• Clinical Nutrition Research
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• 제12권2호
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• pp.154-167
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• 2023

Hepatic encephalopathy (HE) associated with liver failure is accompanied by hyperammonemia, severe inflammation, depression, anxiety, and memory deficits as well as liver injury. Recent studies have focused on the liver-brain-inflammation axis to identify a therapeutic solution for patients with HE. Lipocalin-2 is an inflammation-related glycoprotein that is secreted by various organs and is involved in cellular mechanisms including iron homeostasis, glucose metabolism, cell death, neurite outgrowth, and neurogenesis. In this study, we investigated that the roles of lipocalin-2 both in the brain cortex of mice with HE and in Neuro-2a (N2A) cells. We detected elevated levels of lipocalin-2 both in the plasma and liver in a bile duct ligation mouse model of HE. We confirmed changes in cytokine expression, such as interleukin-1β, cyclooxygenase 2 expression, and iron metabolism related to gene expression through AKT-mediated signaling both in the brain cortex of mice with HE and N2A cells. Our data showed negative effects of hepatic lipocalin-2 on cell survival, iron homeostasis, and neurite outgrowth in N2A cells. Thus, we suggest that regulation of lipocalin-2 in the brain in HE may be a critical therapeutic approach to alleviate neuropathological problems focused on the liver-brain axis.

• Journal of Yeungnam Medical Science
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• 제40권2호
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• pp.136-145
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• 2023

Hepatic encephalopathy (HE) is a severe neuropsychiatric abnormality in patients with either acute or chronic liver failure. Typical brain magnetic resonance imaging findings of HE are bilateral basal ganglia high signal intensities due to manganese deposition in chronic liver disease and hyperintensity in T2, fluid-attenuated inversion recovery, or diffusion-weighted imaging (DWI) with hemispheric white matter changes including the corticospinal tract. Low values on apparent diffusion coefficient mapping of the affected area on DWI, indicating cytotoxic edema, can be observed in acute HE. However, neuropsychological impairment in HE ranges from mild deficits in psychomotor abilities affecting quality of life to stupor or coma with higher grades of hepatic dysfunction. In particular, the long-lasting compensatory mechanisms for the altered metabolism in chronic liver disease make HE imaging results variable. Therefore, the clinical relevance of imaging findings is uncertain and differentiating HE from other metabolic diseases can be difficult. The recent introduction of concepts such as "acute-on-chronic liver failure (ACLF)," a new clinical entity, has led to a change in the clinical view of HE. Accordingly, there is a need to establish a corresponding concept in the field of neuroimaging diagnosis. Herein, we review HE from a historical and etiological perspective to increase understanding of brain imaging and help establish an imaging approach for advanced new concepts such as ACLF. The purpose of this manuscript is to provide an understanding of HE by reviewing neuroimaging findings based on pathological and clinical concepts of HE, thereby assisting in neuroimaging interpretation.

• 대한영상의학회지
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• 제85권2호
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• pp.381-393
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• 2024

목적 간성뇌증(hepatic encephalopathy; 이하 HE)의 대사이상은 뇌부종 또는 탈수초성 질환을 일으켜 자기공명영상에서 대칭적인 지역 뇌부종을 유발한다. 본 연구에서 HE 환자의 뇌 자기공명영상에서 대칭적인 지역 뇌부종 패턴의 군집화 분석을 통해 뇌부전 발생 예측의 유용성을 조사하는 것을 목적으로 한다. 대상과 방법 연속적인 HE 환자 98명을 대상으로 MR 소견과 임상자료를 후향적으로 분석하였다. Symmetric regional cerebral edema (이하 SRCE)의 12개 영역 간의 상관관계는 파이(φ) 계수를 사용하여 계산하였고, φ² 거리 측정과 Ward의 방법을 사용하여 계층적 군집화를 사용하여 패턴을 분류하였다. SRCE의 분류된 패턴은 말기 간 질환 모델(model for endstage liver disease; 이하 MELD) 점수 및 HE 등급과 같은 임상과 상관관계를 조사하였다. 결과 적색 핵과 뇌량(φ = 0.81, p < 0.001), 대뇌 십자 및 적색 핵(φ = 0.72, p < 0.001), 적색핵과 치상핵(φ = 0.66, p < 0.001)을 포함한 22쌍의 관심영역 사이에 유의한 연관성이 발견되었다. 계층적 군집화 후 24건을 I군, 35건을 II군, 39건을 III군으로 분류하였다. 그룹 III은 그룹 I에 비해 MELD 점수(p = 0.04)와 HE 등급(p = 0.002)이 더 높았다. 결론 본 연구는 HE 환자에서 대칭적인 지역 뇌부종의 패턴은 간 보존 및 뇌부전 발생을 예측하는 데 유용할 수 있음을 보여주었다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3131-3135
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• 2015

Objective: To investigate whether the expression of serum soluble neural cell adhesion molecule (sNCAM) is associated with hepatic encephalopathy (HE) in hepatocelular carcinoma (HCC) patients. Materials and Methods: The Oncomine Cancer Microarray database was used to determine the clinical relevance of NCAM expression in different kinds of human cancers. Sera from 75 HCC cases enrolled in this study were assessed for expression of sNCAM by enzyme linked immunosorbent assay (ELISA). Results: Dependent on the Oncomine Cancer Microarray database analysis, NCAM was down regulated in 10 different kinds of cancer, like bladder cancer, brain and central nervous system cancer, while up-regulated in lung cancer, uterine corpus leiomyoma and sarcoma, compared to normal groups. Puzzlingly, NCAM expression demonstrated no significant difference between normal and HCC groups. However, we found by quantitative ELISA that the level of sNCAM in sera from HCC patients with HE ($347.4{\pm}151.9ng/ml$) was significantly more up-regulated than that in HCC patients without HE ($260.3{\pm}104.2ng/ml$), the p-value being 0.008. sNCAM may be an important risk factor of HE in HCC patients, the correlation coefficients was 0.278 (P<0.05) on rank correlation analysis. Conclusions: This study highlights that up-regulated level of serum sNCAM is associated with HE in HCC patients and suggests that the high expression can be used as an indicator.

• 동의생리병리학회지
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• 제23권4호
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• pp.919-924
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• 2009

The liver is one of the principal organs involved in glucose metabolism. Diabetes mellitus(DM) commonly develops in patients with liver cirrhosis as a result of hepatocyte dysfunction. Hepatic encephalopathy(HE) is a major neuropsychiatric complication of liver cirrhosis. HE develops frequently in advanced stage of liver cirrhosis due to portal hypertension. We experienced a case of liver cirrhosis with DM and HE in 67 years old male patient. The patient's symptoms were lethargy, general malaise, asterixis, dizziness, and heavy headedness. Hwangryunjihwang-tang, Saengkankunbi-tang, Injinchija-tang and Injinho-tang were prescribed to the patient. Finally, the symptoms had been improved, however significant change was not observed from serum ammonia, fasting blood sugar and postparandial blood sugar. So we hope that this case report will be helpful in treating patient of liver cirrhosis.

• Journal of Veterinary Science
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• 제21권3호
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• pp.44.1-44.10
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• 2020

Background: Congenital portosystemic shunt (cPSS) is one of the most common congenital disorders diagnosed in dogs. Hepatic encephalopathy (HE) is a frequent complication in dogs with a cPSS and is a major cause of morbidity and mortality. Despite HE been a major cause of morbidity in dogs with a cPSS, little is known about the cellular changes that occur in the central nervous system of dogs with a cPSS. Objectives: The objective of this study was to characterise the histological changes in the cerebral cortex and cerebellum of dogs with cPSS with particular emphasis on astrocyte morphology. Methods: Eight dogs with a confirmed cPSS were included in the study. Results: Six dogs had substantial numbers of Alzheimer type II astrocytes and all cases had increased immunoreactivity for glial fibrillary acidic protein in the cerebral cortex, even if there were minimal other morphological changes. Conclusions: This study demonstrates that dogs with a cPSS have marked cellular changes in the cerebral cortex and cerebellum. The cellular changes that occur in the cerebral cortex and cerebellum of dogs with spontaneously arising HE are similar to changes which occur in humans with HE, further validating dogs with a cPSS as a good model for human HE.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제11권1호
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• pp.56-59
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• 2008

저자들은 간의 거대 종괴와 심방 중격 결손으로 수술을 받았던 환아에서 복부 CT와 간 조직 검사를 통해 확인된 Abernethy 기형 2형 1예를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제11권2호
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• pp.210-213
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• 2008

저자들은 버섯 중독 후 간성 뇌증을 동반한 급성 간부전으로 발현된 소아를 Penicillin GK를 사용한 약물 요법으로 완치할 수 있었다. 소아에서 급성 간부전은 사망률이 높은 위중한 질병이며, 생존을 위하여 간이식이 필요한 경우가 많다. 그러나 일부의 경우에는 본 증례와 같이 정확한 병력 청취에 의하여 특별한 치료를 시행하면 간이식을 시행하지 않고서도 환아의 생명을 구할 수 있다.

• 대한약리학회지
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• 제32권3호
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• pp.293-300
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• 1996

흰쥐에 thioacetamide(TAA)를 투여하면 간성뇌장애가 유발된다. 두가지 행동 상태(꼬리 접촉자극 및 미자극)와 세 단계의 신경학적 이상의 단계(정상, 약한 운동실조, 심한 운동실조)별로 뇌파를 기록하였고, 뇌파 스펙트럼 및 대역 분석을 통하여 간성뇌장애 진행동안 뇌파의 정량적인 변동을 관찰하였다. 정상 쥐에서 자극은 $theta(3.5{\sim}8\;Hz)$ 및 $gamma(30{\sim}50\;Hz)$ 대역의 power을 증가시켰다. 운동실조가 있는 쥐에서 이러한 변화가 일어나지 못하였다. 꼬리 자극을 하는 상태에서 theta 대역의 변화는 gamma 대역의 변화 보다 더욱 일찍 관찰되었다. 신경학적 행동 단계가 심해짐에 따라서 $beta3(21{\sim}30\;Hz)$ 및 gamma 대역에서 power가 점차적으로 감소하였다. 또한 간성뇌장애의 신경학적 증상은 benzodiazepine계 물질에 의하여 야기된다는 가설이 있으므로 beta power의 증가가 관찰될 것으로 기대하였으나 이 연구에서는 관찰하지 못하였다. 이 결과들로 미루어 볼때 이 연구에 사용된 스펙트럼 및 대역 분석이 간성뇌장애동안 신경학적 증상의 정도를 정량화 할 수 있다고 생각된다.

• 대한임상독성학회지
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• 제11권1호
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• pp.28-30
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• 2013

A 66-year-old male with chronic alcoholism presented with tremor, gait disturbance, memory impairment, insomnia, decreased appetite, and confusion. The patient had been taking lithium daily for treatment of bipolar disorder. Brain CT showed no specific abnormality, and serum lithium and ammonia levels were 3.63 mEq/L (therapeutic range, 0.6~1.2 mEq/L) and $85{\mu}g/dL$ (reference range: $19{\sim}54{\mu}g/dL$), respectively. Therefore, the initial differential diagnosis included chronic lithium intoxication, hepatic encephalopathy, Wernicke encephalopathy, or alcohol withdrawal syndrome. Even with the provision of adequate hydration, the patient's neurologic status did not show improvement, so that lactulose enema, thiamine replacement, and continuous venovenous hemodiafiltration (CVVHDF) were started on the third admission day. By the fifth admission day he had made a rapid neurologic recovery, and was discharged on the 20th admission day. Therefore, CVVHDF might be a treatment for patients with chronic lithium intoxication, because, even if serum lithium concentration is normal, lithium concentration in the brain may be different from that of the serum.