Sabato 27 ottobre 2012 - Pacini Editore

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Fig. 2. ductal injury showing “dysplastic-like” modification of the biliary
epithelium (a) with no evidence of ductular reaction (b).
A
B
activated stellate cells which express myofibroblastic antigens
were performed.
The patient developed ileal infarction secondary to atherosclerosis
of the mesenteric vessels and was resected but died soon after.
Results. On histologic examination of the biopsy specimen,
the most striking feature was the presence of dense concentric
hyaline thickening of portal small hepatic artery branches,
highlighted by DPAS (Fig. 1a). The change was reminiscent
of that noted in other organs with diabetic microangiopathy.
Furthermore dense perisinusoidal fibrosis mainly in the centrivenular
area, demonstrated with trichrome staining, was
seen (Fig. 1b) and immunostaining for SMA showed the presence
of extracellular matrix producing activated stellate cells
(Fig. 1c).
Ductal injury showing “dysplastic-like” modification of the biliary
epithelium was noted but no ductular reaction was present
(Fig. 2). At a formal count no evidence of ductopenia was seen.
No copper associated protein deposition was identified. Liver
architecture was altered due to fibrosis and enlargement of portal
tracts with only occasional porto-portal fibrous septa. No steatosis
or necroinflammatory activity were present. No evidence of
sepsis was seen.
Conclusions. The report describes a case of DH characterized
by sinusoidal fibrosis and dense concentric hyaline thickening of
small hepatic artery branches occurring in a young patient with a
history of long-standing insulin-dependent DM.
This lesion was first described by Bernuau in 1982 6 who described
6 diabetic patients with retinopathy who showed marked
CONGRESSO aNNualE di aNatOmia patOlOGiCa SiapEC – iap • fiRENzE, 25-27 OttOBRE 2012
deposition of collagen fibres within the perisinusoidal space. A
second report some years later by Latry et al. 7 showed a direct
correlation between collagenization of Disse’s space and the
presence of diabetic microangiopathy in both type I and type II
DM. McGrath et al. 8 also described a case of hepatic sinusoidal
fibrosis in a diabetic woman.
Only in 2006 was the term DH applied on a case series 3 composed
of liver biopsies from 12 diabetic patients with a non-cirrhotic
form of hepatic sinusoidal fibrosis not associated with NAFDL.
These researchers also suggested that these lesions probably represent
a form of diabetic microangiopathy in the liver.
Further autopsy series identified the incidence of DH in two
studies. Complete autopsies from 57 adults with DM were reviewed
for liver pathology and other diabetic complications by
Hudacko et al. 4 and only 1 case of DH was identified. Furthermore
in another study from the same year, the incidence of DH
was evaluated in a 10 year autopsy series of 976 patients, 159 of
which were diabetic 5 . Approximately 12% of diabetic patients
were shown to have DH even though the majority were clinically
silent. This study also confirms that DH is only related to DM and
is not present with co-existent NAFDL/NASH.
In our report the laboratory findings were characterized by a
cholestatic picture with raised bilirubin, ALP and GGT but normal
transaminases and this is in keeping with the clinical data
from Harrison et al’s series. Abnormal cholestatic laboratory
findings indicate that diabetic hepatosclerosis may be associated
with non-parenchymal hepatic tissue involvement, as opposed
to the direct parenchymal effects associated with NAFLD. Our
case showed evidence of ductal injury, with epithelial modifications
reminiscent of the “dysplastic type lesions” seen in other
acute bile duct lesions such as GVHD or chronic ductopenic
rejection (absence of ductular rejection or copper associated
protein deposition). We postulate that microangiopathy leads
to acute ischemia of the biliary branches and therefore to acute
bile duct lesions and elevation of ALP and GGT. This is the
first report which identifies ductal lesions within this disease
spectrum.
In conclusion, diabetic hepatosclerosis may represent a rare hepatic
form of microvascular disease in DM; the collagenization
of the space of Disse is positively correlated with the presence
of diabetic microangiopathy. The underlying causes remain
unknown at the current time as does prognosis even though the
patient described in our case report died soon after.
Further study is needed to precisely characterize diabetic hepatosclerosis
and to understand the exact mechanism of pathogenesis
as well as correlation with cholestatic laboratory findings and bile
duct injury.
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