dengue infection is the most rapidly spreading mosquito - borne viral disease in the world and an estimated 50 million dengue infections occur annually . case fatality rates for the south - east asian region are 1% , but in india , indonesia and myanmar , focal outbreaks have reported rates of 3%-5% .
unusual manifestations involving liver and central nervous system in dengue infection have been reported , 3 ] .
the degree of liver dysfunction in children with dengue infection varies from mild injury with elevation of transaminases to severe injury with jaundice and liver cell failure [ 47 ] .
the incidence of hepatic dysfunction is more in dengue shock syndrome ( dss ) and dengue hemorrhagic fever ( dhf ) [ 2 , 410 ] .
aminotransferase levels are useful in predicting the occurrence of hepatic dysfunction and spontaneous bleeding . in recent studies from india and thailand ,
dengue infection was the most important cause of acute hepatic failure in children contributing to 18.5% and 34.3% of the cases respectively [ 11 , 12 ] .
hence early recognition and prompt initiation of appropriate supportive treatment can decrease the morbidity and mortality .
most of the data reported on abnormal liver functions in dengue are retrospective [ 2 , 6 , 8 , 9 ] .
therefore this cross sectional study with new data was undertaken to assess the spectrum of hepatic involvement in children with dengue infection .
this prospective study was conducted in the department of pediatrics , jss medical college hospital , mysore , india , from november 2008 to july 2010 .
all clinically suspected dengue infection children as per the who guidelines between 2 months to 14 years of age were screened and only serologically confirmed cases by dengue igm capture elisa were included .
ethical approval was obtained from ethical committee of the jss medical college hospital , mysore and written informed consent was obtained from the parents .
malaria , enteric fever , hepatitis a and hepatitis b were excluded by history , examination and investigations .
all the cases were subjected to following investigations : dengue igm capture elisa , hemoglobin ( hb ) , total count ( tc ) , differential leukocyte count ( dlc ) , platelet count , hematocrit ( hct ) , peripheral blood smear , serum bilirubin , alanine transaminase ( alt ) , aspartate transaminase ( ast ) , alkaline phosphatase ( ap ) , serum albumin , serum globulin , total proteins , prothrombin time ( pt ) activated partial thrombo - plastin time ( aptt ) , quantitative buffy coat for malarial parasite , blood culture , chest x - ray , widal test , igm anti hepatitis a virus , hbsag , ultrasound abdomen and thorax . estimated minimal sample size required for this study was 100 cases of dengue infection .
statistical methods employed for data analysis are descriptive statistics , cross tabs , chi - square test for categorical outcomes and t - test for comparison of means . comparison of multiple means / non parametric data was done using one way - anova .
a total of 115 cases formed the study group out of which 5 were excluded because of associated other infections ( hepatitis a=5 ) .
the study group included 110 children aged between 2-mo-14 years satisfying the who criteria for dengue fever after excluding malaria , enteric fever , hepatitis a and hepatitis b. all 110 children were grouped into dengue fever ( df ) ( 53.6% ) , dhf ( 23.6% ) and dss ( 22.5% ) according to who criteria . the majority ( 76% ) were above 5 years .
fever ( 100% ) was the chief complaint in all cases followed by body aches ( 57% ) , pain in abdomen ( 47% ) , vomiting ( 40% ) facial puffiness ( 40% ) and rashes ( 36% ) .
petichiae and purpura were seen in 30% of cases , while 19% had mucosal bleeding .
79% had hepatomegaly which was noticed more in dhf and dss ( 88.5% and 96% ) than in df ( 67.8% ) group ( p=0.006 ) .
hepatic tenderness was observed in 36.3% of children , which was more in dhf ( 53.8% ) , dss ( 56% ) compared to df(20.3% ) group ( p=0.001 ) .
profile of liver function tests ( lft ) and ultrasound findings in different groups in dengue infection is shown in table 1 .
as shown in table 1 abnormal liver functions were significantly more in dss and dhf group . 
 
profile of liver function test and ultrasound findings in different groups of dengue infection alt : alanine transaminase ; ast : aspartate transaminase ; alk .
ph : alkaline phosphatase ; aptt : activated partial thrombo - plastin time , inr : international normalized ratio 
 table 2 shows the comparison of alt and ast levels between the groups .
the rise in the levels of the enzymes were significantly more in dss and dhf group .
more than 10 fold increase in the levels of both alt and ast were observed mainly in the dss and dhf group . 
 
table 3 shows comparison of liver function tests with or without hepatomegaly and tender / non tender hepatomegaly .
interestingly there was no significant difference in the lft 's in children with or without hepatomegaly . among those with hepatomegaly
also there was no significant difference in the lft 's with / without hepatic tenderness .
ultra sound revealed gall bladder thickening , ascites , and pleural effusion more in the dhf ( 80% , 77% , 73% ) and dss ( 80% , 72% , 68% ) compared to df ( 50.8% , 33.9% , 32.2% ) group . 
 
comparison of liver function tests with or without hepatomegaly and tender and non tender hepatomegaly jaundice was present in 5 ( 4.5% ) cases out of 110 children .
all of them had tender hepatomegaly , decreased platelet count , elevated hematocrit , and deranged liver enzymes .
four children recovered completely by 3 weeks both clinically and biochemically and one was lost for follow up after discharge . out of 110 dengue cases one child ( 6 months old ) with deranged lft , adult respiratory distress syndrome ( ards ) , coagulo - pathy and multi organ dysfunction expired .
hepatic involvement in dengue infections is often demonstrated by hepatomegaly and mild - to - moderate increases in transaminase levels .
high mortality have been reported in children with dengue infection with acute liver cell failure [ 2 , 11 , 12 , 14 ] .
hepatomegaly is one of the common clinical signs of dengue infection . out of 110 cases in our study
, 79% had hepatomegaly which was more common in dhf ( 88.5% ) and dss ( 96% ) group than in df group .
similar association of hepatomegaly in dengue has been reported in 43%-100% of cases in children [ 46 , 9 , 1518 ] .
in fact petdachai and faridi et al reported hepatomegaly in all children with dss[4 , 16 ] .
hepatic tenderness was observed in 36.3% of children and was more in dhf ( 53.8% ) , dss ( 56% ) which is similar to observations made in a study from thailand .
abnormal hepatic enzymes in dengue infection have been reported by various workers and the range varies from 36.4%-96% both in children and adults [ 49 , 16 , 19 , 20 ] .
we observed elevated alt in 69.4% of df , 84.6% of dhf and 92% of dss , and raised ast in 88% of df , 100% of dhf and 96% of dss group .
the hepatic enzymes were elevated significantly in dss and dhf when compared to df group which is similar to other studies [ 410 ] .
we found more than 10 fold rise of ast in 44% of dss , 22.8% of dhf and only in 3.4% of df group .
more than 10 fold rise in alt in 16% of dss , 7.7% of dhf and 0% of df group was observed in our study .
more than 10 fold increase in transaminases levels was observed mainly in dss and dhf group than in df group which was statistically significant . in a large study from brazil , out of 1585 dengue cases ,
elevation in ast and alt were seen in 63.4% and 45% of patients respectively , with 3.8% of cases having 10 fold increase in transaminase levels .
similar increase of more than 10 fold rise in the liver enzymes was recorded by other authors also in adults and it varies between 1.8%-11.2% [ 8 , 19 , 20 ] .
higher incidence of more than 10 fold rise was observed in our study when compared to adult series .
this may indicate that , children are at higher risk of hepatic involvement compared to adults .
detection of abnormally high transaminase enzymes among patients with dengue is important since the possibility of consequent hepatic encephalopathy can be expected .
it is interesting to note that there was no statistical significant difference in mean liver enzyme levels in cases with or without hepatomegaly / hepatic tenderness in our study .
serum ap levels also showed similar trend in our study with raise in 45% of df , 65.3% of dhf and 72% of dss and again the raise was statistically significant in severe groups .
elevation of ast was more compared to alt in the present study and similar observations was made by others also [ 4 , 10 , 14 , 21 ] .
ast rise more than alt in dengue may be due to involvement of myocytes [ 10 , 21 ] .
this differs from the pattern seen in viral hepatitis , in which alt levels are usually higher than or equal to ast levels [ 10 , 21 ] .
we found prolonged pt ( inr>1.5 ) values in 20% of the cases and it was significantly more in dhf ( 31% ) and dss ( 13% ) group .
hypoglobinemia was observed more in dhf ( 69% ) and dss ( 60% ) compared to df group ( 17% ) .
wong et al reported low globulin level in 14.2% and low albumin level in 16.5% , derangements in pt and aptt in 42.5% of his adult cases .
however itha s , et al noticed hypoalbumenemia in 76% , deranged pt and aptt in 7% of adult cases .
the reduction of serum globulin may be an important factor in fluid loss into third space which is indicative of severity of dengue infection .
jaundice has been reported in 2%-25% of cases by several authors [ 5 , 14 , 21 ] .
we observed jaundice in 5 ( 4.5% ) cases and none of them had encephalopathy .
nimmannitya et al reported jaundice and encephalopathy in 18 cases of dhf of whom 10 died .
in recent studies from india and thailand , dengue infection is the most important cause of acute hepatic failure in children contributing to 18.5% and 34.3% of the cases respectively [ 11 , 12 ] . in endemic areas dengue
should be considered as one of the differential diagnosis in children presenting with fever and fulminant hepatic failure [ 3 , 12 , 13 ] .
mechanisms of liver injury in dengue may be due to direct effects of the virus or host immune response on liver cells , circulatory compromise , metabolic acidosis and/or hypoxia caused by hypotension or localized vascular leakage inside the liver [ 5 , 7 , 10 , 14 , 22 ] .
reports have demonstrated a high affinity of the dengue virus for human liver cells and dengue virus has been isolated from the liver of fatal cases [ 10 , 23 ] .
a study from mexico in the mice and humans established the correlation between liver damage and dengue based on the ast activity .
shivbalan et al found alt , tender hepatomegaly and abdominal pain to be significant predictors for bleeding in dengue children .
an indian study reported correlation between mortality and severe liver dysfunction in children with dengue infection .
predictive factors for liver damage have been identified as dhf , dss , secondary infection , thrombocyto - penia , elevated hematocrit , female sex and children by wong et al .
elevated transaminase levels have been suggested as a potential marker to help differentiate dengue from other viral infections during the early febrile phase by the same author . 

strengths of the study : some of the previous studies are retrospective , study group included seronegative dengue cases and they have not excluded common illnesses pertinent to tropical region .
in tropical countries liver can be affected in malaria , enteric fever , and viral hepatitis also .
therefore atmost care was taken to exclude these common disorders clinically and investigation wise in our study . 

limitations : on humanitarian grounds liver biopsy was not done in any children to confirm the diagnosis .
the spectrum of hepatic involvement in dengue varies from jaundice to elevation of liver enzymes .
significant rise of liver enzymes helps in recognition of severe forms of dengue infection ( dhf and dss ) .
presence of fever , jaundice and hepatomegaly in endemic areas should arouse the suspicion of dengue hepatitis .
 objectivehepatic dysfunction is common in dengue infection and the degree of liver dysfunction in children varies from mild injury with elevation of transaminases to severe injury with jaundice . 
 this study was undertaken to assess the spectrum of hepatic involvement in dengue infection.methods110 children with serologically positive dengue fever aged between 2 months - 14 years were studied for their hepatic functions both clinically and biochemically after excluding malaria , enteric fever , hepatitis a and hepatitis b with relevant investigations.findingsall cases were grouped into df ( dengue fever ) , dhf ( dengue hemorrhagic fever ) and dss ( dengue shock syndrome ) according to who criteria . 
 the spectrum of hepatic manifestations included hepatomegaly ( 79% ) , hepatic tenderness ( 56% ) , jaundice ( 4.5% ) , raised levels of aspartate transaminase ( ast)(93% ) , alanine transaminase ( alt)(78% ) , alkaline phosphatase ( ap ) ( 57% ) , prolonged prothrombin time ( pt ) ( 20% ) , reduced levels of serum albumin ( 66% ) and abnormal abdomen ultrasound ( 65%).conclusionhepatic dysfunction was observed more in dhf and dss group compared to df group . 
 about 17.27% of children had > 10 fold increase in the liver enzymes . 
 there was no correlation between the degree of hepatic enlargement or hepatic tenderness with the abnormalities of liver functions . 
 any child with fever , jaundice and tender hepatomegaly in geographical areas where dengue is endemic , the diagnosis of dengue infection should be strongly considered . 