Viral Hepatitis Lecture 7.1 PDF

Hepatitis viruses: ◦Hepatitis definition: Acute vs Chronic ◦5 main strains of the hepatitis virus referred to as A,B, C, D and E ◦While each virus can cause similar symptoms, they are transmitted differently and can affect the liver in different ways ◦Hepatitis A (food borne an...

Hepatitis viruses: ◦Hepatitis definition: Acute vs Chronic ◦5 main strains of the hepatitis virus referred to as A,B, C, D and E ◦While each virus can cause similar symptoms, they are transmitted differently and can affect the liver in different ways ◦Hepatitis A (food borne and water borne) and E (likely to be found in pregnant women) cause short term infections -> self-limiting ◦Type B and C can lead to chronic disease and together are the most common cause of liver cirrhosis ◦Other less common viruses can cause hepatitis including CMV, EBV and rubella Why is it so important?: ◦Estimated 325 million people worldwide live with hepatitis B and/or C - blood borne viruses that can be spread sexually, through blood products, needles etc ◦Disease burden and economic burden due to chronic hepatitis related liver cirrhosis, liver cancer, liver transplant and mortality from the disease -> would need a liver transplant ◦Hepatitis B is preventable due to vaccine. Universal vaccination introduced to UK infant schedule 2017 ◦Hepatitis C is treatable with direct acting antiviral drugs. NICE licensed ◦WHO in 2016 set a target to eliminate viral hepatitis by 2030 Viral structure: ◦Hepatitis A virus is a non-enveloped RNA virus in the Picornavirus family ◦Hepatitis B virus is an enveloped partially double stranded DNA virus in the Hepadnavirus family ‣ The only hepatitis virus where the genetic material is found in DNA. Also has some single stranded DNA, which is first converted into double stranded DNA and then translated ◦Hepatitis C virus is an enveloped single strand RNA virus in the Flavivirus family ◦Hepatitis D virus is a defective virus can't infect a hepatocyte unless already infected with HBV -> co-infect when a person has Hepatitis B, so piggy-backs HBV so it can work ◦Hepatitis E virus is a non enveloped RNA virus in the Hepeviridae family -> not common in the west, more common in pregnancy Hepatitis A: ◦RNA virus Picornaviridae ◦Oral-Faecal route (contaminated water, bad hygiene areas, food etc) ◦114 million affected worldwide ◦Incubation 2-6 weeks ◦Vaccine available ◦Self limiting, complications rare (unlikely to get liver cirrhosis or liver failure) ◦HAV IgM active infection (primary infection, and is the initial infection) ◦HAV IgG recovery/vaccination (infection is being fought by adaptive immune system - memory B cells) Hepatitis E: ◦RNA virus Hepeviridae ◦Oral-faecal route ◦28 million affected worldwide ◦Incubation 40 days ◦Dangerous in pregnant women ◦Self limiting - off licence Ribavarin (antiviral agent used to treat HEV)  ◦HEV IgM active infection ◦HEV IgG recovery Hepatitis B: ◦Vertical transmission (75% globally) ◦Sexual contact ◦IVDU ◦Blood products ◦Needlestick injuries ◦Incubation: 6/52 - 6/12 (6 weeks to 6 months) ◦Chronicity 90% infancy, 20% older children and < 10% adults (the younger the person infected, the more likely they are to carry HBV chronically) ◦Vaccine available Hepatitis C: ◦IVDU (90%) ◦Sexual contact < 1% ◦Infants born to HCV +ve ◦Blood products prior to 1991 ◦Needlestick injuries ◦Incubation: 2/52 - 6/12 (2 weeks to 6 months) ◦Chronicity 80% ◦No vaccine Pathophysiology: ◦Acute infection after inoculation/ingestion of virus ◦Virus enters hepatocytes which are the main site of replication ◦This triggers a cellular immune response by the host's defence mechanisms and release of cytotoxic cytokines and natural killer cells ◦Attack the infected hepatocytes leading to destruction of the hepatocytes and release of liver enzymes ◦Oedema and necrosis ◦Cholestasis - altered blood flow through the liver (bile cannot travel efficiently) ◦Fibrosis - scarring ◦Cirrhosis - severe scarring ◦Carcinoma Signs and symptoms: ◦No symptoms ◦Malaise ◦Lethargy ◦Fever ◦Nausea ◦Anorexia ◦Abdominal pain - due to involvement of liver ◦Jaundice - yellow discolouration of skin and/or sclera  ◦Pruritis (itchy skin) ◦Dark urine, pale stools (bilirubin the blood is excreted in the urine, and flow of bile is reduced/liver isn't producing bile) ◦Hepatomegaly, tender ◦Later signs of liver cirrhosis - palmar erythema (palms of your hands turn red); spider naevi (a cluster of minute red blood vessels visible under the skin), gynaecomastia (condiiton that causes boys' and mens' breasts to swell and become larger than normal) ◦Abdominal distension, caput medusae (a cluster of swollen veins in your abdomen), encephalopathy Investigations: ◦Blood tests ◦Liver function tests: ‣ Liver transaminases: marker of hepatocyte damage - ALT (Alanine transaminase) and AST (aspartate transaminase test) ‣ Alkaline phosphatase: located on the outer layer of cell membrane/indicator of cell damage/cholestasis (reduced or stopped bile flow) ‣ Albumin (protein synthesised in the liver) ‣ Coagulation tests: clotting factors are synthesised in the liver. INR PT (a prothrombin time (PT) test measures how long it takes for a clot to form in a blood sample. An INR (international normalised ratio) is a type of calculation based on PT test results) ◦Immunology - look for viral RNA via PCR, or antigens/antibodies in the blood (IgM or IgG antibodies) ◦Imaging - not usually required for diagnosis ◦Ultrasound, CT scan ◦Liver biopsy Hepatitis B serology: ◦Hepatitis B markers - can be found in the blood of a person who is infected with HBV ‣ HB surface antigen ‣ HB surface antibody ‣ HB core antibody - part of the entity that surrounds the nuclear material (in the blood this can be picked up via tests) ‣ E antigen is known as the envelope antigen and is only found in people with HBV Hepatitis B management: ◦Refer anyone who is HBsAg positive to a gastroenterologist or Infectious disease specialist ◦Anti-virals suppress viral replication e.g. entecavir, tenofovir, lamivudine ◦Education regarding transmission Hepatitis B vaccination: ◦Genetically engineered surface Ag of the virus ◦3 doses + boosters if required ◦Produces antibody response to surface antigen ◦Universal UK infant schedule in 2017:  ‣ 6 in 1 vaccine ‣ Given at 2,3 and 4 months ◦At risk population including babies born to infected mothers, close family or sexual partner, receive regular blood transfusions or products, people whose work puts them at risk, prisoners, IVDU and MSM. Hepatitis C serology: ◦Serology anti hepatitis C antibody only ◦Remains positive even after cure ◦Not protective - can get re-infected ◦Viral PCR - if positive, confirm chronicity Hepatitis C management: ◦Refer to specialist Gastroenterologist or specialist Hepatologist ◦Directly acting antiviral drug combo 8-12 weeks ◦> 90% chance of cure ◦£20-60k per course ◦Can get re-infected Differential diagnosis: ◦Peptic ulcer ◦Pancreatitis ◦Hepatitis ◦Liver cirrhosis ◦Oesophageal varices ◦Hepatocellular carcinoma