AUCTORES
Globalize your Research
Review Article | DOI: https://doi.org/10.31579/2692-9392/182
1 Senior Consultant Pediatric Gastroenterologist, Rainbow Children’s Hospital, Chennai, Tamil Nādu, India.
2 Senior Consultant Pediatrician, Rainbow Children’s Hospital, 157, Anna Salai, Guindy, Chennai-600015, Tamil Nādu, India.
*Corresponding Author: Malathi Sathiyasekaran, Senior Consultant Pediatric Gastroenterologist.
Citation: Malathi Sathiyasekaran and R. Ganesh, (2023), Approach to Metabolic Liver Disease in Children, Archives of Medical Case Reports and Case Study, 7(4); DOI:10.31579/2692-9392/182
Copyright: © 2023, Malathi Sathiyasekaran. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 14 September 2023 | Accepted: 21 September 2023 | Published: 28 September 2023
Keywords: children; metabolic liver disease; gene testing; liver transplant; special diet
Metabolic liver diseases (MLD) is a collective term for inherited single enzyme defects of inborn errors of metabolism (IEM) which primarily or secondarily involve the liver. With recent advances in diagnosis and therapeutics, most inherited metabolic liver disorders are now being diagnosed and treated. This article outlines the important metabolic liver diseases in children and highlights the approach to evaluation and management
Metabolic liver diseases (MLD) is a collective term for inherited single enzyme defects of inborn errors of metabolism (IEM) which primarily or secondarily involve the liver. Since liver plays a pivotal role in several anabolic and catabolic biochemical reactions involving carbohydrates, protein, lipid and minerals, it is the target organ in several IEM. Hepatomegaly, hepatosplenomegaly and / or disturbed liver function or structure form an integral part of this disorder. There are more than 700 disparate IEMs that present with liver disease in infancy and childhood [1]. However the clinical manifestations are limited. MLD are generally considered a rare subset of liver diseases not amenable to treatment. However with advances in diagnosis inclusive of immuno-histochemistry staining in pathology, enzyme estimations, gas chromatography–mass spectrometry in blood/urine and genetic studies it is possible to make a definite diagnosis. A parallel advancement has also occurred in therapeutics in the form of special dietary formulae, enzyme replacement therapy, novel medications, hepatocyte and liver transplantation and gene therapy which has made a positive change in the outlook of MLD. Many inherited metabolic liver disorders are treatable and therefore performing appropriate investigations, making a definitive diagnosis and initiating prompt treatment are essential to ensure a good outcome. This article outlines the important metabolic liver diseases in children and discusses the approach to evaluation and management.
Pathophysiology:
The pathophysiology of MLD appears very complex and is diagramatically represented in Figure 1.
Figure 1 : Schematic representation of pathogenesis of Metabolic liver disease
The metabolic block could leads to organ dysfunction either due to a downstream deficiency of a metabolic product (B) such as glucose in GSD or an upstream excess of the metabolic substrate (A) such as glycogen or an alternative pathway (C) resulting in accumulation of toxic metabolites (tyrosinemia, galactosemia). The disorders can be classified pathophysiologically into three main groups [2]:
1.Disorders that involve the synthesis or catabolism of complex molecules eg: lysosomal and peroxisomal disorders. The partly degraded molecules accumulate in the affected organs, including the liver and disrupts the organ function.
2.Disorders, of energy metabolism caused by a deficiency in energy production and its consequences eg glycogen storage disorders [GSD], fatty acid oxidation and mitochondrial disorders.
3.Disorders caused by the accumulation of toxic compounds arising as a consequence of the enzyme defect, as occurs in galactosemia and tyrosinemia type I.
Incidence of MLD: In India 25000 newborns are born annually with MLD and account for 14 % of childhood liver disease. [3] The incidence of each MLD may vary geographically. Metabolic liver disease constitutes 13-43% of acute liver failure in young children and 5-20% in older children [4]. MLD presenting as chronic liver disease may vary from 10-40 % [5] and 4-12% of neonatal cholestasis syndrome [6].
Age of presentation: MLD can present at any age [ from prenatal, neonatal, infancy to adolescence and even adulthood coinciding with the peaks of catabolism. From the therapeutic point of view, the MLDs can be divided into four-time frames e.g., neonatal age, during infections, puberty and pregnancy. The MLDs differ in the age of presentation and the etiological conditions may vary from centre to centre.
Manifestations of MLD; The manifestation of MLD depends on the age of onset, substrate involved, duration of disease and degree of hepatocyte or other organ injury. The diagnosis is often delayed as the symptoms may be
intermitten tand in the interval period, the patient may be free of clinical or biochemical abnormalities. The altered metabolic environment may affect a single organ or have systemic effects. The organs that have high metabolic rate and /or high energy requirement such as the brain, liver kidney heart and those with a high turnover of cell products such as the bone marrow or the growing skeleton are most susceptible.
Liver involvement usually arises as a primary effect of the IEM itself ; however it may vary from i) No involvement ( Gilbert's syndrome),ii) Normal liver with other organ involvement Crigler Najjar Syndrome (brain ), primary hyperoxaluria ( kidney ).iii) Mild liver involvement with more involvement of other organs,urea cycle defects and organic acidurias,iv) Slow liver damage GSD I and GSD III. v)Significant liver injury in infancy and children (Galactosemia,Tyrosinemia, Wilson disease)
Inheritance : The majority of MLDs are inherited as autosomal recessive though autosomal dominant ( Acute Intermittent Porphyria ), X linked [Ornithine transcarbamylase (OTC) deficiency]or from maternal mitochondrial DNA ( Mitochondrial hepatopathies) can also occur.
Approach to MLD:
I.History: A detailed history as shown in (Table I ) may point towards a diagnosis of MLD. Since MLD is a genetic disorder, the history should extend to include gestation and also extended family members. Children born to mothers with Acute Fatty Liver Pregnancy or HELLP (Hemolysis Elevated Liver Enzymes Low Platelet) should be followed up for Fatty Acid Oxidation defect. Similarly, if there is a history of Intra hepatic Cholestasis of Pregnancy, there is a possibility of PFIC in the child. Galactosemia should be suspected in a neonate with recurrent vomiting. Poor scholastic performance in a child may be a clue for Wilson Disease. Dietary history includes symptoms which occur after ingestion of fructose rich foods such as honey, fruit juices, syrups as in fructose intolerance. Aversion to protein rich foods points towards urea cycle disorders. Craving for protein rich foods and aversion to carbohydrates towards citrin deficiency.
Table I: Clues in history and examination to suspect MLD
II. Physical examination : Assessment of growth and development is essential in all MLDs. A thorough examination is an important step in evaluation before doing sophisticated tests[ Table II].
Table II : Clues in general physical examination to suspect MLD
The phrase " the eyes sees what the mind knows " is very true in MLD. Apart from the abdominal examination a meticulous neurological, cardiac,
respiratory assessment is essential. Ophthalmological examination should be included in the protocol and performed by an experienced opthalmologist for cataract, KF ring [Figure 2], cherry red spot and retinal pimentary changes.
Figure 2. Kayser Fleicher Ring
Clinical Presentation and Common causes of MLDs : Many MLD present in the neonatal period and early infancy but some may manifest later in childhood .
Table III. MLD in neonatal period and infancy
II.MLD in older children : There are 6 common presentations in older children(Table IV) .Three common MLD seen in older children are :
Table IV. MLD in older children
A) Glycogen Storage Disorder: These are a group of AR inherited disorders due to enzyme defect in metabolism of glycogen resulting in increased accumulation of normal or abnormal glycogen in various tissues. Liver is most severely affected, in addition skeletal muscle, heart, kidney, bones and brain may be involved.There are more 13 types of which type I (Glucose-6-phosphatase deficiency) and III (Amylo-1,6 – glucosidase deficiency) are more common. In India GSD account for 8-24 % of MLD3.In GSD I, the features are massive hepatomegaly, hypoglycemia, growth retardation, early morning seizures, renomegaly and mild elevation of transaminases. In GSD III, some distinct features are hepatosplenomegaly, elevated transaminases, muscle involvement in the form of cardiomyopathy or myopathy. Liver biopsy shows swollen hepatocytes with PAS positive diastase sensitive glycogen. Fibrosis may be seen in GSD III. Genetic studies help to confirm the diagnosis. Uncooked corn starch is very effective. Liver transplantation may the definitive treatment for GSD III.
B)Wilson Disease: This is an AR inherited treatable disorder of copper metabolism due to mutations in ATP7B gene located on chromosome13 and is a common MLD worldwide. In India, it accounts for 13 % of pediatric liver disease and 33-53 % of MLD3. The defective pType ATPase interferes with transport of copper from the liver, resulting in abnormal accumulation of copper in various tissues, liver kidney, brain, RBC. WD should be suspected in any child more than 3 years with liver disease. The classic triad
of low ceruloplasmin, KF ring (Figure 2) and elevated 24 hr urine copper is diagnostic but may not be present. Liver biopsy may show steatosis ,glycogen nuclear vacuolation and increased copper content in dry weight. Genetic studies are confirmatory. D Pencillamine and Trientene should be given life long .Liver transplantation is indicated in the presence of acute liver failure or end stage liver disease.
C) Progressive Familial Intrahepatic Cholestasis (PFIC): PFIC is a heterogenous group of autosomal recessive inherited disorders of bile salt transport and excretion resulting in hepatocellular cholestasis presenting usually in infancy and early childhood or rarely later in life and progresses to end stage liver disease and death. PFIC constitutes 10 to 15 % of cholestasis in children7 and 10-15% of liver transplants8. PFIC 1 ,2 and 3 are the most common among the six types of PFIC. which occur due to specific mutations resulting in functional deficiencies of canalicular proteins responsible for transport of bile salts. Pruritus is a predominat symptom (Figure 3) and progression to cirrhosis is universal. Low gamma glutamyl transpeptidase is an important surrogate marker seen in all PFICs except PFIC 3. Liver histopathology with immuno-histochemistry may support however the confirmatory diagnosis is by doing genetic analysis.The response to choleretics is variable .Partial internal or external biliary drainage relieves pruritus in PFIC 1 and PFIC2.Liver transplantation is the definitive therapy for PFIC 2 PFIC3 and PFIC4. [9]
Figure 3: Child with intractable pruritus PFIC /BASD
III. Investigations: Since it is difficult to distinguish clearly between MLD from non IEM liver disorders, it is advisable to include tests for the common and treatable metabolic conditions ( eg Wilson disease) when assessing liver dysfunction due to any cause.
The investigations for MLD comprise of A. Baseline investigations, B. Basic metabolic investigations and C. Advanced metabolic investigations including molecular genetic testing.
A.Basic investigations:
1.Complete blood count and peripheral smear : Anemia may be a feature of Wolman and Gaucher disease. Acanthocytosis on smear is suggestive of Abetalipoproteinemia. vacuolated lymphocytes in Wolman disease or Lysosomal disorders.
2.Liver function tests: Though these tests may be abnormal in several non MLDs it may help in diagnosis of some MLD. Normal or low GGT levels are seen in progressive familial intrahepatic cholestasis 1 to 6 (except PFIC 3 ) and in bile acid synthesis defects ( BASD ) and thus low GGT is an excellent marker to diagnose a subset of metabolic cholestatic disorders.
3.Serum Bile acids(BA): Bile acids are disproportionately increased in inherited Bile salt transport defects PFIC 1 to 6 but decreased in BASD. This helps us to differentiate PFIC and BASD since GTP is low or normal in both these conditions.
4.Serum Uric acid: High levels of serum uric acid points towards Lesch Nyhan syndrome and low levels point towards xanthine/hypoxanthine disorders and Molybdenum cofactor deficiency.
5.Serum Ceruloplasmin( Cp ): It is useful as a screening test for Wilson Disease. The normal value is 20-40 mg /dl . A value < 10>
6.Serum iron and serum Ferritin: Levels are increased in hemochromatosis.
7.Lipid profile: Abnormal lipid profile points towards glycogen storage disorders, lipid storage disorders Wolman disease and Nieman Pick disease.
8.Creatinine Phosphokinase : Levels are increased in GSD III with muscle involvement and mitochondrial disorders.
10.Serum Alphafetoprotein : A high AFP in the absence of hepatic malignancy is a sensitive marker for tyrosinemia.
2 Urine : Reducing substance for glucose may indicate diabetes but Non Glucose Reducing Substance is seen in Galactosemia ,fructosemia.
3.Imaging
i)Xray :Adrenal calcification is seen in Wolman disease[Figure 4], epiphyseal stippling is seen in Zellweger syndrome.
Figure 4: Xray abdomen adrenal calcification in Wolman disease
ii) USG abdomen may show the changes seen in chronic liver disease such as coarse echotexture of liver, ascites and dilated portal vein or collaterals.
4.Bone marrow examination: Presence of large macrophages with crinkled paper cytoplasm is seen in Gaucher disease and foamy cells in Niemann Pick disease[ Figure 5].
Figure 5 : Bone marrow showing large foamy cell in NP disease
5.Liver biopsy: Though an invasive test, liver biopsy may reveal some characteristic changes as seen in GSD I and III [Figure 6],
Figure 6: Liver biopsy showing swollen hepatocytes with glyco gen PAS +ve
the characteristic "fructose holes” in hereditary fructose intolerance, nuclear vacuolation and steatosis with positivity for copper in Wilson disease, bland cholestasis and Byler's bile on Electron microscopy in PFIC I and steatosis in cystic fibrosis ,fatty acid oxidation defect and citrin deficiency.
B. Basic Metabolic investigations--.Initial investigations should include tests for the more common metabolic conditions according to the presenting features. GALAK is a good mnemonic to remember the tests which help in diagnosis of MLD associated with significant biochemical derangements.
i)Glucose: Hypoglycemia - defined as blood glucose levels less than 40 mg/dL (plasma glucose levels < 45mg>
ii)Ammonia: Ammonia estimation should be done from a free flowing blood sample obtained from either arterial or venous puncture and the normal values are <100>
iii) Lactate: Lactate estimation should also be done from a free flowing blood sample .The normal values are 0.2-2.5 mmol/L. Increased lactate levels are seen in poor perfusion states, organic acidemias, fatty acid oxidation disorders, defects in pyruvate metabolism and electron chain defects.
iv)Acid base status: Acidosis is defined as pH less than 7.3 .Metabolic acidosis is seen in organic acidemias, defects in pyruvate metabolism, mitochondrial disorders. Alkalosis is seen in urea cycle disorders.
v)Ketones: Ketonuria, an increase in the urinary excretion of ketones points to organic acidemia. Ketonuria in fed and fasting states can occur in ketone body handling disorders such as succinyl-CoA transferase (SCOT) deficiency or beta-ketothiolase (BKT) deficiency.
C.Advanced investigations: The combination of history,clinical examination ,base line and basic metabolic investigations helps to narrow down the differential diagnosis of MLD to a great extent. The advanced metabolic investigations can now be tailored and selected to confirm diagnosis according to the provisional diagnosis(TableV).
Table V : Advanced Metabolic tests for diagnosis and specific treatment in MLD
Special methods of specimen collection, storage, and transport may be necessary, and it is best to plan such investigations in consultation with a specialist metabolic laboratory before collection.
i)Molecular gene testing: Genetic testing by next generation sequencing in metabolic liver diseases is important for accuracy of diagnosis to provide information on prognosis, for cascade carrier testing and for prenatal or pre-transplantation diagnosis. Whole exon sequencing (WES) that covers exons
and intronic regions of the gene is widely available. WES helps us to arrive at the diagnosis. WES that covers the enitre coding and non-coding areas of
the gene is very expensive. Clinical exome serquencing is useful when the WES is not feasible. Both biochemical tests and NGS are complimentary to each other.
Treatment : The treatment of MLD range from modification of diet in certain conditions like galactosemia, hereditary fructose intolerance and glycogen storage disorders, special enteral formulas in aminoacidopathies, organic acidemia and urea cycle disorders. Specific medications in Crigler Najjar syndrome type II, Tyrosinemia and Wilson disease are recommended. Enzyme replacement and substrate reduction therapies in lysosomal storage disorders. ( Table V)
Hepatocyte Transplantation : Hepatocyte transplantation has been used in treating Crigler-Najjar syndrome type I, GSD type 1a and UCD.
Liver transplant ; LT is indicated in MLD where it will reverse or arrest the disease progression. The common MLDs where LT has changed the natural history of the disease are Tyrosinemia ,wilson disease, GSD IV. LT is
contraindicated in disease with severe multisystemic involvement e.g., mitochondrial defects.
Dual Liver and Kidney transplant : In Primary Oxaluria liver and kidney transplant may be warranted.
Gene therapy. Liver-targeted gene therapy with rAAV8 vectors has efficaciously corrected the glycogen storage of GSD Ia and Pompe disease in preclinical studies and may be the answer in future. [10]
Bone Marrow Transplant : In Wolman disease BMT has been attempted with good results.
The treatment also includes supportive therapy with choleretics in cholestatic disorders, Vitamin supplementation, approriate management of hepatic encephalopathy, blood products and vitamin K in coagulopathies and appropriate recognition and treatment of complications.
Prevention: The preventive components in MLDs include genetic counseling, sibling screening and antenatal diagnosis. Immunisation with Hepatitis B and A vaccines is essential to prevent worsening of underlying disease.
Key Messages.
Funding source: None
Financial disclosure: None
Conflict of Interest: None
Contributors:
RG reviewed literature and drafted manuscript. MS drafted manuscript and reviewed manuscript for intellectual content. MS will act as the guarantor.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
