögren's syndrome and hypothyroidism. Its prevalence and characteristics in Mexican patients is unknown. AimTo determine the frequency and characteristics of autoimmune diseases in a Mexican cohort of patients with primary biliary cholangitis. Materials and methodsThe medical records of patients that presented with primary biliary cholangitis within the time frame of 2005 and 2012 were reviewed and assessed for other autoimmune diseases. ResultsSeventy-eight patients, 75 women and 3 men, were included. Their mean age was 55.8 years. Seventy-three cases had positive antimitochondrial antibodies (94.8%) and disease was confirmed in 5 through liver biopsy. Five patients (8%) had anti-smooth muscle antibodies and 55/78 (70.5%) had antinuclear antibodies by indirect immunofluorescence. Forty-nine patients (62.8%) were positive for an autoimmune disease other than primary biliary cholangitis. Among those, 20 patients had one associated disease, 14 had 2, and 15 patients had 3 concomitant diseases. They included: Sjögren's syndrome in 23/78 patients (29.5%), dysthyroidism in 21/78 cases (26.9%), Raynaud syndrome in 11/78 (14.1%), CREST syndrome in 9/78 patients (11.4%), rheumatoid arthritis in 6/78 patients (7.7%), vitiligo in 5/78 (6.4%), scleroderma in 4/78 patients (5.1%), and other diseases in 8 patients. In 12/78 patients (15.4%), there was a documented family background of autoimmune disease. ConclusionsThe presence of autoimmune associations in our cohort was frequent, and similar in characteristics to the information reported by other groups. The clinical implications of those findings remain to be determined.

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.