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Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."
Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011
Dr. Shankar P.R.
"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."
Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011 Anuradha
Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.
Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020
Original article / research
Full Version
Thyroid Dysfunction in Patients with Liver Cirrhosis and its Association with the Severity of Liver Disease: A Cross-sectional Study
Correspondence Address :
Dr. Rukma Jagannath Kolwalkar,
Kesar, H.No138/7 Angod, Mapusa, Goa, India.
E-mail: rukmadk@gmail.com
Introduction: There exists a complex relation between the thyroid hormones and liver physiology in health and disease. The liver along with the thyroid gland play a significant role in the conversion of inactive Thyroxine (T4) to active Triiodothyronine (T3). The most common thyroid hormone profile in cirrhosis of liver is a low total T3 and free T3, secondary to reduced activity of deiodinase type 1 and increased conversion to rT3.
Aim: To assess the association between the thyroid hormone levels and severity of liver disease, expressed in terms of child pugh score in tertiary care hospital in Goa.
Materials and methods: The cross-sectional observational study included hundred patients with liver cirrhosis, admitted at a tertiary care hospital in Goa, from October 2019 to September 2020. The thyroid hormone levels were estimated from an early morning fasting blood sample within 24 hours of admission, once the patient satisfied the inclusion criteria. The Child Turgott Pugh scoring system was used to classify patients as per their severity of liver disease. The data was entered and analysed in Statistical Package for Social Sciences (SPSS) software version 14.0.
Results: There were 95 males and 5 females. The study showed low mean levels of total T4 and free T3 in patients with cirrhosis of liver, which was significantly associated with Child Pugh classes of liver dysfunction. There was an association between levels of free T3 and the classes of Child Pugh score. The difference in the mean levels of TSH, total T3 and free T4 across the Child Pugh classes were not statistically significant.
Conclusion: The study showed low free T3 levels in patients with cirrhosis of liver as seen in similar studies done in various settings. Thus, Thyroid Function Tests (TFTs) especially free T3 levels have a considerable potential to be used an independent predictor or a proxy to prognosis in patients with liver cirrhosis.
Child pugh score, Free T3, Liver dysfunction, Prognosis, Thyroid function test
India belongs to the lower-middle income countries and liver cirrhosis was the 8th leading cause of death among these countries for the year 2019 (1). India is currently passing through a cultural transition with an escalating adoption of western lifestyle especially sedentary habits and diet including alcohol consumption. This has contributed significantly to the increase in the incidence of liver diseases in India. Liver disease is a leading cause of death in India: it has moved from the 13th to 10th leading cause of death and the number of deaths has nearly doubled since 1990 (2). In Goa, which is the center of the present study, chronic alcohol use is a major cause of morbidity as well as mortality with as much as 11% of deaths attributed to liver disease secondary to chronic alcohol consumption (3).
There exists a complex interrelation between the thyroid hormones and liver physiology in health and disease. The liver plays an important role in the activation, transport and inactivation of the thyroid hormones. The liver along with the thyroid gland and kidneys is involved in the conversion of inactive thyroxine (T4) to active triiodothyronine (T3) (4). It is also the site for synthesis and secretion of the three major thyroid hormone-binding proteins i.e. Thyroxine-Binding Globulin (TBG), transthyretin and albumin which act as carriers of thyroid hormone.
Alteration in thyroid hormone functioning in liver disease is an established fact in medical literature (5). The most common thyroid hormone profile in cirrhosis of liver is a low total T3 and free T3 secondary to reduced activity of deiodinase type 1 and increased conversion to rT3 (6),(7). These biochemical parameters have been used to see response to medical therapy in patients with Alcoholic Liver Disease (ALD) and also has prognostic implications in these patients (8). Conversely, low total T3 and free T3 levels are regarded as an adaptive hypothyroid state to reduce basal metabolic rate within the hepatocytes and preserve liver function and total body protein stores (9). On the other hand, the free T4 levels remain low or unchanged and the TSH levels remain normal or slightly raised in chronic liver diseases (10).
In India, similar to many developing countries, there are a few studies assessing the relation between liver disease and thyroid function and no such study has been reported in the state of Goa. Hence, this study was conducted to assess the association between the thyroid hormone levels and severity of liver disease expressed in terms of child pugh score in tertiary care hospital in Goa (11). The current study also attempts to evaluate if thyroid hormone levels can be used as an independent predictor of prognosis in patients with liver cirrhosis.
The cross-sectional observational study was conducted in Department of Internal Medicine at Goa Medical College, Bambolim, Goa, India (tertiary care hospital), from October 2019 to September 2020. Ethics approval was obtained from Institutional Ethics Committee (Letter no IEC-GMC/Oct-!9/E-5) of Goa Medical College and Hospital prior to commencement of the study. The study included 100 patients with liver cirrhosis admitted under the Department of Medicine. The sampling method used was universal sampling, and hence all the patients admitted during the study period who fulfilled the inclusion criteria were included in the study.
Inclusion criteria: Any patient aged 12 to 80 years admitted in the Medicine ward with established liver cirrhosis who consented to participate in the study.
Exclusion criteria: Patients who had a pre-existing thyroid disease, those on drugs known for interfering with thyroid functions and those in sepsis, cardiac or renal failure were excluded from the study.
Procedure
The diagnosis of cirrhosis was established by radiological means using ultrasound findings showing shrunken coarse echotexture of liver supported by clinical and biochemical parameters. The thyroid hormone levels were estimated using electro-chemiluminescence assay after collecting an early morning fasting blood sample within 24 hours of admission once the patient satisfied the inclusion criteria.
Child Turgott Pugh scoring system
The Child Turgott Pugh scoring system is used to predict prognosis and mortality in patients with liver cirrhosis. Child Pugh score is calculated using serum bilirubin, serum albumin, prothrombin time, grade of hepatic encephalopathy and ascites (11). Scores representing the increasing severity of liver dysfunction:
Score 5-6: Class A
Score 7-9: Class B
Score 10-15: Class C
STATISTICAL ANALYSIS
The data was entered and analysed in Statistical Package for Social Sciences (SPSS) software version 14.0. The continuous variables were expressed in mean±SD while categorical variables were expressed in frequency and percentage. The analysis of variance was used to test the significance of continuous variables within classes. In all tests a p-value <0.05 was considered statistically significant.
A total of 100 patients admitted with cirrhosis were included in the study, of which 95 were males and five were females. Based on the child turgott pugh score, class A included 15 patients, class B included 26, and class C included 59 patients. Thus a majority of 59 patients came at advanced stage of liver dysfunction. There was no significant difference in mean age across the three child pugh categories, with a p-value of 0.73 (Table/Fig 1).
The (Table/Fig 2) shows the mean levels of total T3, T4, TSH and free T3, free T4 in the different child pugh categories and its association with thyroid hormone levels. The mean levels of total T4 were highest i.e. 6.92 μgm/dl in child pugh category A. Whereas, the mean total T4 levels were lowest i.e. 5.5 μgm/dL in child pugh category C. Also, there was a statistically significant difference in mean total T4 levels across the child pugh classes, with an F-statistic of 3.59 and a p-value of 0.031. This implies that patients with severe liver disease had a lower level of total T4.
Similarly, there was a statistically significant difference in mean levels of free T3 across the three child pugh classes, with the highest mean level of free T3 i.e. 2.2 pg/mL being reported in the child pugh class B. In contrast, there was no significant difference in mean total T3, Free T4 and TSH levels across the child pugh categories of liver cirrhosis.
Based on the statistically significant association between total T4 and free T3, these were subjected to post-hoc analysis to assess if there was a statistically significant association within the class. As depicted in (Table/Fig 3), the intraclass comparison was not statistically significant for mean total T4 levels. In contrast, there was a statistically significant difference in the mean free T3 levels across the child pugh class B and class C with a with a p-value of 0.02. This could indicate an association of free T3 levels with a higher child pugh score.
The present study was designed to assess the association between the thyroid hormone levels and severity of liver disease expressed in terms of child pugh score. A majority of the patients enrolled in the study were males. This could be due to the fact that chronic alcohol use is a major contributor toward liver disease related mortality in Goa and the prevalence of male pattern of alcohol consumption reported among the Goans (3),(12). A majority of the patients enrolled in the study belonged to the child pugh class C, thus had a severe liver dysfunction, based on the child pugh classification.
The levels of mean total T4 and free T3 were found to be lower in patients with higher child pugh score. On assessment of difference in mean thyroid hormone levels, it was observed that there was a significant difference in mean T4 and free T3 across the three child pugh classes of severity of liver disease. This finding suggests an association between mean T4 and free T3 across the classes of child pugh classes. In contrast, there was no such statistical association between T3, free T4, and TSH levels across the child pugh classes. This findings are similar to a study done in Lucknow, India by Verma SK et al., where it is reported that a lower free levels are found in patients with increasing severity of liver disease (13). Similar findings were reported by Patira NK et al., in Rajasthan, India, Tas¸ A et al., in Turkey and Kayacetin E et al., in Turkey (14),(15),(16).
There are several hypothesis postulated for the low levels of free T3 observed in severe liver disease. The most common hypothesis for the low free T3 levels in liver disease is the reduced levels of Type I deiodinase and hence reduced peripheral conversion of T4 to T3 (15),(17),(18).(19),(20). Alcohol intake is also associated with impaired deiodinase activity (21). Since chronic alcohol use contributes to the majority of liver disease in Goa, it may be a contributing factor in reduced levels of total T4 and free T3 observed it the study findings (3). Also, release of inflammatory cytokines has been postulated as a factor responsible for low thyroid hormone levels in liver disease which acts by reducing deiodinase activity (22).
In the current study, there was no significant association between free T4 and TSH levels across the child pugh classes of liver dysfunction. This finding was similar to that reported by Mansoer P et al., in Iran (23). The studies done by Borzio M et al., in United States, Penteado et al., in Brazil and Malik R et al., in London reported that there was no association between TSH levels and severity of liver dysfunction (24),(25),(26).
The post-hoc analysis suggests a significant difference only for mean free T3 levels between group B and class C. The difference between mean total T4 levels across each class of child pugh classes was not significant on post hoc analysis. However, due to these confounding level of significance on post hoc analysis, a larger study with a bigger sample size is needed to reaffirm these findings.
Limitation(s)
The study also had other limitations due to its cross-sectional observational design. The findings do not establish a causal relationship between liver cirrhosis and low free T3 levels which can be addressed by having a prospective design with a larger sample size.
The present study was designed to assess the association between the thyroid hormone levels and severity of liver disease expressed in terms of child pugh score. A majority of the patients enrolled in the study were males. This could be due to the fact that chronic alcohol use is a major contributor toward liver disease related mortality in Goa and the prevalence of male pattern of alcohol consumption reported among the Goans (3),(12). A majority of the patients enrolled in the study belonged to the child pugh class C, thus had a severe liver dysfunction, based on the child pugh classification.
The levels of mean total T4 and free T3 were found to be lower in patients with higher child pugh score. On assessment of difference in mean thyroid hormone levels, it was observed that there was a significant difference in mean T4 and free T3 across the three child pugh classes of severity of liver disease. This finding suggests an association between mean T4 and free T3 across the classes of child pugh classes. In contrast, there was no such statistical association between T3, free T4, and TSH levels across the child pugh classes. This findings are similar to a study done in Lucknow, India by Verma SK et al., where it is reported that a lower free levels are found in patients with increasing severity of liver disease (13). Similar findings were reported by Patira NK et al., in Rajasthan, India, Tas¸ A et al., in Turkey and Kayacetin E et al., in Turkey (14),(15),(16).
There are several hypothesis postulated for the low levels of free T3 observed in severe liver disease. The most common hypothesis for the low free T3 levels in liver disease is the reduced levels of Type I deiodinase and hence reduced peripheral conversion of T4 to T3 (15),(17),(18).(19),(20). Alcohol intake is also associated with impaired deiodinase activity (21). Since chronic alcohol use contributes to the majority of liver disease in Goa, it may be a contributing factor in reduced levels of total T4 and free T3 observed it the study findings (3). Also, release of inflammatory cytokines has been postulated as a factor responsible for low thyroid hormone levels in liver disease which acts by reducing deiodinase activity (22).
In the current study, there was no significant association between free T4 and TSH levels across the child pugh classes of liver dysfunction. This finding was similar to that reported by Mansoer P et al., in Iran (23). The studies done by Borzio M et al., in United States, Penteado et al., in Brazil and Malik R et al., in London reported that there was no association between TSH levels and severity of liver dysfunction (24),(25),(26).
The post-hoc analysis suggests a significant difference only for mean free T3 levels between group B and class C. The difference between mean total T4 levels across each class of child pugh classes was not significant on post hoc analysis. However, due to these confounding level of significance on post hoc analysis, a larger study with a bigger sample size is needed to reaffirm these findings.
Limitation(s)
The study also had other limitations due to its cross-sectional observational design. The findings do not establish a causal relationship between liver cirrhosis and low free T3 levels which can be addressed by having a prospective design with a larger sample size.
DOI: 10.7860/JCDR/2022/55480.16603
Date of Submission: Feb 13, 2022
Date of Peer Review: Apr 06, 2022
Date of Acceptance: Apr 21, 2022
Date of Publishing: Jul 01, 2022
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA
PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Feb 17, 2022
• Manual Googling: Apr 20, 2022
• iThenticate Software: Jun 04, 2022 (11%)
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