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DIABETIC MICROANGIOPATHY IN THE
LIVER
AN AUTOPSY STUDY OF INCIDENCE
AND ASSOCIATION WITH OTHER
DIABETIC COMPLICATIONS
Rachel M. Hudako, MD Justin P. Sciancalepore, &Billie S. Fyfe, MD
Am J Clin Pathol 2009 ; 132:494-499
Guide : Dr . J.J.John
By,
Dr. Vishal Srivastava
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Diabetic hepatosclerosis(DH) is a recently
described form of diabetic Microangiopathy
with hepatic sinusoidal fibrosis and basement
membrane deposition without cirrhosis.
Microangiopathy , manifested by thickening of
capillary basement membrane in the vascular
beds of organ and tissue.
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Diabetic liver disease most commonly takes the form of nonalcoholic fatty liver disease [ NAFLD] , which includes simple
steatosis and steatohepatitis with or without steatofibrosis that
usually affect pts with Type 2 DM.
Less common pattern of hepatic injury with Type 1 DM :
Glycogenic Hepatopathy [ Glycogen accumulation and elevated liver
enzyme] can be diagnosed only by liver biopsy.
In 2006 Harrison et al reported a biopsy series of 12 Diabetic
pts with a non cirrhotic form of hepatic sinusoidal fibrosis not
associated with NAFLD.
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They proposed the term diabetic hepatosclerosis [DH] to
describe this entity and suggested that it represents a form
of diabetic Microangiopathy of liver.
All of the patients in the series had long standing DM, most
had clinical evidence of other micro vascular complications
including retinopathy, nephropathy and neuropathy.
Dense perisinusoidal fibrosis was highlighted by Masson
trichrome stain and basement membrane component
including laminin and Type IV collagen, were demonstrated
with immuno stains.
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MATERIAL & METHODS
Complete autopsies of patients with diabetes
performed at Robert Wood Johnson University
hospital, new Brunswick , NJ b/w 1990 and
2007 were reviewed.
Excluded Cases :
Restricted autopsies that did not include
examination of Thoracic and Abdominal cavity
organ .
Liver neoplasia and severe Hepatic necrosis
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Record reviewed :
- Type of DM
- Hypertension
- Retinopathy
- Nephropathy
- Clinical liver abnormality
Masson Trichrome - Hepatic Fibrosis
PAS - Hepatic arteriosclerosis
Grading : 0 - Absent
+1 - Present in few portal tracts
+2 - Present in most portal tracts
+3 - Present in all portal tracts with Luminal obstruction
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Other pathological changes
- Fatty liver disease
- Chronic hepatitis
- Presence of portal fibrosis
- Portal central bridging fibrosis
- Cirrhosis
Kidney sections were evaluated for the presence of Diffuse or nodular
glomerulosclerosi s and Renal arteriosclerosis
Immunohistochemical staining for laminin and Type IV collagen was
performed.
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RESULTS
57autopsies[37-
91yrs]
White 31
African American -15
Others - 11
Type I 4
Type II 39
Non specific - 14
30 Male
27 female
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Clinical diagnosis included :
- Hypertension 44 [ 77 % ]
- Coronary artery disease 44 [ 77 % ]
- Peripheral Neuropathy 10 [ 18 % ]
- Retinopathy 10 [ 18 % ]
- Hepatitis C 4
- Hepatitis B 1
- Hepatitis B & C 1
Aspartate aminotransferase and Alanin aminotransferase levels -
Normal to up to 50 times the normal value
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CATEGORIZATION OF HISTOLOGICAL
FINDINGS
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Laminin and Type IV collagen were used to evaluate the
presence of Basement membrane components in the study
which includes:-
- DH Marked positivity within the sinusoids [1/1]
- Cardiac sclerosis Patchy centrilobular staining [1/5], and
patchy positivity in area of septa formation [2/5]
- NAFLD - Mild periportal positivity [1/4]
-Viral hepatitis [2] No finding
- non- specific findings [1] No finding
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DISCUSSION
Compatibility with the definition of DH proposed
by Harrison et al was evaluated.
1 case of DH was identified in 57 cases.
The case of DH had the most severe hepatic
hyaline arteriosclerosis and diffuse or nodular
glomerulosclerosis of all cases.
Hypertension in coronary artery disease were
seen with equal frequency [77 %].
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Of the pt with Type II DM , 23 % in these study had NAFLD.
The major risk factor for NAFLD are
- Insulin resistance
- Obesity
- Dyslipidemia
NAFLD rarely affect pts with Type I DM [ 0/4 ].
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THE CASE OF DH
The case of DH occurred in a 68 year African
American woman with end stage renal disease
secondary to Type I DM of 58 years duration.
H/o - Hyperlipidemia , Hypertension and Asthma.
No Clinical H/o- retinopathy, neuropathy, coronary
artery disease, peripheral vascular disease or
alcohol use.
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LAB Investigation :
Aspartate Aminotransferase 14 U/L [ 12-45 U/L]
Alanin aminotransferase 17 U/L [ 3-40 U/L ]
Total Bilirubin - 0.9 mg/dl [ 0.1-1.2 mg/dl ]
Albumin - 3.5 gm/dl [ 3.5-5 gm/dl ]
Uric acid - 5.7 mg/dl [ 2-7 mg/dl ]
Alkaline phosphates(ALP) 217 U/L [ 37-107 U/L ]
Hepatitis A positive
Hepatitis B - Negative
Hepatitis C - Negative
Ig M for cytomegalo virus - Negative
Epstein Bar virus - Negative
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Kidney transplant was performed after 8 years of
Hemodialysis.
Pt died after 4 days of transplant.
Anastomosis at the transplant site were intact in autopsy.
Severe coronary artery disease, generalized atherosclerosis
and moderate pulmonary artery atherosclerosis were noted.
Cause of death was assumed to be cardiac related.
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Study by Harrison et al describes 12 pts with liver biopsy
showing DH .
These pts also had Long standing DM treated with Insulin
therapy, end stage renal disease treated with Hemodilysis
and renal transplantation, Hypertension & Normal
aminotransferase level with an elevated ALP level.
ALP is consider to be marker of Space occupying and ,
in DH , is elevated owing to the presence of BM component
occupying the perisinusoidal spaces.
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Two types of Vascular diseases are seen in Diabetic pts:
1 Non occlusive micro circulatory dysfunction involving capillary and
arterioles
2 Macro angiopathy characterized by atherosclerotic lesions
- Capillary BM thickening is structural change seen in retinopathy,
neuropathy and diabetic foot.
- Increase vascular permeability due to non enzymatic glycosylation
of BM with production of AGE s responsible for Nephropathy and
Retinopathy.
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Chronic endothelial damage have an important rolein diabetic angiopathy.
According to study done by Kayacan et al in 61 pts
with diabetes using elevated serum VWF [ Von
willebrand factor ] as marker of endothelial damage
and concluded that Hyperglycemia , Hypertension and
hyperlipidemia are major risk factor associated with
development of Microangiopathy as was in this study.
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In this study, we evaluated the overall incidence of a rare liver
lesion by re-examining specimens from autopsies performed on the
general diabetic population regardless of the presence of clinical
abnormalities.
By examining large tissue sections we were able to identify the
extent of sinusoidal fibrosis more accurately and evaluate
arterioles more thoroughly.
Clinical data of all cases may not be complete owing to
retrospective nature of the study because only 1 case of DH was
identified
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DH is an uncommon pattern of liver
disease in pts with diabetes, is a marker
of severe DM with end-organ damage and
represents a form of micro angiopathy in theliver according to Harrison et al.
DH occurs in pts with type - I more often
than type - II DM , the true prevalence of
the lesion in still unknown.
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THANK YO
U
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