Sleep Disturbance Is Associated With the Presence of Portosystemic Collaterals in Patients With Compensated Cirrhosis.

Disturbed sleep is common among patients with cirrhosis. The extent to which this is associated with the different stages of compensated cirrhosis is unknown. This study examines whether the presence of portosystemic collaterals, an indicator of clinically significant portal hypertension, is associated with sleep disturbance in compensated cirrhosis. We conducted a cross-sectional study among patients with compensated cirrhosis, comparing sleep characteristics, sleep quality, and excessive daytime sleepiness between 21 patients without and 21 patients with portosystemic collaterals. Patients were assessed with wrist actigraphy, Pittsburgh Sleep Quality Index, and the Epworth Sleepiness Scale. Collateral presence was determined by imaging and esophagogastroduodenoscopy. Differences in sleep characteristics were analyzed using t tests and computed effect sizes. Multivariable linear regression analysis was used to evaluate the association between collaterals and sleep disturbance while controlling for possible confounders. The group of patients with collaterals had greater beta-blocker and tobacco use, lower albumin, and higher international normalized ratio compared to the group without collaterals. Patients with collaterals had more sleep fragmentation (Cohen's d = -0.86), lower sleep efficiency (Cohen's d = 0.59), and lower total sleep time (Cohen's d = 0.75) than patients without collaterals. The presence of collaterals was independently associated with greater sleep fragmentation (P = 0.046) and greater daytime sleepiness (P = 0.030). Conclusion: Patients with compensated cirrhosis complicated by portosystemic collaterals experienced more sleep disturbance than those without collaterals.

Soluble guanylyl cyclase stimulation and phosphodiesterase-5 inhibition improve portal hypertension and reduce liver fibrosis in bile duct-ligated rats.

BACKGROUND: In cirrhosis, the nitric oxide-soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway is impaired, which contributes to increased intrahepatic vascular resistance (IHVR) and fibrogenesis. We investigated if sGC stimulation (riociguat (RIO)), sGC activation (cinaciguat (CINA)) or phosphodiesterase (PDE)-5 inhibition (tadalafil (TADA)) improves portal hypertension (PHT) and liver fibrosis. METHODS: Fifty male Sprague-Dawley rats underwent bile-duct ligation (BDL) or sham operation. RIO (0.5 mg/kg), CINA (1 mg/kg), TADA (1.5 mg/kg) or vehicle (VEH) was administered from weeks 2 to 4 after BDL. At week 4, invasive haemodynamic measurements were performed, and liver fibrosis was assessed by histology (chromotrope-aniline blue (CAB), Picro-Sirius red (PSR)) and hepatic hydroxyproline content. RESULTS: Cirrhotic bile duct-ligated rats presented with PHT (13.1 ± 1.0 mmHg) and increased IHVR (4.9 ± 0.5 mmHg⋅min/mL). Both RIO (10.0 ± 0.7 mmHg, p = 0.021) and TADA (10.3 ± 0.9 mmHg, p = 0.050) decreased portal pressure by reducing IHVR (RIO: -41%, p = 0.005; TADA: -21%, p = 0.199) while not impacting heart rate, mean arterial pressure and portosystemic shunting. Hepatic cGMP levels increased upon RIO (+239%, p = 0.006) and TADA (+32%, p = 0.073) therapy. In contrast, CINA dosed at 1 mg/kg caused weight loss, arterial hypotension and hyperlactataemia in bile duct-ligated rats. Liver fibrosis area was significantly decreased by RIO (CAB: -48%, p = 0.011; PSR: -27%, p = 0.121) and TADA (CAB: -21%, p = 0.342; PSR: -52%, p = 0.013) compared to VEH-treated bile duct-ligated rats. Hepatic hydroxyproline content was reduced by RIO (from 503 ± 20 to 350 ± 30 µg/g, p = 0.003) and TADA (282 ± 50 µg/g, p = 0.003), in line with a reduction of the hepatic stellate cell activation markers smooth-muscle actin and phosphorylated moesin. Liver transaminases decreased under RIO (AST: -36%; ALT: -32%) and TADA (AST: -24%; ALT: -27%) treatment. Hepatic interleukin 6 gene expression was reduced in the RIO group (-56%, p = 0.053). CONCLUSION: In a rodent model of biliary cirrhosis, the sGC stimulator RIO and the PDE-5 inhibitor TADA improved PHT. The decrease of sinusoidal vascular resistance was paralleled by a reduction in liver fibrosis and hepatic inflammation, while systemic haemodynamics were not affected.

Endoscopic ultrasound-guided sampling and profiling of portal circulation in human patients for metabolic research studies and biomarker assessment.

Portal and hepatic circulation can now be safely accessed using endoscopic ultrasound (EUS). EUS-guided needle access of the portal vein is performed clinically at select tertiary centers for measurement of portal pressure gradients in patients with chronic liver disease and sampling of portal venous thrombus to diagnose malignancy. We propose that this novel clinical technique can be applied in research studies to allow blood collection from and profiling of portal and hepatic circulation. In this technical report, we present and highlight the technical aspects, feasibility, and safety of EUS: guided portal venous blood collection. As a proof of the concept and the utility of this technique in metabolic research and biomarker assessment and discovery, we present a pilot metabolite profiling study of portal venous blood in a small cohort of patients with cirrhosis and a comparison with a group without cirrhosis. Despite the very small diameter of the endoscopic needle used for the blood collection, the portal samples have the same quality as those collected from systemic circulation, and they can be used for the same downstream applications. Finally, we propose an analytical workflow to screen for promising metabolites that could qualify for further studies to determine their utility as sensitive, early candidate biomarkers of hepatic fibrosis, portal shunt, and hypertension. We hope that this report could stimulate and facilitate the widespread use of EUS-guided techniques for the profiling of portal circulation, which could potentially open a new field of scientific inquiry.NEW & NOTEWORTHY The technical aspects, feasibility, and safety of endoscopic ultrasound (EUS)-guided needle access for portal venous blood collection are presented in this technical report. Despite the very small diameter of the endoscopic needle, portal blood samples have the same quality as those collected from systemic circulation. As a proof of the concept and the utility of this technique in metabolic research and biomarker assessment and discovery, we present a pilot metabolite profiling study of portal venous blood in a small cohort of patients with cirrhosis and a comparison with a group without cirrhosis.

Intrahepatic veno-venous collateralization and misrepresentative hepatic venous pressure gradients in children.

BACKGROUND: Accurate and reproducible means of measuring the portosystemic gradient are essential for risk stratification and treatment of portal hypertension. OBJECTIVE: To report the reliability of hepatic venous pressure gradients in children with intrahepatic veno-venous collateralization. MATERIALS AND METHODS: Between January 2012 and December 2019 (96 months), 39 patients with native livers underwent wedge hepatic venography and hepatic venous pressure gradient measurements at a tertiary pediatric center. All archived images were reviewed for balloon isolation of the hepatic vein and hepatic vein-to-hepatic vein (HV-HV) collaterals. HV-HV collaterals were categorized as present on the basis of non-catheterized segmental venous opacification despite appropriate balloon isolation. Hepatic venous pressure gradient was defined as the difference of wedge and free hepatic venous pressures. Wedge portosystemic gradient was defined as the difference between wedge hepatic venous pressure and right atrial (RA) pressures. For patients subsequently undergoing portal venous catheterization, portosystemic gradient was defined as the difference between main portal vein and RA pressures. RESULTS: Thirteen of 39 (33.3%) patients demonstrated HV-HV collaterals on wedge hepatic venography. The mean hepatic venous pressure gradient was 5.2±3.8 mmHg (range: 0-15 mmHg). The mean hepatic venous pressure gradient was 3.6±2.6 mmHg (range: 0-9 mmHg) in the presence of HV-HV collaterals and 5.9±4.2 mmHg (range: 1-15 mmHg) in the absence of HV-HV collaterals (P=0.043). Twelve (30.8%) patients were found to have varices: 10 gastroesophageal, 1 rectal and 1 stomal. The mean hepatic venous pressure gradient in patients with varices was 5.4±47 mmHg (range: 0-15 mmHg). For patients with varices, mean hepatic venous pressure gradient was 3.0±2.7 mmHg (range: 0-9 mmHg) in the presence of HV-HV collaterals and 10.3±4.1 mmHg (range: 5-15 mmHg) in the absence of HV-HV collaterals (P=0.004). Four (10.3%) patients had extrahepatic portal vein occlusion: 3 with cavernous transformation and 1 with type Ib Abernethy malformation. All patients with extrahepatic portal vein occlusion demonstrated HV-HV collaterals compared with 8 of 35 (22.9%) patients without extrahepatic portal vein occlusion (P=0.002). Four of 39 (10.3%) patients underwent direct portal pressure measurements: 3 via transhepatic and 1 via trans-splenic portal access. All had demonstrated HV-HV collaterals on wedged imaging. One had extrahepatic portal vein occlusion. The mean time between wedge portosystemic gradient and portosystemic gradient measurement was 3.75 days (range: 0-8 days). The mean wedge portosystemic gradient was 4.5±3.1 mmHg (range: 2-9 mmHg) and the mean portosystemic gradient was 14.5±3.7 mmHg (range: 12-20 mmHg) (P=0.006). CONCLUSION: HV-HV collateralization is frequently observed in children undergoing wedged portal venography and leads to misrepresentative hepatic venous pressure gradients. All patients undergoing hepatic venous pressure gradient measurement should have wedged venography to identify HV-HV collaterals and to qualify measured pressures. Additional techniques to obtain representative pressures in the presence of HV-HV collaterals warrant further investigation.

Spontaneous porto-systemic shunts in liver cirrhosis: Clinical and therapeutical aspects.

Spontaneous porto-systemic shunts (SPSS) are frequent in liver cirrhosis and their prevalence increases as liver function deteriorates, probably as a consequence of worsening portal hypertension, but without achieving an effective protection against cirrhosis' complications. Several types of SPSS have been described in the literature, each one associated with different clinical manifestations. In particular, recurrent or persistent hepatic encephalopathy is more frequent in patients with splenorenal shunt, while the presence of gastric varices and consequently the incidence of variceal bleeding is more common in gastrorenal shunt. In the advanced stage, the presence of large SPSS can lead to the so called "portosystemic shunt syndrome", characterized by a progressive deterioration of hepatic function, hepatic encephalopathy and, sometimes, portal vein thrombosis. The detection of SPSS in patients with liver cirrhosis is recommended in order to prevent or treat recurrent hepatic encephalopathy or variceal bleeding.

Is Portal Inflow Modulation Always Necessary for Successful Utilization of Small Volume Living Donor Liver Grafts?

Although the well-accepted lower limit of the graft-to-recipient weight ratio (GRWR) for successful living donor liver transplantation (LDLT) remains 0.80%, many believe grafts with lower GRWR may suffice with portal inflow modulation (PIM), resulting in equally good recipient outcomes. This study was done to evaluate the outcomes of LDLT with small-for-size grafts (GRWR <0.80%). Of 1321 consecutive adult LDLTs from January 2012 to December 2017, 287 (21.7%) had GRWR <0.80%. PIM was performed (hemiportocaval shunt [HPCS], n = 109; splenic artery ligation [SAL], n = 14) in 42.9% patients. No PIM was done if portal pressure (PP) in the dissection phase was <16 mm Hg. Mean age of the cohort was 49.3 ± 9.1 years. Median Model for End-Stage Liver Disease score was 14, and the lowest GRWR was 0.54%. A total of 72 recipients had a GRWR <0.70%, of whom 58 underwent HPCS (1 of whom underwent HPCS + SAL) and 14 underwent no PIM, whereas 215 had GRWR between 0.70% and 0.79%, of whom 51 and 14 underwent HPCS and SAL, respectively. During the same period, 1034 had GRWR ≥0.80% and did not undergo PIM. Small-for-size syndrome developed in 2.8% patients. Three patients needed shunt closure at 1 and 4 weeks and 60 months. The 1-year patient survival rates were comparable. In conclusion, with PIM protocol that optimizes postperfusion PP, low-GRWR grafts can be used for appropriately selected LDLT recipients with acceptable outcomes.

Four-dimensional Flow MRI as a Marker for Risk Stratification of Gastroesophageal Varices in Patients with Liver Cirrhosis.

Purpose To assess the feasibility of four-dimensional (4D) flow MRI as a noninvasive imaging marker for stratifying the risk of variceal bleeding in patients with liver cirrhosis. Materials and Methods This study recruited participants scheduled for both liver MRI and gastroesophageal endoscopy. Risk of variceal bleeding was assessed at endoscopy by using a three-point scale: no varices, low risk, and high risk requiring treatment. Four-dimensional flow MRI was used to create angiograms for evaluating visibility of varices and to measure flow volumes in main portal vein (PV), superior mesenteric vein, splenic vein (SV), and azygos vein. Fractional flow changes in PV and SV were calculated to quantify shunting (outflow) from PV and SV into varices. Logistic analysis was used to identify the independent indicator of high-risk varices. Results There were 23 participants (mean age, 52.3 years; age range, 25-75 years), including 14 men (mean age, 51.7 years; age range, 25-75 years) and nine women (mean age, 53.2 years; age range, 31-72 years) with no varices (n = 8), low-risk varices (n = 8), and high-risk varices (n = 7) determined at endoscopy. Four-dimensional flow MRI-based angiography helped radiologists to view varices in four of 15 participants with varices. Independent indicators of high-risk varices were flow volume in the azygos vein greater than 0.1 L/min (P = .034; 100% sensitivity [seven of seven] and 62% specificity [10 of 16]) and fractional flow change in PV of less than 0 (P < .001; 100% sensitivity [seven of seven] and 94% specificity [15 of 16]). Conclusion Azygos flow greater than 0.1 L/min and portal venous flow less than the sum of splenic and superior mesenteric vein flow are useful markers to stratify the risk of gastroesophageal varices bleeding in patients with liver cirrhosis. © RSNA, 2018 Online supplemental material is available for this article.

The concept of portal system obstruction in Avicenna's canon of medicine

Historical literature on portal hypertension is mainly focused on the contemporary advances in therapeutic methods, especially surgical ones. However, it seems that the origin of the human knowledge on the portal system, its association with the caval system, obstructive pathologies in this system and the gastrointestinal bleeding due to hepatic diseases might be much older than previously believed. Avicenna provided a detailed anatomy of the portal venous system and its feeding branches in the Canon of Medicine. Soddat al-Kabed va al-Masarigha (liver and mesenteric occlusion) is also a disease presented by Avicenna with clinical, etiological and therapeutic descriptions suggesting the fact that Soddat al-Kabed va al-Masarigha has multiple similarities with the currently identified concept of "portal hypertension". He presented sense of heaviness in the liver area with or without mild pain, anemia, pale and inappropriate body color, and loose stool which can be complicated with ascites, infection, fever and abdominal pain as clinical manifestations of this disease. He has also suggested therapeutic approaches including laxative and diuretic herbs to help excreting the obstructive material into stool or urine.

Liver hypertrophy: Underlying mechanisms and promoting procedures before major hepatectomy.

Various procedures can promote hypertrophy of the future liver remnant (FLR) before major hepatectomy to prevent postoperative liver failure. The pathophysiological situation following portal vein embolization (PVE), hepatic artery ligation/embolization or hepatectomy remains unclear. On one hand, the main mechanisms of hepatic regeneration appear to be driven by hepatic hypoxia (involving the hepatic arterial buffer response), an increased portal blood flow inducing shear stress and the involvement of several mediators (inflammatory cytokines, vasoregulators, growth factors, eicosanoids and several hormones). On the other hand, several factors are associated with impaired liver regeneration, such as biliary obstruction, malnutrition, diabetes mellitus, male gender, age, ethanol and viral infection. All these mechanisms may explain the varying degrees of hypertrophy observed following a surgical or radiological procedure promoting hypertrophy the FLR. Radiological procedures include left and right portal vein embolization (extended or not to segment 4), sequential PVE and hepatic vein embolization (HVE), and more recently combined PVE and HVE. Surgical procedures include associated liver partition and portal vein ligation for staged hepatectomy, and more recently the combined portal embolization and arterial ligation procedure. This review aimed to clarify the pathophysiology of liver regeneration; it also describes radiological or surgical procedures employed to improve liver regeneration in terms of volumetric changes, the feasibility of the second step and the benefits and drawbacks of each procedure.

Portosystemic collaterals in living donor liver transplantation: What is all the fuss about?

Portosystemic collaterals are a common finding in patients with cirrhosis undergoing liver transplantation. Recently, there has been a renewed interest regarding their significance in the setting of living donor liver transplantation (LDLT) due to concerns of graft hypoperfusion or hyperperfusion and its impact on early posttransplant outcomes. Presence of these collaterals has greater significance in the LDLT setting when compared with the deceased donor liver transplantation setting as dictated by the difference in the physiology of partial liver grafts. We discuss current thinking of portal flow dynamics and the techniques for dealing with this clinical problem. Liver Transplantation 23 537-544 2017 AASLD.

A Meta-analysis for the Diagnostic Performance of Transient Elastography for Clinically Significant Portal Hypertension.

We aimed to evaluate the correlation between liver stiffness measurement using transient elastography (TE-LSM) and hepatic venous pressure gradient and the diagnostic performance of TE-LSM in assessing clinically significant portal hypertension through meta-analysis. Eleven studies were included from thorough literature research and selection processes. The summary correlation coefficient was 0.783 (95% confidence interval [CI], 0.737-0.823). Summary sensitivity, specificity and area under the hierarchical summary receiver operating characteristic curve (AUC) were 87.5% (95% CI, 75.8-93.9%), 85.3 % (95% CI, 76.9-90.9%) and 0.9, respectively. The subgroup with low cut-off values of 13.6-18 kPa had better summary estimates (sensitivity 91.2%, specificity 81.3% and partial AUC 0.921) than the subgroup with high cut-off values of 21-25 kPa (sensitivity 71.2%, specificity 90.9% and partial AUC 0.769). In summary, TE-LSM correlated well with hepatic venous pressure gradient and represented good diagnostic performance in diagnosing clinically significant portal hypertension. For use as a sensitive screening tool, we propose using low cut-off values of 13.6-18 kPa in TE-LSM.

Graft-to-recipient weight ratio threshold adjusted to the model for end-stage liver disease score for living donor liver transplantation.

The graft-to-recipient weight ratio (GRWR) is an important selection criterion for living donor liver transplantation (LDLT). The generally accepted threshold is known to be 0.8%. We believe that this threshold can be reduced under certain conditions. The aim of this study was to evaluate the results of these patients with GRWR < 0.8%. Between 2004 and 2015, 649 patients underwent right lobe LDLT for end-stage liver disease in adult patients. All recipients who had GRWR < 0.8% were identified. The data of these patients were retrospectively analyzed and compared to patients with GRWR ≥ 0.8%. There were 43 patients with GRWR < 0.8%. Out of these patients, 7 (16%) had GRWR of 0.6%. The median Model for End-Stage Liver Disease (MELD) score was 15, and the median donor age was 30 years. Anterior segment drainage was ensured. Portal inflow modulation was performed by splenic artery ligation according to the portal flow. Postoperative complications were seen in 6 (14%) patients. Of all 43 patients, 3 (7%) died perioperatively within 1 month, and 1 (2%) patient underwent retransplantation due to graft failure. The mean hospital stay was 18 days. The 1-year survival rate was 93%. None of the patients had a laboratory MELD score above 20. The comparison of the results with the patients who had GRWR ≥ 0.8% has shown no significant difference, except MELD score, body mass index (BMI), and rate of anterior segment drainage. The GRWR can be decreased even to 0.6% if the MELD score is below 20, donor age is below 45 years, and there are no signs for any hepatosteatosis of the donor graft. In these patients, it is essential that the anterior segment drainage is secured and the portal inflow modulation is performed according to the portal flow. Liver Transplantation 22 1643-1648 2016 AASLD.

Splenic Artery Syndrome as a Possible Cause of Late Onset Refractory Ascites After Liver Transplantation: Management With Proximal Splenic Artery Embolization.

BACKGROUND: Portal hyperperfusion (PHP) is a hemodynamic condition which may develop after liver transplantation and cause refractory ascites (RA). The diagnosis is established by exclusion of other causes of increased sinusoidal pressure/resistance such as cellular rejection or toxicity and outflow obstruction. PHP as part of the pathogenesis of the splenic artery syndrome (SAS) can be treated with splenic artery embolization (SAE). METHODS: This is a retrospective study on a cohort of first-time whole-size liver transplant recipients diagnosed with RA due to PHP and treated by proximal SAE (pSAE) at the Liver Transplant Unit of the University Hospital of Udine between 2004 and 2014. RESULTS: For this study, 23 patients were identified (prevalence 8%) and treated. Preliminary clinical workup to diagnose SAS was based on exclusion of other possible causes of RA with graft biopsy, cavogram with hepatic venous pressure measurement, computed tomography scan, and angiography. The pSAE was performed 110 ± 61 days after transplantation, and no procedure-related complications occurred. pSAE resulted in a significant decrease of portal vein velocity (P = .01) and wedge hepatic venous pressure (P = .03). The diameter of the spleen showed a slightly significant reduction (P = .047); no modification of hepatic artery resistive index were encountered (P = .34). Moreover, pSAE determined the resolution of RA in all cases. CONCLUSIONS: pSAE is a safe and effective procedure to modulate the hepatic inflow and thus to treat RA secondary to SAS, with a low incidence of complications and a high rate of clinical response.

Angiogenesis and portal-systemic collaterals in portal hypertension.

In patients with advanced liver disease with portal hypertension, portal-systemic collaterals contribute to circulatory disturbance, gastrointestinal hemorrhage, hepatic encephalopathy, ascites, hepatopulmonary syndrome and portopulmonary hypertension. Angiogenesis has a pivotal role in the formation of portal-systemic shunts. Recent research has defined many of the mediators and mechanisms involved in this angiogenic process, linking the central roles of hepatic stellate cells and endothelial cells. Studies of animal models have demonstrated the potential therapeutic impact of drugs to inhibit angiogenesis in cirrhosis. For example, inhibition of VEGF reduces portal pressure, hyperdynamic splanchnic circulation, portosystemic collateralization and liver fibrosis. An improved understanding of the role of other angiogenic factors provides hope for a novel targeted therapy for portal hypertension with a tolerable adverse effect profile.

[Experience in treating portal thromboses in patients with chronic myeloproliferative diseases].

Patients with myeloproliferative diseases (MPD) are noted to be at high risk for portal thromboses. This problem gives rise to disability if it is untimely treated or resistant to therapy. The paper gives the experience of the Outpatient Department of the Hematology Research Center, Ministry of Health of the Russian Federation, in using antithrombin III in MPD patients (3 patients with primary myelofibrosis, 3 with essential thrombocythemia) and acute and subacute portal vein thromboses resistant to therapy with direct anticoagulants. In all 5 cases, the use of antithrombin III in combination with low-molecular-weight heparin showed a positive clinical effect as rapid relief of pain syndrome and comparatively early (3-week to 1.5-2-month) recanalization of thrombosed vessels. Three clinical cases are described in detail.

Modulation of splanchnic circulation: Role in perioperative management of liver transplant patients.

Splanchnic circulation is the primary mechanism that regulates volumes of circulating blood and systemic blood pressure in patients with cirrhosis accompanied by portal hypertension. Recently, interest has been expressed in modulating splanchnic circulation in patients with liver cirrhosis, because this capability might produce beneficial effects in cirrhotic patients undergoing a liver transplant. Pharmacologic modulation of splanchnic circulation by use of vasoconstrictors might minimize venous congestion, replenish central blood flow, and thus optimize management of blood volume during a liver transplant operation. Moreover, splanchnic modulation minimizes any high portal blood flow that may occur following liver resection and the subsequent liver transplant. This effect is significant, because high portal flow impairs liver regeneration, and thus adversely affects the postoperative recovery of a transplant patient. An increase in portal blood flow can be minimized by either surgical methods (e.g., splenic artery ligation, splenectomy or portocaval shunting) or administration of splanchnic vasoconstrictor drugs such as Vasopressin or terlipressin. Finally, modulation of splanchnic circulation can help maintain perioperative renal function. Splanchnic vasoconstrictors such as terlipressin may help protect against acute kidney injury in patients undergoing liver transplantation by reducing portal pressure and the severity of a hyperdynamic state. These effects are especially important in patients who receive a too small for size graft. Terlipressin selectively stimulates V1 receptors, and thus causes arteriolar vasoconstriction in the splanchnic region, with a consequent shift of blood from splanchnic to systemic circulation. As a result, terlipressin enhances renal perfusion by increasing both effective blood volume and mean arterial pressure.

2'-Hydroxyflavanone ameliorates mesenteric angiogenesis and portal-systemic collaterals in rats with liver fibrosis.

BACKGROUND AND AIM: Portal-systemic collaterals lead to dreadful consequences in patients with cirrhosis. Angiogenesis participates in the development of liver fibrosis, hyperdynamic circulation, and portal-systemic collaterals. 2'-Hydroxyflavanone (2'-HF), one of the citrus fruits flavonoids, is known to have antiangiogenesis effect without adverse response. However, the relevant effects in liver fibrosis have not been surveyed. METHODS: Male Wistar rats received thioacetamide (TAA, 100 mg/kg tiw, i.p.) for 6 weeks to induce liver fibrosis. On the 29th to 42nd day, rats randomly received 2'-HF (100 mg/kg, qod, i.p.) or vehicle (corn oil). On the 43rd day, after hemodynamic measurements, the followings were surveyed: (i) severity of collaterals; (ii) mesenteric angiogenesis; (iii) mesenteric proangiogenic factors protein expressions; (iv) Mesenteric vascular endothelial cells apoptosis; and (v) Mesenteric expressions of proteins regulating apoptosis. RESULTS: Compared with the vehicle group, 2'-HF did not significantly change body weight, mean arterial pressure, heart rate, and portal pressure in TAA rats. 2'-HF significantly alleviated the severity of collaterals, but the mesenteric phospho-ERK, ERK, phospho-Akt, Akt, COX1, COX2, VEGF, and VEGFR-2 protein expressions were not altered. The apoptotic index of 2'-HF group was significantly higher and the mesenteric protein expressions of pro-apoptotic factors, NFkB 50, NFkB 65, Bax, phospho-p53, 17 kD cleaved caspase 3, and 17 kD casepase 3 were up-regulated. CONCLUSIONS: 2'-HF does not influence the hemodynamics but alleviated the severity of collaterals in rats with liver fibrosis and early portal hypertension. This is, at least partly, attributed to enhanced apoptosis of mesenteric vascular endothelial cells.