Does Non-Invasive Assessment of Portal Hypertension Using Magnetic Resonance Elastography Predict Clinically Relevant Changes in the Hepatic Venous Pressure Gradient?

( Seong Hee Kang ),( Jhii-hyun Ahn ),( Moon Young Kim ),( Seul Ki Han ),( Bonil Park ),( Young Ju Kim ),( Soon Koo Baik ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Hepatic venous pressure gradient (HVPG) measurement is a validated method, which accurately evaluates changes in portal hypertension (PH). Magnetic resonance elastography (MRE) is a well-established method for liver fibrosis staging. We investigated the correlation between MRE-assessed stiffness of the liver and spleen and HVPG values. Furthermore, we evaluated whether MRE values reflected changes in PH after the administration of ß-blockers. Methods: From January 2018 to September 2019, we enrolled 37 consecutive patients with cirrhosis requiring prophylactic treatment of esophageal varices according to the Baveno VI criteria were prospectively included. At enrollment, patients were initiated on carvedilol starting at a dose of 6.25 mg/day, which was up-titrated to 12.5 mg/day. Patients underwent HVPG measurement and multifrequency MRE at baseline and 6 weeks. Results: The median HVPG and MELD score of the patients was 15.0 mmHg (Interquartile range [IQR], 11.5-20.5) and 11.4 (IQR, 8.5-13.9), respectively. Median baseline values of MRE-assessed liver and spleen stiffness were 5.92 kPa (IQR, 4.89-7.10) and 8.38 kPa (IQR, 7.38-9.43), respectively. Multiple linear regression analysis revealed a significant correlation between HVPG and MRE-assessed liver stiffness (γ=0.485, P=0.004), but not MRE-assessed spleen stiffness (γ=-0.065, P=0.708). Median 6-week changes in MRE-assessed liver stiffness (Δliver), spleen stiffness (Δspleen) and HVPG (ΔHVPG) were -0.4 kPa, -0.13 kPa, and -1.5 mmHg, respectively. Overall, neither MRE-assessed Δliver (γ=0.311, P=0.170) nor MRE-assessed Δspleen (γ=-0.135, P=0.559) was correlated with ΔHVPG. However, using the categorized stage of HVPG, MRE-assessed Δliver significantly correlated with ΔHVPG in patients with low-HVPG ≤16 mmHg (γ=0.575, P=0.040), though not in patients with high-HVPG >16 mmHg (γ=-0.048, P=0.909). Conclusions: MR parameters related to liver stiffness provide excellent accuracy for diagnosing PH, and reflect changes in HVPG following administration of ß blockers for less severe PH.

LC : Which Noninvasive Hepatic Fibrosis Test Most Effectively Predicts Portal Pressure and Survival in Alcoholic Liver Disease Patients?

( Eun Ju Cho ),( Jeong Hoon Lee ),( Il Young Lee ),( Moon Young Kim ),( Jeong Ju Yoo ),( Won Mook Choi ),( Young Youn Cho ),( Min Jong Lee ),( Yuri Cho ),( Dong Hyeon Lee ),( Yun Bin Lee ),( Su Jong Y 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: Hepatic venous pressure gradient (HVPG) is the gold standard for assessing portal pressure. In this study, we investigated which noninvasive fibrosis test most effectively reflects HVPG and predicts prognosis in patients with alcoholic liver disease (ALD). Methods: A total of 195 consecutive patients with ALD were included. Biochemical indices and liver stiffness assessed by transient elastography (TE) were compared with HVPG. Results: During a median follow-up period of 23.1 months, 51 patients died, including 21 liver-related deaths. The diagnostic values of liver stiffness in detecting clinically significant portal hypertension (CSPH; HVPG≥10 mmHg) was significantly higher (AUROC=0.87±0.03) than those of biochemical indices (i.e. APRI, FIB4, P2/MS and platelet count/spleen diameter ratio; all P<0.001). In multivariate analysis, liver stiffness was most significantly correlated to HVPG (P<0.001), whereas other biochemical indices were not. On the other hand, the prognostic values of liver stiffness for liver-related death (AUROC= 0.73±0.07) did not differ from those of FIB4 (0.78±0.04), HVPG (0.70±0.07) and APRI (0.69±0.04). In multivariate analysis, significant risk factors for liver-related death were Child score (hazard ratio [HR]=2.35, P<0.001), varices >F2 (HR=5.85; P=0.002) and FIB4 (HR=1.11, P=0.03), but not liver stiffness and HVPG. For all-cause death, age and FIB4 were independent predictors in compensated patients (P=0.02 and <0.001, respectively), whereas Child score was in decompensated patients (P<0.001). Conclusions: In patients with ALD, liver stiffness most accurately predicts CSPH, but did not improve the prognostic values of traditional risk factors for mortality, whereas FIB4 was independent predictor for liver disease-related death and allcause death.

Rifaximin and Propranolol Combination Therapy Is More Effective than Propranolol Monotherapy for the Reduction of Portal Pressure: An Open Randomized Controlled Pilot Study

( Yoo Li Lim ),( Moon Young Kim ),( Yoon Ok Jang ),( Soon Koo Baik ),( Sang Ok Kwon ) 대한간학회 2017 Gut and Liver Vol.11 No.5

Background/Aims: Non-selective beta blockers (NSBBs) are currently the only accepted regimen for preventing portal hypertension (PHT)-related complications. However, the effect of NSBBs is insufficient in many cases. Bacterial translocation (BT) is one of the aggravating factors of PHT in cirrhosis; therefore, selective intestinal decontamination by rifaximin is a possible therapeutic option for improving PHT. We investigated whether the addition of rifaximin to pro-pranolol therapy can improve hepatic venous pressure gradi-ent (HVPG) response. Methods: Sixty-four cirrhosis patients were randomly assigned to propranolol monotherapy (n=48) versus rifaximin and propranolol combination therapy (n=16). Baseline and post-treatment HVPG values, BT-related mark-ers (lipopolysaccharide [LPS], LPS-binding protein [LBP], interleukin-6 [IL-6], and tumor necrosis factor α [TNF-α]), serological data, and adverse event data were collected. HVPG response rate was the primary endpoint. Results: Combination therapy was associated with better HVPG re-sponse rates than monotherapy (56.2% vs 87.5%, p=0.034). In combination therapy, posttreatment BT-related markers were significantly decreased (LPS, p=0.005; LBP, p=0.005; IL-6, p=0.005; TNF-α, p=0.047). Conclusions: Rifaximin combination therapy showed an additive effect in improving PHT compared to propranolol monotherapy. These pilot data suggest that the addition of rifaximin to NSBBs could be a good therapeutic option for overcoming the limited effective-ness of NSBBs. (Gut Liver 2017;11:702-710)

Original Articles : Relationship between the hepatic venous pressure gradient and first variceal hemorrhage in patients with cirrhosis; a multicenter retrospective study in Korea

( Jin Nyoung Kim ),( Kyoung Min Sohn ),( Moon Young Kim ),( Ki Tae Suk ),( Soung Won Jeong ),( Ho Eun Jung ),( Sae Hwan Lee ),( Sang Gyune Kim ),( Jae Young Jang ),( Young Seok Kim ),( Soon Koo Baik ) 대한간학회 2012 Clinical and Molecular Hepatology(대한간학회지) Vol.18 No.4

Background/Aims: Variceal hemorrhage is one of the major complications of cirrhosis and is associated with significant mortality and morbidity. The development of gastroesophageal varices and variceal hemorrhage is the most direct consequence of portal hypertension. Correlations between the hepatic venous pressure gradient (HVPG) and first variceal hemorrhage were examined. Methods: Patients with cirrhosis who underwent HVPG measurement between July 2009 and September 2010 were enrolled (n=535). All patients underwent esophagogastroduodenoscopy to enable the evaluation of gastroesophageal varices. Results: The HVPG for all patients was 16.46±7.05 mmHg (mean±SD), and was significantly higher among those with first variceal hemorrhage than in those without it. The HVPG was significantly correlated with both Child-Turcotte-Pugh (r=0.488, P<0.001) and Model for End-stage Liver Disease (r=0.478, P<0.001) scores. An HVPG value of 11 mmHg was predictive of first variceal hemorrhage with a sensitivity of 92.4% and a specificity of 27.7%. Conclusions: The HVPG was higher in patients with first variceal hemorrhage than in those without it. (Clin Mol Hepatol 2012;18:391-396)

Correlation of Hepatic Venous Pressure Gradient with Transient Elastography in Patients with Cirrhosis

( Soung Won Jeong ),( Moon Young Kim ),( Seong Hee Kang ),( Young Kwon Kim ),( Jae Young Jang ),( Yong Jae Kim ),( Dong Erk Goo ),( Su Yeon Park ),( Soon Koo Baik ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: To investigate correlation between hepatic venous pressure gradient (HVPG) and transient elastography (TE) in patients with cirrhosis and identify a cut-off value of TE in clinically significant portal hypertension (CSPH, HVPG ≥10mmHg) and severe portal hypertension (SPH, HVPG >12 mmHg). Methods: Between January 2008 and March 2017, 406 patients who underwent HVPG and TE were consecutively enrolled at the two Korean tertiary medical centers. HVPG and TE were performed within 1 month interval. Results: The mean age was 53.1±9.9 years, and the majority (82%) were males. The most common etiology of cirrhosis was alcohol (63%) followed by hepatitis B virus infection (22%). A significant positive correlation was noted between liver stiffness and HVPG levels (r=0.549, p < 0.001). Figure presents the median TE values in various stages of portal hypertension (HVPG ≤ 5 mmHg, 9.8 kPa, HVPG > 5 to < 10 mmHg, 18.1 kPa, HVPG ≥ 10 to 12 mmHg, 27.0 kPa, HVPG > 12 to ≤ 20 mmHg, 41.3 kPa, HVPG > 20 mmHg, 62.7 kPa). The area under receiver operating characteristic curves for TE to diagnose portal hypertension (HVPG >5mmHg), CSPH, and SPH were 0.839 (95%CI: 0.737-0.941), 0.809 (95%CI: 0.761-0.858), and 0.782 (95%CI: 0.737-0.826), respectively. A cut-off values of TE of 27.2 and 35.5 kPa were obtained by using Youden index to best predict CSPH and SPH, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of a TE value ≥ 27.2 and ≥ 35.5 kPa to diagnose CSPH and SPH were 70.1%, 78.6%, 91.1%, and 45.6%, and 52.3%, 86.7%, 92.5%, 36.6%, respectively. Conclusions: TE can be used as a non-invasive modality to assess the degree of portal hypertension. A cut-off TE value of 27.2 and 35.6 kPa identifies CSPH and SPH with a PPV of 91.1% and 92.5%, respectively.

The Accuracy of Ultrasonography for the Evaluation of Portal Hypertension in Patients with Cirrhosis: A Systematic Review

김가은,Youn Zoo Cho,백순구,김문영,Won Ki Hong,권상옥 대한영상의학회 2015 Korean Journal of Radiology Vol.16 No.2

Studies have presented conflicting results regarding the accuracy of ultrasonography (US) for diagnosing portal hypertension (PH). We sought to identify evidence in the literature regarding the accuracy of US for assessing PH in patients with liver cirrhosis. We conducted a systematic review by searching databases, including MEDLINE, EMBASE, and the Cochrane Library, for relevant studies. A total of 14 studies met our inclusion criteria. The US indices were obtained in the portal vein (n = 9), hepatic artery (n = 6), hepatic vein (HV) (n = 4) and other vessels. Using hepatic venous pressure gradient (HVPG) as the reference, the sensitivity (Se) and specificity (Sp) of the portal venous indices were 69–88% and 67–75%, respectively. The correlation coefficients between HVPG and the portal venous indices were approximately 0.296–0.8. No studies assess the Se and Sp of the hepatic arterial indices. The correlation between HVPG and the hepatic arterial indices ranged from 0.01 to 0.83. The Se and Sp of the hepatic venous indices were 75.9–77.8% and 81.8–100%, respectively. In particular, the Se and Sp of HV arrival time for clinically significant PH were 92.7% and 86.7%, respectively. A statistically significant correlation between HVPG and the hepatic venous indices was observed (0.545–0.649). Some US indices, such as HV, exhibited an increased accuracy for diagnosing PH. These indices may be useful in clinical practice for the detection of significant PH.

The Cut-Off Value of Transient Elastography to Hepatic Venous Pressure Gradient for Alcoholic and Viral Cirrhosis in Korean Patients

( Se Ri Ryu ),( Seong Hee Kang ),( Jeong-ju Yoo ),( Soung Won Jeong ),( Moon Young Kim ),( Sang Gyune Kim ),( Jae Young Jang ),( Young Seok Kim ),( Soon Koo Baik ),( Yong Jae Kim ),( Su Yeon Park ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: To investigate correlation between hepatic venous pressure gradient (HVPG) and transient elastography (TE) in patients with cirrhosis and to identify a cut-off value of TE to HVPG in clinically significant portal hypertension (CSPH, HVPG ≥10mmHg) and severe portal hypertension (SPH, HVPG >12mmHg) according to the cause of cirrhosis. Methods: Between January 2008 and March 2017, 553 patients who underwent HVPG and TE were consecutively enrolled at the three Korean tertiary medical centers. HVPG and TE were performed within 1 month interval. Patients were classified with the cause of liver cirrhosis, and the cut-off value of TE was analyzed for patients with alcoholic and viral origin of cirrhosis. Results: The mean age was 53.3±9.8 years, and the majority (81.6%) were male. A significant positive correlation was noted between liver stiffness and HVPG levels (r=0.544, P<0.001). The area under receiver operating characteristic curves for TE to diagnose CSPH and SPH were 0.829 (95%CI: 0.790-0.868) and 0.80.2 (95%CI: 0.765-0.840). Among all cause of liver cirrhosis, the most common etiology was 1)alcohol 335(60.6%) followed by 2)chronic hepatitis B(CHB) 128(23.1%), 3)CHB with alcohol 45(8.1%), 4)cryptogenic 22(4%), 5)chronic hepa-titis C(CHC) 18(3.3%), and 6)CHC with alcohol 5(0.9%). HVPG and TE values were evaluated for total patients, patients with alcoholic(1), and viral [(2)+(5)] cirrhosis. In total patients, a cut-off values of TE of 27.6 and 32.5kPa were obtained by using Youden index to best predict CSPH and SPH, respectively. In alcoholic cirrhosis, a cut-off values of TE were 32.2 kPa and 36.6 kPa, for CSPH and SPH, respectively. In viral cirrhosis, a cut-off values of TE was 18.0 kPa for both CSPH and SPH(Table 1). Conclusions: In the alcoholic cirrhosis, cut off value of TE was higher than that of viral cirrhosis. Therefore, it is necessary to interpret the TE value depending on the cause of liver cirrhosis.

춘계학술대회 : 구연 ; 간경변증 : 문맥압 항진증 평가를 위한 간정맥 압력차 시술의 임상적 고찰

김규홍,백순구,김문영,박동훈,김정민,석기태,조기원,홍진헌,김재우,권상옥 대한간학회 2007 Clinical and Molecular Hepatology(대한간학회지) Vol.13 No.3(S)

Prognostic Significance of Hepatic Venous Pressure Gradient in the Prediction of Hepatocellular Carcinoma

Eun Jin Kim,Sang Hyun Park,Hyo Sun Kim,Chang Seok Bang,Ki Tae Suk,Dong Joon Kim,Hyoung Su Kim,Ji Won Park,Sung Eun Kim,Myoung Kuk Jang,Sang Hoon Park,Myung Seok Lee,Choong Kee Park 한국간담췌외과학회 2014 한국간담췌외과학회 학술대회지 Vol.2014 No.4

Hepatic Venous Pressure Gradient Predicts Long-Term Mortality in Patients with Decompensated Cirrhosis

손주현,김태엽,이재곤,김지연,김선민,김진우,정우경 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.1

Purpose: The present study aimed to investigate the role of hepatic venous pressure gradient (HVPG) for prediction of long-term mortality in patients with decompensated cirrhosis. Materials and Methods: Clinical data from 97 non-critically-ill cirrhotic patients with HVPG measurements were retrospectively and consecutively collected between 2009 and 2012. Patients were classified according to clinical stages and presence of ascites. The prognostic accuracy of HVPG for death, survival curves, and hazard ratios were analyzed. Results: During a median follow-up of 24 (interquartile range, 13–36) months, 22 patients (22.7%) died. The area under the receiveroperating characteristics curves of HVPG for predicting 1-year, 2-year, and overall mortality were 0.801, 0.737, and 0.687, respectively (all p<0.01). The best cut-off value of HVPG for predicting long-term overall mortality in all patients was 17 mm Hg. The mortality rates at 1 and 2 years were 8.9% and 19.2%, respectively: 1.9% and 11.9% with HVPG ≤17 mm Hg and 16.2% and 29.4% with HVPG >17 mm Hg, respectively (p=0.015). In the ascites group, the mortality rates at 1 and 2 years were 3.9% and 17.6% with HVPG ≤17 mm Hg and 17.5% and 35.2% with HVPG >17 mm Hg, respectively (p=0.044). Regarding the risk factors for mortality, both HVPG and model for end-stage liver disease were positively related with long-term mortality in all patients. Particularly,for the patients with ascites, both prothrombin time and HVPG were independent risk factors for predicting poor outcomes. Conclusion: HVPG is useful for predicting the long-term mortality in patients with decompensated cirrhosis, especially in the presence of ascites.