Alterations in the gut microbiome after transjugular intrahepatic portosystemic shunt in patients with hepatitis B virus-related portal hypertension

BACKGROUND Gut microbiota(GM)affects the progression and response to treatment in liver diseases.The GM composition is diverse and associated with different etiologies of liver diseases.Notably,alterations in GM alterations are observed in patients with portal hypertension(PH)secondary to cirrhosis,with hepatitis B virus(HBV)infection being a major cause of cirrhosis in China.Thus,understanding the role of GM alterations in patients with HBV infection-related PH is essential.AIM To evaluate GM alterations in patients with HBV-related PH after transjugular intrahepatic portosystemic shunt(TIPS)placement.METHODS This was a prospective,observational clinical study.There were 30 patients(with a 100%technical success rate)recruited in the present study.Patients with esophagogastric variceal bleeding due to HBV infection-associated PH who underwent TIPS were enrolled.Stool samples were obtained before and one month after TIPS treatment,and GM was analyzed using 16S ribosomal RNA amplicon sequencing.RESULTS One month after TIPS placement,8 patients developed hepatic encephalopathy(HE)and were assigned to the HE group;the other 22 patients were assigned to the non-HE group.There was no substantial disparity in the abundance of GM at the phylum level between the two groups,regardless of TIPS treatment(all,P>0.05).However,following TIPS placement,the following results were observed:(1)The abundance of Haemophilus and Eggerthella increased,whereas that of Anaerostipes,Dialister,Butyricicoccus,and Oscillospira declined in the HE group;(2)The richness of Eggerthella,Streptococcus,and Bilophila increased,whereas that of Roseburia and Ruminococcus decreased in the non-HE group;and(3)Members from the pathogenic genus Morganella appeared in the HE group but not in the non-HE group.CONCLUSION Intestinal microbiota-related synergism may predict the risk of HE following TIPS placement in patients with HBVrelated PH.Prophylactic microbiome therapies may be useful for preventing and treating HE after TIPS placement.

Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension

Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related contraindications.With recent advances in precision medicine,precise drug treatment provides better treatment efficacy.Data sources:Literature search was conducted in PubMed,MEDLINE and Web of Science for relevant articles published up to May 2022.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://www.chictr.org.cn/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs.According to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and others.All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.Conclusions:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

Acute upper gastrointestinal bleeding due to portal hypertension in a patient with primary myelofibrosis:A case report

BACKGROUND Acute upper gastrointestinal bleeding is a common medical emergency that has a 10%hospital mortality rate.According to the etiology,this disease can be divided into acute varicose veins and nonvaricose veins.Bleeding from esophageal varices is a life-threatening complication of portal hypertension.Portal hypertension is a clinical syndrome defined as a portal venous pressure that exceeds 10 mmHg.Cirrhosis is the most common cause of portal hypertension,and thrombosis of the portal system not associated with liver cirrhosis is the second most common cause of portal hypertension in the Western world.Primary myeloproliferative disorders are the main cause of portal venous thrombosis,and somatic mutations in the Janus kinase 2 gene(JAK2 V617F)can be found in approximately 90% of polycythemia vera,50% of essential thrombocyrosis and 50% of primary myelofibrosis.CASE SUMMARY We present a rare case of primary myelofibrosis with gastrointestinal bleeding as the primary manifestation that presented as portal-superior-splenic mesenteric vein thrombosis.Peripheral blood tests revealed the presence of the JAK2 V617F mutation.Bone marrow biopsy ultimately confirmed the diagnosis of myelofibrosis(MF-2 grade).CONCLUSION In patients with acute esophageal variceal bleeding due to portal hypertension and vein thrombosis without cirrhosis,the possibility of myeloproliferative neoplasms should be considered,and the JAK2 mutation test should be performed.

Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors

BACKGROUND Patients with liver cancer complicated by portal hypertension present complex challenges in treatment.AIM To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition.METHODS Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group(n=50)and a control group(n=50)according to the treatment regimen.The research group received radiofrequency ablation(RFA)in combination with sorafenib,and the control group only received RFA.The short-term efficacy of both the research and control groups was observed.Liver function and portal hypertension were compared before and after treatment.Alpha-fetoprotein(AFP),glypican-3(GPC-3),and AFP-L3 levels were compared between the two groups prior to and after treatment.The occurrence of adverse reactions in both groups was observed.The 3-year survival rate was compared between the two groups.Basic data were compared between the survival and non-surviving groups.To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension,multivariate logistic regression analysis was employed.RESULTS When comparing the two groups,the research group's total effective rate(82.00%)was significantly greater than that of the control group(56.00%;P<0.05).Following treatment,alanine aminotransferase and aspartate aminotransferase levels increased,and portal vein pressure decreased in both groups.The degree of improvement for every index was substantially greater in the research group than in the control group(P<0.05).Following treatment,the AFP,GPC-3,and AFP-L3 levels in both groups decreased,with the research group having significantly lower levels than the control group(P<0.05).The incidence of diarrhea,rash,nausea and vomiting,and fatigue in the research group was significantly greater than that in the control group(P<0.05).The 1-,2-,and 3-year survival rates of the research group(94.00%,84.00%,and 72.00%,respectively)were significantly greater than those of the control group(80.00%,64.00%,and 40.00%,respectively;P<0.05).Significant differences were observed between the survival group and the non-surviving group in terms of Child-Pugh grade,history of hepatitis,number of tumors,tumor size,use of sorafenib,stage of liver cancer,histological differentiation,history of splenectomy and other basic data(P<0.05).Logistic regression analysis demonstrated that high Child-Pugh grade,tumor size(6–10 cm),history of hepatitis,no use of sorafenib,liver cancer stage IIIC,and previous splenectomy were independent risk factors for poor prognosis in patients with liver cancer complicated with portal hypertension(P<0.05).CONCLUSION Patients suffering from liver cancer complicated by portal hypertension benefit from the combination of RFA and sorafenib therapy because it effectively restores liver function and increases survival rates.The prognosis of patients suffering from liver cancer complicated by portal hypertension is strongly associated with factors such as high Child-Pugh grade,tumor size(6-10 cm),history of hepatitis,lack of sorafenib use,liver cancer at stage IIIC,and prior splenectomy.

Bayesian network-based survival prediction model for patients having undergone post-transjugular intrahepatic portosystemic shunt for portal hypertension

BACKGROUND Portal hypertension(PHT),primarily induced by cirrhosis,manifests severe symptoms impacting patient survival.Although transjugular intrahepatic portosystemic shunt(TIPS)is a critical intervention for managing PHT,it carries risks like hepatic encephalopathy,thus affecting patient survival prognosis.To our knowledge,existing prognostic models for post-TIPS survival in patients with PHT fail to account for the interplay among and collective impact of various prognostic factors on outcomes.Consequently,the development of an innovative modeling approach is essential to address this limitation.AIM To develop and validate a Bayesian network(BN)-based survival prediction model for patients with cirrhosis-induced PHT having undergone TIPS.METHODS The clinical data of 393 patients with cirrhosis-induced PHT who underwent TIPS surgery at the Second Affiliated Hospital of Chongqing Medical University between January 2015 and May 2022 were retrospectively analyzed.Variables were selected using Cox and least absolute shrinkage and selection operator regression methods,and a BN-based model was established and evaluated to predict survival in patients having undergone TIPS surgery for PHT.RESULTS Variable selection revealed the following as key factors impacting survival:age,ascites,hypertension,indications for TIPS,postoperative portal vein pressure(post-PVP),aspartate aminotransferase,alkaline phosphatase,total bilirubin,prealbumin,the Child-Pugh grade,and the model for end-stage liver disease(MELD)score.Based on the above-mentioned variables,a BN-based 2-year survival prognostic prediction model was constructed,which identified the following factors to be directly linked to the survival time:age,ascites,indications for TIPS,concurrent hypertension,post-PVP,the Child-Pugh grade,and the MELD score.The Bayesian information criterion was 3589.04,and 10-fold cross-validation indicated an average log-likelihood loss of 5.55 with a standard deviation of 0.16.The model’s accuracy,precision,recall,and F1 score were 0.90,0.92,0.97,and 0.95 respectively,with the area under the receiver operating characteristic curve being 0.72.CONCLUSION This study successfully developed a BN-based survival prediction model with good predictive capabilities.It offers valuable insights for treatment strategies and prognostic evaluations in patients having undergone TIPS surgery for PHT.

Insights and future directions in studying intestinal microbiota posttransjugular intrahepatic portosystemic shunt for hepatitis B virusrelated portal hypertension

The gut microbiota(GM)plays a major role in the progression and treatment response of liver diseases,with diverse compositions based on different etiologies.In China,hepatitis B virus(HBV)infection is the leading cause of cirrhosis and affects the GM composition in patients with cirrhosis-related portal hypertension(PH).However,a few studies have been conducted on GM alterations after transjugular intrahepatic portosystemic shunt(TIPS)in patients with HBV-related PH.A recent study investigated the changes in the GM in these patients after TIPS.This study found an increase in potentially pathogenic bacteria and a decrease in beneficial bacteria post-TIPS,particularly in patients with hepatic encephalopathy(HE),indicating the potential role of the GM in HE prediction and management post-TIPS.Nevertheless,the study had several limitations,including a small sample size,limited follow-up,a single time point for sample collection,and inadequate analysis of the correlation between intestinal flora,HBV infection status,and clinical parameters.Future research should address these limitations by expanding the sample size,prolonging the follow-up duration,collecting samples at multiple time points,and conducting compre-hensive analyses to confirm the findings and evaluate the effectiveness of individualized microbiome-based therapies.

Portal hypertension in patients with nonalcoholic fatty liver disease:Current knowledge and challenges

Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH may develop in earlier stages of NAFLD,suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis.The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning,leading to the compression of liver sinusoids.External compression and intraluminal obstacles cause mechanical forces such as strain,shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways,resulting in endothelial dysfunction and the development of fibrosis.The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD.Thus,current diagnostic methods such as hepatic venous pressure gradient(HVPG)measurement tend to underestimate portal pressure(PP)in NAFLD patients,who might decompensate below the HVPG threshold of 10 mmHg,which is traditionally considered the most relevant indicator of clinically significant portal hypertension(CSPH).This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients.In theory,the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component,but more investigations are needed to test its clinical utility for this indication.Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment.Lifestyle change remains the cornerstone of the treatment of PH in NAFLD,together with correcting the components of metabolic syndrome,using nonselective beta blockers,whereas emerging candidate drugs require more robust confirmation from clinical trials.

Glucocorticoid therapy in pancreatic portal hypertension associated with autoimmune pancreatitis:A case report

BACKGROUND Autoimmune pancreatitis(AIP)is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct.Some studies have reported that AIP can cause hemorrhage of gastric varices(GV)related to portal hypertension(PH).However,such cases are rare.In addition,the association of PH with AIP is unclear.At the same time,the efficacy and duration of glucocorticoid therapy is also controversial.CASE SUMMARY In this case,we reported a case of GV in pancreatic PH associated with AIP.Enhanced abdominal computed tomography(CT)suggested splenic vein(SV)and superior mesenteric vein(SMV)thromboses.The patient received a long-term glucocorticoid therapy,that the initial dose of 40 mg is reduced weekly by 5 mg,and then reduced to 5 mg for long-term maintenance.CT and gastroscopic examination after 8 mo of treatment indicated that SV and SMV were recanalized,pancreatic stiffness and swelling were ameliorated,and the GV almost completely disappeared.CONCLUSION Long-term glucocorticoid therapy can alleviate the development of GV in patients with AIP and has potential reversibility.

Spleen volume is associated with overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with portal hypertension

BACKGROUND Portal shunt and immune status related to the spleen are related to the occurrence of hepatic encephalopathy(HE).It is unknown whether spleen volume before transjugular intrahepatic portosystemic shunt(TIPS)is related to postoperative HE.AIM To investigate the relationship between spleen volume and the occurrence of HE.METHODS This study included 135 patients with liver cirrhosis who underwent TIPS,and liver and spleen volumes were elevated upon computed tomography imaging.The Kaplan-Meier curve was used to compare the difference in the incidence rate of HE among patients with different spleen volumes.Univariate and multivariate Cox regression analyses were performed to identify the factors affecting overt HE(OHE).Restricted cubic spline was used to examine the shapes of the dose-response association between spleen volumes and OHE risk.RESULTS The results showed that 37(27.2%)of 135 patients experienced OHE during a 1-year follow-up period.Compared with preoperative spleen volume(901.30±471.90 cm3),there was a significant decrease in spleen volume after TIPS(697.60±281.0 cm^(3))in OHE patients.As the severity of OHE increased,the spleen volume significantly decreased(P<0.05).Compared with patients with a spleen volume≥782.4 cm^(3),those with a spleen volume<782.4 cm^(3) had a higher incidence of HE(P<0.05).Cox regression analysis showed that spleen volume was an independent risk factor for post-TIPS OHE(hazard ratio=0.494,P<0.05).Restricted cubic spline model showed that with an increasing spleen volume,OHE risk showed an initial increase and then decrease(P<0.05).CONCLUSION Spleen volume is related to the occurrence of OHE after TIPS.Preoperative spleen volume is an independent risk factor for post-TIPS OHE.

Milestones to optimize of transjugular intrahepatic portosystemic shunt technique as a method for the treatment of portal hypertension complications

This editorial describes the milestones to optimize of transjugular intrahepatic portosystemic shunt(TIPS)technique,which have made it one of the main methods for the treatment of portal hypertension complications worldwide.Innovative ideas,subsequent experimental studies and preliminary experience of use in cirrhotic patients contributed to the introduction of TIPS into clinical practice.At the moment,the main achievement in optimize of TIPS technique is progress in the qualitative characteristics of stents.The transition from bare metal stents to extended polytetrafluoroethylene–covered stent grafts made it possible to significantly prevent shunt dysfunction.However,the question of its preferred diameter,which contributes to an optimal reduction of portal pressure without the risk of developing post-TIPS hepatic encephalopathy,remains relevant.Currently,hepatic encephalopathy is one of the most common complications of TIPS,significantly affecting its effectiveness and prognosis.Careful selection of patients based on cognitive indicators,nutritional status,assessment of liver function,etc.,will reduce the incidence of post-TIPS hepatic encephalopathy and improve treatment results.Optimize of TIPS technique has significantly expanded the indications for its use and made it one of the main methods for the treatment of portal hypertension complications.At the same time,there are a number of limitations and unresolved issues that require further randomized controlled trials involving a large cohort of patients.

Safety and efficacy of modified endoscopic ultrasound-guided selective N-butyl-2-cyanoacrylate injections for gastric variceal hemorrhage in left-sided portal hypertension

BACKGROUND Gastric variceal hemorrhage is one of the primary manifestations of left-sided portal hypertension(LSPH).The hemorrhage is fatal and requires safe and effective interventions.AIM To evaluate the clinical safety and efficacy of modified endoscopic ultrasound(EUS)-guided selective N-butyl-2-cyanoacrylate(NBC)injections for gastric variceal hemorrhage in LSPH.METHODS A retrospective observational study of patients with LSPH-induced gastric variceal hemorrhage was conducted.Preoperative EUS evaluations were performed.Enrolled patients were divided into modified and conventional groups according to the NBC injection technique.The final selection of NBC injection technique depended on the patients’preferences and clinical status.The technical and clinical success rates,operation time,NBC doses,perioperative complications,postoperative hospital stay,and recurrent bleeding rates were analyzed,respectively.RESULTS A total of 27 patients were enrolled.No statistically significant differences were observed between the two groups regarding baseline characteristics.In comparison to patients in the conventional group,patients in the modified group demonstrated significantly reduced NBC doses(2.0±0.6 mL vs 3.1±1.0 mL;P=0.004)and increased endoscopic operation time(71.9±11.9 min vs 22.5±6.7 min;P<0.001).Meanwhile,the two groups had no significant difference in the technical and clinical success rates,perioperative complications,postoperative hospital stay,and recurrent bleeding rates.CONCLUSION Modified EUS-guided selective NBC injections demonstrated safety and efficacy for LSPH-induced gastric variceal hemorrhage,with advantages of reduced injection dose and no radiation risk.Drawbacks were time consumption and technical challenge.

Portal hypertension and gastrointestinal bleeding:Diagnosis,prevention and management

Bleeding from esophageal varices is a life threatening complication of portal hypertension.Primary prevention of bleeding in patients at risk for a first bleeding episode is therefore a major goal.Medical prophylaxis consists of non-selective beta-blockers like propranolol or carvedilol.Variceal endoscopic band ligation is equally effective but procedure related morbidity is a drawback of the method.Therapy of acute bleeding is based on three strategies:vasopressor drugs like terlipressin,antibiotics and endoscopic therapy.In refractory bleeding,self-expandable stents offer an option for bridging to definite treatments like transjugular intrahepatic portosystemic shunt(TIPS).Treatment of bleeding from gastric varices depends on vasopressor drugs and on injection of varices with cyanoacrylate.Strategies for primary or secondary prevention are based on non-selective beta-blockers but data from large clinical trials is lacking.Therapy of refractory bleeding relies on shuntprocedures like TIPS.Bleeding from ectopic varices,portal hypertensive gastropathy and gastric antral vascular ectasia-syndrome is less common.Possible medical and endoscopic treatment options are discussed.

Clinical implication of VEGF serum levels in cirrhotic patients with or without portal hypertension

AIM To determine whether serum vascular endothelial growth factor (VEGF) levels correlates with the severity of liver cirrhosis and whether portal hypertension impacts on the expression of serum VEGF protein. METHODS Fifty three patients (mean age 56±2 years) with HCV ( n =26), HBV ( n =13), and cryptogenic liver cirrhosis ( n =14) (Child Pughs class A: 24, B: 19 and C: 12) and normal renal function constitute the patient population, who were all diagnosed by clinical, histological and radiological findings. Six healthy people and six patients with acute hepatitis served as controls. Severity of liver disease was evaluated by the CP score. Serum levels of IGF 1 and VEGF were measured by radioimmunoassay and ELISA, respectively. Portal hypertension was assessed using pulsed Doppler ultrasound. RESULTS The mean serum VEGF levels in all cirrhotic patients (73±58) were significantly lower than those of healthy controls (360±217, P <0 01) and acute hepatitis (1123±1261, P <0 01) respectively. No significant difference in median serum VEGF levels were noted among the different Child Pughs classes (class A: median, 49 4ng/L , range, 21ng/L - 260ng/L , Class B: median 59 9ng/L ; range 21-92, and Class C: median 69; range 20ng/L - 247ng/L ). A significant correlation was noted between serum VEGF and two accurate parameters of portal hypertension: portal blood flow velocity ( r =0 6) and spleen size ( r =0 55). No correlation was found between VEGF serum levels and serum albumin, IGF 1, platelets count and aminotrasnferases ( r =0 2, r =0 1, r =0 2 and r =0 2, respectively). CONCLUSION Circulating VEGF level in patients with liver cirrhosis could not serve as an indicator of the progression of chronic liver disease but rather, they may reflect increased portal hypertension or decreased hepatic regenerative activity or the combination of both.

Management of small hepatocellular carcinoma in cirrhosis:Focus on portal hypertension

The incidence of hepatocellular carcinoma(HCC) is rising worldwide being currently the fifth most common cancer and third cause of cancer-related mortality.Early detection of HCC through surveillance programs have enabled the identification of small nodules with higher frequency,and nowadays account for 10%-15% of patients diagnosed in the West and almost 30% in Japan.Patients with small HCC can be candidates for potential curative treatments:liver transplantation,surgical resection and percutaneous ablation,depending on the presence of portal hypertension and co-morbidities.This review will analyze recent advancements in the clinical management of these individuals,focusing on issues related to the role of portal hypertension,the debate between resection and ablative therapies and the future impact of molecular technologies.

Clinical effects and complications of TIPS for portal hypertension due to cirrhosis:A single center

AIM:To determine the clinical effects and complications of transjugular intrahepatic portosystemic shunt(TIPS)for portal hypertension due to cirrhosis.METHODS:Two hundred and eighty patients with portal hypertension due to cirrhosis who underwent TIPS were retrospectively evaluated.Portal trunk pressure was measured before and after surgery.The changes in hemodynamics and the condition of the stent were assessed by ultrasound and the esophageal and fundic veins observed endoscopically.RESULTS:The success rate of TIPS was 99.3%.The portal trunk pressure was 26.8±3.6 cmH2O after surgery and 46.5±3.4 cmH2O before surgery(P<0.01).The velocity of blood flow in the portal vein increased.The internal diameters of the portal and splenic veins were reduced.The short-term hemostasis rate was100%.Esophageal varices disappeared completely in68%of patients and were obviously reduced in 32%.Varices of the stomach fundus disappeared completely in 80%and were obviously reduced in 20%of patients.Ascites disappeared in 62%,were markedly reduced in 24%,but were still apparent in 14%of patients.The total effective rate of ascites reduction was 86%.Hydrothorax completely disappeared in 100%of patients.The incidence of post-operative stent stenosis was 24%at 12 mo and 34%at 24 mo.The incidence of post-operative hepatic encephalopathy was 12%at3 mo,17%at 6 mo and 19%at 12 mo.The incidence of post-operative recurrent hemorrhage was 9%at 12mo,19%at 24 mo and 35%at 36 mo.The cumulative survival rate was 86%at 12 mo,81%at 24 mo,75%at 36 mo,57%at 48 mo and 45%at 60 mo.CONCLUSION:TIPS can effectively lower portal hypertension due to cirrhosis.It is significantly effective for hemorrhage of the digestive tract due to rupture of esophageal and fundic veins and for ascites and hydrothorax caused by portal hypertension.

Contemporary concepts of the medical therapy of portal hypertension under liver cirrhosis

Severe complications of liver cirrhosis are mostly related to portal hypertension. At the base of the pathogenesis of portal hypertension is the increase in hepatic vascular resistance to portal blood flow with subsequent development of hyperdynamic circulation, which, despite of the formation of collateral circulation, promotes progression of portal hypertension. An important role in its pathogenesis is played by the rearrangement of vascular bed and angiogenesis. As a result, strategic directions of the therapy of portal hypertension under liver cirrhosis include selectively decreasing hepatic vascular resistance with preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis, while striving to reduce the hepatic venous pressure gradient to less than 12 mm Hg or 20% of the baseline. Over the last years, substantial progress in understanding the pathophysiological mechanisms of hemodynamic disorders under liver cirrhosis has resulted in the development of new drugs for their correction. Although the majority of them have so far been investigated only in animal experiments, as well as at the molecular and cellular level, it might be expected that the introduction of the new methods in clinical practice will increase the efficacy of the conservative approach to the prophylaxis and treatment of portal hypertension complications. The purpose of the review is to describe the known methods of portal hypertension pharmacotherapy and discuss the drugs that may affect the basic pathogenetic mechanisms of its development.

Current concepts on the role of nitric oxide in portal hypertension

Portal hypertension(PHT) is defined as a pathological increase in portal venous pressure and frequently accompanies cirrhosis.Portal pressure can be increased by a rise in portal blood flow,an increase in vascular resistance,or the combination.In cirrhosis,the primary factor leading to PHT is an increase in intra-hepatic resistance to blood flow.Although much of this increase is a mechanical consequence of architectural disturbances,there is a dynamic and reversible component that represents up to a third of the increased vascular resistance in cirrhosis.Many vasoactive substances contribute to the development of PHT.Among these,nitric oxide(NO) is the key mediator that paradoxically regulates the sinusoidal(intra-hepatic) and systemic/splanchnic circulations.NO deficiency in the liver leads to increased intra-hepatic resistance while increased NO in the circulation contributes to the hyperdynamic systemic/splanchnic circulation.NO mediated-angiogenesis also plays a role in splanchnic vasodilation and collateral circulation formation.NO donors reduce PHT in animals models but the key clinical challenge is the development of an NO donor or drug delivery system that selectively targets the liver.

Abnormal splenic artery diameter/hepatic artery diameter ratio in cirrhosis-induced portal hypertension

AIM:To determine an optimal cutoff value for abnormal splenic artery diameter/proper hepatic artery diameter(S/P) ratio in cirrhosis-induced portal hypertension.METHODS:Patients with cirrhosis and portal hypertension(n = 770) and healthy volunteers(n = 31) underwent volumetric computed tomography threedimensional vascular reconstruction to measure the internal diameters of the splenic artery and proper hepatic artery to calculate the S/P ratio.The cutoff value for abnormal S/P ratio was determined using receiver operating characteristic curve analysis,and the prevalence of abnormal S/P ratio and associations between abnormal S/P ratio and major complications of portal hypertension were studied using logistic regression.RESULTS:The receiver operating characteristic analysis showed that the cutoff points for abnormal splenic artery internal diameter and S/P ratio were > 5.19 mm and > 1.40,respectively.The sensitivity,specificity,positive predictive value,and negative predictive value were 74.2%,45.2%,97.1%,and 6.6%,respectively.The prevalence of an abnormal S/P ratio in the patients with cirrhosis and portal hypertension was 83.4%.Patients with a higher S/P ratio had a lower risk of developing ascites [odds ratio(OR) = 0.708,95%CI:0.508-0.986,P = 0.041] and a higher risk of developing esophageal and gastric varices(OR = 1.483,95%CI:1.010-2.175,P = 0.044) and forming collateral circulation(OR = 1.518,95%CI:1.033-2.230,P = 0.034).After splenectomy,the portal venous pressure and maximum and mean portal venous flow velocities were reduced,while the flow rate and maximum and minimum flow velocities of the hepatic artery were increased(P < 0.05).CONCLUSION:The prevalence of an abnormal S/P ratio is high in patients with cirrhosis and portal hypertension,and it can be used as an important marker of splanchnic hemodynamic disturbances.

Liver surgery in cirrhosis and portal hypertension

The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary ormetastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis.

Two surgical procedures for esophagogastric variceal bleeding in patients with portal hypertension

AIM:To determine the clinical value of a splenorenal shunt plus pericardial devascularization(PCVD)in portal hypertension(PHT)patients with variceal bleeding.METHODS:From January 2008 to November 2012,290 patients with cirrhotic portal hypertension were treated surgically in our department for the prevention of gastroesophageal variceal bleeding:207 patients received a routine PCVD procedure(PCVD group),and83 patients received a PCVD plus a splenorenal shunt procedure(combined group).Changes in hemodynamic parameters,rebleeding,encephalopathy,portal vein thrombosis,and mortality were analyzed.RESULTS:The free portal pressure decreased to 21.43±4.35 mmHg in the combined group compared with24.61±5.42 mmHg in the PCVD group(P<0.05).The changes in hemodynamic parameters were more significant in the combined group(P<0.05).The long-term rebleeding rate was 7.22%in the combined group,which was lower than that in the PCVD group(14.93%),(P<0.05).CONCLUSION:Devascularization plus splenorenal shunt is an effective and safe strategy to control esophagogastric variceal bleeding in PHT.It should be recommended as a first-line treatment for preventing bleeding in PHT patients when surgical interventions are considered.