Pathogenesis Of Portal Hypertension Research Articles

Obliteration of portal venules contributes to portal hypertension in biliary cirrhosis.

The effects of the obliteration of portal venules (OPV) in cirrhotic portal hypertension are poorly understood. To investigate its contribution to portal hypertension in biliary cirrhosis and its underlying mechanism,we evaluated OPV using two-dimensional (2D) histopathology in liver explants from patients with biliary atresia (BA, n = 63), primary biliary cholangitis (PBC, n = 18), and hepatitis B-related cirrhosis (Hep-B-cirrhosis, n = 35). Then, three-dimensional (3D) OPV was measured by X-ray phase-contrast CT in two parallel models in rats following bile duct ligation (BDL) or carbon tetrachloride (CCl4) administration, representing biliary cirrhosis and post-necrotic cirrhosis, respectively. The portal pressure was also measured in the two models. Finally, the effects of proliferative bile ducts on OPV were investigated. We found that OPV was significantly more frequent in patients with biliary cirrhosis, including BA (78.57 ± 16.45%) and PBC (60.00 ± 17.15%), than that in Hep-B-cirrhotic patients (29.43 ± 14.94%, p < 0.001). OPV occurred earlier, evidenced by the paired liver biopsy at a Kasai procedure (KP), and was irreversible even after a successful KP in the patients with BA. OPV was also significantly more frequent in the BDL models than in the CCl4 models, as shown by 2D and 3D quantitative analysis. Portal pressure was significantly higher in the BDL model than that in the CCl4 model. With the proliferation of bile ducts, portal venules were compressed and irreversibly occluded, contributing to the earlier and higher portal pressure in biliary cirrhosis. OPV, as a pre-sinusoidal component, plays a key role in the pathogenesis of portal hypertension in biliary cirrhosis. The proliferated bile ducts and ductules gradually take up the 'territory' originally attributed to portal venules and compress the portal venules, which may lead to OPV in biliary cirrhosis. © 2024 The Pathological Society of Great Britain and Ireland.

Liver-targeted nanoparticles delivering nitric oxide reduce portal hypertension in cirrhotic rats

Nitric oxide (NO) is a small vasodilator playing a key role in the pathogenesis of portal hypertension. Here, we assessed the potential therapeutic effect of a NO donor targeted to the liver by poly(beta-amino ester) nanoparticles (pBAE NPs) in experimental cirrhosis. Retinol-functionalized NO donor pBAE NPs (Ret pBAE NPs) were synthetized with the aim of actively targeting the liver. Administration of Ret pBAE NPs resulted in uptake and transfection by the liver and spleen. NPs were not found in other organs or the systemic circulation. Treatment with NO donor Ret pBAE NPs (30 mg/ kg body weight) significantly decreased aspartate aminotransferase, lactate dehydrogenase and portal pressure (9.75 ± 0.64 mmHg) compared to control NPs (13.4 ± 0.53 mmHg) in cirrhotic rats. There were no effects on mean arterial pressure and cardiac output. Liver-targeted NO donor NPs reduced collagen fibers and steatosis, activation of hepatic stellate cells and mRNA expression of profibrogenic and proinflammatory genes. Finally, Ret pBAE NPs displayed efficient transfection in human liver slices. Overall, liver-specific NO donor NPs effectively target the liver and mitigated inflammation and portal hypertension in cirrhotic rats. The use of Ret pBAE may prove to be an effective therapeutic strategy to treat advanced liver disease.

The genetics of portal hypertension: Recent developments and the road ahead.

Portal hypertension (PH), defined as a pathological increase in the portal vein pressure, has different aetiologies and causes. Intrahepatic PH is mostly secondary to the presence of underlying liver disease leading to cirrhosis, characterized by parenchymal changes with deregulated accumulation of extracellular matrix and vascular abnormalities; liver sinusoidal endothelial cells and hepatic stellate cells are key players in PH progression, able to influence each other. However, PH may also develop independently of parenchymal damage, as occur in portosinusoidal vascular disorder (PSVD), a group of clinical and histological entities characterized by portal vasculature dysfunctions. In this particular group of disorders, the pathophysiology of PH is still poorly understood. In the last years, several genetic studies, based on genome-wide association studies or whole-exome sequencing analysis, have highlighted the importance of genetic heritability in PH pathogenesis, both in cirrhotic and non-cirrhotic cases. The common PNPLA3 p.I148M variant, one of the main determinants of the susceptibility to steatotic liver disease, has also been associated with decompensation in patients with PH. Genetic variations at loci influencing coagulation, mainly the ABO locus, may directly contribute to the pathogenesis of PH. Rare genetic variants have been associated with familiar cases of progressive PSVD. In this review, we summarize the recent knowledges on genetic variants predisposing to PH development, contributing to better understand the role of genetic factors in PH pathogenesis.

Improving Management of Portal Hypertension: The Potential Benefit of Non-Etiological Therapies in Cirrhosis.

Portal hypertension is the consequence of cirrhosis and results from increased sinusoidal vascular resistance and hepatic blood inflow. Etiological therapies represent the first intervention to prevent a significant increase in portal pressure due to chronic liver damage. However, other superimposed pathophysiological drivers may worsen liver disease, including inflammation, bacterial translocation, endothelial dysfunction, and hyperactivation of hemostasis. These mechanisms can be targeted by a specific class of drugs already used in clinical practice. Albumin, rifaximin, statins, aspirin, and anticoagulants have been tested in cirrhosis and were a topic of discussion in the last Baveno consensus as non-etiological therapies. Based on the pathogenesis of portal hypertension in cirrhosis, our review summarizes the main mechanisms targeted by these drugs as well as the clinical evidence that considers them a valid complementary option to manage patients with cirrhosis and portal hypertension.

Influence of Gut–Liver Axis on Portal Hypertension in Advanced Chronic Liver Disease: The Gut Microbiome as a New Protagonist in Therapeutic Management

Clinically significant portal hypertension is associated with most complications of advanced chronic liver disease (ACLD), including variceal bleeding, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy. Gut dysbiosis is a hallmark of ACLD with portal hypertension and consists of the overgrowth of potentially pathogenic bacteria and a decrease in autochthonous bacteria; additionally, congestion makes the intestinal barrier more permeable to bacteria and their products, which contributes to the development of complications through inflammatory mechanisms. This review summarizes current knowledge on the role of the gut–liver axis in the pathogenesis of portal hypertension, with a focus on therapies targeting portal hypertension and the gut microbiota. The modulation of the gut microbiota on several levels represents a major challenge in the upcoming years; in-depth characterization of the molecular and microbiological mechanisms linking the gut–liver axis to portal hypertension in a bidirectional relationship could pave the way to the identification of new therapeutic targets for innovative therapies in the management of ACLD.

Diammonium glycyrrhizinate ameliorates portal hypertension by regulating portal macrophage oxidation and superoxide dismutase 3

Portal hypertension (PHT) is a complication of liver diseases. Increased intrahepatic vascular resistance is attributed to reduced bioavailability of vasodilator substances. The macrophage activation and superoxide dismutase 3 (SOD3) involve in the pathogenesis of PHT. Diammonium glycyrrhizinate (DG) is the salt form of glycyrrhizin derived from Radix glycyrrhizae, exerting anti-oxidant activities and be beneficial for liver injury. Here, we aimed to investigate effects of DG on PHT and explore its underlying mechanisms on regulation of macrophages and SOD3. The carbon tetrachloride induced PHT rats received administration of liposome-encapsulated clodronate for hepatic macrophage depletion, or PBS liposomes for matched control. DG (25 mg/kg) or vehicle was gavaged. Portal pressure in vivo, and serum biomarkers of macrophage activation were measured. The nitric oxide (NO) and prostacyclin (PGI2) bioavailability was evaluated in the isolated portal perfused rat livers. Liver tissues were collected to evaluate cirrhosis, macrophage oxidation, and SOD3 activity. Depletion of hepatic macrophages decreased portal pressure, increased bioavailability of NO and PGI2, and restored SOD3 activity. DG effectively decreased portal pressure, relieved cirrhosis, inhibited macrophage activation. DG increased bioavailability of NO and PGI2 to relax portal veins. DG relieved portal macrophage oxidation through decreasing nicotinamide adenine dinucleotide phosphate oxidase 2 and inducible NO synthase expressions, elevated SOD3 activities and increased SOD3 expressions at portal triads. These findings indicated that DG restored SOD3 activity, against portal macrophage oxidation, protected bioavailability of NO and PGI2, thereby reduced portal pressure. It suggested a potential use of DG for PHT treatment.

Waldenstrom’s Macroglobulinemia and Ascites: A Case Report

BackgroundWaldenstrom’s disease is characterized by the presence of pathological changes in the B lymphocytes that are in the last stages of maturation. One characteristic of WM is the production of an abnormal high amount of IgM and hyper viscosity syndrome. The MW gets worse, symptoms such as fatigue, weight loss, night sweats, fever, recurrent infections and swollen lymph nodes develop in patients who have a known history of MGUS. In this clinical case, our patient without history of MGUS, presents for the first time for medical observation only for ascites and the presence of an interportocaval lymph node package. An atypical presentation of the disease that makes us reflect on the difficulty of making a diagnosis in the elderly patient and on pathogenetic hypotheses of ascites not yet explored.Case PresentationSeventy-three-year-old patient, hospitalized for the onset of ascites with sloping edema, diffuse left pulmonary opacification. At the ultrasound check, cava and portal vessels patent and of regular caliber, however with inversion of flow in correspondence with the right branch and of the door to the hilum, with a subdiaphragmatic retrocaval focus with a maximum diameter of about 3 cm, which cannot be better viewed. CT scan of the abdomen with confirmation of the presence of an interportocaval lymph node package. After evidence of the electrophoretic protein picture of a double component, probably monoclonal with positive urinary immunofixation for free K chains. IgM dosage equal to 2190 mg. Serum immunofixation practice that confirms the diagnosis of type B lymphoproliferative syndrome as per Waldenstrom’s disease, confirmed by bone marrow aspiration with morphological and flow cytometric study. Immediately begin chemotherapy with Bendamustine 120 mg. After 4 weeks of therapy with the reduction of IgM values, the patient no longer presented ascites.ConclusionThis case has an unusual presentation of this disease and we could shed a new light on the possible pathogenesis of portal hypertension in Waldenstrom’disease.

Plasma Cyclic Guanosine Monophosphate Is a Promising Biomarker of Clinically Significant Portal Hypertension in Patients With Liver Cirrhosis.

Introduction: Despite intensive research, reliable blood-derived parameters to detect clinically significant portal hypertension (CSPH) in patients with cirrhosis are lacking. As altered homeostasis of cyclic guanosine monophosphate (cGMP), the central mediator of vasodilatation, is an essential factor in the pathogenesis of portal hypertension, the aim of our study was to evaluate plasma cGMP as potential biomarker of cirrhotic portal hypertension.Methods: Plasma cGMP was analyzed in cirrhotic patients with CSPH (ascites, n = 39; esophageal varices, n = 31), cirrhotic patients without CSPH (n = 21), patients with chronic liver disease without cirrhosis (n = 11) and healthy controls (n = 8). cGMP was evaluated as predictor of CSPH using logistic regression models. Further, the effect of transjugular intrahepatic portosystemic shunt (TIPS) placement on plasma cGMP was investigated in a subgroup of cirrhotic patients (n = 13).Results: Plasma cGMP was significantly elevated in cirrhotic patients with CSPH compared to cirrhotic patients without CSPH [78.1 (67.6–89.2) pmol/ml vs. 39.1 (35.0–45.3) pmol/l, p < 0.001]. Of note, this effect was consistent in the subgroup of patients with esophageal varices detected at screening endoscopy who had no prior manifestations of portal hypertension (p < 0.001). Cirrhotic patients without CSPH displayed no significant elevation of plasma cGMP compared to patients without cirrhosis (p = 0.347) and healthy controls (p = 0.200). Regression analyses confirmed that cGMP was an independent predictor of CSPH (OR 1.042, 95% CI 1.008–1.078, p = 0.016). Interestingly, portal decompression by TIPS implantation did not lead to normalization of plasma cGMP levels (p = 0.101).Conclusions: Plasma cGMP is a promising biomarker of CSPH in patients with cirrhosis, especially with respect to screening for esophageal varices. The lacking normalization of plasma cGMP after portal decompression suggests that elevated plasma cGMP in cirrhotic portal hypertension is mainly a correlate of systemic and splanchnic vasodilatation, as these alterations have been shown to persist after TIPS implantation.

Portal hypertension and hepatocellular carcinoma: Des liaisons dangereuses….

Portal hypertension (PHT) and hepatocellular carcinoma (HCC) are major complication of cirrhosis which significantly contribute to morbidity and mortality. In this review, we aim to describe the consequences of both angiogenesis and inflammation in the pathogenesis of PHT and HCC, but also the difficulty to propose adapted treatment when PHT and HCC coexist in the same patients. Studies for review in this article were retrieved from the PubMed database using literature published in English until March 2021. Portal hypertension occurs secondary to an increase of intrahepatic vascular resistances, the opening of portosystemic collateral vessels and the formation of neovessels, related to vascular endothelial growth factor (VEGF). Recently, bacterial translocation-mediated inflammation was also identified as a major contributor to PHT. Interestingly, VEGF and chronic inflammation also contribute to HCC occurrence. As PHT and HCC often coexist in the same patient, management of PHT and its related complications as well as HCC treatment appear more complex. Indeed, PHT-related complications such as significant ascites may hamper the access to HCC treatment and the presence of HCC is also independently associated with poor prognosis in patients with acute variceal bleeding related to PHT. Due to their respective mechanism of action, the combination of Atezolizumab and Bevacizumab for advanced HCC may impact the level of PHT and its related complications and to date, no real-life data are available. Appropriate evaluation and treatment of PHT remains a major issue in order to improve the outcome of HCC patients.

GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension.

Portal hypertension is a major contributor to decompensation and death from liver disease, a global health problem. Here, we demonstrate homozygous damaging mutations in GIMAP5, a small organellar GTPase, in four families with unexplained portal hypertension. We show that GIMAP5 is expressed in hepatic endothelial cells and that its loss in both humans and mice results in capillarization of liver sinusoidal endothelial cells (LSECs); this effect is also seen when GIMAP5 is selectively deleted in endothelial cells. Single-cell RNA-sequencing analysis in a GIMAP5-deficient mouse model reveals replacement of LSECs with capillarized endothelial cells, a reduction of macrovascular hepatic endothelial cells, and places GIMAP5 upstream of GATA4, a transcription factor required for LSEC specification. Thus, GIMAP5 is a critical regulator of liver endothelial cell homeostasis and, when absent, produces portal hypertension. These findings provide new insight into the pathogenesis of portal hypertension, a major contributor to morbidity and mortality from liver disease.

S3541 Sinistral Portal Hypertension Secondary to Splenic Artery Aneurysm: An Exceedingly Rare Entity

INTRODUCTION: Splenic artery aneurysm (SAA) is a common form of visceral aneurysm accounting for 60% of the cases, which is third most common site for aneurysm after abdominal aorta and iliac artery. It most commonly affects females with a female to male ratio of 4:1. SAA is very rarely associated with portal hypertension. Here we present a rare case of splenic artery aneurysm with isolated splenomegaly and portal hypertension. CASE DESCRIPTION/METHODS: The patient is an 82 year-old male with a medical history of diabetes dellitus who presented to the emergency department after an elevated blood sugar level at home. Vital signs on arrival were within normal limits. Notable laboratory workup included a Glucose of 564 mg/dL. Notable imaging included a chest x-ray (CXR) showing a mild increase in interstitial markings and more notably a non-specific, large calcified structure in the left abdomen. The patient was then admitted to the medical ward to undergo further treatment. Upon admission the patient underwent a CT scan of the abdomen with contrast to further evaluate the calcification that was found on CXR. This was done and showed a hypodense lesion in the left upper abdomen measuring 7.1 × 7.8 × 7.3 cm consistent with a calcified splenic artery aneurysm (Figure 1). This was accompanied by multiple varices in the peri-gastric and peri-splenic region. After these findings the gastroenterology service was consulted and the impression was sinistral portal hypertension as evidenced by the development of peri-gastric and peri-splenic varices. Due to the patient being asymptomatic no treatement was pursued. The patient’s hyperglycemia resolved after two days of admission and he was subsequently discharged with follow up appointments scheduled. DISCUSSION: Sinistral portal hypertension has an incidence rate of 0.01-0.2% The pathogenesis of portal hypertension is due to compression of the splenic vein which causes stasis of the blood and forms thrombosis. Given the higher mortality rate it is very important for a gastroenterologist to screen for splenic artery aneurysms in a patient with sinistral portal hypertension, and isolated gastric varices. Arteriography is the gold standard technique for the diagnosis, however multi detector CT scan and ultrasound with doppler can be used for diagnosis of SAA. Treatment is only recommended in symptomatic patients or with aneurysm size > 2 cm. Treatment options include aneurysectyomy, trans catheter embolization with coils or stent graft placement with or without splenectomy.Figure 1.: CT of the abdomen showing a calcified splenic artery aneurysm (blue arrows) with peri-splenic varices (red arrow).

Application of Color Doppler Ultrasound in the Treatment of Vascular Diseases Around the Cardia

Objective: This paper uses color Doppler ultrasound technology to study the hemodynamic characteristics of portal hypertension and splenectomy plus pericardial vascular disruption, to understand the pathogenesis of portal hypertension, and to understand the spleen. The effects of resection and pericardial vascular dissection on portal vein and hepatic artery hemodynamics were analyzed. Methods: Nine male in our hospital’s hepatobiliary surgery from January 2017 to December 2018 were selected. The preoperative upper gastrointestinal barium meal or gastroscopy confirmed that all patients had moderate to severe esophageal and gastric fundus. The surgical method was splenectomy and pericardial vascular disconnection. Color Doppler ultrasound was performed on portal vein and hepatic arterial hemodynamics to observe the presence or absence of portal vein thrombosis. Result: Preoperative hemodynamic status of the case group: the diameter of the hepatic artery was (0.34±0.01) cm, the value is 0.34 cm; the maximum flow velocity of the hepatic artery was (64.6±5.0) cm/s, the value of 64.7 cm/s; The postoperative hemodynamic status of the case group: the diameter of the hepatic artery was (0.41±0.02) cm, the value of 0.41 cm; the maximum flow velocity of the hepatic artery was (88.5±6.1) cm/s, the value of 89.6 cm/s. Conclusion: Color Doppler ultrasound has obvious application value in the treatment of pericardial vascular diseases. 1 splenectomy and pericardial vascular disconnection can increase the flow of hepatic artery, and reduce the total blood flow into the liver after surgery. The proportion of hepatic arterial blood flow increased, and the oxygen supply to increase.

Portal Hypertension in NASH: Is It Different from Other Aetiologies?

In non-alcoholic fatty liver disease (NAFLD), an increased portal pressure is observed before signs of cirrhosis or even inflammation or fibrosis are histologically present. This review describes the differences between the mechanisms of cirrhotic portal hypertension (PHT) and PHT in non-cirrhotic NAFLD. The increased portal pressure in NAFLD is primarily a result of an increased intrahepatic vascular resistance. Vasodilation is decreased by endothelial dysfunction and the sensitivity to vasoconstrictors is increased. Furthermore, the activation of hepatic stellate cells and the presence of microvascular thrombosis could also be involved in the pathogenesis of PHT in NAFLD. Although the increased portal pressure in early NAFLD is not considered clinically significant PHT, it might play a role in the pathophysiology of NAFLD. Due to the increased intrahepatic vascular resistance, the hepatic blood flow is impaired and hence the oxygen delivery is decreased, potentially triggering transition to steatohepatitis. The underlying mechanisms of these alterations therefore represent promising targets for pharmacological treatment.

Future Pharmacological Therapies of Portal Hypertension.

To provide an overview of recent pharmacological treatments for portal hypertension evaluated in early clinical trials, with particular emphasis on the pathophysiological basis of their use. In patients with compensated cirrhosis, even small decreases in portal pressure (as small as 1 mmHg) are associated with a lower probability of decompensation. In patients with decompensated cirrhosis, portal pressure "response" to non-selective beta-blocker (NSBB) therapy is associated with a lower mortality. When present, significant portal hypertension persists even after elimination of the etiology of cirrhosis and this justifies the continued development of new drugs that target portal hypertension. Over several decades we have gained great depth in the understanding of portal hypertension, its mechanisms and complications. NSBBs, which act by reducing portal venous inflow (an extrahepatic target), are effective in reducing portal pressure and have been the mainstay of therapy for portal hypertension in the last 35 years -being effective in preventing decompensation and variceal hemorrhage. However, because not all patients will have a sufficient response to NSBB and some may be intolerant to NSBB, alternative drugs or drugs that will augment the effect of NSBB on portal pressure are being tested in pre-clinical and early-clinical trials. Many of these drugs target more than one of the intrahepatic or extrahepatic mechanisms implicated in the pathogenesis of portal hypertension in cirrhosis. Out of these proposed therapies, statins have emerged as the most promising new pharmacological therapy for the treatment of portal hypertension.

Prospects of Antiangiogenic Therapy for Portal Hypertension in Liver Cirrhosis

Aim.This paper is aimed at reviewing existing literature that investigates the role of angiogenesis in portal hypertension pathogenesis in liver cirrhosis and the possibilities of its antiangiogenic therapy, along with the description of angiogenesis inhibiting drugs and their action mechanisms.Key points. A relevant literature and reference list search was performed using PubMed and RSCI and Google Scholar, and covered the 2000–2017 period. The following keywords were used: liver cirrhosis, portal hypertension, pathogenesis, angiogenesis, antiangiogenic therapy. The inclusion criteria were limited to the antiangiogenic therapy of portal hypertension. Angiogenesis is shown to play an important role in the pathogenesis of liver cirrhosis. Angiogenesis is the basis for the development of associated portal hypertension that causes its characteristic complications. The experimental studies reviewed in this paper investigate the action mechanism of angiogenesis inhibiting drugs and their effect on portal hypertension. It is shown that, so far, only tyrosine kinase inhibitors have been tested in patients with liver cirrhosis as an antiangiogenic therapy for portal hypertension.Conclusion.Antiangiogenic therapy, selectively directed at unusually growing newly-formed vessels, can be a pathogenetically justified method for treating portal hypertension in liver cirrhosis on its subclinical stage.

Pathogenesis of Portal Hypertension and Esophageal Varices

Esophageal varices are the major complication of portal hypertension. It is detected in about 50% of cirrhosis patients. Portal hypertensionis associated with both increased portal inflow and increased intrahepatic vascular resistance. Intrahepatic vascular resistance is caused by the architectural distortion of the liver resulting from fibrosis and by increased sinusoidal tone. Portal venous inflow results from a combination of ahyperdynamic circulatory state and increased plasma volume. In response to the increased portal pressure, collateral circulation develops by the opening of preexisting vascular channels. Esophagogastric varices are the most important collateral vessels: they tend to increase in size with the increase of portal pressure and rupture when wall tension exceeds a critical value.

Research progress on signaling pathways in cirrhotic portal hypertension.

Portal hypertension (PHT) is an important consequence of liver cirrhosis, which can lead to complications that adversely affect a patient’s quality of life and survival, such as upper gastrointestinal bleeding, ascites, and portosystemic encephalopathy. In recent years, advances in molecular biology have led to major discoveries in the pathological processes of PHT, including the signaling pathways that may be involved: PI3K-AKT-mTOR, RhoA/Rho-kinase, JAK2/STAT3, and farnesoid X receptor. However, the pathogenesis of PHT is complex and there are numerous pathways involved. Therefore, the targeting of signaling pathways for medical management is lagging. This article summarizes the progress that has been made in understanding the signaling pathways in PHT, and provides ideas for treatment of the disorder.

Antiangiogenic therapy for portal hypertension in liver cirrhosis: Current progress and perspectives.

Developing medicines for hemodynamic disorders that are characteristic of cirrhosis of the liver is a relevant problem in modern hepatology. The increase in hepatic vascular resistance to portal blood flow and subsequent hyperdynamic circulation underlie portal hypertension (PH) and promote its progression, despite the formation of portosystemic collaterals. Angiogenesis and vascular bed restructurization play an important role in PH pathogenesis as well. In this regard, strategic directions in the therapy for PH in cirrhosis include selectively decreasing hepatic vascular resistance while preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis. The aim of this review is to describe the mechanisms of angiogenesis in PH and the methods of antiangiogenic therapy. The PubMed database, the Google Scholar retrieval system, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 2000-2017 using the keywords: “liver cirrhosis”, “portal hypertension”, “pathogenesis”, “angiogenesis”, and “antiangiogenic therapy”. Antiangiogenic therapy for PH was the inclusion criterion. In this review, we have described angiogenesis inhibitors and their mechanism of action in relation to PH. Although most of them were studied only in animal experiments, this selective therapy for abnormally growing newly formed vessels is pathogenetically reasonable to treat PH and associated complications.

Hepatology Basic Science

Hepatology Basic Science

ACE I allele is associated with more severe portal hypertension in patients with liver cirrhosis: A pilot study

BackgroundIn liver cirrhosis, the renin-angiotensin-aldosterone system is involved in the pathogenesis of portal hypertension. Its effector, angiotensin II, is generated by angiotensin-converting enzyme (ACE). Serum ACE levels are affected by I/D polymorphism of its gene, with alleles I and D being associated, respectively, with lesser and greater activity of the enzyme. In cirrhotic patients carrying the ACE I allele, an increased risk for gastro-oesophageal varices was observed. AimThe aim of our study was to evaluate whether ACE I/D polymorphism influenced portal pressure. MethodsFifty-one consecutive cirrhotic patients were divided based on ACE genotype (DD, ID, and II). Kidney and liver function tests, upper endoscopy, and hepatic venous pressure gradient measurement (HVPG) were performed in all patients. ResultsThe presence of the ACE I allele was associated with a higher HVPG value (18.7±6.4 vs 10.3±6.3mmHg; P<.001), higher frequency of large gastrooesophageal varices (59.3% vs 25.0%; P<.05), and higher frequency of variceal bleeding (63.0% vs 29.2%; P<.05). No significant differences were found between patients with and those without the ACE I allele regarding Child-Pugh score, MELD score, ascites, and hepatic encephalopathy. ConclusionACE I/D polymorphism seems to influence the severity of portal hypertension and the risk of variceal bleeding in liver cirrhosis, regardless of the severity of liver disease.