Median Hepatic Venous Pressure Gradient Research Articles

Successful Transjugular Portosystemic Shunt Treatment of Pediatric Sinusoidal Obstruction: Case Report and Review of Literature.

In adults with medically refractory sinusoidal obstruction syndrome (SOS), a transjugular intrahepatic portosystemic shunt (TIPS) has been used successfully to improve portal hypertension and symptoms such as ascites. There is limited data on the use of TIPS for SOS in pediatric patients. The index case was reviewed retrospectively. PubMed and Medline databases were searched to identify other cases. A 4-year-old male with high-risk neuroblastoma, developed SOS after tandem autologous stem cell transplant. He was medically managed with defibrotide, diuretics, and peritoneal drainage, but, due to refractoriness, he underwent TIPS day +54 following bone marrow transplant. Hepatic venous pressure gradient improved from 17 to 8 mm Hg following TIPS placement with significant improvement in the patient's clinical status and ascites. However, 15 months later, his shunt remained patent, and he remains clinically well with stable liver enzymes. A literature review identified 13 pediatric cases of TIPS for SOS due to varied causes. TIPS caused a median hepatic venous pressure gradient of 9 mmHg (range, 2-38 mm Hg). The mortality following the procedure was 15%, with 2 cases who died at 2- and 11-days post-TIPS. At the time of the last follow-up (range 8-25 months), 5 patients were alive, and 8 were lost to follow-up. We present here a pediatric case of SOS due to stem cell transplant treated successfully with TIPS with a review of the literature. A timely, individualized application of TIPS can be effective in treating children with medication-refractory SOS.

Diabetes impairs the haemodynamic response to non-selective betablockers in compensated cirrhosis and predisposes to hepatic decompensation.

Non-selective betablockers (NSBBs) reduce the risk of hepatic decompensation in patients with compensated advanced chronic liver disease (cACLD). Metabolic co-morbidities (MetC) are increasingly observed in cACLD patients. To investigate the impact of MetC on the haemodynamic effects of NSBB and hepatic decompensation in cACLD. cACLD patients undergoing paired hepatic venous pressure gradient (HVPG) measurements before/under NSBB therapy were retrospectively considered for this study. We recorded baseline characteristics on MetC (obesity, dyslipidaemia and diabetes), as well as hepatic decompensation and liver-related mortality during follow-up. We included 92 patients (Child-A n = 80, 87%; Child-B n = 12, 13%). MetC were found in 34 (37%) patients: 19 (20.7%) with obesity, 14 (15.2%) with dyslipidaemia and 23 (34.8%) with diabetes. The median baseline HVPG of 18 (IQR:15-21) mmHg decreased to 15 (IQR:9-12) mmHg under NSBB. HVPG-response (decrease ≥10% or to ≤12 mmHg) was achieved in 60 (65.2.%) patients. Patients with diabetes (OR: 0.35, p = 0.021) and higher BMI (OR: 0.89 per kg/m2 , p = 0.031) were less likely to achieve HVPG-response. During a median follow-up of 2.3 (0.5-4.2) years, 18 (19.5%) patients experienced hepatic decompensation. Child-B (adjusted subdistribution hazard ratio, aSHR: 4.3 [95% CI:1.5-12.2], p = 0.006), HVPG-response (aSHR: 0.3 [95% CI:0.1-0.9], p = 0.037) and diabetes (aSHR: 2.8 [95% CI:1.1-7.2], p = 0.036) were independently associated with hepatic decompensation. In patients with cACLD, diabetes and a higher BMI impair the HVPG-response to NSBB. Furthermore, diabetes-independently from Child B and lack of HVPG-response-increases the risk ofhepatic decompensation.

Hepatic recompensation according to Baveno VII criteria is linked to a significant survival benefit in decompensated alcohol-related cirrhosis.

Removing the primary aetiological factor in decompensated cirrhosis may lead to a restoration of hepatic function. In this study, we investigated the clinical implications of recompensation and the subsequent survival in patients with decompensated alcohol-related cirrhosis. The rate of recompensation was evaluated in patients with decompensated alcohol-related cirrhosis and persistent alcohol abstinence undergoing a hepatic venous pressure gradient (HVPG) measurement. Recompensation was defined according to Baveno VII criteria as resolution of ascites and hepatic encephalopathy, absence of variceal bleeding and improvement in liver function. Two hundred and four abstinent patients with decompensated alcohol-related cirrhosis (age: 57.2 [IQR:50.1-63.7] years; 75.0% male; median MELD: 15 [IQR:11-19]) and a median HVPG of 20 (IQR:18-24) mmHg were included. During a median follow-up of 24.4 (IQR:10.9-50.4) months, 37 patients (18.1%) achieved abstinence-induced recompensation. Lower baseline HVPG, lower Child-Pugh score, lower BMI, higher albumin and higher mean arterial pressure were linked to a higher probability of recompensation. After adjusting for age, disease severity, portal hypertension and systemic inflammation, achieving recompensation resulted in a significant and considerable reduction in liver-related mortality (adjusted HR: 0.091 [95% CI: 0.012-0.677]; p = .019). Only 13 patients (6.4%) developed hepatocellular carcinoma, with a tendency towards a lower risk upon recompensation (HR: 0.398 [95% CI: 0.084-1.878]; p = .245), yet this finding did not reach statistical significance and requires further investigation. Alcohol abstinence led to recompensation in 18.1% of our cohort of HVPG-characterised patients with decompensated alcohol-related cirrhosis. Achieving hepatic recompensation resulted in a >90% risk reduction in liver-related mortality.

Bacterial translocation occurs early in cirrhosis and triggers a selective inflammatory response

BackgroundExperimental data suggest that bacterial translocation (BT) promotes systemic inflammation, portal hypertension, and circulatory dysfunction in advanced chronic liver disease (ACLD).MethodsPatients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement and absence of acute decompensation or infections were included (n = 249). Serum biomarkers of BT (lipopolysaccharide [LPS], lipoteichoic acid [LTA], bacterial DNA [bactDNA]), systemic inflammation and markers of circulatory dysfunction were assessed. T-cell subsets in intestinal biopsies (n = 7 ACLD, n = 4 controls) were analyzed by flow cytometry.ResultsPatients had a median HVPG of 18 (12–21) mmHg and 56% had decompensated ACLD. LPS (0.04 [0.02–0.06] vs. 0.64 [0.30–1.06] EU/mL), LTA (4.53 [3.58–5.97] vs. 43.2 [23.2–109] pg/mL), and detection of bactDNA (≥ 5 pg/mL; 5% vs. 41%) were markedly higher in patients with ACLD than healthy controls (n = 40; p < 0.001) but were similar between different clinical stages of compensated and decompensated ACLD and displayed no meaningful correlation with HVPG and systemic hemodynamics. TNF-α and IL-10 correlated with LPS (Spearman’s rs = 0.523, p < 0.001/rs = 0.143, p = 0.024) but not with LTA. Presence of bactDNA was associated with higher LPS (0.54 [0.28–0.95] vs. 0.88 [0.32–1.31] EU/mL, p = 0.001) and TNF-α (15.3 [6.31–28.1] vs. 20.9 [13.8–32.9] pg/mL). Patients with ACLD exhibited a decreased CD4:CD8-ratio and increased TH1-cells in the intestinal mucosa as compared to controls. During a median FU of 14.7 (8.20–26.5) months, bacterial antigens did not predict decompensation or liver-related death (in contrast to HVPG, IL-6, and MAP) as well as infections at 24 months.ConclusionBT occurs already in early ACLD stages and triggers a systemic inflammatory response via TNF-α and IL-10. Interestingly, BT markers showed no clear correlation with portal hypertension and circulatory dysfunction in patients with stable ACLD.Clinical trial numberNCT03267615.

Alcohol Abstinence Improves Prognosis Across All Stages of Portal Hypertension in Alcohol-Related Cirrhosis

Background and AimsAlcohol-related liver disease is a leading cause of liver-related mortality. The effect of alcohol abstinence on the natural history of alcohol-related cirrhosis across distinct stages of portal hypertension has not been thoroughly investigated. In this study, we assessed the clinical implications of abstinence in patients with alcohol-related cirrhosis and clinically significant portal hypertension. MethodsAlcohol abstinence, hepatic decompensation, and mortality were assessed in patients with alcohol-related cirrhosis who underwent a baseline hepatic venous pressure gradient (HVPG) measurement and were diagnosed with clinically significant portal hypertension (HVPG ≥10 mm Hg). ResultsA total of 320 patients with alcohol-related cirrhosis (median age: 57 [interquartile range (IQR), 49.7-63.1] years; 75.6% male; 87.5% decompensated) and a median HVPG of 20 (IQR, 17-23) mm Hg were followed up for a median of 36 (IQR, 14-80) months. Overall, 241 (75.3%) patients remained abstinent, while 79 (24.7%) patients had active alcohol consumption. Alcohol abstinence was linked to a significantly reduced risk of hepatic decompensation (adjusted hazard ratio [aHR], 0.391; P < .001), as well as liver-related (aHR, 0.428; P < .001) and all-cause (aHR, 0.453; P < .001) mortality, after adjusting for baseline HVPG, MELD, and previous decompensation. Importantly, alcohol abstinence significantly reduced the cumulative incidence of hepatic decompensation in both groups with HVPG 10–19 mm Hg (P < .001) and HVPG ≥20 mm Hg (P = .002). The 3-year decompensation probability was 32.4% vs 60.0% in HVPG 10–19 mm Hg and 57.5% vs 82.6% in HVPG ≥20 mm Hg for abstinent patients vs active drinkers, respectively. ConclusionsAlcohol abstinence improves prognosis across all stages of portal hypertension in alcohol-related cirrhosis, including in patients who have already progressed to high-risk portal hypertension. (ClinicalTrials.gov, Number: NCT03267615).

CT-282 Case Report: Successful Management of Severe Veno-Occlusive Disease after Allogeneic Stem Cell Transplantation Using a Transjugular Intrahepatic Portosystemic Shunt

Veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (VOD/SOS), of the liver is a complication of allogeneic bone marrow or peripheral stem cell transplantation and is known to be an unpredictable, life-threatening complication with high mortality. We report here a case of a 24-year-old male patient who was diagnosed in 2019 at Gustave Roussy institute with AML. The patient was treated with the AML protocol 3+7 in December 2019 with a complete cytologic response and a positive MRD. Leukemia relapse was observed in September 2020, treated by gemtuzumab ozogomycin and cytarabine with a negative MRD. A successful allogeneic bone marrow transplantation from an HLA-matched pheno-identical related donor was conducted on December 22, 2020, using a myeloablative conditioning regimen. The patient was always controlled by a daily blood test and controlled blood transfusions, and a weekly repeated Doppler ultrasound examination did not indicate a high-risk profile of VOD. However, 12 days post transplant, the patient's condition deteriorated with the appearance of abdominal ascites, weight gain of 6 kg (per base 76 kg), and liver cytolysis with ASAT 72 UI/L, ALAT 86 UI/L, and normal bilirubin. Worsening cytolysis was observed, with ASAT 659 UI/L, ALAT 557 UI/L, and normal bilirubin. A Doppler ultrasound found 5 positive criteria of VOD (hepatomegaly, portal dilation, enlargement of the gall bladder wall, splenomegaly, ascites, decrease in the diameter of the subhepatic veins). Defibrotide was initiated. The patient's condition worsened and was refractory to medical therapy. Transjugular intrahepatic portosystemic shunting (TIPS) was performed 13 days after transplantation without technical complications in any case. The median hepatic venous pressure gradient prior to the procedure was 20 mmHg with a drop to 12 mmHg. An abdominal CT scan showed an under hepatic hematoma with hemorrhagic syndrome. Ascites puncture with abdominal drain installation was done. In summary, following TIPS, the patient showed clinical improvement, and VOD resolved subsequently with a complete remission post allogeneic transplant.

Carvedilol Achieves Higher Hemodynamic Response and Lower Rebleeding Rates Than Propranolol in Secondary Prophylaxis

Carvedilol induces stronger decreases in hepatic venous pressure gradient (HVPG) than conventional nonselective β-blockers (ie, propranolol). Limited data exist on the efficacy of carvedilol in secondary prophylaxis of variceal bleeding. Patients undergoing paired HVPG measurements for guiding secondary prophylaxis with either carvedilol or propranolol were included in this retrospective analysis. All patients also underwent band ligation. Changes in HVPG and systemic hemodynamics were compared between the 2 groups. Long-term follow-up data on rebleeding, acute kidney injury, nonbleeding decompensation, and liver-related death were analyzed applying competing risk regression. Eighty-seven patients (carvedilol/propranolol, n= 45/42) were included in our study. The median baseline HVPG was 21 mm Hg (interquartile range, 18-24 mm Hg), and 39.1%/48.3%/12.6% had Child-Turcotte-Pugh A/B/C cirrhosis, respectively. Upon nonselective β-blocker initiation, HVPG decreased more strongly in carvedilol users (median relative decrease, -20% [interquartile range: -29% to -10%] vs -11% [-22% to -5%] for propranolol; P= .027), who also achieved chronic HVPG response more often (53.3% vs 28.6%; P= .034). Cumulative incidences for rebleeding (Gray test, P= .027) and liver-related death (P= .036) were significantly lower in patients taking carvedilol compared with propranolol. Notably, ascites development/worsening also was observed less commonly in carvedilol patients (P= .012). Meanwhile, acute kidney injury rates did not differ between the 2 groups (P= .255). Stratifying patients by HVPG response status yielded similar results. The prognostic value of carvedilol intake was confirmed in competing risk regression models. Carvedilol induces more marked reductions in HVPG than propranolol in secondary prophylaxis of variceal bleeding, and thus is associated with lower rates of rebleeding, liver-related death, and further nonbleeding decompensation.

Long-Term Outcome of HBV-Infected Patients with Clinically Significant Portal Hypertension Achieving Viral Suppression.

Background: Nucleos(t)ide analog (NA) treatment for hepatitis B virus (HBV) infection may improve clinically significant portal hypertension (CSPH). Data on hepatic venous pressure gradient (HVPG) and non-invasive tests (NITs) for risk re-stratification in virally suppressed HBV-infected patients with pre-treatment CSPH are limited. Methods: We retrospectively included patients with long-term (>12 months) suppression of HBV replication and pre-treatment CSPH (i.e., varices, collaterals on cross-sectional imaging, or ascites). Patients were monitored by on-treatment liver stiffness measurement (LSM) and HVPG assessment. The primary outcome was (further) hepatic decompensation (including liver-related mortality). Results: Forty-two patients (n = 12 (28.6%) with previous decompensation, HBeAg-negative: n = 36 (85.7%)) were included and followed for 2.1 (0.6; 5.3) years. The median HVPG (available in n = 17) was 15 (10; 22) mmHg and the median LSM 22.5 (12.5; 41.0) kPa. LSM correlated strongly with HVPG (Spearman’s ρ: 0.725, p < 0.001) and moderately with the model for end-stage liver disease (MELD) score (ρ: 0.459, p = 0.002). LSM, MELD and albumin levels had good prognostic value for decompensation (area under the receiver operated characteristics curve (AUROC) >0.850 for all). LSM predicted (further) decompensation in competing risk regression (subdistribution hazard ratio (SHR): 1.05 (95% confidence interval(CI) 1.03–1.06); p < 0.001), even after adjusting for other factors. An LSM cut-off at 25kPa accurately stratified patients into a low-risk (n = 23, zero events during follow-up) and a high-risk (n = 19; n = 12 (63.2%) developed events during follow-up) group. Conclusions: Patients with HBV-induced CSPH who achieved long-term viral suppression were protected from decompensation, if LSM was <25 kPa. LSM ≥ 25 kPa indicates a persisting risk for decompensation, despite long-term HBV suppression.

Decompensation in Advanced Nonalcoholic Fatty Liver Disease May Occur at Lower Hepatic Venous Pressure Gradient Levels Than in Patients With Viral Disease

Portal hypertension is the strongest predictor of hepatic decompensation and death in patients with cirrhosis. However, its discriminatory accuracy in patients with nonalcoholic fatty liver disease (NAFLD) has been challenged because hepatic vein catheterization may not reflect the real portal vein pressure as accurately as in patients with other etiologies. We aimed to evaluate the relationship between hepatic venous pressure gradient (HVPG) and presence of portal hypertension-related decompensation in patients with advanced NAFLD (aNAFLD). Multicenter cross-sectional study included 548 patients with aNAFLD and 444 with advanced RNA-positive hepatitis C (aHCV) who had detailed portal hypertension evaluation (HVPG measurement, gastroscopy, and abdominal imaging). We examined the relationship between etiology, HVPG, and decompensation by logistic regression models. We also compared the proportions of compensated/decompensated patients at different HVPG levels. Both cohorts, aNAFLD and aHVC, had similar baseline age, gender, Child-Pugh score, and Model for End-Stage Liver Disease score. Median HVPG was lower in the aNAFLD cohort (13 vs 15 mmHg) despite similar liver function and higher rates of decompensation in aNAFLD group (32% vs 25%; P= .019) than in the aHCV group. For any of the HVPG cutoff analyzed (&lt;10, 10-12, or 12 mmHg) the prevalence of decompensation was higher in the aNAFLD group than in the aHCV group. Patients with aNAFLD have higher prevalence of portal hypertension-related decompensation at any value of HVPG as compared with aHCV patients. Longitudinal studies aiming to identify HVPG thresholds able to predict decompensation and long-term outcomes in aNAFLD population are strongly needed.

Per‐rectal portal scintigraphy as an alternative measure of hepatic venous pressure gradient in chronic liver disease: A preliminary report

Hepatic venous pressure gradient (HVPG) measurement is a gold standard for the diagnosis of portal hypertension but can be invasive and difficult to conduct. Per-rectal portal scintigraphy (PRPS) can estimate portal haemodynamics noninvasively. However, no report to date has examined the association between HVPG and PRPS in patients with chronic liver disease, including cirrhosis. This single-centre study included a total of 21 patients with chronic liver disease who underwent HVPG measurement and PRPS. For PRPS, the transit times from injection of the radiotracer to its inflow into the liver (TTL) and heart (TTH) were set and the time difference between TTL and TTH (TDLH) was calculated, while the shunt index (SI) was measured. Cirrhosis was observed in 18 cases (86%), and the median HVPG was 13mmHg. HVPG (p=0.028), TTL (p=0.018), TDLH (p=0.003) and SI (p=0.033) were higher in patients with oesophageal varices (EV). Considering the diagnostic ability for EV, the area under the curve was 0.88 for TDLH and 0.80 for HVPG. TDLH was significantly correlated with the risk of EV rupture (p=0.004). Patients with chronic liver disease should undergo upper gastrointestinal endoscopy when the TDLH is high.

Prognostic impact of sarcopenia in cirrhotic patients stratified by different severity of portal hypertension.

Background and AimsPortal hypertension (PH) and sarcopenia are common in patients with advanced chronic liver disease (ACLD). However, the interaction between PH and sarcopenia and their specific and independent impact on prognosis and mortality has yet to be systematically investigated in patients with ACLD.MethodsConsecutive patients with ACLD and hepatic venous pressure gradient (HVPG) ≥10 mm Hg with available CT/MRI imaging were included. Sarcopenia was defined by transversal psoas muscle thickness (TPMT) at <12 mm/m in men and <8 mm/m in women at the level of the third lumbar vertebrae. Hepatic decompensation and mortality was recorded during follow‐up.ResultsAmong 203 patients (68% male, age: 55 ± 11, model for end‐stage liver disease [MELD]: 12 [9‐15]), sarcopenia was observed in 77 (37.9%) and HVPG was ≥20 mm Hg in 98 (48.3%). There was no correlation between TPMT and HVPG (r = .031, P = .66), median HVPG was not different between patients with vs without sarcopenia (P = .211). Sarcopenia was significantly associated with first/further decompensation both in compensated (SHR: 3.05, P = .041) and in decompensated patients (SHR: 1.86, P = .021). Furthermore, sarcopenia (SARC) was a significant predictor of mortality irrespective of HVPG (HVPG < 20‐SARC: SHR: 2.25, P = .021; HVPG ≥ 20‐SARC: SHR: 3.33, P = .001). On multivariate analysis adjusted for age, HVPG and MELD, sarcopenia was an independent risk factor for mortality (aHR: 1.99, 95% confidence interval: 1.2‐3.3, P = .007).ConclusionSarcopenia has a major impact on clinical outcomes both in compensated and in decompensated ACLD patients. The presence of sarcopenia doubled the risk for mortality independently from the severity of PH.

Amelioration of systemic inflammation in advanced chronic liver disease upon beta-blocker therapy translates into improved clinical outcomes

ObjectiveSystemic inflammation promotes the development of clinical events in patients with advanced chronic liver disease (ACLD). We assessed whether (1) non-selective beta blocker (NSBB) treatment initiation impacts biomarkers of systemic...

Transjugular Intrahepatic Portosystemic Shunt for Very Severe Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) after Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation with Post-transplantation Cyclophosphamide.

Hepatic veno-occlusive disease or sinusoidal obstruction syndrome (VOD/SOS) is a threatening complication after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT), with high mortality rates despite early medical treatment, including the use of defibrotide (DF). We retrospectively analyzed 185 unmanipulated haploidentical (haplo-) HSCT with post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis performed consecutively between 2011 and June 2019 in a single center. Seventeen patients (9.2%) were diagnosed with VOD/SOS. Based on revised European Society for Blood and Marrow Transplantation severity criteria, the VOD/SOS cases were classified as mild in 2 patients (11.7%), moderate in 2 (11.7%), severe in 2 (11.7%), and very severe in 11 (64.9%). Thirteen patients (76%) were treated with DF, including all patients with severe or very severe VOD/SOS, except 1 patient with CNS hemorrhage. Sixteen patients (94%) were alive at day +100 after HSCT. Seven patients (41%) with very severe VOD/SOS were treated with transjugular intrahepatic portosystemic shunt (TIPS) owing to rapid clinical or analytical deterioration or refractory hepatorenal syndrome despite medical treatment, including DF. TIPS insertion was performed at a median time since VOD/SOS diagnosis of 4 days (range, 1 to 28 days) without technical complications in any case. The median hepatic venous pressure gradient before and after TIPS treatment was 24 mmHg (range, 14 to 29 mmHg) and 7 mmHg (range, 2 to 11 mmHg), respectively, with a median drop of 16 mmHg (range, 9 to 19 mmHg). Following TIPS insertion, all patients showed clinical improvement with hepatomegaly, ascites, and renal failure resolution, and all showed analytical improvement with reduced alanine aminotransferase (ALT), creatinine, and international normalized ratio values, except for patient 2, whose indication for TIPS was refractory hepatorenal syndrome with a normal ALT level. The 6 patients who had initiated DF before TIPS insertion completed 21 days of treatment. All patients met the criteria for complete remission (CR) at a median of 8 days after TIPS insertion (range, 2 to 82 days). The 100-day overall survival was 100%. For patients with rapid progressive VOD/SOS, early TIPS insertion allowed completion of DF therapy. The use of TIPS together with DF resulted in CR and no associated complications with no VOD/SOS-associated mortality despite high severity. In our experience, timely and individualized use of TIPS significantly improves outcomes of very severe VOD/SOS after haplo-HSCT. Therefore, TIPS should be promptly considered in rapidly progressive cases.

Liver resection for hepatocellular carcinoma in patients with clinically significant portal hypertension.

Background & AimsLiver resection (LR) in patients with hepatocellular carcinoma (HCC) and clinically significant portal hypertension (CSPH) defined as a hepatic venous pressure gradient (HVPG) ≥10 mmHg is not encouraged. Here, we reappraised the outcomes of patients with cirrhosis and CSPH who underwent LR for HCC in highly specialised liver centres.MethodsThis was a retrospective multicentre study from 1999 to 2019. Predictors for postoperative liver decompensation and textbook outcomes were identified.ResultsIn total, 79 patients with a median age of 65 years were included. The Child-Pugh grade was A in 99% of patients, and the median model for end-stage liver disease (MELD) score was 8. The median HVPG was 12 mmHg. Major hepatectomies and laparoscopies were performed in 28% and 34% of patients, respectively. Ninety-day mortality and severe morbidity rates were 6% and 27%, respectively. Postoperative and persistent liver decompensation occurred in 35% and 10% of patients at 3 months. Predictors of liver decompensation included increased preoperative HVPG (p = 0.004), increased serum total bilirubin (p = 0.02), and open approach (p = 0.03). Of the patients, 34% achieved a textbook outcome, of which the laparoscopic approach was the sole predictor (p = 0.004). The 5-year overall survival and recurrence-free survival rates were 55% and 43%, respectively.ConclusionsPatients with cirrhosis, HCC and HVPG ≥10 mmHg can undergo LR with acceptable mortality, morbidity, and liver decompensation rates. The laparoscopic approach was the sole predictor of a textbook outcome.Lay summaryPatients with cirrhosis, hepatocellular carcinoma, and clinically significant portal hypertension (defined as a hepatic venous pressure gradient ≥10 mmHg) can undergo resection with acceptable mortality, morbidity, liver decompensation rates, and a textbook outcome. These results can be achieved in selected patients with preserved liver function, good general status, and sufficient remnant liver volume.

Transjugular Intrahepatic Portosystemic Shunt (TIPS) for Very Severe Veno-Occlusive Disease after Unmanipulated Haploidentical HSCT with Post-Transplant Cyclophosphamide

Background: The use of unmanipulated Haploidentical HSCT (Haplo-HSCT) with post-transplant Cyclophosphamide (PT-Cy) as GVHD prophylaxis has widely extended. Veno-occlusive disease (VOD) is a threatening complication after both autologous and allogeneic HSCT, with high mortality rates despite early medical treatment, including the use of defibrotide. The objective of this study was to describe characteristics and outcomes of patients with refractory very severe VOD after Haplo-HSCT with PT-Cy, treated with TIPS as salvage procedure. Methods: We retrospectively analysed 176 Haplo-HSCT with Cy-post consecutively performed between 2011 and May 2019 in a single centre. VOD was defined according to modified Seattle, Baltimore or revised EBMT criteria. Severity was retrospectively graded according to revised EBMT severity criteria into four categories: mild, moderate, severe and very severe. Complete response (CR) was defined as a normal total bilirubin level (&lt;2 mg/dL) or, in patients with normal bilirubin or alternative causes of hyperbilirubinemia, as normalized renal function, reduction of elevated transaminase level &lt;50%, tense ascites resolution, and no need for oxygen supplement in the absence of alternative hypoxemia causes. Results: Sixteen patients (9.1%) met the modified Seattle, Baltimore or revised EBMT diagnostic criteria for VOD. Ultrasound with Doppler ultrasonography was performed in all patients, and at least indirect signs of VOD were found in all cases. Based on revised EBMT severity criteria, there were 2 mild (12.5%), 2 moderate (12.5%), 2 severe (12.5%) and 10 very severe (62.5%) grade VOD. Twelve patients (75%) were treated with defibrotide, including all patients with very severe VOD, except one with CNS hemorrhage (Patient 1). Six patients with very severe VOD, were treated with TIPS due to rapid clinical or analytical deterioration or refractory hepatorenal syndrome, despite medical treatment including defibrotide (Table 1). All were male patients, with a median age of 31 years (range 22-36), all transplanted with myeloablative conditioning regimen. TIPS insertion was performed on a median time since VOD diagnosis of 5 days (range 1-28) without technical complications in any case. Median total bilirubin, ALT, creatinine and INR the day of procedure were 3 mg/dL (range 2.2-11.2), 1120 UI/L (range 10-2595), 2.45 mg/dL (range 2.06-3.58) and 1.96 (range 1.1-4) respectively. Median hepatic venous pressure gradient (HVPG) prior to and after TIPS was 22.5 (range 14-29) and 6.5 (range 2-10) mmHg respectively, with a median drop of 16.5 mmHg (range 9-19). Following TIPS, all patients showed clinical improvement with hepatomegaly, ascites and renal failure resolution, and all showed analytical improvement with bilirubin, creatinine and ALT values reduction, except for patient 2, whose TIPS indication was refractory hepatorenal syndrome with normal ALT levels (Figure 1). The 5 patients who had iniciated defibrotide before TIPS, completed 21 days of treatment. All patients met criteria for CR in a median of 8 days after TIPS insertion (range 2-82). The 100-day overall survival (OS) was 100%. Five patients were alive with normal liver and renal function at last follow up, and one patient died due to infection 7 months after Haplo-HSCT, with VOD in complete resolution. Conclusions: Incidence of VOD after Haplo-HSCT with PT-Cy is comparable to those reported after HLA-identical HSCT series. Most of the patients developed very severe VOD according to revised EBMT severity criteria. For patients with rapid progressive VOD, early TIPS insertion allowed completion of defibrotide therapy. The use of TIPS together with defibrotide resulted in complete response and no associated complications with a 0% of VOD associated mortality in spite of high severity. ALT values may be the best predictor of CR after TIPS procedure. In our experience, timely and individualized use of TIPS significantly improves outcome of very severe VOD after Haplo-HSCT. Therefore, TIPS should be promptly considered in rapid progressive cases. Disclosures No relevant conflicts of interest to declare.

Performance of Controlled Attenuation Parameter in Patients with Advanced Chronic Liver Disease and Portal Hypertension

BackgroundLiver stiffness (LS) measured by vibration-controlled transient elastography (VCTE) is influenced by liver fibrosis and hepatic perfusion pressure. VCTE-based controlled attenuation parameter (CAP) is a noninvasive marker for hepatic steatosis (HS).AimsTo investigate the diagnostic performance of CAP in patients with advanced chronic liver disease (ACLD)/portal hypertension (PHT: hepatic venous pressure gradient (HVPG) ≥ 6 mmHg).MethodsEighty-eight patients with LS ≥ 10 kPa and/or HVPG ≥ 6 mmHg who underwent simultaneous liver biopsy, CAP, and HVPG measurement were included. HS was histologically graded according to the modified Brunt classification.ResultsPatient characteristics: Mean MELD:11 (standard derivation [SD] ± 4), median HVPG:16 (interquartile range [IQR]10–19) mmHg, median LS:27.4 (IQR 16.2–48.9) kPa, and mean CAP:221 (SD ± 75) dB/m. According to histology, 47 (53.4%) patients had no HS (S0), 28 (31.8%) had S1, 11 (12.5%) had S2, and 2 (2.3%) had S3. The area under the receiver operating characteristic curve (AUROC) of CAP for diagnosing any HS (S0 vs. ≥ S1) was 0.692 (95% confidence interval [95% CI] 0.582–0.802) in the overall cohort, 0.830 (95% CI 0.637–1.0) in patients with HVPG < 10 mmHg, and 0.629 (95% CI 0.497–0.761) in patients with clinically significant portal hypertension (CSPH; HVPG ≥ 10 mmHg; n = 69). Using the established cutoff for any HS (248 dB/m), the sensitivity/specificity of CAP was only 48.8%/76.6%, respectively. In contrast, the AUROC and sensitivity/specificity (cutoff 268 dB/m) for diagnosing HS ≥ S2 were 0.842 (95% CI 0.747–0.936) and 84.6%/81.3%, respectively. CAP correlated with the percentage of steatotic hepatocytes (Spearman’s ρ = 0.402; p ≤ 0.001) and showed a weak correlation with liver stiffness (ρ = 0.225; p = 0.035).ConclusionsThe diagnostic performance of CAP for any HS seems to be limited in patients with ACLD, if CSPH is present.

Non-invasive aspartate aminotransferase to platelet ratio index correlates well with invasive hepatic venous pressure gradient in cirrhosis.

Hepatic venous pressure gradient (HVPG) is the best recommended tool to measure portal pressure, but is invasive. HVPG helps in prognosticating cirrhosis and predictits complications. Aminotransferase to platelet ratio index (APRI) is a simple non-invasive marker of hepatic fibrosis. We aimed to correlate APRI with HVPG and to determine the usefulness of APRI in predicting complication of cirrhosis. APRI and HVPG were measured in consecutive patients of cirrhosis aged 18 to 70 years. Spearman's rho was used to estimate their correlation; acut-off valueof APRI topredict severe portal hypertension (HVPG > 12mmHg) was determined. This study, conducted between August 2011 and December 2014, included 277 patients, median age 51 (range: 16-90) years, 84% males. Etiology of cirrhosis was alcohol in 135 (49%), cryptogenic/nonalcoholic steatohepatitis (NASH) in 104 (38%), viral in 34 (12%), and others in 4 (1%). Median Child-Turcott-Pugh (CTP) and model for end-stage liver disease (MELD) scores were 7 (5-11) and 11 (6-33), respectively. Median HVPG was 17.0 (1.5-33) mmHg and median APRI was 1.09 (0.21-12.22). There was positive correlation between APRI andHVPG (Spearman's rho 0.450, p < 0.001). The area under the receiver operating characteristic (ROC) curve of APRI for predicting severe portal hypertension was 0.763 (p < 0.01). Youden's index defined the cut-off of APRI for predicting HVPG > 12mmHg was 0.876 with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 71%, 78%, 94%, 38%, and 73%, respectively. APRI also correlated well with CTP, variceal size, bleeding status, ascites but not with MELD. APRI score of 0.876 has an acceptable accuracy topredictsevere portal hypertension (HVPG > 12mmHg). High APRI also correlated with severity of cirrhosis and its complications. Thus, APRI may be used as a simple, bedside, non-invasive, and inexpensive tool for evaluating portal hypertension and complications of cirrhosis.

Spectrum of histopathological changes in patients with non-cirrhotic portal fibrosis.

Non-cirrhotic portal fibrosis (NCPF) is a clinical disorder characterized by features of portal hypertension in the absence of significant fibrosis. It is one of the commonest causes of portal hypertension in India. This study aimed to analyze histomorphological spectrum of NCPF in detail. There were 67 specimens from 66 patients which included 43 (65.2%) male and 23 (34.8%) female patients with a mean age of 31years (range: 7-61years). The liver function tests showed only a mild derangement. The average length of biopsy was 1.4cm (median: 1.2cm, range: 0.8-3.4cm) and the mean number of portal tracts per biopsy was 11.1 (median: 10, range: 5-30). Most cases showed a combination of histological features; the mean number of histological features per biopsy was 7.4 (median: 7, range: 3-12). Obliterative portal venopathy was seen in 47.8% cases. Portal angiomatosis (61.2%), paraportal shunt vessels (61.2%), portal vein dilatation (74.6%), hypoplastic portal tracts (56.7%), megasinusoids (64.1%), and abnormally dilated central veins (64.1%) were other prevalent features. Portal/periportal fibrosis and perisinusoidal fibrosis were seen in 77.6% and 61.2% cases; none showed bridging fibrosis or cirrhosis. The median hepatic venous pressure gradient (HVPG) and liver stiffness (LS) values were 8mm of Hg (range: 5-20mm of Hg) and 9.2kPa (range: 4.4-26.3kPa). There was no correlation of HVPG or LS with either portal/periportal fibrosis or perisinusoidal fibrosis. Due to relatively non-specific and non-pathognomonic nature, a combination of different histological features in the absence of significant fibrosis and appropriate clinico-radiological background is needed for diagnosing NCPF.

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’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 < 0.001). The area under ROC curve for TE in predicting CSPH was 0.740 (95%CI: 0.662-0.818) (P < 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%.

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

To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention. 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. 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. The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.