This document provides an overview of the approach to paediatric hepatitis. It discusses the main causes of hepatitis including viral (HAV, HBV, HCV, HDV, HEV), autoimmune, and drug-induced. For viral hepatitis, it covers the etiology, pathogenesis, clinical features, diagnosis, and management of each virus. It provides details on HAV including transmission via the fecal-oral route, clinical presentation of acute hepatitis, diagnosis via IgM antibodies, and treatment involving immunoglobulin for prevention. For HBV, it discusses the various modes of transmission including perinatal, clinical phases from acute to chronic infection, diagnostic markers, and treatment of acute versus chronic cases.
The primary treatment goals for patients with hepatitis B (HBV) infection are to prevent progression of the disease, particularly to cirrhosis, liver failure, and hepatocellular carcinoma (HCC).
Risk factors for progression of chronic HBV include the following :
Persistently elevated levels of HBV DNA and, in some patients, alanine aminotransferase (ALT), as well as the presence of core and precore mutations seen most commonly in HBV genotype C and D infections
Male sex
Older age
Family history of HCC
Alcohol use
Elevated alpha-fetoprotein (AFP)
Coinfection with hepatitis D (delta) virus (HDV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
A synergistic approach of suppressing viral load and boosting the patient’s immune response with immunotherapeutic interventions is needed for the best prognosis. The prevention of HCC often includes the use of antiviral treatment using pegylated interferon (PEG-IFN) or nucleos(t)ide analogues.
HBV infection can be self-limited or chronic. No specific therapy is available for persons with acute hepatitis B; treatment is supportive.
The primary treatment goals for patients with hepatitis B (HBV) infection are to prevent progression of the disease, particularly to cirrhosis, liver failure, and hepatocellular carcinoma (HCC).
Risk factors for progression of chronic HBV include the following :
Persistently elevated levels of HBV DNA and, in some patients, alanine aminotransferase (ALT), as well as the presence of core and precore mutations seen most commonly in HBV genotype C and D infections
Male sex
Older age
Family history of HCC
Alcohol use
Elevated alpha-fetoprotein (AFP)
Coinfection with hepatitis D (delta) virus (HDV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
A synergistic approach of suppressing viral load and boosting the patient’s immune response with immunotherapeutic interventions is needed for the best prognosis. The prevention of HCC often includes the use of antiviral treatment using pegylated interferon (PEG-IFN) or nucleos(t)ide analogues.
HBV infection can be self-limited or chronic. No specific therapy is available for persons with acute hepatitis B; treatment is supportive.
Hepatitis: inflammation of the liver.
Causes of viral hepatitis:
Common:
Hepatitis A virus (HAV)
Hepatitis B virus (HBV)
hepatitis C virus (HCV)
Hepatitis D virus (HDV)
Hepatitis E virus (HEV)
HBV-associated delta agent
Introduction to chronic Hepatitis B Infection in Malaysia, epidemiology and common treatment. Phases of chronic Hepatitis B Infection, clinical presentation and complications.
Similar to Approach to a case of paediatric hepatitis (20)
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Evaluation of antidepressant activity of clitoris ternatea in animals
Approach to a case of paediatric hepatitis
1. Approach to a case of
Paediatric Hepatitis
Dr Raghav Kakar
M.D. Paediatrics
2. We will be covering:
Viral hepatitis – Aetiology
Pathogenesis
Clinical features
Diagnosis
Management
Autoimmune hepatitis
Drug induced hepatitis
3. HEPATITIS
• Inflammation of liver parenchyma
• 2 types
• Acute – duration < 6 months
• Chronic – duration ≥ 6 months
• It’s commonly caused by a viral infection, but there are other
possible causes of hepatitis. These include autoimmune hepatitis
and hepatitis that occurs as a secondary result of medications,
drugs, toxins, and alcohol.
4. Etiology
1. Viral
• Hepatotropic viruses – HAV, HBV (serum virus), HCV, HDV, HEV
• Non hepatotropic viruses – CMV, EBV, Adenovirus, HSV, Dengue virus etc.
2. Non viral – Leptospirosis, Enteric fever, TB, Histoplasmosis, Amebiasis.
3. Drug and toxin induced – Acetaminophen, Phenytoin, INH,
Nitrofurantoin, Methotrexate, Alcohol.
4. Autoimmune - Autoimmune hepatitis, SLE, JRA
5. Metabolic – Tyrosinemia, Wilson disease
6. Ischaemic hepatitis – Shock, CHF
7. Non alcoholic fatty liver disease – Reye syndrome
5. Viral hepatitis
• Most common cause worldwide
• Caused by 5 pathogenic hepatotropic viruses : Hepatitides A (HAV),
B(HBV), C(HCV), D(HDV) and E(HEV) viruses.
• HAV – most common in India , > 80% children
• Although the agents can be distinguished by their antigenic properties,
the 5 kinds of viruses may produce clinically similar illness.
6. Viruses Type Incubation
period (days)
Transmission Chronic
infection
Fulminant
disease
HAV RNA 15-19 Faeco-oral No Rare
HBV DNA 60-180 Parenteral, sexual,
perinatal
Yes Yes
HCV RNA 14-160 Parenteral, sexual,
perinatal
Yes Rare
HDV RNA 21-42 Parenteral, sexual,
perinatal
Yes Yes
HEV RNA 21-63 Faeco-oral No Yes
7. Pathogenesis
• The viruses do not directly cause apoptosis. Rather, infection of liver
cells activates the innate and adaptive immune system leading to an
inflammatory response which causes cellular damage and death.
• Depending on the strength of the immune response, the types of
immune cells involved and the ability of the virus to evade the body's
defense, infection can either lead to clearance (acute disease) or
persistence (chronic disease) of the virus.
• The acute response of the liver to hepatotropic viruses involves a direct
cytopathic and an immune mediated injury.
8. • The chronic presence of the virus within liver cells results in multiple
waves of inflammation, injury and wound healing that overtime lead
to scarring or fibrosis and culminate in HCC
• With recovery, the liver morphology returns to normal within 3
months.
• In chronic case, inflammatory infiltrate settles in periportal areas and
leads to progressive scarring – HBV, HCV
10. Hepatitis A
• Most prevalent
• HAV – RNA virus, picornavirus family
• Host – human and other primates
• Transmission – Faeco oral route
• Faecal excretion of virus starts late in the incubation period and reaches
the peak just before the onset of symptoms and resolves within 2 weeks
after onset of jaundice
11. CLINICAL FEATURES:
• Illness is usually symptomatic in older children
• Acute febrile illness with abrupt onset of anorexia, malaise ,
vomiting, jaundice
• Duration is usually 7-14 days
• Hepatomegaly , regional lymph nodes and spleen may be enlarged
• Acute pancreatitis, gastrointestinal ulcers , myocarditis, nephritis,
arthritis – circulating immune complexes
12. DIAGNOSIS
• Detection of Anti-HAV Ig M antibodies – symptoms are apparent,
remains for 4-6 months
• Viral particles in faeces
• Ig G type is detected within 8 weeks of infection
• Rise in serum transaminases, bilirubin and alkaline phosphatase is
universal and hence cannot distinguish between other forms of
hepatitis
13. COMPLICATIONS:
• Most patients – full recovery
• Acute liver failure – rare. Seen in immunocompromised and those with
underlying liver disorders
• Prolonged cholestatic syndrome - persistent hyperbilirubinemia,
pruritus, and constitutional symptoms that last for 12-16 weeks in the
absence of biliary obstruction on sonograms.
14. Treatment
• No specific treatment
• Fat soluble vitamins for prolonged cholestatic form.
• Serial monitoring for signs of ALF.
• Patients contagious 2 weeks before and 7 days after onset of jaundice.
• Handwashing after toilet
15. • Intravenous immunoglobulin – ‘Pre exposure prophylaxis’ for travellers to
endemic regions. Provides protection upto 3 months
AGE EXPECTED EXPOSURE
DURATION
DOSE
< 1 year <3 months
3-5 months
> 5 months
0.02 ml/kg
0.06 ml/kg
0.06 ml/kg , repeated every
5 months
≥ 1 year Healthy
Immunocompromised /
chronic liver disease
HAV vaccine
HAV vaccine + 0.02 ml/kg
16. Post exposure prophylaxis with Ig –
• Not effective 2 weeks after exposure.
• For exposure less than 2 weeks:
< 1 y.o. child - 0.02 ml/kg. For immunocompromised host and those with
chronic liver disease – give HAV as well.
> 1 year – HAV vaccine. Ig is optional.
• Vaccine : - Inactivated vaccine ( Haverix) 0.5 ml I.M in deltoid, 2 doses > 1
year of age 6 months apart.
• Live vaccine is also available in India (Biovac A) – Single dose of H2 strain.
17. Hepatitis B
• DNA virus, Hepadnaviridae family.
• Discovered in 1966.
• Also known as Dane Particle.
• HBV is present in high concentrations in blood , serum and serous
exudates and moderate concentrations in semen, vaginal fluid and
saliva
18.
19. Modes of Transmission:
• Perinatal – Vertical transmission from mother to baby
• Parentral – Transfusion of infected blood and its products,
using non sterile syringes,needles and medical instruments.
• Sexual
• Risk of transmission increases with the level of HBV DNA in
serum and HBeAg positive
20. • In children, most important mode is vertical transmission.
• 90% of these infants remain chronically infected if untreated
• Intrauterine infection occurs in 2.5 %
• HBsAg is inconsistently recovered from human milk of infected mothers.
• Breastfeeding of non immunized infant by an infected mother does not
confer a greater risk of hepatitis than formula feeding.
21. CLINICAL FEATURES:
• Clinicopathologic syndromes include the following:
1. Acute hepatitis with resolution:
2. Chronic hepatitis, with or without progression to cirrhosis
3. Fulminant hepatitis with massive liver necrosis
4. Coinfection/Superinfection with hepatitis D virus
• Acute symptomatic similar to HAV and HCV, but more severe
• In some, illness preceeded by serum sickness like prodrome – arthralgia,
skin lesions including urticarial, purpural or maculopapular rash.
22. • Dark urine, clay-colored or light stools, and abdominal pain
• Tender hepatomegaly
• Splenomegaly in 15 -20% cases
• A few spider angiomas may appear during the icteric phase and disappear
during convalescence
• Chronic carrier state – 10 %
23.
24. Phases of HBV Infection
1. Replicative phase with Immune Tolerance : It represents the
incubation period and lasts several weeks..
2. Replicative phase with Immune Clearance : The immune
system of the host responds to the virus resulting in hepatic
inflammation and direct cell lysis. Lasts for 4-6 weeks. If the
immune response is ineffective it may persist for many years.
25. 3. Integrative phase with no replication : The immune response
of the host is successful and active viral replication ends. HBV
DNA becomes undectable and HBeAg becomes positive.
4. Integrative phase with viral clearance : Viral replication
completely stops and HBsAg becomes negative. Patients who
recover from acute hepatitis B will reach this phase but those
with chronic infection, never reach it.
26. DIAGNOSIS:
• LFT’s - Elevations of ALT and AST levels are hallmarks of acute hepatitis.
Values as high as 1000-2000 IU/L are typical, with ALT values higher than
AST values.
• The prothrombin time is the best indicator of prognosis
• HBsAg (also known as the Australia antigen) is the surface antigen of the
hepatitis B virus (HBV). Its presence indicates current hepatitis B infection.
• Definitive diagnosis depends on serologic testing for HBV infection.
27. Serological Diagnosis in Hepatitis B
HBsAg HBeAg Anti HBsAg Anti HBeAg Anti HBcAg
Acute Infection + + - - +
Chronic Infection + + - - +++
Recently Cured
HBV
- - ++ + ++
Past infection - - + - +
Healthy Carrier + - - + +++
Vaccinated - - ++ - -
28.
29. • Patients with signs of chronic
disease may require a liver
biopsy - extent of histologic
involvement and response
to therapeutic protocols.
• Pathognomonic ground glass
hepatocyte inclusions (arrows)
distributed singly in a haphazard
fashion with no zoning preference.
30. COMPLICATIONS:
• Acute liver failure with coagulopathy, encephalopathy and cerebral
edema ( more in superinfection with HDV)
• Chronic hepatits may lead to cirrhosis and end stage liver disease
• Hepatocellular carcinoma
• Membrano – glomerular nephritis – deposition of complement and
HBeAg in the glomerulus
31. Age at infection
Acquire infection
perinatally:
Poor prognosis
30 % children, 5 %
neonates full recovery
Adults or older
children:
Good prognosis
95% full recovery
Older age:
Poor prognosis
32. Treatment
• Acute HBV – largely supportive, close monitoring for ALF
• Chronic HBV - Treatment indicated for those with immune active form:
1. Interferon alpha 2 b – immune modulatory agent, given s.c for 24 weeks
2. Lamivudine – oral nucleoside analogue that inhibits viral enzyme reverse
transcriptase. Used for more than 6 months
3. Other agents –Adefovir, tenofovir, entecavir.
4. Immune tolerant patients – those with normal ALT, AST, HbeAg positive
with positive viral load - monitor
33. PREVENTION:
• Screening of pregnant women
• Use of HBIG and HBV vaccine infants
• Mothers with HBV DNA load > 200,000 IU/ml – lamivudine or tenofovir
during 3rd trimester should be given.
• HBV is not spread by sharing utensils, breastfeeding, hugging
• Vaccine – Recombinant vaccine 0.5 ml given IM on anterolateral thigh
at birth, then 6 weeks, 6 months
• Infants born to HBsAg positive mothers – 0.5 ml HBIG within 12 hours
of birth along with 1st dose of HBV vaccine
34. • If mother’s status is not known, vaccine should be administered
regardless of birth weight within 12 hours of birth
-Infants < 2000g , HBIG and HBV should be given
-Mother’s HBsAg status should be identified and if she is positive
and the infant is > 2000g, HBIG should be given no later than 1 week
• Post vaccination testing for HbsAg – 9-18 months.
-If positive for anti HBs , then the child is immune to HBV
-If result is positive for HBs Ag only – paediatric gastroenterologist
-If negative for both – second complete HBV vaccine series
• Administration of 4 doses of vaccine is permissible when combination
vaccines are used after birth dose – does not increase vaccine response
35. • Exposure following intimate or identifiable blood exposure :
HBIG + HBV at exposure, then HBV at 1, 6 months
0-19 years – Recombivax vaccine 5 microgram
>19 years -10 microgram
• Household contancts – HBV vaccine at exposure, 1,6 months. Same dose as
above
• Immunocompromised – 40 microgram Recombivax at exposure, 1 , 6
months along with HBIG at exposure
36. Hepatitis C
• RNA, Flaviviridae
• 6 major phenotypes
• HCV is uncommon in the pediatric population
• Seroprevalence is 0.2 % in < 11 yrs and 0.4 % in ≥ 11 yrs
• Mode of transmission – Illegal drug abuse, sexual transmission. Blood
transfusion before 1992, occupational exposure
• Vertical transmission in children – main – 20 %
• Incubation period= 7-9 weeks.
37. CLINICAL FEATURES:
Acute HCV:
• Mild, insidious onset
• Nausea
• Vomitting
• Pain abdomen
• Icterus
• Dark urine
Chronic HCV :
Most likely to progress to chronic infection
38.
39. DIAGNOSIS
• Detection of antibodies to HCV antigen by EIA ( enzyme immune assay)
• Detection of Viral RNA by PCR. Usually detectable within 1-2 weeks of
exposure.
• Anti HCV is not a protective antibody and therefore does not confer
immunity
• Acute infection - The peak serum ALT level is less than 2000 IU/mL in most
patients with acute HCV infection, and 50% have a peak serum ALT level
of less than 800 IU/mL. Overall, this peak is generally less than that seen
in hepatitis A or B infections.
• Liver biopsy – assess presence and extent of hepatic fibrosis
40. Treatment
• Children has a higher spontaneous clearance rate than adults ( 45% till 19
yrs).
• Peginterferon has been approved by FDA for those > 3 yrs
• Treatment considered for those with evidence of advanced fibrosis or
injury on liver biopsy
• Current recommendation – 48 weeks of peginterferon and ribavirin
• Those with normal biochemical profile and mild histological change – no
specific treatment
• Screen yearly with liver ultrasound and alpha fetoprotein for HCC
• No vaccine yet available
41. Hepatitis D
• RNA virus
• Defective – only can cause infection along with HBV as it is incapable of
making its own coat proteins
• Co-infection or superinfection, uncommon in children
CLINICAL MANIFESTATIONS –
• Symptoms similar to infection with other hepatitis viruses, but more
severe.
• In co infection, acute hepatitis is much more severe than for HBV alone
42. • In super infection, acute illness is rare, but chronic hepatitis is common.
Risk of acute liver failure is highest
DIAGNOSIS
• HDV – not yet isolated
• IgM antibody to HDV – 2-4 weeks after co infection, 10 weeks after super
infection
COMPLICATIONS
• HDV to be considered in all cases of acute liver failure
43. Hepatitis E
• RNA virus
• Epidemic form of what was formerly called as non A non B hepatitis
• Transmission – faecal-oral route
CLINICAL FEATURES:
• Similar to that of HAV but more severe. Chronic illness does not occur
• Major pathogen in pregnant women – acute liver failure with higher
fatality incidence
44. DIAGNOSIS:
• HEV-RNA can be detected in stool from 1 week prior to the onset of
symptoms and for more than 2 weeks after the onset.
• Detection of IgM antibody 1 week after illness
45. Treatment
• No specific HDV or HEV targeted treatments yet
• Control and treat HBV infection without which HDV cannot induce
hepatitis.
• Ongoing trials – Interferons
• No vaccine available for both
Once chronic infection is identified, close follow up and referral to
paediatric gastroenterologist is recommended.
46.
47. Autoimmune hepatitis
• Chronic hepatic inflammatory process
• It is manifested by – Elevated AST/ALT, Liver associated serum auto antibodies,
hyper gammaglobulinemia – Antinuclear antibody(ANA), antibody against
liver kidney microsome( Anti LKM-1) and smooth muscle antibodies (SMA)
• It is a Clinical constellation s/o immune mediated process, responsive to
immunosuppresive therapy.
• Trigger factors – infection, drugs, toxins in a genetically susceptible host
• 25-30 % children – mimic viral hepatitis. Patients can be asymptomatic or
have fatigue, malaise, behavioural changes, anorexia.
48. • Mild to moderate jaundice with hepatomegaly and in some case,
splenomegaly and ascites
• Serum bilirubin may be normal in mild cases.
• Serum aminotransferases range between 100-300 IU/l.
• Hypoalbuminemia and Hypergammaglobulinemia are common.
• Prothrombin Time is prolonged mostly due to Vit K deficiency and
also as a reflection of impaired hepatocellular function.
49. TREATMENT:
• Prednisolone with or without azathioprine – improves clinical, biological and
histological features.
• Prednisolone 1-2 mg/kg/day till aminotransferases return to less than twice the
upper limit of normal, then decrease the dose.
• Azathioprine 1.5-2 mg/kg/day – with frequent monitoring for bone marrow
suppression
• Cyclosporine, Tacrolimus and Mycophenolate Mofetil have been used in
refractory cases.
• Steroid resistant hepatitis in some cases is seen and these may progress to
cirrhosis or end stage liver disease – liver transplantation.
51. Drug induced hepatitis
Paracetamol
• In Single large dose or in repeated doses it causes acute hepatitis.
• The pathways for paracetamol metabolism get saturated at high
doses, which leads to production of a toxic metabolite, NAPQI, which
leads to cell death.
• A single dose of 120-150mg/kg could be hepatotoxic.
• Rectal administration of acetaminophen can also cause hepatotoxixity.
52. • Nausea, persistent vomiting for 24 hours followed by tender
hepatomegaly, jaundice and coagulopathy is seen.
• N-Acetyl Cystiene is the most effective antidote.
• Mortality rate in well managed cases is <1%.
• The hypatic dysfunction resolves in 2-3 weeks.
53. Valproic Acid
• More common in young children.
• Children below 3 years, on multiple anticonvulsants, and
presence of associated medical problems like MR are more
likely to develop hepatotoxicity with valproate.
• Recent studies show that very early Carnitine supplementation
has a beneficial role
54. Phenytoin
• Phenytoin induced hepatitis is ‘drug hypersensitivity reaction’
• Fever, rash, Steven Johnson syndrome and lymphadenopathy
may be the presenting features.
• Elevation of ALT/AST with jaundice is seen.
• Concurrent administration of phenobarbitone aggravates the
hepatic injury.
55. • IV Methyl Prednisolone 2mg/kg/day has been effective in
some patients.
• IVIG has been benefitial in those wiith SJS.
56. Anti Tubercular drugs
• The risk of hepatic dysfunction is more in children who are
receiving Isoniazid along with Rifampicin and Pyrezinamide.
• INH hepatotoxicity is mainly due to a toxic metabolite,
Acetylisoniazid.
57. • Treatment is mainly supportive
• Withdraw the offending agent
• Corticosteroids may have a role in immune mediated disease
• Prognosis – Injury is usually completely reversible when the agent is
withdrawn
58. To summarise
• Aggressive perinatal, childhood and adolescent immunisation
strategies can reduce the disease burden due to viral hepatitis.
• Early detection and treatment of viral hepatitis can improve
outcome.
• Educating the community regarding the disease and its prevention
should be implemented.
• Drugs causing hepatitis should be used with caution.
Wilson Disease= genetic disorder of copper metabolism. Copper accumulates in the body causing vomiting, weakness ,icterus, liver failure, psychological changes
Tyrosinaemia =error of metabolism, in which the body cannot effectively break down the amino acid tyrosine. Symptoms include liver and kidney disturbances and intellectual disability. Untreated, tyrosinemia can be fatal.
Reyes syndrome= secondary to aspirin use in children. Consists of liver damage and rapidly progressive encephalopathy.
Lobar architecture intact
Balloon degeneration and necrosis of parenchyma
Bile duct proliferation
Kupfer cell Hyperplasia
Giant cell response in neonates.....Fatty changes in HCV
transmission
Candidates for post exposure prophylaxis include household and sexual contacts of infected patients, contacts in childcare centers during outbreaks
Vaccine – 720 ELISA units and aluminium hydroxide is the adjuvant. Efficacy of 95-100%
Catch up – if serum negative fro HAV
> 13 year – give adult vaccine 1440 units
It is an exceedingly resistant virus, capable of withstanding extreme temperatures and humidity.
-HBV has a circular double stranded DNA genome, 3200 nucleotide.
The surface of virus includes particles designated as HBsAg, 22nm diameter, 22 nm width
The inner portion of virion contains HBcAg, the nucleocapsid, that encodes viral DNA..and a NON structural HBeAg, derived by proteolytic self cleavage from HBcAg, serving as a marker for active viral replication.
Then there is X gene which encodes proteins that act as transcriptional transactivators that aid viral replication. Evidence strongly suggests that these transactivators may be involved in carcinogenesis.
For acute hepTITISViral antigens combine with class 1 MHC proteins and opsonise the cell for cytotoxic t cells
Gianotti crosti syndrome – Papular acrodermatitis...also due to EBV
Because the symptoms of acute HBV infection and the laboratory indicators of hepatocellular dysfunction are indistinguishable from those of other forms of viral hepatitis,
HBV surface antigen (HBsAg) appears before the onset of symptoms, peaks during overt disease, and then declines to undetectable levels in 3-6 months. Acute HBV infection is characterized by the presence of HBsAg in the serum.
Hepatitis B envelope antigen HBeAg, HBV DNA, and DNA polymerase appear in the serum soon after the appearance of HBsAg, and all signify active viral replication. Measuring HBV DNA with quantitative DNA polymerase chain reaction (PCR) is ideal for monitoring disease progression and effect of treatment
Anti-HBc(IgM) becomes detectable in serum shortly before the onset of symptoms, concurrent with the onset of elevation of serum aminotransferases. Over months, the IgM antibody is replaced by (IgG) anti-HBc. Detection of IgM HBcAb is diagnostic of acute HBV infection
During recovery from acute phase, HBsAg level falls before the symtpoms wane, IgM HBcAg may be the only marker of infection
IgG anti-HBc does not rise until the acute disease is over and is usually not detectable for a few weeks to several months after the disappearance of HBsAg. Anti-HBs may persist for life, conferring protection
Hepatitis B surface antibody (HBsAb), but not hepatitis B core antibody (HBcAb), is detected in persons who have received the hepatitis B vaccine
The carrier state is defined by the presence of HBsAg in the serum for 6 months or longer after its initial detection.
During convalescence, HBsAg and HBeAg are cleared, and IgG antibodies to HBsAg, HBcAg, and HBeAg develop.
Seroprevalence – level of pathogen in a population
HCV – most likely virus to cause chronic infection
< 15 % clear the virus
Rest develop chronic hepatitis
Chronic HCV infection is usually clinically silent until a compliation develops
Serum aminotransferases fluctuates and are sometimes normal but histologic inflammation is universal
20 % ultiamytely cirrhosis
Extra hepatic manifestations – mainly adults – curaneous vasculitis, membranoproliferative GN, peripheral vascultitis
Biopsy – recommended only before starting any treatment and to rule out other causes of overt liver disese
Histology - In patients with chronic HCV infection, inflammatory cells accumulate in the portal tracts. They may also have foci of inflammation accompanied by necrosis in the parenchyma.
SOFOSBUVIR and SIMEPREVIR are the newer drugs for HCV
Co infection – HDV along with HBV..occurs simaltaneously..MORE SEVERE
Super infection – HDV in a person already infected with HBV, leads to chronic HDV infection, worsens the preexisting HBV infection
- characterised by Necroinflammation and relentless deposition of collagen into development of cirrhosis and HCC
It refers to a hepatocytic specific response
Sclerosing cholangitis- predominated by intra and extra hepatic bile duct injury. T/t by UrsaDeoxyCholic Acid (UDCA)
Overlap is common in children
Type 1- ANA, SMA, ANTIACTIN, p-ANCA
Type 2- LKM-1, LKM-3 Liver cytosol-1
ANA - Antinuclear antibody
Anti LKM-1 -Antibody against liver kidney microsome
SMA - smooth muscle antibodies
PANCA – perinuclear antineutrophilic cytoplasm antibody
EMA antibody to endomysium
SLA- SOlublE Liver Antigen
Sulfation and glucourinidation are the pathways for paracetamol metabolism.
At high dose, minor pathway of cytochrome p450 is used for its metabolism
NAPQI- N-Acetyl p-L Benzoquinone imine ----alters calcium metabolism
Rumack Mathew Normogram ( X-axis = Hours Post ingestion ; Y-axis = Acitaminophen concenteration in plasma)
N acetyl cystiene = 140 mg/kg within 10 hours of ingestion, followed by 70 mg/kg every 4 hours for 72 hours.
It should be diluted to 5% concenteration and given via NG tube as IV infusion is not superior to oral route.
Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) it forms a spectrum of disease, with SJS being less severe.
The most common cause is certain medications such as lamotrigine, carbamazepine, allopurinol, sulfonamide antibiotics, and nevirapine
A leading cause appears to be the use of antibiotics, particularly sulfa drugs.