Lower Portal Pressure Research Articles

Rho-Kinase Inhibitor Coupled to Peptide-Modified Albumin Carrier Reduces Portal Pressure and Increases Renal Perfusion in Cirrhotic Rats

Background: Rho-kinase (ROCK) activation in hepatic stellate cells (HSC) is a key mechanism promoting liver fibrosis and portal hypertension (PTH). Specific delivery of ROCK-inhibitor Y-27632 (Y27) to HSC targeting mannose-6-phosphate-receptors reduces portal pressure and fibrogenesis. In decompensated cirrhosis, presence of ascites is associated with reduced renal perfusion. Since in cirrhosis, platelet-derived growth factor receptor beta (PDGFRβ) is upregulated in the liver as well as the kidney, this study coupled Y27 to human serum albumin (HSA) substituted with PDGFRβ-recognizing peptides (pPB), and investigated its effect on PTH in cirrhotic rats. Methods: In vitro collagen contraction assays tested biological activity on LX2 cells. Hemodynamics were analyzed in BDL and CCl4 cirrhotic rats 3h, 6h and 24h after i.v. administration of Y27pPBHSA (0.5/1mg/kg b.w). Phosphorylation of moesin and myosin light chain (MLC) assessed ROCK activity in liver, femoral muscle, mesenteric artery, kidney and heart. Findings: Three Y27 molecules were coupled to pPBHSA as confirmed by HPLC/MS, which was sufficient to relax LX2 cells. In vivo, Y27pPBHSA-treated rats exhibited lower portal pressure, hepatic vascular resistance without effect on systemic vascular resistance, but a tendency towards lower cardiac output compared to non-treated cirrhotic rats. Y27pPBHSA reduced intrahepatic resistance by reduction of phosphorylation of moesin and MLC in Y27pPBHSA-treated cirrhotic rats. Y27pPBHSA was found in the liver of rats up to 6 hours after its injection, in the HSC demonstrated by double-immunostainings. Interestingly, Y27pPBHSA increased renal arterial flow over time combined with an antifibrotic effect as shown by decreased renal acta2 and col1a1 mRNA expression. Interpretation: Targeting the ROCK inhibitor Y27 to PDGFRI² decreases portal pressure with potential beneficial effects in the kidney. This unique approach should be tested in human cirrhosis. Funding: J. Trebicka is supported by grants from the Deutsche Forschungsgemeinschaft Grant SFB TRR57 P18, European Commission DirectorateGeneral for Research and Innovation Grant 668031, and Cellex Foundation. Declaration of Interest: The authors have no conflict of interest. Ethical Approval: All experiments were performed in accordance with the German Animal Protection Law and the Guidelines of the animal care facility (Haus fur experimentelle Therapie, University Portal and renal effects of targeted Rho-kinase inhibitor Clinics Bonn, Germany), and approved by the North Rhine-Westphalia State Agency for Nature, Environment, and Consumer Protection (LANUV, file reference LANUV NRW, 8402.04.2014.A137).

Hepatic Hemodynamics and Portal Flow Modulation: The A2ALL Experience.

A principal aim of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study was to study hepatic blood flow and effect of portal flow modulation on graft outcomes in the setting of increasing use of smaller and left lobe grafts. Recipients of 274 living donor liver transplant were enrolled in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, including 233 (85.0%) right lobes, 40 (14.6%) left lobes, and 1 (0.5%) left lateral section. Hepatic hemodynamics were recorded after reperfusion. A total of 57 portal flow modulations were performed on 52 subjects. Modulation lowered portal pressure in 68% of subjects with inconsistent effects on hepatic arterial and portal flow. A higher rate of graft dysfunction was observed in modulated vs. unmodulated subjects (31% vs. 18%; P = 0.03); however, graft survival in modulated subjects was not different from unmodulated subjects at 3 years. These results suggest the need for a study using a prespecified portal flow modulation protocol with defined indications to better define the effects of these interventions.

Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies

Hepatic stellate cells (HSC) play a key role in the development of chronic liver disease (CLD). Liraglutide, well-established in type 2 diabetes, showed anti-inflammatory and anti-oxidant properties. We evaluated the effects of liraglutide on HSC phenotype and hepatic microvascular function using diverse pre-clinical models of CLD. Human and rat HSC were in vitro treated with liraglutide, or vehicle, and their phenotype, viability and proliferation were evaluated. In addition, liraglutide or vehicle was administered to rats with CLD. Liver microvascular function, fibrosis, HSC phenotype and sinusoidal endothelial phenotype were determined. Additionally, the effects of liraglutide on HSC phenotype were analysed in human precision-cut liver slices. Liraglutide markedly improved HSC phenotype and diminished cell proliferation. Cirrhotic rats receiving liraglutide exhibited significantly improved liver microvascular function, as evidenced by lower portal pressure, improved intrahepatic vascular resistance, and marked ameliorations in fibrosis, HSC phenotype and endothelial function. The anti-fibrotic effects of liraglutide were confirmed in human liver tissue and, although requiring further investigation, its underlying molecular mechanisms suggested a GLP1-R-independent and NF-κB-Sox9-dependent one. This study demonstrates for the first time that liraglutide improves the liver sinusoidal milieu in pre-clinical models of cirrhosis, encouraging its clinical evaluation in the treatment of chronic liver disease.

African Americans have a lower prevalence of portal vein thrombosis at the time of liver transplantation

BackgroundPerioperative vascular thrombotic events in patients undergoing liver transplantation (LT) are associated with significant morbidity and mortality. MethodsIn this retrospective UNOS database analysis, we evaluated the prevalence of portal vein thrombosis (PVT) and factors contributing to PVT development in different ethnic groups. ResultsOf the 47 953 LT performed between 2002 and 2015, we identified 3642 cases of PVT. African Americans (AA) had a significantly lower prevalence of PVT compared to other ethnic groups (p = 0.0001). Multivariable regression analysis confirmed that AA were less likely than other ethnicities to have PVT (OR = 0.6). AA cohort was more likely to have infectious or autoimmune causes of liver failure (OR = 1.6, 1.7 respectively) as well as higher creatinine and INR compared to other groups (OR = 1.6, 1.3 respectively). AA's were less likely to have encephalopathy, ascites, or variceal bleeding, which might indicate lower portal pressures. AA's were listed for LT later than other ethnicities and had both a lower functional status and higher MELD score at the time of registration. DiscussionAA's had a significantly lower prevalence of preoperative PVT despite having a greater number of factors predisposing to thrombosis. This predisposition should be considered before instituting perioperative antithrombotic therapy.

Dihydroartemisinin counteracts fibrotic portal hypertension via farnesoid X receptor-dependent inhibition of hepatic stellate cell contraction.

Portal hypertension is a frequent pathological symptom occurring especially in hepatic fibrosis and cirrhosis. Current paradigms indicate that inhibition of hepatic stellate cell (HSC) activation and contraction is anticipated to be an attractive therapeutic strategy, because activated HSC dominantly facilitates an increase in intrahepatic vein pressure through secreting extracellular matrix and contracting. Our previous in vitro study indicated that dihydroartemisinin (DHA) inhibited contractility of cultured HSC by activating intracellular farnesoid X receptor (FXR). However, the effect of DHA on fibrosis-related portal hypertension still requires clarification. In this study, gain- and loss-of-function models of FXR in HSC were established to investigate the mechanisms underlying DHA protection against chronic CCl4 -caused hepatic fibrosis and portal hypertension. Immunofluorescence staining visually showed a decrease in FXR expression in CCl4 -administrated rat HSC but an increase in that in DHA-treated rat HSC. Serum diagnostics and morphological analyses consistently indicated that DHA exhibited hepatoprotective effects on CCl4 -induced liver injury. DHA also reduced CCl4 -caused inflammatory mediator expression and inflammatory cell infiltration. These improvements were further enhanced by INT-747 but weakened by Z-guggulsterone. Noteworthily, DHA, analogous to INT-747, significantly lowered portal vein pressure and suppressed fibrogenesis. Experiments on mice using FXR shRNA lentivirus consolidated the results above. Mechanistically, inhibition of HSC activation and contraction was found as a cellular basis for DHA to relieve portal hypertension. These findings demonstrated that DHA attenuated portal hypertension in fibrotic rodents possibly by targeting HSC contraction via a FXR activation-dependent mechanism. FXR could be a target molecule for reducing portal hypertension during hepatic fibrosis.

Cirrhotic Fundal Variceal Bleeders Have Lower Portal Pressure as Compared to Cirrhotic Esophageal Variceal Bleeders: A Comparative Analysis of 80 Patients

Cirrhotic Fundal Variceal Bleeders Have Lower Portal Pressure as Compared to Cirrhotic Esophageal Variceal Bleeders: A Comparative Analysis of 80 Patients

Techniques for Transjugular Intrahepatic Portosystemic Shunt Reduction and Occlusion

Transjugular intrahepatic portosystemic shunts (TIPS) effectively lower portal pressure and are commonly used to manage selected patients with variceal bleeding. Unfortunately, significant consequences are not infrequently encountered as a result of this diversion of portal venous flow. These consequences include disabling hepatic encephalopathy as well as hepatic decompensation. To manage these complications, therapeutic options include TIPS reduction and TIPS occlusion. TIPS reduction is the favored technique because of the potential for venous thrombosis and recurrent variceal hemorrhage after acute TIPS occlusion. Techniques and indications for TIPS reduction and TIPS occlusion are reviewed.

Vasopressin‐induced changes in splanchnic blood flow and hepatic and portal venous pressures in liver resection

To minimize blood loss during hepatic surgery, various methods are used to reduce pressure and flow within the hepato-splanchnic circulation. In this study, the effect of low- to moderate doses of vasopressin, a potent splanchnic vasoconstrictor, on changes in portal and hepatic venous pressures and splanchnic and hepato-splanchnic blood flows were assessed in elective liver resection surgery. Twelve patients were studied. Cardiac output (CO), stroke volume (SV), mean arterial (MAP), central venous (CVP), portal venous (PVP) and hepatic venous pressures (HVP) were measured, intraoperatively, at baseline and during vasopressin infusion at two infusion rates (2.4 and 4.8 U/h). From arterial and venous blood gases, the portal (splanchnic) and hepato-splanchnic blood flow changes were calculated, using Fick's equation. CO, SV, MAP and CVP increased slightly, but significantly, while systemic vascular resistance and heart rate remained unchanged at the highest infusion rate of vasopressin. PVP was not affected by vasopressin, while HVP increased slightly. Vasopressin infusion at 2.4 and 4.8 U/h reduced portal blood flow (-26% and -37%, respectively) and to a lesser extent hepato-splanchnic blood flow (-9% and -14%, respectively). The arterial-portal vein lactate gradient was not significantly affected by vasopressin. Postoperative serum creatinine was not affected by vasopressin. Short-term low to moderate infusion rates of vasopressin induced a splanchnic vasoconstriction without metabolic signs of splanchnic hypoperfusion or subsequent renal impairment. Vasopressin caused a centralization of blood volume and increased cardiac output. Vasopressin does not lower portal or hepatic venous pressures in this clinical setting.

Usefulness of portal vein pressure for predicting the effects of tolvaptan in cirrhotic patients.

To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention. We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient (HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response. Subjects comprised patients with a median age of 65 (range, 40-82) years. According to the Child-Pugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were -1.0 kg (P = 2.04 × 10(-6)) and -1.3 kg (P = 1.83 × 10(-5)), respectively. The median HVPG value was 240 (range, 105-580) mmH2O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mmH2O in predicting treatment response. The response rate was 87.5% (7/8) in patients with HVPG of 190 mmH2O or less, whereas it was only 12.5% (2/16) in those with HVPG of greater than 190 mmH2O (P = 7.46 × 10(-4)). We compared each characteristics factors between responders and non-responders. As a result, HVPG (P = 0.045) and serum hyaluronic acid (P = 0.017) were detected as useful factors. The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.

Role of estrogen receptor β selective agonist in ameliorating portal hypertension in rats with CCl4-induced liver cirrhosis.

To investigate the role of diarylpropionitrile (DPN), a selective agonist of estrogen receptor β (ERβ), in liver cirrhosis with portal hypertension (PHT) and isolated hepatic stellate cells (HSCs). Female Sprague-Dawley rats were ovariectomized (OVX), and liver cirrhosis with PHT was induced by CCl4 injection. DPN and PHTPP, the selective ERβ agonist and antagonist, were used as drug interventions. Liver fibrosis was assessed by hematoxylin and eosin (HE) and Masson's trichrome staining and by analyzing smooth muscle actin expression. Hemodynamic parameters were determined in vivo using colored microspheres technique. Protein expression and phosphorylation were determined by immunohistochemical staining and Western blot analysis. Messenger RNA levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Collagen gel contraction assay was performed using gel lattices containing HSCs treated with DPN, PHTPP, or Y-27632 prior to ET-1 addition. Treatment with DPN in vivo greatly lowered portal pressure and improved hemodynamic parameters without affecting mean arterial pressure, which was associated with the attenuation of liver fibrosis and intrahepatic vascular resistance (IHVR). In CCl4-treated rat livers, DPN significantly decreased the expression of RhoA and ROCK II, and even suppressed ROCK II activity. Moreover, DPN remarkedly increased the levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS, and promoted the activities of protein kinase G (PKG), which is an NO effector in the liver. Furthermore, DPN reduced the contractility of activated HSCs in the 3-dimensional stress-relaxed collagen lattices, and decreased the ROCK II activity in activated HSCs. Finally, in vivo/in vitro experiments demonstrated that MLC activity was inhibited by DPN. For OVX rats with liver cirrhosis, DPN suppressed liver RhoA/ROCK signal, facilitated NO/PKG pathways, and decreased IHVR, giving rise to reduced portal pressure. Therefore, DPN represents a relevant treatment choice against PHT in cirrhotic patients, especially postmenopausal women.

Development of hyperdynamic circulation and response to β-blockers in compensated cirrhosis with portal hypertension.

Nonselective β-blockers are useful to prevent bleeding in patients with cirrhosis and large varices but not to prevent the development of varices in those with compensated cirrhosis and portal hypertension (PHT). This suggests that the evolutionary stage of PHT may influence the response to β-blockers. To characterize the hemodynamic profile of each stage of PHT in compensated cirrhosis and the response to β-blockers according to stage, we performed a prospective, multicenter (tertiary care setting), cross-sectional study. Hepatic venous pressure gradient (HVPG) and systemic hemodynamic were measured in 273 patients with compensated cirrhosis before and after intravenous propranolol (0.15 mg/kg): 194 patients had an HVPG ≥10 mm Hg (clinically significant PHT [CSPH]), with either no varices (n = 80) or small varices (n = 114), and 79 had an HVPG >5 and <10 mm Hg (subclinical PHT). Patients with CSPH had higher liver stiffness (P < 0.001), worse Model for End-Stage Liver Disease score (P < 0.001), more portosystemic collaterals (P = 0.01) and splenomegaly (P = 0.01) on ultrasound, and lower platelet count (P < 0.001) than those with subclinical PHT. Patients with CSPH had lower systemic vascular resistance (1336 ± 423 versus 1469 ± 335 dyne · s · cm(-5) , P < 0.05) and higher cardiac index (3.3 ± 0.9 versus 2.8 ± 0.4 L/min/m(2) , P < 0.01). After propranolol, the HVPG decreased significantly in both groups, although the reduction was greater in those with CSPH (-16 ± 12% versus -8 ± 9%, P < 0.01). The HVPG decreased ≥10% from baseline in 69% of patients with CSPH versus 35% with subclinical PHT (P < 0.001) and decreased ≥20% in 40% versus 13%, respectively (P = 0.001). Patients with subclinical PHT have less hyperdynamic circulation and significantly lower portal pressure reduction after acute β-blockade than those with CSPH, suggesting that β-blockers are more suitable to prevent decompensation of cirrhosis in patients with CSPH than in earlier stages.

Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis

ObjectiveAngiotensin II (AngII) activates via angiotensin-II-type-I receptor (AT1R) Janus-kinase-2 (JAK2)/Arhgef1 pathway and subsequently RHOA/Rho-kinase (ROCK), which induces experimental and probably human liver fibrosis. This study investigated the relationship of JAK2...

Metformin reduces hepatic resistance and portal pressure in cirrhotic rats.

Increased hepatic vascular resistance is the primary factor in the development of portal hypertension. Metformin ameliorates vascular cells function in several vascular beds. Our study was aimed at evaluating the effects, and the underlying mechanisms, of metformin on hepatic and systemic hemodynamics in cirrhotic rats and its possible interaction with the effects of propranolol (Prop), the current standard treatment for portal hypertension. CCl4-cirrhotic rats received by gavage metformin 300 mg/kg or its vehicle once a day for 1 wk, before mean arterial pressure (MAP), portal pressure (PP), portal blood flow (PBF), hepatic vascular resistance, and putative molecular/cellular mechanisms were measured. In a subgroup of cirrhotic rats, the hemodynamic response to acute Prop (5 mg/kg iv) was assessed. Effects of metformin ± Prop on PP and MAP were validated in common bile duct ligated-cirrhotic rats. Metformin-treated CCl4-cirrhotic rats had lower PP and hepatic vascular resistance than vehicle-treated rats, without significant changes in MAP or PBF. Metformin caused a significant reduction in liver fibrosis (Sirius red), hepatic stellate cell activation (α-smooth muscle actin, platelet-derived growth factor receptor β polypeptide, transforming growth factor-βR1, and Rho kinase), hepatic inflammation (CD68 and CD163), superoxide (dihydroethidium staining), and nitric oxide scavenging (protein nitrotyrosination). Prop, by decreasing PBF, further reduced PP. Similar findings were observed in common bile duct ligated-cirrhotic rats. Metformin administration reduces PP by decreasing the structural and functional components of the elevated hepatic resistance of cirrhosis. This effect is additive to that of Prop. The potential impact of this pharmacological combination, otherwise commonly used in patients with cirrhosis and diabetes, needs clinical evaluation.

Feasible usage of ABO incompatible grafts in living donor liver transplantation.

The use of ABO incompatible (ABOi) graft in living donor liver transplantation (LDLT) has not been an established procedure worldwide. Four hundred and eight adult LDLTs, using ABOi (n=19) and non-ABOi (n=389) grafts, were performed as a single center experience. In ABOi-LDLT group (n=19), median isoagglutinin titer before plasma exchange (PE) at LDLT and after LDLT (max) was ×256, ×32 and ×32, respectively. Rituximab was given at 21.8±6.1 days before LDLT and PE was performed 3.7±1.6 times. Although ABOi-LDLTs had increased rate of splenectomy (89.4% vs. 44.7%, P<0.001) and lower portal venous pressure (PVP) at the end of surgery (13.8±1.1 vs. 16.9±0.2 mmHg, P=0.003), other operative factors including graft ischemic time, operative time and blood loss were not different between the groups. Although ABOi-LDLTs had increased incidence of cytomegalovirus infection (52.6% vs. 22.9%, P=0.007), other post-transplant complications including bacterial sepsis and acute rejection were not different between the groups. The 5-year graft survival rate was 87.9% in ABOi-LDLTs and 80.3% in non-ABOi-LDLTs (P=0.373). ABOi-LDLT could be safely performed, especially under rituximab-based protocol.

Efficacy of transjugular intrahepatic portosystemic shunt with covered stents in the treatment of portal hypertension in 46 patients with primary hepatocellular carcinoma

Objective To investigate the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) with covered stent in the treatment of portal hypertension in patients with hepatocellular carcinoma. Methods The clinical data of 46 patients with primary hepatocellular carcinoma and portal hypertension who received TIPS with stent treatment were retrospectively analyzed. After treatment, liver function, shunt patency, re-bleeding rate, hepatic encephalopathy, ascites, gastric intestinal symptoms, lifetime and causes of death were analyzed. Compare t test was performed for measurement data comparison among groups. The survival curves were used to analyse the cumulative stent shunt patency rate, the incidence of hepatic encephalopathy and the survival rate. Results After the operation, portal vein pressure significantly decreased compared with that before operation [(16.2±4.6) mmHg vs (28.3±5.1) mmHg, 1 mmHg=0.133 kPa], and the difference was statistically significant (t=21.30, P 0.05]. Cumulative stent shunt patency at 3, 6, 12, 24, 36 month after operation was 100.0%, 95.6%, 93.5%, 91.3% and 91.3%, respectively. The cumulative incidence of hepatic encephalopathy was 6.5%, 8.7%, 13.0%, 17.4% and 26.1%, respectively; cumulative survival rate was 95.7%, 82.6%, 67.4%, 43.5% and 32.6%, respectively. In 10 cases of refractory ascites, ascites of all the patients reduced with different degree after operation and gastrointestinal uncomfortable symptoms were relieved. Conclusion In patients with primary hepatocellular carcinoma and portal hypertension, who have gastrointestinal bleeding or refractory ascites, treatment of TIPS with covered stents could effectively lower portal pressure, prevent re-bleeding and reduce the volume of ascites. Key words: Portosystemic shunt, transjugular intrahepatic; Primary hepatocellular carcinoma; Liver cirrhosis; Hypertension, portal

KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: behind the molecular mechanisms of statins

ObjectiveIn the liver, the transcription factor, Kruppel-like factor 2 (KLF2), is induced early during progression of cirrhosis to lessen the development of vascular dysfunction; nevertheless, its endogenous expression results insufficient...

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Peripancreatic Enhancing Lesion in a Cirrhotic Patient

Question: A 74-year-old white man with a history of decompensated alcoholic liver disease was referred to our clinic for further management of his cirrhosis. The patient initially presented to an outside hospital 2 months prior with increasing abdominal girth and confusion. Small, nonbleeding esophageal varices were visualized on upper endoscopy. Doppler ultrasonography revealed a portal vein thrombus with cavernous transformation. The patient was initiated on warfarin. He presented to us for a second opinion. Physical examination revealed an elderly, ill-appearing gentleman with anicteric sclera, shifting dullness and bilateral lower extremity edema. Laboratory testing was notable for a total bilirubin of 0.8 mg/dL, alanine and aspartate aminotransferases 190 and 150 U/L, respectively, and alkaline phosphatase 1000 U/D. International Normalized Ratio was prolonged (on warfarin) at 4.2; creatinine was 1.1 mg/dL and albumin 3.2 g/dL. Triphasic computed tomography of the abdomen and pelvis demonstrated a large peripancreatic lesion enhancing on portal venous phase with resultant mass effect on adjacent structures (Figure A). What is the diagnosis? Look on page 324 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Triphasic computed tomography of the abdomen reveals an 8.2 × 6.5-cm portal vein aneurysm containing subacute thrombi. Compression of the remnant thrombosed portal vein demonstrates mass effect from the aneurysm (Figure A). Cavernous transformation of the liver secondary to portal vein thrombosis can be seen distal to the aneurysm (Figure B). Coronal and sagittal views further demonstrate the extent of the aneurysm (Figures C, D). Portal vein aneurysm is a rare clinical entity that mainly occurs at bifurcations and confluences of the portal venous system, both intra- and extrahepatically. In patients without preexisting liver disease, it may result from congenital malformations, such as intrinsic weakness of the vein wall or diverticular remnant of a primitive portal precursor.1Lau H. Chew D.K. Belkin M. Extrahepatic portal vein aneurysm: a case report and review of the literature.Cardiovasc Surg. 2002; 10: 58-61Crossref PubMed Scopus (0) Google Scholar In cases of acquired portal vein aneurysm, portal hypertension secondary to cirrhosis is the most frequently reported cause. Portal hypertension initially leads to compensatory medial hypertrophy that is eventually replaced by fibrous tissue with weak tensile strength.2Rafiq S.A. Sitrin M.D. Portal vein aneurysm: case report and review of the literature.Gastroenterol Hepatol. 2007; 3: 296-298PubMed Google Scholar However, portal vein aneurysms are still rare in patients with known cirrhosis, suggesting that an existing congenital abnormality may be present for portal hypertension to result in aneurysmal dilation.1Lau H. Chew D.K. Belkin M. Extrahepatic portal vein aneurysm: a case report and review of the literature.Cardiovasc Surg. 2002; 10: 58-61Crossref PubMed Scopus (0) Google Scholar Because most patients are asymptomatic, portal vein aneurysms are generally found incidentally on abdominal imaging. Conservative management with serial imaging is appropriate for small aneurysms in asymptomatic patients without concomitant portal hypertension or cirrhosis. Complications from portal vein aneurysm include thrombosis, rupture, and symptoms related to compression on adjacent organs such as the common bile duct, duodenum, and vena cava. Rupture of portal vein aneurysm is unusual because of low portal venous pressure, but the risk of rupture does increase in the presence of portal hypertension. Patients with portal hypertension and portal vein thrombosis may benefit from surgical shunts to reduce portal pressure and prevent progressive dilation of the aneurysm.3Brock P.A. Jordan P.H. Barth M.H. et al.Portal vein aneurysm: a rare but important vascular condition.Surgery. 1997; 121: 105-108Abstract Full Text PDF PubMed Scopus (69) Google Scholar This particular patient had several risk factors for acquired portal vein aneurysm, including decompensated alcoholic cirrhosis with portal hypertension as well as radiographic evidence of chronic pancreatitis. Given the patient's age, multiple comorbidities, and rapid deterioration, it was the family's request not to pursue aggressive measures. His anticoagulation with warfarin was discontinued.

Fenofibrate A peroxisome proliferator activated receptor-α agonist treatment ameliorates Concanavalin A-induced hepatitis in rats

Peroxisome proliferator-activated receptor-α (PPARα) is physiologically highly expressed by hepatocytes, where it plays a pivotal anti-inflammatory and metabolic role. The decrease expression and functional activity of PPARα in hepatocytes during hepatitis C virus infection may contribute to the pathogenesis of the disease in humans. This study aims at evaluating the effects of PPARα activation with fenofibrate (FF) on liver inflammation, fibrosis and portal pressure (PP) in Concanavalin A (Con A)- induced hepatitis in rats. The rats were randomly divided to 3 groups; control (1ml saline iv/wk) group, Con A (20mg/kg/iv/wk) group and Con A with FF (100mg/kg/day p.o) group. Blood samples and livers were collected by the end of the first, second, fourth and eighth injections of Con A for biochemical, histopathological and immunohistochemistry studies for α-smooth muscle actin (α SMA). Measurement of PP was performed by the end of the 8th week. FF group had a significant (P<0.05) decrease of serum alanine and aspartate aminotransferases with significant reduction of hepatic tumor necrosis factor alpha and malondialdehyde levels than Con A group. Histopathological examination revealed that treatment with FF significantly suppressed early inflammation, reduced α SMA, and apoptosis of hepatocytes induced by Con A, thereby preventing the progression of chronic liver injury and fibrosis. In addition FF group had a significantly lower PP (−89.0%) than Con A group. In conclusion PPARα activation significantly reduced liver inflammation, fibrosis and PP in Con A model of hepatitis that may represent a new therapeutic strategy for hepatitis and its complications.

Attenuation of Portal Hypertension by Continuous Portal Infusion of PGE1 and Immunologic Impact in Adult-to-Adult Living-Donor Liver Transplantation

Small-for-size syndrome remains the greatest limiting factor of expanding segmental liver transplantation from living donors. Portal hyperperfusion is considered to substantially contribute to small-for-size syndrome. We investigated the impact of continuous portal infusion of prostaglandin E1 (PGE1) on small-for-size grafts (SFSGs) in adult-to-adult living-donor liver transplantation (LDLT). From July 2003 to December 2009, LDLT was performed in 122 patients. We introduced continuous portal infusion of PGE1 to five SFSG patients (PG group) from November 2007 to December 2009 and retrospectively compared them with a historical control group of eight relevant SFSG patients without PGE1 infusion (non-PG group) from July 2003 to October 2007 to determine the safety and efficacy of continuous PGE1 portal infusion for SFSGs. Splenectomy cases were excluded from analysis. The PG group demonstrated significantly lower postoperative portal pressure than the non-PG group. Moreover, the PG group demonstrated significantly improved liver function in the early posttransplantation period and significantly better recovery from hyperammonemia at 1 week after transplantation and from hyperbilirubinemia in the late posttransplantation period. Overall survival was significantly better in the PG group than in the non-PG group. Three patients in the non-PG group died of rejection-related reasons. Interestingly, immunomonitoring assay revealed that antidonor immune responses were significantly accelerated in the non-PG group compared with the PG group after LDLT. In contrast, the PG group showed well-suppressed antidonor immune responses. Continuous portal infusion of PGE1 for SFSG attenuated portal hypertension, improved graft function, and suppressed antidonor immune responses, resulting in better survival.