AIDS and HEPATITIS

sexually transmitted -AIDS

1. TOPIC: ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) CONTENTS: • INTRODUCTION • DEFINITION • INCIDENCE & PREVALENCE • MORPHOLOGY OF VIRUS • NODES OF TRANSMISSION • PATHOGENESIS • CLINICAL FEATURES • SIGNS & SYMPTOMS OF AIDS ORAL LESIONS IN INFECTION • CLASSIFICATION SYSTEM FOR HIV INFECTION AND EXPANDED AIDS SURVEILLANCE CASE DEFINITION FOR

2. ADOLESCENTS & ADULTS • DIAGNOSIS • MANAGEMENT Virus based Tests. Anti HIV antibody Test • HIGHLY ACTIVE ANTI RETROVIRAL THERAPY (HAART) • PREVENTION & CONTROL • POST EXPOSURE PROPHYLAXIS REFERENCES: 1. SHAFER'S - TEXTBOOK OF ORAL PATHOLOGY- 8th EDITION; Page: 335 2. ANIL GOVINDRAD GHOM -TEXTBOOK OF ORAL MEDICINE - 2nd EDITION; Page: 856 3. Dr. S.N. CHUGH-TEXTBOOK OF CLINICAL MEDICINE - 4th EDITION Page: 343 4 Dr. CP BAVEJA. TEXTBOOK OF MICROBIOLOGY - 6th EDITION Page: 305

3. TOPIC: HEPATITIS CONTENTS: INTRODUCTION • DEFINITION • CLASSIFICATION •ACUTE HEPATITIS Pathology: Causes (Acute Viral Hepatitis) HEPATITIS A  Introduction  Morphology  Clinical features  Investigations  Treatment  Prophylaxis

4. HEPATITIS B  Introduction  Structure of Hepatitis B  Mode of transmission  Clinical features  Investigations  Treatment  Prophylaxis  Indication for Hepatitis B Vaccination in Endemic Areas HEPATITIS C  Introduction  Mode of infection  Clinical features  Treatment

5. HEPATITIS D  Introduction  Morphology  Clinical features  Investigations  Prophylaxis HEPATITIS E  Introduction  Pathogenesis  Laboratory diagnosis  Prophylaxis ACUTE HEPATIC ENCEPHALOPATHY DIFFERENCES BETWEEN ACUTE AND CHRONIC HEPATIC ENCEPHALOPATHY

6. CHRONIC HEPATITIS  Etiology  Pathology  Diagnosis CHRONIC HEPATITIS B  Clinical features  Investigations  Treatment  Prognosis CHRONIC HEPATITIS C  Clinical features  Treatment CHRONIC AUTO IMMONE HEPATITIS  Clinical manifestations  Investigations  Treatment

7. • REFERENCES 1. Dr. S.N CHUGH-TEXTBOOK OF CLINICAL MEDICINE - 4 EDITION Page: 86 2 ANIL GOVINDRAO GHOM TEXT BOOK OF ORAL MEDICINE - 2nd EDITION Pg.: 801 3. Dr.CP BHAVEJA -TEXT BOOK

8. INTRODUCTION: AIDS is a divesting disease which is in epidemic form throughout the world. It is an incurable viral sexually transmitted disease which is caused by Human immunodeficiency Virus (HIV). It stands for: A- Acquired i.e. contagious not inherited I- Immune i.e. power to resist disease D- Deficiency S- Syndrome i.e. Number of signs & symptoms; indicative of a particular disease.

9. - It is characterized by immunosuppression, which leads to a spectrum of clinical manifestations that include opportunistic infections, secondary neoplasms & neurological manifestations. Two genetically distinct populations of viruses known to cause AIDS & HIV-1 & HIV-2. HIV-1 most common to cause AIDS in Central Africa & rest of the world, HIV-2 Virus is responsible in West Africa & India.

10. DEFINITION WHO has given the following definition of AIDS One or more opportunistic infections listed in clinical features that are at least moderately indicative of underlying cellular immune deficiency. Absence of all known underlying causes g cellular immune defiency (other than HIV) & absence of all other causes of reduced resistance reported to be associated with at least one of those opportunistic diseases.

11. INCIDENCE AND PREVALENCE In 1983, HIV was identified as the causative Organism of AIDS. Current WHO estimates indicate that 40 million adults are infected worldwide of who 2.5 million have died. WHO estimate predict that about 80 million people will get infected with AIDS by the turn of 20th century, the reason for greater risk for transmission is heterosexual intercourse in Africa & Asia than USA. The incidence of other Sexually transmitted disease is decreasing with increase in the incidence of AIDS. In UK, women currently account for 15% of known HIV infections & 6% of AIDS cases reported.

12. Morphology of Virus: HIV is spherical enveloped virus, about 90-120 nm in diameter. It contains two identical copies of single stranded RNA genome. In association with viral RNA is the reverse transcriptase enzyme. The virus contains a lipoprotein envelope. The major virus coded envelope glycoproteins are projecting spikes on surface & anchoring trans membrane pedicels.

13. MODES OF TRANSMISSION Sexual transmission : It is in 90% Cases. It depends upon number of sexual partners, receptive anal intercourse & presence of other STD’s. Use of contaminated blood products Intravenous drug uses, HIV Contaminated blood transfusion, blood clotting concentrate & Organ transplantation. Perinatal transmission : It occurs in 13% among children born to liv seropositive mother. Other nosocomial routes : Transmission from patient to patient due to reuse of contaminated & Shared needles.

14. Professional hazards : The risk of transmission from HIV patient to health care worker is more than health care worker to patient. Saliva transmission : The virus is found to be present in saliva. It reduces the ability of HIV to infect the target cells, so transmission through. Saliva is rare possibility .

15. PATHOGENESIS: HIV principally affect all cells expressing T₁ antigen to which HIV attaches for replication i.e. CD4 helper T. lymphocyte which air suspensible for initiation of nearly all immunological responses to pathogens Following infection by HIV, there is reduction in CD4 population resulting in gradual failure of cell mediated immunity. The exact mechanisms of immunopathology is unknown. There will be involvement of other cell such as lymphocytes. Monocytes, macrophage, dendritic cells & B lymphocytes by HIV had been implicated .

16. The extent of reduction in CD4 cell count also correlates to various complications of HIV disease & determines the time when anti-retroviral to be employed, therapy & antibiotic therapy is to be employed. Direct involvement of CNS in HIV disease is due to migration of HIV infected monocytes to the brain where they become microglial cells, whereas most diseases induced by HIV infection are as a consequence of immune system failure resulting in opportunistic infections & Secondary neoplasms.

17. Clinical features. 1. Acute primary infection / seroconversion: • Majority are asymptomatic, but a small number of patients with nonspecific illness characterized by fever, arthralgia, myalgia, lethargy, lymphadenopathy, sore throat • Neurological manifestations: Headache, photophobia, myopathy, neuropathy & rarely encephalopathy. 2. Asymptomatic infection: • Depletion of percentages of CD4 lymphocyte count

18. 3. Persistent generalized lymphadenopathy 4. Symptomatic HIV infection:  Susceptibility to opportunistic infections and tumors.  Presence of multiple infections at one time.  lack of typical signs & symptoms due to failure of inflammatory response • Raised CD8 lymphocyte count & percentages • Raised serum & urinary neopterin.

19. Signs & Symptoms: • Weight loss, might sweats, • Diarrhea • Bacterial & fungal, vital infections • Intellectual & cognitive impairment, • Polyneuropathy • Anemia, neutropenia • Thrombocytopenia

20. Oral lesions in HIV infection: Oral candidiasis Oral squamous cell carcinoma Oral hairy leukoplakia Thrombocytopenic purpura Kaposi sarcoma non-Hodgkin lymphoma Aphthous ulcer Hyperpigmentation Molluscum contagiousum

21. Classification system for HIV infection & expanded AIDS Surveillance case definition for adolescents & adults: A B C CD4+ T CELLCATEGORIES ASYMPTOMATIC ACUTE HIV SMPTOMATIC NOT (A)OR (C) AIDS INDICATOR CONDITIONS 500/mm 3 A1 B1 C1 200-499/mm3 A2 B2 C2 Less than 200/mm3 A3 B3 C3

22. DIAGNOSIS: I) Virus based tests: [Viral culture] It directly detects the Virus & hence is highly specific. H is positive even during the window period of during the terminal phase when the viral load is high & ELISA may be negative. Polymerase chain reaction: 2 Types of PCR: available PER for DNA of provirus present in the infected host cells, PCR for HIV RNA from plasma, which detect the -free virus present in plasma PCR can defect as low as 20 copies/mm of plasma, & is a test. It is very useful for the early diagnosis of HIV infection highly sensitive & specific in new-born.

23. Result of PCR are available in 24-48h unlike viral culture that take 3-4 weeks. Quantitative PCR can be done to define viral load in copies pre milli liter of plasma. This is useful before starting therapy & monitoring response & relapse following retroviral drugs. P24 antigen detection: It is delectable during the window period & Take phase of infections when the virus is replicating fast. It is often not detectable at other time. As viral replication is low. Hence, this test is not sensitive enough to be of use for routine diagnosis. It is useful in blood banks where the P24 antigen, along with ELISA, Can shorten the window period & diagnosis to less than 2 weeks.

24. Anti-HIV Antibody tests: 1 . Enzyme - linked immunosorbent assay or Immunofluorescence ELISA that have nearly 99% sensitivity & specificity, especially on repeated testing. There are also much Cheaper than PCR & Culture & can be done at any center. If 2 or 3 ELISA tests are positive, a person is confirmed au HIV infected. One will have to wait for 18 months to diagnose HIV infection in newborn if one uses ELISA only. It cannot help in early diagnosis. It is negative during the window period, that is 6-12 weeks following HIV exposure & sometimes during the last phase of HIV infection due to severe immunodeficiency leading to severe hypogammaglobulinemia

25. 2. Western blot analysis: This detects specific antibodies & shows them as separate bands on gels. Hence it is more specific than ELISA It is interpreted as positive if at least two of the three bands i.e. p24, gp41, gp126 /160 bands are positive. If none are positive, it is labelled as negative. If only one band is positive, labelled as indeterminate when test is indeterminate, one needs to repeat both ELISA & western blot 1 and twice a week

26. Immunological Tests & Surrogate Markers: CD4 + T cell count, CD4 + T cell / & CDA: CD8 ratio are the text done to determine immune status. A gradual decline in CD4+ T cell is more constant, whereas absolute CD4 is age-dependent. Salivary tests: The immunoglobulin content of oral fluids is similar to that of blood but their levels are lower. However the use of an HIV IgG antibody capture ELISA assay, designed specifically for testing oral fluids, has produced encouraging results.

27. Management: Nucleoside reverse transcriptase inhibitors: o Zidovudine 600mg o Didanosine 400 mg o Stavudine 40 mg o Lamivudine 150 mg Nucleotide reverse transcriptase inhibitors: Tenofovir Non-nucleoside reverse transcriptase inhibitors: Nevirapine 200mg

28. Protease inhibitors o Amprenavir o Indinaver Protease inhibitors boosted with ritonavir: o Lopinavir R o Ritonavir / Indinavir Fusion inhibitors o Enfavirtide Integrase inhibitors: o Reltegravir

29. HAART The parameter of efficacy of HAART is viral load of £50 copies /ml within 3-6 months. Once ARV therapy is initiated, the viral load < 1000 copies /m/ must be achieved within 4 weeks if treatment is adequate. CDC count should be measured at 12 weeks & then at 3 monthly intervals. 2 NRTI (tenofovir / emtricitabine) NNRTIs (efaviren 2) 2 NRTIS (tenofovir / emtricitabine) Pi (darunavir / ritonavir). Alternative regimen 3 NRTIs usually not recommended except for patients with low except viral load & major adherence concern.

30. Prevention & Control The development of an effective vaccine against this is being purisued , so far, no success has been made in this field. Education programs imparting knowledge & strategies are important to prevent Transmission of infection. Use of Condoms reduced the spread of infection. Use of clean needles & syringes & to prevent sharing of needles among drug abusers is important for prevention of AIDS. Screening of blood products has reduced HIV disease remarkably. The need for blood transfusion in developing countries could be reduced by improved control of conditions such malaria & hookworm which cause anemia. .

31. Availability & accessibility of HIV testing is important & provide an opportunity for individual health education & Risk of transmission POST EXPOSURE PROPHYLAXIS (PEP) Exposure to blood, body fluids, other potentially infected material on an instrument contaminated with one of these materials may lead to risk of acquiring HIV infection. The risk of infection varies with type of exposure & other factors. Following exposure, PEP required depending upon the category of exposure & HIV status of exposure source.

32. Two drug regimen Zidovudine 300 mg BD Lamivudine 150 mg BD. Protease inhibitor (Iponavir400mg BD) 3 drug regimen. Ritonovir100 mg BD These drugs to be started within first 72 hours & ideally within 2 hours. PEP should continue for a period of 4 weeks. Besides PEP, injured site on the wound should be Thoroughly washed with soap & water.

33. HEPATITIS INTRODUCTION: It is an acute, inflammatory & infective infection. Caused by Hepatitis A, B, C, D & NANB Viruses. Dentists are 3-4 times more likely to be exposed to hepatitis than with general population. Types: Hepatitis A: Also called as infectious hepatitis - It is endemic & occurs in person who lives in poor living condition to spread of hepatitis A - by Oro fecal route. Hepatitis B: Also called serum hepatitis. It is transmitted by parenteral route for e.g.: blood & blood products, contaminated needles. Transmitted due to close contact .

34. Hepatitis C: It is responsible for sporadic viral hepatitis in intravenous drug users & in patient with renal dialysis Hepatitis D: It is called by Delta agents. It is incomplete. Virus carried within hepatitis B virus & will replicate in presence of HBsAg. Hepatitis G: Many of this patients’ infected with hepatitis C virus. It produces clinical symptoms less Severe to hepatitis C DE FINITION Hepatitis’s is an acute parenchymal disease of liver due to variety of causes in which variable number of hepatocytes undergo necrosis. These episodes are largely due to infective or toxic agents.

35. Classification Depending on the onset & Course of liver cell injury, hepatitis in classified into acute & chronic. ACUTE HEPATITIS Acute parenchymal disease of the liver evolving within hours, days to -few weeks is called acute hepatitis. Pathology: 3 stages can be recognized histopathologically in acute viral hepatitis, if disease is progressive. 1- Mild liver cells injury (inflammatory damage or liver cells necrosis)

36. There is wide spread liver cells damage predominantly in centrilobular zone's though individual lobules are Variably affected Damaged liver cells have swollen granular appearance, while damaged cells appear shrunken & deeply stained, may lose their nuclei to form eosinophilia bodies called councilman bodies. 2. More severe damage (sub-acute bridging necrosis) At this stage, there is collapse of reticulin supporting network between the central veins & portal tracts with the result that they become linked to each other called sub-acute bridging necrosis.

37. 3. Very severe damage - Destruction of lobules resulting in acute liver cell atrophy resulting in a lesion commonly seen in patients with acute fulminant hepatitis.

38. Causes : Infective causes Viral o Hepatitis A, B, C, D, E, o Cytomegalovirus, o Epstein Bari virus o Herpes simplex virus o Yellow fever virus. Post viral: Reyes syndrome Non-viral: leptospira Toxoplasma Non infective causes Drugs: Paracetamol, rifampicin, methyldopa Poisons: Carbon-tetrachloride Aflatoxin

39. Acute viral Hepatitis: Hepatitis A Introduction It is also called as Infectious hepatitis. It is a sub-acute disease occurring mainly in children & Young adults. It enters the body by oral route. The large majority of infections are asymptomatic .The clinical disease has 2 stages. Morphology HAV is 27nm non -enveloped single stranded RNA virus with an icosahedral symmetry belongs to pi coronavirus family.

40. Clinical features: A Prodromal symptoms: Occurs before the development of jaundice due to viremia. Fever, chills, headache, malaise, aches & pain & accompanied by Gastrointestinal symptoms, nausea, vomiting distaste for food & Smoking. B. Icteric phase: with clinical onset of Jaundice fever usually disappears along with other prodromal symptoms but weight loss liver is enlarged, tender & associated with right hypochondriac pain.

41. C. Recovery phase: occurs in all cases and takes 2-8 weeks - The prodromal symptoms disappear & Jaundice starts Digressing but lives enlargement & biochemical abnormalities persist Investigations - Rise in serum transaminases (SGOT & SGPT) starts during prodromal phase & maximum during icteric phase & fall during recovery phase. -Serum albumin levels are normal

42. Urobilinogen is increased in early phase disease. - Ultrasound of liver shows an enlarged liver with normal echo texture. -The Ig G type of antibodies in the absence of Ig M antibodies indicate previous HAV infection Or immunity. Prothrombin time normal in mild disease but gets prolonged in severe cases. - Serum alkaline phosphatase levels normal

43. Treatment : There is no specific therapy. Barrier nursing care should be enforced with proper disposal of urine & feces. Proper hand wash after each bowel evacuation is required Bed rest Diet: Good amount of protein intake should be encouraged. Drugs: No specific drug therapy Exercise, alcohol, hepatotoxic drugs should be avoided. Recovery occurs with rest & diet.

44. Prophylaxis: Isolation & proper disposal of faeces & urine Immune serum globulins (anti-HAV) have been employed in close contacts, pregnant women & in persons travelling to endemic areas. Vaccine for hepatitis A is available

45. HEPATITIS B Introduction It is caused by hepatitis B - The virus only replicate in the liver. Its route of transmission is parenteral mostly through infected blood & blood products. Hence called transfusion hepatitis. • Tattooing & acupuncture may also spread it as needles are reused. Perinatal transmission also occurs in infant born to HBsAg Carrier mothers to mothers suffering from acute HBV infection .

46. Clinical features: Transient rashes arthralgia, arthritis, myalgia, pneumonia agranulocytosis, aplastic anemia hemolytic anemia, glomerulonephritis Investigations Serum bilirubin is raised Serum enzymes (SPOT & SGPT) are raised, Serum alkaline phosphatase may or may not be raised depending on cholestasis, Plasma albumin may be low, but is usually normal Urine may contain excessive Urobilinogen but bile salts & bite pigments are absent. Prothrombin time may be normal

47. Treatment : It is similar to hepatitis. A. Strict isolation & barrier nursing care is Necessary. Disposable needles & Syringes should be used while taking blood samples or for Parenteral therapy. Prophylaxis A recombinant hepatitis B vaccine containing HBsAg capable of producing active immunization in 95%. of normal individuals. 3 injections of recombinant vaccine given IM at 0,1 & 6 months, gives protection over 90%.

48. Indications for hepatitis B Vaccination o Parenteral drug abusers o Male homosexuals o Close contacts of infected persons. o Patient receiving maintenance dialysis o Laboratory staff o Medical personnel o Paramedical (nursing staff.

49. HEPATITIS C Introduction : HCV is a single stranded RNA virus with 6. Genotypes. The diagnosis is made by presence of Antibodies to HCV in the serum. - It belongs to the family Flaviviridae. It is a 50- 60nm, virus with a linear single stranded RNA. Made of infections. It is transmitted by needle stick injuries, use of contaminated needles & syringes, transfusion of infected blood & blood products, & sexual intercourse, Maternal-neonatal transmission has also been reported.

50. Clinical features : Clinical infect on with hepatitis C it generally less severe, with milder symptoms, absent of less marked jaundice. Treatment: Interferon has been used in acute cases to prevent chronic disease. Patients with cc genotype & chronic hepatitis C patients respond to it. Duration of treatment depends on genotype Ribavirin may be added if HCV RNA fails to clear after 3 months therapy with interferon but some combine both at the start .

51. HEPATITIS D Introduction : HDV is a defective virus as it is dependent on the help en function of HBV for its replication & expression. It belongs to genus Delta virus. It is spherical, 36-80 mm diameter, RNA particle surrounded by HBsAg envelope. The genome is a single stranded Small circular molecule of RNA. It encodes its own nucleoprotein, the delta antigen or HD Ag, but the outer envelope of HDV is encoded by genome of HBV Co infecting the Same cell. HBV is necessary for the production of HDV virions.

52. Clinical features: HDV infection can occur in presence of HBV under two situations 1. Simultaneous infection with both HDV & HBV 2. Super infection of an HBsAg Carter by HDV. Transmission occurs parentally. Co infection with HBV & HDV results in hepatitis of increased severity than the disease caused by HBV alone.

53. Investigations: Diagnosis can be made by detecting Ig M anti-delta antibody in serum. ELISA & RIA kit are commercially available for detection of antibodies to HDV. •HDAg expressed in liver cell nuclei, where it can be detected by immunofluorescence. Prophylaxis : No specific prophylaxis exists, but immunization with the hepatitis B vaccine is effective because delta antigen cannot infect persons immune to HBV. Screening of blood donors for HBsAg will also limit blood borne HDV infection.

54. HEPATITIS E Introduction : Hepatitis E virus belongs to family Calciviridae & genus Calcivirus. They are spherical, non-enveloped & 27-38 nm in diameter. They posers single stranded RNA genome, which is surrounded by icosahedral capsid. Pathogenesis Hepatitis E has been shown to occur in epidemic endemic & sporadic forms almost exclusively in developing countries. It is primarily associated with ingestion of faecally contaminated drinking water.

55. Laboratory diagnosis: 1. Exclusion of hepatitis A & hepatitis B 2. .Immuno electron microscopy. 3. ELISA test & Western blot assay 4. Polymerase chain reaction Prophylaxis Hepatitis E can be prevented by: - Improved standards of sanitation Chlorinated water

56. ACUTE HEPATIC ENCEPHALOPATHY It is said to be present when a previously healthy person develops acute hepatitis & goes into hepatic encephalopathy within 8 weeks of illness. Cases that evolve at a slower pace within 8 weeks to 6 months are called sub-acute or sub fulminant hepatitis or hepatic failure. It is a life threatening syndrome characterized by fever, jaundice & mental features.

57. Causes: Acute viral hepatitis Drugs -all hepatotoxic drugs especially acetaminophen Pregnancy with hepatitis Wilson's disease Poisons- Carbon tetrachloride, phosphorus poisonous fungi. -Reyes syndrome. -Shock, hyperthermia

58. Pathology : There is extensive parenchymal necrosis of the liver. In acute fulminant hepatic failure, it is Estimated that only less than 30%. Liver cells appear viable. Fatty degeneration can be seen in hepatitis associated with pregnancy. Or Reye Syndrome.

59. Clinical features: - Poor alertness, disturbed Concentration, behavioral changes, drowsiness, confusion Jaundice Fetor hepaticas Flapping tremors liver dullness Bleeding diathesis Signs of portal hypertension: Ascites, edema Neurological manifestations: Cerebral edema, Hepatorenal syndrome.

60. DIFFERENCES BETWEEN ACUTE & CHRONIC HEPATIC ENCEPHALOPATHY. Onset acute, develops within 8 weeks - Insidious, occurs in pt. Chronic liver disease No preceding liver disease Pre-existing liver disease with or without signs of portal hypertension.   No precipitating illness of factor Precipitating factors include high protein diet, bleeding Sedatives, alcohol, hepatotoxic drugs Fulminant course slow insidious Course Requires vigorous therapy. Requires less vigorous therapy

61. Investigations o Bilirubin is raised. o Serum transaminases are raised o Serum albumin is usually normal to low o Prothrombin time may be prolonged in severe form of disease. o Leucocytosis without an evidence of infection o Urine may contain Urobilinogen, bilirubin o Serum ammonia levels are high.

62. Treatment: o No sedation is given unless the patient is violent. o Care of comatose patients. Care of back, bowel bladder, skin, respiration, pulse & BP. o IV Vit k, 10 mg daily for 3 days o IV Vit c 500mg daily o PTI is prolonged o IV H₂ blockers, ranitidine 50mg twice a day. o Penicillin c - Used for mushroom poisoning o Plasmapheresis with D penicillamine is given in Wilson’s disease.

63. CHRONIC HEPATITIS Chronic parenchymal disease manifests either as chronic hepatitis or cirrhosis of liver. Etiology: Infective: Hepatitis B, C, D Toxic: Drugs (alpha-methyldopa, isoniazid) Alcoholic steo hepatitis Nonalcoholic steo hepatitis Metabolic: Hemochromatosis Wilson's disease and alpha - antitrypsin deficiency. Unknown: Autoimmune hepatitis

64. Pathology: 1. Persistent hepatitis: It affects portal tracks only. There is infiltration by chronic inflammatory cells limited to portal tracts, but sometimes may extend into parenchyma. Changes in liver are absent or slight in the form of small of liver cell necrosis 2. Active hepatitis: There is involvement of both portal tracts & parenchyma, lobular architecture becomes distorted & cirrhosis develops with formation of regenerating nodules. o Piecemeal necrosis o Sub-acute bridging o Infiltration by chronic inflammatory cells

65. 3- Lobular hepatitis: Changes are identical to acute viral hepatitis. Diagnosis The diagnosis of chronic hepatitis should be made once liver disease has been present on clinical or biochemical parameters for at least 6 months & a liver biopsy is to be done for confirmation.

66. CHRONIC HEPATITIS B This type of hepatitis Occurs commonly in men over 30 years of age. It is considered present retrospectively when features of cirrhosis develop. In some cases, infection by pre-core mutant of HBV & spontaneous mutation of pre-core or core promoter region of HBV genome may result in chronic hepatitis called HBe Ag - negative hepatitis B. Clinical features: Nonspecific features include ill health, fatigue, and weakness Systemic features other than arthralgia. The physical signs include tender hepatomegaly as Abnormality.

67. Investigations: Moderate increase in serum bilirubin & transaminases. Hypoalbuminaemia is present, if disease is advanced. Hyperglobulinaemia is mild Liver biopsy Treatment : HBV DNA >105 copies/mL / 220,000 IVI positive in serum with elevated aminotransferase -treated with nucleoside or nucleotide analogue Pegylated Interferon- & 2 a Recombinant human interferon alpha

68. Prognosis The disease shows slow relentless progression in patients with evidence of active hepatitis B replication or combined hepatitis B&D infection. Leading eventually to cirrhosis & hepatocellular Carcinoma.

69. CHRONIC HEPATITIS C It is a mild illness & recognized only when a previous episode of hepatitis does not resolve completely within 12 weeks of fitness. It is characterized by malaise, fatigue, ill health, poor appetite. Upper abdominal pain over the liver. Treatment: Indicated for patients with chronic hepatitis C. On histology who have HCV RNA in their serum & have raised serum transaminases for more than 6 months. The presence of cirrhosis is no contraindication but decompensated cirrhotic patients should be considered for liver transplantation

70. - Recently, it has been recommended that patients infected with HCV genotype 2 or 3 may treated without a liver biopsy. Ribavirin well tolerated but dose related side effects such as hemolysis, pruritus & nasal congestion may occur.

71. CHRONIC AUTOIMMUNE HEPATITIS - Occurs commonly in women during 2 & 3rd decades of life & it produces the florid manifestations of disease, though milder cases also occur. Clinical manifestations: The disease presents in two peaks. One around menopause & second around 20-25 years. Patients in menopausal group are asymptomatic while second group with fatigue, anorexia jaundice. - Fever, arthralgia & epistaxis are common.

72. Investigations; o Raised serum bilirubin, globulins, and transaminases . o Auto antibodies are seen in high titers. o Anemia & thrombocytopenia may present. o Liver biopsy,

73. Treatment: o Corticosteroids & azathioprine o Prednisolone 30 mg/day – 2 weeks followed by maintenance dose of 10-15 mg/day along with azathioprine 1-2 mg/kg/day o Cyclosporine, Mycophenolate. o Liver transplantation - required in treatment failure cases & patients with fulminant o Hepatitis.