A STUDY ON ETIOLOGICAL PROFILE OF ACUTE HEPATITIS IN CHILDREN
DISSERTATION SUBMITTED FOR THE DEGREE OF M.D BRANCH VII
(PAEDIATRIC MEDICINE)
REG.NO: 201717101 MAY 2020
THE TAMILNADU
D.R M.G.R MEDICAL UNIVERSITY CHENNAI, TAMILNADU
CERTIFICATE
This is to certify that the dissertation entitled “A STUDY ON ETIOLOGICAL PROFILE OF ACUTE HEPATITIS IN CHILDREN” is the bonafide work of Dr. G.KAMALESHWARAN in
partial fulfilment of the university regulations of the Tamil Nadu Dr. M.G.R Medical University, Chennai, for M.D Degree Branch VII –
PAEDIATRIC MEDICINE examination to be held in May 2020.
Dr. K. VANITHA M.D., DCH., Dean,
Madurai Medical College, Government Rajaji Hospital, Madurai.
CERTIFICATE
This is to certify that the dissertation entitled “A STUDY ON ETIOLOGICAL PROFILE OF ACUTE HEPATITIS IN CHILDREN” is the bonafide work of Dr.G.KAMALESHWARAN in
partial fulfilment of the university regulations of the Tamil Nadu Dr. M.G.R Medical University, Chennai, for M.D Degree Branch VII –
PAEDIATRIC MEDICINE examination to be held in May 2020.
Dr. S. BALASANKAR MD., DCH., Director & Professor of Pediatrics
Institute of Child Health & Research Centre Madurai Medical College.
CERTIFICATE
This is to certify that the dissertation entitled “A STUDY ON ETIOLOGICAL PROFILE OF ACUTE HEPATITIS IN CHILDREN” is the bonafide work of Dr.G.KAMALESHWARAN in
partial fulfilment of the university regulations of the Tamil Nadu Dr. M.G.R Medical University, Chennai, for M.D Degree Branch VII –
PAEDIATRIC MEDICINE examination to be held in May 2020.
Dr. M. BALASUBRAMANIAN, MD., DCH., Professor of pediatrics
Institute of Child Health & Research Centre Madurai Medical College
DECLARATION
I, Dr.G.KAMALESHWARAN, solemnly declare that the dissertation titled “A STUDY ON ETIOLOGICAL PROFILE OF ACUTE HEPATITIS IN CHILDREN” has been conducted by me at the Institute of Child Health and Research centre, Madurai under the guidance
and supervision of my Chief Prof.Dr.M.BALASUBRAMANIAN M.D., D.C.H.
This is submitted in part of fulfillment of the award of the degree of M.D. (Pediatrics) for the April 2020 examination to be held under the Tamil Nadu Dr. M.G.R Medical University, Chennai. This has not been submitted previously by me for any Degree or Diploma from any other University.
Place: Madurai Dr.G.KAMALESHWARAN Date:
CERTIFICATE - II
This is to certify that this dissertation work titled “A STUDY ON ETIOLOGICAL PROFILE ON ACUTE HEPATITIS IN CHILDREN” of the candidate Dr.G.KAMALESHWARAN with registration Number 201717101 for the award of M.D., in the branch of PAEDIATRICS personally verified the urkund.com website for the purpose of plagiarism Check. I found that the uploaded thesis file contains from introduction to conclusion pages and result shows 1 percentage of plagiarism in the dissertation.
Guide & Supervisor sign with Seal.
ACKNOWLEDGEMENT
First of all I thank the Almighty for everything. To begin with, I sincerely thank Prof.Dr.K.VANITHA MD, the Dean, Government Rajaji
Hospital and Madurai Medical College for permitting me to do this study.
I express my profound gratitude and sincere thanks to Prof.Dr.S.BALASANKAR MD DCH, Professor and Director, Institute of
Child Health & Research Centre, Madurai, for his able supervision, encouragement, valuable suggestions and support for this study.
I express my sincere thanks to my Chiefs Prof.Dr.Nandini Kuppusamy, Prof.Dr.M.Balasubramanian and Prof. Dr.D.Rajkumar for their guidance and encouragement throughout the study.
I would like to express my sincere gratitude to my former Professors
Prof.Dr.S.Shanmuga Sundaram, Prof.Dr.M.Kulandaivel, Prof. Dr.M.S.Rajarajeswaran for their support and guidance in doing my
study.
I would like to thank my former Assistant professor Prof. Dr. E.Sivakumar for his immense support and valuable guidance for
my study.
I thank my Registrar Dr. J.Balasubramaniam sir and my Assistant
Professors Dr.P.Ramasubramaniam, Dr.S.Murugesa Lakshmanan,
Dr. P.Kannan, Dr. K.Ramya, Dr. A.Abubackar Siddiq, Dr. B.Vanitha and Dr. T.Suganthi for their valuable suggestions and support.
I thank the Institutional Ethical Committee for granting me permission to do this study. I thank the Institute of Microbiology and Prof.Dr.V.Dhanalakshmi MD for helping me in investigation part.
I whole heartedly thank all my dear fellow Postgraduates for their help and co-operation in conducting this study.
Last but not the least, I thank all my dear patients and their kind hearted parents for participating in this study and helping me complete this study successfully.
CONTENTS
Sl.
No Title Page no
1. INTRODUCTION 1
2. AIMS AND OBJECTIVES 52
3. REVIEW OF LITERATURE 53
4. MATERIALS AND METHODS 57
5. OBSERVATION AND RESULTS 59
6. DISCUSSION 75
7. CONCLUSION 79
8. LIMITATIONS 80
ANNEXURES
BIBLIOGRAPHY
PROFORMA
ABBREVIATIONS
CONSENT FORM
MASTER CHART
1
INTRODUCTION
Hepatitis, the inflammation of the liver has a wide range of etiological factors. Acute hepatitis remains one of the major causes of morbidity and mortality in paediatric population. The pattern of liver diseases in children has changed considerably over the years. There are not much studies at present about the etiological pattern of hepatitis in children, in southern parts of India. It is very important to study about the causative agents of acute hepatitis in children, because these causes vary according to the demography, environmental factors, age group and various other factors. Also some of the causes of hepatitis are almost completely preventable such as viral hepatitis and some others are treatable causes such as Galactosemia when diagnosed early. Hence this study aims to find out the etiological profile of acute hepatitis in children attending our Government Rajaji Hospital, Madurai which is a Tertiary care institution and one of the leading referral centre for the whole southern parts of Tamilnadu.
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HEPATITIS
Liver is one of the most important organs for a human being, as it carries out a wide range of functions which are inevitable for survival. Its functions can be classified as synthetic, metabolic, biotransformation, excretory and other minor functions.
Metabolic functions of liver include its role in metabolism of all three major substrates respectively carbohydrates, proteins and lipids.
Synthetic functions include synthesis of clotting factors, major circulatory proteins and primary bile acids namely cholic acid and chenodeoxy cholic acid.
Biotransformation is the most characteristic and an exclusive function of the liver which determines the pharmacokinetics of most of the drugs. At the same time, liver also gets injured by some drugs leading to drug induced hepatitis. Some drugs such as anti tubercular agents and anti convulsants are more notorious to cause hepatitis which should be titrated properly and used with precautions.
3
JAUNDICE (ICTERUS)
It refers to the yellowish discoloration of the conjunctiva, sclera and mucous membranes. It is caused due to hyperbilirubinemia.
Jaundice will be clinically apparent only when the serum bilirubin levels are raised above 2-3 mg/dl. Icterus may be the earliest manifestation, sometimes the only manifestation of underlying liver disorder.
Jaundice is quantified by measuring the concentration of bilirubin in serum. Bilirubin exists in plasma as four forms:
1) unconjugated bilirubin 2) conjugated bilirubin 3) free or unbound bilirubin 4) the delta fraction
Of all these four forms, conjugated bilirubin is the only fraction that appears in urine. Free bilirubin having the ability to cross the cell membranes causes Kernicterus. Unconjugated bilirubin and the delta fraction are both bound to albumin, with the unconjugated bilirubin being tightly bound and the delta fraction being covalently bound. The delta fraction appears in serum only when the hepatic excretion of conjugated bilirubin is defective in case of hepatobiliary disease. The direct fraction
4
of bilirubin is the inclusion of both unconjugated bilirubin and the delta fraction
Unconjugated hyperbilirubinemia occurs in conditions of increased production, hemolytic disorders, decreased hepatic removal and in disorders of altered metabolisms of bilirubin.
Conjugated hyperbilirubinemia occurs due to defective excretion by the damaged liver parenchyma or biliary tract disorders which in turn caused by obstruction, septicemia, toxins, inflammation, genetic disorders or metabolic diseases.
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CAUSES OF ACUTE HEPATITIS IN CHILDREN
Infectious causes
•
Viral infectionsHepatotropic viruses
*
Hepatitis A,B,C,D and E virusesSystemic viral infections
*
HSV, HIV, Varicella, Enterovirus and others•
Non viral infections*
Bacterial Sepsis*
Leptospirosis*
Tuberculosis*
Amebiasis*
Others6
Non infectious causes
•
Autoimmune hepatitis*
SLE , JRA•
Metabolic disorders*
Wilsons Disease*
Alpha-1 AT Deficiency*
Tyrosinemia•
Toxic etiology*
Drug Induced hepatitis•
Other causes*
Non Alcoholic Fatty Liver Disease*
Hemodynamic Causes*
Surgical Causes7
VIRAL HEPATITIS
Viral hepatitis is the inflammation of liver caused mainly by the pathogenic Hepatotropic viruses Hepatitis A,Hepatitis B,Hepatitis C,Hepatitis D,Hepatitis E viruses and also by other viruses such as Cytomegalovirus, Herpes Simplex virus, Varicella-zoster virus, HIV, Epstein Barr virus, arbo viruses and adeno viruses.
The hepatotropic viruses belong to a heterogenous group but they all will cause similar type of illness.
PATHOGENESIS
The whole liver will be involved, with centrilobular necrosis.
Inflammatory infiltrates will be predominant in portal areas but can be seen in lobules also. The acute phase of hepatitis is caused due to both direct cytopathic effect and immune mediated injury. The lobular architecture will not be affected in acute injury but there will be parenchymal collapse in cases of fulminant hepatitis.
The liver morphology will recover to the normal structure within 3 months from the acute infection. If the injury progresses to chronic hepatitis as seen with HBV and HCV, there will be inflammatory infiltrates in periportal areas and progressive scarring. These 2 changes are the hallmark findings of chronic hepatitis.
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BIOCHEMICAL PROFILE
Acute injury to the liver caused by the hepatotropic viruses will manifest in 3 main liver functions.
1) cytopathic injury 2) cholestasis
3) synthetic function abnormalities Cytopathic injury
It will cause elevated levels of bilirubin and liver enzymes Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) in serum.
Usually the serum bilirubin levels will normalize first during recovery followed by ALT and AST levels which tend to improve over several weeks.
In case, if there is a rapid fall in aminotransferase levels in the background of raising serum bilirubin and a prolonged prothrombin time, then it indicates massive liver injury and a poor outcome.
CHOLESTASIS
Damage to hepatocytes and release of inflammatory mediators will lead to abnormal bile flow at the level of canaliculi and cellular level.
It is characterized by increased serum levels of conjugated bilirubin,
9
Alkaline phosphatase (ALP), Gamma Glutamyl Transpeptidase ( GGT) and urobilinogen.
There will be improvement in cholestasis as acute hepatitis resolves, but at the same time absence of these cholestatic markers will not rule out progesssion to chronic hepatitis in cases of HBV and HCV infections.
SYNTHETIC FUNCTION ABNORMALITIES
It is the most important marker for liver injury ant it should be the main focus of monitoring for follow-up, determining severity and deciding treatment and intervention.
Altered synthetic function is reflected by
•
prolonged PT, INR•
decreased serum albumin•
metabolic abnormalities such as hypoglycemia, hyperammonemia and lactic acidosis•
neurological manifestations – hepatic encephalopathy•
poor clearance of drugs whose metabolism is liver dependent10
Serial assessment to look for these complications is needed as progression from liver injury to failure will not follow a linear pathway.
In presence of hepatic failure signs and symptoms, the child should be referred to a transplant centre.
HEPATITIS A
It is an RNA virus belonging to the picornavirus family. It is transmitted almost always through faeco-oral route from person to person. It is highly contagious and the most prevalent among the hepatotropic viruses.
Incubation period is 3 weeks approximately. Excretion of HAV in the faeces starts in the late incubation period , attaining peak just before the clinical symptoms arise and resolves usually 2 weeks after the onset of icterus in older children. The duration of fecal excretion is more in infants. Thus the affected person is contagious before the onset of symptoms and remains so till the cessation of viral shedding.
CLINICAL MANIFESTATIONS
Often acute HAV hepatitis manifests as an anicteric illness very similar to other forms of viral gastroenteritis in children. It will be more symptomatic in cases of adolescents, adults, in immunocompromised persons and in those who have underlying liver disorders.
11
Duation of the illness will be around 7-14 days characterised by abrupt onset of nausea, anorexia, vomiting, malaise and icterus. Other uncommon manifestations include splenomegaly, regional lymph node enlargement, acute pancreatitis, myocarditis, anemia, arthritis, nephritis and vasculitis.
DIAGNOSIS
HAV hepatitis is diagnosed by measuring IgM anti HAV antibodies in the serum. Anti HAV is detectable in th serum when the clinical symptoms become apparent and it remains positive upto 4-6 months after the acute infection.
Neutralizing antibodies IgG anti HAV will be detected within 8 weeks from the onset of clinical symptoms and it confers long term protection.
Complications
There are 2 important complications seen in HAV hepatitis – *) Acute liver failure – rare in paediatric population
*) Prolonged cholestatic syndrome – it occurs without any synthetic function abnormalities and its course will be waxing & waning over several months. There will be pruritus and fat malabsorption which
12
are to be managed with anti pruritic drugs and fat soluble vitamins.
Usually this syndrome will have a complete recovery without any sequalae.
Prevention
Patients infected with HAV to be excluded from school/day care centres during the contagious period. Hand washing and food safety precautions to be followed to prevent the spread of the disease.
Immunoglobulin
Ig prophylaxis for HAV is preferred in children less than 12 months of age, in immuno compromised persons, those with underlying chronic liver disorders and for whom vaccine is contraindicated.
It is more preferable for travelers who are travellin to endemic areas of HAV, when administered it will provide protection upto 3 months. In post exposure prophylaxis, Ig should be given within a period of 2 weeks after which it will not be useful.
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HAV vaccine
There are 2 vaccines available for prevention of HAV infection.
Both of them are inactivated vaccines, highly immunogenic and very safe for use. Both of them are indicated for children more than 12 months of age.
2 doses are administered with an interval of 6-12 months with seroconversion rates of 90% and almost 100% after the first and second doses respectively. Protection will last upto 10 years. HAV vaccines can be given simultaneously with other vaccines.
HAV prophylaxis schedule
Pre exposure prophylaxis : (travelers to endemic areas)
• < 1 year of age : Ig
• > 1 year of age : HAV vaccine for healthy hosts and both HAV
& Ig for immunocompromised hosts and persons with liver disorders
Post exposure prophylaxis
• < 2 weeks from exposure :
< 1 year – Ig
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> 1 year (healthy host) – HAV vaccine, Ig is optional (both HAV & Ig for immunocompromised hosts and persons with liver disorders)
• > 2 weeks from exposure : None
Prophylaxis is not indicated for sporadic non-household or close contact exposure.
HEPATITIS B
Hepatitis B virus belongs to Hepadnaviridae family. It is a DNA virus with circular, partially double stranded DNA consisting of around 3200 nucleotides. There are 4 main genes – S (surface), C(core),X and P(polymer) genes.
The virus surface contains the characteristic
Hepatitis B surface antigen and the inner portion contains HBcAg, HBeAg and the nucleocapsid which codes for the DNA of the virus.
HBeAg is the marker of active replication, correlating with the levels of HBV DNA. HBV replicates mainly in the liver but also in lymphocytes, spleen, kidney and pancreas.
HBV has 8 genotypes from A to H. Of all these A is the pandemic one and B & C are the ones prevalent in Asia.
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Transmission
Main transmission is through sexual contact and exposure to infected blood. Risk factors for children and adolescents are intravenous drugs/blood products, contaminated needles, sexual contact and intimate contact with carriers.
The mode important mode of acquisition of HBV in children is through perinatal transmission. If the mother is positive for HBe Ag also, then the risk of transmission will be the greatest. Breastfeeding by infected mothers doesn’t pose a great risk for hepatitis.
Chronic HBV infection is defined as HBs Ag positive for more than 6 months. The risk of chronic infection is inversely proportional to the age of acquisition with 90 % in infants, 30 % in 1-5 years and only 2
% in adult population. Chronic infection will eventually lead to chronic liver disease and hepatocellular carcinoma.
Pathogenesis
Acute hepatitis phase will be similar to other hepatotropic viruses as discussed already. But HBV unlike the other counterparts, is predominantly noncytopathogenic and causes damage mainly by immune mediated process. Those immune mediated mechanisms mainly the circulating immune complexes are responsible for the extra hepatic
16
manifestations of HBV infection such as Polyarteritis nodosa, Guillain- Barre syndrome, leukocytoclastic vasculitis and membrano proliferative glomerulonephritis.
Chronic hepatitis mechanisms are not much understood. But the phenomenon of tolerance which may be due to non recognition of core protein / MHC 1 protein, cytotoxic lymphocytes not getting activated or some other unknown factors results in persistent infection of HBV in children with normal levels of liver enzymes and markedly increased levels of HBV DNA.
Clinical manifestations
Acute hepatitis due to HBV will be similar to HAV and HCV infections, but may be more severe in nature involving skin and joints also. Anorexia, malaise and fatigue will occur 6 to 7 weeks after exposure. Icterus will be present in apround 25% of patients with acute infection, beginning 8 weeks after exposure and lasting upto 4 weeks.
Most patients will recover with reslotuin of symptoms by 6 to 8 weeks. The chronic carrier state complicates around 10% of infections acquired in adulthood.
17
Chronic HBV infection has three phases 1) immune tolerant
2) immune active 3) inactive
Out of these most of the affected children fall into the immune tolerant phase for which no effective treatment is available. Most therapies are directed against the immune active phase which is characterized by active inflammation, increased liver enzyme levels and progressive fibrosis.
Spontaneous seroconversion occurs with development of anti HBe antibodies and HBe negativity. This seroconversion is more commin in childhood acquired infections rather than the perinatal transmission. It will take place in the immune tolerant phase sometimes over a period of many years.
Reactivation of the chronic infection may happen in immunocompromised children causing an increased risk of acute liver failure of rapidly progressive fibrotic liver disease.
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DIAGNOSIS
Serological diagnosis of HBV is a comppkex procedure involving many markers.
HBsAg is the first marker to appear in serum and will be positive in all infections. During recovery HBsAg levels fall and anti HBc IgM will appear being the only marker of acute infection. Anti HBc IgM persists for months and will be replaced by anti HBc IgG which remains in serum for years.
• Acute infection – HBs Ag followed by anti HBc IgM and IgG
• Chronic infection - HBs Ag > 6 months
• Vaccinated persons – only anti HBs
• Resolved infection - anti HBs and anti HBc
• Marker of infectivity in both acute and chronic infections – HBeAg
• Seroconversion – development of anti HBe
• Acute infections and chronic carriers – HBV DNA
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Complications
* Acute liver failure – characterized by coagulopathy, hepatic encephalopathy and cerebral edema; more common with HBV than any other hepatotropic viruses
* Chronic hepatitis – leading to cirrhosis, end stage liver disease and hepatocellular carcinoma
Membranous glomerulonephritis is a rare complication of HBV infection.
Treatment
Management of acute hepatitis is largely supportive.
Chronic hepatitis management should be individualized and should be always under the supervision of a Paediatric Gastroenterologist.
Treatment is now indicated for immune active phase only and the goal is to attain reduction of viral replication defined by undetectable HBV DNA in serum and to attain seroconversion defined by development of anti HBe.
Prevention
Screening of pregnant mothers for HBsAg and use of Hepatitis B vaccine and Hepatitis B Immunoglobulin are the most effective prevention strategies. HBsAg Mothers who are positive for HBeAg are
20
10% more likely to transmit the infection to their children than the HBeAg
Negative mothers. So recent guidelines suggest the use of anti viral drugs such as lamivudine, tenofovir or telbivudine during the 3rd trimester for mother who have viral load > 2 lakh I.U / ml , especially if they already have a child who developed chronic HBV hepatitis even after receiving HBV vaccine and HBIG.
Children with HBV should not be withdrawn from school/play as HBV is not spread by hugging, kissing, sharing water or utensils. All HBsAg positive cases should be noticed to the local health department.
Hepatitis B Immunoglobulin
It plays an important role in preventing perinatal transmission of HBV when administered to the baby within 12 hours of birth. Otherwise it is indicated only for post exposure prophylaxis and it will offer only temporary protection for 3 to 6 months.
Universal Vaccination
Centers for Disease Control and Prevention Advisory Committee has given the following recommendations for HBV vaccination after revision in 2005. These recommendations have been included in the
21
vaccine schedule of AAP – American Academy of Pediatrics which are explained as follows :
Main focus being the universal vaccination of infants – which begins at birth targeted at prevention of prenatal infection and infection in early childhood.
The safety profile is excellent for HBV vaccine. Seropositivity of
> 95 % will be attained after the second dose of all vaccines in most of the patients. The 3rd dose will serve as a booster and will help to maintain long term immunity.
A fourth dose is recommended for the infants weighing < 2 kgs at birth and for the children who are immunocompromised.
Administering 4 doses of HBV vaccine after the birth dose is permissible if combination vaccines are used but this will not increase the vaccine response.
Infants born to HBsAg negative mothers
• Stable infants > 2 kgs at birth – first dose of HBV vaccine should be administered before discharge. Single dose vaccine should be used for the birth dose. Subsequent doses at 1-4 months and at 6-18 months should be given to complete the schedule.
• Preterm infants < 2 kgs at birth – birth dose of HBV vaccine should be delayed upto 1 month of age
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Infants born to HBsAg positive mothers
Should receive their vaccination as follows – first dose at birth, subsequent doses at 1-2 months and 6 months. The birth dose should be accompanied by HBIG administration (0.5 ml) as soon as possible after delivery, maximum within 12 hours of birth.
Infants born to HBsAg unknown mothers
HBV vaccine should be administered within 12 hours of delivery, irrespective of birth weight to all infants. For those infants < 2 kgs HBIG should also be given along with vaccine. For infants > 2 kgs mother’s HBsAg status should be tested as soon as possible and if positive, HBIG should be given within 1 week of age.
Post vaccination testing
Done at 9 to 18 months of age to test for HBsAg and anti- HBs.
• Positive for anti-HBs : child is immune
• Postive for HBsAg only : child should be evaluated by a paediatric gastroenterologist
• Positive for both HBsAg and anti-HBs: a second complete schedule of HBV vaccine should be given, followed by testing for anti-HBs to decide for further doses.
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Special considerations
Patients with underlying cirrhosis will not respond to the HBV vaccines well. So higher dosages / short interval between the doses may increase the effectiveness of the vaccination followed by frequent testing for anti-HBs titres.
Patients with Inflammatory bowel disease have less anti-HBs titres which may be due to not vaccinating them with HBV vaccine / their poor immunity to HBV. Those children are at risk for developing fulminant HBV, if they are going to be started on immunosuppressive aagents especially Infliximab.
Prognosis
Generally the outcome of acute HBV infection is a favorable one. Perinatal transmission causing chronic infection is the most important factor for high incidence of hepatocellular carcinoma in younger adults, where HBV is endemic.
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BIOCHEMICAL PATTERN OF HBV INFECTION
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HEPATITIS C
Hepatitis C virus belongs to the Flaviviridae family. It is a single stranded RNA virus. It has a marked genetic heterogenecity with 6 major genotypes. It has numerous aubtypes and quasi species which enables it to escape from the host immune surveillance. Genotype 1b is the least responsive to the current available treatment.
Epidemiology
Before 1992 blood transfusion was the most common route of transmission, but with the screening practices currently practiced the risk of transmission is only 0.001% per unit of blood transfused.
In adults, intravenous drug abuse with exposure to blood products from the persons infected with HIV is responsible for upto 50% of cases.
Next to that, sexual transmission especially with multiple sex partners is the most common cause.
In children, perinatal transmission remains the most prevalent route of infection. Perinatal transmission occurs in upto 5% of babies born to HCV infected mothers. In cases of coinfection with HIV and high viral load of HCV RNA, the rate of transmission will be as high as 20%.
The incubation period ranges from 2 to 24 weeks with mean incubation period of 7 to 9 weeks.
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Pathogenesis
Acute liver injury is similar to all other hepatotropic viruses, at the same time the least severe of all hepatotropic virus infections. In chronic infection, lymphoid aggregates or follicles eill be seen in portal areas. Also steatosis will be present. The mechanism of injury is mainly cytopathic but immune mediated injury can also take place.
Clinical manifestations
Acute infection will be mild and insidious in nature. Acute liver failure is rare.Among all the hepatotropic viruses, HCV is the one most likely to cause chronic infection.
Of the infected population, only <15% of adults and 6 to 19% of children clear the virus and the rest will develop chronic hepatitis.
Chronic HCV infection usually remains silent until a complication arises. Histologic inflammation will be always present irrespective of the liver enzyme levels in serum. Around 25 % of the affected adults progress to cirrhosis. Hepatic failure and hepatocellular carcinoma over a period of 20-30 years. Eventhough progression is rare in children, cirrhosis and HCC are reported.
Chronic infection can be associated with small vessel vascilitis.
Other extra hepatic manifestations of chronic HCV infection are
27
cutaneous vasculitis, MPGN, nephritic syndrome and cerebritis which are more predominant in adults.
DIAGNOSIS
There are 2 methods for the detection of HCV infection.
1) Detection of anti HCV antibodies in serum - It is the most widely serological test for HCV diagnosis. Anti HCV antibody is not a protective one and it doesn’t confer any immunity. Sometimes it will not be seen till 1 to 3 months after infection, so false negative results are common. False positives also seen.
2) Detection of HCV RNA by PCR - It is the most commonly used serological assay for HCV. It can detect even small quantities of viral RNA in tissue and serum samples within days after infection.
• Qualitative PCR: very sensitive. For perinatal/recent infection, in patients with hypogammaglobulinemia, immunocompromised persons.
• Quantitative PCR: for identification of patients who are likey to respond to treatment and for monitoring the response to treatment.
28
Determining the genotype of HCV is important before starting the treatment as response to therapy varies with genotypes. Genotypes 2 and 3 are more responsive to therapy than the genotype 1 which is poorly responsive.
A liver biopsy should be done before starting the treatment because hepatic fibrosis and its extent can be well studied only by a biopsy. Also liver biopsy is necessary to rule out other causes of liver disease.
Screening
Screening for HCV should be done in patients with history of drug abuse (even if its only once), who have received blood products before 1992, who have received clotting factors before 1987 and in children born to HCV infected mothers (qualitative PCR for infants and anti HCV anibodies after 12 to 18 months of age)
Routine screening of all pregnant mothers is not recommended
Complications
Development of chronic hepatitis is the most important complication. Risk factors for fibrosis are older age, males, obesity and alcohol consumption. Cirrhosis and HCC are the manor causes of morbidity and most common indications for liver transplantation.
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Treatment
The goal of treatment is to achieve SVR – Sustained Viral Response. SVR is defined as the absence of viremia 6 months after stopping treatment. It is associated with decreased morbidity.
Peadiatric population which is more responsive to therapy are age
< 12 years, genotypes 2 & 3, HCV RNA < 2 million/ml in case of genotype 1b.
Peginterferon, Ribavirin and IFN-α2b are the currently FDA approved treatment modalities in children older than 3 years. IFN monotherapy in children showed a higher SVR and better compliance when compared to adults.
Treatment should be considered for all children infected with HCV with genotypes 2 & 3 and in those having fibrosis on liver biopsy.
Peadiatric guidelines recommend therapy for eradication of HCV infection, prevention of cirrhosis and HCC. Current therapy is 48 weeks duration of Peginterferon and Ribavirin (should be stopped if PCR is positive at 24 weeks of treatment).
In HCV infected children with genotype 1, the treatment options are controversial.
30
Newer options : peginterferon and direct acting antivirals such as telaprevir and boceprevir (viral protease inhibitors) show improved SVR in adult population. Newer drugs such as sofosbuvir and simeprevir have replaced telaprevir and boceprevir, but studies are still pending in children. Varying IFN free regimens are available with complete oral drus without the use of IFN. It is vital to getting updated with the latest treatment options from www.hcvguidelines.org in order to provide quality care.
Prevention
• No vaccine is available at present
• Current immunoglobulin preparation are not useful
• Vaccinating the HCV infected patients with HAV and HBV vaccines will prevent against superinfection and complications Monitoring
Once a person gets HCV infection, he/she should be yearly screened for viral RNA titres, Ultrasound abdomen, serum alpha fetoprotein for HCC and for other manifestations of liver disease.
31
HEPATITIS D
It is an RNA virus with single stranded circular RNA which is present in the inner core. The outer coat cannot be synthesized by the HDV on its own and it is derived from the excess HBsAg of HBV. Hence it cannot cause infection without HBV and so it is considered as defective virus.
Epidemiology
It can infect at the same time of HBV infection – coinfection or it can infect an already HBV infected patient – superinfection. Mode of transmission is inimate contact in high prevalence areas and parenteral transmission in low prevalence areas.
Incubation period for coinfection is ths same as that of HBV and 2 to 8 weeks for superinfection.
Pathogenesis
Causes liver injury mainly by cytopathic effects in contrast to HBV. Coinfection with HBV causes the HBV infection to become more severe.
32
Clinical manifestations
Clinical symptoms are similar but more severe than the other hepatotropic viruses. In coinfection – acute hepatitis will be more severe and low risk for chronic hepatitis, whereas in superinfection – acute illness is rare and chronic hepatitis will be more common.
The risk of ALF is highest in cases of superinfection, so HDV must be considered in any child with ALF.
Diagnosis
By detection of IgM anibodies against HDV which will develop 2-4 weeks after a coinfection and 10 weeks in superinfection
Treatment
No specific treatment for HDV infection and only supportive measures to be taken. Therapy is based mainly on treating and controlling the HBV infection without which HDV cannot cause hepatic injury.
Prevention
No vaccines for HDV available. Vaccination against HBV also protects against HDV. HBV vaccine and HBV immunoglobulin can be used as for HBV infection alone.
33
HEPATITIS E
It is a RNA virus similar to calciviruses in structure.
Epidemiology
It is the epidemic form of formerly termed non-A,non-B hepatitis. It is transmitted faeco-orally being more prevalent in India, Mexico, Middle east and South east Asia. Incubation period is 40 days ranging from 15 to 60 days. It has been postulated to be the most common cause of hepatitis and jaundice worldwide.
Clinical features
Affects older patients in age group of 15 to 34 years. Clinical picture similar to that of HAV but chronic infection doesn’t occurs as with HAV.
HEV is a major pathogen in pregnant women and associated with higher mortality. HEV could also cause decompensation of already existing chronic liver disease.
Diagnosis
By detection of IgM and IgG antibodies for acute and resolved infections respectively. IgM antibodies will be detectable 1 week after the infection. PCR can detect viral RNA in stool and serum.
34
Prevention
* Recombinant vaccine is available for HEV which if highly effective in adults.
* Immunoglobulin pooled from the affected persons in the endemic regions might be effective.
Hepatitis due to Nonhepatotropic viruses
Epstein-Barr virus infection manifests as Infectious mononucleosis along with acute hepatitis.
Cytomegalovirus can present with mononucleosis like syndrome with acute hepatitis as a feature if this syndrome.
Herpes Simples Virus and Enterovirus can cause acute hepatitis and even acute liver failure in newborn period. So all children presenting with neonatal liver failure should be treated with Acyclovir for HSV, before confirming the diagnosis as the delay in diagnosis may be fatal.
In India, Dengue virus infection is known to cause acute hepatitis with elevated liver enzymes. As dengue has become more or less endemic in South India especially Tamilnadu, it should be considered as one of the possible diagnosis for acute hepatitis.
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Hepatitis due to nonviral infections
Leptospirosis
It is one of the important causes of acute febrile hepatitis in our country. It has a biphasic illness and it can be anicteric also. The second phase of leptospirosis manifests as aseptic meningitis, nausea, vomiting and myalgia. In the severe form, it can present as febrile icteric illness with highly elevated serum bilirubin levels and moderate elevation of liver enzymes. This dissociation is due to the fact that there will not be hepatic necrosis in leptospirosis.
Acute tubular necrosis due to acute kidney injury, febrile illness, presence of similar cases in an endemic area and the dissociation between the bilirubin and the liver enzyme levels will help in differentiating leptospirosis from other infections.
Enteric fever
It is a common infection in our country and also a common differential diagnosis for the viral hepatitis. The major feature which differentiates it from viral hepatitis is the presence of fever. The icterus of enteric fever will be mild.
The acute hepatic phase of enteric fever can cause acute liver failure even. If the ratio of Alanine transaminase to Lactate
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dehydrogenase is < 4, then it is suggestive of enteric fever. Also it can be confirmed by widal test, cultures of blood / urine / stool according to the duration of illness and time of presentation.
Malaria
It is another common endemic infection in India. It can present as conjugated jaundice in severe cases because of hepatopathy. Malarial hepatopathy is a febrile illness with usually low levels of the liver enzymes. Acute inflammation of the liver is never seen in malaria, hence it is advisable to use the term malarial hepatopathy than hepatitis.
The typical presentation of fever spikes, chills, residence / travel to the endemic areas and lab investigations such a Rapid card test / Malarial smear can establish the diagnosis.
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Metabolic causes of acute hepatitis
Wilson’s disease
It is otherwise called as hepatolenticular degeneration. It is an autosomal recessive disorder due to defect in the gene located in 13q14.3, which encodes for a Copper transporting P-type ATPase – ATP7B. Its incidence is 1 in 30,000-50,000 births worldwide.
Early diagnosis of the disease especially in suspected children > 5 years of age is essential not only because the disease is rapidly progressive and potentially fatal but there is specific effective treatment available for this metabolic condition.
Pathogenesis
ATP7B is expressed mainly in the hepatocytes and is necessary for biliray copper excretion and incorporation of copper into ceruloplasmin.
Absence or defective function of ATP7B will lead to decreased copper excretion ultimately resulting in diffuse copper accumulation in the cytoplasm of hepatocytes. With progress of time, liver cells get overloaded and the excess copper will be redistributed to the other vital organs including kidneys and brain causing toxicity. Ionic copper acts as a potent inhibitor of enzymes such as Pyruvate oxidase in brain and
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ATPase in the cell membranes resulting in decreased levels of adenosine triphosphate-phosphocreatine and Potassium in the tissues.
More than 500 mutations of the affected gene identifies till now with 380 mutations playing a confirmed role in causation of disease.
Hence it becomes very difficult to establish the diagnosis by genetic means. Milder mutations of the gene can manifest later at an age of 80 years, but at the same time complete knock-out mutations can manifest very early at 2 to 3 years of age when Wilson’s disease will not be usually considered as a differential diagnosis.
Clinical manifestations :
Wilson’s disease can present in three distinct forms as follows
1. Hepatomegaly (with / without splenomaegaly) which is aymptomatic
2. Subacute / chronic hepatitis
3. Acute liver failure ( with / without hemolytic anemia )
Other clinical manifestations are ascites, edema, portal hypertension, variceal bleeding ,cryptogenic cirrhosis and features of hepatic dysfunction such as coagulopathy, amenorrhoea and delayed puberty.
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Disease presentation is variable. Female children are 3 times more likely to present with acute liver failure when compared to males.
Agewise, the younger the patient the more will be the hepatic involvement compared to neurological symptoms. Liver disease will precede the neurological manifestations by a period of around 10 years.
After 20 years of age, there will be predominant symptoms of nervous system involvement.
Neurological manifestations can arise suddenly or insidiously including dystonia, dysarthria, chorea, Parkinsonism, intentional tremors, poor scholastic performance and behavioral changes.
Psychiatric symptoms may be depression, anxiety, psychosis or personality changes.
Kayser-Fleischer ring (K-F ring)
It is due to the deposition of copper in the Descemet’s membrane of cornea, which will be seen as a greenish brown ring at the outer margin of cornea. Slit lamp examination is essential to confirm its presence.
K-F rings will not be seen in half of the patients with only hepatic manifestations whereas it will be present in 95% of patients with neurological manifestations.
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Hemolytic anemia
Sometimes Wilson’s disease may initially present as hemlolytic anemia which will be Coombs negative. Hemolysis may be due to the huge amounts of copper released from the damaged hepatocytes. During the episodes of hemolysis, urinary copper and serum free copper levels are highly elevated. This hemolytic form of Wilson’s disease may end up in fatality unless liver transplantation done.
Unusual manifestations of Wilson’s disease are Renal Fanconi syndrome and renal failure, arthritis, nephrolithiasis, pancreatitis, recurrent abortions / infertility, hypoparathyroidism and cardiomyopathy.
Pathology
All grades of liver injury will occur in Wilson’s disease.
Histologically the earliest feature will be only a mild steatotic change which may be mistaken for nonalcoholic steatohepatitis / nonalcoholic fatty liver disease. Also the lesion cannot be distinguished from the autoimmune hepatitis. With progression of the disease, parenchymal damage continues leading to fibrosis and cirrhosis. Ultrastructurally, mitochondria is the one primarily involved. Changes in mitochondria are increase in matrix density, lipid & granular inclusions and increase in the intracristal space with the tips of cristae getting dilated.
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Diagnosis
Following are the clinical situations where Wilson’s disease to be suspected :
• Unexplained acute / chronic liver disease in children and adolescents
• Neurological symptoms of unknown etiology
• Acute hemolytic anemia
• Psychiatric symptoms
• Behavioral abnormalities
• Fanconi syndrome
• Unexplained osteoporosis, myopathy, fractures
Serum seruloplasmin levels will be decreased (< 20 mg/dl).
Because the copper is not incorporated into the ceruloplasmin, its half life becomes shorter and hence reduced steady state concentration of ceruloplasmin in the circulation.
Serum ceruloplasmin levels should be interpreted with caution because ceruloplasmin may be elevated apart from Wilson’s disease in acute inflammatory conditions and in conditions of elevated estrogen levels such as pregnancy, ues of oral contraceptives and estrogen supplementation. At the same time, Serum ceruloplasmin may be low in
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conditions like celiac disease, autoimmune hepatitis, familial aceruloplasminemia and in persons who are heterozygous carriers for ATP7B mutations not exhibiting copper overload disease.
Serum free copper level will be elevated in early phase of Wilson’s disease (>1.6 μmol/L) and urinary copper excretion (which is usually <
40 μg/day) will be increased upto > 100 μg/day and sometimes upto 1000 μg or more per day. Typically urinary copper excretion in Wilson’s disease will be >0.64 μmol/ 24 hrs in children.
In suspected case with equivocal results, urinary copper excretion to be measured after chelation therapy. Two doses of D-Penicillamine 500 mg to be given orally 12hrs apart, during the 24 hour urine collection period. Persons affected with Wilson’s disease will excrete more than 1600 μg/day .
Demonstration of K-F rings needs a slit lamp examination by an ophthalmologist. Kayser-Fleischer rings will resolve after adequate treatment.
Liver biopsy
Biopsy will help to assess the severity and the extent of disease and hepatic copper measurement can be done. But liver biopsy is indicated only in circumstances when the diagnosis of Wilson’s disease
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cannot be made by clinical signs and noninvasive laboratory investigations.
Measuring the copper content of liver parenchyma is the method of diagnosis for Wilson’s disease because Hepatic copper accumulation is the hallmark change seen.
Normal hepatic copper content is < 10 μg/g dry weight which will exceed 250 μg/g dry weight in Wilson’s disease. (though > 4 μmol/g dry weight may provide the best biochemical evidence for Wilson’s disease, lowering the threshold to 1.2 μmol/g dry weight will help to increase th sensitivity without affecting the specificity)
In later stages of Wilson’s disease, cirrhosis will develop leading to varying distribution of hepatic copper. So, hepatic copper measurement will be unreliable.
Screening
Family members of confirmed case should be screened for presymptomatic Wilson’s disease by measuring serum ceruloplasmin and urinary copper output. If the results come as positive or even equivocal, then they should undergo liver biopsy to measure hepatic copper and to determine the liver morphology.
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Genetic screening is also possible, if the mutation for the proband case is known or in case where the patient belongs to an endemic area with already kmown mutation. The methods used for genetic screening are linkage analysis / direct DNA mutation analysis.
Treatment
Treatment is a lifelong process for Wilson’s disease. First of all, dietary copper intake should be limited to < 1 mg/day. Copper containing foods such as chocolate, shell fish, liver and nuts to be avoided.
Demineralization of drinking water is necessary if its copper content exceeds 0.1 mg / L.
Administration of oral copper chelating agents will increase the urinary copper excretion. Common chelating agents used are
• D-Penicillamine (BB dimethyl cysteine) at a dose of 20 mg/kg/day in children and 1 g/day for adults (or)
• Trientine (triethylene tetramine dihydrochloride) at the dose of 20 mg/kg/day in children and 0.5-2.0 g/day for adults Urinary copper excretion will increase markedly after chelation and will eventually become normal with continued administration of chelating agents. Simultaneously there will be considerable improvement in hepatic and neurological functions and the K-F rings will also disappear.
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Around 10-50% of patients treated with penicillamine for neurologic symptoms will worsen due to its adverse effects.
Toxic effects of penicillamine will occur in 10-20% of patients and include hypersensitivity reactions, zinc deficiency, aplastic anemia and
nephrosis. Vitamin B6 should be supplemented along with D-penicillamine as it is an antimetabolite of vitamin B6. For the above
said reasons, Trientine is preferred over D-penicillamine as the first-line therapy for patients who experience adverse effects of penicillamine.
Ammonium tetrathiomolybdate is another chelating agent being investigated for patients having neurological symptoms. Initial results show that this drug will cause less severe neurologic deterioration when compared with penicillamine. Dosage is 120mg/day. Its adverse effects include pancytopenia, elevation of liver enzymes and antiangiogenic effects.
Zinc will impair the gastrointestinal absorption of copper and because of this unique feature, zinc can be used as adjuvant therapy, maintenance therapy or even as primary therapy in presymptomatic patients. Dosage is 25-50 mg of elemental zinc 3 times a day for adults and 25 mg 3 times a day for children > 5 years. Zinc monotherapy is controversial in symptomatic liver disease and at present it is not recommended.
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As per the Current guidelines for the treatment of Wilson’s disease, all symptomatic patients should be given chelating agent either penicillamine or trientine.
Antioxidants such as vitamin E and pharmacologic chaperones like 4-phenylbutyrate and curcumin are under research for use as adjunctive therapy.
Prognosis
Wilson’s disease if untreated can cause death due to complications be it hepatic, renal, neurological or hematological. Prognosis of patients receiving Penicillamine is variable. Liver transplantation is curative showing 85 to 90% survival rate. Transplantation is indicated in cases of fulminant hepatitis, decompensated cirrhosis and progressive neurological deterioration. Siblings of the affected patients can be prevented from expression of Wilson’s disease if they are given chelation or zinc therapy early during their asymptomatic period.
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Drug-induced Liver Disease
Various drugs can cause liver injury with varying spectrum of clinical features. Acute hepatitis is the most common presentation of drug induced hepatic injury.
Histological manifestations will include inflammatory infiltrates with bridging, patchy or panlobular necrosis depending on the offending drug.
Biochemically, damage to the hepatocytes will cause elevation of ALT levels. ALT levels more than 2 times the normal or the ratio of ALT to ALP more than or equal to 5 marks the diagnosis of drug induced hepatitis.
Drug induced liver disease is classified into 2 distinct types based on the clinical symptoms and laboratory features:
1) Immunoallergic type :
• Has no relation to the dose of the offending drug.
• Hepatitis manifests usually after 2 to 10 weeks from starting the drug.
• Not affected by the drugs given along with the offending drug
• Fever will be usually present
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• Extrahepatic manifestations may be seen like lymphadenopathy and rash
• Peripheral eosinophilia and Autoantibodies can be seen
• Clinical features resolve rapidly when the drug is withdrawn but will reappear suddenly within a few days of restarting the drug.
2) Hepatitis due to metabolic idiosyncrasies
• Few drugs have a partial relation of their dose to the degree of hepatic injury
• Liver injury takes place after a long duration of 2 weeks to 6 months, sometimes even upto 1 year
• Drugs administered along with the offending drugs can affect the metabolic pathways potentially and can augment the hepatic injury
• Fever and extrahepatic manifestations are unsual
• There will not be any autoantibodies or eosinophilia
• As seen in immunoallergic type, dramatic recovery will not be seen with the withdrawal of the drug. Rather the affected children may worsen or tend to recover slowly.
• In contrast to the immunoallergic type, one third of the affected children can tolerate the offending drug without any symptoms, when it is reintroduced after a period of withdrawal.
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Phenytoin toxicity – Prototype for Immunoallergic reactions
Liver injury due to Phenytoin can cause a wide range of manifestations, the commonest being acute hepatitis. The hepatitis can be a less severe one with only mild jaundice or it can lead on to liver cell failure with ascites and hepatic encephalopathy.
Phenytoin induced Hepatitis can be mistaken for mononucleosis like syndrome as it causes fever, leukocytosis, lymphadenopathy and lymphocytosis. Eosinophilia is also seen.
Skin rashes will be present ranging from morbilliform lesions to Steven Johnson Syndrome and Toxic Epidermal Necrolysis.
Postulated mode of injury is deficiency of the enzyme –epoxide hydrolase which is responsible for the detoxication of the arene oxide metabolite of Phenytoin. This will lead to formation of haptens which initiate the immunological injury. Another anticonvulsant Phenobarbitone when administered along with Phenytoin may increase the severity of its hepatotoxicity.
Management includes withdrawal of the offender – phenytoin and administration of steroids which are often used for managing phenytoin induced hepatitis.
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Isoniazid induced hepatitis – prototype for metabolic idiosyncrasies
Isoniazid an antitubercular agent is one of the common causes of acute hepatitis in our country. The frequency of hepatitis is high when used simultaneously with pyrazinamide and rifampicin. Children with severe forms of Tuberculosis and malnourished children are more prone to develop acute hepatitis. Simultaneous use of phenobarbitone is a potential risk factor for liver injury because of P450 stimulation by phenibarbitone.
Rapid acetylators who produce the acetyl isoniazid intermediate faster than others will have high rate of hepatic injury.
Elevation of trasaminases > 5 times normal is an indication for withdrawal of the drug. Elevation > 10 times normal will produce very severe clinical symptoms.
Histologically it is difficult to distinguish the isoniazid induced hepatitis from other causes of acute hepatitis. Massive hepatocellular necrosis will be seen in severe forms leading to liver failure.
Symptoms are nausea,vomiting and anorexia. Systemic involvement will not be seen. Sometimes the patients can develop liver failure which has a poor prognosis and needs liver transplantation.
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Stopping the drug early, well before the onset of liver failure will result in good outcome. Reintroduction of the drug can cause recurrence of the symptoms but studies in India show that, when the drug is reintroduced gradually most children can be started on the drug again.
Serial monitoring of serum levels of liver enzymes after starting Isoniazid is advised but it will not prevent hepatitis in all cases. Clinical attention to the symptoms and the non specific features can be helpful.
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AIMS AND OBJECTIVES
To study the etiological profile of acute hepatitis in children attending Govt Rajaji Hospital, Madurai
INCLUSION CRITERIA
All children in the age group of 1 to 12 years with jaundice of duration less than 3 months
EXCLUSION CRITERIA
•
Children with clinical / ultrasonogram evidence of obstructive jaundice•
Known cases of chronic liver disorder53
REVIEW OF LITERATURE
Meena Kumari Mili et al (2019) conducted a prospective observational study, during the period of August 2016 to July 2017 about the spectrum of acute hepatitis in children. The study was done at Gauhati Medical College Hospital, Assam in the Department of Paediatrics.
Totally 46 patients of age group 1 to 12 years were included in the study.
They reported that Viral hepatitis caused by Hepatitis A virus (80.4%) was the most common cause of acute hepatitis in children.
Jaundice (95.6%) with fever (91.3%) was the most common symptom reported followed by fatigue and vomiting. Serum bilirubin and liver enzymes were found to be elevated in almost all cases.
Their recommendations for prevention of Hepatitis A infection are proper hygiene, creating awareness among the public and vaccination against Hepatitis A. They also recommended universal immunization for prevention of Hepatitis B infection and proper blood screening techniques for prevention of Hepatitis B and C infections.
Swanand S. Rewatkar et al (2017) conducted a prospective study regarding the etiology of hepatitis in children with a sample size of 100 patients in the age group of 1 month – 18 years. The study was conducted at Moolchand Medcity Hospital, New Delhi from August 2008 to August
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2010. They got their study results as Hepatitis A (88%) was the commonest cause of acute hepatitis in children followed by Enteric fever (5%) and Hepatitis E (3%). Out of the 100 children, 2 children went in for fulminate hepatic failure – one recovered and the other was referred for liver transplantation.
They reported that the average period of the illness was 4 to 8 weeks. The average period of clinical recovery was 12 to 24 days followed by biological recovery 23 to 59 days.
Gp Capt B Nandi et al conducted a prospective hospital based study on the Spectrum of Acute Viral Hepatitis in Southern India during the period of 1st July 2003 to 31st December 2004. The study was conducted at Multi Speciality Military hospital in Bangalore, India.
Totally 252 cases of acute hepatitis studied out of which 224 patients with viral etiology were selected for the statistical analysis.
Results of the study were Hepatitis A was the commonest cause of acute hepatitis in children whereas Hepatitis E found to be the commonest cause in adults and overall. 16 cases of mixed infection by Hepatitis A + E seen.
Relapsing hepatitis was found in 4 patients, all of which caused by Hepatitis A. Cholestasis was common in Hepatitis E.
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Liver failure occurred in 4 patients out of which 2 patients expired.
Fatal cases was caused by Hepatitis A and Hepatitis E each.
Girish N et al conducted a prospective observational study in Department of Paediatrics, KIMS hospital, Bangalore on Viral hepatitis in children. The study was done from August 2015 to July 2016. Children aged < 18 years were included in the study. Initially 61 children of acute hepatitis were studied for the etiological cause and 48 (78.6%) cases were found to be viral hepatitis. Those 48 cases were studied further for the clinical and biochemical presentation.
Hepatitis A was the commonest cause (83.3 %) among those viral hepatitis cases attributing to 40 out of 48 cases. 1 case was due to Hepatitis B and the remaining 7 were due to Hepatitis C.
2 out of those 48 cases went in for Hepatic encephalopathy and eventually died. One death was Hepatitis A and the other was Hepatitis B infection.
This study suggested the importance of creating awareness among the society and education of the public about the clinical presentation of the viral hepatitis as vital factors for the prevention and timely management of this public health problem.
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Salahuddin Mahmud et al had done a prospective descriptive study on recent spectrum of viral hepatitis in children from January to December of the year 2016. The study was conducted at the Department of Pediatric Gastroenterology, Hepatology & Nutrition, Dhaka Shishu (Children) Hospital, a tertiary care centre located at Dhaka of Bangladesh.
Totally 100 children of the age group 1 to 15 years were studied.
Out of them, 76 cases (76 %) were positive for Hepatitis A and 14 cases (14 %) for Hepatitis E. Coinfection with Hepatitis A and Hepatitis E were 4 cases (4%). Hepatitis B and Hepatitis C were 4 cases (4%) and 2 cases (2 %) respectively.
There was no mortality reported in this study. Hepatitis A was predominant in the age group of 1 to 10 years and Hepatitis B in 10 to 15 years of age.
As with previous studies, the recommendations of proper hygiene, correct techniques of sewage disposal, clean drinking water and public awareness were made in this study also.
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MATERIALS AND METHODS
Ours is a prospective descriptive hospital based study conducted at the Government Rajaji Hospital affiliated to Madurai Medical College, Madurai. The study included children in the age group of 1 to 12 years from both in-patients and out-patients who attended our Institute of Child Health & Research Centre of Government Rajaji Hospital, Madurai.
All children in the 1 to 12 years age group who presented with jaundice of less than 3 months duration were included in the study.
Children with clinical and ultrasound evidence of obstructive pathology were excluded in the due course of the study.
A detailed history of their symptoms made out followed by a thorough systematic clinical examination as per the proforma.
After that, all children were subjected to the following baseline investigations such as
Complete Blood Count
Liver Function Tests (Serum Bilirubin and Liver Enzymes)
Coagulation Profile(PT,APTT,INR)
Urine – Bile Salts And Bile Pigments
USG abdomen and pelvis
