1. 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

2. 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

3. 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.

4. 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,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

5. EXTRAHEPATIC ASSOCIATIONS OF HEPATITIS C
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

6. 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 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, 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

7. 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 !

8. MANAGEMENT Progression usually seen in those who drink excess 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

9. 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 mg/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.

10. SIDE-EFFECTS OF HC TREATMENT
Influenza-like symptoms
Nausea
Weight loss
Autoimmune reactions
Depression
Lethargy
Hypersensitivity
Myelosuppression
Hypo/hyperthyroidism
Hair loss

11. 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

12. 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.

13. 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.

14. 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.

15. INVESTIGATIONS HBV serology:HBsAg indicates ongoing infection;
HBe Ag confirms high viral replication ,may be negative in HBe-ve chronic HB, anti-HBc IgM(acute infection); anti-HBc 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

16. MANAGEMENT
Usual goal of treatment is to supress HBV replication,induce HBeAg seroconversion(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 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.

17. 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.