Altered intrahepatic microcirculation of idiopathic portal hypertension in relation to glutamine synthetase expression

Sato, Yasunori; Harada, Kenichi; Sasaki, Motoko; Nakanuma, Yasuni

doi:10.1111/hepr.12506

Cited by 6 publications

(4 citation statements)

References 16 publications

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“…If any ammonia escapes the periportal hepatocytes, it can be scavenged and detoxified by perivenular hepatocytes through a high-affinity but low-capacity system involving GS [33]. Recently, significant expansion of the area of GS-expressing hepatocytes in human liver has been demonstrated in certain circumstances such as FNH, cirrhosis due to various causes, and idiopathic portal hypertension [19–22]. Because these conditions are well known to have altered microcirculation due to the presence of shunt vessels or abnormalities in venous and/or arterial vessels, we tested the GS expression status based on the assumption that an impaired sinusoidal microcirculation in CSI may lead to altered GS expression.…”

Section: Discussionmentioning

confidence: 99%

“…While centrilobular perisinusoidal/venular fibrosis is often reported in cases with OX-induced liver injury, the expression status of SMA by HSCs has only been sporadically described in this clinical setting [17, 18]. In the normal liver, GS is expressed exclusively in a narrow rim of pericentral hepatocytes; however, the area of GS-expressing hepatocytes has recently been shown to be significantly expanded in several pathologic conditions including focal nodular hyperplasia (FNH), liver cirrhosis of various etiologies, and idiopathic portal hypertension [19–22]. Because these conditions are associated with altered intrahepatic blood flow caused by shunt vessels or the presence of aberrant vasculature, impaired sinusoidal microcirculation in SOS may also lead to altered GS expression in the hepatic lobules.…”

Section: Introductionmentioning

confidence: 99%

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Chemotherapy-induced Sinusoidal Injury (CSI) score: a novel histologic assessment of chemotherapy-related hepatic sinusoidal injury in patients with colorectal liver metastasis

2017

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BackgroundPreoperative neoadjuvant therapy for colorectal liver metastases (CRLM) is increasing in use and can lead to chemotherapy-induced damage to sinusoidal integrity, namely sinusoidal obstruction syndrome (SOS). SOS has been associated with an increased need for intraoperative blood transfusions, increased length of hospitalization post-surgery, decreased tumor response, and a shorter overall survival after resection due to liver insufficiency. It is critical for clinicians and pathologists to be aware of this type of liver injury, and for pathologists to include the status of the background, non-neoplastic liver parenchyma in their pathology reports. In this study, expression of CD34 by sinusoidal endothelial cells (SECs), increased expression of smooth muscle actin (SMA) by hepatic stellate cells (HSCs), and aberrant expression of glutamine synthetase (GS) by noncentrizonal hepatocytes were semiquantitatively evaluated in liver resection or biopsy specimens from patients with CRLM to determine their diagnostic value for assessing chemotherapy-induced sinusoidal injury (CSI).MethodsThe expression of each marker was compared among 22 patients with CRLM with histologically evident SOS (SOS+) and 8 patients with CRLM who had not undergone chemotherapy. Each case was given a histologic grade using the sinusoidal obstruction syndrome index score (SOS-I) to assess the likelihood of SOS. Cases were also given an immunohistochemical grade using the total CSI score calculated as the sum of CD34, SMA, and GS scores.ResultsAbnormal staining patterns for CD34 and SMA were significantly more frequent and extensive in SOS+ cases than in the controls (81.8% vs. 25%, P < 0.01; 72.7% vs. 25%, P = 0.03). Aberrant GS expression in midzonal and periportal hepatocytes was only observed in SOS+ cases (31.8% vs. 0%), but this difference did not reach statistical significance. The CSI score was significantly higher in the SOS+ cases when compared to controls (P < 0.01), and was associated with a higher SOS histologic grade (P = 0.02).ConclusionsThe CSI score, calculated using an immunohistochemical panel consisting of CD34, SMA, and GS, may serve as an objective marker of chemotherapy-induced sinusoidal injury and could help diagnose this peculiar form of liver injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chemotherapy-induced Sinusoidal Injury (CSI) score: a novel histologic assessment of chemotherapy-related hepatic sinusoidal injury in patients with colorectal liver metastasis

2017

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“…Normal GS expression is defined as a rim of 2–3 layers of strongly positive hepatocytes around the hepatic veins (perivenular pattern) [ 30 ]. In NRH, besides pericentral hepatocytes, immunoreaction in zone 2 hepatocytes [ 29 ] and diffuse hepatocellular immunoreaction were also reported [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the histologic and immunohistochemical (CD34, glutamine synthetase) findings in idiopathic non-cirrhotic portal hypertension (INCPH)

Büyük,

Berker,

Bakkaloğlu

et al. 2024

Hepatol Int

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Aim Idiopathic non-cirrhotic portal hypertension (INCPH) is a vascular disorder of uncertain origin. Diagnosis can be challenging on liver biopsy. Despite diverse histomorphologic findings documented in literature, studies on the frequency of these findings are lacking. This study aims to assess both the histomorphologic features and the immunoexpression patterns of CD34 and glutamine synthetase (GS) in liver biopsies and searched for their contribution to the pathologic diagnosis of INCPH. Materials and methods Hematoxylin–eosin, CD34, and GS-stained liver needle biopsy sections of 16 patients clinically diagnosed with INCPH were retrospectively analyzed. Histologic findings such as portal vein narrowing, obliteration, or loss were grouped as major findings, while portal vein herniation, hypervascularized portal tracts, and periportal abnormal vessels were grouped as minor findings, and their frequency were evaluated. Periportal endothelial CD34 stained areas were measured via ocular micrometer. The distribution of GS immunoexpression was evaluated. Eighteen healthy liver donor biopsies were evaluated as controls. Results In INCPH cases, 58% of portal tracts showed major findings, compared to 15% in the control group (p < 0.001). Minor findings were observed in 16% of INCPH cases and 7% of controls (p = 0.014). The number of portal tracts with histologic findings is significantly higher in INCPH than in control liver biopsies. Abnormal portal tract distribution, like being close to each other, was seen in 75% of INCPH cases but not in controls (p < 0.001). Nodular regenerative hyperplasia (NRH) was present in 31% of cases. Periportal CD34 expression was higher in INCPH, and affected areas were larger than in controls (p < 0.001). Irregular GS staining, i.e. GS staining with patchy distribution in zone 3, and/or periportal and zone 2 hepatocytes, was found in 62% of INCPH cases, while controls showed the usual pattern (p < 0.001). Conclusion In the biopsy diagnosis of INCPH, in addition to the presence of major histologic findings and the amount of portal tracts displaying these features, the expression of endothelial CD34 in periportal areas, and irregular hepatocellular GS expression can also be considered as supporting feature.

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“…Ohbu et al also observed no shunt between aberrant vessels and the central vein [16]. However, Sato et al recently reported shunt formation in the liver with INCPF [17]. Aberrant vessels in INCPH have been investigated from various viewpoints, as described above, but the pathologic clarification is still insufficient.…”

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confidence: 99%

Pathology of idiopathic non-cirrhotic portal hypertension

Kage

2017

Hepatol Int

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Altered intrahepatic microcirculation of idiopathic portal hypertension in relation to glutamine synthetase expression

Abstract: GS immunostaining revealed microcirculatory disturbances of IPH that were associated with abnormalities in both venous and arterial vessels.

Cited by 6 publications

References 16 publications

Chemotherapy-induced Sinusoidal Injury (CSI) score: a novel histologic assessment of chemotherapy-related hepatic sinusoidal injury in patients with colorectal liver metastasis

Chemotherapy-induced Sinusoidal Injury (CSI) score: a novel histologic assessment of chemotherapy-related hepatic sinusoidal injury in patients with colorectal liver metastasis

Evaluation of the histologic and immunohistochemical (CD34, glutamine synthetase) findings in idiopathic non-cirrhotic portal hypertension (INCPH)

Pathology of idiopathic non-cirrhotic portal hypertension

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