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Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review

  • Youwen Tan EMAIL logo and Li Chen
Published/Copyright: September 7, 2021
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Open Medicine
From the journal Open Medicine Volume 16 Issue 1

Abstract

Hepatitis A virus immunoglobulin M (HAV-IgM) is often used to diagnose acute hepatitis A virus (HAV) infection serologically. However, false-positive test results can interfere with the diagnosis. A 56-year-old woman was readmitted to the hospital owing to abnormal liver function tests for the last 18 months. She had been diagnosed with acute HAV and was hospitalized in isolation based on a positive HAV-IgM test 18 months ago. Regular follow-up after discharge showed abnormal liver function and an elevated level of antinuclear antibodies and immunoglobulin G. For the last 15 days, the patient had fatigue, decreased appetite, and yellow urine, signaling recrudescence. Liver function tests were also abnormal. Liver biopsy revealed histological changes consistent with typical autoimmune hepatitis. After 2 months of methylprednisolone treatment, liver function returned to normal, and HAV-IgM turned negative. The diagnosis of acute HAV in nonendemic areas requires a comprehensive analysis of epidemic history, clinical characteristics, etiology, etc.

Key words: immunoglobulin M; hepatitis A; false-positive

1 Introduction

Immunoglobulin M (IgM) is a marker for acute viral infection and has definitive clinical value. Therefore, physicians depend on the serum marker for the diagnosis of active infection. However, an increased number of false-positive test results can lead to misdiagnosis and incorrect treatment. Relying solely on this test result further compounds the problem. Many healthcare professionals are still unaware of this issue. False-positive IgM results can occur with any pathogen. We report a case of HAV-IgM with persistently abnormal liver function tests that lasted for 18 months. The patient was incorrectly diagnosed with acute hepatitis A and, finally, with autoimmune hepatitis (AIH).

2 Case report

A 56-year-old woman was readmitted to the hospital with abnormal liver function tests, persisting for the last 18 months. Her hepatic markers were as follows, tested 18 months ago: alanine aminotransferase (ALT) 113 U/L, aspartate aminotransferase (AST) 104 U/L, alkaline phosphatase (ALP) 124 U/L, and glutamate aminotransferase (GGT) 78 U/L. This was attributed to a positive HAV-IgM (ELISA, OD value of attributed absorbance ≥2.1, determined to be positive). She was diagnosed with acute hepatitis A and hospitalized in isolation for treatment. Abnormal symptoms, such as fever, fatigue, abdominal pain, or yellow urine, were not observed. She was treated with glutathione 0.9 g and glycyrrhetinic acid 150 mg/day for 45 days. The liver function recovered, and the markers were as follows: ALT 56 U/L, AST 43 U/L, ALP 109 U/L, and GGT 65 U/L. However, HAV-IgM was still positive. During this time, anti-nuclear antibodies (ANA) 47 U/L (normal <10 U/L) were also detected. Tests for antimitochondrial antibodies (AMAs) and anti-liver kidney microsomal (LKM) antibodies, and anti-smooth muscle antibodies (SMAs) were negative. The immunoglobulin G (IgG) level was 18.3 g/L (normal range 6.2–16.1 g/L) and the IgM level was 2.71 g/L (normal range 0.98–2.04 g/L). Following discharge, regular monthly reexamination showed abnormal liver function with repeated fluctuations (Figure 1). The patient developed fatigue, decreased appetite, and yellow urine for 15 days, thus indicating recrudescence. Liver function tests showed abnormal results [total bilirubin (TBIL) 43 mol/L, ALT 452 U/L, AST 254 U/L, ALP 175 U/L, GGT95 U/L]. Further testing revealed the ANA level of 102 U/L, IgG 26.3 g/L, IgM 2.71 g/L, and IgA 5.32 g/L (normal range: 0.76–3.9 g/L). The analysis of a liver biopsy specimen revealed histological changes consistent with typical autoimmune hepatitis. There was moderate to severe interfacial inflammation, numerous lympho-plasma cell infiltrates, lymphocytic penetration, and rosette-like hepatocytes (Figure 2). HAV-IgM was positive. To rule out the possibility of HAV infection, a reverse transcription-polymerase chain reaction (RT-PCR) was conducted to detect HAV RNA in the serum. The analysis of the current samples, as well as those from a year ago, was found to be negative. Clinical diagnosis of AIH was made with a false-positive HAV-IgM. Methylprednisolone 32 mg/day was administered, which was tapered to 20 mg/day after 1 month. The liver function tests, done daily, returned to normal after 2 months, following which, methylprednisolone was further tapered to 8 mg/day as a maintenance treatment. On reexamination, the patient was negative for HAV-IgM and HAV RNA. The tests for Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus, and adenovirus were negative. There was also no drug-induced liver injury or history of alcohol addiction.

Figure 1 Changes in the liver function and immunological indexes (LB: liver biopsy; MP: methyl prednisolone).
Figure 1

Changes in the liver function and immunological indexes (LB: liver biopsy; MP: methyl prednisolone).

Figure 2 Pathological features of the liver (hematoxylin-eosin staining). (a) Severe interfacial inflammation (thick arrow), ×100 and (b) lympho-plasma cell infiltration (thick arrow), lymphocytes penetrate into the hepatocytes (thin arrow), and rose cluster hepatocytes (arrow), ×200.
Figure 2

Pathological features of the liver (hematoxylin-eosin staining). (a) Severe interfacial inflammation (thick arrow), ×100 and (b) lympho-plasma cell infiltration (thick arrow), lymphocytes penetrate into the hepatocytes (thin arrow), and rose cluster hepatocytes (arrow), ×200.

  1. Ethics statement: Ethics Statement is not applicable for the case report according to the Medical Ethics Committee of the Third Hospital of Zhenjiang Affiliated Jiangsu University, but Informed consent was obtained from the patient for publication of this case report and accompanying images. The study was conducted in accordance with the Declaration of Helsinki.

3 Discussion

HAV is a globally prevalent infectious agent causing intestinal disease. It is mainly transmitted by the fecal-oral route, usually developing as an acute infection followed by self-recovery [1]. HAV-IgM is indicative evidence of an active HAV infection. It appears one week after HAV infection and generally lasts for 3–6 months. HAV-IgM has rarely been detected beyond 1 year [2,3]. Compared to HAV RNA detection, HAV-IgM detection is convenient and fast. It is the primary indicator of current infection with HAV, especially in endemic areas. The accuracy of anti-HAV IgM testing is comparable to HAV RNA detection in the diagnosis of acute hepatitis A [4]. In the absence of a hepatitis A outbreak, a disadvantage of the HAV RNA RT-PCR assay is its high cost as it is not a routine investigation in our country, nor in most other countries. Conversely, it has the advantage of being able to detect acute hepatitis A in its early stages, especially during a hepatitis A epidemic [5]. This will prove to be of great significance to control the further spread of the disease. Another limitation of the HAV RNA assay is that it is susceptible to environmental contamination and is not a genuine test for the HAV virus. However, HAV RNA can be present in the blood for a long time (mean: 79 days) and has also been reported to be present for more than 1 year [6].

The HAV vaccine was included in China’s immunization program from 2008. With the universal vaccination of children, the reported incidence of HAV in China has decreased significantly, from 7.34/100,000 in 2004 to 1.66/100,000 in 2015, thus indicating that the prevalence of HAV has been controlled [7]. HAV-RNA is no longer used as a routine diagnostic test having been replaced by the more convenient and cheaper method of IgM antibody testing. In countries where HAV outbreaks are under control, real cases of HAV are rare. For example, in the United States, 10,735 HAV-IgM samples were collected from Kansas City, Missouri, from January 2007 to December 2010. Among them, 49 HAV-IgM positive test results were found in 35 patients. Finally, only 4 patients were detected with acute HAV (11%) [8]. In conclusion, in areas where HAV is controlled, the diagnosis of acute HAV infection should take into account a comprehensive analysis of epidemic history, clinical characteristics, and laboratory examination [9]. Testing HAV-IgM in individuals with asymptomatic infection or with no history of epidemic disease is not recommended [10]. An investigative report shows that the Department of Health and the Centers for Disease Control and Prevention in the United States conducted a survey on individuals with HAV-IgM positivity from 2002 to 2004 [6]. Those who did not meet the clinical criteria for the case were defined as HAV. The report shows that most of the positive test results did not represent a recent, acute HAV infection. In order to improve the predictive value of positive HAV-IgM detection, clinicians should limit laboratory detection of acute HAV infection to those with typical clinical manifestations or those who have been exposed to suspected hepatitis infection in an environment favoring transmission.

The false-positive IgM mechanism is complex and is the result of comprehensive factors, such as polyclonal B cell activation [11,12], vigorous immune response [11,12], influenza vaccination [13], cross-reactive antibodies [14,15,16], autoimmune disease [17], heterologous reactions to similar viruses [18,19,20], subclinical reactivation of latent viruses [21], interfering substances (e.g., rheumatoid factor) [22,23], and naturally occurring biotin IgM antibodies [24]. In addition to the above, cutoff values being set too low [25,26], faulty reagents [27], technical errors (e.g., overreading weakly reactive bands on immunoblots) [28], low pretest probability [8], and inappropriate testing [6,8] also affect the results.

Although a false-positive HAV-IgM should be common in areas where hepatitis A has been controlled, there is a lack of sizeable data based on population surveys. Our search on PubMed, EMBAS, Web of science, and other databases, using the keywords “False-positive HAV-IgM,” or “False-positive hepatitis A IgM,” revealed a total of 3 cases, with a false-positive HAV-IgM and related conditions [17,29,30]. Two cases of false-positive HAV-IgM were associated with AIH [17,29]; Table 1.

Table 1

False-positive HAV-IgM cases reported

Case Country Age Sex True etiology LFT Immunologic test False HAV-IgM Potential impact Report
1 Australia 54 F Idiopathic scleritis;DILI by infliximab ALT, 829 U/L; AST, 554 U/L IgG, 18.4 g/L; IgM, 5.71 g/L; ANA), 1:640 Measured on 2 occasions Infliximab treatment was discontinued, biochemical improvement within 11 weeks Elaine Tennant [17]
1 USA 78 F Congestive heart failure Mildly abnormal liver enzyme levels, which resolved as her CHF was treated N/A Low index, twice the cutoff Public health investigation, exclusion from adult daycare center Marie Louise Landry [30]
1 Switzerland 38 F Autoimmune hepatitis and EBV infection ALT,424 U/L; AST, 244 U/L ANA ≥ 1:320; SMA ≥ 1:80 Three times were detected, HAVIgM (+, +, −); HAVIgG (+, −, −) N/A Marika Valota [29]

False positives for IgM usually occur under three circumstances. First, diseases with similar clinical presentation, such as infectious mononucleosis, CMV infection, EBV infection, human immunodeficiency virus infection [16,19,20], rubella, measles [31,32], hepatitis A, and hepatitis E viral infection [12,33,34]. However, false positives of HAV-IgM caused by CMV, EBV, and HIV are still reported in individual cases, and the mechanism is thought to be an immune cross-reaction. For example, EBV and HAV may induce autologous production of antibodies against triosephosphate isomerase (IgM anti-TPI)) [35]. Abnormal autoantibody-induced immune damage can lead to hemolysis.

Secondly, when there is an overlap with the etiology of other diseases. Finally, IgM positivity with no corresponding clinical symptoms, biochemical indicators, or histological evidence.

False-positive IgM results can lead to a disproportionate response in the prevention and control of infectious disease, thus delaying the treatment of the original disease. This patient was diagnosed with acute HAV, and this attracted the attention of the disease control department. The residence was disinfected, and the patient was forcibly hospitalized in isolation. This inconvenienced both, her work and her life, in addition to mental trauma. Simultaneously, the treatment of AIH was also delayed to a certain extent. The same confusion was seen in other case reports. A 76-year-old woman with congestive heart failure was diagnosed as having HAV by a community doctor in view of a positive HAV-IgM test, which resulted in her being barred from living in the community [30]. False-positive HAV-IgM leads to misdiagnosis of the original condition, leading to the failure of timely and correct diagnosis and treatment of the primary disease. For example, in this case, corticosteroid therapy was used to control the disease until AIH was confirmed by liver histological examination. In China, if liver function is abnormal, especially if liver enzyme levels are elevated, hepatologists often prescribe dicyclol and other drugs, which have been proven to be beneficial for liver inflammation repair, improvement of fibrosis, and alleviation of liver enzymes [36,37]. Although these drugs are yet to be validated in prospective, randomized, controlled, multicenter studies, no significant side effects have been found with these drugs. Some patients use Chinese herbs, including Schisandra fruit and Chuangcao, to protect the liver [38,39]. These herbs have also been shown to be beneficial for treating liver diseases.

Therefore, even though a positive HAV-IgM test forms the basis for the diagnosis of acute HAV, it should not be accepted as the only confirmatory test, especially when results persist, the patient’s condition is severe enough to require hospitalization, or when there are no epidemiological findings. Instead, wherever possible, the diagnosis should be confirmed by other means.

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Appendix

Table A1

Changes of main indexes of liver function and immunoglobulin G

Time (w) TBIL (mol/L) ALT (U/L) AST (U/L) ALP (U/L) GGT (U/L) IgG (g/L)
0 8.3 56 45 109 65 18.3
1 12.7 131.2 89 97 49
4 7.8 104 77 115 64
20 11.7 86 48 142 90 21.6
36 5.4 147 112 108 57
48 13.5 123 94 142 59 26.3
49 21.7 327 227 128 86
50 43 572 554 175 112
51 32.5 164.4 107 118 89 19.5
52 12.6 137.1 84 97 57
56 11.7 86.4 56 115 49
60 10.6 35.2 28 138 63 13.8
64 8.5 31.6 22 96 38
68 10.7 28.6 18 69 36
72 9.4 25.2 23 79 47 8.5

W: week; TIL: total bilirubin; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ALP: alkaline phosphatase; GGT: glutamine transpeptidase.

  1. Funding information: No funding was received.

  2. Author contributions: Y.W. Tan designed the research; L. Chen collected and analyzed the data, and drafted the manuscript; Y.W. Tan wrote and revised the manuscript; all authors have read and approved the final version to be published.

  3. Conflict of interest: The authors declare that they have no conflict of interest.

  4. Data availability statement: The data of the study are available from the corresponding author on reasonable request.

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Received: 2021-05-30
Revised: 2021-07-19
Accepted: 2021-07-22
Published Online: 2021-09-07

© 2021 Youwen Tan and Li Chen, published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  72. Accurate diagnosis of prostate cancer using logistic regression
  73. miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
  74. Prognostic significance of TRIM28 expression in patients with breast carcinoma
  75. Integrative bioinformatics analysis of KPNA2 in six major human cancers
  76. Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
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  78. Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression
  79. Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
  80. Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
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  86. Relation between IL-8 level and obstructive sleep apnea syndrome
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  88. Nomogram prediction model for renal anaemia in IgA nephropathy patients
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  90. NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
  91. A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
  92. Clinical and prognostic features of MMP-2 and VEGF in AEG patients
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  94. Functional implications of PABPC1 in the development of ovarian cancer
  95. Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
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  97. Prediction of improvement after anterior cruciate ligament reconstruction
  98. Effluent Osteopontin levels reflect the peritoneal solute transport rate
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  104. Knee alterations in rheumatoid arthritis: Comparison of US and MRI
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  106. lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
  107. Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
  108. Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
  109. Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
  110. Travelers’ vaccines and their adverse events in Nara, Japan
  111. Association between Tfh and PGA in children with Henoch–Schönlein purpura
  112. Can exchange transfusion be replaced by double-LED phototherapy?
  113. circ_0005962 functions as an oncogene to aggravate NSCLC progression
  114. Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
  115. Serum intact fibroblast growth factor 23 in healthy paediatric population
  116. Algorithm of rational approach to reconstruction in Fournier’s disease
  117. A meta-analysis of exosome in the treatment of spinal cord injury
  118. Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
  119. Dexmedetomidine may decrease the bupivacaine toxicity to heart
  120. Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
  121. Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
  122. External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
  123. miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
  124. HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
  125. Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
  126. Cell population data in identifying active tuberculosis and community-acquired pneumonia
  127. Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
  128. Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
  129. 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
  130. Association of gene polymorphisms with women urinary incontinence
  131. Influence of COVID-19 pandemic on stress levels of urologic patients
  132. miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
  133. miR-519d downregulates LEP expression to inhibit preeclampsia development
  134. Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
  135. Fluorescent light energy modulates healing in skin grafted mouse model
  136. Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
  137. Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
  138. Severe postoperative hyperbilirubinemia in congenital heart disease
  139. Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
  140. Clinical factors predicting ureteral stent failure in patients with external ureteral compression
  141. Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
  142. Triple-Endobutton and clavicular hook: A propensity score matching analysis
  143. Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
  144. Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
  145. miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
  146. Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
  147. The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
  148. Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
  149. No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
  150. circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
  151. Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
  152. Educational program for orthopedic surgeons’ influences for osteoporosis
  153. Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
  154. GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
  155. lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
  156. Anticoagulation is the answer in treating noncritical COVID-19 patients
  157. Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
  158. Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
  159. VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
  160. Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
  161. Treatment of osteoporosis with teriparatide: The Slovenian experience
  162. New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
  163. Superenhancer–transcription factor regulatory network in malignant tumors
  164. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
  165. Clinical features of atypical tuberculosis mimicking bacterial pneumonia
  166. Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
  167. Effect of electromagnetic field on abortion: A systematic review and meta-analysis
  168. miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
  169. MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
  170. Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
  171. miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
  172. Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
  173. MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
  174. Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
  175. circATP2A2 promotes osteosarcoma progression by upregulating MYH9
  176. Prognostic role of oxytocin receptor in colon adenocarcinoma
  177. Review Articles
  178. The function of non-coding RNAs in idiopathic pulmonary fibrosis
  179. Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
  180. Role of cesarean section in the development of neonatal gut microbiota: A systematic review
  181. Small cell lung cancer transformation during antitumor therapies: A systematic review
  182. Research progress of gut microbiota and frailty syndrome
  183. Recommendations for outpatient activity in COVID-19 pandemic
  184. Rapid Communication
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  186. Use of microspheres in embolization for unruptured renal angiomyolipomas
  187. COVID-19 cases with delayed absorption of lung lesion
  188. A triple combination of treatments on moderate COVID-19
  189. Social networks and eating disorders during the Covid-19 pandemic
  190. Letter
  191. COVID-19, WHO guidelines, pedagogy, and respite
  192. Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
  193. COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
  194. What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
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  197. CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
  198. Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
  199. Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
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  203. Ovarian female adnexal tumor of probable Wolffian origin – Case report
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  206. Primary orbital ganglioneuroblastoma: A case report
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  208. Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
  209. Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
  210. Chondroblastoma of mandibular condyle: Case report and literature review
  211. Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
  212. Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
  213. Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
  214. High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
  215. Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
  216. Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
  217. Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
  218. Retraction
  219. Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
  220. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
  221. An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
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https://doi.org/10.1515/med-2021-0336
Keywords for this article
immunoglobulin M; hepatitis A; false-positive
Creative Commons
BY 4.0

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  70. FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer
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  73. miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
  74. Prognostic significance of TRIM28 expression in patients with breast carcinoma
  75. Integrative bioinformatics analysis of KPNA2 in six major human cancers
  76. Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
  77. A four-lncRNA signature for predicting prognosis of recurrence patients with gastric cancer
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  79. Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
  80. Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
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  88. Nomogram prediction model for renal anaemia in IgA nephropathy patients
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  121. Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
  122. External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
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  125. Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
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  127. Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
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  129. 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
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  131. Influence of COVID-19 pandemic on stress levels of urologic patients
  132. miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
  133. miR-519d downregulates LEP expression to inhibit preeclampsia development
  134. Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
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  136. Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
  137. Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
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  139. Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
  140. Clinical factors predicting ureteral stent failure in patients with external ureteral compression
  141. Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
  142. Triple-Endobutton and clavicular hook: A propensity score matching analysis
  143. Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
  144. Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
  145. miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
  146. Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
  147. The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
  148. Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
  149. No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
  150. circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
  151. Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
  152. Educational program for orthopedic surgeons’ influences for osteoporosis
  153. Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
  154. GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
  155. lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
  156. Anticoagulation is the answer in treating noncritical COVID-19 patients
  157. Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
  158. Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
  159. VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
  160. Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
  161. Treatment of osteoporosis with teriparatide: The Slovenian experience
  162. New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
  163. Superenhancer–transcription factor regulatory network in malignant tumors
  164. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
  165. Clinical features of atypical tuberculosis mimicking bacterial pneumonia
  166. Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
  167. Effect of electromagnetic field on abortion: A systematic review and meta-analysis
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  169. MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
  170. Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
  171. miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
  172. Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
  173. MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
  174. Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
  175. circATP2A2 promotes osteosarcoma progression by upregulating MYH9
  176. Prognostic role of oxytocin receptor in colon adenocarcinoma
  177. Review Articles
  178. The function of non-coding RNAs in idiopathic pulmonary fibrosis
  179. Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
  180. Role of cesarean section in the development of neonatal gut microbiota: A systematic review
  181. Small cell lung cancer transformation during antitumor therapies: A systematic review
  182. Research progress of gut microbiota and frailty syndrome
  183. Recommendations for outpatient activity in COVID-19 pandemic
  184. Rapid Communication
  185. Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
  186. Use of microspheres in embolization for unruptured renal angiomyolipomas
  187. COVID-19 cases with delayed absorption of lung lesion
  188. A triple combination of treatments on moderate COVID-19
  189. Social networks and eating disorders during the Covid-19 pandemic
  190. Letter
  191. COVID-19, WHO guidelines, pedagogy, and respite
  192. Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
  193. COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
  194. What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
  195. Case Report
  196. Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
  197. CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
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