Contributed by Anthony J. Demetris, M.D.
PATIENT HISTORY:
Per referral report, the patient is an elderly male. S/P liver transplant for end stage liver disease secondary to hepatocellular carcinoma and cirrhosis--HCV related. The patient underwent liver biopsy because of a progressive increase of liver function tests. The diagnosis was: Changes consistent with drug toxicity (secondary to azathioprine). The patient was getting better after suspension of azathioprine. That confirmed the histological diagnosis. Recent history of elevated liver function tests. The patient is HCV-RNA positive. He is no longer receiving the drug. PRE-OP DIAGNOSIS: Elevated liver function tests. POST-OP DIAGNOSIS: Rule out chronic rejection. PROCEDURE: Liver biopsy.

Final Diagnosis (Case 75)


PART 1:
ALLOGRAFT LIVER, NEEDLE BIOPSY (Part 1) -
  1. PORTAL AND LOBULAR INFLAMMATION CONSISTENT WITH RECURRENCE OF CHRONIC HEPATITIS, VIRUS TYPE C INFECTION, WITH LOW-GRADE ACTIVITY (HAI=1+1+3+1=6/22).
  2. MINIMAL TO NO EVIDENCE OF ACUTE OR CHRONIC REJECTION.

    PART 2:
    ALLOGRAFT LIVER, NEEDLE BIOPSY (Part 2) -

    1. MILD LOBULAR DISARRAY, HEPATOCYTE SWELLING AND SPOTTY ACIDOPHILIC HEPATOCYTE NECROSIS(see microscopic description).
    2. MILD CENTRILOBULAR PIGMENT LADENED MACROPHAGE DEPOSITION.

    Previous Biopsies on this Patient:
    None

    TPIS Related Resources:
    Liver Transplant Topics

    Gross Description (Case 75)


    The specimen consists of nine (9) consult slides with an accompanying surgical pathology report.

    Microscopic Description (Case 75)


    Part 1:
    (1 HE, 1 PAS, 1 Reticulin, 1 CAM5.2, 2 Blanks)
    The normal lobular architecture is distorted because of mild portal expansion, because of mild mononuclear inflammation and mild cholangiolar reactivity. No bile duct damage, nor bile duct loss nor portal venulitis is seen. Within most of the portal tracts, clusters of pigment-laden macrophage deposition are appreciated. The presence of intact bile ducts is confirmed by CAM5.2 staining.

    Throughout the lobule, there is mild disarray with moderate spotty acidophilic necrosis of hepatocytes, sinusoidal lymphocytosis and occasional ceroid-ladened macrophages. No ground glass cells or viral inclusions are seen. No large PAS/D- positive globules are present. The reticulin stain confirms the mildly distorted architecture.

    Overall, the biopsy has the histopathological appearance of chronic hepatitis with low-grade activity, consistent with recurrent viral type C. Compared to the previous biopsy (Part 2), the hepatitis seems to be more advanced because of the appearance in the recent biopsy of chronic portal inflammation, without duct damage or venulitis. Although there is no significant rejection activity at this time, clinical follow up with liver injury tests (particularly gamma glutamyltranspeptidase and ALT) and possibly re-biopsy, if indicated, are suggested. The Knodell score is assessed as follows:

    KNODELL'S HISTOLOGY ACTIVITY INDEX
    Feature RANGE SCORE
    Periportal and bridging necrosis (0-10) 1
    Intralobular degeneration and necrosis (0-4) 1
    Portal inflammation (0-4) 3
    Fibrosis (0-4) 1
    TOTAL (0-22) 6/22

    The numerical scoring system of histologic activity index (HAI) has been developed to grade the liver biopsies of chronic active hepatitis. This is based on four categories of periportal and bridging necrosis, intralobular degeneration and necrosis, portal inflammation and fibrosis, with total score of up to 22. This scoring system is correlated well with the severity of disease. A copy of the original paper published by the American Association for the Study of Liver Disease [Hepatology 1:431, 1981] is available at the Department of Pathology upon request.

    The numerical scoring system of histologic activity index (HAI) has been developed to grade the liver biopsies of chronic active hepatitis. This is based on four categories of periportal and bridging necrosis, intralobular degeneration and necrosis, portal inflammation and fibrosis, with total score of up to 22. This scoring system is correlated well with the severity of disease. A copy of the original paper published by the American Association for the Study of Liver Disease [Hepatology 1:431 (1981)] is available at the Department of Pathology upon request.

    Part 2:
    (1 HE)
    The normal liver architecture is intact. Eight portal tracts are identified, all of which are free of inflammation. Bile duct are present in normal numbers and are intact.

    Throughout the lobule, there is mild spotty acidophilic necrosis of hepatocytes. Marked golden green pigment deposition is seen in centrilobular hepatocytes and macrophages. Diffuse hepatocellular swelling is also appreciated.

    Overall, the histopathological changes are not specific for a particular etiology, but are suggestive of early recurrent type C viral hepatitis. Azathioprine treatment might also have contributed to the changes, because withdrawal of the agent apparently resulted in improvement of the liver injury test results.

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