This document provides an overview of viral hepatitis types A through E. It discusses the history and key discoveries related to identifying the different hepatitis viruses. The common features of acute viral hepatitis are described. Differential features of hepatitis A, B, C, D and E are outlined including transmission routes, incubation periods and likelihood of chronic infection. Evaluation, treatment recommendations and prevention strategies are summarized for each type of viral hepatitis.
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
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
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.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
2. A Long History of Human Misery
500 B.C. written accounts of jaundice in Babylonia
400 B.C. Hippocrates describes “epidemic jaundice”
1883 jaundice noted to occur after inoculation of human sera
1941 post-vaccination jaundice occurs in >28,000 U.S. soldiers
1947 infectious hepatitis designated Hepatitis A; serum hepatitis
designated Hepatitis B
1963 Hepatitis B Surface Antigen identified
1973 Hepatitis A identified by electron microscopy
Mid-1970’s Hepatitis D recognized
Mid-1970’s Non-A, Non-B hepatitis described
Mid-1980’s epidemics of “non-hepatitis A” enteric hepatitis
1989 Hepatitis C cloned and serological tests developed
1990 Hepatitis E cloned and characterized
3. Viral Hepatitis
Common Features
Early Prodromal Phase
serum sickness like syndrome
occurs 2-3 weeks before jaundice
arthalgias, arthritis, rash, angioneurotic edema, fever
Preicteric Phase
GI symptoms
nausea, vomiting, abdominal pain, anorexia, changes
in taste and smell, weight loss
generalized malaise, myalgias, headache, fever
Icteric Phase
fever declines
constitutional symptoms improve
Convalescent phase
full recovery usually within 6 months
4. Viral Hepatitis
Differential Features
Features Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E
Genome type Ss RNA Ds DNA Ss RNA Ss RNA Ss RNA
Genome size 7.5 kB 3.2 kB 9.4 kB 1.7 kB 7.5 kB
Incubation
period, days
(mean)
15-49 (30) 28-160
(70-80)
15-160
(50)
21-140
(35)
15-65 (42)
Fecal-oral
transmission
yes no no no yes
Parenteral
transmission
rare yes yes yes no
Sexual
transmission
no yes, common yes,
uncommon
yes,
uncommon
no
Fulminant
hepatitis
<1% <1% rare 2-7.5% ~1%, 30% in
pregnancy
Chronic
hepatitis
no 10% 85% 90% with
superinfection
no
5. Acute Hepatitis
Evaluation and Recommendations
Access for viral hepatitis A, B, C,
– Hep A IgM, Hep B Surface Ag, Core IgM, Hep C Ab (or PCR)
– Consider alcohol and drug toxicity, autoimmune hepatitis, ischemia
– Consider biliary tract disease: CBD stone, PSC
– Consider other viruses: CMV, EBV, HSV, etc.
Hospitalization for excessive anorexia, nausea, vomiting
– Rising total bilirubin >15
– Rising pro time > 15
– Rapidly falling transaminases while bilirubin is rising
– Liver failure: hepatic encephalopathy, ascites
Bed rest prn
Consider high protein high calorie diet
Minimize medications: phenothiazines, ? vitamin K are OK; stop OCP’s,
Etoh, acetaminophen, etc.
Office visit and LFT’s twice a week while LFT’s rising, and every 1-2 weeks
while improving
Immunoprophylaxis for contacts of HAV, HBV
6. Hepatitis A
Picornaviridae
Transmitted by fecal oral route, contaminated food, water, shellfish
Most infections are sub clinical
– Incidence peaks in fall and winter
– 80% infected children are anicteric
– 10-50% infected college students are anicteric
– 30-50% U.S. adults are HAV IgG+, but only 3-5% recall prior jaundice
– High attack rate: 70-90% exposed become infected
>60,000 clinical cases per year in U.S.
– Incubation 15-49 days (mean 30 days)
– HAV Ag appears in liver at 1-2 weeks
– HAV then appears in bile and stool
– Fecal infectivity begins 2-3 weeks before jaundice, lasts 4-5 weeks,
ends 2 weeks after peak transaminitis
Chronic infection never occurs
– 60% have normal LFT’s at 2 months; 100% normal at 6 months
7. Hepatitis A
Atypical Features
Death is uncommon
– Overall mortality rate is 0.14%
– If age > 40, mortality rate is 1.1%
Prolonged cholestasis >3 months
– Severe pruritis, fatigue, weight loss, diarrhea
– May improve with steroids
Relapsing hepatitis
– Occurs in 6-12% of cases, 4-15 weeks after recovery
Extrahepatic manifestations
– Rash (14%), arthralgias (11%),
– Immune complex diseases: leukocytoclastic vasculitis,
glomerulonephritis, arthritis, cryroglobulinemia
– Extremely rare: myocarditis, transverse myelitis, optic neuritis,
polyneuritis, aplastic anemia
8. Hepatitis A
Prevention
General prevention
– Water chlorination
– Boil water 20 minutes
– Wash hands
– Avoid contaminated food
HAV Immunoglobulin
– Can prevent 85-95% infections if given within two weeks of exposure
– Household and sexual contacts
– Day care contacts
– Prison contacts
– Common source outbreaks
HAV Vaccine
– 90-98% successful with one injection, 100% with two injections
– Protection begins after 1-2 weeks, may last 20 years
– Give to all of the above
– Travelers to endemic areas
– Homosexuals, IV drug abusers
– Persons with HCV and HBV
– Military
9. Hepatitis B
Hepadnaviridae
Transmission route is variable
– HBV is found in blood and all body fluids except stool
– “Western” societies: percutaneous, hetero/homosexual contact is most
common
– “Non-western” societies: perinatal transmission is most common
Epidemiology
– Worldwide
2 billion people have markers of infection
400 million have chronic infection (5%)
– U.S.
1.25 million chronic infections (50% Asian)
200 thousand acute infections per year
250 deaths/year from fulminant HBV
4000 deaths/year from chronic HBV
800 deaths/year from HBV related hepatomas
10. Hepatitis B
90% cases are self-limited with spontaneous resolution
– >50% are anicteric
– 10% become chronic
– <1% are fulminant (10% if “E Ag mutant”)
– 3-5% in U.S. have HBV markers
Surface Ag appears 1-12 weeks after exposure
– Clinical hepatitis and Core IgM occur 4 weeks after Surface antigen
– E Ag indicates period of infectivity
– S Ab indicates resolving infection
– Rare “window period” occurs when Surface Ag disappears and before Surface
Ab appears; Core Ab will be positive
Extrahepatic manifestations
– Arthralgias and rash (25%)
– Angioneurotic edema, polyarteritis nodosa, mononeuritis, membranoproliferative
GN, arthritis, Raynaud’s phenomena, Type II mixed essential cryroglobulinemia,
Guillan Barre Syndrome, pancreatitis, pericarditis
11. Chronic Hepatitis B
Persistent Surface Ag, E Ag, DNA > 6 months
Risk of chronicity is dependent on host age and immune status
– 90% perinatal infection
– 30% childhood infection age < 6 years
– 5% adult acute infection
– 30% with HIV co-infection
Prognosis is dependent on HBV stage
– Immune tolerant: Surface Ag +, E Ag +, DNA +, ALT normal
Prognosis good, hepatoma risk low
– Integrated state: Surface Ag +, E Ag -, DNA –, ALT usually normal
Prognosis good, hepatoma risk low
– Chronic active hepatitis: Surface Ag +, E Ag +, DNA +, ALT >2x normal
20% develop cirrhosis in 5 years
10% per year lose E Ag
1% per year lose S Ag
Increased risk of hepatoma 400 x
12. Hepatitis B
Prevention
Modify risk factors
– Eliminate high risk behavior; use condoms
– Incidence of acute HBV has decreased by 40% in U.S. over 15 years
Screen pregnant mothers for HBV Surface Ag
– HBIG + HBV vaccination at birth prevents 80-90% perinatal transmission
Hepatitis B Immune Globulin
– Perinatal exposure
– Needle stick exposure
– Sexual, mucosal or percutaneous exposures
HBV Vaccination
– Perinatal exposure
– Persons with sexual, mucosal, percutaneous exposures
– Persons with HCV or IV drug abuse
– Homosexuals
– Health care workers
– Hemodialysis
– Universal vaccination for children
13. Hepatitis B
Treatment
Who to treat?
– Chronic active disease > 6 months
– Surface Ag +, DNA +, E Ag + or – (if E Ag mutant)
– ALT > 100, and/or active hepatitis on biopsy
Goal of treatment
– Stop viral replication, HBV DNA becomes neg
– Convert E Ag pos to neg, E AB becomes pos
– Improvement in histology, prevention of progression
to cirrhosis
– With successful treatment, loss of Surface Ag may
occur in 1-2% per year
14. Hepatitis B Treatment
Alpha-interferon 2b
5 mu sq qd for 16 weeks
40 % will have successful response and lose E Ag, 10% lose Surface Ag
Hepatitis flare is common during treatment
Favorable pretreatment variables
– Low HBV DNA < 200 pg/ml
– High ALT > 100
– Active hepatitis on biopsy
– Shorter duration of infection
– Others: female, lack of immunosuppression, HBV E Ag +, h/o jaundice,
horizontal transmission
Pros
– Short, finite duration of treatment
– Effective, viral response persists in 95%
Cons
– Expensive: $2000 per month
– Numerous side effects
– May cause cirrhosis to decompensate
15. Hepatitis B Treatment
Nucleoside Analogues
Lamivudine
– Inhibits HBV reverse transcription
– Minimal side effects
– YMDD escape mutants occur 15-30% per year
Adefovir
– Inhibits HBV reverse transcription
– Active against lamivudine resistance
– Minimal side effects (proteinuria, increased Cr)
– resistance is rare so far…..1.8-2.5% at 2 years
Famciclovir
– Inhibits DNA polymerase
– Less effective than lamivudine, numerous resistance mutations
– Minimal side effects
Entecavir Active against lamivudine resistance; phase 2 trials
Emtricitabine some cross resistance with lamivudine mutants, phase 2 trials
Clevudine phase 1-2 trials
B-L-Thymodine B-nucleoside, phase 1-2 trials
16. Hepatitis B Treatment
Lamivudine and Adefovir
Lamivudine 100 mg po qd
– After one year of treatment
17% lost HBV E Ag
15-30% per year YMDD resistant mutation
56% have improved histology
– After four years of treatment
47% have lost HBV E Ag
67% have resistant mutation
ALT and DNA levels remain lower even with mutants
– Effective against E Ag mutants, and safe in cirrhosis
– Treatment must continue until loss of E Ag
– Loss of E Ag persists in 70-90% after discontinuation
Cost $ 164 per month
Adefovir 10 mg po qd
– After one year treatment
48% normal ALT
12% HBV E Ag seroconversion
53% improved inflammation, 34% improved fibrosis scores
Resistance in 1.8-2.5% at 2 years
Effective in Lamivudine resistance, E Ag mutants, and safe in cirrhosis
Cost $ 566 per month
17. Liver Transplant in Hepatitis B
10% liver transplants are for HBV
Prior to effective immunoprophylaxis 80% of transplants
became reinfected with very poor survival
Most centers stopped transplanting for active HBV
Reinfection rate can now be reduced effectively:
– HBIG for 6-12 months
20% reinfected
– Addition of Lamivudine to HBIG
5-10% reinfected
2 year survival with transplant is now 70-80%
18. Hepatitis C
Flaviviridae
Transmission is primarily percutaneous; sexual and perinatal infection can occur
– Transfusional HCV risk is now low: 1:1,935,000
– 50-90% of IV drug abusers have HCV
– 10% needle stick injuries transmit HCV
– 4% sexual partners have HCV; Risk of sexual transmission <0.5%/year
– Perinatal transmission 1-10%
100 million chronic carriers world wide (>3%)
4 million with chronic HCV in U.S. (1.5-2%)
– 30 thousand new HCV cases per year in U.S. (incidence decreasing)
– 10 thousand deaths/year from HCV (incidence increasing)
Acute hepatitis is rare
– Fulminant hepatitis is extremely rare
– 15% can spontaneously resolve infection
– 85% develop chronic infection
– HCV RNA becomes + 2 weeks after exposure
– “incubation” period is 6-7 weeks
– HCV Ab becomes + by 12 weeks in most
19. Hepatitis C
Prevalence
Risk Factor Prevalence (%)
Clotting factors < 1987 87
IVDA 79
HIV + 25
Increased ALT 15
Hemodialysis 10
> 50 sexual partners 9
h/o STD 6
Homosexual 4
General population 1.8
Health care workers 1.0
Healthy blood donors 0.16
21. HCV Natural History
30% with HCV have normal ALT
– 20% have normal or minimal histology
– 80% have abnormal histology
– 15% have advanced histology
– Disease progression is slower
Mean progression in U.S.
– Chronic hepatitis 13.7 years
– Cirrhosis 20.6 years
– Hepatoma 28.3 years
– 20% have cirrhosis at 20 years
Other studies
– Post-transfusion HCV in Italy: 32% have cirrhosis at 7.5 years
– HCV infected sera given to Irish women: 2% have cirrhosis at 18 years
– HCV infected RH Ig given to German women: 0% have cirrhosis at 15 years
Complications of HCV Cirrhosis
– Decompensation 5% per year
– Hepatoma 1-4% per year
22. Hepatitis C
Factors Associated with Disease Progression
Age > 40
Male
Alcohol > 50 gm/d
Immunosuppression: HIV, transplant, etc.
Infection by blood transfusion
Co-infection with HBV
Genotype 1
23. Hepatitis C
Goals of Therapy
Biochemical response normal ALT
Virological response loss of HCV RNA
End of treatment response loss of HCV RNA at end of treatment
Early Virological response (EVR)
– HCV RNA neg or 2 log reduction at 12 weeks
Overall 67 % with EVR achieve SVR
80% who are HCV RNA neg achieve SVR
40% who are RNA +, but have 2 log reduction achieve SVR
– Patients w/o EVR
Only 1.6% achieve SVR
Sustained virological response (SVR)
– Undetectable HCV RNA 6 months after treatment ends
– 95% have persistent SVR over 10 years
– 80% have reduction in fibrosis
25. Hepatitis C
Treatment Side Effects
Ribaviron
– Hemolytic anemia
10% will drop Hgb < 10; most will drop Hgb by 3 gm/dl
Relatively contraindicated with CAD, advanced age, renal insufficiency
Improves with dose reduction or erythropoietin
– Headache
– Teratogenic
Women must be infertile or on OCP
Men cannot conceive on therapy and 6 months off therapy
Interferon
– Anemia, neutropenia, thrombocytopenia
– Flu-like side effects
– Depression
– Insomnia
– Fatigue
– Headaches
– Memory and cognitive dysfunction
– Alopecia
– Pruritis, rashes, dry skin
– Hypo/hyper thyroidism
– Autoimmune disease (SLE, RA, thyroid)
26. Hepatitis C
Treatment Dilemmas
Age <18 or >60
Decompensated cirrhosis
Renal insufficiency
Normal ALT with minimal histological changes
Co-infection with HIV
Membranoproliferative GN and
Cryroglobulinemia
Acute HCV
27. Delta Hepatitis
Defective RNA virus, requires presence of HBV Surface Ag
7500 new cases/year in U.S.
– More common in southern, eastern Europe, Middle East, and South America
Transmission is similar to HBV
Diagnosis: HDV Ag, HDV RNA, HDV IgG and IgM
Acute Hepatitis
– Co-infection with HBV
Fulminant hepatitis more common (34%)
Progression to chronic infection is uncommon
– Super-infection of HBV
Acute exacerbation of ongoing hepatitis
Chronic liver disease occurs in 90%
Chronic Hepatitis B + D
– More progressive than HBV alone
– 15% have rapid progression to cirrhosis in 1 year
Treatment
– a-interferon 2b 3-9 mu sq tiw, Rx > 12 months
– 21-50% lose HDV RNA and have improved histology
– Relapse occurs in almost all patients stopping treatment
– Can stop treatment if HBV Surface Ag disappears (rare)
28. Hepatitis E
Related to Rubella virus
Endemic in equatorial regions of world
– India, Africa, Central America, Asia
– May account for 50% hepatitis cases in endemic areas
– Antibodies found in pigs, other mammals
Fecal oral transmission
– Contaminated water
– Household transmission rates are low 1-2%
Rare in U.S. except travelers to endemic regions
– 1-2% U.S. blood donors have HEV Ab (?cross reactivity)
Incubation period is 15-60 days (mean 40)
HEV IgM + at 27-39 days
1-4% overall mortality; 20-30% mortality if pregnant
29. Other Viruses Causing Hepatitis
Hepatitis G and GB related to HCV
TT Virus post-transfusional hepatitis in Japan
Sanban, Yonban, TLMV related to TT virus, post-transfusional hepatitis in Japan
Giant Cell Hepatitis paramyxovirus; 7 small series ~100 patents
Herpes Viruses
– HSV 1 and 2 90% are immunosupressed or in last trimester of pregnancy
– HSV 6 and 7 case reports
– Cytomegalovirus after transfusion or transplant
– Epstein Barr Virus 11% become jaundiced
Rift Valley Fever Virus
Yellow Fever Virus
Lassa Virus
Marburg Virus
Ebola Virus
Adenoviures
Enteorviruses
Coxsackie Viruses
SARS 60% have hepatitis, virus found in liver by PCR