CLASSIFICATION OF ESOPHAGITIS SAVARYMILLER Grade 1 unconfluent eritematous

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

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 150 milion 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, 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 �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 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, 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 180 microgr. /weekly)+RIBAVIRIN 1000 -1200 mg/day(>75 kg) , 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 �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 CYP 3 A 4/5 �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 HBe. Ag+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: HBs. Ag indicates ongoing infection; �HBe Ag confirms high viral replication , may be negative in HBe-ve chronic HB, anti-HBc Ig. M(acute infection); anti. HBc Ig. G-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 HBe. Ag seroconversion(clearance of HBe. Ag ; appearance of anti. HBe) and reduce liver injury. �Ultimate goal is to clear HBs. Ag 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 HBe. Ag seroconversion in 30% at 1 year course of treatment. �Lamivudine 100 mg/day in naive patients, induces HBe. Ag 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 � 5 mg/day in naive patients, unlimited administration � 10 mg/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 -20 mcg HBs. Ag given at 0, 1, 6 months.