The Open Rheumatology Journal




ISSN: 1874-3129 ― Volume 14, 2020
CASE REPORT

Multiple Hepatic Micro-Hypodensities as a Presenting Sign in Systemic Lupus Erythematosus- A Case Report



Samarth Mathapathi1, *, Michael Preziosi1
1 Department of Internal Medicine, Scripps Clinic-Green Hospital, California, USA

Abstract

Systemic Lupus Erythematosus (SLE) is a chronic multisystemic inflammatory disorder that can present with a wide array of signs and symptoms. Hepatic involvement is commonly limited to a subclinical biochemical transaminitis while clinically significant liver disease is rare. A case of a 22-year-old female who presented with abdominal pain, fevers, arthralgia, and several hepatic hypodense lesions with normal liver function tests is reported in this study. She failed to improve with antibiotics and infectious workup was largely unrevealing. She was found to have a positive ANA, high titers of anti-double-stranded DNA antibody, and was ultimately diagnosed with new-onset SLE with hepatic aseptic micro-abscesses. Her symptoms were self-limiting, and she was later started on a low-dose prednisone taper and hydroxychloroquine. This case demonstrates that hepatic involvement, despite normal liver function tests, should be considered in SLE patients presenting with abdominal pain.

Keywords: SLE, Transaminitis, Hepatic vasculitis, Aseptic micro-abscess, Abdominal pain, Anti-dsDNA.


Article Information


Identifiers and Pagination:

Year: 2020
Volume: 14
First Page: 22
Last Page: 27
Publisher Id: TORJ-14-22
DOI: 10.2174/1874312902014010022

Article History:

Received Date: 02/04/2020
Revision Received Date: 09/06/2020
Acceptance Date: 19/06/2020
Electronic publication date: 08/09/2020
Collection year: 2020

© 2020 Mathapathi and Preziosi.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the Department of Internal Medicine, Scripps Clinic-Green Hospital, California, United States; E-mail: mathapathi.samarth@scrippshealth.org





1. INTRODUCTION

Systemic Lupus Erythematosus (SLE) is a complex chronic inflammatory disorder often with multi-organ involvement. The underlying etiology is unknown, and pathophysiology involves the production of several pathological auto-antibodies. Any organ system from musculoskeletal, renal, cutaneous, cardiovascular, hematological, and CNS has known to be affected in SLE. Gastrointestinal (GI) involvement has been described in various forms, from enteritis and protein-losing enteropathy to small bowel obstruction [1Fava A, Petri M. Systemic lupus erythematosus: Diagnosis and clinical management. J Autoimmun 2019; 96: 1-13.
[http://dx.doi.org/10.1016/j.jaut.2018.11.001] [PMID: 30448290]
-3Hoffman BI, Katz WA. The gastrointestinal manifestations of systemic lupus erythematosus: A review of the literature. Semin Arthritis Rheum 1980; 9(4): 237-47.
[http://dx.doi.org/10.1016/0049-0172(80)90016-5] [PMID: 6996096]
]. The most common hepatic injury in SLE is a subclinical transaminitis in either hepatocellular or cholestatic patterns [2Brewer BN, Kamen DL. Gastrointestinal and hepatic disease in systemic lupus erythematosus. Rheum Dis Clin North Am 2018; 44(1): 165-75.
[http://dx.doi.org/10.1016/j.rdc.2017.09.011] [PMID: 29149925]
-5Chowdhary VR, Crowson CS, Poterucha JJ, Moder KG. Liver involvement in systemic lupus erythematosus: Case review of 40 patients. J Rheumatol 2008; 35(11): 2159-64.
[http://dx.doi.org/10.3899/jrheum.080336] [PMID: 18793002]
]. Here, a case of a young woman with normal liver function tests presenting with multiple hepatic lesions directly related to an initial presentation of SLE, is reported.

2. CASE PRESENTATION

A 22-year-old female presented to the emergency room with abdominal pain and headache. Her symptoms began ten days ago with sharp, non-radiating right upper quadrant abdominal pain that progressively worsened to 7/10 in severity. There was no association with food intake, loss of appetite, diarrhea, nausea, or vomiting. She denied any change in bowel

habits or characteristics. Three days after the onset of pain, she developed several symptoms a sore throat with multiple painful oral ulcers, diffuse arthralgia, non-productive cough, intermittent fevers up to 102° F, and a 15lb weight loss in the last two months. She denied any Raynaud’s phenomenon, joint swelling, or skin changes. She reported a history of occasional painful vaginal ulcers in the past and noticed them a few days prior that seemed to have resolved. She was previously tested for sexually transmitted diseases and was found to be negative for HSV, gonorrhea/chlamydia, and HIV.

Four days before admission, she presented to local urgent care and was diagnosed with an acute viral syndrome. She was started on amoxicillin/clavulanic acid for a possible developing bacterial respiratory infection. Other than an improvement in her oral ulcers, she denied any change in her symptoms and represented to the emergency room for ongoing abdominal pain and a new frontal headache. The headache was constant and minimally responsive to acetaminophen. She had no associated vision/hearing changes, vertigo, auras, and this was not like her baseline migraines.

Her medical history was notable for migraines, as mentioned above, and she had a strong family history of autoimmunity. Her father had Grave’s disease, and mother and maternal aunt had SLE. She was sexually active and used barrier contraception with a monogamous partner. She denied any recent travel, new or undercooked foods, sick contacts, significant smoking, alcohol use, or illicit drug use.

Her initial vital signs were: blood pressure of 115/76 mmHg, heart rate of 75, temperature of 36.8 °C, respiratory rate of 18 breaths/min, and oxygen saturation of 97% on room air. She appeared non-toxic, well-nourished, and well-developed. No oral or genital ulcers were observed. The cardiac and pulmonary exam was unremarkable. An abdominal exam was notable for normoactive bowel sounds and moderate-severe right upper quadrant tenderness without any rebound tenderness, distention, palpable masses, or hepatosplenomegaly. There were no rashes, jaundice, or skin pallor. There was no palpable lymphadenopathy. The musculoskeletal exam was also unremarkable with an intact range of motion and no extremity edema, synovitis, or weakness. There was no palpable nuchal rigidity, and Brudzinski's and Kernig signs were negative. The remainder of the exam was also unremarkable.

The initial differential focused on an infectious etiology. Pertinent results are noted in Tables 1-3. No table labs were: serum white blood cell count 12.5 K/mcL, hemoglobin 12.0 g/dL, platelets 262 K/mcL, creatinine of 0.7 mg/dL, aspartate aminotransaminase 25 U/L, alanine aminotransaminase 12 U/L, total bilirubin 0.4 mg/dL, partial thromboplastin time 12.6 seconds, international normalized ratio 1.1, albumin 4.1 g/dL and total protein of 7.4 g/dL. Microscopic urinalysis was notable for no proteins/casts, 3-5 WBC/HPF, small leukocyte esterase, negative nitrites, and negative for urine hCG. Since she also complained of a new headache, we performed a lumbar puncture. The results are as follows: CSF protein 13 mg/dL, glucose 62 mg/dL, cell count with 1 nucleated cell and 93 red blood cells/mcL, and a negative gram stain. MRI of her brain and cervical spine did not reveal any concerning findings.

Table 1
Selected results of the initial diagnostic workup.


Table 2
Results of infectious workup.


Table 3
Results of pertinent rheumatological workup. ANA= anti-nuclear antibody.


Chest x-ray was notable for new mild bilateral pleural effusions (Fig. 1). Right upper quadrant ultrasound with doppler did not reveal any concerning lesions, and portal vasculature was patent. Subsequent computerized tomography of her abdomen and pelvis without contrast revealed several hepatic lesions concerning micro-abscesses (Fig. 2).

Pertinent results of the infectious workup were: hepatitis A IgM negative, hepatitis B surface antigen and core antibody negative, hepatitis C antibody negative, HIV p24 antigen/IgM/IgG negative, QuantiFERON gold negative, histoplasma antigen negative. The remainder of the infectious workup is listed in Table 2, but it was overall unrevealing. Based on the negative infectious workup, the focus was subsequently shifted to a rheumatological workup detailed in Table 3: estimated sedimentation rate 59 mm/hr, c-reactive protein 88.9, anti-neutrophil antibody 1:40, anti-double stranded DNA 118 IU, anti-nuclear cytoplasm antibody negative-PR3/MPO negative, anti-Sjogren's syndrome A/B negative, anti-smith antibody negative, anti-cardiolipin IgG < 10, dilute Russell viper venom time screen ratio (DRVVT) 3.44, C3 72 mg/dL, C4 15 mg/dL, rheumatoid factor < 10, and ferritin 104 ng/mL. Unfortunately, no biopsy was done due to the size and characteristics of the lesions.

Fig. (1)
PA-lateral chest x-ray on admission. Arrows highlight small bilateral pleural effusions.


Fig. (2)
CT scan without contrast of the abdomen and pelvis. Arrows highlight selected hepatic lesions initially concerning for micro-abscesses.


She was started on broad-spectrum antibiotics with intravenous vancomycin, cefepime, and metronidazole for possible pyogenic vs. amoebic hepatic abscesses. However, she did not improve following three days of IV antibiotics, and her abdominal pain and arthralgia persisted. Based on her strong family history, clinical symptoms, positive anti-dsDNA, positive ANA, low C3, and elevated DRVVT, she was ultimately diagnosed with new-onset SLE. Parenteral corticosteroids were not initially started due to ongoing concern for an underlying infectious process. Her arthralgia, abdominal pain, and fevers started to improve spontaneously with naproxen prior to initiation of parenteral corticosteroids, hence they were not administered, and she was monitored closely. She was discharged on hospital day eight and started on hydroxychloroquine and low-dose prednisone taper as an outpatient with significant clinical improvement.

3. DISCUSSION

Gastrointestinal involvement has been well described and nearly 40% of all individuals with SLE are reported to have some form of GI involvement in their lifetime [3Hoffman BI, Katz WA. The gastrointestinal manifestations of systemic lupus erythematosus: A review of the literature. Semin Arthritis Rheum 1980; 9(4): 237-47.
[http://dx.doi.org/10.1016/0049-0172(80)90016-5] [PMID: 6996096]
]. Hepatic involvement is commonly seen as a non-specific transaminitis with either cholestatic or hepatocellular pattern, but clinically significant hepatic dysfunction from SLE is thought to be uncommon [4Runyon BA, LaBrecque DR, Anuras S. The spectrum of liver disease in systemic lupus erythematosus. Report of 33 histologically-proved cases and review of the literature. Am J Med 1980; 69(2): 187-94.
[http://dx.doi.org/10.1016/0002-9343(80)90378-2] [PMID: 7405944]
, 5Chowdhary VR, Crowson CS, Poterucha JJ, Moder KG. Liver involvement in systemic lupus erythematosus: Case review of 40 patients. J Rheumatol 2008; 35(11): 2159-64.
[http://dx.doi.org/10.3899/jrheum.080336] [PMID: 18793002]
]. In one review of 40 SLE patients with clinically significant hepatic dysfunction, the underlying etiologies were found to be due to: primary biliary cholangitis (n=3), drug-induced (n=4), viral hepatitis (n=8), NAFLD (n=8), autoimmune hepatitis (n=8) and miscellaneous (n=11)- liver involvement from infection [2Brewer BN, Kamen DL. Gastrointestinal and hepatic disease in systemic lupus erythematosus. Rheum Dis Clin North Am 2018; 44(1): 165-75.
[http://dx.doi.org/10.1016/j.rdc.2017.09.011] [PMID: 29149925]
], cryptogenic cirrhosis [2Brewer BN, Kamen DL. Gastrointestinal and hepatic disease in systemic lupus erythematosus. Rheum Dis Clin North Am 2018; 44(1): 165-75.
[http://dx.doi.org/10.1016/j.rdc.2017.09.011] [PMID: 29149925]
], lymphoma [1Fava A, Petri M. Systemic lupus erythematosus: Diagnosis and clinical management. J Autoimmun 2019; 96: 1-13.
[http://dx.doi.org/10.1016/j.jaut.2018.11.001] [PMID: 30448290]
], and indeterminate [6Miller MH, Urowitz MB, Gladman DD, Blendis LM. The liver in systemic lupus erythematosus. Q J Med 1984; 53(211): 401-9.
[PMID: 6484120]
]. Following a median follow-up of 44 months, 5-year serious liver disease-free survival was 93% [5Chowdhary VR, Crowson CS, Poterucha JJ, Moder KG. Liver involvement in systemic lupus erythematosus: Case review of 40 patients. J Rheumatol 2008; 35(11): 2159-64.
[http://dx.doi.org/10.3899/jrheum.080336] [PMID: 18793002]
]. Runyon et al. reported that out of 238 SLE patients, 60% of patients were found to have at least one liver function test abnormality, but only 20% showed any existence of a clinical liver disease. The diagnosis of liver disease in that cohort occurred either up to four years before or five years after the diagnosis of SLE [4Runyon BA, LaBrecque DR, Anuras S. The spectrum of liver disease in systemic lupus erythematosus. Report of 33 histologically-proved cases and review of the literature. Am J Med 1980; 69(2): 187-94.
[http://dx.doi.org/10.1016/0002-9343(80)90378-2] [PMID: 7405944]
]. In another retrospective review of 100 SLE patients with transaminitis, only 23% showed an elevation in liver function test thought to be due to SLE hepatic involvement with no other explainable cause for the liver disease [6Miller MH, Urowitz MB, Gladman DD, Blendis LM. The liver in systemic lupus erythematosus. Q J Med 1984; 53(211): 401-9.
[PMID: 6484120]
]. These reports highlight that liver function abnormalities in SLE patients often may have another underlying etiology to explain their abnormality, and true hepatic involvement from SLE is less common. Moreover, frank hepatic lesions in SLE are a rare subset in true hepatic involvement. It is suspected the hepatic lesions in this case were related to a new SLE diagnosis since no other discernable etiology was found. Alanazi et al. reported a similar case in a young woman with SLE who developed right upper quadrant pain, elevated liver function tests, and later was found to have hepatic vasculitis mimicking as liver abscesses. Biopsy of that hepatic lesion showed generalized mild chronic inflammation [7Alanazi T, Alqahtani M, Al Duraihim H, et al. Hepatic vasculitis mimicking liver abscesses in a patient with systemic lupus erythematosus. Ann Saudi Med 2009; 29(6): 474-7.
[http://dx.doi.org/10.4103/0256-4947.57172] [PMID: 19847087]
]. Miyake et al. also reported a patient with distinct liver densities and elevated liver function tests that were concerning for lupus-related vasculitis. Biopsy showed inflammatory cell infiltration and subtle necrosis [8Miyake Y, Tada S, Nakamura Y, Kojima K, Takeda N, Jitsunari F. [A young male of systemic lupus erythematosus with hepatic lesions showing multiple low density spots in CT of liver]. Nihon Rinsho Meneki Gakkai Kaishi 1999; 22(1): 23-9. [Article in Japanese].
[http://dx.doi.org/10.2177/jsci.22.23] [PMID: 11185688]
]. Both of those cases were treated with high dose corticosteroids with improvement in symptoms and lesions. This case reflected either an underlying vasculitic process or aseptic micro-abscesses directly related to underlying SLE. Unfortunately, no biopsy was done to help aid the diagnostic process. Aseptic liver abscesses have been described in inflammatory bowel disease, particularly Crohn’s, but are rare in systemic inflammatory conditions [9Zakout R, Fonseca M, Santos JM, et al. Multiple aseptic liver abscesses as the initial manifestation of Crohn’s disease: Report of a case. Dis Colon Rectum 2009; 52(2): 343-5.
[http://dx.doi.org/10.1007/DCR.0b013e318199db60] [PMID: 19279433]
]. Maeshima et al. reported a case of aseptic abscesses in a patient with Behcet’s disease that improved with corticosteroid therapy [10Maeshima K, Ishii K, Inoue M, Himeno K, Seike M. Behçet’s disease complicated by multiple aseptic abscesses of the liver and spleen. World J Gastroenterol 2013; 19(20): 3165-8.
[http://dx.doi.org/10.3748/wjg.v19.i20.3165] [PMID: 23717000]
, 11Kavanaugh AF, Solomon DH. Guidelines for immunologic laboratory testing in the rheumatic diseases: Anti-DNA antibody tests. Arthritis Rheum 2002; 47(5): 546-55.
[http://dx.doi.org/10.1002/art.10558] [PMID: 12382306]
]. The diagnosis of Behçet’s was considered based on her reported painful oral and vaginal lesions but similar lesions in SLE have also been reported [12Uva L, Miguel D, Pinheiro C, Freitas JP, Marques Gomes M, Filipe P. Cutaneous manifestations of systemic lupus erythematosus. Autoimmune Dis 2012; 2012834291
[http://dx.doi.org/10.1155/2012/834291] [PMID: 22888407]
]. Ultimately, she satisfied the 2019 ACR/EULAR criteria for SLE with positive ANA, arthralgias, mucosal ulcers, pleural effusion, elevated anti-dsDNA, and elevated DRVVT [13Aringer M, Costenbader K, Daikh D, et al. 2019 European league against rheumatism/american college of rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol 2019; 71(9): 1400-12.
[http://dx.doi.org/10.1002/art.40930] [PMID: 31385462]
, 14Gibson T, Myers AR. Subclinical liver disease in systemic lupus erythematosus. J Rheumatol 1981; 8(5): 752-9.
[PMID: 7310775]
]. However, it was noted that her ANA titer is below the recognized titer of 1:80 noted in the most recent ACR/EULAR criteria. Her diagnosis was corroborated by high titers of anti-dsDNA antibody that has a reported specificity of up to 97.4% and a positive LR > 10 for SLE and her overall clinical picture in this setting was felt to be sufficient to meet the diagnosis of SLE [11Kavanaugh AF, Solomon DH. Guidelines for immunologic laboratory testing in the rheumatic diseases: Anti-DNA antibody tests. Arthritis Rheum 2002; 47(5): 546-55.
[http://dx.doi.org/10.1002/art.10558] [PMID: 12382306]
].

This case interestingly did not present with a transaminitis. The studies discussed above involved some form of liver function test abnormality consistent with common hepatic findings. This case may have been in its early stages and had not yet reached a point of precipitating a transaminitis, but her serological studies and clinical presentation was consistent with a flare and not a subclinical state suggesting that hepatic involvement may not reflect the underlying stage of SLE.

CONCLUSION

SLE can be difficult to diagnose due to the variability in presentation, organ system involvement, and seropositivity. Symptoms can be non-specific and serological workup can often only be suggestive. Hepatic involvement should be considered if transaminitis is present and not explained by other more common etiologies such as infectious, ischemic, or local inflammatory. Autoimmune hepatitis (AIH) is often a consideration and was on differential. AIH is thought to have distinct pathophysiology from hepatic involvement in SLE but can present similarly with transaminitis, arthralgia, and constitutional symptoms. Apart from ANA, several different auto-antibodies-notably anti-smooth muscle, anti-actin, anti-SLA/LP, and anti-mitochondrial can be involved in AIH and usually does not involve anti-phospholipid antibodies. Moreover, there are no characteristic imaging findings in AIH, unlike with SLE, as seen in this case. Imaging findings are often unremarkable and do not aid in the diagnosis of AIH. AIH histopathological studies often show abundant plasma and lymphocytic infiltration with necrosis compared to SLE involvement, which tends to have milder inflammation with a paucity of lymphocytes. The prognosis without treatment is poor in AIH and can lead to cirrhosis compared to hepatic involvement in SLE, which can be benign [15Heneghan MA, Yeoman AD, Verma S, Smith AD, Longhi MS. Autoimmune hepatitis. Lancet 2013; 382(9902): 1433-44.
[http://dx.doi.org/10.1016/S0140-6736(12)62163-1] [PMID: 23768844]
, 16Hofer H, Oesterreicher C, Wrba F, Ferenci P, Penner E. Centrilobular necrosis in autoimmune hepatitis: A histological feature associated with acute clinical presentation. J Clin Pathol 2006; 59(3): 246-9.
[http://dx.doi.org/10.1136/jcp.2005.029348] [PMID: 16505273]
].

Overall, hepatic involvement varies in degree and character in SLE and should be considered in patients with abdominal symptoms, even in the setting of normal liver function tests. The severity of hepatic involvement can vary and may not reflect the severity of underlying SLE.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

Not applicable.

HUMAN AND ANIMAL RIGHTS

Not applicable.

CONSENT FOR PUBLICATION

Informed consent was taken from all the participants when they were enrolled.

STANDARDS OF REPORTING

CARE guidelines have been followed in this study.

FUNDING

None.

CONFLICT OF INTEREST

The authors have no relevant conflicts of interest or financial supports to disclose. To protect patient privacy, identifying information including names, initials, or hospital rooms are not described in manuscript and figures.

ACKNOWLEDGEMENTS

Declared none.

REFERENCES

[1] Fava A, Petri M. Systemic lupus erythematosus: Diagnosis and clinical management. J Autoimmun 2019; 96: 1-13.
[http://dx.doi.org/10.1016/j.jaut.2018.11.001] [PMID: 30448290]
[2] Brewer BN, Kamen DL. Gastrointestinal and hepatic disease in systemic lupus erythematosus. Rheum Dis Clin North Am 2018; 44(1): 165-75.
[http://dx.doi.org/10.1016/j.rdc.2017.09.011] [PMID: 29149925]
[3] Hoffman BI, Katz WA. The gastrointestinal manifestations of systemic lupus erythematosus: A review of the literature. Semin Arthritis Rheum 1980; 9(4): 237-47.
[http://dx.doi.org/10.1016/0049-0172(80)90016-5] [PMID: 6996096]
[4] Runyon BA, LaBrecque DR, Anuras S. The spectrum of liver disease in systemic lupus erythematosus. Report of 33 histologically-proved cases and review of the literature. Am J Med 1980; 69(2): 187-94.
[http://dx.doi.org/10.1016/0002-9343(80)90378-2] [PMID: 7405944]
[5] Chowdhary VR, Crowson CS, Poterucha JJ, Moder KG. Liver involvement in systemic lupus erythematosus: Case review of 40 patients. J Rheumatol 2008; 35(11): 2159-64.
[http://dx.doi.org/10.3899/jrheum.080336] [PMID: 18793002]
[6] Miller MH, Urowitz MB, Gladman DD, Blendis LM. The liver in systemic lupus erythematosus. Q J Med 1984; 53(211): 401-9.
[PMID: 6484120]
[7] Alanazi T, Alqahtani M, Al Duraihim H, et al. Hepatic vasculitis mimicking liver abscesses in a patient with systemic lupus erythematosus. Ann Saudi Med 2009; 29(6): 474-7.
[http://dx.doi.org/10.4103/0256-4947.57172] [PMID: 19847087]
[8] Miyake Y, Tada S, Nakamura Y, Kojima K, Takeda N, Jitsunari F. [A young male of systemic lupus erythematosus with hepatic lesions showing multiple low density spots in CT of liver]. Nihon Rinsho Meneki Gakkai Kaishi 1999; 22(1): 23-9. [Article in Japanese].
[http://dx.doi.org/10.2177/jsci.22.23] [PMID: 11185688]
[9] Zakout R, Fonseca M, Santos JM, et al. Multiple aseptic liver abscesses as the initial manifestation of Crohn’s disease: Report of a case. Dis Colon Rectum 2009; 52(2): 343-5.
[http://dx.doi.org/10.1007/DCR.0b013e318199db60] [PMID: 19279433]
[10] Maeshima K, Ishii K, Inoue M, Himeno K, Seike M. Behçet’s disease complicated by multiple aseptic abscesses of the liver and spleen. World J Gastroenterol 2013; 19(20): 3165-8.
[http://dx.doi.org/10.3748/wjg.v19.i20.3165] [PMID: 23717000]
[11] Kavanaugh AF, Solomon DH. Guidelines for immunologic laboratory testing in the rheumatic diseases: Anti-DNA antibody tests. Arthritis Rheum 2002; 47(5): 546-55.
[http://dx.doi.org/10.1002/art.10558] [PMID: 12382306]
[12] Uva L, Miguel D, Pinheiro C, Freitas JP, Marques Gomes M, Filipe P. Cutaneous manifestations of systemic lupus erythematosus. Autoimmune Dis 2012; 2012834291
[http://dx.doi.org/10.1155/2012/834291] [PMID: 22888407]
[13] Aringer M, Costenbader K, Daikh D, et al. 2019 European league against rheumatism/american college of rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol 2019; 71(9): 1400-12.
[http://dx.doi.org/10.1002/art.40930] [PMID: 31385462]
[14] Gibson T, Myers AR. Subclinical liver disease in systemic lupus erythematosus. J Rheumatol 1981; 8(5): 752-9.
[PMID: 7310775]
[15] Heneghan MA, Yeoman AD, Verma S, Smith AD, Longhi MS. Autoimmune hepatitis. Lancet 2013; 382(9902): 1433-44.
[http://dx.doi.org/10.1016/S0140-6736(12)62163-1] [PMID: 23768844]
[16] Hofer H, Oesterreicher C, Wrba F, Ferenci P, Penner E. Centrilobular necrosis in autoimmune hepatitis: A histological feature associated with acute clinical presentation. J Clin Pathol 2006; 59(3): 246-9.
[http://dx.doi.org/10.1136/jcp.2005.029348] [PMID: 16505273]
Track Your Manuscript:


Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


SCImago Journal Ranking

SCImago Journal & Country Rank

Browse Contents




Webmaster Contact: info@benthamopen.net
Copyright © 2020 Bentham Open