Liver Functions as a marker of severity of disease in children with Dengue fever

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1 Article ID: WMC ISSN Liver Functions as a marker of severity of disease in children with Dengue fever Peer review status: No Corresponding Author: Dr. Sampada A Tambolkar, Associate Professor, Pediatrics,Dr. D.Y Patil Medical College,Pune, plot no 10 C Ram indu park baner pune , India Submitting Author: Dr. Sampada A Tambolkar, Associate Professor, Pediatrics,Dr. D.Y Patil Medical College,Pune, plot no 10 C Ram indu park baner pune , India Other Authors: Dr. Ambrish Mishra, Associate Professor, Pediatrics,Dr. D.Y Patil Medical College,Pune, A702 Runwal Regency Camp Pune411001, India Dr. Himanshi Joshi, Resident, Pediatrics,Dr. D.Y Patil Medical College,Pune, Dept of Pediatrics Dr.DY Patil Medical college Pimpri Pune, India Dr. Sharad Agarkhedkar, Professor and Head, Pediatrics,Dr. D.Y Patil Medical College,Pune, Flat D 101 Hill View Residency Baner Road Baner Pune, India Article ID: WMC Article Type: Original Articles Submitted on:16-aug-2015, 05:42:20 PM GMT Article URL: Subject Categories:PAEDIATRICS Published on: 17-Aug-2015, 07:46:11 AM GMT Keywords:Dengue fever, children,liver function tests severity,morbidity,discharge criteria,followup How to cite the article:tambolkar SA, Mishra A, Joshi H, Agarkhedkar S. Liver Functions as a marker of severity of disease in children with Dengue fever. WebmedCentral PAEDIATRICS 2015;6(8):WMC Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License(CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source(s) of Funding: No funding Competing Interests: No competing interests WebmedCentral > Original Articles Page 1 of 7

2 Liver Functions as a marker of severity of disease in children with Dengue fever Author(s): Tambolkar SA, Mishra A, Joshi H, Agarkhedkar S Abstract Objective : To study liver function in dengue infection and to correlate it with the severity of disease. Follow up liver function studied at discharge. Design : prospective cross sectional study. Methods: Fifty patients admitted with clinical diagnosis of dengue at D. Y. Patil medical college Pune were included and their liver functions were documented. Liver functions were correlated with severity of disease and followed at discharge. Results: out of 50 pts, 32 had DF,13 DHF, 5DSS. Liver function on admission was deranged significantly in patients with DSS than DHF. Least derangement was seen in pts with DF. Liver function improved in all patients. In patients with DSS liver function remained deranged at discharge. Conclusion: severe derangement in liver function at admission indicates severe disease. This can be used as an early predictor of disease severity. Introduction Dengue is the most rapidly spreading mosquito borne viral disease in the world. Dengue is an epidemic in large areas of tropics and subtropics (1). The classical infection is acute self-limiting, characterised by high fever, headache, bone pain,myalgia, rash, prostration, leukopenia and thrombocytopenia. Incubation period is 5-8 days and duration of illness is 7-9 days. It is caused by four antigenically distinct serotypes DEN 1/2/3/4(2). Second infection with different serotype results in severe disease ( dengue haemorrhagic fever (DHF), dengue shock syndrome(dss) ). Atypical presentations include encephalitis, Guillian Barre syndrome, dengue hepatitis, myocarditis, acute respiratory distress syndrome (3). Hepatic injury in dengue infection varies from mild injury with elevated transaminase, hepatomegaly, to severe injury with fulminant hepatic failure (4). Although liver is not the primary target organ, several pathological findings including fatty change, monocytic infiltration, centrilobular necrosis, have been reported (5). Hepatomegaly is a common danger sign in dengue fever. An increased amino transferase level is often seen. Severity of liver dysfunction is more in complicated dengue (6). However very few studies have correlated hepatic dysfunction with severity of dengue illness and followed till discharge.to study relation between severity of liver dysfunction and outcome of disease, present study was undertake. Methods Study was conducted at D Y Patil medical college Pimpri Pune, from July 2011 to September After ethics committee approval, 50 children, aged less than12 years with clinical diagnosis of dengue were enrolled.. WHO recommended criteria was used for the diagnosis of Dengue. These include acute febrile illness of 2-7days duration with two or more of - 1- headach 2- retro orbital pain 3- myalgia / arthralgia 4- rash 5-leucopenia 6- hemorrhagic manifestation ( petechia and positive tourniquet test ). Venous blood was collected for haemogram, haematocrit,platelet count, ALT, AST,ALP, Total serum protein,albumin,globulin,prothrombin time,inr, NS1 antigen, IgG, IgM antibodies against dengue and other tests to ascertain the cause of fever were done as per need. Liver function tests and haemogram were repeated at the time of discharge. Children with past history of liver disease were excluded. Statistical analysis was done using SPSS version 11 for window. Observations Age distribution of the group showed that maximum number of cases were in age group 6-10 years.(50% ) WebmedCentral > Original Articles Page 2 of 7

3 . Besides fever, hepatomegaly was most common finding( 80 % ). Severe dengue occurred more commonly bellow 5 years. Mean duration of fever does not depend on severity of the dengue illness. None of presenting signs and symptoms help early prediction of disease severity and progression. Central nervous involvement or hepatomegaly may predict severe disease and poor outcome. Liver function test done on admission revealed that derangement in liver function correlate with clinical severity. AST,ALT,PT INR values increased as severity of disease increased. This increase in LFT was statistically highly significant. Even in patients without hepatomegaly there is borderline increase in ALT while AST values remained normal. As disease recovered liver function test showed improvement,in patients of dengue fever it became normal, while in severe cases it showed improvement but remained mildly abnormal. On admission severe dengue showed haemo-concentration which recovered at the time of discharge. Platelet count was low on admission, as disease severity increased number of platelets decreased. Most severe form of disease had lowest platelet count. At discharge platelet count increased significantly, in milder disease this reached above normal range. NS1,IgM,IgG positivity helped in diagnosis of dengue disease but did not correlate with liver function. Discussion In a developing country like India, incidence and prevalence of infectious diseases like dengue is very high with frequent dengue outbreaks. There is clinical overlap of dengue hepatitis with other viral, enteric,malarial and Bacterial hepatitis. It was observed that dengue is the disease of school going children. 50% of children in this study were between 6-10 years age. Gomber et al from Delhi(7) and Narayan et al from Chennai(8) had similar observation. Liver function tests showed that dengue hepatitis is primarily anicteric. Liver enzymes are moderately raised. Rise in severe dengue is significantly more than classical dengue(p< 0.001). Rise in AST,is more than ALT. This is probably due to multi organ affection in dengue, hence other sources of AST contribute in its rise (erythrocytes,cardiac,skeletal, renal, brain ). Similar trend was documented by Ira Shah(10) and Brijmohan et al(11). PT, INR was mildly deranged in severe cases and was normal in classical dengue. Serum proteins were normal,as were serum albumin and globulin.this could be due to moderate short lived hepatic injury in dengue. Study done by Srivenu Ithaca et al(12) also suggested no significance of serum albumin in all three groups. Alkaline phosphatase is increased in dengue fever, its increase is significantly more in severe cases. S Fadilah et al reported higher levels of ALP in DHF as compared to DF. On discharge liver function tests improved and became normal in DF while were still abnormal in DHF and DSS. Severity of liver function abnormality on admission can predict outcome and severity of disease. but to determine the cut off for the same, larger study should be planned. Conclusion Severe derangement in liver function at admission indicates severe disease. This can be used as an early predictor of disease severity. Hepatomegaly,vomiting, abdominal pain,rash, myalgia were common reasons for admission. Bleeding in form of hematemesis epistaxis,melena were seen in 16% of cases. Hepatomegaly is the commonest sign in dengue infection. It's incidence varies from % in various studies,due to different definitions of hepatomegaly. In this study 80 % of cases had hepatomegaly. Hepatomegaly is more frequently seen in complicated dengue than classical. In our study 69% children with dengue fever had hepatomegaly as compared to 100% children with severe dengue. Ole Wichmann et al had figure of 43% and 70% respectively(9). WebmedCentral > Original Articles Page 3 of 7

4 Illustrations Illustration 1 INCIDENCE OF SIGNS IN DIFFERENT SEVERITY GROUPS CLINICAL SIGNS DF (N-32) DHF(N-13) DSS (N-5) P- VALUE Abdominal pain 28% 76.9% 60% < 0.01 Vomiting 40% 53.8% 40% >0.05 Rash 37.5% 46% 60% >0.05 Myalgia 21% 46% 20% >0.05 Bodyache 21.8% 38.4% 20% >0.05 Joint pain % 20% >0.05 Retro orbital pain 28% 23% 20% >0.05 Oedema 15.6% 30% 40% >0.05 Bleeding 0 38% 60% < Positive Hess test 6% 84.3% 60% < Petechiae 6% 53.8% 40% < WebmedCentral > Original Articles Page 4 of 7

5 Convulsion % < Altered sensorium 0 23% 40% < Hepatomegaly 68.8% 100% 100% < 0.05 Fever (days) 6.22+/ / / >0.05 WebmedCentral > Original Articles Page 5 of 7

6 Illustration 2 LFTs ON ADMISSION IN VARIOUS SEVERITY GROUPS LFT Admission DF DHF DSS P Value Mean+/- SD Mean+/- SD Mean +/- SD Bilirubin Total < Bilirubin direct >0.05 ALP < AST < ALT < PT < PT-INR < Total protein < 0.05 Albumin >0.05 Globulin >0.05 Blood Sugar >0.05 WebmedCentral > Original Articles Page 6 of 7

7 Illustration 3 LFTs ON DISCHARGE IN VARIOUS SEVERITY GROUPS LFT on discharge DF DHF DSS P-value Mean +/- SD Mean+/-SD Mean+/- SD Bilirubin Total >0.05 Bilirubin Direct >0.05 ALP >0.05 AST < ALT < PT < 0.01 PT-INR < 0.05 Total protein >0.05 Albumin >0.05 Globulin 2, >0.05 BSL >0.05 WebmedCentral > Original Articles Page 7 of 7