Liver biopsy interpretation
Transcript of Liver biopsy interpretation
![Page 1: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/1.jpg)
Liver biopsy interpretation
Presenter - Dr. Dhanya A N Moderator – Dr. Ramesh S T
![Page 2: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/2.jpg)
Contents • Indications of liver biopsy • Lab investigations • Techniques of liver biopsy • Needles of liver biopsy• Processing and staining • Normal histology • Approach to liver biopsy interpretation • Interpretation of different pathological
conditions
![Page 3: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/3.jpg)
Indications of liver biopsy
• Make or confirm the diagnosis
• Assess the severity of liver damage
• Assess the prognosis of a given case
• Monitor the response to the treatment
![Page 4: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/4.jpg)
Clinical and lab investigations
• History and general physical examination • Lab investigation
– Liver function tests – CBC– Prothrombin time, aPTT – Bleeding time – Clotting time – USG,CT, MRI
![Page 5: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/5.jpg)
Liver function tests • Hepatic integrity
– Serum aspartate aminotransferase– Serum alanine aminotransferase– Serum lactate dehydrogenase
• Biliary excretory functions– Serum bilirubin– Serum alkaline transferase – gamma glutamyl transferase
• Hepatocyte synthetic function– Serum proteins– Coagulation proteins – Serum ammonia
![Page 6: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/6.jpg)
Techniques of liver biopsy 1. Percutaneous - Transthoracic
– Subcostal • Blind procedure • Image guided – USG, CT,
MRI• Plugged liver biopsy
– Gelatin, gel foam plugged
![Page 7: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/7.jpg)
2. Transvenous (Transjugular)
• Done in coagulation disorders or ascites
• Performed in a vascular catheterisation laboratory with videofluoroscopy equipment and proper cardiac monitoring
![Page 8: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/8.jpg)
3. Laparoscopic liver biopsy
• Transvenous liver biopsy is not available,
• In patients who have a combination of a focal liver lesion and a coagulopathy.
![Page 9: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/9.jpg)
Needles for liver biopsy
Broadly classified into • Suction needles
– Menghini, – Klatskin,
• Cutting needles – Vim-Silverman, – Tru-cut (commonly used)
• Spring-loaded cutting needles that have a triggering mechanism.
![Page 10: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/10.jpg)
![Page 11: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/11.jpg)
Vim silverman needle
![Page 12: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/12.jpg)
Tru cut needle
![Page 13: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/13.jpg)
Processing the sample
• Place on the filter paper • Fix immediately
– Buffered formalin (routine)– Alcohol (glycogen storage disorder)– 2.5% buffered gluteraldehyde (for EM)– Frozen sections (for fat)
• Fix overnight • Take sections • Stain
![Page 14: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/14.jpg)
Special stains
Masson trichrome, stains blue color to collagen and red color to hepatocyes H & E stain of hepatic lobule
![Page 15: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/15.jpg)
Special stains
Perls prussian blue for iron, heoatocytes have taken the blue stain
PAS positive in glycogen storage right side and after treating it with diastase, left side
![Page 16: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/16.jpg)
Special stains
PAS+diastase for aplha1 antitrypsin deficiencyHapatocytes have taken magenta color
Oil Red O stain highlighting fat globules in a frozen section of theliver.
![Page 17: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/17.jpg)
Special stains
Rhodanin stain for copper, hepatocytes have taken orange red color in the upper nodule
Congo red stain orange-staining of vascular amyloid deposition,characteristic apple-green birefringence under polarizedmicroscopy (inset)
![Page 18: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/18.jpg)
Special stains
Orcein stain for elastic fibres is positive in two portal tracts (P) but not in the intervening area of collapse. A necrotic bridge (arrow) is also negative. Inset: This contrasts with an elastic fibre-rich septum in chronic liver disease.
PP
Reticulin stain of micronodular cirrhosisStains collagen
![Page 19: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/19.jpg)
Adequacy of liver biopsy
• Biopsy length - > 1 cm • At least 10 portal tracts should be seen• Any amount of tissue that yields diagnosis • Transjugular biopsy : smaller, thinner,
fragmented tissue cores (4 fragmented cores) or at least 4-6 portal tracts
• Best is laparoscopic biopsy
![Page 20: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/20.jpg)
Histology
Lobular model • 2-3 mm diameter lobule • Hexagonal shape • The central hepatic vein
(terminal hepatic vein)• Portal tracts at the
periphery • Portal tract- portal vein,
hepatic artery, bile duct
![Page 21: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/21.jpg)
Conti..
• Hepatocytes around – central vein -centrilobular(zone3), – portal tract - periportal (zone 1), – in between mid zonal (zone 2)
• Hepatocytes – polygonal, central single nucleus, cells arranged in plates
• Sinusoids on either side of cell plate
• Sinusoids – lined by fenestrated endothelial cells
P
BD
![Page 22: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/22.jpg)
Conti..• Space of disse – lies below the endothelial lining of
sinusoids has stellate cells • Kupffer cells- mononuclear phagocytic cells, on luminal
side of sinusoids
![Page 23: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/23.jpg)
Conti..
Bile canaliculi – seen in between hepatocytes, 1-2 𝛍 diameter, drain into canal of hering, in turn drain into bile duct
![Page 24: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/24.jpg)
Acute Injury Response of liver parenchyma to acute injury • Necrosis
– Hepatocytes swells– Blebs are formed and carry out organelles out of the cell– Cell rupture – Macrophage infiltration at the site of necrosis
• Apoptosis – Nuclear pyknosis, karyorrhexis– Acidophilic bodies – councilman bodies
![Page 25: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/25.jpg)
Disease process continues • Spotty necrosis/ focal necrosis - Death of
individual hepatocytes or small groups of these cells
• Confluent necrosis – widespread parenchymal loss, a zonal loss of hepatocytes
![Page 26: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/26.jpg)
• Bridging necrosis – necrosis link central veins to portal tracts or bridge the adjacent portal tract
• Panlobular and multilobular necrosis - confluent necrosis involving entire single lobules or several adjacent lobules respectively
![Page 27: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/27.jpg)
Bridging necrosis
p
c
![Page 28: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/28.jpg)
Panlobular and multilobular necrosis
![Page 29: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/29.jpg)
Scar formation and regression
• Stellate cells – most important, myofibroblastic properties
![Page 30: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/30.jpg)
Approach to liver biopsy interpretation • Architecture
– Maintained – Collapse – Fibrosis
• Hepatocellular changes – Necrosis – apoptosis
• Cholestasis – Canalicular – Ductular
• Portal tract – Inflammation– Edema – Bile ductular reaction– Ductopenia – Fibrosis
• Inflammatory infiltrate – Neutrophils – Eosinophil's– Mononuclear cell
![Page 31: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/31.jpg)
Acute viral hepatitis
![Page 32: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/32.jpg)
Acute viral hepatitis
• Usually Pan lobular – Centrilobular – hepatitis B, C– Periportal – hepatitis A
• Hepatocytes – ballooning, pale granular cytoplasm or shrinkage, nuclear pyknosis – acidophilic bodies (Councilman bodies),
• Bilirubinostasis • Mononuclear and lymphocytic
infiltration • Spotty necrosis
![Page 33: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/33.jpg)
Acute viral hepatitis
bridging necrosis. curved lines of necrotic debris and collapse extend from a portal tract to cetral venule.
C
P
![Page 34: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/34.jpg)
Acute viral hepatitis
multilobular necrosis Portal tract (arrow) can be identified but the parenchyma has been replaced by inflammatory cells, necrotic debris
![Page 35: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/35.jpg)
Fate and morphological sequel of acute viral hepatitis
• Resolution• Scarring• Chronic hepatitis• Cirrhosis• Acute liver failure • Hepatocellular carcinoma
![Page 36: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/36.jpg)
Chronic hepatitis
Classic causes of chronic hepatitis• Hepatitis B, with or without HDV infection • Hepatitis C • Autoimmune hepatitis • Drug-induced hepatitis – methotrexate, OCP,
vitamin A, acetaminophin • Chronic hepatitis of unknown cause
![Page 37: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/37.jpg)
Chronic hepatitis
The portal tract is heavily infiltrated with lymphocytes (H&E)
Interface hepatitis-process of inflammation and erosion of the hepatic parenchyma at its junction with portal tracts or fibrous septa (H&E)
![Page 38: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/38.jpg)
Chronic hepatitis
Chronic hepatitis with lobular activity. Clumps of inflammatory cells, some of them associated with hepatocyte loss, extend through the parenchyma. The portal tract above is inflamed. (H&E.)
![Page 39: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/39.jpg)
Chronic hepatitis B
the central part of the cytoplasm has a homogeneous ground-glass appearance. Sanded nuclei – fine granular, eiosinophilic
Cytoplasmic inclusions of HBsAg are present.
![Page 40: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/40.jpg)
Chronic hepatitis C
• The portal tract is heavily infiltrated by lymphocytes,
• A lymphoid follicle with germinal center has formed
• 15-25% may have steatosis
![Page 41: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/41.jpg)
Autoimmune hepatitis
• Female predilection • Chronic progressive hepatitis with features of
autoimmune diseases – Genetic predisposition– Associated with other autoimmune disorders – Therapeutic response to immunosuppression
![Page 42: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/42.jpg)
Autoimmune hepatitis 1. Type 1
– Any age (Middle aged to old age)– Presence of antinuclear antibodies (ANA), anti
smooth muscle actin antibodies (SMA), anti soluble liver antigen/liver- pancreas antigen( anti-SLA/LP), anti mitochondrial (AMA) antibodies
• Type 2 – Children and teenagers – Anti liver kidney microsome-1 antibodies
![Page 43: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/43.jpg)
Autoimmune hepatitis
Interface hepatitis Plasma cell predominates in the mononuclear inflammatory infiltrate
![Page 44: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/44.jpg)
Autoimmune hepatitis
Hepatocytes rosettes in areas of activity Confluent necrosis, parenchymal collapsePlasma cell infiltration seen (characteristic)
![Page 45: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/45.jpg)
Drug induced hepatitis
![Page 46: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/46.jpg)
Conti..
![Page 47: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/47.jpg)
Necroinflammatory score for chronic hepatitis (HAI/Knodell score)
![Page 48: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/48.jpg)
Conti…
![Page 49: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/49.jpg)
Grading for chronic hepatitis
Minimal activity (grade 1). Inflammation is confined to the portal tracts and there is no interface hepatitis. The lobular parenchyma is quiescent
Mild activity (grade 2). Focal interface hepatitis present (right periportal region) in addition to portal tract inflammation. A few lobular necroinflammatory foci are also seen at right
![Page 50: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/50.jpg)
Grading for chronic hepatitis
Moderate activity (grade 3). More extensive interface hepatitis is present than in grade 2, but involving <50% of the circumference of most portal tracts.
Marked activity (grade 4). The portal tract is diffusely inflamed and shows extensive circumferential interface hepatitis. Similar changes affect virtually all portal tracts with this grade of activity, often with considerable lobular activity.
![Page 51: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/51.jpg)
Cirrhosis • Results from interplay between parenchymal
damage, fibrinogenesis, fibrinolysis and hepatocellular regeneration
• Main Causes – Hepatitis B, C, – Alcohol abuse– Biliary diseases– Metabolic disorders – Drugs, toxins– Autoimmune hepatitis – Venous out flow obstruction
![Page 52: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/52.jpg)
Criteria for cirrhosis 1. Fundamental
– Nodularity – Fibrosis
2. Relative • Fragmentation • Abnormal structure • Hepatocellular changes
– Regenerative hyperplasia – Pleomorphism – Large-cell dysplasia (large-cell change) – Small-cell dysplasia (small-cell change)
![Page 53: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/53.jpg)
Classification
based on size of the nodule• Micronodule - < 3 mm causes - Alcohol, Metabolic, Hemachromatosis, Wilson's Disease
• Macronodule - > 3 mm causes – Viruses (B,C), Toxins, Poisoning
• Mixed – equal number of both nodules
![Page 54: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/54.jpg)
Cirrhosis
Cirrhosis: micronodular pattern. Nodules are of lobular size or smaller , reticulin stain
Cirrhosis: macronodular pattern. Nodules are larger than 3 mm, reticulin stain
![Page 55: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/55.jpg)
Fragmented sample
Cirrhosis: fragmented sample. A specimen obtained by the biopsy method has broken into rounded fragments peripherally circumscribed by fibrosis, reticulin stain
![Page 56: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/56.jpg)
Abnormal structures
Cirrhosis: selective sampling. A nodule has been cored out of the connective tissue by the biopsy procedure, but a thin layer of connective tissue (arrow) has adhered to the nodule margin. (Needle biopsy, reticulin.)
Cirrhosis: distorted reticulin pattern. The distortion has resulted from abnormal and irregular hepatocyte growth patterns. (Needle biopsy, reticulin.)
![Page 57: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/57.jpg)
Hepatocellular changes
Cirrhosis: hepatocellular regeneration. Liver-cell plates are two or more cells thick, indicating active growth. (Needle biopsy, H&E.)
Cirrhosis: large-cell dysplasia , nuclei of the enlarged hepatocytes irregular in shape and vary greatly in size and staining intensity. Cells are multinucleated. The normal hepatocytes at right and in the upper left-hand corner. (Wedge biopsy, H&E.)
![Page 58: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/58.jpg)
Hepatocellular changes
Cirrhosis: small-cell dysplasia (small-cell change). The hepatocytes below and to the right have normal-sized nuclei, but their overall size is reduced. Nuclear– cytoplasmic ratios are therefore increased. (Needle biopsy, H&E.)
![Page 59: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/59.jpg)
Assessment of cause for cirrhosis • Pattern of nodules
and fibrosis – regular– irregular
• Bile ducts – Ductular reaction– Ductopenia– fibrosis
• Blood vessels – Narrowing
– Ischemic changes• Steatohepatitis • Evidence of viral
infection • Abnormal deposits
– Iron – Copper, copper-
associated protein – α1-Antitrypsin
globules
![Page 60: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/60.jpg)
Ishak score for Staging of fibrosis
![Page 61: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/61.jpg)
Alcoholic liver disease
3 forms of alcoholic liver injury • Hepatocellular steatosis• Alcoholic hepatitis (steatohepatitis)• Steatofibrosis
![Page 62: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/62.jpg)
Hepatic steatosis
There are large fat vacuoles in perivenular hepatocytes, displacing the nuclei to the edges of the cells. (Needle biopsy, H&E.)
![Page 63: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/63.jpg)
Steatohepatitis
Alcoholic steatohepatitis. Ballooning, necrosis,. Inflammatory cells, mainly neutrophils. contain densely stained Mallory bodies (arrows). Many hepatocytes contain large fat vacuoles. (Needle biopsy, H&E.) ASH cannot be differentiated from NASH
Mallory bodies. The Mallory bodies in this example of steatohepatitis stain strongly for ubiquitin (arrows)
![Page 64: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/64.jpg)
Steatofibrosis
Micro nodules entrapped in blue-staining fibrous tissue.Fat accumulation no longer seen, burned out stage. (masson trichrome stain)
![Page 65: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/65.jpg)
Metabolic liver diseases
• Non alcoholic fatty liver disease• Hemochromatosis• Wilson disease • 𝛂1 antitrypsin deficiency• Glycogen storage diseases • Gaucher’s disease• Niemann–Pick disease
![Page 66: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/66.jpg)
Non alcoholic fatty liver disease• NAFLD is a group of conditions that have in common
the presence of hepatic steatosis (fatty liver), in individuals who do not consume alcohol, or do so in very small quantities (less than 20 g of ethanol/week)
• NAFLD – Fatty liver– NASH– Fibrosis – Cirrhosis
• Associated with metabolic syndrome
![Page 67: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/67.jpg)
Non alcoholic fatty liver disease
NASH predominantly mononuclear inflammatory cell in filtrate with both small and large fat droplets (H&E)
Steatofibrosis prominent at portal region, extending along the sinusoids in a chicken wire pattern around the hepatocytes ( masson trichrome )
![Page 68: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/68.jpg)
NAFLD Score
![Page 69: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/69.jpg)
Hemochromatosis • Excessive iron absorption, most of which is
deposited in parenchymal organs like liver, pancreas, heart, joints, endocrine organs
• Normal iron pool 2-6 gm in adults • 0.5 gm stored in liver (98% in hepatocytes)• Disease manifestation appear when the iron
load > 20gm
![Page 70: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/70.jpg)
Hemochromatosis
• Mutations of TFR1, TFR2, HJV, HFE gene mutation lead to decrease production of hepcidin and increased absorption of iron and increased release into circulation
• Serum ferritin >1000 µg/L• Transferrin saturation > 45% • Serum iron > 150 µg/dl
![Page 71: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/71.jpg)
Classification of hemochromatosis
![Page 72: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/72.jpg)
Hemochromatosis
Hepatocytes showing iron over load, stained blue color in perl’s prussian blue stain, note the inflammation characteristically absent.
![Page 73: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/73.jpg)
Wilson disease
• Autosomal recessive disorder • Mutation of the ATP7B gene, • Impaired copper excretion into bile and a
failure to incorporate copper into ceruloplasmin• Copper accumulate in liver and later brain• Serum ceruloplasmin < 20 mg/dl• 24 hr Urine copper > 100 𝛍g/dl• Total serum Cu < 60 𝛍g/dl
![Page 74: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/74.jpg)
Wilson’s disease
Fatty change, mild to moderate hepatocytic necrosis, with inflammatory infiltrate, intranuclear glycogen inclusions also seen.
The upper nodule is strongly positive for copper, stained orange-red. The lower nodule is completely negative. (Wedge biopsy, rhodanine.)
![Page 75: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/75.jpg)
Glycogen Storage Diseases
• A hereditary deficiency of one of the enzymes involved in the synthesis or sequential degradation of glycogen
• The liver is important in glycogen metabolism. • Type 1( von Gierke) is most common for liver –
absence of glucose 6 phosphatase
![Page 76: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/76.jpg)
Von Gierke disease
type I glycogen storage disease, PAS positive and after treating with diastase hepatocytes are swollen and resemble plant cells ,the abundant glycogen displaces the organelles of affected cells to the periphery. Sinusoids are compressed. Slender periportal fibrous scars often develop
![Page 77: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/77.jpg)
Gaucher’s disease
• Autosomal recessive disorders resulting from mutations in the gene encoding glucocerebrosidase
• Glucocerebrosidase - cleaves the glucose residue from ceramide.
• The enzyme defect, glucocerebroside accumulates in phagocytes, kupffer cells
![Page 78: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/78.jpg)
Gaucher’s disease
Pale-staining, striated Kupffer cells containing stored lipid are present within sinusoids. The affected cells compress hepatocytes and sinusoids and may give rise to portal hypertension. Pericellular fibrosis is a common finding
![Page 79: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/79.jpg)
Niemann–Pick disease
• Lysosomal accumulation of sphingomyelin due to an inherited deficiency of sphingomyelinase
![Page 80: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/80.jpg)
Niemann–Pick disease
accumulation of sphingomyelin in both hepatocytes and macrophages. The latter are greatly swollen, foamy and diastase–PAS-positive to a variable extent , Niemann–Pick disease may progress to cirrhosis
![Page 81: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/81.jpg)
𝛂1- Antitrypsin deficiency
• Autosomal recessive disorder • low levels of α1-antitrypsin• Normal functions – inhibitors of protease,
elastase, protease 3, cathepsin G which are released by neutrophils at the site of inflammation
• Mutated α1-antitrypsin protein abnormally folded inside the ER and lead to apoptosis of cell.
![Page 82: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/82.jpg)
𝛂1- Antitrypsin deficiency
Hepatocytes near periportal region contain mutated proteins, and stained magenta color for PAS+diastase . May also show steatosis, necrosis and fibrosis
![Page 83: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/83.jpg)
Cholestasis diseases
• Refers to impairment of bile flow.
• In light microscope- bile pigment within bile canaliculi, hepatocytes and other sites.
• Bile is seen in the form of bile thrombi (bile plugs) in dilated canaliculi
![Page 84: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/84.jpg)
Large bile-duct obstruction
• Causes in children – Biliary atresia – Cystic fibrosis– Choledochal cyst
• Causes in adults – Gall stones– Malignancies of biliary tree, head of pancreas– Stricture from previous surgery
![Page 85: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/85.jpg)
Large bile-duct obstruction
• Dilatation intercanaliculi
• Portal tract edema• Bile duct proliferation
at the margin of portal tract
• Mild inflammatory infiltrate
![Page 86: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/86.jpg)
Chronic bile-duct obstruction and biliary cirrhosis(secondary biliary cirrhosis)
Bile duct obstruction persists, bile duct infarct and increasing fibrosis. Jigsaw puzzle shape
![Page 87: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/87.jpg)
Primary biliary cirrhosis
• Autoimmune disease characterized by nonsuppurative, inflammatory destruction of small and medium sized intrahepatic bile ducts
• Antimitochondrial antibodies recognize E2 component of pyruvate dehydrogenase complex of mitochondrial membrane,
• Altered MHC II of bile ductal epithelial cells seen, causes autoactivation of T cells
![Page 88: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/88.jpg)
Stages of primary biliary cirrhosis
![Page 89: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/89.jpg)
Primary biliary cirrhosis
Grannulomatous lesion surrounding bile duct with mononuclear cell infiltration
Florid duct lesion
![Page 90: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/90.jpg)
Primary biliary cirrhosis
Ductular reaction with periportal hepatitis A lymphoid aggregate and a follicle with a germinal Centre (arrow)
![Page 91: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/91.jpg)
Primary biliary cirrhosis
Scarring; bridging necrosis, septal fibrosis There is extensive scarring with irregular nodule formation. Aggregates of lymphocytes mark the former sites of bile ducts
![Page 92: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/92.jpg)
Primary sclerosing cholangitis
• Inflammation and obliterative fibrosis of intrahepatic and extrahepatic bile ducts, with dilation of preserved segments
• Immunological mediated injury to bile duct• T cells in periductal region• Autoantibodies to HLA-B8, MHC antigens • pANCA can be noted in circulation • On cholangiographic demonstration of the characteristic
beading of bile ducts • May be associated with inflammatory bowel disease
![Page 93: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/93.jpg)
Primary sclerosing cholangitis
A bile duct undergoing degeneration is entrapped in a dense, “onion-skin” concentric scar
![Page 94: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/94.jpg)
Cholestasis of sepsis
• By 3 main mechanism1. Direct effect of intrahepatic bacterial
infection (abscess, bacterial cholangitis) 2. Ischemia relating to hypotension due to
sepsis ( when liver is cirrhotic)3. Response to circulatory microbial products
(most common)
![Page 95: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/95.jpg)
Cholestasis of sepsis
Canalicular cholestasis – bile plug at centilobular canliculi , sometime associate with kuffer cell activity and mild poratl tract inflammation
Ductular cholestasis – dilated canal of hering and bile ductules at the interface of portal tracts and parenchyma become dilate and contains bile plug
![Page 96: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/96.jpg)
Biliary atresia
• Partial or complete obstruction of the lumen of the extrahepati biliary tree within the first 3 months of life
• Most common cause of neonatal cholestasis • 2 types
– Fetal type (20%)– Perinatal type (80%)
![Page 97: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/97.jpg)
Cont..
• Fetal form – Malrotation of abdominal viscera – Interruptured inferior vena cava – Polysplenia – Congenital heart disease
• Perinatal form– Viral (reovirus, rotavirus, CMV)– Autoimmune reaction
![Page 98: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/98.jpg)
Biliary atresia
An expanded, inflamed portal tract at left contains many proliferated bile ducts, some of which are filled with inspissated bile.
![Page 99: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/99.jpg)
Congenital hepatic fibrosis
• Autosomal recessive inherited condition • Due to Ductal plate malformation• Presents with hepatomegaly or portal
hypertension, usually in childhood but occasionally in adults
• Associated with polycystic disease of kidney• Misdiagnosed as cirrhosis
![Page 100: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/100.jpg)
Congenital hepatic fibrosis
Several portal tracts are interconnected by bridging fibrous septa containing ductal plate malformations. The fibrosis surrounds normal parenchyma with a terminal venule (short arrow) preserved in a central position. Inset: Higher magnification of the abnormal duct structures seen at lower left (long arrow).
![Page 101: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/101.jpg)
Indian childhood cirrhosis
• High mortality affecting young Indian children (and Indian subcontinent)
• Brass- and copper-containing vessels used for milk-feeding - identified as sources of copper contamination
• Large amounts of copper and copper-associated protein accumulate in affected hepatocytes
![Page 102: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/102.jpg)
Indian childhood cirrhosis
Many liver cells are swollen (centre), and surrounded by fibrosis and mononuclear cells. Regenerating hepatocytes are organised into small clusters. Disease progress l/t micronodular cirrhosis (H&E.)
![Page 103: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/103.jpg)
Granulomatous lesion
![Page 104: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/104.jpg)
TB GranulomaSarcoid Granuloma
PBC Granuloma Fibrin Granuloma
![Page 105: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/105.jpg)
Nodules and tumors
![Page 106: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/106.jpg)
Hepatocellular adenoma
Liver cells appear normal or contain fat vacuoles. Blood vessels but no portal tracts are seen within the lesion. (H&E.)
![Page 107: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/107.jpg)
Focal nodular hyperplasia (FNH)
Central scar with arteriole, periphery shows fibrous septa with bile duct proliferation (arrow), surrounding the scar is the nodule consists of normal hepotocytes .
![Page 108: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/108.jpg)
Nodular regenerative hyperplasia(NRH)
This abnormal, nodular growth pattern is not accompanied by fibrosis and therefore differs from cirrhosis. The parenchymal nodules (N) are often adjacent to nodule (at left) or surrounding portal tracts. The intervening liver shows flattened and compressed liver-cell plates and/or sinusoidal dilatation (H/E)
N
N
![Page 109: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/109.jpg)
Bile-duct adenoma
This subcapsular tumour consists of closely packed well formed bile ducts set in a dense fibrous stroma. A dense collection of lymphocytes is seen at the edge of the lesion (bottom). (H&E.)
![Page 110: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/110.jpg)
Hemangioma
Locate beneath the capsule. Blood-filled spaces are separated by fibrous septa. A thick capsule is seen at right. ( H&E.)
![Page 111: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/111.jpg)
Hepatocellular carcinoma
• Precursors of hepatocellular carcinoma 1. Chronic cirrhosis 2. Large cell dysplasia 3. Small cell dysplasia 4. Macroregenerative nodule 5. Dysplastic nodule
![Page 112: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/112.jpg)
Macroregenerative nodule
This low-magnification view demonstrates the increased size of the nodule at left compared with the cirrhotic nodules at right.
![Page 113: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/113.jpg)
Dysplastic nodule
The dysplastic nodule at right shows hepatocytes arranged in pseudoacini, with a less cohesive growth pattern centrally. A cirrhotic nodule is present at lower left. Cells show nuclear atypia , (H&E)
![Page 114: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/114.jpg)
Hepatocellular carcinoma
Trabeculae-sinusoidal pattern, trabeculae are thicker and reticulin is often scanty or even absent, (HandE)
Reticulin is scanty in this example. Reticulin stain
![Page 115: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/115.jpg)
Hepatocellular carcinoma
Adenoid pattern.
![Page 116: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/116.jpg)
Grading of HCC
Grade 1 (well differentiated) tumours have small, round nuclei prominent nucleoli almost similar to those of normal and cirrhotic liver. HandE
Grades 2 show progressive alterations in nuclear contour, chromatin coarseness and hyper chromaticity
![Page 117: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/117.jpg)
Conti..
Grade 3- more nuclear atypia compared to grade 2 and nuclear crowding is seen
Grade 4 shows marked anaplasia with giant, multinucleated tumour cells and atypical mitotic figures
![Page 118: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/118.jpg)
HCC - Fibrolamellar type
Occur under the age of 30yrs, occur as single large, hard, scirrhous tumor.Tumor cells are well differentiated, shows oncocytic change, separated by parellel lamellae of dense collagen bundles.
![Page 119: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/119.jpg)
Heptatocellular carcinoma
• Immunostaining 1. Hep Par 1 (hepatocyte) 2. Polyclonal CEA 3. Cytokeratin 7/20 pair (−/− staining) 4. GPC-3/GS/HSP70 trio (recent and confirmative,
any 2 +ve indicates HCC) – Glypican- 3 (GPC-3)– Glutamine synthetase (GS) – Heat shock protein 70 (HSP70)
![Page 120: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/120.jpg)
Hepatoblastoma
• Most common liver tumor of early childhood • Occur at the age of 3yr• 2 variants
– Epithelial – polygonal fetal or embryonal cells arranged in acini, tubules, papillary
– Mixed epithelial and mesenchymal – admixed with osteoid, chondroid, striated muscle
![Page 121: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/121.jpg)
Hepatoblastoma
Epithelial type - The tumour grows in cords of small hepatocytes with a ‘light-and-dark’ cells due to the admixed clear (glycogenated) and eosinophilic liver cells.( H & E.)
![Page 122: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/122.jpg)
cholangiocarcinoma
• Malignancy of the biliary tree, arising from the bile duct within and outside of the liver
• Risk factors – Chronic inflammatory conditions – Primary sclerosing cholangitis– Hepatolithiasis – Fibropolycystic disease
![Page 123: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/123.jpg)
Conti..
• 2 types – Intra hepatic – Extra hepatic (perihilar, klatskin tumor)
• Premalignant lesions – biliary intraepithelial neoplasias (BilN)– Low grade BilN 1 and 2– High grade BilN3
![Page 124: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/124.jpg)
cholangiocarcinoma
There are islands of adenocarcinoma in the connective tissue, well formed glands lined by malignant tumor epithelial cells. Lymphovascular and perivascular invasions are common
![Page 125: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/125.jpg)
Liver allograft rejection
• Acute cellular rejection – Most common within one month, but can occur
later – Traid – – portal inflammation, – bile-duct damage & – endothelitis
• Chronic rejection – Occur after 6 months of transplantation
![Page 126: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/126.jpg)
Host vs graft reaction
Acute rejection- Heterogeneous portal inflammation consisting of lymphocytes, plasma cells and scattered neutrophils infiltrates the bile duct (between arrows) and the portal vein branch at top. (Needle biopsy, H&E.)
Endotheliitis in acute rejection. An efferent vein shows lymphocytic infiltration of its wall. The endothelium is focally lifted off the underlying vein wall and partially destroyed. (Needle biopsy, H&E.)
![Page 127: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/127.jpg)
Graft vs host reaction
Chronic (ductopenic) rejection. An hepatic artery branch (arrow) is present in the portal tract but the corresponding interlobular bile duct has disappeared as a result of rejection. A sparse lymphocytic infiltrate remains. (Explanted donor liver, H&E.)
![Page 128: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/128.jpg)
Vanishing duct syndrome
• Neonatal age– Biliary atresia – Alagalie syndrome
• Adult age– PBC– PSC– Overlap syndrome– Drug induced– Chronic graft vs host rejection– Idiopathic
![Page 129: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/129.jpg)
Summary
• Acute severe liver injury and in advanced stages of fibrosis/cirrhosis – etiological diagnosis usually not possible
• Drug induced liver injury can present with any form of liver injury. Hence we cannot exclude if clinically suspected.
• Fibrosis with normal liver architecture – suspect congenital hepatic fibrosis
![Page 130: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/130.jpg)
Summary
• Excess iron in liver is not always hemochromatosis. Infact most common cause is alcoholic cirrhosis
• Clinically suspected cirrhosis but no fibrosis on biopsy than look for NRH, and hepatic venous outflow obstruction
• Poorly differentiated HCC and cholangiocarcinoma difficult to differentiate – use IHC
![Page 131: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/131.jpg)
![Page 132: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/132.jpg)
References
1. Theise ND. Liver and gall bladder. In: kumar, Abbas, Aster, Robbins and Cotran Pathologic Basis of Disease. 9th ed. New Delhi: Reed Elsevier India Private limited; 2014. 185-263
2. Desmet VJ, Rosai J. Liver. In: Rosai J, Rosai and ackerman’s surgical pathology. 10th ed. New Delhi: Reed Elsevier India Private limited; 2012. 857-942
![Page 133: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/133.jpg)
3 Gill RM, Kakar s, Washington K. non neoplastic liver diseases and masses of the liver. In: Greenson JK, Hornick JL, Longacre TA, Reuter VE, Sternberg’s diagnositc surgical pathology. 6th ed. China: Wolters Kluwer; 2015. 1663-1704
4 Lefkowitch HJ. SCHEUER’S Liver Biopsy Interpretation. 8th ed. China: Reed Elsevier; 2010
![Page 134: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/134.jpg)
5. Feldman M, Friedman LS, Brandt L. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 9th ed. Philadelphia. Reed Elsvier; 2010
6. Sanai FM, Keeffe EB. Liver Biopsy for Histological Assessment – The Case. AgainstSaudi J Gastroenterol. 2010 Apr-Jun;16(2):124-32
![Page 135: Liver biopsy interpretation](https://reader035.fdocuments.net/reader035/viewer/2022062904/5872cfdd1a28ab74188b4d05/html5/thumbnails/135.jpg)
7. Schiff ER, Maddrey WC, Sorrell MF. Schiff’s Diseases of Liver.11th ed. London: Wiley blackwell; 2012.