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CLASSIFICATION 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.
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CLASSIFICATION OF ESOPHAGITIS SAVARY-MILLER Grade 1: unconfluenteritematouserosions,one or more Grade 2: multiple confluent, uncircumferenceal erosions Grade 3: confluent,circumferenceal erosions of esophagus Grade 4: complications:ulcer,stenosis,Barrettmetaplasia
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 INFECTIONEPIDEMIOLOGY • 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 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,malesex,alcoholexcess,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 • Cryoglobulinaemia in 35-55% of chronic patients • -most patients are asymptomatic • - pruritus and arthralgia in18% • -neuropathy and membranous glomerulonephritis in 2% • Lichen planus • Autoimune hepatitis • Thyroiditis • Polymyositis • Polyarteritisnodosum • Porphyriacutaneatarda • Sjogren’s syndrome
INVESTIGATIONS • Anti-HCV antibody.ELISA test +(RIBA)confirms 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 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 alcohol! • Vaccinate against hepatitis A and B ,as co-infection may lead to disease progression,orfulminant 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’’forassesssing 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 • 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 (HBeAg+,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,weightloss,in compensated disease.
INVESTIGATIONS • HBV serology:HBsAg indicates ongoing infection; • HBeAg confirms high viral replication ,may be negative in HBe-vechronic HB, anti-HBcIgM(acute infection); anti-HBcIgG-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,induceHBeAgseroconversion(clearance of HBeAg ;appearance of anti-HBe) 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 HBeAgseroconversion in 30% at 1 year course of treatment. • Lamivudine 100 mg/day in naive patients,inducesHBeAgseroconversion 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.