Chronic Viral Hepatitis - Part 1 - Kuwait

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  • The prevalence of disease was based on the NHANES III data. The analysis assumed a population distribution that matched the 1991 US population census estimates (the midpoint of the NHANES III study), which divided the 251 million Americans into 12 age groups. Because none of the patients younger than 6 years were tested for HCV antibodies, the computer simulation considered 9 age groups. The 30- to 39-year-old group had the highest prevalence of HCV antibody—3.9%, for an estimated 1.6 million HCV infected individuals. Among those who were antibody positive, an estimated 2.7 million people (70% of those infected) had detectable serum HCV RNA. Currently, persons aged 40 to 59 years have the highest prevalence of HCV infection, and in this age group, the prevalence is highest in African Americans (6.1 percent). However, uncertainty persists regarding its natural history and future health burden. In 1991, nearly 4 million Americans had antibody evidence of hepatitis C exposure. Computer projections corroborated CDC predictions that mortality from HCV-related liver disease may increase 2- to 3-fold over the next 10 to 20 years.
  • Based on studies conducted in the last decade since the publication by Kiyosawa et al., it has become possible to formulate an algorithm of the natural history of hepatitis C using data from a combination of prospective studies of posttransfusion and long-term follow-up of patients with established HCV infection. 75%-85% of patients will become chronically infected. Over a variable time period 10-20 years, 20% of patients will develop cirrhosis.
  • Based on studies conducted in the last decade since the publication by Kiyosawa et al., it has become possible to formulate an algorithm of the natural history of hepatitis C using data from a combination of prospective studies of posttransfusion and long-term follow-up of patients with established HCV infection. Of the 20% of cirrhotic patients, approximately 6% of patients can be expected to develop hepatic decompensation per year , 4% will develop HCC per year, and 3% to 4% per year can be expected to die or require liver transplantation.
  • HCV is usually only fatal when it leads to cirrhosis, the final stage of liver fibrosis. Therefore, an estimate of fibrosis progression represents an important surrogate end-point for the evaluation of the vulnerability of an individual patient. Progression of liver fibrosis in patients with chronic hepatitis C is variable. Using the median fibrosis progression rate, in untreated patients, the median expected time to cirrhosis was 30 years (intermediate progressors); 33% of patients had an expected median time to cirrhosis of less than 20 years (rapid progressors) and 31% will only progress to cirrhosis after more than 50 years, if ever (slow progressors). Several factors have been clearly shown to be associated with fibrosis progression rate including duration of infection, age, male gender, consumption of alcohol, HIV co-infection and low CD 4 count. The progression from infection to cirrhosis depends strongly on sex and age.
  • Factors Associated With Disease Progression Key Points Age older than 40 years, male gender, and consumption of alcohol are significant risk factors for fibrosis progression. An immunocompromised state, occurring secondary to HIV or HBV infection, also increases the risk for progression. Objective : To assess the natural history of liver fibrosis progression in patients with hepatitis C and determine the factors associated with this progression. Methods : Treatment-naïve patients with documented HCV and at least one liver biopsy were enrolled in the study. Fibrosis progression was defined as the ratio between fibrosis stage in METAVIR units and duration of infection. A 2-step process was used to identify factors associated with progression: analysis between progression and 9 risk factors, and analysis of the association between fibrosis stage and the risk factors. Results : A total of 2235 subjects participated in the study; among those for whom the duration of infection was known (1157), the mean rate of fibrosis progression was 0.252 (median, 0.133). The mean duration from infection to cirrhosis was 30 years. A highly statistically significant ( P <.0001) association was identified between stage of fibrosis and age at biopsy and duration of infection. Risk factors associated with fibrosis progression included consumption of alcohol daily ( P <.001), male gender ( P <.001), and infection occurring at age 40 years or older ( P <.001). Factors that were not associated with risk for progression were cause of infection, genotype, and viremia. Conclusion : Host factors—age, male gender, and alcohol consumption—have a stronger relationship with risk for fibrosis progression than virologic factors. Immunosuppression secondary to HIV coinfection and HBV, also increases the risk for progression, perhaps through immune dysfunction and/or direct cytotoxicity. References National Institutes of Health Consensus Development Conference Statement. Management of hepatitis C: 2002. Bethesda, Md: National Institutes of Health; June 10-12, 2002. Poynard T, Bedrossa P, Opolon P, for the OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC group. Randomised trial of interferon alfa-2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alfa-2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C. Lancet . 1997;349:825-832.
  • Utility of Liver Biopsy In the last 50 years, use of the liver biopsy has grown to serve multiple purposes: (1) confirmation of clinical diagnosis, (2) assessment of severity of necroinflammation and fibrosis, (3) evaluation of possible concomitant disease processes, and (4) assessment of therapeutic intervention. Liver biopsy remains the best method for assessing the severity of hepatitis C however remains controversial. For many clinicians, the histologic appearance of the liver substantially influences the decision of whom to treat and whether to continue treatment in patients with non-life threatening adverse reactions. The findings may also serve as a baseline in establishing extent of liver damage and determining the prognosis. Although the current guidelines for use of biopsy are controversial, as therapy becomes more successful and safer, it is likely that HCV-infected persons will routinely be started on therapy without biopsy. If necessary, patient may be referred to a radiologist for the liver biopsy. Reference Brunt E. Grading and staging the histopathological lesions of chronic hepatitis: the Knodell histology activity index and beyond. Hepatology. 2000;31:241-246.
  • Utility of Liver Biopsy In the last 50 years, use of the liver biopsy has grown to serve multiple purposes: (1) confirmation of clinical diagnosis, (2) assessment of severity of necroinflammation and fibrosis, (3) evaluation of possible concomitant disease processes, and (4) assessment of therapeutic intervention. Liver biopsy remains the best method for assessing the severity of hepatitis C however remains controversial. For many clinicians, the histologic appearance of the liver substantially influences the decision of whom to treat and whether to continue treatment in patients with non-life threatening adverse reactions. The findings may also serve as a baseline in establishing extent of liver damage and determining the prognosis. Although the current guidelines for use of biopsy are controversial, as therapy becomes more successful and safer, it is likely that HCV-infected persons will routinely be started on therapy without biopsy. If necessary, patient may be referred to a radiologist for the liver biopsy. Reference Brunt E. Grading and staging the histopathological lesions of chronic hepatitis: the Knodell histology activity index and beyond. Hepatology. 2000;31:241-246.
  • Chronic Viral Hepatitis - Part 1 - Kuwait

    1. 1. Neil D. Theise, MD Depts. of Pathology and Medicine (Digestive Diseases) Beth Israel Medical Center – Albert Einstein College of Medicine New York City www.neiltheise.com Chronic Viral Hepatitis
    2. 2. Neil D. Theise, MD Depts. of Pathology and Medicine (Digestive Diseases) Beth Israel Medical Center – Albert Einstein College of Medicine New York City SLIDESHARE.NET www.neiltheise.com See: “Chronic Viral Hepatitis: A Personal, Practical Guide” Chronic Viral Hepatitis
    3. 3. <ul><li>The Viruses </li></ul><ul><li>Clinical Aspects </li></ul><ul><li>Role of Liver Biopsy, part 1 </li></ul><ul><li>Histologic/Immunostaining features </li></ul>
    4. 4. <ul><li>The Viruses </li></ul><ul><li>Clinical Aspects </li></ul><ul><li>Role of Liver Biopsy, part 1 </li></ul><ul><li>Histologic/Immunostaining features </li></ul>
    5. 5. A C U T E
    6. 6. A C U T E HAV HEV
    7. 7. A C U T E HAV HEV Incidence in Kuwait: 13/100,000 Incidence in Kuwait: 1.4/100,000 RATE OF SPORADIC ENTERICALLY TRANSMITTED VIRAL HEPATITIS IN KUWAIT BETWEEN 1998 AND 2001 AQ Al-Anezi, R Al-Awayesh, F Al-Ali, KM Peltekian Kuwait Health Sciences Centre, Kuwait City, Kuwait & Division of Gastroenterology, Dalhousie University, Halifax, Nova Scotia
    8. 8. C H R O N I C
    9. 9. C O N S O N A N T S H R O N I C
    10. 10. HBV HCV HDV C O N S O N A N T S H R O N I C
    11. 11. HBV HCV HDV Prevalence: 4.6% Prevalence of Hepatitis B and C infection in patients admitted at Tertiary Eye Care Centre: A hospital based study. Junejo SA, Khan NA, Lodhi AA. Pak J Med Sci 2009;25(4):597-600. Prevalence: 13% C O N S O N A N T S H R O N I C
    12. 12. HBV HCV HDV Prevalence of Hepatitis B and C infection in patients admitted at Tertiary Eye Care Centre: A hospital based study. Junejo SA, Khan NA, Lodhi AA. Pak J Med Sci 2009;25(4):597-600. Prevalence of co-infection: 3.9% C O N S O N A N T S H R O N I C
    13. 14. HBV HCV HDV Prevalence: 4% in acute HBV 31% in chronic HBV C O N S O N A N T S H R O N I C Hepatitis delta virus infection in acute hepatitis in Kuwait. Al-Kandari S, Nordenfelt E, Al-Nakib B, Hansson BG, Ljunggren K, Al-Nakib Scand J Infect Dis. 1988;20(1):15-9.
    14. 15. <ul><li>The Viruses </li></ul><ul><li>Clinical Aspects </li></ul><ul><li>Role of Liver Biopsy, Part 1 </li></ul><ul><li>Histologic/Immunostaining features </li></ul>
    15. 16. Prevalence of HCV Antibody NHANES III Adapted from Alter MJ, et al.,. N Engl J Med. 1999;341:556–562. 0 500,000 1,000,000 1,500,000 2,000,000 Prevalence 6-11 12-19 20-29 30-39 40-49 50-59 60-69 70-79 80+ Age distribution 90s 00s
    16. 17. Natural History of Hepatitis C Acute Hepatitis C Chronic Hepatitis 75%- 85 % Cirrhosis 20 % 10-20+ years - Hoofnagle JH, Hepatology. 1997 - Di Bisceglie A, Hepatology, 2000
    17. 18. Decompensation, 6% HCC, 4% Death or Tx, 4% Annual rate - Hoofnagle JH, Hepatology. 1997 - Di Bisceglie A, Hepatology, 2000 Natural History of Hepatitis C Cirrhosis, 20 %
    18. 19. Liver Fibrosis in Chronic Hepatitis C Intermediate progressors Slow progressors Poynard et al, Hepatology 1999 n=1157 0 1 2 3 4 0 10 20 30 40 50 Years F Metavir Rapid progressors
    19. 20. Factors Associated with Disease Progression <ul><li>Alcohol consumption </li></ul><ul><ul><li>30 g/day in men </li></ul></ul><ul><ul><li>20 g/day in women </li></ul></ul><ul><li>Disease acquisition at >40 years </li></ul><ul><li>Male gender </li></ul><ul><li>HIV co-infection (treated vs. untreated) </li></ul><ul><li>Fatty liver </li></ul><ul><li>Hepatitis B virus co-infection </li></ul><ul><li>Immunosuppression </li></ul>NIH Consensus Development Conference Statement. 2002. Poynard et al. Lancet. 1997;349:825-832. ~ 2 drinks per day
    20. 21. Natural History of Chronic Liver Disease Chronic hepatitis with fibrosis 10-50 years Cirrhosis Normal liver Hepatocellular Carcnoma
    21. 22. <ul><li>The Viruses </li></ul><ul><li>Clinical Aspects </li></ul><ul><li>Role of Liver Biopsy, Part 1 </li></ul><ul><li>Histologic/Immunostaining features </li></ul>
    22. 23. Role of Liver Biopsy <ul><li>Confirm clinical diagnosis </li></ul>
    23. 24. Role of Liver Biopsy <ul><li>Confirm clinical diagnosis </li></ul>Grade necroinflammation Stage fibrosis
    24. 25. The Normal Liver Lobule:
    25. 27. The Limiting Plate
    26. 28. Portal inflammation DEFINES Chronic Hepatitis
    27. 31. “ Piecemeal Necrosis” or, better, “ Interface Hepatitis”
    28. 35. Chronic Persistent Hepatitis
    29. 36. Chronic Active Hepatitis
    30. 37. Chronic Lobular Hepatitis
    31. 40. Recovery Death/Transplant Chronic Hepatitis CPH CAH CLH
    32. 41. Recovery Death/Transplant Chronic Hepatitis CPH CAH CLH Cirrhosis Progression Unlikely
    33. 42. Recovery Death/Transplant Chronic Hepatitis CPH CAH CLH Cirrhosis Progression Unlikely
    34. 43. <ul><li>Gnomes’ clinical problems: </li></ul><ul><ul><ul><ul><ul><li>Chronic hepatitis B </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Autoimmune hepatitis </li></ul></ul></ul></ul></ul>1968
    35. 44. <ul><li>Gnomes’ clinical problems: </li></ul><ul><ul><ul><ul><ul><li>Chronic hepatitis B </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Autoimmune hepatitis </li></ul></ul></ul></ul></ul><ul><li>Contemporary clinical problems: </li></ul><ul><ul><ul><ul><ul><li>Chronic hepatitis C </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Mixed viral infections </li></ul></ul></ul></ul></ul>1968 1990’s
    36. 45. Recovery Death/Transplant Chronic Hepatitis CPH CAH CLH Cirrhosis Progression Unlikely
    37. 46. Recovery Death/Transplant Chronic Hepatitis STAGING Of Progression GRADING Of Activity
    38. 47. GRADING Of Activity <ul><li>Portal inflammation </li></ul><ul><li>Interface hepatitis </li></ul><ul><li>Lobular hepatitis </li></ul><ul><li>Confluent necrosis </li></ul>
    39. 48. GRADING Of Activity <ul><li>Portal inflammation </li></ul><ul><li>Interface hepatitis </li></ul><ul><li>Lobular hepatitis </li></ul><ul><li>Confluent necrosis </li></ul>
    40. 49. GRADING Of Activity <ul><li>Portal inflammation </li></ul><ul><li>Interface hepatitis </li></ul><ul><li>Lobular hepatitis </li></ul><ul><li>Confluent necrosis </li></ul>
    41. 50. GRADING Of Activity <ul><li>Portal inflammation </li></ul><ul><li>Interface hepatitis </li></ul><ul><li>Lobular hepatitis </li></ul><ul><li>Confluent necrosis </li></ul>
    42. 51. Confluent Necrosis
    43. 52. Confluent Necrosis
    44. 53. Confluent Necrosis
    45. 55. Bridging confluent necrosis
    46. 56. Confluent necrosis, think about: - HBeAg to Ab conversion - HDV super-infection on HBV - HCV acute exacerbation - HIV co-infection - Autoimmune hepatitis - Drug induced injury, as always
    47. 57. LIVER: NEEDLE BIOPSY - Chronic hepatitis, ………. active with……. (stage …/4), compatible with hepatitis C. Comment: A. Interface hepatitis: Absent (0/4). A. Interface hepatitis: Focal, few portal areas (1/4). A. Interface hepatitis: Focal, most portal areas, >5-50% (2/4). A. Interface hepatitis: Continuous around <50% of tracts/septa (3/4). A. Interface hepatitis: Continuous around >50% of tracts/septa (4/4). B. Confluent necrosis: Absent (0/6). B. Confluent necrosis: Focal (1/6). B. Confluent necrosis: Zone 3 necrosis in some areas (2/6). B. Confluent necrosis: Zone 3 necrosis in most areas (3/6). B. Confluent necrosis: Occasional portal-central bridging necrosis (4/6). B. Confluent necrosis: Frequent portal-central bridging necrosis (5/6). B. Confluent necrosis: Panacinar or multiacinar collapse (6/6). C. Lobular necrosis or inflammation: Absent (0/4) C. Lobular necrosis or inflammation: < 1 focus per acinus (1/4) C. Lobular necrosis or inflammation: 2-4 foci per acinus or nodule (2/4). C. Lobular necrosis or inflammation: 5-10 foci per acinus or nodule (3/4). C. Lobular necrosis or inflammation: >10 foci per acinus nodule (4/4). D. Portal inflammation: None (0/4). D. Portal inflammation: Mild, some or all portal tracats (1/4). D. Portal inflammation: Moderate, some or all portal areas (2/4). D. Portal inflammation: Marked, not all portal areas (3/4). D. Portal inflammation: Marked, all portal areas (4/4). E. Staging: No fibrosis (0/4). E. Staging: Fibrous portal enlargement (1/4). E. Staging: Fibrous septa (2/4). E. Staging: Transition to cirrhosis (3/4). E. Staging: Cirrhosis (4/4).
    48. 58. No fibrosis 0 Fibrous expansion of some portal areas, with or without short fibrous septa 1 Fibrous expansion of most portal areas, with or without short fibrous septa 2 Fibrous expansion of most portal areas, with occasional portal to portal bridging 3 Fibrous expansion of portal areas with marked bridging portal-portal and/or portal-central 4 Marked bridging (portal-portal and/or portal-central) with occasional nodules (incomplete cirrhosis) 5 Cirrhosis, probable or definite 6 So what do I do…?
    49. 59. LIVER: NEEDLE BIOPSY - Chronic hepatitis, ………. active with……. (stage …/4), compatible with hepatitis C. Comment: A. Interface hepatitis: Absent (0/4). A. Interface hepatitis: Focal, few portal areas (1/4). A. Interface hepatitis: Focal, most portal areas, >5-50% (2/4). A. Interface hepatitis: Continuous around <50% of tracts/septa (3/4). A. Interface hepatitis: Continuous around >50% of tracts/septa (4/4). B. Confluent necrosis: Absent (0/6). B. Confluent necrosis: Focal (1/6). B. Confluent necrosis: Zone 3 necrosis in some areas (2/6). B. Confluent necrosis: Zone 3 necrosis in most areas (3/6). B. Confluent necrosis: Occasional portal-central bridging necrosis (4/6). B. Confluent necrosis: Frequent portal-central bridging necrosis (5/6). B. Confluent necrosis: Panacinar or multiacinar collapse (6/6). C. Lobular necrosis or inflammation: Absent (0/4) C. Lobular necrosis or inflammation: < 1 focus per acinus (1/4) C. Lobular necrosis or inflammation: 2-4 foci per acinus or nodule (2/4). C. Lobular necrosis or inflammation: 5-10 foci per acinus or nodule (3/4). C. Lobular necrosis or inflammation: >10 foci per acinus nodule (4/4). D. Portal inflammation: None (0/4). D. Portal inflammation: Mild, some or all portal tracats (1/4). D. Portal inflammation: Moderate, some or all portal areas (2/4). D. Portal inflammation: Marked, not all portal areas (3/4). D. Portal inflammation: Marked, all portal areas (4/4). E. Staging: No fibrosis (0/4). E. Staging: Fibrous portal enlargement (1/4). E. Staging: Fibrous septa (2/4). E. Staging: Transition to cirrhosis (3/4). E. Staging: Cirrhosis (4/4).
    50. 60. LIVER: NEEDLE BIOPSY - Chronic hepatitis, ………. active with……. (stage …/4), compatible with hepatitis C. Comment: A. Interface hepatitis: Absent (0/4). A. Interface hepatitis: Focal, few portal areas (1/4). A. Interface hepatitis: Focal, most portal areas, >5-50% (2/4). A. Interface hepatitis: Continuous around <50% of tracts/septa (3/4). A. Interface hepatitis: Continuous around >50% of tracts/septa (4/4). B. Confluent necrosis: Absent (0/6). B. Confluent necrosis: Focal (1/6). B. Confluent necrosis: Zone 3 necrosis in some areas (2/6). B. Confluent necrosis: Zone 3 necrosis in most areas (3/6). B. Confluent necrosis: Occasional portal-central bridging necrosis (4/6). B. Confluent necrosis: Frequent portal-central bridging necrosis (5/6). B. Confluent necrosis: Panacinar or multiacinar collapse (6/6). C. Lobular necrosis or inflammation: Absent (0/4) C. Lobular necrosis or inflammation: < 1 focus per acinus (1/4) C. Lobular necrosis or inflammation: 2-4 foci per acinus or nodule (2/4). C. Lobular necrosis or inflammation: 5-10 foci per acinus or nodule (3/4). C. Lobular necrosis or inflammation: >10 foci per acinus nodule (4/4). D. Portal inflammation: None (0/4). D. Portal inflammation: Mild, some or all portal tracats (1/4). D. Portal inflammation: Moderate, some or all portal areas (2/4). D. Portal inflammation: Marked, not all portal areas (3/4). D. Portal inflammation: Marked, all portal areas (4/4). E. Staging: No fibrosis (0/4). E. Staging: Fibrous portal enlargement (1/4). E. Staging: Fibrous septa (2/4). E. Staging: Transition to cirrhosis (3/4). E. Staging: Cirrhosis (4/4). Mild Moderate Severe
    51. 61. STAGING
    52. 70. No fibrosis 0 Fibrous expansion of some portal areas, with or without short fibrous septa 1 Fibrous expansion of most portal areas, with or without short fibrous septa 2 Fibrous expansion of most portal areas, with occasional portal to portal bridging 3 Fibrous expansion of portal areas with marked bridging portal-portal and/or portal-central 4 Marked bridging (portal-portal and/or portal-central) with occasional nodules (incomplete cirrhosis) 5 Cirrhosis, probable or definite 6 No fibrosis 0 Fibrous expansion of some portal areas, with or without short fibrous septa 1 Fibrous expansion of most portal areas, with or without short fibrous septa 2 Fibrous expansion of most portal areas, with occasional portal to portal bridging 3 Fibrous expansion of portal areas with marked bridging, portal-portal and/or portal-central 4 Marked bridging (portal-portal and/or portal-central) with occasional nodules (incomplete cirrhosis) 5 Cirrhosis, probable or definite 6 Ishak et al. staging scheme
    53. 71. No fibrosis 0 Fibrous expansion of some portal areas, with or without short fibrous septa 1 Fibrous expansion of most portal areas, with or without short fibrous septa 2 Fibrous expansion of most portal areas, with occasional portal to portal bridging 3 Fibrous expansion of portal areas with marked bridging portal-portal and/or portal-central 4 Marked bridging (portal-portal and/or portal-central) with occasional nodules (incomplete cirrhosis) 5 Cirrhosis, probable or definite 6 No fibrosis 0 Portal fibrosis 1 Focal Septa 2 Frequent septa 3 Cirrhosis, probable or definite 4 METAVIR staging
    54. 72. No fibrosis 0 Portal fibrosis 1 Focal Septa 2 Frequent septa 3 ? Cirrhosis, probable or definite 4 METAVIR staging ?
    55. 73. No fibrosis 0 Fibrous expansion of some portal areas, with or without short fibrous septa 1 Fibrous expansion of most portal areas, with or without short fibrous septa 2 Fibrous expansion of most portal areas, with occasional portal to portal bridging 3 Fibrous expansion of portal areas with marked bridging portal-portal and/or portal-central 4 Marked bridging (portal-portal and/or portal-central) with occasional nodules (incomplete cirrhosis) 5 Cirrhosis, probable or definite 6 So what do I do…?
    56. 74. No fibrosis 0 Focal portal fibrosis, w or w/o short fibrous septa 1 Widespread portal fibrosis, w or w/o short fibrous septa 2 Focal portal-portal septa 3 Frequent septa (portal-central and/or portal portal) 4 Marked septa with occasional nodules 5 Cirrhosis, probable or definite 6 No fibrosis 0 Portal fibrosis 1 Focal Septa 2 Transition to cirrhosis 3 Cirrhosis, probable or definite 4 Theise modification of Ishak staging ? Ishak et al. staging scheme
    57. 75. Stages of Fibrosis 5 6 1 2 focal frequent 1 2 3 4 Portal Fibosis Fibrous Septa Transition to Cirrhosis Cirrhosis 1 4 2 3 focal frequent Metavir Theise ND. Human Pathology 2007 Modified Ishak  Batts-Ludwig 3 4 focal frequent Ishak
    58. 76. How much tissue is enough?
    59. 77. How much tissue is enough? 1.8 cm? 2.2 cm? 2.5 cm?
    60. 78. How much tissue is enough? 1.8 cm? 2.2 cm? 2.5 cm? How much is too little???
    61. 79. Case 1A 34 year old woman Hepatitis C positive; biopsy for staging and grading.
    62. 80. Case 1A, 4x, H&E
    63. 81. Case 1A, 4x, H&E
    64. 82. Case 1A, 4x, H&E
    65. 83. Case 1A, 4x, Trichrome
    66. 84. Case 1A, 4x, Trichrome
    67. 85. Case 1A, 10x, Trichrome
    68. 86. For example: LIVER: NEEDLE BIOPSY - Chronic hepatitis, mildly active with transition to cirrhosis (modified Ishak stage 3/4), compatible with hepatitis C.
    69. 87. For example: LIVER: NEEDLE BIOPSY - Chronic hepatitis, mildly active with transition to cirrhosis (modified Ishak stage 3/4), compatible with hepatitis C. Comment: There is a mild to moderate portal/septal mononuclear infiltrate associated with widespread interface hepatitis and focal lobular hepatitis.
    70. 88. For example: LIVER: NEEDLE BIOPSY - Chronic hepatitis, mildly active with transition to cirrhosis (modified Ishak stage 3/4), compatible with hepatitis C. Comment: There is a mild to moderate portal/septal mononuclear infiltrate associated with widespread interface hepatitis and focal lobular hepatitis. There is no confluent necrosis.
    71. 89. For example: LIVER: NEEDLE BIOPSY - Chronic hepatitis, moderately active with transition to cirrhosis (modified Ishak stage 3/4), compatible with hepatitis C. Comment: There is a mild to moderate portal/septal mononuclear infiltrate associated with widespread interface hepatitis and focal lobular hepatitis. There is no confluent necrosis. Trichrome and reticulin stains highlight focal fibrous septa, and focal nodularity Indicative of cirrhosis.
    72. 90. For example: LIVER: NEEDLE BIOPSY - Chronic hepatitis, moderately active with transition to cirrhosis (modified Ishak stage 3/4), compatible with hepatitis C. Comment: There is a mild to moderate portal/septal mononuclear infiltrate associated with widespread interface hepatitis and focal lobular hepatitis. There is no confluent necrosis. Trichrome and reticulin stains highlight focal fibrous septa, and focal nodularity Indicative of cirrhosis. There is focal steatosis in a pattern typical of that seen with chronic hepatitis C.
    73. 91. For example: LIVER: NEEDLE BIOPSY - Chronic hepatitis, moderately active with transition to cirrhosis (modified Ishak stage 3/4), compatible with hepatitis C. Comment: There is a mild to moderate portal/septal mononuclear infiltrate associated with widespread interface hepatitis and focal lobular hepatitis. There is no confluent necrosis. Trichrome and reticulin stains highlight focal fibrous septa, and focal nodularity Indicative of cirrhosis. There is focal steatosis in a pattern typical of that seen with chronic hepatitis C. No significant hemosiderosis or alpha-1-antitrypsin globules are identified (iron, PAS-D stains).
    74. 92. For example: LIVER: NEEDLE BIOPSY - Chronic hepatitis, moderately active with transition to cirrhosis (modified Ishak stage 3/4), compatible with hepatitis C. Comment: There is a mild to moderate portal/septal mononuclear infiltrate associated with widespread interface hepatitis and focal lobular hepatitis. There is no confluent necrosis. Trichrome and reticulin stains highlight focal fibrous septa, and focal nodularity Indicative of cirrhosis. There is focal steatosis in a pattern typical of that seen with chronic hepatitis C. No significant hemosiderosis or alpha-1-antitrypsin globules are identified (iron, PAS-D stains).
    75. 93. Case 1B 47 year old man Hepatitis C positive; ultrasound guided biopsy of left lobe, for staging and grading.
    76. 94. Case 1B, 2x, H&E GLISSON’S CAPSULE
    77. 95. Case 1B, 4x, H&E SUBCAPSULAR ZONE
    78. 96. Case 1B, 2x, H&E
    79. 97. Case 1B, 2x, H&E
    80. 98. LIVER: NEEDLE BIOPSY - Chronic hepatitis, mildly active with portal fibrosis (modified Ishak stage 1/4), compatible with hepatitis C.
    81. 99. <ul><li>The Viruses </li></ul><ul><li>Clinical Aspects </li></ul><ul><li>Role of Liver Biopsy, Part 1 </li></ul><ul><li>Histologic/Immunostaining features </li></ul>
    82. 100. HBV: Ground glass hepatocytes
    83. 101. HBV: Ground glass cells (surface antigen inclusions)
    84. 102. Immunostain: HBV Surface Antigen
    85. 103. HCV: lymphoid aggregates
    86. 104. Plasma cells in Autoimmune Hepatitis
    87. 105. Mixed Viral Infections
    88. 106. HBV + ? = utility of immunostains for HBV core Ag
    89. 107. Immunostain for HBcAG: Confirms active viral replication
    90. 108. Another example: LIVER: NEEDLE BIOPSY - Chronic hepatitis B, mildly active with transition to cirrhosis (stage 3/4). Comment: … .Ground glass hepatocytes (or immunostains for HBV surface antigen) confirm chronic hepatitis B virus infection. Immunostain for core antigen confirms hepatitis B viral replication….
    91. 109. No HBcAg Suspect: HBV DNA neg., Spontaneously resolved or treated infection or sampling or Co-infection with HCV,HDV
    92. 111. Diffuse HBcAg Suspect: Immunosuppression, in particular: HBV + HIV!!!
    93. 112. HCV + HIV? Increased Activity Decreased Activity Increase rate of progression Decreased rate of progression
    94. 113. HCV + HIV? On HAART: In large cohorts, possibly more aggressive, but individual biopsies look the same as HCV alone. Beware: drug toxicity
    95. 114. HCV + HIV? Untreated: Often more severe activity. Often more advanced disease.
    96. 115. HCV + HIV? Untreated: Often more severe activity. Often more advanced disease. Rare: fibrosing cholestatic hepatitis
    97. 116. HCV + HIV? Untreated: Often more severe activity. Often more advanced disease. Rare: fibrosing cholestatic hepatitis Beware: Infiltrating neoplasms, granulomas, HSV, CMV, biliary tract disease, etc.
    98. 117. ? Home Work

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