Insulin resistance in noncirrhotic idiopathic portal hypertension

To explore further the pathogenesis of glucose intolerance and insulin resistance observed in patients with cirrhosis and portal hypertension, we studied a 35-year-old woman with presinusoidal portal hypertension without cirrhosis due to nodular regenerative hyperplasia of the liver. After oral glucose ingestion, glucose tolerance remained normal; however, this occurred at the expense of a markedly hyperinsulinemic plasma response, suggesting the presence of insulin resistance. To examine this question more directly, we performed a stepwise euglycemic insulin clamp study in combination with an infusion of [6-3H]glucose and [1-14C]palmitate and indirect calorimetry. The ability of insulin to promote total body (primarily muscle) glucose uptake was markedly impaired, whereas its effect to suppress hepatic glucose production was normal compared with results obtained in nine healthy subjects. Moreover, insulin failed to normally suppress plasma free fatty acid turnover and oxidation in this patient. This informative case demonstrates that portal hypertension alone, without hepatic dysfunction from cirrhosis, is associated with impaired insulin-mediated glucose and plasma free fatty acid metabolism and may also play a predominant role in the development of insulin resistance in many cirrhotic patients.     

急性肝内窦前型门静脉高压症大鼠肝内门体分流的变化及其意义

目的探讨急性肝内窦前型门静脉高压症时肝内门体分流的变化及其意义。方法经大鼠门静脉注射乳胶微球造成急性肝内窦前型门静脉高压症。采用肝山梨醇摄取率法测定功能性肝血流量和肝内门体分流量,采用放射性微球法测定肝内较大门体分流侧支(直径>15μm)的分流率。结果对照组肝山梨醇摄取率为(97.9±0.5)％,肝总血流量为每100g体重(2.52±0.23)ml／min。微球组,肝山梨醇摄取率锐减至(12.8±4.3)％,微球加肝动脉结扎组则下降至(4.1±0.7)％,t值为3.541和3.668,P值均<0.01;肝内门体分流量对照组、微球组、微球加肝动脉结扎组分别为每100g体重(0.06±0.02)、(1.46±0.15)和(1.16±0.19)ml／min,t值分别为5.468和6.869,P值均<0.01;门静脉血流量3组差异无统计学意义。结论肝内门体分流的直径大多<15μm。其开放可使70％的门静脉血绕过肝窦而直接注入肝静脉,并有效阻止了门静脉压力的升高。     

Arsenicosis,possibly from contaminated groundwater,associated with noncirrhotic intrahepatic portal hypertension

Background and Aims

Idiopathic noncirrhotic intrahepatic portal hypertension (NCIPH), a chronic microangiopathy of the liver caused by arsenicosis from use of contaminated groundwater, was reported from Asia. This study aimed to see, if in the twenty-first century, arsenicosis was present in NCIPH patients at our hospital and, if present, to look for groundwater contamination by arsenic in their residential locality.

Methods

Twenty-seven liver biopsy proven NCIPH patients, 25 portal hypertensive controls with hepatitis B or C related cirrhosis and 25 healthy controls, matched for residential locality, were studied. Eighty-four percent to 96 % of study subjects belonged to middle or lower socioeconomic category. Arsenicosis was looked for by estimation of arsenic levels in finger/toe nails and by skin examination. Arsenic levels in nails and in ground water (in NCIPH patients with arsenicosis) was estimated by mass spectrometry.

Results

Nail arsenic levels were raised in five (10 %) portal hypertensive study subjects [two NCIPH patients (both had skin arsenicosis) and three portal hypertensive controls]. All of these five patients were residents of West Bengal or Bangladesh. Skin arsenicosis was noted in three NCIPH patients (11 %) compared to none of disease/healthy controls. Ground water from residential locality of one NCIPH patient with arsenicosis (from Bangladesh) showed extremely high level of arsenic (79.5 μg/L).

Conclusions

Arsenicosis and microangiopathy of liver, possibly caused by environmental contamination continues in parts of Asia. Further studies are needed to understand the mechanisms of such ‘poverty-linked thrombophilia’.

     

Molecular mechanisms of increased intrahepatic resistance in portal hypertension

Portal hypertension is associated with changes in the intrahepatic, systemic, and portosystemic collateral circulation. Alterations in vasoreactivity (vasodilation and vasoconstriction) play a central role in the pathogenesis of portal hypertension by contributing to increased intrahepatic resistance, hyperdynamic circulation, and expansion of the collateral circulation. Portal hypertension is also importantly characterized by changes in vascular structure; termed vascular remodeling, which is an adaptive response of the vessel wall that occurs in response to chronic changes in the environment such as shear stress. These complementary processes of vasoreactivity and vascular remodeling contribute importantly to increased intrahepatic resistance and represent important targets in the treatment of portal hypertension. This review will focus on these processes within the intrahepatic circulation, a circulatory bed whose study, that Dr Roberto Groszmann has pioneered.     

Surgical treatment of a descending aortic aneurysm in a patient with noncirrhotic portal hypertension and a portal systemic shunt.

A 63-year-old male with atrial fibrillation and mild mitral valve regurgitation was referred to hospital because of a descending aortic aneurysm. During the evaluation, he developed an encephalopathy because of hyperammoniaemia. Further examination revealed a portal systemic shunt, perhaps caused by the noncirrhotic portal hypertension. The patient underwent successful replacement of the aneurysm after controlling the blood ammonia level by eliminating protein from the diet and removal of nitrogen from the gastrointestinal tract. Cardiovascular surgery in a patient with noncirrhotic portal hypertension and a portal systemic shunt has not been previously reported. Meticulous management of the perioperative blood ammonia concentration is essential.     

Prevalence of autonomic dysfunction in cirrhotic and noncirrhotic portal hypertension

OBJECTIVE: Autonomic dysfunction is common in patients with cirrhosis of the liver, but more so in patients with decompensated state, and is associated with increased mortality. We evaluated the presence and extent of autonomic dysfunction in patients with extrahepatic portal venous obstruction (EHPVO) and noncirrhotic portal fibrosis (NCPF), diseases with relatively preserved liver functions. METHODS: Heart rate variability in response to standing, deep breathing, and Valsalva maneuver and blood pressure response to sustained handgrip and standing were studied in 18 patients with EHPVO (13 mol/L, 5 F, mean age 15.2 +/- 6 yr), 12 patients with NCPF (5 mol/L, 7 F, mean age 26.4 +/- 8 yr), 15 patients with cirrhosis (7 mol/L, 8 F, mean age 12.6 +/- 6 yr), and 17 healthy controls (11 mol/L, 6 F, mean age 18.6 +/- 3 yr). Time-domain parameters of heart rate variability on 24-h ambulatory monitoring were assessed in all the patients. RESULTS: Autonomic dysfunction was observed in 67% of EHPVO, 25% of NCPF, and 80% of cirrhotic subjects but none of the healthy controls (p < 0.05). Four of five time-domain heart rate variability indices showed significant abnormalities in patients with EHPVO (p < 0.05) and cirrhosis (p < 0.05), when compared with patients with NCPF and healthy controls. CONCLUSIONS: Autonomic dysfunction is frequently encountered in patients with EHPVO and cirrhosis, and the presence of autonomic dysfunction in patients with noncirrhotic portal hypertension suggests a primary role of portal hypertension per se in the dysfunction.     

Idiopathic non-cirrhotic intrahepatic portal hypertension: common cause of cryptogenic intrahepatic portal hypertension in a Southern Indian tertiary hospital

Background and aim  

Patients with intrahepatic portal hypertension and negative etiological work-up for liver disease are often labeled as having cryptogenic cirrhosis. The aim of this study was to evaluate causes of liver disease in patients with unexplained intrahepatic portal hypertension.     

Intrahepatic portal occlusion by microspheres: a new model of portal hypertension in the rat.

Available experimental models of portal hypertension are based either on cirrhosis or externally applied portal vein constricting devices. A new method is described of raising portal pressure, which uses intraportally injected microspheres to block intrahepatic portal radicles, which has the advantages of retaining normal liver architecture and providing a more clinically relevant intrahepatic obstruction to portal flow. Measured aliquots of microspheres (15, 25, 50, 90 microns) or equivalent volumes of saline were injected into a peripheral portal tributary (caecal vein) of 22 normal rats. The resultant changes in arterial, portal, and splenic pulp pressures were monitored. Sequential microsphere injections produced graduated rises in portal pressure up to a peak of 18.5-22.5 mm Hg (8.7-12.4 mm Hg increase from basal), which declined gradually to a steady state pressure of 13.3-15.1 mm Hg (4.0-5.0 mm Hg increase). There was no significant difference between pressure increases produced by microspheres of differing sizes. It is concluded that portal hypertension can be produced acutely by blocking portal radicles with microspheres. The maximum pressure achieved, however, is substantially less than that obtained by total portal vein occlusion (mean: 57.6 mm Hg). This suggests the existence of functional intrahepatic portal systemic shunts not previously described in the normal liver.     

Hepatoportal sclerosis as a cause of noncirrhotic portal hypertension in patients with HIV

BACKGROUND: Hepatoportal sclerosis (HPS) is a cause of noncirrhotic portal hypertension, with patients typically presenting with variceal bleeding. It is idiopathic in nature but is felt to be due to an abnormality of the intrahepatic vasculature. HPS is characterized by varying degrees of portal fibrosis, sclerosis of portal vein branches and dilatation of sinusoidal spaces. Nodular regenerative hyperplasia (NRH), another cause of noncirrhotic portal hypertension, has also been recently described in HIV patients initially diagnosed as having cryptogenic liver disease. METHODS/RESULTS: We describe four cases of HIV+ patients presenting with noncirrhotic portal hypertension; liver biopsies were reviewed by an experienced liver pathologist and found to be consistent with HPS. No other etiologies for their liver disease were found. CONCLUSIONS: HPS has been recently identified as a cause of noncirrhotic portal hypertension in patients with HIV. It should be considered in the differential diagnosis of HIV patients presenting with variceal bleeding. We postulate that it may be due to intrahepatic microthrombosis or an altered hepatic fibrogenesis related to highly active antiretroviral therapy or due to HIV itself.     

The relationship between intrahepatic portal systemic shunts and microsphere induced portal hypertension in the rat liver

Background—Portal hypertension is associated withgross haemodynamic disturbances characterised by high cardiac output,low peripheral vascular resistance, increased splanchnic blood flow, and portal systemic shunting.
Aims—To study the relationship betweenintrahepatic portal systemic shunts and microsphere induced portalhypertension in the rat liver.
Methods—Different sized microspheres weresequentially injected into the portal vein of male Wistar rats.
Results—Steady state portal venous pressure wasincreased by 102.2 (35.6)% (14.9 (3.6) mm Hg) and 272.3 (78.0)% (24.0 (2.2) mm Hg) above the basal pressure following sequential injections of 15 and 80 µm diameter microspheres, respectively. Sequential injection of 15, 40, and 80 µm diameter microspheres in either ascending or descending order of size did not generate further increases in portal venous pressure. A single injection of 1.8× 10⁵ 80 µm microspheres consistently produced a steadystate portal venous pressure of 19.0 (1.3) mm Hg but did not approachthe much higher value of 36.6 (43.2) mm Hg measured during clamping of the portal vein. These data indicate that the opening of patent intrahepatic shunts was responsible for the reduced pressures observedduring microsphere injections and further evidence for this wasprovided by the location of microspheres in the pulmonary vascular bed.The elevation in portal venous pressure achieved by microsphereinjections was not significantly different to that produced in ratssubjected to partial portal vein ligation (20.7(0.5) mm Hg, p>0.05).Wedged hepatic venous pressure decreased from 6.7 (0.7) to 3.0 (0.6) mmHg following injection of 80 µm microspheres, suggesting a decreasein total hepatic blood flow. Conversely, injection of 15 µmmicrospheres induced an increase in wedged hepatic venous pressure from7.0 (1.0) mm Hg to 12.4(1.8) mm Hg, indicating a localisedredistribution of blood flow at the presinusoidal level of the portalvenous vascular network and increased intrahepatic shunt flow.
Conclusion—It is suggested that there may be aprotective pathophysiological role for these shunts when the liver issubjected to changes which induce acute portal hypertension.

     

隐源性非硬化性门脉高压症患者临床和肝组织病理学表现

正特发性非硬化性门脉高压症(Idiopathoc noncirrhotic portal hypertension,INCPH)是近来提出的名词,代替门脉性肝硬化、隐源性门脉高压、不完全间隔性硬化或再生性结节性增生(NRH)等,用来描述由于未知原因引起肝窦前性门脉高压,其特征是门脉高压(食管静脉曲张,非恶性腹水,侧枝循环),脾肿大,门静脉和肝静脉通畅,而没有临床和     

Altered intrahepatic pathway of para-umbilical vein in portal hypertension

The object of this study was to determine the frequency and characteristics of altered paraumbilical vein in the hepatic parenchyma, developed from portal hypertension, using computed tomography (CT). Two hundred and ninety-two patients who presented with portal hypertension from 1986 to 1996 were studied retrospectively. The pathway of the dilated para-umbilical vein was demonstrated by contrast-enhanced CT. Thirty-one (11%) patients had a dilated para-umbilical vein arising from the left portal vein into the falciform ligament. In 24 (77%) of these patients, the para-umbilical vein followed the expected route, passing through the fissure of ligamentum teres hepatis. The remaining seven patients (23%) displayed the unusual pathway, with the vein arising from the left branch of the portal vein and passing into the hepatic parenchyma. In these seven patients, four had one collateral vein, and three patients had two collateral veins in the liver parenchyma. The dilated para-umbilical vein frequently passes through the hepatic parenchyma in patients with portal hypertension.     

系统性硬化症合并非肝硬化性门静脉高压症一例并文献复习

目的 提高风湿科医生对非肝硬化性门静脉高压症的认识.方法 报告1例系统性硬化症合并非肝硬化性门静脉高压症的认识并复习相关文献.结果 患者为51岁女性,病程较长,以门静脉高压为最突出的临床表现,有脾大,全血细胞减少,门静脉重度曲张.肝脏的生化、病毒学以及形态学指标均正常.腹部增强CT未见门静脉血栓形成.最后,诊断为系统性硬化症合并非肝硬化性门静脉高压症.给予小剂量激素及免疫抑制剂治疗,病情稳定.结论 非肝硬化性门静脉高压症是一种少见病,临床上最突出的表现是门静脉高压,该病与风湿性疾病尤其是系统性硬化症合并鲜有报道,风湿科医生应予以重视.     

非肝硬化门脉高压患者临床特点分析

目的 总结非肝硬化门脉高压症(NCPH)患者的临床特点和肝静脉压力梯度(HVPG)的变化.方法 2017年1月～2019年12月南京市第二医院住院的28例NCPH患者,采用Seldinger法穿刺右侧颈内静脉,使用一次性球囊导管测定肝静脉压力,计算HVPG,接受肝活检检查.结果 在本组28例NCPH患者中,诊断特发性门...