@Diabetic Microangiopathy in the Liver - Copy

8/8/2019 @Diabetic Microangiopathy in the Liver - Copy

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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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