Pre-transjugular-intrahepatic-portosystemic-shunt measurement of hepatic venous pressure gradient and its clinical application: A comparison study

BACKGROUND It is controversial whether transjugular intrahepatic portosystemic shunt(TIPS)placement can improve long-term survival.AIM To assess whether TIPS placement improves survival in patients with hepaticvenous-pressure-gradient(HVPG)≥16 mmHg,based on HVPG-related risk stratification.METHODS Consecutive variceal bleeding patients treated with endoscopic therapy+nonselectiveβ-blockers(NSBBs)or covered TIPS placement were retrospectively enrolled between January 2013 and December 2019.HVPG measurements were performed before therapy.The primary outcome was transplant-free survival;secondary endpoints were rebleeding and overt hepatic ence-phalopathy(OHE).RESULTS A total of 184 patients were analyzed(mean age,55.27 years±13.86,107 males;102 in the EVL+NSBB group,82 in the covered TIPS group).Based on the HVPG guided risk stratification,70 patients had HVPG<16 mmHg,and 114 patients had HVPG≥16 mmHg.The median follow-up time of the cohort was 49.5 mo.There was no significant difference in transplant-free survival between the two treatment groups overall(hazard ratio[HR],0.61;95%confidence interval[CI]:0.35-1.05;P=0.07).In the high-HVPG tier,transplant-free survival was higher in the TIPS group(HR,0.44;95%CI:0.23-0.85;P=0.004).In the low-HVPG tier,transplantfree survival after the two treatments was similar(HR,0.86;95%CI:0.33-0.23;P=0.74).Covered TIPS placement decreased the rate of rebleeding independent of the HVPG tier(P<0.001).The difference in OHE between the two groups was not statistically significant(P=0.09;P=0.48).CONCLUSION TIPS placement can effectively improve transplant-free survival when the HVPG is greater than 16 mmHg.

Hepatic venous pressure gradient: Inaccurately estimates portal venous pressure gradient in alcoholic cirrhosis and portal hypertension

BACKGROUND Portal hypertension(PHT)in patients with alcoholic cirrhosis causes a range of clinical symptoms,including gastroesophageal varices and ascites.The hepatic venous pressure gradient(HVPG),which is easier to measure,has replaced the portal venous pressure gradient(PPG)as the gold standard for diagnosing PHT in clinical practice.Therefore,attention should be paid to the correlation between HVPG and PPG.METHODS Between January 2017 and June 2020,134 patients with alcoholic cirrhosis and PHT who met the inclusion criteria underwent various pressure measurements during transjugular intrahepatic portosystemic shunt procedures.Correlations were assessed using Pearson’s correlation coefficient to estimate the correlation coefficient(r)and determination coefficient(R^(2)).Bland-Altman plots were constructed to further analyze the agreement between the measurements.Disagreements were analyzed using paired t tests,and P values<0.05 were considered statistically significant.RESULTS In this study,the correlation coefficient(r)and determination coefficient(R2)between HVPG and PPG were 0.201 and 0.040,respectively(P=0.020).In the 108 patients with no collateral branch,the average wedged hepatic venous pressure was lower than the average portal venous pressure(30.65±8.17 vs.33.25±6.60 mmHg,P=0.002).Hepatic collaterals were identified in 26 cases with balloon occlusion hepatic venography(19.4%),while the average PPG was significantly higher than the average HVPG(25.94±7.42 mmHg vs 9.86±7.44 mmHg;P<0.001).The differences between HVPG and PPG<5 mmHg in the collateral vs no collateral branch groups were three cases(11.54%)and 44 cases(40.74%),respectively.CONCLUSION In most patients,HVPG cannot accurately represent PPG.The formation of hepatic collaterals is a vital reason for the strong underestimation of HVPG.

Comparison of hepatic venous pressure gradient and endoscopic grading of esophageal varices

AIM: To determine the correlation between the hepatic venous pressure gradient and the endoscopic grade of esophageal varices.METHODS: From September 2009 to March 2013, a total of 176 measurements of hepatic venous pressure gradient (HVPG) were done in 146 patients. Each transjugular HVPG was measured twice, first using an end whole catheter (EH-HVPG), and then using a balloon catheter (B-HVPG). The HVPG was compared with the endoscopic grade of esophageal varices (according to the general rules for recording endoscopic findings of esophagogastric varices), which was recorded within a month of the measurement of HVPG.RESULTS: The study included 110 men and 36 women, with a mean age of 56.1 years (range, 43-76 years). The technical success rate of the pressure measurements was 100% and there were no complication related to the procedures. Mean HVPG was 15.3 mmHg as measured using the end hole catheter method and 16.5 mmHg as measured using the balloon catheter method. Mean HVPG (both EH-HVPG and B-HVPG) was not significantly different among patients with different characteristics, including sex and comorbid factors, except for cases with hepatocellular carcinoma (B-HVPG, P = 0.01; EH-HVPG, P = 0.02). Portal hypertension (&#x0003e; 12 mmHg HVPG) occurred in 66% of patients according to EH-HVPG and 83% of patients according to B-HVGP, and significantly correlated with Child&#x02019;s status (B-HVPG, P &#x0003c; 0.000; EH-HVGP, P &#x0003c; 0.000) and esophageal varies observed upon endoscopy (EH-HVGP, P = 0.003; B-HVGP, P = 0.006). One hundred and thirty-five endoscopies were performed, of which 15 showed normal findings, 27 showed grade 1 endoscopic esophageal varices, 49 showed grade 2 varices, and 44 showed grade 3 varices. When comparing endoscopic esophageal variceal grades and HVPG using univariate analysis, the P value was 0.004 for EH-HVPG and 0.002 for B-HVPG.CONCLUSION: Both EH-HVPG and B-HVPG showed a positive correlation with the endoscopic grade of esophageal varices, with B-HVPG showing a stronger correlation than EH-HVPG.

Hepatic venous pressure gradient measurement before TIPS for acute variceal bleeding

Hepatic venous pressure gradient(HVPG)is an independent predictor of variceal rebleeding in patients with cirrhosis.After pharmacological and/or endoscopic therapy,the use of a transjugular intrahepatic portosystemic shunt(TIPS)may be necessary in HVPG non-responders,but not in responders.Thus,HVPG measurement may be incorporated into the treatment algorithm for acute variceal bleeding,which further identifies the candidates that should undergo early insertion of TIPS or maintain the traditional pharmacological and/or endoscopic therapy.The potential benefits are to reduce the cost and prevent TIPS-related complications.

Computed tomography perfusion in liver and spleen for hepatitis B virus-related portal hypertension:A correlation study with hepatic venous pressure gradient

BACKGROUND Hepatic venous pressure gradient(HVPG)is the gold standard for diagnosis of portal hypertension(PH).However,its use can be limited because it is an invasive procedure.Therefore,it is necessary to explore a non-invasive method to assess PH.AIM To investigate the correlation of computed tomography(CT)perfusion of the liver with HVPG and Child-Pugh score in hepatitis B virus(HBV)-related PH.METHODS Twenty-eight patients(4 female,24 male)with gastroesophageal variceal bleeding induced by HBV-related PH were recruited in our study.All patients received CT perfusion of the liver before transjugular intrahepatic portosystemic stent-shunt(TIPS)therapy.Quantitative parameters of CT perfusion of the liver,including liver blood flow(LBF),liver blood volume(LBV),hepatic artery fraction,splenic blood flow and splenic blood volume were measured.HVPG was recorded during TIPS therapy.Correlation of liver perfusion with Child-Pugh score and HVPG were analyzed,and the receiver operating characteristic curve was analyzed.Based on HVPG(>12 mmHg vs≤12 mmHg),patients were divided into moderate and severe groups,and all parameters were compared.RESULTS Based on HVPG,18 patients were classified into the moderate group and 10 patients were classified into the severe group.The Child-Pugh score,HVPG,LBF and LBV were significantly higher in the moderate group compared to the severe group(all P<0.05).LBF and LBV were negatively associated with HVPG(r=-0.473,P<0.05 and r=-0.503,P<0.01,respectively),whereas splenic blood flow was positively associated with hepatic artery fraction(r=0.434,P<0.05).LBV was negatively correlated with Child-Pugh score.Child-Pugh score was not related to HVPG.Using a cutoff value of 17.85 mL/min/100 g for LBV,the sensitivity and specificity of HVPG≥12 mmHg for diagnosis were 80%and 89%,respectively.CONCLUSION LBV and LBF were negatively correlated with HVPG and Child-Pugh scores.CT perfusion imaging is a potential non-invasive quantitative predictor for PH in HBV-related liver cirrhosis.

Sildenafil does not influence hepatic venous pressure gradient in patients with cirrhosis

AIM： To investigate if sildenafil increases splanchnic blood flow and changes the hepatic venous pressure gradient （HVPG） in patients with cirrhosis. Phosphodiesterase type-5 inhibitors are valuable in the treatment of erectile dysfunction and pulmonary hypertension in patients with end-stage liver disease. However, the effect of phosphodiesterase type-5 inhibitors on splanchnic blood flow and portal hypertension remains essentially unknown. METHODS： Ten patients with biopsy proven cirrhosis （five females/five males, mean age 54：1：8 years） and an HVPG above 12 mmHg were studied after informed consent. Measurement of splanchnic blood flow and the HVPG during liver vein catheterization were done before and 80 min after oral administration of 50 mg sildenafil. Blood flow was estimated by use of indocyanine green clearance technique and Fick＇s principle, with correction for non-steady state. RESULTS： The plasma concentration of sildenafil was 222 ± 136 ng/mL 80 min after administration. Mean arterial blood pressure decreased from 77 ±7 mmHg to 66 ± 12 mmHg, P = 0.003, while the splanchnicblood flow and oxygen consumption remained unchanged at 1.14 ± 0.71 L/min and 2.3 ± 0.6 mmol/ min, respectively. Also the HVPG remained unchanged （18 ± 2 mmHg vs 16 ± 2 mmHg） with individual changes ranging from -8 mmHg to ±2 mmHg. In seven patients, HVPG decreased and in three it increased. CONCLUSION： In spite of arterial blood pressure decreases 80 min after administration of the phosphodiesterase type-5 inhibitor sildenafil, the present study could not demonstrate any clinical relevant influence on splanichnic blood flow, oxygen consumption or the HVPG.

Hepatic venous pressure gradient measurement guiding nonselective beta-blocker therapy in a patient with clinically significant portal hypertension

Clinically significant portal hypertension(CSPH),defined as a hepatic venous pressure gradient(HVPG)≥10 mmHg,is an independent risk factor for decompensated events in patients with compensated cirrhosis.Currently,the Baveno VII consensus recommends using nonselective beta-blockers to treat compensated cirrhosis in patients with CSPH.Here,we report a unusual case of compensated cirrhosis with CSPH caused by hepatitis B,and we successfully adjust NSBBs drug treatment strategies monitoring by HVPG results and achieve response standards.Timely adjustment of NSBBs drug treatment strategies based on HVPG test results for patients with CSPH can improve the final response rate.

Correlation of pressure gradient in three hepatic veins with portal pressure gradient

BACKGROUND The liver is one of the most important organs in the human body,with functions such as detoxification,digestion,and blood coagulation.In terms of vascular anatomy,the liver is divided into the left and the right liver by the main portal vein,and there are three hepatic efferent veins(right,middle,and left)and two portal branches.Patients with impaired liver function have increased intrahepatic vascular resistance and splanchnic vasodilation,which may lead to an increase in the portal pressure gradient(PPG)and cause portal hypertension(PHT).In order to measure the increased pressure gradient of portal vein,the hepatic venous pressure gradient(HVPG)can be measured to reflect it in clinical practice.The accuracy of PPG measurements is directly related to patient prognosis.AIM To analyze the correlation between HVPG of three hepatic veins and PPG in patients with PHT.METHODS From January 2017 to December 2019,102 patients with PHT who met the inclusion criteria were evaluated during the transjugular intrahepatic portosystemic shunt procedure and analyzed.RESULTS The mean HVPG of the middle hepatic vein was 17.47±10.25 mmHg,and the mean HVPG of the right and left hepatic veins was 16.34±7.60 and 16.52±8.15 mmHg,respectively.The average PPG was 26.03±9.24 mmHg.The correlation coefficient and coefficient of determination of the right hepatic vein,middle hepatic vein,and left hepatic vein were 0.15 and 0.02(P=0.164);0.25 and 0.05(P=0.013);and 0.14 and 0.02(P=0.013),respectively.The mean wedged hepatic vein/venous pressure(WHVP)of the middle and left hepatic veins was similar at 29.71±12.48 and 29.1±10.91 mmHg,respectively,and the mean WHVP of the right hepatic vein was slightly lower at 28.01±8.95 mmHg.The mean portal vein pressure was 34.11±8.56 mmHg.The correlation coefficient and coefficient of determination of the right hepatic vein,middle hepatic vein,and left hepatic vein were 0.26 and 0.07(P=0.009);0.38 and 0.15(P<0.001);and 0.26 and 0.07(P=0.008),respectively.The average free hepatic venous pressure(FHVP)of the right hepatic vein was lowest at 11.67±5.34 mmHg,and the average FHVP of the middle and left hepatic veins was slightly higher at 12.19±4.88 and 11.67±5.34 mmHg,respectively.The average inferior vena cava pressure was 8.27±4.04 mmHg.The correlation coefficient and coefficient of determination of the right hepatic vein,middle hepatic vein,and left hepatic vein were 0.30 and 0.09(P=0.002);0.18 and 0.03(P=0.078);and 0.16 and 0.03(P=0.111),respectively.CONCLUSION Measurement of the middle hepatic vein HVPG could better represent PPG.Considering the high success rate of clinical measurement of the right hepatic vein,it can be the second choice.

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.

Future directions of noninvasive prediction of esophageal variceal bleeding:No worry about the present computed tomography inefficiency

In this editorial,we comment on the minireview by Martino A,published in the recent issue of World Journal of Gastrointestinal Endoscopy 2023;15(12):681-689.We focused mainly on the possibility of replacing the hepatic venous pressure gradient(HVPG)and endoscopy with noninvasive methods for predicting esophageal variceal bleeding.The risk factors for bleeding were the size of the varices,the red sign and the Child-Pugh score.The intrinsic core factor that drove these changes was the HVPG.Therefore,the present studies investigating noninvasive methods,including computed tomography,magnetic resonance imaging,elastography,and laboratory tests,are working on correlating imaging or serum marker data with intravenous pressure and clinical outcomes,such as bleeding.A single parameter is usually not enough to construct an efficient model.Therefore,multiple factors were used in most of the studies to construct predictive models.Encouraging results have been obtained,in which bleeding prediction was partly reached.However,these methods are not satisfactory enough to replace invasive methods,due to the many drawbacks of different studies.There is still plenty of room for future improvement.Prediction of the precise timing of bleeding using various models,and extracting the texture of variceal walls using high-definition imaging modalities to predict the red sign are interesting directions to lay investment on.

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

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

Subharmonic aided pressure estimation in portal hypertension:A noninvasive ultrasound-based technique to assess portal pressure gradient

Portal hypertension(PH)is a clinical syndrome,characterized by elevated pressure gradient between portal vein and inferior vena cava.These elevated pressures gradient due to increased vascular resistance and/or increased volume of blood flowing through the portal vein circulation,results in blood outflow difficulty from portal vein to hepatic veins and inferior vena cava.

Osteopontin: A non-invasive parameter of portal hypertension and prognostic marker of cirrhosis

AIM: To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value.METHODS: A cohort of 154 patients with confirmed liver cirrhosis (112 ethylic, 108 men, age 34-72 years) were enrolled in the study. Hepatic venous pressure gradient (HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay (ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals.RESULTS: The mean value of HVPG was 16.18 &#x000b1; 5.6 mmHg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher (P &#x0003c; 0.001). The plasma levels of osteopontin were positively related to HVPG (P = 0.0022, r = 0.25) and differed among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/mL osteopontin distinguished patients with significant portal hypertension (HVPG above 10 mmHg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 &#x000b1; 2.6 years. The probability of cumulative survival was 39% for patients with HVPG &#x0003e; 10 mmHg and 65% for those with HVPG &#x02264; 10 mmHg (P = 0.0086, odds ratio (OR), 2.92, 95% confidence interval (CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/mL had significantly lower cumulative survival compared to those with osteopontin &#x02264; 80 ng/mL (37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68).CONCLUSION: Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival.

Invasive and non-invasive diagnosis of cirrhosis and portal hypertension

With advances in the management and treatment of advanced liver disease,including the use of antiviral therapy,a simple,one stage description for advanced fibrotic liver disease has become inadequate.Although refining the diagnosis of cirrhosis to reflect disease heterogeneity is essential,current diagnostic tests have not kept pace with the progression of this new paradigm.Liver biopsy and hepatic venous pressure gradient measurement are the gold standards for the estimation of hepatic fibrosis and portal hypertension(PHT),respectively,and they have diagnostic and prognostic value.However,they are invasive and,as such,cannot be used repeatedly in clinical practice.The ideal noninvasive test should be safe,easy to perform,inexpensive,reproducible as well as to give numerical and accurate results in real time.It should be predictive of long term outcomes related with fibrosis and PHT to allow prognostic stratification.Recently,many types of noninvasive alternative tests have been developed and are under investigation.In particular,imaging and ultrasound based tests,such as transient elastography,have shown promising results.Although most of these noninvasive tests effectively identify severe fibrosis and PHT,the methods available for diagnosing moderate disease status are still insufficient,and further investigation is essential to predict outcomes and individualize therapy in this field.

Hemodynamic effects of propranolol with spironolactone in patients with variceal bleeds: A randomized controlled trial

AIM: To study the hemodynamic effects of spironolactone with propranolol vs propranolol alone in the secondary prophylaxis of variceal bleeding. METHODS: Thirty-five cirrhotics with variceal bleeding randomly received propranolol (n = 17: Group A) or spironolactone plus propranolol (n = 18: Group B). Hemodynamic assessment was performed at baseline and on the eighth day. RESULTS: Spironolactone with propranolol caused a greater reduction in the hepatic venous pressure gradient than propranolol alone (26.94% vs 10.2%; P < 0.01). Fourteen out of eighteen patients on the combination treatment had a reduction in hepatic venous pressure gradient to ≤ 12 mmHg or a 20% reduction from baseline in contrast to only six out of seventeen (6/17) on propranolol alone (P < 0.05). CONCLUSION: Spironolactone with propranolol results in a better response with a greater reduction in hepatic venous pressure gradient in the secondary prophylaxis of variceal bleeding. A greater number of patients may be protected by this combination therapy than by propranolol alone. Hence, this combination may be recommended for secondary prophylaxis in patients with variceal bleeding.

Endogenous motion of liver correlates to the severity of portal hypertension

BACKGROUND Degree of portal hypertension(PH)is the most important prognostic factor for the decompensation of liver cirrhosis and death,therefore adequate care for patients with liver cirrhosis requires timely detection and evaluation of the presence of clinically significant PH(CSPH)and severe PH(SPH).As the most accurate method for the assessment of PH is an invasive direct measurement of hepatic venous pressure gradient(HVPG),the search for non-invasive methods to diagnose these conditions is actively ongoing.AIM To evaluate the feasibility of parameters of endogenously induced displacements and strain of liver to assess degree of PH.METHODS Of 36 patients with liver cirrhosis and measured HVPG were included in the casecontrol study.Endogenous motion of the liver was characterized by derived parameters of region average tissue displacement signal(dantero,dretro,dRMS)and results of endogenous tissue strain imaging using specific radiofrequency signal processing algorithm.Average endogenous strainμand standard deviationσof strain were assessed in the regions of interest(ROI)(1 cm×1 cm and 2 cm×2 cm in size)and different frequency subbands of endogenous motion(0-10 Hz and 10-20 Hz).RESULTS Four parameters showed statistically significant(P<0.05)correlation with HVPG measurement.The strongest correlation was obtained for the standard deviation of strain(estimated at 0-10 Hz and 2 cm×2 cm ROI size).Three parameters showed statistically significant differences between patient groups with CSPH,but only dretro showed significant results in SPH analysis.According to ROC analysis area under the curve(AUC)of theσROI[0…10Hz,2 cm×2 cm]parameter reached 0.71(P=0.036)for the diagnosis of CSPH;with a cut-off value of 1.28μm/cm providing 73%sensitivity and 70%specificity.AUC for the diagnosis of CSPH forμROI[0…10Hz,1 cm×1 cm]was 0.78(P=0.0024);with a cut-off value of 3.92μm/cm providing 73%sensitivity and 80%specificity.Dretro parameter had an AUC of 0.86(P=0.0001)for the diagnosis of CSPH and 0.84(P=0.0001)for the diagnosis of SPH.A cut-off value of-132.34μm yielded 100%sensitivity for both conditions,whereas specificity was 80%and 72%for CSPH and SPH respectively.CONCLUSION The parameters of endogenously induced displacements and strain of the liver correlated with HVPG and might be used for non-invasive diagnosis of PH.

Sexual dysfunctions and their treatment in liver diseases

Sexual dysfunction(SD)is a prevalent but very commonly ignored aspect in the treatment of liver diseases and cirrhosis.The etiology of SD is multifactorial and therefore treatment strategies are complex,especially in females.Phosphodiesterase inhibitors are useful and effective in erectile dysfunction in males but in females,no single drug is available for SD,therefore multimodal treatment is required depending upon the cause.The foremost and fundamental requirement in both genders is to be stress-free and have adequate control of liver diseases.Improved quality of life is helpful in improving SD and vice versa is also true.Therefore,patients suffering from liver diseases should come forward and ask for treatment for SD,and physicians should actively enquire about SD while history taking and evaluating these patients.SD results in deterioration of quality of life,and both are modifiable and treatable aspects of liver diseases,which are never addressed actively,due to social taboos and fears of SD treatment in the presence of liver diseases.The diagnosis of SD does not require costly investigations,as the diagnosis can be established based on validated questionnaires available for both genders,therefore detailed targeted history taking using questionnaires is essential.Data are emerging in this area but is still at an early stage.More studies should be dedicated to SD in liver diseases.

Portal Hypertension in Nonalcoholic Fatty Liver Disease: Challenges and Paradigms

Portal hypertension in cirrhosis is defined as an increase in the portal pressure gradient(PPG)between the portal and hepatic veins and is traditionally estimated by the hepatic venous pressure gradient(HVPG),which is the difference in pressure between the free-floating and wedged positions of a balloon catheter in the hepatic vein.By convention,􀀫HVPG≥10mmHg indicates clinically significant portal hypertension,which is associated with adverse clinical outcomes.Nonalcoholic fatty liver disease(NAFLD)is a common disorder with a heterogeneous clinical course,which includes the development of portal hypertension.There is increasing evidence that portal hypertension in NAFLD deserves special considerations.First,elevated PPG often precedes fibrosis in NAFLD,suggesting a bidirectional relationship between these pathological processes.Second,HVPG underestimates PPG in NAFLD,suggesting that portal hypertension is more prevalent in this condition than currently believed.Third,cellular mechanoresponses generated early in the pathogenesis of NAFLD provide a mechanistic explanation for the pressurefibrosis paradigm.Finally,a better understanding of liver mechanobiology in NAFLD may aid in the development of novel pharmaceutical targets for prevention and management of this disease.

Noncontrast-enhanced MRI-based Noninvasive Score for Portal Hypertension(CHESS1802):An International Multicenter Study

Background and Aims:This study aimed to determine the performance of the non-invasive score using noncontrastenhanced MRI(CHESS-DIS score)for detecting portal hy-pertension in cirrhosis.Methods:In this international multicenter,diagnostic study(ClinicalTrials.gov,NCT03766880),patients with cirrhosis who had hepatic venous pressure gradient(HVPG)measurement and noncontrast-enhanced MRI were prospectively recruited from four university hospitals in China(n=4)and Turkey(n=1)between December 2018 and April 2019.A cohort of patients was retrospectively recruited from a university hospital in Italy between March 2015 and November 2017.After segmentation of the liver on fat-suppressed T1-weighted MRI maps,CHESS-DIS score was calculated automatically by an in-house developed code based on the quantification of liver surface nodularity.Results:A total of 149 patients were included,of which 124 were from four Chinese hospitals(training cohort)and 25 were from two international hospitals(validation cohort).A positive correlation between CHESS-DIS score and HVPG was found with the correlation coefficients of 0.36(p<0.0001)and 0.55(p<0.01)for the training and validation cohorts,respectively.The area under the receiver operating characteristic curve of CHESS-DIS score in detection of clinically significant portal hypertension(CSPH)was 0.81 and 0.9 in the training and validation cohorts,respectively.The intra-class correlation coefficients for assessing the inter-and intra-observer agreement were 0.846 and 0.841,respectively.Conclusions:A non-invasive score using noncontrast-enhanced MRI was developed and proved to be significantly correlated with invasive HVPG.Besides,this score could be used to detect CSPH in patients with cirrhosis.

Diagnosis of cirrhosis and portal hypertension:imaging,non-invasive markers of fibrosis and liver biopsy

The concept of‘cirrhosis’is evolving and it is now clear that compensated and decompensated cirrhosis are completely different in terms of prognosis.Furthermore,the term‘advanced chronic liver disease(ACLD)’better reflects the continuum of histological changes occurring in the liver,which continue to progress even after cirrhosis has developed,and might regress after removing the etiological factor causing the liver disease.In compensated ACLD,portal hypertension marks the progression to a stage with higher risk of clinical complication and requires an appropriate evaluation and treatment.Invasive tests to diagnose cirrhosis(liver biopsy)and portal hypertension(hepatic venous pressure gradient measurement and endoscopy)remain of crucial importance in several difficult clinical scenarios,but their need can be reduced by using different non-invasive tests in standard cases.Among non-invasive tests,the accepted use,major limitations and major benefits of serum markers of fibrosis,elastography and imaging methods are summarized in the present review.