Biomarkers for neuromyelitis optica:a visual analysis of emerging research trends

Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis.Over the past 20 years,the search for biomarke rs for neuromyelitis optica has been ongoing.Here,we used a bibliometric approach to analyze the main research focus in the field of biomarkers for neuromyelitis optica.Research in this area is consistently increasing,with China and the United States leading the way on the number of studies conducted.The Mayo Clinic is a highly reputable institution in the United States,and was identified as the most authoritative institution in this field.Furthermore,Professor Wingerchuk from the Mayo Clinic was the most authoritative expe rt in this field.Keyword analysis revealed that the terms "neuro myelitis optica"(261 times), "multiple sclerosis"(220 times), "neuromyelitis optica spectrum disorder"(132 times), "aquaporin4"(99 times),and "optical neuritis"(87 times) were the most frequently used keywords in literature related to this field.Comprehensive analysis of the classical literature showed that the majority of publications provide conclusive research evidence supporting the use of aquaporin-4-IgG and neuromyelitis optica-IgG to effectively diagnose and differentiate neuromyelitis optica from multiple sclerosis.Furthermore,aquaporin-4-IgG has emerged as a highly specific diagnostic biomarker for neuromyelitis optica spectrum disorder.Myelin oligodendrocyte glycoprotein-IgG is a diagnostic biomarke r for myelin oligodendrocyte glycoprotein antibody-associated disease.Recent biomarkers for neuromyelitis optica in clude cerebrospinal fluid immunological biomarkers such as glial fibrillary acidic protein,serum astrocyte damage biomarkers like FAM19A5,serum albumin,and gammaaminobutyric acid.The latest prospective clinical trials are exploring the potential of these biomarkers.Preliminary results indicate that glial fibrillary acidic protein is emerging as a promising candidate biomarker for neuromyelitis optica spectrum disorder.The ultimate goal of future research is to identify non-invasive biomarkers with high sensitivity,specificity,and safety for the accurate diagnosis of neuro myelitis optica.

Unmet needs in biomarkers for autoimmune pancreatitis diagnosis

Autoimmune pancreatitis(AIP)is a rare chronic autoimmune disorder.The diagnosis of AIP mainly depends on histopathology,imaging and response to treatment.Serum immunoglobulin 4(IgG4)is used only as collateral evidence in diagnostic criteria for AIP because of its moderate sensitivity.Serum IgG4 levels are normal in 15%-37%of type 1 AIP and most of type 2 AIP patients.In these patients,the indeterminate imaging and histopathology may lead to the difficulty in definitive diagnosis of AIP.Therefore,discovery of new biomarkers is impor-tant for AIP diagnosis.Here,we provide some views on the progression and challenges in identifying novel serological biomarkers in AIP diagnosis.

Enzyme-linked immunosorbent assay of 3 Screen Islet Cell Autoantibody in patients with autoimmune thyroid disease

BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes(T1D).While it has been established that 20%-30%of T1D patients suffer from autoimmune thyroid disease(AITD),there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients.Among commercially available anti-islet autoantibodies,glutamic acid decarboxylase 65 autoantibodies(GADAs)are often the first marker measured in general clinical practice.AIM To investigate the frequency of anti-islet autoantibodies in AITD patients.METHODS Our study involved four hundred ninety-five AITD patients,categorized into three distinct groups:AITD with T1D(n=18),AITD with phenotypic type 2 diabetes(T2D)(n=81),and AITD without diabetes(n=396),and the enzyme-linked immunosorbent assay(ELISA)was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody(3 Screen ICA),GADA,insulinoma-associated antigen-2 autoantibodies(IA-2As),and zinc transporter 8 autoantibodies(ZnT8As)within these groups.RESULTS The frequency of 3 Screen ICA in AITD patients with T1D,T2D,and those without diabetes were 88.9%,6.2%,and 5.1%,respectively,with no significant difference seen between the latter two groups.Notably,the frequency of 3 Screen ICA was 11.1%higher in AITD patients with T1D,1.3%higher in AITD patients with T2D,and 1.1%higher in AITD patients without diabetes compared to GADA,respectively.Furthermore,12.5%,20.0%,and 20.0%of the 3 Screen ICA-positive patients were negative for GADA.Additionally,1.3%of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies.Among the 3 Screen ICA-positive patients,there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes(37.5%vs 5.0%,P<0.05).However,this proportion was similar to that in AITD patients with T2D(20.0%).Nevertheless,there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes(436.8±66.4 vs 308.1±66.4 index).Additionally,no significant difference in 3 Screen ICA titers was observed between Graves’disease and Hashimoto’s thyroiditis in any of the groups.CONCLUSION Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D.Thus,3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.

Exogenous insulin autoimmune syndrome:A case report and review of literature

BACKGROUND Insulin autoimmune syndrome(IAS)is a severe manifestation of spontaneous hypoglycemia.It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies(IAAs),which are induced by endogenous insulin circulating in the bloodstream.It is distinguished by recurring instances of spontaneous hypoglycemia,the presence of IAA within the body,a substantial elevation in serum insulin levels,and an absence of prior exogenous insulin administration.Nevertheless,recent studies show that both conventional insulin and its analogs can induce IAS episodes,giving rise to the notion of nonclassical IAS.Therefore,more attention should be paid to these diseases.CASE SUMMARY In this case report,we present a rare case of non-classical IAS in an 83-year-old male patient who present with symptoms of a psychiatric disorder.Upon symptom onset,the patient exhibited Whipple's triad(including hypoglycemia,blood glucose level less than 2.8 mmol/L during onset,and rapid relief of hypoglycemic symptoms after glucose administration).Concurrently,his serum insulin level was significantly elevated,which contradicted his C-peptide levels.After a comprehensive examination,the patient was diagnosed with exogenous insulin autoimmune syndrome.Considering that the patient had type 2 diabetes mellitus and a history of exogenous insulin use before disease onset,it was presumed that non classical IAS was induced by this condition.The PubMed database was used to search for previous cases of IAS and non-classical IAS to analyze their characteristics and treatment approaches.CONCLUSION The occurrence of non-classical IAS is associated with exogenous insulin or its analogs,as well as with sulfhydryl drugs.Symptoms can be effectively alleviated through the discontinuation of relevant medications,administration of hormones or immunosuppressants,plasma exchange,and lifestyle adjustments.

Autoantibodies related to ataxia and other central nervous system manifestations of gluten enteropathy

Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.

A Large, Inflamed Knee, Pulling down the Wolf Mask

Introduction: Joint manifestations are common in systemic lupus, affecting multiple joints or just one. These manifestations are present in 95% of patients. Pseudo-septic arthritis is a subset of systemic lupus that mimics septic arthritis caused by the deposition of lipid droplets in the joint. We present the case of a patient hospitalized for mono-arthritis, which revealed systemic lupus. Observation: The patient is a 19-year-old woman, single, without children, and with no previous medical history, who was hospitalized for fever and inflammatory polyarthralgia. The clinical examination revealed an inflammatory swelling of the right knee with patellar ballottement, yellow citrine synovial fluid, an inflammatory tumor on the left arm, which was round, mobile, and fluctuating with purulent content, edema of the lower limbs, and facial puffiness, along with a systemic inflammatory response syndrome. Paraclinical examination showed hyperleukocytosis with neutrophil predominance, microcytic anemia, thrombocytopenia, antistreptolysin O (ASLO) 3, suggesting inflammatory arthritis. Bacteriological tests did not isolate any pathogens. An arthrotomy with synovial biopsy was performed, and the histopathological examination supported non-specific synovitis. A joint ultrasound showed signs of arthritis with a septic appearance. During the third hospitalization for persistent fever, she presented with facial puffiness, anemia syndrome, systemic inflammatory response syndrome, and a malar rash across the bridge of the nose. Antinuclear antibodies returned positive with a titer of 1280 and a speckled fluorescence pattern, and anti-native DNA antibodies were positive at 60.1 (normal Conclusion: Pseudo-septic arthritis is a feature of lupus that can mimic septic arthritis. Monoarticular involvement is rare but possible. The absence of pathogens and the inflammatory nature of the synovial fluid should prompt consideration of a lupus-related etiology.

Profile of Autoantibodies and Clinical Symptoms in Guinean Patients with Connective Tissue Diseases

Connective tissue diseases (CTDs) are Autoimmune diseases (AIDs) characterized by the appearance of autoantibodies, which are diagnostic markers. Investigations of these autoantibodies play a major role in the management of several autoimmune diseases. The objective of this study was to describe the profile of anti-ENA antibodies according to the clinical symptoms of mixed CTDs in Conakry teaching Hospital. We performed a cross-sectional study during six months. A total of 20 patients was recruited and we measured antibodies using the ELISA technique. The mean age of our patients was 36.5 years, with a predominance of females. Cutaneous and rheumatological signs were the main clinical manifestations. SLP was the most frequent CTDs;the threshold of ENA antibodies positivity was higher in scleroderma with and SLP. Anti-ENA identification reveals the frequency of anti-SSA (83.33%), anti-U1RNP (66.66%) and anti-histone (50%) antibodies. Antinuclear antibodies (ANA) react with various components of the cell nucleus. Their detection is of major interest in the diagnosis of CTDs. Our results highlight the importance of determining the specificity of these antibodies to guide differential diagnosis.

What is new in the pathogenesis and treatment of IgA glomerulonephritis

Recently,new findings have been clarified concerning both pathogenesis and treatment of IgA nephritis.The four hits theory has been confirmed but several genetic wide association studies have allowed finding several genes connected with the pathogenesis of the disease.All these new genes apply to each of the four hits.Additionally,new discoveries concerning the microbiota and its connection with immune system and IgA generation have allowed finding out the role of the mucosa in IgA nephropathy pathogenesis.The IgA treatment is also changed included the future possibilities.The treatment of the chronic kidney disease,associated with the nephropathy,is mandatory,since the beginning of the disease.The classical immunosuppressive agents have poor effect.The corticosteroids remain an important cornerstone in any phase of the disease.More effect is related to the treatment of B cells and plasma cells.In particular,in very recent studies have been documented the efficacy of anti B cell-activating factor and anti A proliferation-inducing ligand agents.Most of these studies are to date in phase II/III.Finally,new agents targeting complement are arising.These agents also are still in randomized trials and act principally in hit 4 where the immunocomplexes in the mesangium activate the different pathways of the complement cascade.

Prognostic and predictive blood biomarkers in gastric cancer and the potential application of circulating tumor cells

Gastric cancer(GC), with its high incidence and mortality rates, is a highly fatal cancer that is common in East Asia particularly in China. Its recurrence and metastasis are the main causes of its poor prognosis. Circulating tumor cells(CTCs) or other blood biomarkers that are released into the circulating blood stream by tumors are thought to play a crucial role in the recurrence and metastasis of gastric cancer. Therefore, the detection of CTCs and other blood biomarkers has an important clinical significance; in fact, they can help predict the prognosis, assess the staging, monitor the therapeutic effects and determine the drug susceptibility. Recent research has identified many blood biomarkers in GC, such as various serum proteins, autoantibodies against tumor associated antigens, and cell-free DNAs. The analysis of CTCs and circulating cell-free tumor DNA(ctDNA) in the peripheral blood of patients with gastric cancer is called as liquid biopsy. These blood biomarkers provide the disease status for individuals and have clinical meaning. In this review, we focus on the recent scientific advances regarding CTCs and other blood biomarkers, and discuss their origins and clinical meaning.

Blood-based biomarkers for early detection of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC)is a common malignant tumor of the digestive system worldwide,especially in China.Due to the lack of effective early detection methods,ESCC patients often present at an advanced stage at the time of diagnosis,which seriously affects the prognosis of patients.At present,early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy.Therefore,there is an unmet need for a noninvasive method to detect ESCC in the early stages.With the emergence of a large class of non-invasive diagnostic tools,serum tumor markers have attracted much attention because of their potential for detection of early tumors.Therefore,the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC.This article reviews the recent advances in the discovery of blood-based ESCC biomarkers,and discusses the origins,clinical applications,and technical challenges of clinical validation of various types of biomarkers.

Primary biliary cirrhosis:What do autoantibodies tell us?

Primary biliary cirrhosis(PBC) is a chronic,progressive,cholestatic,organ-specific autoimmune disease of unknown etiology.It predominantly affects middle-aged women,and is characterized by autoimmune-mediated destruction of small-and medium-size intrahepatic bile ducts,portal inflammation and progressive scarring,which without proper treatment can ultimately lead to fibrosis and hepatic failure.Serum autoantibodies are crucial tools for differential diagnosis of PBC.While it is currently accepted that antimitochondrial antibodies are the most important serological markers of PBC,during the last five decades more than sixty autoantibodies have been explored in these patients,some of which had previously been thought to be specific for other autoimmune diseases.

Autoantibodies in Chinese patients with chronic hepatitis B:Prevalence and clinical associations

AIM: To investigate the prevalence of autoantibodies and their associations with clinical features in Chinesepatients with chronic hepatitis B(CHB).METHODS: A total of 325 Chinese patients with CHB were enrolled in this retrospective,hospitalbased study.Patients with chronic hepatitis C(CHC),autoimmune hepatitis(AIH),or primary biliary cirrhosis(PBC) were included,with healthy donors acting as controls.A panel of autoantibodies that serologically define AIH and PBC was tested by indirect immunofluorescence assay and line immunoassay.The AIH-related autoantibody profile included homogeneous anti-nuclear antibodies(ANA-H),smooth-muscle antibodies,anti-liver kidney microsome type 1,antiliver cytosolic antigen type 1,and anti-soluble liver antigen/liver pancreas; the PBC-related antibodies were characterized by ANA-nuclear dots/membranous rimlike,anti-mitochondrial antibodies-M2(AMA-M2),antiBPO(recombinant antigen targeted by AMA-M2),antiSp100,anti-promyelocytic leukemia protein(anti-PML),and anti-gp210.The dichotomization of clustering was used to unequivocally designate the AIH or PBC profiles for each case.Anti-Ro52 antibodies were also tested.RESULTS: The prevalence of any autoantibody in CHB amounted to 58.2%,which was similar to the 66.2% prevalence in CHC,significantly higher than the 6.7% in the healthy controls(P < 0.001),and lower than the 100% found in AIH and PBC(P = 0.004 and P < 0.001,respectively).There were more anti-PML and anti-gp210 antibodies among the CHB patients than the CHC patients(11.1% vs 0%,P = 0.003; 12.6% vs 0%,P < 0.001,respectively).The prevalence and titer of AMA,anti-BPO,anti-PML,and anti-gp210 were higher in PBC than in those with CHB.Among the CHB patients,the prevalence of ANA,especially ANA-H,was significantly lower in patients with compensated and decompensated cirrhosis compared with patients without cirrhosis.Thirty-eight cases of hepatocellular carcinoma(HCC) in CHB showed a significant differencecompared with non-HCC patients in the prevalence of anti-PML(0% vs 12.5%,P = 0.013).Dichotomization of the autoantibodies revealed that the PBC profile was more prevalent in patients with CHB than in those with CHC,and that it was strongly correlated with both compensated and decompensated cirrhosis.In contrast,the prevalence of the AIH profile was significantly higher in non-cirrhosis patients with CHB than in those with compensated cirrhosis(18.5% vs 8.2%,P = 0.039).Moreover,the AIH profile was also closely associated with hepatitis B e-antigen positivity.CONCLUSION: ANA-H could be an indicator of earlystage CHB.Dichotomizing the autoantibody profiles revealed that the PBC profile is strongly associated with cirrhosis in CHB.

Immunological alterations in hepatitis C virus infection

A higher prevalence of immunological processes has recently been reported in patients with hepatitis C virus(HCV)infection,focusing the attention of physicians and researchers on the close association between HCV and immune disorders.HCV lymphotropism represents the most important step in the pathogenesis of virusrelated immunological diseases and experimental,virologic,and clinical evidence has demonstrated a trigger role for HCV both in systemic autoimmune diseases,such as rheumatoid arthritis,Sj?gren syndrome,hemolytic anemia and severe thrombocytopenia,and in organ-specific autoimmune diseases,such as autoimmune hepatitis,thyroid disorders and diabetes.This review will outline the principal aspects of such HCVinduced immunological alterations,focusing on the prevalence of these less characterized HCV extrahepatic manifestations.

Autoantibodies in primary biliary cirrhosis:Recent progress in research on the pathogenetic and clinical significance

Primary biliary cirrhosis(PBC)is a chronic progressive cholestatic liver disease characterized by immunemediated destruction of the small-and medium-sized intrahepatic bile ducts and the presence of antimitochondrial antibodies(AMA)in the serum.AMA are detected in over 90%of patients with PBC,whereas their prevalence in the general population is extremely low,varying from 0.16%to 1%.Previous studies have shown that the unique characteristics of biliary epithelial cells undergoing apoptosis may result in a highly direct and very specific immune response to mitochondrial autoantigens.Moreover,recent studies have demonstrated that serum from AMA-positive PBC patients is reactive with a number of xenobiotic modified E2 subunits of the pyruvate dehydrogenase complex,which is not observed in the serum of normal individuals.These findings indicate that chemicals originating from the environment may be associated with a breakdown in the tolerance to mitochondrial autoantigens.While it is currently generally accepted that AMA are the most specific serological markers of PBC,more than 60 au-toantibodies have been investigated in patients with PBC,and some have previously been considered specific to other autoimmune diseases.This review covers the recent progress in research on the pathogenetic and clinical significance of important autoantibodies in PBC.Determining the pathogenic role of those autoantibodies in PBC remains a priority of basic and clinical research.

Useful biomarkers for assessment of hepatitis C virus infection-associated autoimmune disorders

During the course of chronic hepatitis C virus(HCV)infection,various extrahepatic manifestations of autoimmune disorders may occur,including arthralgia/arthritis,sicca complex,purpura,cutaneous ulcer,and thyroid dysfunction.In addition,the prevalence of circulating autoantibodies is high among patients with HCV infection.Commonly detected autoantibodies in HCVinfected patients include rheumatoid factor,antinuclear antibody,anti-SSA/anti-SSB antibody,cryoglobulin,antineutrophil cytoplasmic antibody,anti-smooth muscle antibody,anti-liver and anti-thyroid autoantibodies.These autoantibodies may be associated with underlying autoimmune disorders or liver inflammation in HCV infection.A possible reason for antibody production is overactivation and proliferation of B lymphocytes,via the interaction with the surface protein of HCV.Because immunotherapy can cause HCV flare-up or liver damage,overdiagnosis of HCV-related autoimmune symptoms as primary autoimmune disorders should be avoided.This review describes biomarkers that are useful in clinically evaluating autoimmune manifestations and disorders associated with HCV infection.

High concentration of antimitochondrial antibodies predicts progressive primary biliary cirrhosis

AIM： To evaluate the serum concentration of antimitochondrial antibodies （AMAs） as a prognostic indicator of progressive primary biliary cirrhosis （pPBC）. METHODS： Serum concentrations of AMA subtypes （anti-M2, anti-M4, and anti-M9）, biochemical indices of liver function and Mayo risk factor （MRF） were determined in 30 women with diagnosed primary biliary cirrhosis （PBC） selected among 348 females with elevated alkaline phosphatase but without signs of hepatic decompensation. They were followed up for 5 years for possible development of hepatic decompensation. RESULTS： Anti-M2 concentration was significantly correlated with bilirubin and albumin levels as well as MRF, whereas anti-M4 was significantly correlated with albumin level, prothrombin time and MRF. During the 5-year follow-up, progressive PBC （pPBC） was diagnosed in 3 among 23 patients available for evaluation. These 3 patients were positive for both anti-M2 and anti-M4. Anti-M2 serum concentration exceeded 1 300 RU/mL in patients with pPBC and only in 1 among 20 non-progressive PBC persons （5%）. Anti-M4 serum concentration exceeded 400 RU/mL in 2 of the progressive patients and none in the non-progressive group. In contrast, anti-M9 serum concentration was below 100 RU/mL in all patients with pPBC, and higher than 100 RU/mL in 11 women （55%） among the non-progressive group. CONCLUSION： Females with elevated alkaline phosphatase and high anti-M2 and anti-M4 concentrations are at a high risk for developing pPBC. Quantitative AMA detection should be considered as a method for early diagnosis of pPBC. 2005 The WJG Press and Elsevier Inc. All rights reserved.

Autoantibodies against tumor-associated antigens for detection of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common tumors worldwide. The survival rate after the onset of symptoms is generally less than one year for the late presentation of HCC, and reliable tools for early diagnosis are lacking. Therefore, novel biomarkers for the early detection of HCC are urgently required. Recent studies show that the abnormal release of proteins by tumor cells can elicit humoral immune responses to self-antigens called tumor-associated antigens(TAAs). The corresponding autoantibodies can be detected before the clinical diagnosis of cancer. Therefore, there is growing interest in using serum autoantibodies as cancer biomarkers. In this review, we focus on the advances in research on autoantibodies against TAAs as serum biomarker for detection of HCC, the mechanism of the production of TAAs, and the association of autoantibodies with patients' clinical characteristics.

Clinical characteristics of drug-induced liver injury and primary biliary cirrhosis

AIM To summarize and compare the clinical characteristics of drug-induced liver injury(DILI) and primary biliary cirrhosis(PBC).METHODS A total of 124 patients with DILI and 116 patients with PBC treated at Shengjing Hospital Affiliated to China Medical University from 2005 to 2013 were included. Demographic data(sex and age),biochemical indexes(total protein,albumin,alanine aminotransferase,aspartate aminotransferase,total bilirubin,direct bilirubin,indirect bilirubin,alkaline phosphatase,and gamma glutamyltransferase),immunological indexes [immunoglobulin(Ig) A,Ig G,Ig M,antinuclear antibody,anti-smooth muscle antibody,anti-mitochondrial antibody,and anti-mitochondrial antibodies] and pathological findings were compared in PBC patients,untyped DILI patients and patients with different types of DILI(hepatocellular type,cholestatic type and mixed type). RESULTS There were significant differences in age and gender distribution between DILI patients and PBC patients. Biochemical indexes(except ALB),immunological indexes,positive rates of autoantibodies(except SMA),and number of cases of patients with different ANA titers(except the group at a titer of 1:10000)significantly differed between DILI patients and PBC patients. Biochemical indexes,immunological indexes,and positive rate of autoantibodies were not quite similar in different types of DILI. PBC was histologically characterized mainly by edematous degeneration of hepatocytes(n = 30),inflammatory cell infiltration around bile ducts(n = 29),and atypical hyperplasia of small bile ducts(n = 28). DILI manifested mainly as fatty degeneration of hepatocytes(n = 15) and spotty necrosis or loss of hepatocytes(n = 14).CONCLUSION Although DILI and PBC share some similar laboratory tests(biochemical and immunological indexes) and pathological findings,they also show some distinct characteristics,which are helpful to the differential diagnosis of the two diseases.

Pernicious anemia: New insights from a gastroenterological point of view

Pernicious anemia （PA） is a macrocytic anemia that is caused by vitamin B12 deficiency, as a result of intrinsic factor deficiency. PA is associated with atrophic body gastritis （ABG）, whose diagnosis is based on histological confirmation of gastric body atrophy. Serological markers that suggest oxyntic mucosa damage are increased fasting gastrin and decreased pepsinogen I. Without performing Schilling＇s test, intrinsic factor deficiency may not be proven, and intrinsic factor and parietal cell antibodies are use- ful surrogate markers of PA, with 73% sensitivity and 100% specificity. PA is mainly considered a disease of the elderly, but younger patients represent about 15% of patients. PA patients may seek medical advice due to symptoms related to anemia, such as weak-ness and asthenia. Less commonly, the disease is suspected to be caused by dyspepsia. PA is frequently associated with autoimmune thyroid disease （40%） and other autoimmune disorders, such as diabetes mellitus （10%）, as part of the autoimmune polyen-docrine syndrome. PA is the end-stage of ABG. Long- standing Helicobacter pylori infection probably plays a role in many patients with PA, in whom the active infectious process has been gradually replaced by an autoimmune disease that terminates in a burned-out infection and the irreversible destruction of the gastric body mucosa. Human leucocyte antigen-DR genotypes suggest a role for genetic susceptibility in PA. PA patients should be managed by cobalamin replacement treatment and monitoring for onset of iron deficiency. Moreover, they should be advised about possible gastrointestinal long-term consequences, such as gastric cancer and carcinoids.

Clinical characteristics and corticosteroid therapy in patients with autoimmune-hepatitis-induced liver failure

AIM: To investigate the clinical features, response to corticosteroids, and prognosis of autoimmune hepatitis (AIH)-induced liver failure in China.