HCV: Hepatitis C Virus Information PDF

Lab-3 By Dr: Magdy M. Awny  HEPATITIS INFLAMMATION OF THE LIVER” CAUSED BY: VIRUSES- OTHER HEPATITIS A, CHEMICALS INFECTIONS B, C, D, E alcohol...

Lab-3 By Dr: Magdy M. Awny  HEPATITIS INFLAMMATION OF THE LIVER” CAUSED BY: VIRUSES- OTHER HEPATITIS A, CHEMICALS INFECTIONS B, C, D, E alcohol Acetaminophen 2  Viral HEPATITIS Hep A INFECTIOUS HEPATITIS (HAV) Infected food or drink Not chronic Vaccine available Hep B SERUM HEPATITIS (HBV) Sexually transmitted + blood contact Chronic case in 6% of patients Vaccine available Hep C PREVIOUSLY CALLED NON - A NON –B (HCV) NOW HCV Infected blood(blood borne) Chronic in 5 % of those infected NO VACCINE AVAILABLE Hep D RNA virus – need virus B to infect (HDV) Hep E LIKE A, ORAL/FECAL TRANSMITTED (HEV) 3  What is hepatitis C infection is an inflammation of the liver caused by the hepatitis C virus (HCV). The virus can stay in the body, usually for a lifetime, and eventually can cause chronic, serious liver diseases. It is blood borne disease (blood to blood contact)  What are hepatitis C genotypes? Each type of virus has slightly difference in arrangement of its genetic material (RNA). The specific arrangement of RNA is called Genotype Genotypes 1, Genotype Genotype 5 Genotype 6 2 and 3 4 North America Africa, Africa and China and and Egypt and the Middle the Western the Middle East Southeast Europe East Asia What are importance of hepatitis C genotypes? Predict Determination sustained of appropriate duration of viral treatment response A 36-week course of combination treatment is typically adequate for those (SVR) with genotype 4 How is hepatitis C virus spread Who is at high risk ? users of injectable drugs Children born to chronically infected mothers People who received blood, blood products, or transplanted organs  Other risk factors : Liver disease or abnormal liver function test Body piercing and tattoo Health care workers who had blood exposure to mucous membrane or needle stick injury HIV co-infection Alcohol dependent Hep C is not Spread via: Public toiltes Swimming pools Coughing or sneezing Kissing Sharing food  Symptoms Hepatitis C is less likely than the other hepatitis viruses to cause serious illness at first (only 25% of the people infected actually develop symptoms) But about 85% of those infected develop chronic liver disease. a- At least 20% of those develop liver cirrhosis b-1-5% will get hepato-cellular carcinoma. Early symptoms Later symptoms mild fever and headache dark coffee-colored urine light-colored or gray muscle aches and fatigue stool loss of appetite nausea, abdominal pain vomiting and diarrhea. jaundice  Hepatic Complications portal hypertension, jaundice, ascites (accumulation of fluid in the cirrhosis abdominal cavity), varices (enlarged veins, especially in the stomach and esophagus), hepatic encephalopathy Liver cancer Liver failure A liver that is severely damaged by hepatitis C may be unable to function. Some extrahepatic complications include: hematological disorder, renal and endocrine diseases  Diagnosis 1.Physical Examination  2. Blood tests LFTs ALT/AST/… HCV antibody test (serology test) HCV RNA test It detects the presence Quantitative Hepatitis C of antibodies to the virus in the blood (HCV viral load) virus Screening test for past It detects and measures the genotyping exposure and current amount of viral RNA in the infection blood It guide s the Appears after 3-6 months treatment Appears after 1-2 weeks of infection protocol and duration This test cannot To determine the response distinguish whether the to therapy by comparing patient has an active or a the amount of virus before, previous HCV infection. during, and after treatment  What is Viral Load & why it is important? A blood tests that measure HCV (RNA, or genetic material) in a ml of blood. The presence of viral RNA indicates that the virus is actively replicating (reproducing and infecting new cells). A viral load test is usually first done after a person has tested positive for exposure to HCV based on an antibody test. Viral load test results were previously measured in number of copies/ml, but are now reported in terms of International Units per milliliter (IU/mL).  Viral Load ❑ Is the level of virus in the blood ❑ Measured by polymerase chain reaction (PCR) ❑ Viral load is often reported as low or high. Expressed as copies/mL: Low: < 2 million copies High: > 2 million copies Expressed as International Units (IU/mL): Low: < 800,000 IU/mL High: > 800,000 IU/mL ❑ HCV viral load help doctor to i. Diagnose hepatitis C ii. Predict the chances of a successful hepatitis C treatment iii. See how well treatment for hepatitis C is working.  3. Liver biopsy a small piece of the liver may be removed for microscopic examination -Only way to determine the amount of scarring  Treatment Who should receive antiviral therapy for hepatitis C virus infection? ❑ Treatment is recommended in patients at high risk for cirrhosis unless there are reasons that would make treatment unsafe. ❑ Acc to the National Institutes of Health (NIH) pts at ↑ risk for cirrhosis would include those with HCV infection and: Persistent elevation of ALT ( normal: 9-40 u/l) High levels of HCV RNA Evidence of early fibrosis (scarring) or moderate inflammation and injury of liver cells on liver biopsy ✓ The NIH also recommends treatment for patients who are co-infected with HCV and HIV, because these patients have a more rapid course of liver injury. Treatment of acute hepatitis C Doctors When people recommend bed There are no first acquire rest, preventing specific HCV, the dehydration, a treatments for infection is said healthy diet and the symptoms of to be acute avoidance of acute hepatitis (first 6 months) alcoholic beverages Treatment of chronic hepatitis C 3- The direct- acting antiviral (DAA) 1- PEG agents Liver 2- Ribavirin (1) nonstructural interferon alfa transplant (for (given orally) proteins 3/4A (given S.C( (NS3/4A) protease liver cirrhosis) inhibitors (2) NS5A inhibitors (3) NS5B polymerase inhibitors include the nucleoside analogs and nonnucleoside analogs  Interferon (INF) Direct inhibition of viral Indirect inhibition of viral replication by replication by altering a- induction of 2’5’ oligo- cytokine synthesis ➔↑cytotoxic adenylate synthetase that impair T cell and NK cell response to RNA synthesis virally infected cells. B-reduction in viral protein synthesis and inhibition of viral RNA amplification.  PEGylated interferon ↑ duration of ↓ rate of action →↓ ↑ absorption elimination & frequency of & distribution proteolysis of administration of INF INF to once weekly 2 forms of pegylated INF:- [Instead of 3 times a week for peg interferon α2a [ pegasys®] ……..S.C. of the slandered INF so 180 µg/week →↓suffering of side effects peg interferon α2b [pegintron®]……….Wt After each S.C. administration based dose of 1.5 µg/kg/week  may cause transient bone marrow Flu-like symptoms suppression and depression resulting in leucopenia and anemia Side Erythropoietin can be used to effects of improve the Interferon anemia  Ribavirin it inhibit viral mRNA It is a purine synthesis by The dosage for adult nucleoside analogue inhibition of DNA subjects was weight- (synthetic guanosine dependent RNA based at 1000-1200 nucleoside) which polymerase ,Inosine mg daily converted into monophosphate administered in two Ribavirin tri dehydrogenase & divided doses phosphate Various viral GTP- (orally taken) dependent enzymes  nausea, cough, shortness of breath, rash, itching, insomnia and loss of appetite. anemia due to the destruction of red birth defects and blood cells miscarriage (hemolysis). Anemia improves A pregnancy test with a reduction in the dose of Side -2 months prior to starting the TTT. ribavirin. effects of -Monthly throughout the duration of the treatment. -6 months post-treatment Ribavirin to reduce the risk of fetal harm in case of accidental pregnancy. Direct Acting Antivirals (DAAs) asvir Sbuvir/abuvir Previr Sovaldi (Sofosbuvir) Advantages Mechanism of action 1-Sofosbuvir exhibits a relatively high potency -is a nucleotide prodrug than previously used →intracellular metabolism → drugs pharmacologically active uridine analogue triphosphate. 2-sofosbuvir-based regimens provide a -It serves as a defective higher cure rate, fewer substrate for the NS5B protein side effects, and a 2-4 (viral RNA polymerase), thus acts fold reduced duration as an inhibitor of viral RNA of therapy. synthesis. -The NS5B protein is a RNA- 3-Sofosbuvir allows dependent RNA most pts to be treated polymerase critical for the viral successfully without reproduction cycle. the use of peg-INF  Sovaldi (Sofosbuvir) Recommended Dose Sovaldi Adult Dose for CHC: 400 mg orally once a day Recommended Regimen Genotype/case Treatment regimen Duration Genotype 1 or 4 Sovaldi, pegINF & 12 weeks chronic hepatitis C ribavirin (CHC) Genotype 2 CHC Sovaldi and ribavirin 12 weeks Genotype 3 CHC Sovaldi and ribavirin 24 weeks HCC awaiting liver Sovaldi and ribavirin up to 48 wks or until transplantation time of liver transplantation Side effects of Sovaldi -Are signs of an allergic reaction to Sovaldi: e.g. Hives, difficult breathing; swelling of face, lips, tongue, or throat N.B. Interferon-free regimen of sofosbuvir + ribavirin produced post-treatment Sustained Viral Response (SVR) rate of 100% for previously untreated patients with HCV genotypes 2 or 3.  Sustained Viral Response (SVR) It means that the hepatitis C virus (RNA) remains undetectable in the blood during treatment and 12 weeks or more (24 weeks) after completing treatment SVR12 was the primary endpoint which was defined as HCV RNA less than the lower limit of quantification (LLOQ) of 25 IU per mL at 12 weeks after the end of treatment.  Sovaldi (Sofosbuvir) Sovaldi and pregnancy Category B, no effects on the development of the fetus in rats, no studies for Sofosbuvir in pregnant women. Its combination with ribavirin or peginterferon alfa/ribavirin (Category X) is C.I in women who are pregnant or may become pregnant and men whose female partners are pregnant because of the risks for birth defects and fetal death caused by ribavirin. A pregnancy test 2 months prior to starting combination TTT. Monthly throughout the duration of the treatment. 6 months post-treatment to reduce the risk of fetal harm in case of accidental pregnancy.  Other Direct Acting Antivirals (DAAs) Genotypes DAA All Genotypes Epclusa (400 mg of sofosbuvir and 100 mg of velpatasvir) Genotypes 1 and 4 Sovaldi (sofosbuvir) Viekira XR (dasabuvir, ombitasvir, paritaprevir, and ritonavir) Technivie (ombitasvir, paritaprevir, and ritonavir) Harvoni (ledipasvir/sofosbuvir) Zepatier (elbasvir/grazoprevir) Olysio (simeprevir) Genotypes 2 or 3 Sovaldi (sofosbuvir) Daklinza (daclatasvir) Genotype 6 Harvoni (ledipasvir/sofosbuvir) Recommended HCV Regimens for Persons With Decompensated Cirrhosis Genotype Regimen Duration Daclatasvir plus sofosbuvir plus ribavirin 12 weeks HCV genotype Harvoni (Ledipasvir/sofosbuvir) Or 24 weeks 1 or 4 plus ribavirin (without Sofosbuvir/velpatasvir plus ribavirin) ribavirin Daclatasvir plus sofosbuvir plus HCV genotype ribavirin 12 weeks 2 or 3 Epclusa (Sofosbuvir/velpatasvir) plus ribavirin  Case study A 39 year old man was first found to have abnormal liver biochemical tests when he went to see his family physician for a routine checkup. At the age of 17 he had begun injecting drugs and at age 18 he had an episode of acute hepatitis. Despite this he continued to be an injecting drug user for another 3 years. He had never been a heavy drinker, consuming no more than 3 beers per month. He has been overweight since he was a teenager. His mother is said to have died of liver cancer. The patient was first referred to a hepatology clinic after being tested and found positive for hepatitis C. His liver function tests were normal; serum bilirubin 11μmol/L and serum albumin 48g/L. His liver biochemical tests revealed an aspartate aminotransferase (AST) of 81I U/L (normal: 10-40 U/L) and an alanine aminotransferase (ALT) of 160 IU/L (normal:7-56 U/L), serum alkaline phosphatase levels were normal (