Gut microbiota shifts in hepatitis B-related portal hypertension after transjugular intrahepatic portosystemic shunt:Mechanistic and clinical implications

In this article,we provide commentary on the recent article by Zhao et al.We focus on the shifts in the gut microbiota of patients with hepatitis B virus(HBV)-associated cirrhosis/portal hypertension(PH)following transjugular intrahepatic portosystemic shunt(TIPS)and the implications for understanding the mechanisms,diagnosis,and treatment.By comparing the gut microbiota composition and dynamic changes before and after TIPS in patients with and without hepatic encephalopathy,the authors found an increase in non-probiotic bacteria in those who developed hepatic encephalopathy post-TIPS,with Morganella species present only in the hepatic encephalopathy group.The gut microbiota changes post-TIPS among patients without the occurrence of hepatic encephalopathy suggest potential therapeutic benefits through prophylactic microbiome therapies.Furthermore,the specific gut microbiota alterations may hold promise to predict the risk of hepatic encephalopathy in individuals undergoing TIPS for HBVrelated PH.Despite these promising findings,future studies are needed to address limitations,including a small sample size,a relatively short evaluation period for gut microbiota alterations,the absence of data on dynamic alterations in gut microbiota post-TIPS and their correlation with blood ammonia levels,and the lack of validation in animal models.In conclusion,Zhao et al's study has shed new light on the link of gut microbiota with post-TIPS hepatic encephalopathy,potentially through the intricate gut-liver axis,and has important clinical implications for improving the management of patients with HBV-related PH.

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.

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.

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.

A rabbit model of non- cirrhotic portal hypertension by repeated injections of E. coli through indwelling cannulation of the gastrosplenic vein

BACKGROUND: Non-cirrhotic portal hypertension is acommon cause of portal hypertension in developing coun-tries. To understand its etiopathogenesis we developed ananimal model by repeated portal endotoxemia inducedthrough the gastrosplenic vein.METHODS: Twenty-nine rabbits (1.5-2.0 kg) were divid-ed into control (group n = 13) and experimental ( groupn = 16) groups. Heat killed E. coli were injected throughan indwelling cannula into the gastrosplenic vein in pre-sensitized animals. The animals were sacriflced at 1, 3 and6 months.RESULTS: The mean portal pressure in group animalswas significantly (P < 0. 05) higher than in group at 1(17.5 ±3.4 vs 10.4±2.2 mmHg), 3 (17.8±1.3 vs7.2 +3.6mmHg), and 6 (19.8±3.1 vs 10.3±4.8 mmHg) months.Similarly, the mean splenic weight in group was signifi-cantly greater than in group (P <0.05). Histopathologi-cally, the spleen showed medullary congestion, hemosid-rin-laden macrophages and mild fibrosis. Histologically,the liver had normal parenchyma with mild portal lympho-cytic infiltrates and kupffer cell hyperplasia. No significantanomalies were detected by liver function tests.CONCLUSIONS: The rabbit model showed significantsplenomegaly with a persistent increase in portal pressureand mild fibrosis without hepatic parenchymal injury, quiteakin to non-cirrhotic portal fibrosis as seen in humans. Re-current intra-abdominal infection may play an importantrole in the pathogenesis of non-cirrhotic portal fibrosis.

Pre-and postoperative systemic hemodynamic evaluation in patients subjected to esophagogastric devascularization plus splenectomy and distal splenorenal shunt:A comparative study in schistomomal portal hypertension

AIM: To investigate the systemic hemodynamic effects of two surgical procedures largely employed for treatment of schistosomal portal hypertension. METHODS: Thirty-six patients undergoing elective surgical treatment of portal hypertension due to hepatosplenic mansonic schistosomiasis were prospectively evaluated. All patients were subjected to preoperative pulmonary artery catheterization; 17 were submitted to esophagogastric devascularization and splenectomy (EGDS) and 19 to distal splenorenal shunt (DSRS). The systemic hemodynamic assessment was repeated 4 d after the surgical procedure. RESULTS: Preoperative evaluation revealed (mean ± SD) an increased cardiac index (4.78 ± 1.13 L/min per m2),associated with a reduction in systemic vascular resistance index (1457 ± 380.7 dynes.s/cm5.m2). The mean pulmonary artery pressure (18 ± 5.1 mmHg) as well as the right atrial pressure (7.9 ± 2.5 mmHg) were increased,while the pulmonary vascular resistance index (133 ± 62 dynes.s/cm5.m2) was decreased. Four days after EGDS,a significant reduction in cardiac index (3.80 ± 0.4 L/min per m2,P < 0.001) and increase in systemic vascular resistance index (1901.4 ± 330.2 dynes.s/cm5. m2,P < 0.001) toward normal levels were observed. There was also a significant reduction in pulmonary artery pressure (12.65 ± 4.7 mmHg,P < 0.001) and no significant changes in the pulmonary vascular resistance index (141.6 ± 102.9 dynes.s/cm5.m2). Four days after DSRS,a non-significant increase in cardiac index (5.2 ± 0.76 L/min per m2) and systemic vascular resistance index (1389 ± 311 dynes.s/cm5.m2) was observed. There was also a non-significant increase in pulmonary artery pressure (19.84 ± 5.2 mmHg),right cardiac work index (1.38 ± 0.4 kg.m/m2) and right ventricular systolic work index (16.3 ± 6.3 g.m/m2),without significant changes in the pulmonary vascular resistance index (139.7 ± 67.8 dynes.s/cm5.m2). CONCLUSION: The hyperdynamic circulatory state observed in mansonic schistosomiasis was corrected by EGDS,but was maintained in patients who underwent DSRS. Similarly,the elevated mean pulmonary artery pressure was corrected after EGDS and maintained after DSRS. EGDS seems to be the most physiologic surgery for patients with schistosomal portal hypertension.

Correlation of transient elastography with hepatic venous pressure gradient in patients with cirrhotic portal hypertension: A study of 326 patients from India

AIMTo study the diagnostic accuracy of transient elastography (TE) for detecting clinically significant portal hypertension (CSPH) in Indian patients with cirrhotic portal hypertension.METHODSThis retrospective study was conducted at the Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, on consecutive patients with cirrhosis greater than 15 years of age who underwent hepatic venous pressure gradient (HVPG) and TE from July 2011 to May 2016. Correlation between HVPG and TE was analyzed using the Spearman&#x02019;s correlation test. Receiver operating characteristic (ROC) curves were prepared for determining the utility of TE in predicting various stages of portal hypertension. The best cut-off value of TE for the diagnosis of CSPH was obtained using the Youden index.RESULTSThe study included 326 patients [median age 52 (range 16-90) years; 81% males]. The most common etiology of cirrhosis was cryptogenic (45%) followed by alcohol (34%). The median HVPG was 16.0 (range 1.5 to 30.5) mmHg. Eighty-five percent of patients had CSPH. A significant positive correlation was noted between TE and HVPG (rho 0.361, P &#x0003c; 0.001). The area under ROC curve for TE in predicting CSPH was 0.740 (95%CI: 0.662-0.818) (P &#x0003c; 0.01). A cut-off value of TE of 21.6 kPa best predicted CSPH with a positive predictive value (PPV) of 93%.CONCLUSIONTE has a fair positive correlation with HVPG; thus, TE can be used as a non-invasive modality to assess the degree of portal hypertension. A cut-off TE value of 21.6 kPa identifies CSPH with a PPV of 93%.

Computed tomography combined with gastroscopy for assessment of pancreatic segmental portal hypertension

BACKGROUND Pancreatic segmental portal hypertension(PSPH) is the only type of portal hypertension that can be completely cured. However, it can easily cause varicose veins in the esophagus and stomach and hemorrhage in the digestive tract.AIM To explore the application of computed tomography(CT) to examine the characteristics of PSPH and assess the risk level.METHODS This was a retrospective analysis of CT images of 22 patients diagnosed with PSPH at our center. Spearman correlation analysis was performed using the range of esophageal and gastric varices(measured by the vertical gastric wall), the ratio of the width of the splenic portal vein to that of the compression site(S/C ratio), the degree of splenomegaly, and the stage determined by gastroscopy. This study examined whether patients experienced gastrointestinal bleeding within 2 wk and combined CT and gastroscopy to explore the connection between bleeding and CT findings.RESULTS The range of esophageal and gastric varices showed the best correlation in the diagnosis of PSPH(P < 0.001), and the S/C ratio(P = 0.007) was correlated with the degree of splenomegaly(P = 0.021) and PSPH(P < 0.05). This study revealed that male patients were more likely than females to progress to grade 2 or grade 3 as determined by gastroscopy. CT demonstrated excellent performance, with an area under the curve of 0.879.CONCLUSION CT can be used to effectively analyze the imaging signs of PSPH, and CT combined with gastroscopy can effectively predict the risk level of gastrointestinal bleeding.

Intraoperative pulmonary hypertension occurred in an asymptomatic patient with pre-existent liver cirrhotic and portal hypertension

Portopulmonary hypertension(PPH) is clinically defined as the development of pulmonary arterial hypertension complicated by portal hypertension,with or without advanced hepatic disease.Physical signs may be absent in mild to moderate PPH and only appear in a hyperdynamic circulatory state.Similar signs of advanced liver disease can be observed in severe PPH,with ascites and lower extremity edema.Pulmonary hypertension is usually diagnosed after anesthetic induction during liver transplantation(LT).We present intraoperative pulmonary hypertension in a 41-year-old male patient with hepatic cirrhosis.Since this patient had no preoperation laboratory data supporting the diagnosises of pulmonary hypertension and was asymptomatic for a number of years,it was necessary to send him to the intensive care unit after operation.Further study should be focued on the diagnosis and treatment of pulmonary arterial hypertension in order to reduce its mortality.

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.

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.

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.

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.

Peripheral blood cell variations in cirrhotic portal hypertension patients with hypersplenism

Objective: To explore peripheral blood cell variations in hepatic cirrhosis portal hypertension patients with hypersplenism. Methods: Clinical data of 322 hypersplenism patients with decreased peripheral blood cells, admitted with cirrhotic portal hypertension, was retrospectively studied over the last 17 years. Results: In 64% (206/322) of patients, more than 2 kinds of blood cell were decreased, including 89 cases of pancytopenia (43.2%), 52 cases of WBC + PLT decrease (25.2%), 29 cases of RBC + PLT decrease (14.1%), and 36 cases of WBC + RBC decrease (17.5%); in 36% (116/322) of patients, single type blood cell decrease occurred, including 31 cases of PLT decrease (26.7%), 29 cases of WBC decrease (25%) and 56 cases of RBC decrease (48.3%). Of 227 routine bone marrow examinations, bone marrow hyperplasia was observed in 118 cases (52.0%), the remainder showed no hyperplasia. For the distinct scope and extent of peripheralblood cell decreases, preoperative blood component transfusions were carried out, then treated by surgery, after whole group splenectomy, the peripheral blood cell count was significantly higher ( P <0.05). Conclusions: Of portal hypertensive patients with splenomegaly and hypersplenism, 64% have simultaneous decrease in various blood cells, 36% have decrease in single type blood cells, 52% of patients have bone marrow hyperplasia. A splenectomy can significantly increase the reduction of peripheral blood cells.