Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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On Sep 2018




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On Sep 2018




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"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Professor and Head
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Lucknow
On Sep 2018




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Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
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Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


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.
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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

Important Notice

Original article / research
Year : 2010 | Month : April | Volume : 4 | Issue : 2 | Page : 2190 - 2197 Full Version

A Prospective Study Of Hepatic Involvement In Plasmodium Falciparum Malaria


Published: April 1, 2010 | DOI: https://doi.org/10.7860/JCDR/2010/.692
SINGH R*, KAUR M**, ARORA D***

*(Asst.Prof.), Department of Internal Medicine, (Asst. Prof),Department of Radiodiagnosis, (Asst.Prof.) Department of Microbiology, Adesh Institute of Medical Sciences & Research. Bhatinda, Punjab, -151001 (India).

Correspondence Address :
Dr. Rakendra Singh (Asst. Prof.)
Department of Internal Medicine, Adesh Institute of Medical Sciences & Research.Bathinda, Punjab, India-151001.
E-mail: rakendrasingh@hotmail.com
TEL NO: +919815409999 / +919779109999
FAX NO: +911642742902

Abstract

Introduction: Malaria counts among the worst scourges of humankind. It amounts to an immeasurable health burden and inhibits economic prosperity in numerous tropical countries.
Material & Methods: The study included adult patients with Plasmodium Falciparum malaria with evidence of jaundice conventional thick and thin Pbfs stained with geimsa were examined under oil immersion. Detailed clinical, biochemical, and radiological examinations were conducted to establish the diagnosis of malaria and the various clinical manifestations. Histopathological examination was conducted in the category B of the patients.
Observations: About two thirds were male. The age of the patients ranged between 16-56 years (mean 28.14±7.23). Serum bilirubin levels ranged from 1 to 32 mg% (mean 5.65). 41.46% had serum bilirubin of <3 mg%, 40.24% had 3-10 mg% and 18.29% had >10 mg%.
The most frequent sonographic finding of liver was normal sized liver with normal echogenicity. Swollen hepatocytes was seen in all the cases while hemozoin deposition seen in about three fourths.80% of the patients with serum bilirubin >10mg developed acute renal failure as compared to 17.65% in those with bilirubin level <3 mg.
Conclusion: Hepatic involvement is a common accompaniment of acute P. Falciparum malaria, and hepatic dysfunction ranges from a mild elevation of liver enzymes to the range of acute hepatitis.the presence of hepatitis in patients with falciparum malaria indicates a more severe illness with a higher incidence of complications, multiorgan failure and supposedly a bad prognosis.

Keywords

P. Falciparum, Malaria, malarial hepatitis, Swollen hepatocytes, Hemozoin deposition

Introduction
Malaria is an ancient disease and references to what was almost certainly malaria occur in a Chinese document from about 2700 BC, clay tablets from Mesopotamia from 2000 BC, Egyptian papyri from 1570 BC and Hindu texts as far back as the sixth century BC. Malaria counts among the worst scourges of humankind, accounting for some 500 million clinical cases per year and more than one million deaths, mostly children (1). It amounts to an immeasurable health burden and inhibits economic prosperity in numerous tropical countries, most extensively in Africa & Asia. Plasmodium falciparum is the most virulent among the four Plasmodium species parasitic to humans, accounting for about 85% of all malaria cases, and nearly all of the mortality. The extreme pathogenicity of P. falciparum has suggested that it is a recent human parasite, acquired by transfer from a nonhuman host (2).

Clinical presentation of falciparum malaria may vary in individuals depending upon the level of parasitemia and immune status of the patient. Jaundice is one of the common manifestations of severe falciparum malaria. It is seen more in adults than children and may present alone or with other complications (3). It results from the intravascular haemolysis of parasitized erythrocytes, hepatic dysfunction and possibly an element of microangiopathic haemolysis associated with disseminated intravascular coagulation. Severe jaundice associated with Plasmodium (P.) falciparum malaria is now a well-known entity, and high incidences are being reported from many countries of south-east Asia, including India more so in recent years (4),(5). The majority of the cases have either isolated infection with P. falciparum or a mixed infection with both P. falciparum and P. vivax (6),(7).Malarial hepatitis is a term commonly used to describe hepatocyte dysfunction in severe and complicated malaria (8). It is characterized by a rise in serum bilirubin along with the rise in serum transaminase levels to more than three times the upper limit of normal (9).

Hence malarial hepatitis is a component of multiorgan failure and supposedly a bad prognostic sign in Falciparum Malaria. So, the present study was designed to determine the clinical, biochemical and sonographic changes in patients with falciparum malaria presenting with jaundice and thus prognosticate the disease.

Material and Methods

This prospective study was conducted on 82 admitted adult patients in the medicine ward of Adesh Institute of Medical Sciences & Research, a 750 bedded teaching hospital in North India. The time period of the study was from July 2006 through December 2009. Detailed clinical, biochemical, and radiological examinations were conducted to establish the diagnosis of malaria and the various clinical manifestations. Histopathological examination was conducted in the category B of the patients.(those in the middle group.)

Selection Criteria
It included adult patients of both sexes and different ages with Plasmodium falciparum malaria with evidence of jaundice after obtaining the formal consent from the patient or relatives.

Exclusion Criteria
Patients who had other concurrent illness or having negative peripheral blood smear for PF (or having only vivax infection) were not included in the study.

The study was designed to include the Demographic, clinical information, biochemical and hematological changes observed in the patients. The data was entered into a structured proforma separately. Management was done as per standard guidelines. Patients were discharged from the hospital after significant improvement in clinical as well as hematological and biochemical parameters.
Any patient with evidence of liver disease (e.g. viral hepatitis, cirrhosis, portal hypertension, liver abscess, unexplained hepatomegaly, ascites, history of alcoholism/ hepatotoxic drugs, past history of jaundice) was excluded on the basis of history, clinical examination and relevant investigations.

Detailed clinical examination was done in all patients. All these patients of Plasmodium falciparum malaria with jaundice were evaluated clinically for history of fever, headache, vomiting, altered sensorium, convulsions, pallor, icterus, hepatosplenomegaly, decreased urine output and coma.

A total of 82 patients conformed to the selection criteria and were included as a part of the sample size. The diagnosis of malaria was confirmed by the demonstration of asexual forms of Plasmodium falciparum in the peripheral smear alongwith jaundice. Conventional thick and thin PBFs stained with Geimsa were examined under oil immersion. Slides were considered negative when there were no parasites in 100 high power fields.

The laboratory investigations done in all the patients included a complete hemogram, ESR, platelet count, BT, CT, random blood sugar, urea, creatinine and S. electrolytes. Liver function was evaluated by determining the levels of S. bilirubin (both conjugated and unconjugated), AST and ALT, S. protein, and prothrombin time (PTI). Blood for hepatitis B and C was done in all the patients to rule out possibility of concomitant viral hepatitis. Urine was evaluated for urobilinogen, bile pigment and bile salts.

Based on serum bilirubin level, the patients were categorized in group A (serum bilirubin < 3mg %), group B (serum bilirubin 3-10 mg %) and in group C (serum bilirubin >10 mg %).

Detailed ultrasonography was done to check the size and echo texture of the liver, and to check for gallbladder abnormality, intrahepatic or extrahepatic biliary duct dilatation and signs of portal hypertension. Criteria used to diagnose malarial hepatopathy were demonstration of Plasmodium falciparum infection, at least three-fold rise in transaminases (especially ALT, demonstrated in two samples, taken 24 hours apart,) absence of clinical or serological evidence of viral hepatitis and response to anti-malarial therapy (12).

Liver biopsy was done by gun shot method through micro invasive needle using transthoracic approach in ninth or tenth intercostal space in the mid-axillary line in all the thirty three patients of group B after obtaining reports of BT, CT, PT, platelet count and patients consent. The formalin fixed liver tissue was stained with hematoxylin and eosin, periodic acid Schiff’s and reticulin stains.

Formal approval of hospital ethical committee and written consent of the patients were obtained for this study.

Observations
A total of 82 patients fulfilled the inclusion criteria, 56 (68.29%) were males and 26 (31.71%) females. The age of the patients ranged between 16-56 years (mean 28.14±7.23). The most common presenting symptoms were high-grade fever with chills & rigors along with vomiting followed by abdominal pain, headache & impaired consciousness. The average duration of illness was 1-8 days before the patients presented to the hospital.

The important findings were icterus in all the patients, pallor in 53 (64.63%), splenomegaly in 42 (51.22%), hepatomegaly in 48 (58.54%) and impaired consciousness in 17 (20.73%) cases. The details of biochemical investigations are mentioned in the (Table/Fig 1). Serum bilirubin levels ranged from 1 to 32 mg% with mean bilirubin level of 5.65±2.64 mg/dl. 34 patients (41.46%) had serum bilirubin of <3 mg%, 33 (40.24%) had 3-10 mg% and 15 (18.29%) had >10 mg%.

ALT (alanine transaminases) levels ranged from 32-1240 IU/L with mean ALT levels 78.62±41U/L. AST (Aspartate transaminases) levels ranged from 28- 1460 IU/L with a mean of 62.48±32.24. In 11 patients (13.41%), serum transaminase levels were more than thrice the upper limit of normal. Prothrombin time was within normal limits in most patients except a few with severe malaria with very high serum bilirubin levels. Prothrombin time index (INR) ranged from 1-2.3 with a mean level of 1.4. Anemia was found in 58 (70.73%) patients with mean Hb% 9.85±3 gm/dl. 22 (26.83%) patients had evidence of thrombocytopenia with mean platelet count 2.36±59.28x103 cells/ul. Only 2 (2.44%) patients had leucocytosis. Creatinine was increased in 32 (39.02%) patients with mean serum creatinine level of 1.8±0.8 mg/dl. 7 (8.54%) patients died due to various complications of malaria like cerebral malaria or multi-organ dysfunction.

The most frequent sonographic finding of liver was normal sized liver with normal echogenicity (36.59%) followed closely by hepatomegaly with normal echogenicity (34.15%) (Table/Fig 2). In all the patients with hepatomegaly and/or decreased echogenicity on ultrasonography, transaminases were found to be more than thrice normal. There was no evidence of intrahepatic or extrahepatic biliary duct dilatation, portal hypertension or ascites.

The important histopathological features were the presence of swollen hepatocytes in 33 (100%) cases, presence of malarial pigment (hemozoin) deposition in 24 (72.73%) cases, portal infiltration by mononuclear cells in 18 (54.55%), congestion of hepatocytes in 15 (45.45%), Kupffer cell hyperplasia in 10 (30.30%), centrizonal necrosis in 8 (24.24%) and fatty infiltration in 4 (12.12%) of cases (Table/Fig 3).

Discussion

Hepatic dysfunction in a case of falciparum infection has been recognized since the beginning and various causes have been attributed for the same. According to WHO, the jaundice is one of the important manifestations of severe malaria. There is evidence of focal hepatocyte necrosis, cholestasis, bile stasis, granulomatous lesion or malarial nodules (18).Jaundice in severe P.falciparum malaria is multifactorial; intravascular haemolysis of parasitized red blood cells, haemolysis of non-parasitized red blood cells (innocent bystanders), hepatic dysfunction, associated haemoglobinopathies and drug induced haemolysis (including Quinine). The other causes of jaundice in malaria could be coexistent viral hepatitis, especially infections with hepatitis E virus or hepatitis A virus (16).

Many studies have attributed malarial hepatitis to be an important contributory factor for the jaundice (5), (12), (23). Malarial hepatitis is a term commonly used to describe liver cell dysfunction in severe and complicated malaria. Malarial hepatitis is characterized by a rise in serum bilirubin along with the rise in serum Alanine transaminase levels to more than three times the upper limit of normal (4). The incidence of jaundice and hepatocellular dysfunctions in severe malarial infection has been reported variably, which may be due to the geographic conditions, endemicity of malaria in the region from where the reports have originated, the age groups studied, the epidemic form of infections reported and coexistent viral hepatitis (8). The incidence of jaundice is more in adults (3) and it varies from 32-37% with predominant unconjugated hyperbilirubinemia as reported by Harris at al. (10) In patients with severe malarial infection, the incidence of jaundice is reported to be 2-57% (11).

Kochar et al. has reported that in P.falciparum malaria, the serum bilirubin is elevated and it is the conjugated fraction which is dominant in patients who develop hepatic dysfunction and liver enzymes are elevated 2-3 times the normal and may be much beyond this level (14). The findings of our study are consistent with the above study as we also noted dominant conjugated hyperbilirubinemia in those patients who had deranged LFTs and in 13.42% of the patients, ALT was >3 times of normal level.

Many workers have proposed the role of hepatocellular damage in patients having hyperbilirubinemia of greater magnitude (19),(20).According to WHO, the patients of severe falciparum malaria with jaundice rarely have the serum bilirubin levels of more than 10mg%(18) but in our study 18.29% patients had serum bilirubin levels of >10mg% and the maximum value was 32 mg%. Earlier similar findings were recorded by many workers from this subcontinent (4),(21). The reason for this could be due to endemicity of malaria in our part of the world and more drug resistant virulent strains. Moreover, haemolysis alone can produce predominantly unconjugated hyperbilirubinemia which usually does not exceed more then 10 mg%. In patients having serum bilirubin levels of more then 10 mg%, there are more chances of associated hepatocellular injury as compared to the patients having serum bilirubin levels of less then 10 mg%.

The presence of hepatitis in patients with falciparum malaria indicates a more severe illness with a higher incidence of complications and a poor prognosis. In our study, out of the patients with serum bilirubin >10mg, 80% developed acute renal compromise as compared to 42.42% with bilirubin level between 3-10 and, 17.65% in those with bilirubin level <3 mg. Higher mortality rate was observed (33.33% vs. 6.06%) in category C compared with category B, while there was no mortality in category A. Similar observations have been reported by other studies (4). In a study on severe FM presenting as multi-organ failure, multiple organ involvement was associated with increased mortality and hepatic failure was associated with around 50% mortality rate (22). Similar reports have been published by others (23).

It has also been observed that higher serum bilirubin levels are associated with increased incidents of complications and mortality (12). In this study we also observed raised serum enzyme levels in some of these patients and 9 out of 12 patients having serum bilirubin levels of more then 10mg% also had very high levels of serum enzymes. Earlier Chawla et al and Anand et al also had similar observation in the patients of PF malaria (4),(21) All these observations of this study and other workers further support the possible role of hepatic dysfunction in the causation of jaundice.

We noted a higher incidence of thrombocytopenia (66.67% vs 11.76%) and anemia (86.67% vs. 52.94%) in patients with category C compared with category A. Similar reports of thrombocytopenia due to P.falciparum malaria were also documented by Kochar et al. and other studies (14),(15). We document a couple of patients with markedly elevated Prothrombin time. These patients however fall into category C that is, these patients had severe P.falciparum malaria and significant disturbance was observed in the coagulation profile. However severe coagulopathy is almost never seen in isolation with severe malaria and prothrombin time is usually within normal limits even in patients with marked elevation of liver enzymes (11).

In acute malaria, hepatic dysfunction is reversible in all the patients developing malarial hepatopathy who respond favourably to antimalarial therapy and no residual effects have been documented in survivors (17). Bilirubin normally recedes by 72 hours of starting treatment but it may be delayed in patients having coexisting renal dysfunction. In this study, we also noted significant improvement in liver function test with malaria treatment and bilirubin and ALT reduced to reference range in almost all of the patients at the time of discharge.

The predominant histopathological changes in malarial liver comprises of a reticulo endothelial response i.e., Kupffer cell hyperplasia, presence of malarial pigment and congestion alongwith minor effects on hepatocytes (21),(22),(23) Malarial parasites are not found in the biopsy specimens (24). These changes may be non-specific but the presence of centrizonal necrosis and hyperplastic Kupffer cells loaded with malarial pigment is a strong indicator of hepatic damage (25) .

Thus, in our opinion the evidence of predominantly conjugated hyperbilirubinemia and increased levels of ALT, AST and LDH levels along with evidence of hepatocllular necrosis in histopathological examination in few patients are evidence of hepatocytic dysfunction in patients of Plasmodium falciparum malaria with jaundice.

Regarding liver function tests, the maximum value of serum bilirubin observed in this study was 32 mg% while in a study done by Kocher et al., it was 48mg% (14). Highest level of ALT and AST was 1240 IU/L and 1460 IU/L respectively while in Kocher et al’s study, it was 1120 IU/L and 1245 IU/L respectively. Chawla et al. studied 31 patients, of whom 14 (45.16%) had serum bilirubin >10 mg%, with predominantly conjugated hyperbilirubinemia. (21) Anand et al. studied 39 patients, out of whom, 13 (33.33%) had serum bilirubin in the range of 16±6.3 mg%, and most had predominantly conjugated hyperbilirubinemia (4). In a study done by Ahsan et al. the incidence of jaundice was 46.05%, among whom, (57.14%) had bilirubin >10 mg/dl; mean serum ALT in patients with serum bilirubin 3-10 mg/dl, was 41±16 IU/L as compared to 53.46±31.24 IU/L in patients with serum bilirubin levels >10 mg/dl (6).

In this study, the most common sonographic finding was normal size and normal echogenic liver followed closely by hepatomegaly and normal echogenicity of liver. Similarly Hepatomegaly and normal prothrombin time in the setting of FHF are suggestive of malaria. (25). Although the authors mentioned that hepatomegaly is associated with MHsFHF, it appears that splenomegaly is similarly associated (48% in patients with MHsFHF vs none in the viral FHF group) (11), (26). In all those patients, transaminases were found to be more than thrice the upper limit of normal. The observation of linear elevation of AST and ALT levels in patients with different bilirubin levels, hepatomegaly with low echogenicity and increased gallbladder wall thickness on ultrasound examination were important features of widespread hepatocyte dysfunction.

Conclusion

Hence we conclude that hepatic involvement is a common accompaniment of acute P. falciparum malaria, and hepatic dysfunction ranges from a mild elevation of liver enzymes to the range of acute hepatitis. Malarial hepatopathy is a well recognized entity which can be reliably diagnosed on the basis of clinical, biochemical and sonographic parameters and should be suspected in patients with acute febrile illness, jaundice and raised transaminases and there is no role for histopathology. Furthermore, it was also noted that hepatic dysfunction with jaundice is a serious development in acute P.falciparum malaria and it indicates severe illness with higher incidence of complication and mortality. To help mitigate the expanding global impact of malaria, with its associated increasing drug resistance, implementation of prompt and accurate diagnosis is needed. Numerous malaria RDTs have been developed and are widely available; however, an assortment of issues related to these products have become apparent (27),(28).

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