Spectrum of Liver Diseases among Children in Kashmir Valley

Gulzar Ahmad Dar,a  Showkat A Zarger,b  Kowsar Jan,c  Mohammad Ishaq Malik,d Tariq Abdullah Mir,a Maqsood Ahmad Dara

a. Department of Medicine, Government Medical College, Srinagar, Kashmir, India; b. Department Gastroenterology, SKIMS,  Srinagar, India; c. Department of Anatomy, Government Medical College, Srinagar, India; d. Department of Paediatrics, Government Medical College, Srinagar, India

Abstract

A hospital based descriptive study was conducted to assess the magnitude and spectrum of liver disorders among children attending department of gastroenterology at SKIMS.  The study included children <18 yrs with liver disorders.  A total of 186 children with confirmed diagnosis of liver disease were included in the study.  Mean age of patients was 9.3 ± 4.8 yrs with a range of 1-18 yrs.  The diagnosis of all liver diseases was based on established clinical and diagnostic criteria.  These children were divided into subgroups of Acute Liver Disease (ALD), Chronic liver disease (CLD), Neonatal Cholestasis Syndrome and miscellaneous disorders.  Severity of chronic liver disease was defined using Child grading.

Spectrum of liver diseases in children included chronic liver disease (50%), acute liver disease (31%), hydatid liver (7.5%), congenital hyperbilirubinemia (3%) and miscellaneous. Jaundice (75%), ascitis (64%), encephalopathy (29%) were presenting symptoms in chronic liver disease patients indicating decompensation at presentation. Features of portal hypertension were seen in 65%.  Etiology was found to be HBV in 18%, Wilsons disease in 16%, HCV  in 6.4%, autoimmune in 5.3% and alpha-1 antitrypsin deficiency in 1.1%  and no etiology could be found in 52% (cryptogenic).  In acute liver diseases HAV was cause in 43%, HBV in 27% and HEV in 7% cases.

Keywords: , , , , ,

Introduction

Liver diseases among children include a broad spectrum of disorders such as infections, developmental abnormalities and metabolic disorders that finally result in hepatic dysfunction and cirrhosis.  The spectrum of liver disorders in children is different from those of adults and includes a variety of acute and chronic disorders.  The pattern of liver diseases, especially those with genetic and metabolic basis, show geographical variation.  These reported variations are attributable to different factors, eating habits, socio-economic factors and other reasons.  There is emergence of relatively newer liver disorders in children like NAFLD (non-alcoholic fatty liver disease) that were rare in our subcontinent especially in children.  There is therefore a continuing need for studies on various aspects of liver diseases in different communities and environments.

Acute and chronic liver diseases constitute the majority of liver disorders among children.  The etiology of acute liver diseases varies from country to country and from region to region within same country and within same regions from time to time.  Whereas hepatitis A and E are the common causes of acute liver disease in developing and underdeveloped countries, metabolic causes predominate in developed countries.  Furthermore infectious diseases such as sepsis, enteric fever and malaria can cause acute liver disease.  The etiologic profile of chronic liver diseases also shows geographical variation.  Hepatitis virus is the leading cause of chronic liver disease in South East Asia, Middle East and some other Asian countries (Zhang et al).11  It is predominantly due to high prevalence of hepatitis in general population in these countries.

Certain biliary disorders such as biliary atresia present as chronic liver disease in regions where diagnosis is delayed beyond twelve weeks.  Such children often present with cirrhosis and portal hypertension.  Likewise in some regions of the world where oriental cholangiohepatitis (OCH) is endemic, it can cause secondary biliary cirrhosis and portal hypertension in children if left untreated.  The profile of metabolic diseases producing chronic liver disease has not been well documented from developing and underdeveloped countries because of poor diagnostic facilities in these regions.

It is worth mentioning that a chronic liver disease named Indian childhood cirrhosis which was predominant among children in the Indian subcontinent has been vanishing due to adaption of preventive measures.  This disease used to kill affected children before 5 years of age and is now rarely reported from India (Bhave SA et al).29,35  Some of the parasitic liver disease such as hydatid and schistosomiasis  continue to form a part of liver disease in endemic belts.

Fulminant hepatic failure is a well-recognized complication of acute liver disease and has been reported from all over the world.  Although hepatitis A and E are well known causes of fulminant hepatic failure, a number of drugs are also responsible for fulminant hepatic failure. (Bendreet al)26

In recent years, non-alcoholic steatohepatitis (NASH) has been described as a common cause of liver disease in children which is related to obesity, hyperinsulinemia, insulin resistance, and liver cell injury from free fatty acid toxicity or other oxidant stress (Roberts EA).15   Overall prevalence of fatty liver in children is 2.6-12.5% (Tominaga K et al).28

The department of Gastroenterology Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir regularly admits children with suspected hepatobiliary  and pancreatic disorders for management. This institution is the only speciality medical centre in Kashmir and serves the indigent population of about 4.2 million people.  It is the only centre in Kashmir having facilities for therapeutic endoscopic procedures related to gastrointestinal and biliary diseases. Consequently we get referred patients from the whole Kashmir.  Furthermore department of Gastroenterology runs an outpatient clinic exclusively for children with liver, pancreaticobiliary and gastrointestinal disorders. With this background we were prompted to undertake this study to define the magnitude, spectrum, modes of diagnosis and treatment of liver disorders in children in the Kashmiri population.

Materials and Methods

This study was conducted in the department of Gastroenterology Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India.  It included analysis of records from January 2005 to June 2006 and collection of data from patients attending the hospital between July 2007 and December 2008  from the medical records information in terms of history, clinical examination, laboratory investigations, liver biopsy (if done) and others were obtained. Patients with incomplete records were not included in the study.

For all actual patients, a detailed history and clinical examination was performed in all children with suspected liver disorders. All patients underwent routine laboratory investigations and ultrasound scan of abdomen.  Complete blood count, serum biochemistry including complete liver function tests, coagulogram and hepatitis serology were done.  In patients with suspected chronic liver disease in addition to baseline investigations, ANA, ceruloplasmin level, iron profile, 24 hr urinary copper and slit lamp eye examination for Keyser-Fleischer ring were done. Alpha-1-antitrypsin levels were done for those patients in whom no etiology was found.  Upper gastrointestinal endoscopy was done for esophagealvarices.  Liver biopsy was done in those cases were there was no contraindication and parents gave written consent.

The contraindications were as follows:

  1. Bleeding disorder
  2. Lack of consent by parents or uncooperative patients.
  3. Dilated biliary radicles on imaging.
  4. Vascular tumors
  5. Suppurative cholangitis
  6. Right empyemiathoracis

Severity of chronic liver disease was defined using Child grading. The grading of esophagealvarices was done as per previously defined criteria (Zarger SA et al).17

  • Grade 0: No definite varices visible.
  • Grade 1: One or more varices less than 4mm diameter and less than 4 cm in length.
  • Grade 2: Multiple varices 4-10 cm in extent.
  • Grade 3: Multiple varices more than 10 cm long.

Informed consent for all invasive procedures was taken from parents/guardian. The diagnosis of all liver diseases were based on established clinical and diagnostic criteria.  These children were divided into subgroups of acute liver disease (ALD), Chronic liver disease (CLD), neonatal cholestasis syndrome and miscellaneous disorders.

Statistical Analysis

Summary statistics for quantitative data was mean and standard deviation (SD). Quantitative data between two treatment groups were compared with the use of Student t-test for parametric data and Mann-Whitney U test for non-parametric data (hospital stay and medical costs).  Pearson Chi-square test or Fisher`s exact test were used for categorical data.  All p values were two tailed; p values <0.05 were considered statistically significant.  All statistical analysis was performed with SPSS10 statistical software program.

Table 1. Age and Sex distribution of children with liver diseases

Table 1. Age and Sex distribution of children with liver diseases

Observations

During the 4 year study period encompassing between 2005 to December 2008 a total of 186 children with confirmed diagnosis of liver diseases were seen in the In and Out patient of Department of Gastroenterology out of which data for 80 children were obtained from records.

Table 2. Etiological  causes  of  liver diseases in 186 children

Table 2. Etiological causes of liver diseases in 186 children

The mean age of patient was 9.34±4.8 years with a range of 1-18 years.  Table 1 summarizes age and sex distribution of 186 children with liver diseases.  Majority of our patients were in the age group 6-10 and 11-15 years of age. In our study males and females were almost equal.

Table 2 shows the pattern of liver diseases during the study period. Acute and chronic liver diseases constitute more than 80% of total patient.

Table 3. Clinical presentation of various Liver Diseases

Table 3. Clinical presentation of various Liver Diseases

Patients of chronic liver disease presented with jaundice (74.5%), ascitis (64%), encephalopathy (29%).

Acute liver diseases patients presented with jaundice (100%), low-grade fever (76%) and itching (26%).

Table 4. Etiology of chronic liver disease in children

Table 4. Etiology of chronic liver disease in children

Remaining patients with other liver disorders had non-specific symptoms (Table 3).

In almost half of the children with chronic liver disease no etiology was found, whereas in remaining half HBV and Wilsons disease were major causes (Table 4).

Out of 94 patients endoscoped,  44 patients were having esophageal varices. Most patients were having grade 2-3 varices (Table 5).

Table 5. Grade of varices in various Liver Diseases

Table 5. Grade of varices in various Liver Diseases

Whereas hepatitis serology was frequently negative in patients of chronic liver disease, HBV was relatively more common amongst the hepatotrophic viruses. Acute liver disease was frequently caused by HAV followed by HBV and HEV (Table 6).

Table 6. Hepatitis serology in various Liver diseases

Table 6. Hepatitis serology in various Liver diseases

Majority of children with chronic liver disease presented in advanced stage, almost half were in grade C as per Child-Pugh scoring system (Table 7).

Discussion

Table 7. Distribution of chronic liver disease patients as per CTP grade

Table 7. Distribution of chronic liver disease patients as per CTP grade

In our study  we  found  that  chronic liver  disease  (90, 50.5%),  acute liver disease (58,31.2%), hydatid liver (14,7.5%), Congenital hyperbilirubinemia (6, 3.2%) and neonatal cholestasis were the predominant liver disorders in children in Kashmir. These findings correlate with that of other authors such as Yachha et al25 and Murtaza et al.8  However others have reported different patterns than this, e.g. Burki et al19 reported that chronic liver disease especially cirrhosis of liver was not common in their set up whereas Maryam et al1 reported hepatic iron overload due to thalassemia as predominant finding in their study and Ramakrishna et al30 reported neonatal cholestasis as predominant disorder after cirrhosis.  Obafuna et al31 reported hepatic schistosomiasis as major cause of liver disease in children which is in contradiction to our study.  Both schistosomiasis and thalassemia are not prevalent in community.

In our study the male (91, 48.9%) and female (95, 51.1%) subjects were almost equal with slight male predominance.  Similar sex distribution was observed by Burki et al19 and Akinbami et al.12 Maryam et al1 noticed male to female ratio of 1.42:1 which is in contrary to that of ours. The mean age in our study 9.34 ± 4.8 years with a range of 1 month 18 years which is in agreement with  as reported  by  Maryam et al1 and Ramakrishna et al.20  However series reported by Zhang et al11 were of lower age (mean 8.7 years) with a range of 1 month to 16 years.

In our study Chronic liver disease was the most frequently diagnosed entity constituting about half of the total cases (94 patients, 50.5%).  This is in agreement with Yachha et al.25  But this finding is in contrary to Ramakrishna et al30 (20%), Obafuna et al31 25% and Burki et al19 (0%).  The mean age of chronic liver disease patients in our study was 10.4 ± 4.0 years which is higher than 5 years as reported by Al- Lawati et al,2 4.5 years  in study conducted by Mehnaz A21 and 8.28 years by Hanif et al.13  The reason for higher mean age in our study was that neonates were not admitted in our department.  The male (42, 45%) : female (52, 55%) ratio in our study was slightly favourable to females  which is in contrary to other studies reporting a male predominance Akinbami et al31 (male 56%) and Hanif et al13 (male 58%).  Jaundice (75%), ascites (64%) and encephalopathy (29%) were presenting symptoms in chronic liver disease  patients in our study  as reported by Dangwal et al.23  This was lower than reported by Hanif et al,13 (80%), and higher than as reported by Mehnaz A21 and Malik et al.20  This high incidence of ascites, jaundice and encephalopathy in our study indicates fairly advanced liver disease with decompensation at presentation.  Hepatomegaly was seen in 22% cases while in remaining liver was shrunken or normal in size signifying that liver may be shrunken, normal or enlarged in size depending upon stage of chronic liver disease.  Ultrasonographic splenomegaly and dilated portal vein was seen in 65% cases denoting portal hypertension as reported by Hanif et al13 and Dangwal et al23 reported.  In our study 39 (42%) were in Child-Pugh grade-C, 33 (35%) in grade-B and 22 (24%) in grade-A further indicates fairly advanced liver disease with decompensation. These results were in accordance with Hanif et al,13 but in contrary to Dangwal et al.23  Out of 94 patients 44 patients had varices grade-1 in 5 grade-2 in 25, grade-3 in 11 and grade-4 in 3.  Upper gastrointestinal bleed history was present in 16% cases of liver disease indicating that these patients have esophageal varices without history of GIT bleed.  Prophylactic beta blockers and endoscopic ligation can prevent bleeding.   On evaluation we found that no etiology could be found in50 patients (52%), HBV (18%), Wilson (16%), HCV (6.4), autoimmune (5.3%), alpha-1-antitrypsin deficiency (1.1%). Similar pattern was noticed by Murtaza et al,8 Yachha et al25 and Rajeshwari, Gogia3 while as Al-Lawati et al2 and Hanif et al13 noticed a different pattern.

In this study HBV was commonest etiologic factor causing CLD in 18% patients as observed by Mehnaz A21 (18%), while as Malik et al20 (47%) and Murtaza et al8 (32%) reported higher incidence.  Dangwal et al23 reported lower incidence of 12%.

HCV was causative agent in about 6.4% cases of CLD is same as observed by Murtaza et al8 (8.5%), Dangwal et al23 (7.5%) while Hanif et al13 reported no case with HCV infection.

In 16% patients cause of CLD was identified as Wilson`s disease. Similar results were seen in other studies by Hanif et al13 (16%), Murtaza et al8 (17%) and Mehnaz A,21 however Yachha et al25 (21%), Zhang et al11 (20%) reported higher incidence.  The high incidence of Wilsons disease in our and other local studies is alarming and has remained under diagnosed so should be searched for in any child in whom etiology remains undetermined otherwise.

In present study autoimmune hepatitis was established as etiology in 5 ( 5.3%) patients of CLD as shown by  Yachha et al25,18 (4%), Rafeey et al5 (5.6), Zhang et al11 (7%). Other authors showed a higher incidence like Hanif et al13 (16%). Mehnaz A21 (1.2%), Choudhari et al9 (1.7%) and Murtaza et al8 (2%) reported a lower incidence.

Another autosomal recessive disorder, alpha-1 –antitrypsin deficiency was found to be cause in 1(1.1%) patient.  Studies conducted by Murtaza et al8 and Khanna et al7 reported no case of alpha-1 –antitrypsin deficiency  as cause of CLD whereas Yachha et al25 (3.5%) and Odeivre et al37 (4.7%) showed its presence.  It is a rare cause of CLD and liver transplant is only modality of treatment , Carlton et al.34

Fifty percent of CLD patients in our study remained idiopathic.  The incidence in other studies are as follows, Murtaza et al8 (42.5%), Hanif et al13 (44%), Yachha et al25 (40%), Malik et al20 (26.7). This high frequency of idiopatic CLD reflects our financial constrains as well as non-availability of advanced and specific diagnostic tools to find out the underlying cause of CLD. The frequency of idiopathic CLD varies in different parts of world e.g. United Kingdom it is about 5-10%.8 As specific diagnostic tools   appear, percentage of idiopathic CLD  falls , like advent of HbsAg and anti-HCV transferred many previously labeled idiopathic CLD. Still there remains significant percentage of patients  as idiopathic and etiological diagnosis  in these patients awaits development of specific diagnostic tools.

In our study acute liver disease was second frequently diagnosed entity constituting about 31% of the total cases ( 58 patients). This is in accordance with Yachha et al25 (28%), Murtaza et al8 (35.5%).  Burki et al19 reported higher incidence of 60%. The mean age of acute liver disease patients in our study was 8.7 ± 5.0 years with a range of 2-18years and commonest age group affected was 6-10 years. Similar observations were made by Yachha et al,25 Murtaza et al8 and Burki et al.19  Lower mean age was reported by Ossama et al33 (4 ± 2.4 years).  The male (33, 57%) : female (25, 43%) ratio in our study was slightly favourable to males  which is in  accordance with other authors like Burki et al19 (males 62%), Bendre et al26 (males 60%) and Maryam et al,1 however Rashed24 observed no sex difference.  Jaundice (100%), low grade fever (75%), vomiting were most common presenting complaints.  These findings were in accordance with Kour et al16 who reported jaundice in 93% patients. Hepatomegaly was noticed in 41% and splenomegaly 2% of acute liver disease patients in our study. Kour et al16 reported hepatomegaly in 39% and splenomegaly in 12% cases where as Rodrigues et al14 noticed hepatomegaly in 63% and splenomegaly in 40% cases. High incidence of  hepatomegaly  and splenomegaly  in study of  Rodrigues et al14 can be due to low number of studied subjects (35 cases).  In our study we found that hepatitis A virus was cause of acute hepatitis in 43% of our patients of acute liver disease in children which was in accordance with the observations made by Ossama et al33 (41%) and Rashed24 (52%). Thapa et al27 (78%) and Yachha et al25 reported higher incidence while as Murtaza et al8 (27.6%) reported lower incidence.  HBV was causing acute hepatitis in 27% cases of  acute liver disease was similar as reported by Yachha et al25 (26%), Ossama et al33 (22%), however Li-Min Hauag et al4 (64%), Murtaza et al8 (42%) and Rapiceeta et al32 (40%) observed higher incidence.  Other authors like Burki et al19 (1.5%), Thapa et al27 (8%) and Dangwal et al23 (12.5%) reported lower incidence than that of ours.  No patient of acute liver disease was anti-HCV positive as reported by Burki et al,19  Thapa et al27 Yachha et al25 etc., however Murtaza et al8 (10.3%) is in contradiction to our and other studies.  In our study HEV contributed 6.8% cases of acute liver disease in children while no case of HEV was reported in studies conducted by Burki et al,19 Murtaza et al.8 Kour et al16 reported HEV 45 (90%) patients out of 49 adults with acute hepatitis. In about 20% of patients with acute hepatitishepatitis serology was negative for all hepatotrophic viruses same as reported by Bendre et al26 (22%), while it was higher than as reported by Murtaza et al8 (14%). In these cases intake of hepatotoxic drugs was excluded by history.  Some of these cases were because of other viruses like CMV etc. and a part of sepsis syndrome.

Hydatid disease is a parasitic infection caused by the larval form of echinococcusgranulosus.  Hydatid disease is a major endemic health problem in certain areas of the world. The commonest sites of infestation are the liver and lungs. Hydatid disease is endemic in countries around the Mediterranean, Australia, South America and a few areas in North America and the U.K. An accurate diagnosis can be made by a combination of clinical, serological, and radiological examinations.  Hydatid disease of liver contributed 8% cases in our study. Mean age in our study was 12.5 ± 3.5 years with a range of 4-17 years. Similar mean age was observed by Goktay et al10 (9.4years), Mottaghian et al36 and Talaiezadeh6, however Al-Bassam et al22 reported a lower mean age of 6.5 years with range of 3-12 years. There was a striking difference between male (3 cases, 22%) and females (11cases, 78%) in our study which was in opposition to Talaiezadeh6 who reported the series with male preponderance (males 60%) while as Mottaghian et al36 (50%M:50%F) and Al-Bassam et al22 (47%M:53%F) reported equal distribution among sexes.  Goktay et al10 (56%F:44%M) also noted more incidence in females. The chief presenting clinical features in our study were pain upper abdomen (100%), Hepatomegaly (93%) with or without mass. None had jaundice or fever which was in accordance to findings of Mottaghian et al36 however Talaiezadeh6 reported pain in 55% and palpable mass in 35%, Al-Bassam et al22 reported pain in 38%, distention in 71% and hepatomegaly in 57%.  Percutaneous treatment (PAIR) of uncomplicated type I and type II liver hydatid cysts in paediatric patients is an efficient and safe treatment with short hospitalization (Goktay et al).10  However surgery seems to offer the best therapeutic option at present.  Primary closure of the cyst cavity without drainage is best for patients with uncomplicated hepatic hydatid disease because it is associated with a shorter hospital stay and a low complication rate (Al-Bassam et al).22

Neonatal cholestasis syndrome contributed about 3% cases in our series. This was very less as compared to Maryam et al1 (8.7%), Burki et al19 (5%), Yachha et al25 (26%).  The reason for this low percentage is that neonates and infants are taken care by other hospitals.

Congenital hyperbilirubinemia contributed to about 3.2 % cases (6 cases) in our study.  Among them Criglar-Najjar syndrome was diagnosed in 3 cases and Gilbert syndrome in 3 cases.  Similar incidence was reported by Burki et al19 and Yachha et al25 (5%).

Conclusions

  • This study was a hospital based, descriptive study to find the spectrum and magnitude of liver disorders in  children aged <18years.
  • A total of 186 children with confirmed diagnosis of liver disease were included in study.
  • The mean age of patient was 9.34±4.8 years with a range of 1-18 years.
  • Spectrum of liver diseases in children included, chronic liver disease (50%), acute liver disease (31%), hydatid liver (7.5%), congenital  hyperbilirubinemia (3%)  and miscellaneous .
  • Chronic liver disease was most frequently diagnosed entity constituting about half of the total cases (94 patients, 50.5%).
  • The mean age of chronic liver disease patients was 10.4 ± 4.0 years. The male (42, 45%) : female (52, 55%) ratio was slightly favourable to females.
  • Jaundice (75%), ascites (64%) and encephalopathy (29%) were presenting symptoms in chronic liver disease patients.
  • This high incidence of ascites, jaundice and encephalopathy in our study indicates fairly advanced liver disease with decompensation at presentation.
  • Ultrasonographic splenomegaly and dilated portal vein was seen in 65% cases denoting portal hypertension.
  • Out of94 CLD patients 39 (42%) were in Child-Pugh grade-C, 33 (35%) in grade-B and 22 (24%) in grade-A further indicates fairly advanced liver disease.
  • Out of 94 patients 44 patients had varices grade-1in 5 grade-2 in 25, grade-3 in 11 and grade-4 in 3. Upper gastrointestinal bleed history was present  in 16% cases of liver disease.
  • On evaluation we found that no etiology could be found in50 patients (52%), HBV in 18%, Wilson in 16%, HCV in 6.4%, autoimmune in 5.3% & alpha-1-antitrypsin deficiency in 1.1% cases of CLD.
  • The high frequency of idiopathic CLD reflects our financial constrains as well as non-availability of advanced and specific diagnostic tools.
  • In our study acute liver disease was second frequently diagnosed entity constituting about 31% of the total cases (58 patients).
  • The mean age of acute liver disease patients in our study was 8.7 ± 5.0 years with a range of 2-18years and commonest age group affected was 6-10 years.
  • The male (33, 57%) : female (25, 43%) ratio in our study was slightly favourable to males.
  • Jaundice (100%), low grade fever (75%), vomiting were most common presenting complaints in acute hepatitis.
  • Hepatomegaly was noticed in 41% and splenomegaly 2% of acute liver disease patients in our study.
  • In our study we found that hepatitis A virus was cause of acute hepatitis in 43%, HBV in 27% and HEV in 7% cases.
  • Hydatid disease of liver contributed 8% cases in our study.  Mean age in our study was 12.5 ± 3.5 years with a range of 4-17 years.

Limitations

The present study has number of limitations. First, the study contains record based data which has its own inherent limitations of inadequate data. Many patients were excluded because of non-availability of detailed information. We believe there were more patients during retrospective period than we finally enrolled. Second, many patients with acute liver disease were missed because such patients were treated outside by general practitioners and other hospitals. For past one year since the start of Paediatric Gastroenterology OPD, we have enrolled more patients especially those with acute liver disease compared with past years. Therefore the present study underscores the number of with acute liver disease especially acute hepatitis. Third, due to non-availability of advanced biochemical laboratory and investigation rarer metabolic disorders were missed. Although metabolic profile including Wilsons, alpha-1-antitrypsin levels, autoimmune, glycogen storage disorders etc. were screened, patients with rarer metabolic disorders might have been missed due to non-availability  of such investigations in our set up.

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Author Information

  1. Gulzar Ahmad Dar, Registrar, Department of Medicine, Government Medical College, Srinagar, Kashmir, India.  Email: drgulzar37@gmail.com,  Mobile:  +919622639353
  2. Showkat A Zarger, Head of Department Gastroenterology, SKIMS, Srinagar, India
  3. Kowsar Jan, Department of Anatomy, Government Medical College, Srinagar, India
  4. Mohammad Ishaq Malik,  Department of Paediatrics, Government Medical College, Srinagar, India
  5. Tariq Abdullah Mir, Department of Medicine, Government Medical College, Srinagar, India
  6. Maqsood Ahmad Dar, Department of Medicine, Government Medical College, Srinagar, India

Conflict of Interest: None Declared

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