Anti-smooth Muscle Antibodies Research Articles

Lack of Any Relationship Between Circulating Autoantibodies and Interleukin–6 Levels in Egyptian Patients Infected with the Hepatitis C Virus

Introduction:Elevated serum interleukin (IL) 6 has been reported in patients infected with the hepatitis C virus (HCV), but it remains debatable whether this influences the production of autoantibodies and the biochemical profile of HCV disease. Therefore, this current study was conducted to evaluate the relationship between IL-6 and circulating autoantibody levels in HCV positive patients.Methods:Levels of IL-6 in serum samples from 102 patients with HCV and 103 normal controls were determined by enzyme linked immunosorbent assay (ELISA). Autoantibodies were detected by immunofluorescence.Results:Levels of IL-6 were significantly higher (p=0.028) in patients infected with (HCV) compared with normal group. Autoantibodies were noted in in 43.1% of the patients; of these, 23.5% featured anti-nuclear antibodies (ANA+), 16.7% anti-smooth muscle antibodies (ASMA+), 7.8% anti-mitochondrial antibodies (AMA+), 17.6% anti-parietal cell antibodies (APCA+), 7.8% anti canalicular antibodies, and 2.9% anti reticulin antibodies (ARA+). No patients were found to be positive for anti-brush border antibodies (ABBA) or anti-ribosomal antibodies. (ARiA). No links with IL-6 levels were apparent.Conclusions:IL-6 levels are increased in patients infected with HCV disease and could influence the production of autoantibodies. However, this study did not provide evidence of a specific relationship between IL6 and circulating autoantibodies in such cases.

Brain Atrophy, Anti-Smooth Muscle Antibody and Cognitive Impairment: An Association Study.

Cortical atrophy, neuronal loss, beta-amyloid deposition, neuritic plaques, and neurofibrillary tangles are neuropathological key features in the Alzheimer's disease (AD). Antibodies against beta-amyloid, neurotransmitters, microvascular endothelium components and microglial cells have been detected in AD serum suggesting that AD could be another autoimmune disease and provides a link between vascular pathology, endothelium dysfunction and neuronal cells death. Aim of the present study was to evaluate the association between autoantibody profile and cognitive impairment in geriatric patients, accounting for ApoE genotype as a potential confounding factor. Three hundred and forty-four geriatric patients, attending the clinic for the cognitive decline, underwent a biochemical and immunological profile, chest X-ray, cerebral computed tomography scan and complete cognitive evaluation. All patients were also screened for the ApoE genotype. A significantly higher prevalence of Anti-Smooth Muscle Antibody (ASMA) positivity was found in 89/204 (43.63%) patients with diagnosed neuroradiological signs of cerebral atrophy compared with 15/140 (10.71%) patients without the condition (p<0.001). Multivariable logistic model evidenced that such association was independent of patient's age, gender and Mini-Mental State Examination (OR=8.25, 95%CI: 4.26-15.99) and achieved a good discriminatory power (c-statistic=0.783). Results were also independent of ApoE genotype, which resulted not associated both with the presence of brain atrophy and with the presence of ASMA positivity. Our results shows a strong association between brain atrophy and ASMA positivity and are consistent with several studies that focused attention on the mechanisms of endothelial immune response in the development of dementia.

Autoimmune Hepatitis in Association With Sofosbuvir.

Sofosbuvir in combination with ribavirin was approved by the Food and Drug Administration as a treatment option for hepatitis C (HepC) in 2013. We describe a case of autoimmune hepatitis triggered in a patient on therapy with sofosbuvir and ribavirin. A 65-year-old woman with a medical history of diabetes mellitus, hypertension, and HepC (genotype 2) underwent pretreatment liver biopsy in May 2012, which demonstrated mild chronic active hepatitis with focal piece-meal necrosis and mild stage 1 periportal fibrosis with no increased iron deposition. No features of autoimmune hepatitis were seen on biopsy. The patient was administered 400 milligrams (mg) sofosbuvir and weight-based 1000 mg ribavirin for a planned duration of 12 weeks. Liver function tests (LFTs) initially improved on therapy; however, 3 weeks after the treatment initiation, the patient started complaining of weakness and fatigue. Repeat tests revealed elevated LFTs. Autoimmune titers were positive for antinuclear antibody, anti-smooth muscle antibody with elevated immunoglobulin (IgG), and serum gamma globulin levels. Repeat liver biopsy in June 2014 showed markedly distorted architecture secondary to formation of nodules completely enclosed by fibrous septa and areas of confluent necrosis with mild to moderate chronic inflammation consisting mainly of lymphocytes and plasma cells along with moderate to severe interface hepatitis. Ballooning degeneration of hepatocytes, with rosette formation possibly associated with regenerative activity was seen, consistent with superimposed autoimmune hepatitis. Based on laboratory and biopsy findings, diagnosis of drug-induced autoimmune hepatitis was made, and the treatment for HepC with sofosbuvir and ribavirin was discontinued. The patient was subsequently administered prednisolone with improvement in LFTs. We describe a patient with autoimmune hepatitis after initiation of sofosbuvir and ribavirin. To our knowledge, this complication has never been reported before in association with sofosbuvir. The most frequent adverse events noticed with this combination regimen have been headache, anemia, fatigue, and nausea.

Non-secreting, Non-fibrotic Hepatocellular Carcinoma in an Average Risk Population

Introduction: Hepatocellular carcinoma (HCC) is the fifth leading cancer worldwide. Non-fibrotic HCC (NFHCC) has been fairly reported especially in chronic hepatitis B infection. Nonetheless, recent epidemiological data indicates an overwhelming 12-42% of HCC arising from NAFLD (Non-Alcoholic Fatty Liver Disease) without cirrhosis or fibrosis revealing unexplored thoughts for carcinogenesis. Herein, we present a case of non-secreting NFHCC in an obese male with no apparent risk factors. Methods: We present a 63 year old Caucasian obese male (BMI 35.2 Kg/m2) with no significant past medical history who sustained injuries during a motor vehicle accident. Subsequently, trauma work up was significant for spinal fracture and an incidental right hepatic lesion. On further questioning, the patient denied alcohol abuse, exposure to toxins or family history for GI malignancy. The physical examination was unremarkable as well liver function test, coagulation profile, viral hepatitis serology, anti-nuclear antibody, anti-smooth muscle antibody, iron profile and alpha-fetoprotein(AFP) level. Results: To further investigate the hepatic lesion, a MRI of the abdomen with IV contrast revealed a 3.8 cm heterogenous lesion with ring enhancement suspicious for malignancy and diffuse steatosis otherwise normal biliary tree and pancreatic duct appearance. Malignancy was confirmed by liver biopsy. Subsequent colonoscopy result was benign.Figure 1Figure 2Figure 3After a discussion with the patient and surgery department, the plan was to proceed with surgical resection of the isolated hepatic tumor. The patient successfully underwent a laparoscopic hand-assisted resection of the segment 6 and 7 of the liver. The final surgical pathology confirmed a moderately differentiated HCC with hepatic steatosis. Conclusion: During the last decades, obesity and type 2 diabetes have strongly been associated to NAFLD related NFHCC driven by diverse intrahepatic cellular mechanisms. To the best of our knowledge, the behavior of non-secreting tumors, those lacking AFP, has not been entirely studied in association with NFHCC attributed to NAFLD. Partial resection of liver may be the appropriate option in a good surgical candidate like our patient or in Child-Pugh A cirrotics. If resected timely, a single HCC lesion in minimally to non-fibrotic liver has been reported to have better overall survival irrespective of tumor size. Finally, screening and management of HCC in apparent average risk populations will continue to be a matter of active debate.

Liver Failure Secondary to Amyloid Light-Chain Amyloidosis

Presentation: A 61 year-old African-American male previously in good health presented with subacute onset of swelling in his abdomen and lower extremities over 2 months. Physical exam was significant for bilateral lower extremity edema, tense ascites, and jugular venous distention. Labs were significant for albumin 2.1 g/dL, alkaline phosphatase (AP) 718 IU/L, AST 158 IU/L, ALT 119 IU/L, total bilirubin (TB) 0.5 mg/dL, INR 1.07, creatinine of 0.9 mg/dL and nephrotic range proteinuria. A viral hepatitis panel, anti-nuclear antibody, anti-smooth muscle antibody, anti-mitochondrial antibody, ferritin, SPEP, and ceruloplasmin were normal. An abdominal CT showed ascites with a possibly nodular liver and no hepatosplenomegaly. Paracentesis revealed a serum albumin ascites gradient > 1.1, and was negative for infection; cytology was negative for malignancy. Transthoracic echocardiogram showed left ventricular hypertrophy concerning for an infiltrative process. A sigmoid biopsy was positive for amyloid and mass spectroscopy performed on the biopsy showed a peptide profile consistent with primary (AL) amyloidosis. The patient was discharged, and was readmitted approximately 1 month later with worsening ascites and new onset jaundice. TB had increased to 21.6 mg/dL, AP to 1317 IU/L, AST to 260 and ALT to 104 IU/L. A transjugular liver biopsy confirmed amyloidosis without significant inflammation or granulomas. No fibrosis or malignancy were identified. The patient's MELD score increased from 14 to 29, and his renal function worsened. Liver transplant was considered, but his multi-organ involvement with amyloid precluded the patient from being listed. He was transitioned to comfort care and died 1 week after discharge in hospice. Discussion: Systemic primary (AL) amyloidosis involves the liver in 60-90% of cases and is commonly clinically silent, characterized by mild abnormalities in liver function with hepatomegaly. However, a subset of patients with AL amyloidosis present with severe cholestatic liver failure. Once jaundice is present, the median survival is 3 months, compared to 2 years in AL amyloidosis patients with liver involvement without jaundice. Liver failure also limits treatment options as potential therapies such as bortezomib and melphalan are metabolized by the liver. Although AL amyloidosis rarely presents with liver failure, this universally fatal entity should be considered by clinicians, and evaluation should be initiated promptly.

A Case of Acute Liver Failure Following Initiation of Valproic Acid

Introduction: Valproic acid (VPA), an anticonvulsant used in the treatment of seizure disorders, migraines, and bipolar disorder, has been shown to cause drug-induced liver injury (DILI) in 5-10% of individuals. Effects can range from subclinical transaminase elevations to acute liver failure and death. Herein, we report a case of acute liver failure 18 days following initiation of VPA. Case Report: A 39 year-old woman with a history of a seizure disorder and schizophrenia treated with olanzapine presented to an outside hospital with breakthrough seizures. She was successfully treated with an anti-epileptic regimen including phenytoin, levetiracetam, VPA and lacosamide and discharged. Two days later she was readmitted to our institution with altered mental status and incontinence. Physical exam revealed orientation only to self, flat affect, and icteric sclera. Labs were significant for pH 7.1, lactate 7.1, AST 282, ALT 343, total bilirubin 2.2 and INR 1.1. A non-contrast head CT was normal. She was treated with IV fluids and IV bicarbonate, and was admitted to the medical ICU. By hospital day 5, her labs revealed AST 2129, ALT 1625 and INR 2.4. Initial serologic testing, including levels for acetaminophen, salicylates, alcohol and carbamazepine, a viral hepatitis panel, toxicology screen, anti-mitochondrial antibody, anti-smooth muscle antibody, HIV, CMV, EBV, HSV, RPR, VZV, and AFP, was negative. A transjugular liver biopsy (Figure) was consistent with VPA induced hepatotoxicity. Despite discontinuing all anti-epileptic medications and initiating IV carnitine, the patient developed ventilator-dependent respiratory failure and acute kidney injury requiring hemodialysis and was listed for liver transplantation. Several weeks following the termination of VPA, the patient's liver associated enzymes and renal function normalized. The patient experienced a recurrent seizure and was restarted on levetiracetam prior to being discharged on hospital day 83. Discussion: The absence of other risk factors, the livery biopsy histology, and the timing of liver injury and recovery are all consistent with VPA-induced acute liver failure. A Roussel Uclaf Causality Assessment Method score of 8 was calculated. The mechanism of toxicity is thought to be due to impairment of liver mitochondrial function. Treatment with VPA requires a high index of suspicion for DILI and early discontinuation of this medication may spare patients from liver transplantation or death.Figure 1

Serological markers of autoimmunity in children with hepatitis A: relation to acute and fulminant presentation.

Hepatitis A virus (HAV) infection tends to be a self-limiting disease without serious sequelae, but fulminant hepatitis, with a high mortality, develops in 0.1-0.2% of the cases. Sometimes, HAV infection precipitates autoimmune hepatitis (AIH). We aimed to assess the frequency and clinical significance of serologic markers of autoimmunity during hepatitis A infection with an acute or fulminant presentation compared with those in AIH. The study included 126 children: 46 with HAV infection (33 with acute and 13 with fulminant presentation), 53 with AIH, and 27 healthy controls. In all, we measured autoantibodies titer (antinuclear antibody, antismooth muscle antibody, and liver kidney microsomal antibody-1) and serum gammaglobulins. Autoantibodies were detected in the majority of HAV (63.1%) and AIH (79.2%) groups, but in none of the controls. Gammaglobulins were significantly higher in the HAV group (1.93±0.57 g/dl) than in the controls (1.32±0.29 g/dl), but lower than that in the AIH group (2.93±1.2 g/dl) (P<0.0001 for all). In the HAV group, gammaglobulins were significantly higher in those with fulminant (2.21±0.46 g/dl) than in those with acute presentation (1.82±0.57 g/dl) (P=0.019), but comparable with that in AIH (P=0.095). Gammaglobulins correlated significantly with disease severity in both HAV and AIH groups. Hypergammaglobulinemia and a high occurrence of autoantibodies are encountered in HAV infection. This may support the immunological basis of its pathogenesis. Moreover, the higher gammaglobulins in fulminant HAV, with an insignificant difference from that in AIH, suggest that a more aggressive immunological reaction is related to this presentation.

Goldenseal Root Powder (Hydrastis Canadensis) Associated Hepatotoxicity

Introduction: The use of herbal supplements has increased in the United States in last decade. It may be associated with significant side effects. We report a patient with hepatotoxicity following ingestion of herbal preparation, Goldenseal root powder. Case report: A 60-year-old female was admitted to the hospital with delusional behavior. A family member had recently noticed that she was jaundiced. The patient had no prior history of liver disease. Her past medical history was significant for paranoid schizophrenia and diabetes mellitus. She denied taking any medication apart from goldenseal root powder for four months prior to admission, for general wellbeing. She did not smoke or drink alcohol. There was no history of drug abuse. Her physical examination was unremarkable apart from icteric sclera. Her liver function test showed total bilirubin of 18.8 mg/dL, direct bilirubin 11.8 mg/dL, aspartate transaminase (AST) 94 U/L, alanine transaminase (ALT) 76 U/L, alkaline phosphatase 1832 U/L, albumin 2.4 g/dL, and INR 1.0. An abdominal computed tomography (CT) and liver ultrasound showed hepatomegaly without signs of cholecystitis or extra hepatic obstruction. Viral hepatitis serology, antinuclear antibody, anti-mitochondrial antibody, anti-smooth muscle antibody, liver/kidney microsome antibodies, ceruloplasmin level, and iron panel were normal. A liver biopsy showed cholestasis with canalicular and intraductular bile plugs, compatible with drug-induced cholestatic hepatitis. The patient's jaundice improved while in the hospital. Patient was instructed to stop using goldenseal root powder. Outpatient follow-up showed continued improvement in her liver function test. Discussion: Herbal medicines are widely perceived by the public as an innocuous health aid. Goldenseal root powder is thought to be hepatoprotective in animal models by inhibiting CYP2E1 enzyme.1 However, some herbal medicines may be associated with hepatotoxicity. Our patient's liver function improved after discontinuation of goldenseal root powder and no other etiology of cholestatic hepatitis was identified. This appears to be the first case report in english literature on goldenseal root powder associated hepatotoxicity. Our case highlights that hepatotoxicity should be considered in anyone taking goldenseal root powder.

A Case Report of IgG4-Related Autoimmune Cholangitis

Introduction: Autoimmune cholangitis is a biliary manifestation of IgG4 related disease (IgG4-RD) which can affect many organs and only rarely occurs in the absence of autoimmune pancreatitis. We present a case of IgG4 related cholangitis and discuss differential diagnosis and the role of clinical, laboratory and radiologic findings in establishing the diagnosis. Methods: N/A. Results: A 66 year old man was sent to the ED from his gastroenterologist's office for 3 weeks of jaundice, lower abdominal cramping, pale yellow stools 3-4 times daily, and dark orange urine. An outpatient abdominal ultrasound showed biliary obstruction and diffuse thickening of the common duct. In the ED, the patient appeared jaundiced but hemodynamically stable. Laboratory studies showed total bilirubin 11, direct bilirubin 8.9, AST 60, ALT 45, ALKP 265, amylase 65, and lipase 278. MRCP showed proximal and distal common bile duct strictures with intrahepatic and common duct dilation, circumferential biliary hyperenhancement, and bilateral striated heterogeneous nephrograms. The combination of these findings suggested the possibility of autoimmune cholangitis. ERCP was not initially performed due the location of the more proximal stricture and the possible risk of bacterial seeding of an obstructed biliary system. IgG4 levels were drawn and the patient was discharged on prednisone 40mg daily. Total IgG level and IgG4 returned elevated at 2641 and 459, respectively. Antinuclear antibody and anti-smooth muscle antibody were negative. After 2 weeks of steroid therapy, total bilirubin decreased to 2.4. Conclusion: IgG4 associated cholangitis was first described in the literature in 1995 and since then, there have been only a few case reports. IAC can further be classified into type 1 or 2; type 1 stenosis is exclusively located in the distal CBD, whereas type 2 stenosis is affects intra- and extrahepatic bile ducts. Diagnosis of biliary strictures with painless jaundice is also concerning for cholangiocarcinoma and pancreatic neoplasm, and these should be ruled out in the process of working up for an autoimmune cause. Steroid therapy is the initial treatment modality and many patients have good response. Changes in LFTs are best seen 5 and 10 days after therapy initiation and earlier initiation of therapy reduces risk of biliary cirrhosis. This case highlights the importance of laboratory and radiologic data in obtaining an accurate diagnosis.

Isolated Extrapulmonary Hepatic and Splenic Sarcoidosis With Hepatomegaly and Symptomatic Massive Splenomegaly

A 28-year-old white male with a history of chronic abdominal pain, GERD and IV drug abuse presented to the Emergency Department complaining of fatigue, abdominal pain, nausea and vomiting for 3-4 months, and rapid weight loss of 90 lbs. CT scan of his abdomen revealed hepatosplenomegaly, portal hypertension and portacaval lymphadenopathy. Initial labs were remarkable for pancytopenia, elevated serum creatinine of 2.9, elevated serum calcium of 12.7, elevated AST of 69 and ALT of 65, and alkaline phosphatase of 506. Hepatitis C antibody was positive with a negative viral load. Due to the concern for underlying malignant process, he underwent endoscopic ultrasound with periportal lymph node biopsy which was nondiagnostic. SPEP was unremarkable, alpha-1 antitrypsin was normal, ferritin was mildly elevated, ceruloplasmin was elevated, ANA was negative, antimitochondrial antibodies weakly positive, ANCA negative, anti-smooth muscle antibody moderately to strongly positive, light chains elevated, the CMV and EBV viral load were negative, HIV was negative, and ACE level was elevated. Pt then underwent bone marrow biopsy, no evidence of a lymphoproliferative disorder was found. Subsequently, a liver biopsy and splenectomy was performed. Pathology revealed diffuse non-necrotizing granulomatous inflammation consistent with sarcoidosis of both the liver and spleen, and a diagnosis of extrapulmonary sarcoidosis was made. Resected spleen weighed 2,022 g easily meeting criteria for massive splenomegaly by weight. Pathology also revealed stage 2-3 fibrosis of the liver, iron staining and AFB staining was negative for mycobacteria in both organs. Pt never had any pulmonary symptoms and multiple chest x-rays failed to demonstrate the hallmark hilar lymphadenopathy and reticular opacities of pulmonary sarcoidosis. Sarcoidosis is a disease of unknown origin, characterized by noncaseating granulomas in involved organs with pulmonary involvement in 90% of cases. Isolated extrapulmonary disease is rare, occuring in only 10% of cases. This patient's presentation with symptomatic massive splenomegaly and pancytopenia in the setting of isolated hepatic and splenic sarcoidosis is very rare. After nearly a month long hospitalization, he was discharged on ursodiol. On follow up, he was then transitioned to prednisone and later to methotrexate with the discontinuation of prednisone due to an elevation in his LFTs. As a result of his treatment, the patient gained back some weight, his liver enzymes decreased to AST of 97 and ALT of 89, alkaline phosphatase decreased to 305, and his pancytopenia completely resolved.Figure 1

Endoscopic Ultrasound: Role in Diagnosis of Hepatic Sarcoidosis

A 46-year-old female presented with shortness of breath, dry cough, and diffuse abdominal pain for one week. She denied issues with weight loss, pruritus, rectal bleeding, or hematemesis. Family history was notable for asthma; there was no family history of lung cancer or sarcoidosis. Physical exam was unremarkable with no cutaneous findings. Significant laboratory values included: aspartate aminotransferase (AST) 48, alanine aminotransferase (ALT) 64, alkaline phosphatase 375, erythrocyte sedimentation rate (ESR) 35, angiotensin-converting enzyme (ACE) 116. Tuberculosis testing, anti-mitochondrial and anti-smooth muscle antibody markers were negative. Due to her unknown etiology of abdominal pain, computed tomography (CT) abdomen and pelvis with contrast was performed showing mild dilatation of the pancreatic duct and a suggestion of a mass in the head of the pancreas (Fig. 1). Magnetic resonance imaging (MRI) of the abdomen confirmed abnormal-appearing confluent soft tissue within the porta hepatis and liver hilum, encircling the patient's main portal vein and extending into the periceliac and gastrohepatic regions. It appeared separate and of different signal intensity than adjacent pancreas and liver. An endoscopic ultrasound (EUS) was performed noting the mass (Fig. 2). Fine needle aspiration (FNA) followed with subsequent analysis. Cytology noted findings consistent with sarcoidosis. CT chest confirmed pulmonary involvement, including mediastinal and hilar lymphadenopathy.Figure 1Figure 2Roughly 50-65% of patients with sarcoidosis have hepatic granulomas on biopsy but only 5-15% of the patients present with symptoms. Unlike traditional cytologic diagnosis of hepatic sarcoidosis via invasive liver biopsy, our patient had an EUS-FNA of a suspicious mass located in the hilum of the liver. Traditionally, bronchoscopy with transbronchial lung biopsy is performed in suspected sarcoidosis patients. If unsuccessful, mediastinoscopy is often performed as the next diagnostic procedure. EUS-FNA provides a nonsurgical alternative by aspirating mediastinal lymph nodes from the esophagus. Our case is unique in that EUS-FNA did not sample mediastinal lymph nodes, but instead sampled the actual mass in the hilum of the liver. Hepatic granulomas may be due to other underlying causes, such as tuberculosis, primary biliary sclerosis, or drug-induced disease. Thus, in suspected cases of hepatic sarcoidosis, liver biopsy is recommended for moderate-severe liver function abnormalities to rule out other causes. EUS-FNA has superior predictive value and lower complication risk than traditional liver biopsy and should be considered as a modality for diagnosis of hepatic sarcoidosis.

Autoimmune Markers Do Not Impact Clinical Presentation or Natural History of Steatohepatitis-Related Liver Disease.

Autoimmune (AI) markers are reported in patients with steatohepatitis-related liver disease. However, their clinical significance is unclear. Charts of patients due to alcoholic liver disease (ALD) or nonalcoholic fatty liver disease (NAFLD) were stratified for antinuclear antigen (ANA > 1:80), antismooth muscle antibody (ASMA > 1:40), or antimitochondrial antibody (AMA > 1:20). Study outcomes were patient survival and complications of liver disease. Of 607 patients (401 NAFLD), information about AI markers was available for 398 (mean age 50 ± 15 year; 52% males; median body mass index (BMI) 38; 44% diabetic; 62% nonalcoholic steatohepatitis (NASH) as type of steatohepatitis; median MELD score 9). A total of 78 (19.6%) patients were positive for AI markers without differences for ALD versus NAFLD, cirrhosis versus no cirrhosis, and NASH versus no NASH. There were no differences for age, gender, BMI, cirrhosis at presentation, MELD score, endoscopic findings, and histology based on AI markers. Serum ALT was higher among patients with AI markers (65 ± 46 vs. 59 ± 66 IU/l; P = 0.048). Data remained unchanged on analyzing NAFLD patients. None of the 11 ANA-positive patients (1:640 in 4) showed findings of AI hepatitis. Biopsy in three AMA-positive patients showed mild bile duct damage in one patient. On median follow-up of about 3 years, there were no differences in liver disease outcomes (ascites, encephalopathy, variceal bleeding), hepatocellular carcinoma, transplantation, and survival. Autoimmune markers are frequently present in steatohepatitis-related liver disease patients. Their presence is an epiphenomenon without histological changes of autoimmune hepatitis. Further, their presence does not impact clinical presentation and follow-up outcomes.

Liver injury correlates with biomarkers of autoimmunity and disease activity and represents an organ system involvement in patients with systemic lupus erythematosus

Liver disease (LD), defined as ≥2-fold elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT), was examined in a longitudinal study of systemic lupus erythematosus (SLE) patients. Among 435 patients, 90 (20.7%) had LD with a greater prevalence in males (15/39; 38.5%) than females (75/396; 18.9%; p=0.01). SLE disease activity index (SLEDAI) was greater in LD patients (7.8±0.7) relative to those without (5.8±0.3; p=0.0025). Anti-smooth muscle antibodies, anti-DNA antibodies, hypocomplementemia, proteinuria, leucopenia, thrombocytopenia, and anti-phospholipid syndrome were increased in LD. An absence of LD was noted in patients receiving rapamycin relative to azathioprine, cyclosporine A, or cyclophosphamide. An absence of LD was also noted in patients treated with N-acetylcysteine. LFTs were normalized and SLEDAI was diminished with increased prednisone use in 76/90 LD patients over 12.1±2.6months. Thus, LD is attributed to autoimmunity and disease activity, it responds to prednisone, and it is potentially preventable by rapamycin or N-acetylcysteine treatment.

330 Hepatopulmonary syndrome may mask cystic fibrosis

Clinically significant hepatobiliary manifestations of CF are reported to occur in 15–30% of children and cirrhosis is reported in 5–10% of pediatric populations. A 7 year-old boy consultated to pediatric pulmonology clinic with chronic cough, decreased exercise tolerance for six months and cyanosis for 15 days, in terms of hepatopulmonary syndrome. He was under investigation because of hepatosplenomegaly for one year. Physical examination demonstrated tachypnea, mild clubbing, orthodeoxia (saturation 81–82% in the upright position and 86–88% in the supine position) and common crepitan crackles on the auscaltation. On abdominal examination hepatosplenomegaly were present. The calculated alveolar-arterial oxygen gradient was 43 mmHg. Chest x-ray and CT demonstrated dilated peripheral vasculature and bronchiectasis. Liver function tests, coagulation profiles, serum ceruloplasmin, alpha-1 antitrypsin, antinuclear antibodies, anti smooth muscle antibody were all normal. Endoscopy of upper gastrointestinal tract showed no esophageal varices. Liver biopsy findings resulted as cirrhotic liver showing signs of ascending cholangitis. But definitive diagnosis was not determined for one year. Contrast-enhanced echocardography with agitated saline was compatible with intrapulmonary shunting. Although patient denied recurrent lower respiratory tract infection, diarrhea, malnutrition, CF was diagnosed with p.G85E (c.254G>A), p.I148T (c443T>C) mutation. Cystic fibrosis should be investigated in cirrhotic patients with respiratory signs. Hepatosplenomegaly may be the first sign of CF.

Evaluation of hearing functions in patients with euthyroid Hashimoto's thyroiditis.

Sensorineural hearing loss has been reported in various autoimmune diseases. The relationship between Hashimoto's thyroiditis (HT) and the auditory system has not been previously evaluated. In this study, we investigated the effect of euthyroid HT on the hearing ability of adult patients. The study included 30 patients with newly diagnosed euthyroid HT and 30 age- and gender-matched healthy controls. All subjects had a normal otoscopic examination and tympanometry, and they were negative for rheumatoid factor, antinuclear, anti-smooth muscle, antimitochondrial, antineutrophilcytoplasmic, and antigliadin antibodies. Pure tone audiometry exams at 250, 500, 1000, 2000, 4000, 6000, and 8000 Hertz (Hz) were performed in both groups. Thyroid peroxidase antibody and thyroglobulin antibody (anti-Tg) levels were higher in HT group while TSH, free T4, free T3, plasma electrolytes, glucose, lipid profile, vitamin B12, and blood pressure measurements were similar between the two groups. Higher audiometric thresholds and a higher prevalence of hearing loss at 250, 500, and 6000 Hz were detected in the HT patients than in the healthy controls (P < 0.05). Hearing levels at 250 and 500 Hz correlated positively with anti-Tg levels (ρ = 0.650, P = 0.002; ρ = 0.719, P < 0.001, respectively), and this association remained significant in linear regression analysis. Anti-Tg-positive HT patients had higher hearing thresholds at 250 and 500 Hz than anti-Tg-negative HT patients. Hearing thresholds were similar between anti-Tg-negative HT patients and the control subjects. This study demonstrated that hearing functions are impaired in HT patients. Thyroid autoimmunity seems to have an important impact on a decreased hearing ability, particularly at lower frequencies, in this population of patients.

Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is defined by elevated serum transaminases along with the presence of one or more characteristic serum autoantibodies, including antinuclear antibody (ANA), anti–smooth muscle antibody (ASMA), and anti–liver-kidney microsomal type 1 antibody (anti-LKM-1); elevated levels of serum immunoglobulin G (IgG); interface hepatitis on histology; and responsiveness to immunosuppressive therapy. AIH has been classified into two disease subtypes based on serologic markers: type 1, which is characterized by the presence of either ANA or ASMA, and type 2, which is characterized by the presence of either anti-LKM-1 or anti–liver-cytosol antibody type 1 (anti-LC-1). This review addresses the epidemiology, natural history, pathogenesis, and management of AIH, as well as ongoing challenges. Several recent advances are highlighted, including the creation of a simplified diagnostic scoring system and the use of budesonide for AIH treatment. Figures show the pathology of AIH, treatment approach of moderate to severe AIH with combination therapy, azathioprine metabolism, and management of treatment outcomes. Tables list a comparison of type 1 and type 2 AIH, antibodies in AIH, the revised diagnostic scoring system (including a simplified version), indications for treatment in AIH, recommended treatment regimens for AIH by the American Association for the Study of Liver Diseases, and adverse effects associated with therapy for AIH. This review contains 4 highly rendered figures, 7 tables, and 146 references.

Type 1 and type 2 autoimmune hepatitis in adults share the same clinical phenotype.

Autoimmune hepatitis (AIH) is historically classified into type 1 and type 2 on the basis of the autoantibody profile, anti-nuclear and/or anti-smooth muscle antibodies being the serological markers of type 1 AIH, whereas anti-liver/kidney microsomal antibody type 1 and/or anti-liver cytosol antibody type 1 characterise type 2 AIH. To evaluate whether such a distinction is justified on the basis of different expression of the disease in adults. Twenty-six adult patients with type 2 AIH and 52 age- and sex-matched patients with type 1 AIH, representative of the entire cohort of adults with type 1 AIH, were compared at onset and during follow-up. At diagnosis, median age was 26years (range 17-53), female sex 86%, acute presentation 43%, severe liver histology 54%, cirrhosis 14%, complete response to treatment 52%, progression of the disease 17%, and median disease duration 72months (range 12-280). HLA-DRB1*0301 was present in 26%, HLA-DRB1*0401 in 23% and HLA-DRB1*0701 in 25%. Clinical presentation, biochemical parameters, severe liver histology, genetic profile, response rate and progression of the disease were identical between type 1 and type 2 AIH. There is not enough clinical, biochemical, histological or genetic reason to subdivide adults with autoimmune hepatitis into type 1 and type 2 on the basis of the autoantibody profile, and the term 'autoimmune hepatitis' without qualification should be preferred.

Distinct Features in Natural History and Outcomes of Acute Hepatitis C

Acute hepatitis C (AHCV) provides a diagnostic challenge with diverse clinical presentations. This study was aimed to examine the clinical and demographic features as well as outcomes in AHCV patients identified from inpatient and outpatient hospital settings. Patients with suspected AHCV were recruited from Philadelphia VA Medical Center, Hospital of University of Pennsylvania and Brooklyn VA Medical Center between 2000 and 2010. AHCV was diagnosed by acute serum alanine aminotransferase elevation with anti-hepatitis C virus (HCV) seroconversion, HCV-RNA fluctuations above 1 log, and/or recent high-risk exposure without prior HCV infection, excluding those with human immunodeficiency virus infection. Clinical and therapeutic outcomes were monitored for at least 6 months. A total of 40 AHCV patients were enrolled with a median follow-up of 129 weeks. They were mostly men (68%) and whites (73%) with median age of 43 years, diverse risk factors (33% injection drugs, 20% health care-associated, 3% sexual, and 45% unknown), and wide variations in peak alanine aminotransferase (143 to 3435 U/L) and total bilirubin levels (0.4 to 19.3 mg/dL). Viremia resolved spontaneously in 23% and persisted without therapy in 27%, whereas 50% received interferon α-based therapy with 90% cure (18/20). Distinct clinical scenarios included: (1) wide viremic fluctuations >1 log (65%) and intermittent HCV-RNA negativity; (2) autoantibodies (25% antinuclear antibodies, 69% antismooth muscle antibodies) or autoimmune features; (3) delayed spontaneous viral clearance in 2 patients; (4) rapid cirrhosis progression in 2 patients. AHCV is a heterogenous disease that requires careful monitoring. The lack of apparent risk factor in high proportion of patients and its diverse presentations warrant diagnostic vigilance.

Autoimmune Hepatitis-Primary Biliary Cirrhosis: Overlap Syndrome Concomitant with Unexpected Myasthenia and Thymoma

The myasthenia gravis is an autoimmune disease which can be associated frequently with a thymoma and also with autoimmune pathologies. We report the case of a 64-year-old man affected an overlap syndrome corresponding to the association of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). He also presented concomitant myasthenia gravis and thymoma. The physical examination notes only a disturbed voice. The liver tests showed: alkaline phosphatase 600 U/l, alanine aminotransferase 1280 U/l, and aspartate aminotransferase 985 U/l. Viral serologies of hepatitis were all negative, as well as antinuclear, antimitochondrial and antismooth muscle antibodies. The diagnosis of an overlap syndrome was posed according to the biological and hepatic histhological results. An associated myasthenia was confirmed by the results of the EMG and the positivity of the anti-acetylcholine receptor antibody. A chest CT revealed a thymoma. The treatment consisted of ursodeoxycholic acid, prednisone, azathioprine and pyridostigmine. And the patient improved his voice and the liver function. Thymectomy was practiced without incidents.

Profile of liver biopsies in a tertiary care centre in coastal eastern India

The aim of this study was to evaluate the profile of liver biopsies in a tertiary referral centre in eastern India. A total of 54 patients over a period of 1 year, diagnosed by clinical, biochemical, radiological and histopathological parameters, were evaluated for aetiology. Investigations included serological tests for the markers of hepatitis B virus (HBV) and hepatitis C virus (HCV). Autoimmune markers, including antinuclear antibody (ANA), antismooth muscle antibody (ASMA) and antimitochondrial antibody (AMA-M2), were carried out where clinically indicated. Histopathological study with routine haematoxylin and eosin (HE) stain and special stains, including Masson’s trichrome and reticulin stain, were carried out. A total of 24 (46%) patients had non-alcoholic fatty liver disease (NAFLD), 18 (34%) patients had chronic viral hepatitis and 10 (20%) patients had other liver disorders. HBV was present in 16 (88.2%) cases and HCV in 2 (11.8%) cases in the category of clinically chronic viral hepatitis patients. None had infection with both viruses. Cholestatic liver disease, cirrhosis and amyloidosis were the aetiological factors, amongst others. Biopsy was inadequate in two cases. This study showed NAFLD, closely followed by HBV infection, as the most common cause of liver disease in the study population. Alcoholics were excluded from the study. The study reflects the referral pattern in a tertiary centre. However, larger and longer studies are required to delineate the exact prevalence of liver disease in this geographical area