Download clasification of esophagitis

SAVARY-MILLER
Grade 1: unconfluent eritematous erosions,one
or more
Grade 2: multiple confluent, uncircumferenceal
erosions
Grade 3: confluent,circumferenceal erosions of
esophagus
Grade 4: complications:ulcer,stenosis,Barrett
metaplasia
LOS ANGELES CLASSIFICATION OF
ESOPHAGITIS
A. One or more erosions, lenght less than 5 mm
B. At least one erosion longer than 5 mm, but
unconfluent
C. One or more erosions extended between 3/4
mucosa folds, uncircumferenceal
D . Circumferenceal erosions
HEPATITIS C INFECTION
EPIDEMIOLOGY
 More than 150milion people worldwide are infected with hepatitis C
virus(HCV),an RNA virus of the flavivirus family.
 Transmision mainly through injection-drug use(>60% of cases in UK) or
blood-product transfusion(eliminated due to screening of donated blood).
 Skin piercing procedures ,transmission in monogamous heterosexual
relationships <6%.
 Mother to infant transmission occurs in 5% of cases,increased in 18% if mother
co-infected with HIV.
 Breastfeeding transmission is not reported .
 6 main HCV genotypes 1,2,3 in Europe,USA, 4 in Egypt,Middle East
 subtypes a-c.
CLINICAL FEATURES
 Less than 15% of patients develop acute icteric hepatitis
 Chronic infection in 50-85% of cases,as defined by persistence of
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HCV RNA in the serum,usually clinically silent ,with liver
damage occuring over many years.
<20% will develop severe fibrosis/cirrhosis after 20 years of
infection in the absence of cofactors(alcohol).
Risk factors for disease progression:high circulating virus
level,long duration of disease,older age at acquisition,male
sex,alcohol excess,co-infection with HIV/hepatitis B.
4% of patients per year with HCV cirrhosis develop HCC.
Non-specific complaints:fatigue,headache ,poor concentration
EXTRAHEPATIC ASSOCIATIONS OF
HEPATITIS C
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Cryoglobulinaemia in 35-55% of chronic patients
-most patients are asymptomatic
- pruritus and arthralgia in 18%
-neuropathy and membranous glomerulonephritis in 2%
Lichen planus
Autoimune hepatitis
Thyroiditis
Polymyositis
Polyarteritis nodosum
Porphyria cutanea tarda
Sjogren’s syndrome
INVESTIGATIONS
 Anti-HCV antibody.ELISA test +(RIBA)confirms
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exposure to HCV,but no persistence of infection.
HCV RNA by PCR confirms ongoing infection,with cut-off
variable,usually 100-1000 viral copies/ml.
HCV genotype is essential to be determined in patients
considered for treatment,as influences treatment response.
Liver function tests.ALT/AST elevated,1.5-2.5 UL,but
fluctuations are common with poor correlation between
the level of viraemia or severity of histological findings.
Liver biopsy-invasive method of assessing the degree of
inflammation and fibrosis;should be considered in all HCV
RNA+patients,if AST/ALT abnormal.
FIBROSCAN,FIBROMAX-non-invasive methods
INVESTIGATIONS
 Additional blood tests.ASM antibodies-autoimune
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hepatitis association which can be exacerbated by
antiviral therapy.
Thyroid function tests
HBs Ag for chronic hepatitis B,more progressive
histological disease in those with HCV.
HIV testing
Abdominal US to identify features of cirrhosis and
portal hypertension;repeat 6 monthly+ AFP in
patients with proven cirrhosis-risk of HCC !
MANAGEMENT
 Progression usually seen in those who drink excess
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alcohol!
Vaccinate against hepatitis A and B ,as co-infection
may lead to disease progression,or fulminant liver
failure.
Patients should be advised not to donate blood ,the
risk of shared needles by drug users
Avoid sharing razors and toothbrushes
Sexual transmission,condoms should be used during
casual sexual contacts
ANTIVIRAL TREATMENT
 Indicated in a patient with positive anti-HCV antibody,
 + HCV-RNA,raised liver enzymes(ALT,AST) and moderate to severe hepatitis
on liver biopsy, FIBROSCAN/FIBROMAX (non-invasive explorations).
 Long-acting pegylated-alpha Interferon(PEG IFN
180microgr./weekly)+RIBAVIRIN 1000-1200mg/day(>75kg) ,12 months is the
treatment of choice.
 ‘’Gold standard’’for assesssing treatment response is sustained virological
response(SVR),defined as negative HCV RNA 6 months after completing
treatment.
 Genotype 1 is less responsive,with 45-55% SVR,genotype 2/3 gives SVR of 80%
on 6 months course,even 4 if HCV-RNA is negative at 6 weeks.
 End-stage liver disease due to chronic hepatitis is the commonest indication for
liver transplantation.
 Recurrence of HCV in the grafted liver is almost universal,with cirrhosis
occurring at an accelerated rate in these immunocompromised patients.
SIDE-EFFECTS OF HC TREATMENT
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Influenza-like symptoms
Nausea
Weight loss
Autoimmune reactions
Depression
Lethargy
Hypersensitivity
Myelosuppression
Hypo/hyperthyroidism
Hair loss
PREDICTORS OF LONG-TERM
RESPONSE TO IFN
 Non-viral genotype 1
 Low pre-treatment viraemia
 Negative HCV-RNA after 1 month of treatment
 Younger age
 Non-black racial origin
 Absence of cirrhosis on biopsy
 ALT normalized in first 12 weeks of treatment
 Female
 Low hepatic iron stores
TRIPLE THERAPY IN HCV
 BOCEPREVIR-proteaze inhibitor (PI),enzyme CYP3A4/5
 IFN+RBV+BCV-at relapsers,non-responders,genotype 1;
 3 adm.each 7-9 hours,over 4 weeks of
doubletherapy(,,Lead-in T’’),after meals.
 Side effects: anemia,disgeuzia
 Eritropoetine(EPO),expansive and hard to find !
 TELAPREVIR-PI-3 adm.each 8 hours, greasy meals,with
IFN+RBV ,12 weeks,than only double therapy,36 weeks .
Side effects: Cutaneous reactions (dermatologist
consult),abdominal pain,diarrhea.
HEPATITIS B
 Route of transmission is perinatally(90% infection rate
in infants born to HBeAg+ve mothers)
 Blood inoculation through unclean needles remains
important
 Sexual transmission accounts for 30% of infections in
developed countries
 More than 300 milion people worldwide are infected
with HVB chronic infection , 2% in Western Europe
and USA,20% in areas of Southeast Asia.
CLINICAL FEATURES
 Age at infection strongly determines
chronicity,reflecting host imunity (>90% in neonates,
20-50% 1-5 years , <5% in adults).
 Highest rate of complications in highly replicating
disease (HBe Ag+,precore mutant infection )
 Spontaneous clearance of infection (Hbs Ag-ve occurs
in 1% of chronic infected patients/year).
 Fatigue,weakness,discomfort in the right upper
quadrant,weight loss,in compensated disease.
INVESTIGATIONS
 HBV serology:HBsAg indicates ongoing infection;
 HBe Ag confirms high viral replication ,may be negative in
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HBe-ve chronic HB, anti-HBc IgM(acute infection); antiHBc IgG-previous or ongoing infection
Anti-HBs-resolved infection or vaccinated
HBV DNA by PCR
Liver function tests: ALT/AST
AFP perform 6 monthly with liver ultrasound,especially in
cirrhotics-HCC risk !
Liver biopsy,Fibroscan,Fibromax when treatment is
considered
HIV testing
MANAGEMENT
 Usual goal of treatment is to supress HBV replication,induce
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HBeAg seroconversion(clearance of HBeAg ;appearance of antiHBe) and reduce liver injury.
Ultimate goal is to clear HBsAg and prevent cirrhosis and HCC.
Treatment is indicated for those with replicative disease
(HBe+ve,pre-core infection)and hepatic damage.
PEG IFN alpha 6 months induces HBeAg seroconversion in 30%
at 1 year course of treatment.
Lamivudine 100 mg/day in naive patients,induces HBeAg
seroconversion in 25% after one year of use,56% at 3 years,but
treatment-resistant may develop in >40% after 3 years of use.
LV+PEG IFN ,no additional benefit.
LV use to be drug of choice in patients with decompensated
cirrhosis and prior to liver transplantation ,to control replication.
NUCLEOTIDE ANALOGUES
 ENTECAVIR
 5mg/day in naive patients,unlimited administration
 10mg/day in those who didn’t respond to other treatment
 ADEFOVIR
 TENOFOVIR
 Hepatitis B vaccination:
 passive immunization with HBIG,0.1 ml/kg body weight
after exposure or birth to chronically infected mother and
active immunization,10-20mcg HBsAg given at 0,1,6
months.