Hepatitis C virus

PREPARED BY: MUHAMMAD ARIFF B. MAHDZUB

BACHELOR MEDICINE AND SURGERY (MBBS)
UNIVERSITY COLLEGE SHAHPUTRA, KUANTAN

1. MD-2204 (Respiratory System) MD-2204 (Respiratory System) PREPARED BY: MUHAMMAD ARIFF B. MAHDZUB BACHELOR MEDICINE AND SURGERY (MBBS) UNIVERSITY COLLEGE SHAHPUTRA, KUANTAN DR. MISHAL MD-2204 (DIGESTIVE SYSTEM) PROBLEM BASED LEARNING (PBL ) Hepatitis C virus

2. LEARNING ISSUES PATIENT HISTORY, SIGNS AND SYMPTOMES ANATOMY OF THE LIVER (GROSS ANATOMY) HISTOLOGY OF THE LIVER BLOOD TEST AND NORMAL VALUES PHYSIOLOGY OF LIVER HEPATITIS TRANSFUSION-TRANSMITTED DISEASES (TTD) LIVER BIOPSY DIFFERENTIAL DIAGNOSIS TREATMENT & MANAGEMENT

3. TRIGGER 1 MR HABID 50 Y/O MALE, OBESE PHYSICAL EXAM, NORMAL BLOOD TEST, LIVER ENZ. & GLOBULIN FRAC. HIGH

4. TRIGGER 2 (FOLLOW-UP VISIT) DENIED ALCOHOL/DRUG NO JAUNDICE HISTORY WIDOWER (3 MONTH), NOT ADMIT EXTRA SEX AGE 40, HAVE BLEEDING STOMACH ULCER NEED SURGERY, AND TRANSFUSION 4 UNITS OF BLOOD

5. TRIGGERS 3 (NEXT VISIT) NO JAUDICE, NO HEPATOSPLENOMEGALY, NO PORTAL HYPERTENSION RT-PCR FOR HCV IS DONE, GENOTYPE OF HCV IS DETERMINED, LIVER BIOPSY DIAGNOSE : INFECTIOS ETIOLOGY OF TTD

6. CLARIFY DIFFICULT WORD TTD :  virus, parasite, or other potential pathogen that can be transmitted through a  transfusion  to a recipient RT PTC: spesific type of technology in molecular biology used to amplify a single copy or a few copies of a piece of RNA

7. CLINICAL SIGNIFICANCE OF RT-PCR To identifies the presence of viral RNA and the actual virus Detection and confirmation of chronic HCV infection very sensitive to low viremia so, usefull for person who was infected with HCV very recently, called acute infection , as not develop antibodies yet

8. ANATOMY OF LIVER (GROSS)

9. ANATOMY OF LIVER Largest visceral organ Triangular organ Upper part abdominal cavity just beneath diaphragm Occupies : -right hypochondrium - epigastrium -left hypochondrium Lobes : -right , left, caudate, quadrate

10. ANATOMY OF LIVER LOBES - liver is divided into a larger right lobe and a smaller left lobe by the falciform ligament RIGHT LOBES -Largest lobe - Quadrate lobe and caudate lobe. - Divided into anterior and posterior sections by the right hepatic vein

11. ANATOMY OF LIVER QUADRATE LOBE - Inferior surface of Rt.lobe -Boundaries : Ant. – Inf. border of liver Sup. – porta hepatis Rt. – fossa for gallbladder Lt. – fissure for ligamentum teres CAUDATE LOBE -Posterior surface of Rt. Lobe -Boundaries : Inf. – porta hepatis Rt. – groove for inf. vena cava Lt. – fossa for lig . venosum

12. ANATOMY OF LIVER LEFT LOBES -smaller and more flattened than the right -Divided into lateral and medial segments by the left hep a tic vein COUINAUD CLASSIFICATION - Right hepatic vein divides Rt. lobe into ant. and post. segments. -Middle hepatic vein divides liver into Rt. and Lt. lobe -Left hepatic vein divides Lt. lobe into a medial and lateral part. -Portal vein divides liver into upper and lower segments

13. ANATOMY OF LIVER BLOOD SUPPLY OF LIVER Right & Left hepatic arteries Portal vein Hepatic veins

14. ANATOMY OF LIVER

15. LIVER HISTOLOGY

16. INFLOW TO THE LIVER Hepatic Artey (O2 blood) Portal Vein (nutrients and compound absorbed from GIT) OUTFLOW FROM LIVER Hepatic Vein (drain into vena cava) Common hepatic duct

17. Characteristic of liver: Hepatocyte Sinusoid Major characteristic: Portal Triad 2) Central vein

18. Portal Triad consist of portal vein, hepatic artery and bile duct Central vein  Sublobular vein  Collecting vein  Hepatic vein  Vena cava Sinusoid : Capillary-like vessel lined by fenestrated discontinous epithelium

19. Space of Disse : A space between hepatocyte and sinusoidal epithelial cell which a space for exchange between hepatocyte and blood Kupffer cells : Interspersed among endothelial cell. Fixed macrophage within hepatic tissue Enter sinusoidal lumen to function like other macrophage Breakdown damaged RBC hemoglobin

20. HEPATIC LOBULE Structural unit of liver Roughly hexagonal in shape Centered on a terminal hepatic venule (central vein) Portal tract (portal triad) situated at the angle of hexagon HEPATIC ACINUS Roughly berry-shaped unit of liver parenchyma Have 3 zone Zone 1 : near to portal tract (receive most oxygenated blood Zone 2 Zone 3 : far from portal tract (receive least oxygenated blood)

21. Acute viral hepatitis Characterized by: diffuse cell injury with swelling Spotty necrosis Process mediated by lymphocyte : alter the cell membrane antigen  destroy the hepatocytes At the same time of damage , compensatory hypertrophy and replication of hepatocytes happen Finally, inflammation reaction most intense around portal tracts and also diffuse through sinusoid Most case resolve , but type B and C disease can become chronic . Lobular disarray and spotty necrosis

22. C hronic Viral Hepatitis Characterized by : hepatic necroinflammation (chronic inflammatory infiltrate and necrosis of hepatocyte) Fibrosis According to necroinflammatory activity , chronic hepatitis might be mild, moderate and severe Mild Chronic Viral hepatitis : dense lymphocytic portal reaction. However, there is very little spillage of these lymphoid cells into the lobules In addition, there is spotty necrosis, but necrotic cells are quite rare no evidence of diffuse liver cell injury. Figure: This low-power hematoxylin and eosin-stained liver biopsy demonstrates a periportal mononuclear infiltrate and mild periportal fibrosis

23. Moderately chronic hepatitis was characterized by: dense portal and periportal inflammation and extensive piecemeal necrosis , affecting 50% of the circumference of almost all the portal tracts, and lobular necrosis and inflammation were significant, with damage of 1/3-2/3 the lobe. The liver parenchyma showed moderate lymphocytic infiltrate in the portal tracts and portal fibrosis. Intralobular moderate inflammatory infiltrate was present.

24. Severe Chronic Viral Hepatitis : destruction of large chunks of parenchyma, even tracts or bridges, beginnings of scars . lymphoid infiltrate with prominent extension into the periphery of the lobule and further extension deeper into the parenchyma. associated with considerable spotty necrosis and occasionally with confluent necrosis as well, which may bridge between central and portal zones. Liver cells may be trapped within these zones of confluent necrosis, a degree and pattern of necrosis that is a potential precursor of cirrhosis .

25. BLOOD TEST AND NORMAL VALUES NOTED “BASE ON THE TRIGGER 1, BLOOD TEST WAS ORDERED WHICH SHOW THE ELEVATION OF LIVER ENZYMES APPROXIMATELY 3 TIMES THE UPPER LIMITS OF NORMAL AND ALSO RAISED GLOBULIN FRACTION”

26. WHAT IS BLOOD TEST??? A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick . Multiple tests for specific blood components (such as a glucose test or a cholesterol test) are often grouped together into one test panel called a blood panel or blood work. Blood tests are often used in health care to determine physiological and biochemical states, such as disease, mineral content, pharmaceutical drug effectiveness, and organ function. Typical clinical blood panels include a basic metabolic panel or a complete blood count . Blood tests are also used in drug tests to detect drug abuse.

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28. Continue... A basic metabolic panel measures sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), magnesium, creatinine, glucose, and sometimes includes calcium. Blood tests focusing on cholesterol levels can determine LDL and HDL cholesterol levels, as well as triglyceride levels . Some blood tests, such as those that measure glucose or a lipid profile, require fasting (or no food consumption) eight to twelve hours prior to the drawing of the blood sample . For the majority of blood tests, blood is usually obtained from the patient's vein. However, other specialized blood tests, such as the arterial blood gas, require blood extracted from an artery. Blood gas analysis of arterial blood is primarily used to monitor carbon dioxide and oxygen levels related to pulmonary function, but it is also used to measure blood pH and bicarbonate levels for certain metabolic conditions . While the regular glucose test is taken at a certain point in time, the glucose tolerance test involves repeated testing to determine the rate at which glucose is processed by the body .

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31. Physiology of liver

32. Digestion Metabolism Detoxification Storage Production Immunity

33. Digestion production of bile mixture of water, bile salts, cholesterol, and the pigment bilirubin stored in the gallbladder cholecystokinin stimulates the gallbladder to release bile. emulsifies large masses of fat easier for the body to digest.

34. Metabolism metabolizing carbohydrate, lipids, and proteins Hepatocytes absorb much of glucose and store it as the macromolecule glycogen absorption and release of glucose by the hepatocytes helps to maintain homeostasis Fatty acids are absorbed by hepatocytes and metabolized to produce energy in the form of ATP. Glycerol is converted into glucose by hepatocytes through gluconeogenesis Hepatocytes first remove the amine groups of the amino acids and convert them into ammonia and eventually urea. amino acids can be broken down into ATP or converted into new glucose molecules through gluconeogenesis.

35. Detoxification hepatocytes of the liver monitor the contents of the blood and remove many potentially toxic substances before they can reach the rest of the body. metabolize alcohol and drugs into their inactive metabolites

36. Storage storage of many essential nutrients, vitamins, and minerals Glucose is transported into hepatocytes under the influence of the hormone insulin and stored as the polysaccharide glycogen. absorb and store fatty acids from digested triglycerides stores vitamins and minerals - such as vitamins A, D, E, K, and B12, and the minerals iron and copper

37. Production production of several vital protein components of blood plasma: prothrombin , fibrinogen, and albumins.

38. Immunity function of the Kupffer cells that line the sinusoids. capturing and digesting bacteria, fungi, parasites, worn-out blood cells, and cellular debris large volume of blood passing through the hepatic portal system and the liver allows Kupffer cells to clean large volumes of blood very quickly.

39. Billirubin

40. Bilirubin consists of an open chain of four  pyrrole -like rings ( tetrapyrrole ). In  heme , these four rings are connected into a larger ring, called a  porphyrin  ring. Bilirubin can be conjugated and unconjugated .

41. Unconjugated Erythrocytes generated in the bone marrow are disposed of in the spleen when they get old or damaged. This releases  hemoglobin , which is broken down to  heme  as the globin parts are turned into amino acids. The heme is then turned into unconjugated bilirubin in the monocyte macrophages system of the spleen. This unconjugated bilirubin is not soluble in water, due to intramolecular hydrogen bonding. It is then bound to albumin and sent to the liver.

42. In the liver, bilirubin is conjugated with  glucuronic acid by the enzyme  glucuronyltransferase , making it soluble in water: the conjugated version is also often called "direct" bilirubin . Much of it goes into the bile and thus out into the small intestine. Though most bile acid is resorbed in the terminal ileum to participate in  enterohepatic circulation, conjugated bilirubin is not absorbed and instead passes into the colon. Conjugated

43. There, colonic bacteria deconjugate and metabolize the bilirubin into colorless   urobilinogen , which can be oxidized to form  urobilin and   stercobilin : these give stool its characteristic brown color .

44. Hepatitis B

45. Introductions of Hepatitis B

46. Morphology of the virus 3 forms: Spherical particles measuring 22nm in diameter Tubular or filamentous forms same diameter but may be over 200nm long result from overproduction of HBs Ag Larger 42nm (Dane particles) containing partially ds circular DNA The outer surface contains HBsAg S urrounds an inner nucleocapsid core that contains HBcAg DNA polymerase is associated with the core Genome: partially double stranded circular DNA

47. Signs & symptoms

48. Mode of Transmission Vertical transmission Sexual intercourse Parenteral High risk groups: Blood transfusion & transfusion with other human blood product Dialysis Health care personnel Living with infected person Contact with non-intact skin or mucous membrane with secretions or saliva containing HBV Travel in countries where the infection rate is high Tattooing & acupuncture (less common with improved sterility) Re-use of contaminated needles & syringes (IVDU ) Exposure to infectious blood or body fluids containing blood

49. Pathogenesis of Hepatitis B

50. Diagnosis Detection of Dane particles in blood by electron microscopy Immunoassays for detection of hepatitis B virus infection involve  serum or blood tests that detect either viral antigens (proteins produced by the virus) or antibodies produced by the host Hepatitis B surface antigen (HBsAg) Used to screen the presence of infections May not present in early infection May be undetectable later in the infection as it is being cleared by the host Shortly after the appearance of the HBsAg, another antigen called hepatitis B e antigen ( HBeAg ) which are important indicator of transmissibility will appear the presence of HBeAg in a host's serum is associated with much higher rates of viral replication and enhanced infectivity

51. Prevention

52. HEPATITIS D VIRUS

53. HEPATITIS A,E,G VIRUS

54. HEPATITIS A

55. ROUTE OF TRANSMISSION Fecal route transmission Eat and drink food that come in contact with feces;  houseflies poor cleaning after handling feces homosexsual,bisexual Blood transfusion Rarely transmitted,low level viremia,low chronic infection

56. RISK FACTORS Travellers-asia,south africa,central America Iv drugs user Living in nursing home center Working in food,health care,sewage industry

57. SYMPTOMS

58. EXAM & TEST Physical exam-liver enlarged and tender Raised IgM and IgG Liver function test-elevated transaminase enzyme level Treatment No specific treatment Rest Avoid alcohol,drugs toxic to liver Vaccine

59. HEPATITIS E

60. HEPATITIS G

61. Viral agents Human immunodeficiency virus (HIV) Hepatitis viruses West Nile virus (WNV) Cytomegalovirus (CMV) Human T-cell lymphotrophic viruses (HTLVs) Parvovirus B19

62. HIV : a member of the Lentivirus family of retroviruses, is the causative agent of acquired immunodeficiency syndrome (AIDS). WNV : a flavivirus , is transmitted by mosquito bite. The organism has the potential of being transmitted through blood. CMV : belongs to the herpes group of viruses. The organism's transmission is prevented by transfusing leukocyte-depleted blood products, which is consistent with the fact that CMV is a leukocyte-associated pathogen. Human T-cell lymphotrophic virus–1 (HTLV-1) and HTLV-2 have been shown to be transmitted by blood transfusion. Infection with these retroviruses may result in HTLV-related myelopathy /tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia /lymphoma. Parvovirus : a nonenveloped virus that is usually transmitted by vertically from mother to child blood products.Transmission by blood products is common because the virus does not have a lipid envelope, rendering inactivation methods 

63. Hepatitis C virus The hepatitis C virus (HCV) is a : Spherical Enveloped single-stranded RNA virus Flaviviridae family HCV is predominantly transmitted by means of : percutaneous exposure to infected blood. In developed countries, most new HCV infections are related to : intravenous (IV) drug abuse The use of the polymerase chain reaction (PCR) assay has reduced the risk of acquiring HCV from blood transfusions to 1 in 230,000 donations.

64. Bacterial Infections Bacteria that potentially evades the sterility of the transfusion loop can come from : donor's blood skin contaminated environment. The incidence of bacterial transmission depends on : blood product definition of the cases. The estimated residual risk of contamination of blood products with bacterial agents is : 1 in 5,000 for platelets 1 in 30,000 for red blood cells .

65. Microbiologic spectrum of bacterial contamination A multitude of microorganisms have been isolated from contaminated blood products. Some of these organisms and species include the following: Yersinia Proteus Pseudomonas Escherichia Klebsiella Acinetobacter Serratia Staphylococcus ,  Bacillus,  and  Enterococcus  

66. LIVER BIOPSY

67. DEFINITION I s a procedure in which tissue samples from the liver are removed for examination under a microscope to look for signs of damage or disease. During a liver biopsy, a special needle is used to determine if cancer or other abnormal cells are present, or to determine how well the liver is working.

68. 3 types of liver biopsies Percutaneous or needle biopsy (common) Laparoscopic or open biopsy Transvenous biopsy

69. Your doctor may recommend a liver biopsy if you have: Abnormal liver test results that cannot be explained A mass ( tumor ) or other abnormalities on your liver as seen on imaging tests Ongoing, unexplained fevers

70. INDICATION OF LIVER BIOPSY Liver biopsy has three major indications: for diagnosis for assessment of prognosis to assist in the management of patient with known liver disease.

71. WHY IT IS DONE ? Find the cause of abnormal blood test results from aspartate aminotransferase (AST) and alanine aminotransferase (ALT) tests. See how much the liver is inflamed or scarred by hepatitis or other liver diseases See whether other liver conditions, such as hemochromatosis and Wilson's disease, are present. Check the response to treatment for liver disease. Check the function of a transplanted liver

72. RISKS Pain -most common complication after a liver biopsy. If pain makes you uncomfortable, you may be given a narcotic pain medication, such as acetaminophen with codeine (Tylenol with Codeine). Bleeding -Excessive bleeding may require you to be hospitalized for a blood transfusion or surgery to stop the bleeding. Infection - Rarely, bacteria may enter the abdominal cavity or bloodstream. Accidental injury to a nearby organ-In rare instances, the needle may stick another internal organ, such as the gallbladder or a lung, during a liver biopsy.

73. If you have a transjugular liver biopsy, other infrequent risks include: Collection of blood (hematoma) in the neck . Blood may pool around the site where the catheter was inserted, potentially causing pain and swelling. Temporary problems with the facial nerves.can injure nerves and affect the face and eyes, causing short-term problems, such as a drooping eyelid. Temporary voice problems . You may be hoarse, have a weak voice or lose your voice for a short time. Puncture of the lung . If the needle accidentally sticks your lung, the result may be a collapsed lung (pneumothorax).

74. CONTRAINDICATIONS Liver biopsies should not usually be performed when there is biliary obstruction and cholangitis. Abnormal coagulation indices: A percutaneous biopsy will not usually be undertaken if the INR is greater than 1.3. Thrombocytopenia : if the platelet count is >60 x 109/L then the biopsy can be safely performed. If the platelet count is 40-60 x 109/L then platelet transfusion may increase the count enough for the biopsy to be performed safely Drugs that affect platelet function (such as aspirin or clopidogrel ) should bediscontinued (where possible) 5-10 days before biopsy. Warfarin must be stopped and the INR monitored until it falls to 1.3 or less before the biopsy is undertaken.

75. RESULT

76. Normal liver cell liver cirrhosis Liver cirrhosis hepatitis

77. Differential Diagnosis (A man bearing a silent killer)

78. Fatty liver, or steatosis , is a broad term that describes the buildup of fats in the liver Cirrhosis is a slowly progressing disease in which healthy liver tissue is replaced with scar tissue, eventually preventing the liver from functioning properly Typhoid fever is an infection that causes diarrhea and a rash. It is most commonly due to a type of bacterium called  Salmonella typhi  ( S. typhi ). Hepatitis C is an infection of the liver. It's caused by the hepatitis C virus

79. Trigger 1 Sign & Symptoms Typhoid fever Hepatitis Liver cirrhosis Steatosis (fatty liver Obesity / / Liver enzyme elevated / / Raised globulin fraction / / plumber /

80. Trigger 2 Sign & Symptoms Typhoid fever Hepatitis Liver cirrhosis Steatosis (fatty liver) Alcohol / / Drug use / (shared) / (tolerance) / Bleeding stomach ulcer / / Extra-marital sex /  (HIV infection, several sex partners, or have rough sex)

81. Trigger 3 Sign & Symptom Typhoid fever Hepatitis Liver cirrhosis Steatosis (fatty liver) Hepato-splenomegaly / / Portal hypertesion / Infection / (salmonella typhi) / / Hepatits panel / (+ anti-HCV) / Genetic / / (cystic fibrosis) Jaundice / /

82. Conclusion Based on the table : Although liver cirrhosis have major of the sign n symptom But the most likely disease is hepatitis C Sign & symptom for the disease is same as patient’s complaint and investigation

83. TREATMENT & MANAGEMENT

84. TREATMENT Treatment for hepatitis C, depending on: How damaged the liver is. Other health conditions have. How much hepatitis C  virus contain in body. type (genotype) of hepatitis C Treatment isn't always an option because have serious side effects, are expensive, don't work for everyone.

85. Acute Hepatitis C Mostly not treated as it is asymptomatic

86. Chronic Hepatitis C common for people to live with hepatitis C for years because it is asymptomatic most people diagnosed with hepatitis C find out that they already have chronic infection. If no damage to your liver, no treatment needed routine blood tests needed to determine liver function The medicines usually used to treat hepatitis C are  interferons combined with ribavirin  plus a protease inhibitor  e.g boceprevir or telaprevir . Used for 6 months to a year and help get rid of the virus.

87. Management Patient must get vaccinated to protect from Hepatitis A and B virus Patient must have enough sleep Careful with drugs and alcohol Relax and avoid depression and anxiety