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. AIM: To explore the correlation between HVPG and PPG in patients with alcoholic cirrhosis and PHT. 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 (R2). 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.

Computed tomography perfusion in differentiating 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), invasiveness and potential risks in the process of measurement limited its widespread use. AIM: To investigate the correlation of computed tomography (CT) perfusion parameters with HVPG in PH, and quantitatively assess the blood supply changes in liver and spleen parenchyma before and after transjugular intrahepatic portosystemic shunt (TIPS). METHODS: Twenty-four PH related gastrointestinal bleeding patients were recruited in this study, and all patients were performed perfusion CT before and after TIPS surgery within 2 wk. Quantitative parameters of CT perfusion, including liver blood volume (LBV), liver blood flow (LBF), hepatic arterial fraction (HAF), spleen blood volume (SBV) and spleen blood flow (SBF), were measured and compared before and after TIPS, and the quantitative parameters between clinically significant PH (CSPH) and non-CSPH (NCSPH) group were also compared. Then the correlation of CT perfusion parameters with HVPG were analyzed, with statistical significance as P < 0.05. RESULTS: For all 24 PH patients after TIPS, CT perfusion parameters demonstrated decreased LBV, increased HAF, SBV and SBF, with no statistical difference in LBF. Compared with NCSPH, CSPH showed higher HAF, with no difference in other CT perfusion parameters. HAF before TIPS showed positive correlation with HVPG (r = 0.530, P = 0.008), while no correlation was found in other CT perfusion parameters with HVPG and Child-Pugh scores. CONCLUSION: HAF, an index of CT perfusion, was positive correlation with HVPG, and higher in CSPH than NCSPH before TIPS. While increased HAF, SBF and SBV, and decreased LBV, were found after TIPS, which accommodates a potential non-invasive imaging tool for evaluation of PH.

Short-term efficacy assessment of transarterial chemoembolization combined with radioactive iodine therapy in primary hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) is an effective treatment for primary hepatocellular carcinoma (PHC). Radioactive iodine therapy has been used in the treatment of advanced PHC, especially in patients with portal vein tumor thrombosis. However, data on the therapeutic effect of TACE combined with radioactive iodine therapy in PHC are scarce. AIM: To investigate the clinical efficacy of TACE combined with radioactive iodine implantation therapy in advanced PHC via perfusion computed tomography (CT). METHODS: For this study, 98 advanced PHC patients were recruited and divided randomly into the study and control groups. Patients in the study group were treated with TACE combined radioactive iodine implantation therapy. Patients in the control group were treated with only TACE. The tumor lesion length, clinical effect, serum alpha-fetoprotein (AFP) and CT perfusion parameters were compared before and after therapy, and statistical analysis was performed. RESULTS: There was no significant difference in tumor length and serum AFP between the study and control groups (P > 0.05) before treatment. However, the tumor length and serum AFP in the study group were lower than those in the control group 1 mo and 3 mo after therapy. After 3 mo of treatment, the complete and partial remission rate of the study group was 93.88%, which was significantly higher than the control group (77.55%) (P < 0.05). Before treatment, there were no significant differences between the two groups on the perfusion CT variables, including the lesion blood volume, permeability surface, blood flow, hepatic artery flow and mean transit time (P > 0.05). After 3 mo of treatment, all perfusion CT variables were lower in the study group compared to the control group (P < 0.05). The survival time of patients in the study group was 22 mo compared to 18 mo in the control group, which was significantly different [log rank (Mantel-Cox) = 4.318, P = 0.038]. CONCLUSION: TACE combined with radioactive iodine implantation in the treatment of advanced PHC can inhibit the formation of blood vessels in tumor tissue and reduce the perfusion level of tumor lesions, thereby improving the clinical efficacy and prolonging the survival time of patients.

Transjugular intrahepatic portosystemic shunt with radioactive seed strand for main portal vein tumor thrombosis with cirrhotic portal hypertension.

BACKGROUND: Patients with hepatocellular carcinoma complicated with main portal vein tumor thrombosis (mPVTT) and cirrhotic portal hypertension (CPH) have an extremely poor prognosis, and there is a lack of a clinically effective treatment paradigm. AIM: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with radioactive seed strand for the treatment of mPVTT patients with CPH. METHODS: The clinical data of 83 consecutive patients who underwent TIPS combined with 125I seed strand placement for mPVTT and CPH from January 2015 to December 2018 were retrospectively reviewed. Procedure-related data (success rate, relief of portal vein pressure and CPH symptoms, and adverse events), PVTT response, and patient survival were assessed through a 2-year follow-up. RESULTS: The success rate was 100.0% without perioperative death or procedure-related severe adverse events. The mean portal vein pressure was significantly decreased after the procedure (22.25 ± 7.33 mmHg vs 35.12 ± 7.94 mmHg, t = 20.61, P < 0.001). The symptoms of CPH were all effectively relieved within 1 mo. The objective response rate of PVTT was 67.5%. During a mean follow-up of 14.5 ± 9.4 mo (range 1-37 mo), the cumulative survival rates at 6, 12 and 24 mo were 83.1%, 49.7%, and 21.8%, respectively. The median survival time was 12.0 ± 1.3 mo (95% confidence interval: 9.5-14.5). In multivariate Cox regression analysis, body mass index, Child-Pugh grade, cTNM stage, and PVTT response were independent prognostic factors (P < 0.05). CONCLUSION: TIPS combined with radioactive seed strand might be effective and safe in treating mPVTT patients with CPH.

Comparative study of indocyanine green-R15, Child-Pugh score, and model for end-stage liver disease score for prediction of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt.

BACKGROUND: Hepatic encephalopathy (HE) remains an enormous challenge in patients who undergo transjugular intrahepatic portosystemic shunt (TIPS) implantation. The preoperative indocyanine green retention rate at 15 min (ICG-R15), as one of the liver function assessment tools, has been developed as a prognostic indicator in patients undergoing surgery, but there are limited data on its role in TIPS. AIM: To determine whether the ICG-R15 can be used for prediction of post-TIPS HE in decompensated cirrhosis patients with portal hypertension (PHT) and compare the clinical value of ICG-R15, Child-Pugh score (CPS), and model for end-stage liver disease (MELD) score in predicting post-TIPS HE with PHT. METHODS: This retrospective study included 195 patients with PHT who underwent elective TIPS at Beijing Shijitan Hospital from January 2018 to June 2019. All patients underwent the ICG-R15 test, CPS evaluation, and MELD scoring 1 wk before TIPS. According to whether they developed HE or not, the patients were divided into two groups: HE group and non-HE group. The prediction of one-year post-TIPS HE by ICG-R15, CPS and MELD score was evaluated by the areas under the receiver operating characteristic curves (AUCs). RESULTS: A total of 195 patients with portal hypertension were included and 23% (45/195) of the patients developed post-TIPS HE. The ICG-R15 was identified as an independent predictor of post-TIPS HE. The AUCs for the ICG-R15, CPS, and MELD score for predicting post-TIPS HE were 0.664 (95% confidence interval [CI]: 0.557-0.743, P = 0.0046), 0.596 (95%CI: 0.508-0.679, P = 0.087), and 0.641 (95%CI: 0.554-0.721, P = 0.021), respectively. The non-parametric approach (Delong-Delong & Clarke-Pearson) showed that there was statistical significance in pairwise comparison between AUCs of ICG-R15 and MELD score (P = 0.0229). CONCLUSION: The ICG-R15 has appreciated clinical value for predicting the occurrence of post-TIPS HE and is a choice for evaluating the prognosis of patients undergoing TIPS.

Accurate ultrasonography-based portal pressure assessment in patients with hepatocellular carcinoma.

BACKGROUND: Portal pressure is of great significance in the treatment of hepatocellular carcinoma (HCC), but direct measurement is complicated and costly; thus, non-invasive measurement methods are urgently needed. AIM: To investigate whether ultrasonography (US)-based portal pressure assessment could replace invasive transjugular measurement. METHODS: A cohort of 102 patients with HCC was selected (mean age: 54 ± 13 years, male/female: 65/37). Pre-operative US parameters were assessed by two independent investigators, and multivariate logistic analysis and linear regression analysis were conducted to develop a predictive formula for the portal pressure gradient (PPG). The estimated PPG predictors were compared with the transjugular PPG measurements. Validation was conducted on another cohort of 20 non-surgical patients. RESULTS: The mean PPG was 17.32 ± 1.97 mmHg. Univariate analysis identified the association of the following four parameters with PPG: Spleen volume, portal vein diameter, portal vein velocity (PVV), and portal blood flow (PBF). Multiple linear regression analysis was performed, and the predictive formula using the PVV and PBF was as follows: PPG score = 19.336 - 0.312 × PVV (cm/s) + 0.001 × PBF (mL/min). The PPG score was confirmed to have good accuracy with an area under the curve (AUC) of 0.75 (0.68-0.81) in training patients. The formula was also accurate in the validation patients with an AUC of 0.820 (0.53-0.83). CONCLUSION: The formula based on ultrasonographic Doppler flow parameters shows a significant correlation with invasive PPG and, if further confirmed by prospective validation, may replace the invasive transjugular assessment.

Iodine-125 implantation with transjugular intrahepatic portosystemic shunt for main portal vein tumor thrombus.

BACKGROUND: Main portal vein tumor thrombus (MPVTT), which has a high incidence, is the major complication of terminal liver cancer. The occurrence of MPVTT is always a negative prognostic factor for patients with hepatocellular carcinoma (HCC). Therefore, attention should be paid to the treatment of MPVTT and its complications. AIM: To evaluate the efficacy of transarterial chemoembolization/transarterial embolization (TACE/TAE)+125I seeds implantation with transjugular intrahepatic portosystemic shunt (TIPS) in treating MPVTT and its complications. METHODS: From January 2007 to March 2015, 85 consecutive patients with MPVTT were nonrandomly assigned to undergo treatment with TACE/TAE + TIPS and 125I implantation (TIPS-125I group) or TACE/TAE + TIPS only (TIPS only group) in Beijing Shijitan Hospital, and all clinical data were collected. During 24 mo follow-up, the incidence of overall survival, stent stenosis and symptom recurrence was analyzed to evaluate the efficacy of TIPS-125I. RESULTS: During 24 mo follow-up of all patients, we collected data at 6, 12 and 24 mo. The rates of survival were 80%, 45%, and 20%, respectively, in the TIPS-125I group, whereas those in the TIPS only group were 64.4%, 24.4%, and 4.4%, respectively (P < 0.05). The rates of symptom recurrence were 7.5%, 22.5%, and 35%, respectively, in the TIPS-125I group, whereas those in the TIPS only group were 31.1%, 62.2%, and 82.2% (P < 0.05). The rates of stent restenosis were 12.5%, 27.5%, and 42.5%, respectively, in the TIPS-125I group, and 42.2%, 68.9%, and 84.4%, respectively, in the TIPS only group (P < 0.05). TIPS-125I was found to be significantly favorable in treating MPVTT and its complications in patients with HCC. CONCLUSION: TACE/TAE+125I combined with TIPS is effective in treating MPVTT and its complications, improving quality of life of patients and reducing mortality.

Pathological Features of Mitochondrial Ultrastructure Predict Susceptibility to Post-TIPS Hepatic Encephalopathy.

Background: Post-TIPS hepatic encephalopathy (PSE) is a complex process involving numerous risk factors; the root cause is unclear, but an elevation of blood ammonia due to portosystemic shunt and metabolic disorders in hepatocytes has been proposed as an important risk factor. Aims: The aim of this study was to investigate the impact of pathological features of mitochondrial ultrastructure on PSE via transjugular liver biopsy at TIPS implantation. Methods: We evaluated the pathological damage of mitochondrial ultrastructure on recruited patients by the Flameng classification system. A score ≤2 (no or low damage) was defined as group A, and a score >2 (high damage level) was defined as group B; routine follow-up was required at 1 and 2 years; the incidence of PSE and multiple clinical data were recorded. Results: A total of 78 cases in group A and 42 in group B completed the study. The incidence of PSE after 1 and 2 years in group B (35.7% and 45.2%, respectively) was significantly higher than that in group A (16.7% and 24.4%, respectively); the 1- and 2-year OR (95% CI) were 2.778 (1.166-6.615) and 2.565 (1.155-5.696), respectively, for groups A and B. Importantly, group B had worse incidence of PSE than group A [P=0.014, hazard ratio (95%CI): 2.172 (1.190-4.678)]. Conclusion: Aggressive damage to mitochondrial ultrastructure in liver shunt predicts susceptibility to PSE. The registration number is NCT02540382.

Stents combined with iodine-125 implantation to treat main portal vein tumor thrombus.

AIM: To evaluate the efficacy of main portal vein stents combined with iodine-125 (125I) to treat main portal vein tumor thrombus. METHODS: From January 1, 2010 to January 1, 2015, 111 patients were diagnosed with liver cancer combined with main portal vein tumor thrombus. They were non-randomly assigned to undergo treatment with transarterial chemoembolization (TACE)/transarterial embolization (TAE) + portal vein stents combined with 125I implantation (Group A) and TACE/TAE + portal vein stents only (Group B). After the operation, scheduled follow-up was performed at 6, 12 and 24 mo. The recorded information included clinical manifestations, survival rate, and stent restenosis rate. Kaplan-Meier curves, log-rank test and Cox regression were used for data analyses. RESULTS: From January 1, 2010 to January 1, 2015, 54 and 57 patients were allocated to Groups A and B, respectively. The survival rates at 6, 12 and 24 mo were 85.2%, 42.6% and 22.2% in Group A and 50.9%, 10.5% and 0% in Group B. The differences were significant [log rank P < 0.05, hazard ratio (HR): 0.37, 95%CI: 0.24-0.56]. The rates of stent restenosis were 18.5%, 55.6% and 83.3% in Group A and 43.9%, 82.5% and 96.5% in Group B. The differences were significant (log rank P < 0.05, HR: 0.42, 95%CI: 0.27-0.63). Cox regression identified that treatment was the only factor affecting survival rate in this study. CONCLUSION: Main portal vein stents combined with 125I can significantly improve survival rate and reduce the rate of stent restenosis.

Combined transjugular intrahepatic portosystemic shunt and other interventions for hepatocellular carcinoma with portal hypertension.

AIM: To evaluate combination transjugular intrahepatic portosystemic shunt (TIPS) and other interventions for hepatocellular carcinoma (HCC) and portal hypertension. METHODS: Two hundred and sixty-one patients with HCC and portal hypertension underwent TIPS combined with other interventional treatments (transarterial chemoembolization/transarterial embolization, radiofrequency ablation, hepatic arterio-portal fistulas embolization, and splenic artery embolization) from January 1997 to January 2010 at Beijing Shijitan Hospital. Two hundred and nine patients (121 male and 88 female, aged 25-69 years, mean 48.3 ± 12.5 years) with complete clinical data were recruited. We evaluated the safety of the procedure (procedure-related death and serious complications), change of portal vein pressure before and after TIPS, symptom relief [e.g., ascites, hydrothorax, esophageal gastric-fundus variceal bleeding (EGVB)], cumulative rates of survival, and distributary channel restenosis. The characteristics of the patients surviving ≥ 5 and < 5 years were also analyzed. RESULTS: The portosystemic pressure was decreased from 29.0 ± 4.1 mmHg before TIPS to 18.1 ± 2.9 mmHg after TIPS (t = 69.32, P < 0.05). Portosystemic pressure was decreased and portal hypertension symptoms were ameliorated. During the 5 year follow-up, the total recurrence rate of resistant ascites or hydrothorax was 7.2% (15/209); 36.8% (77/209) for EGVB; and 39.2% (82/209) for hepatic encephalopathy. The cumulative rates of distributary channel restenosis at 1, 2, 3, 4, and 5 years were 17.2% (36/209), 29.7% (62/209), 36.8% (77/209), 45.5% (95/209) and 58.4% (122/209), respectively. No procedure-related deaths and serious complications (e.g., abdominal bleeding, hepatic failure, and distant metastasis) occurred. Moreover, Child-Pugh score, portal vein tumor thrombosis, lesion diameter, hepatic arterio-portal fistulas, HCC diagnosed before or after TIPS, stent type, hepatic encephalopathy, and type of other interventional treatments were related to 5 year survival after comparing patient characteristics. CONCLUSION: TIPS combined with other interventional treatments seems to be safe and efficacious in patients with HCC and portal hypertension.

Establishment of a hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol.

AIM: To determine the feasibility and safety of establishing a porcine hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol. METHODS: Twenty-one healthy Guizhou miniature pigs were randomly divided into three experimental groups and three control groups. The pigs in the three experimental groups were subjected to hepatic arterial perfusion with 7, 12 and 17 mL of 80% alcohol, respectively, while those in the three control groups underwent hepatic arterial perfusion with 7, 12 and 17 mL of saline, respectively. Hepatic arteriography and direct portal phlebography were performed on all animals before and after perfusion, and the portal venous pressure and diameter were measured before perfusion, immediately after perfusion, and at 2, 4 and 6 wk after perfusion. The following procedures were performed at different time points: routine blood sampling, blood biochemistry, blood coagulation and blood ammonia tests before surgery, and at 2, 4 and 6 wk after surgery; hepatic biopsy before surgery, within 6 h after surgery, and at 1, 2, 3, 4 and 5 wk after surgery; abdominal enhanced computed tomography examination before surgery and at 6 wk after surgery; autopsy and multi-point sampling of various liver lobes for histological examination at 6 wk after surgery. RESULTS: In experimental group 1, different degrees of hepatic fibrosis were observed, and one pig developed hepatic cirrhosis. In experimental group 2, there were cases of hepatic cirrhosis, different degrees of increased portal venous pressure, and intrahepatic portal venous bypass, but neither extrahepatic portal-systemic bypass circulation nor death occurred. In experimental group 3, two animals died and three animals developed hepatic cirrhosis, and different degrees of increased portal venous pressure and intrahepatic portal venous bypass were also observed, but there was no extrahepatic portal-systemic bypass circulation. CONCLUSION: It is feasible to establish an animal model of hepatic cirrhosis and portal hypertension by hepatic arterial perfusion with 80% alcohol, however, the safety of this model depends on a suitable perfusion dose.

Transjugular intrahepatic portosystemic shunt for severe jaundice in patients with acute Budd-Chiari syndrome.

AIM: To evaluate the feasibility of transjugular intrahepatic portosystemic shunt (TIPS) for severe jaundice secondary to acute Budd-Chiari syndrome (BCS). METHODS: From February 2009 to March 2013, 37 patients with severe jaundice secondary to acute BCS were treated. Sixteen patients without hepatic venule, hepatic veins (HV) obstruction underwent percutaneous angioplasty of the inferior vena cava (IVC) and/or HVs. Twenty-one patients with HV occlusion underwent TIPS. Serum bilirubin, liver function, demographic data and operative data of the two groups of patients were analyzed. RESULTS: Twenty-one patients underwent TIPS and the technical success rate was 100%, with no technical complications. Sixteen patients underwent recanalization of the IVC and/or HVs and the technical success rate was 100%. The mean procedure time for TIPS was 84.0±12.11 min and angioplasty was 44.11±5.12 min (P<0.01). The mean portosystemic pressure in the TIPS group decreased significantly from 40.50±4.32 to 16.05±3.50 mmHg (P<0.01). The mean portosystemic pressure gradient decreased significantly from 33.60±2.62 to 7.30±2.21 mmHg (P<0.01). At 8 wk after the procedures, in the TIPS group, total bilirubin (TBIL) decreased significantly from 266.24±122.03 before surgery to 40.11±3.52 µmol/L (P<0.01) and direct bilirubin (DBIL) decreased significantly from 194.22±69.82 µmol/L to 29.82±3.10 µmol/L (P<0.01). In the angioplasty group, bilirubin returned to the normal range, with TBIL decreased significantly from 258.22±72.71 µmol/L to 13.33±3.54 µmol/L (P<0.01) and DBIL from 175.08±39.27 to 4.03±1.74 µmol/L (P<0.01). Liver function improved faster than TBIL. After 2 wk, in the TIPS group, alanine aminotransferase (ALT) decreased significantly from 50.33±40.61 U/L to 28.67±7.02 U/L (P<0.01) and aspartate aminotransferase (AST) from 49.46±34.33 U/L to 26.89±8.68 U/L (P<0.01). In the angioplasty group, ALT decreased significantly from 51.56±27.90 to 14.22±2.59 µmol/L (P<0.01) and AST from 60.66±39.89 µmol/L to 8.18±1.89 µmol/L (P<0.01). After mean follow-up of 12.6 mo, there was no recurrence of jaundice in either group. CONCLUSION: Severe jaundice is not a contraindication for TIPS in patients with acute BCS and TIPS is appropriate for severe jaundice due to BCS.

Parallel transjugular intrahepatic portosystemic shunt for controlling portal hypertension complications in cirrhotic patients.

AIM: To evaluate the feasibility of a second parallel transjugular intrahepatic portosystemic shunt (TIPS) to reduce portal venous pressure and control complications of portal hypertension. METHODS: From January 2011 to December 2012, 10 cirrhotic patients were treated for complications of portal hypertension. The demographic data, operative data, postoperative recovery data, hemodynamic data, and complications were analyzed. RESULTS: Ten patients underwent a primary and parallel TIPS. Technical success rate was 100% with no technical complications. The mean duration of the first operation was 89.20 ± 29.46 min and the second operation was 57.0 ± 12.99 min. The mean portal system pressure decreased from 54.80 ± 4.16 mmHg to 39.0 ± 3.20 mmHg after the primary TIPS and from 44.40 ± 3.95 mmHg to 26.10 ± 4.07 mmHg after the parallel TIPS creation. The mean portosystemic pressure gradient decreased from 43.80 ± 6.18 mmHg to 31.90 ± 2.85 mmHg after the primary TIPS and from 35.60 ± 2.72 mmHg to 15.30 ± 3.27 mmHg after the parallel TIPS creation. Clinical improvement was seen in all patients after the parallel TIPS creation. One patient suffered from transient grade I hepatic encephalopathy (HE) after the primary TIPS and four patients experienced transient grade I-II after the parallel TIPS procedure. Mean hospital stay after the first and second operations were 15.0 ± 3.71 d and 16.90 ± 5.11 d (P = 0.014), respectively. After a mean 14.0 ± 3.13 mo follow-up, ascites and bleeding were well controlled and no stenosis of the stents was found. CONCLUSION: Parallel TIPS is an effective approach for controlling portal hypertension complications.