Severe Portal Hypertension Research Articles

Surgical Complications Requiring an Early Relaparotomy in HIV-Infected Liver Transplant Recipients: Risk Factors and Impact on Survival

AimWe aimed to analyze the risk factors for early surgical complications requiring relaparotomy and the related impact on overall survival (OS) in HIV-infected patients submitted to liver transplantation. MethodsWe performed a retrospective study on a nationwide multicenter cohort of 157 HIV-infected patients submitted to liver transplantation in 6 Italian transplant units between 2004 to 2014. ResultsThe median preoperative model for end-stage liver disease score was 18 (interquartile range 12-26.5). An early relaparotomy was performed in 24.8% of patients, and the underlying clinical causes were biliary leak (8.2%), bleeding (8.2%), intestinal perforation (4.5%), and suspected vascular complications (3.8%). The OS at 1, 3, and 5 years was 74.3%, 68.0%, and 60.0%, respectively, and an early relaparotomy was not a prognostic factor itself, but an increasing number of relaparotomies was associated with decreased survival (hazard ratio = 1.40, 95% confidence interval [CI] 1.07-1.81, P = .01). In the multivariate analysis, preoperative refractory ascites (odds ratio 3.32, 95% CI 1.18-6.47, P = .02) and Roux-en-Y choledochojejunostomy reconstruction (odds ratio 12.712, 95% CI 2.47-65.38, P ≤ .01) were identified as significant risk factors for early relaparotomy. ConclusionsIn HIV-infected liver transplant recipients, an increasing number of early relaparotomies due to surgical complications did negatively affect the OS. Preoperative refractory ascites reflecting a severe portal hypertension and a difficult biliary tract reconstruction requiring a Roux-en-Y choledochojejunostomy were associated with an increased risk of early relaparotomy.

Use Of Quantitative Modelling To Elucidate The Roles Of The Liver, Gut, Kidney, And Muscle In Ammonia Homeostasis And How Lactulose And Rifaximin Alter This Homeostasis.

Humans must eliminate approximately 1M of ammonia per day while maintaining the blood concentration of this potent neurotoxin at a concentration of only about 30 µM. The mechanisms producing such effective ammonia homeostasis are poorly understood by clinicians due to the multiple organs (liver, gut, kidney and muscle) involved in ammonia homeostasis. Based on literature values we present a novel, simplified description of normal and disordered ammonia and the potential mechanisms whereby the drugs used to treat hepatic encephalopathy, lactulose and rifaximin, lower the blood ammonia concentration. Concepts discussed include the following: 1) only about 44 mmol of ammonia/day (4.4% of total production) reaches the peripheral circulation due to the efficient linkage of amino deamination and the urea cycle in hepatic mitochondria; 2) the gut and kidney contribute roughly equally to delivery of this 44 mmol/day to systemic blood; 3) the bulk of gut ammonia production seemingly originates in the small bowel from bacterial deamination of urea by bacteria and mucosal deamination of circulating and ingested glutamine; 4) the apparent production of ammonia in the small bowel markedly exceeds that quantity that enters the portal blood, indicating that ammonia disposal mechanisms in the small bowel play a major role in ammonia homeostasis. With regard to the hyperammonemia of chronic liver disease: 1) shunting of portal blood around the liver, by itself, can account for commonly observed ammonia elevations; 2) severe portal hypertension causes an increased release of ammonia by the kidney; 3) high blood ammonia is associated with an unexplained massive increase in the muscle uptake of ammonia that could play an important role in limiting hyperammonemia; and 4) a major action of lactulose administration may be the enhancement of ammonia uptake by small bowel bacteria, while the mechanism of action of rifaximin is unclear.

The potential of radionuclide diagnostic imaging in diffuse liver disease and portal hypertension

Objective. The study objective was to assess the scintigraphy potential in the evaluation of portal hypertension and the severity of liver damage in diffuse diseases and after liver transplantation.Material and methods. The study enrolled 325 patients suffering from hepatitis and liver cirrhosis of various etiology and severity, including those after liver transplantation, namely, the patients with hepatitis (n=96), patients with liver cirrhosis of Child–Pugh class A (n=24), class B (n=87), and class C (n=118); 11 more healthy volunteers without clinical and laboratory signs of diffuse liver disease were enrolled as controls. The assessment of liver reticuloendothelial system was performed by scintigraphy with (99m)Tc-phytate colloid in a static planar mode and "whole body" mode by SPECT (Infinia II, GE).Results. In contrast to the control group, significant radionuclide signs of hepatosplenomegaly were revealed with the predominant functional activity of the left lobe; the liver function was found impaired that correlated with the cirrhosis severity evaluated according to the Child–Pugh Сlassification. The analysis of scintigraphy quantitative parameters showed that the most informative of them were the intensity of radiopharmaceutical accumulation in the spleen (S%) and in bone marrow (Вm%), and the radiopharmaceutical uptake by the reticuloendothelial cells of the liver and spleen in percentage from the administered activity (Lwb%, Swb%). Depending on the cirrhosis severity assessed by the Child–Pugh Score, the changes in quantitative parameters were accompanied by a progressive enlargement of the spleen, liver left lobe, the increase of (99m)Tc-phytate uptake by the bone marrow with a decreased radiopharmaceutical uptake by the liver. The study results showed that among the Child–Pugh class C patients, the impairment of liver reticuloendothelial function was more pronounced in the patients with cirrhosis of viral and mixed etiology, when compared to those with alcoholic cirrhosis.Conclusion. The paper has identified the most informative parameters characterizing portal hypertension and the reticuloendothelial function for all Child–Pugh defined classes of cirrhosis. These parameters include the increase of (99m) Tc-phytate accumulation in the spleen (S%) and bone marrow (Bm%); the liver and spleen uptake of the radiopharmaceutical in percentage from the administered activity (Lwb%, Swb%). The calculation of the remaining parameters is necessary for a detailed description of the organ function and for the assessment of the portal hypertension severity in repeated studies.Summary. Criteria for the objective assessment of reticuloendothelial function and portal hypertension in diffuse liver diseases, including after liver transplantation, have been developed. Contrary to the control group, in patients with diffuse liver diseases, the radionuclide signs of hepatosplenomegaly (or a decreased liver size) with a predominant functional activity of the left lobe were identified, as were the changes in the quantitative parameters of the radiopharmaceutical uptake by the liver (Lwb%), including the radiopharmaceutical accumulation in the liver left lobe (Ll%), spleen (Swb%), bone marrow (Bm%), and the liver-to-spleen area ratio (Lar/Sar). The informative and reliable (p<0.05) parameters of the function Lwb%, S%, Swb% and Bm% correlating with the cirrhosis classes assessed by Child–Pugh were identified. The radionuclide method, being highly reproducible one, can be recommended for an objective assessment of liver function and the detection of portal hypertension in hepatitis and cirrhosis, as well as for post-transplant monitoring of the liver function to prevent complications in the early and late postoperative periods.

Von Willebrand factor as a biomarker of clinically significant portal hypertension and severe portal hypertension: a systematic review and meta-analysis

ObjectiveThis meta-analysis was performed to investigate the correlation between von Willebrand factor (vWF) antigen and hepatic venous pressure gradient (HVPG) and to evaluate the diagnostic performance of vWF to detect...

Enhanced processing of von Willebrand factor reflects disease severity and discriminates severe portal hypertension in cirrhosis.

Portal hypertension in cirrhosis is associated with endothelial dysfunction, impaired wound healing, and decreased platelet count. Increased von Willebrand factor (VWF) formation has been suggested as a compensatory mechanism, but the role of VWF processing has not been directly assessed. The aim was to measure the processing of activated VWF (VWF-A) in addition to VWF release (VWF-N) to investigate the association of primary hemostasis with disease activity and portal hypertension in liver cirrhosis. Plasma samples from 105 participants undergoing liver vein catheterization and with liver cirrhosis of varying severity were included in the study together with 20 controls without liver disease. Competitive enzyme-linked immunosorbent assay format was used to estimate biomarkers of VWF turnover using neo-epitope-specific monoclonal antibodies. VWF-N levels and VWF-A levels were significantly elevated in cirrhotic patients compared with controls (P<0.0001), and both markers could discriminate mild from severe cirrhosis (VWF-N, P<0.0001; VWF-A, P<0.05). Both markers correlated well with increasing portal hypertension and could identify patients with clinically significant portal hypertension (VWF-N, area under the curve: 0.78; VWF-A, area under the curve: 0.67). Only VWF-A significantly separated compensated from decompensated patients (P<0.05). The data indicate that both VWF release and processing of active VWF are increased in cirrhosis, reflecting ongoing wound healing initiation. VWF-N and VWF-A may specifically contain information to assess the presence and severity of PHT as an early indicator of cirrhosis, and for acute damage in decompensated cirrhosis. Whether the increased wound healing affects long-term outcome needs to be addressed in future studies.

Adipopenia correlates with higher portal pressure in patients with cirrhosis.

In cirrhosis, hepatic venous pressure gradient (HVPG) and imaging body composition assessment can influence prognosis. We assessed whether adipose and skeletal muscle tissues reflect the severity of portal hypertension (PH), and whether they improve non-invasive prediction of decompensation and death. We included 84 cirrhosis patients with HVPG and computed tomography (CT) within 12weeks of HVPG at a single centre. L3 vertebra CT images were used for body composition indexes (cm2 /m2 ): total adipose tissue index (TATI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), intramuscular adipose tissue index (IMATI), skeletal muscle index (SMI) and psoas muscle index (PMI). Correlations were calculated between indexes, HVPG and standard non-invasive tests for PH. Twelve-month decompensation and death predictors were determined. The following were the characteristics for the patients included in the study: male 61%; BMI 28±5kg/m2 ; alcoholic liver disease in 51%, non-alcoholic steatohepatitis in 24%; HVPG 14±6mmHg; 45% compensated. The median follow-up was 11 (4-17) months. HVPG correlated with SATI (r=-0.282, P=0.01), TATI (r=-0.220, P=0.045) and SATI/VATI index (r=-0.240, P=0.03). In compensated patients, lower VATI (HR 0.94 (0.90-0.99), P=0.01) was associated with 12-month decompensation. Combining TATI and liver stiffness×spleen size over-platelet count risk score added discriminative capacity for 12-month decompensation (AUROC 0.91 vs 0.87). IMATI was independently associated with mortality in decompensated patients. MELD-Na combined with IMATI discriminated excellently for mortality (AUROC 0.94; P<0.001). Hepatic venous pressure gradient inversely correlates with imaging markers of adipose tissue, while markers of sarcopenia were unrelated to PH. In compensated patients, TATI improves non-invasive prediction of decompensation. In decompensated patients, IMATI independently predicted mortality.

320.4: Use of Arterial Embolisation to Facilitate Exenteration during Multi-visceral and Intestinal Transplantation

Introduction: Exenteration during multi-visceral and intestinal transplantation is associated with significant blood loss that increases patient instability intra-operatively and may affect the subsequent post-operative course. This is particularly the case for multi-visceral transplantation (MVT) for porto-mesenteric thrombosis (PMVT). Methods: Embolisation was undertaken in theatre following anaesthesia and placement of lines. Amplatzer arterial plugs (St Jude), either type I (8mm in length) or type II (16–24 mm) were utilised. In the case of full MVT, the plugs occluded both coeliac axis (CA) and superior mesenteric arteries (SMA). In circumstances where the stomach was retained the SMA, hepatic and splenic arteries were occluded and the left gastric artery preserved. Results: Pre-operative embolisation was performed in 13 patients who have had either MVT, liver/small bowel transplant (LSB), or small bowel/ pancreas/colon transplant (SBP). Nine of the 13 cases were embolised for severe portal hypertension (PHT). We have compared blood loss and use of blood products in this group to a historical cohort of intestine containing transplants in patients with severe PHT (table 1). By performing embolisation in the operating theatre there was minimal delay in the explant procedure and no increase in the cold ischaemic time. There was a reduction in intra-operative blood loss, blood products and metabolic instability. One patient undergoing a full MVT for PMVT required no blood products intra-operatively. There were no complications associated with the embolisation procedure. Conclusion: We believe that arterial embolisation is a very useful technique to minimize the blood loss associated with severe PHT during intestine containing transplantation. It reduces blood loss, blood products and metabolic instability. The use of arterial plugs substantially reduces the time required for embolisation and the selective occlusion of visceral arterial branches allows for the preservation of the stomach.

Plasma Nogo-A and placental growth factor levels are associated with portal hypertension in patients with liver cirrhosis.

BACKGROUNDClinically significant portal hypertension (CSPH) and severe portal hypertension (SPH) increase the risk for decompensation and life-threatening complications in liver cirrhosis. Pathologic angiogenesis might contribute to the formation of these conditions. Placental growth factor (PlGF) and Nogo-A protein are biomarkers of pathological angiogenesis, but data on their role in liver cirrhosis and portal hypertension is scarce.AIMTo determine plasma levels of PlGF and Nogo-A in patients with liver cirrhosis, CSPH, SPH and potential to predict portal hypertension.METHODSA cohort of 122 patients with hepatitis C virus and/or alcohol-induced liver cirrhosis with characterized hepatic venous pressure gradient (HVPG) were included in the study. Demographic data, medical history, Child-Turcotte-Pugh and Model of End Stage liver disease score, clinical chemistry, liver stiffness values were recorded on the day of the procedure prior HVPG measurement. The degree of portal hypertension was determined by the invasive HVPG measurement. Nogo-A and PlGF plasma levels were evaluated using enzyme linked immunosorbent assay. The control group consisted of 30 healthy age- and sex- matched individuals.RESULTSPeripheral PlGF levels were higher and Nogo-A levels were lower in patients with liver cirrhosis (23.20 vs 9.85; P < 0.0001 and 2.19 vs 3.12; P = 0.004 respectively). There was a positive linear correlation between peripheral levels of PlGF and HVPG (r = 0.338, P = 0.001) and negative linear correlation between the peripheral Nogo-A levels and HVPG (r = -0.267, P = 0.007). PlGF levels were higher in CSPH and SPH (P = 0.006; P < 0.0001) whereas Nogo-A levels were lower (P = 0.01; P < 0.033). Area under the curve for the diagnosis of CSPH for PlGF was 0.68 (P = 0.003) and for Nogo-A - 0.67 (P = 0.01); for SPH 0.714 (P < 0.0001) and 0.65 (P = 0.014) respectively. PlGF levels were higher and Nogo-A levels were lower in patients with esophageal varices (P < 0.05). PlGF cut-off value of 25 pg/mL distinguished patients with CSPH at 55.7% sensitivity and 76.7% specificity; whereas Nogo-A cut-off value of 1.12 ng/mL was highly specific (93.1%) for the diagnosis of CSPH.CONCLUSIONPlasma PlGF levels were higher while Nogo-A levels were lower in patients with liver cirrhosis and portal hypertension. Biomarkers showed moderate predictive value in determining CSPH and SPH.

Somatostatin as Inflow Modulator in Liver-transplant Recipients With Severe Portal Hypertension: A Randomized Trial.

To investigate the safety and efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing liver transplantation (LT) (ClinicalTrials.gov number,01290172). In LT, portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT. Thirty-three patients undergoing LT for ESLD and CSPH were randomized double-blindly to receive somatostatin or placebo (2:1). The study drug was administered intraoperatively as 5-mL bolus (somatostatin: 500 μg), followed by a 2.5 mL/h infusion (somatostatin: 250 μg/h) for 5 days. Hepatic and systemic hemodynamics were measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) was analyzed through histological and protein expression analysis. Twenty-nine patients (18 receiving somatostatin, 11 placebo) were included in the final analysis. Ten patients responded to somatostatin bolus, with a significant decrease in hepatic venous portal gradient (HVPG) and portal flow of -28.3% and -29.1%, respectively. At graft reperfusion, HVPG was lower in patients receiving somatostatin (-81.7% vs -58.8%; P = 0.0084), whereas no difference was observed in the portal flow (P = 0.4185). Somatostatin infusion counteracted the decrease in arterial flow (-10% vs -45%; P = 0.0431). There was no difference between the groups in the severity of IRI, incidence of adverse events, long-term complications, graft, and patient survival. Somatostatin infusion during LT in patients with CSPH is safe, reduces the HVPG, and preserves the arterial inflow to the graft. This study establishes the efficacy of somatostatin as a liver inflow modulator.

Liver stiffness in chronic hepatitis C virus infection.

The severity of liver fibrosis can be assessed noninvasively today by liver stiffness measurements. Vibration-controlled transient elastography, shear wave elastography or magnetic resonance elastography are techniques increasingly used for this purpose. This article presents the recent advances in the use of new techniques for liver fibrosis assessment in chronic hepatitis C: the correlation between liver stiffness values and liver fibrosis estimated by liver biopsies, the prognosis role of liver stiffness values, their usefulness in monitoring the treatment response, in assessing the severity of portal hypertension and in estimating the presence of esophageal varices. Scientific articles from January 2017 to January 2018 were searched in PubMed and PubMed Central databases, using the terms "liver stiffness" and "hepatitis C". The median liver stiffness values measured with different techniques are not identical, so that FibroScan thresholds cannot be used on any other elastographic machine. The higher the liver's stiffness measurement, the higher the liver-related events in patients with chronic hepatitis C. A liver stiffness measurement over 17 kPa could be an independent predictor for the presence of esophageal varices as well as a spleen with a longitudinal span ≥ 15 cm for patients with a value of liver stiffness < 17 kPa. A progressive and persistent decrease in liver stiffness is dependent on sustained virological response achievement. The lack of liver stiffness decrease has been associated with relapsers and a low value of liver stiffness at baseline. Liver stiffness provides clues about the severity and evolution of liver disease.

Early post-liver transplant surgical morbidity in HIV-infected recipients: risk factor for overall survival? A nationwide retrospective study.

The aim of the study was to analyse the risk factors for early surgical complications requiring relaparotomy and the related impact on overall survival (OS) in HIV-infected patients submitted to liver transplantation. Thus a retrospective investigation was conducted on a nationwide multicentre cohort of 157 HIV patients submitted to liver transplantation in six Italian Transplant Units between 2004 and 2014. An early relaparotomy was performed in 24.8% of cases and the underlying clinical causes were biliary leak (8.2%), bleeding (8.2%), intestinal perforation (4.5%) and suspect of vascular complications(3.8%). No differences in terms of prevalence for either overall or cause-specific early relaparotomies were noted when compared with a non-HIV control group, matched for MELD, recipient age, HCV-RNA positivity and HBV prevalence. While in the control group an early relaparotomy appeared a negative prognostic factor, such impact on OS was not noted in HIV recipients. Nonetheless increasing number of relaparotomies were associated with decreased survival. In multivariate analysis, preoperative refractory ascites and Roux-en-Y choledochojejunostomy reconstruction were significant risk factors for early relaparotomy. To conclude, in HIV liver transplanted patients, an increasing number of early relaparotomies because of surgical complications does negatively affect the OS. Preoperative refractory ascites reflecting a severe portal hypertension and a difficult biliary tract reconstruction requiring a Roux-en-Y choledochojejunostomy are associated with increased risk of early relaparotomy.

Incidence, predictive factors and clinical significance of development of portal vein thrombosis in cirrhosis: A prospective study.

The role of portal vein thrombosis (PVT) in the natural history of cirrhosis is controversial. There are few prospective studies validating risk factors for development of PVT. We analysed the incidence, factors associated with PVT development and its influence on cirrhosis decompensations and orthotopic liver transplant (OLT)-free survival. In this prospective observational study between January 2014 and March 2019, 445 consecutive patients with chronic liver disease were screened and finally 241 with cirrhosis included. Factors associated with PVT development and its influence on cirrhosis decompensations and OLT-free survival by time dependent covariate coding were analysed. Majority of patients belonged to Child-Pugh class A 184 (76.3%) and the average MELD score was 10±5. Previous cirrhosis decompensations occurred in 125 (52.1%), 63 (26.1%) were on NSBB and 59 (27.2%) had undergone banding for bleeding prophylaxis. Median follow-up was 29 (1-58)months. Cumulative incidence of PVT was 3.7% and 7.6% at 1 and 3years. Previous decompensation of cirrhosis and low platelet counts but not NSBB independently predicted the development of PVT. During follow-up, 82/236 (34.7%) patients developed cirrhosis decompensations. OLT-free survival was 100% and 82.8% at 3years, with and without PVT respectively. MELD score, but not PVT, independently predicted cirrhosis decompensations (HR 1.14; 95%CI:1.09-1.19) and OLT-free survival (HR 1.16;95%CI:1.11-1.21). Previous decompensations of cirrhosis and thrombocytopenia predict PVT development in cirrhosis suggesting a pathophysiologic role for severity of portal hypertension. PVT development did not independently predict cirrhosis decompensations or lower OLT-free survival.

Predictive Value of Hepatic Venous Pressure Gradient for Graft Hemodynamics in Living Donor Liver Transplantation

The hepatic venous pressure gradient (HVPG) measurement is known to correlate with the severity of portal hypertension in patients with liver cirrhosis. This retrospective study investigated the clinical value of preoperative measurement of HVPG in patients who underwent adult-to-adult living donor liver transplantation (LDLT) and its predictive value for hepatic hemodynamics after graft reperfusion. For this study, 75 patients who underwent adult-to-adult LDLT were divided into 2 groups (HVPG<16mm Hg or HVPG≥16mm Hg) to investigate the correlation between preoperative HVPG and characteristics and surgical outcomes of the patients, including portal vein flow (PVF) and hepatic artery flow (HAF) after graft reperfusion. In total, 35 (46.7%) patients had an HVPG≥16mm Hg. These patients had significantly higher international normalized ratio values, serum creatinine levels, and Model for End-Stage Liver Disease scores compared with the 40 patients with HVPG<16mm Hg. They also had higher rates of variceal bleeding, encephalopathy, and intractable ascites as well as lower serum albumin levels and platelet counts compared with those patients with HVPG<16mm Hg. Portal inflow modulation (PIM) was frequently performed in the patients with HVPG≥16mm Hg compared with those with HVPG<16mm Hg. No significant differences in surgical outcomes after LDLT were found between these 2 groups except for postoperative ascites. Preoperative HVPG showed a positive correlation with PVF and a negative correlation with HAF after graft reperfusion (false discovery rate [FDR] P=0.08 and FDR P=0.08, respectively). In linear regression analyses, preoperative HVPG was independently associated with PVF after graft reperfusion. In conclusion, our findings indicate that preoperative HVPG is associated with hepatic hemodynamics after graft implantation in LDLT. HVPG as a routine preoperative evaluation may be helpful for surgical planning of PIM.

Su1566 – Doppler Ultrasound Hepatic Vein Waveform As a Non-Invasive Tool in the Assessment of Severity of Portal Hypertension (DPH Trial)

Su1566 – Doppler Ultrasound Hepatic Vein Waveform As a Non-Invasive Tool in the Assessment of Severity of Portal Hypertension (DPH Trial)

A different gut microbiome linked to inflammation found in cirrhotic patients with and without hepatocellular carcinoma

Introduction and aimA pro-oncogenic intestinal microbiome was observed in murine models; however, no specific microbiome in patients with hepatocellular carcinoma (HCC) has been reported. We aimed to compare the gut microbiome found in cirrhotic patients with or without HCC. Materials and methodsFrom 407 patients with Child Pugh A/B cirrhosis prospectively followed, 25 with HCC (cases) were matched with 25 without HCC (wo-HCC) in a 1:1 ratio according to age, gender, etiology, Child Pugh and severity of portal hypertension. In addition, results were also compared with 25 healthy subjects. Fecal stool samples were sequenced for the V3–V4 region of the microbial 16S rRNA (Illumina MiSeq Platform). Plasma cytokines were quantified including interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). ResultsWe found a differential abundance in family members of Firmicutes with a 3-fold increase of Erysipelotrichaceae and a 5-fold decrease in family Leuconostocaceae in HCC when compared to wo-HCC controls. Genus Fusobacterium was found to be 5-fold decreased in HCC vs wo-HCC. The ratio bacteriodes/prevotella was increased in HCC. Three operational taxonomic units (OTUs), genus Odoribacter and Butyricimonas were more abundant in HCC, whereas a decreased abundance in Lachnospiraceae family genus Dorea was observed in HCC patients. A Random Forest model trained with differential abundant taxa correctly classified HCC individuals. This pattern was associated with an inflammatory milieu with a putative increased activation of NOD-like receptor pathways. ConclusionWe found a pattern of microbiome linked to inflammation that could be potentially useful as HCC biomarker after follow-up validation studies.

HVPG Measurements as a Surrogate of Clinical Events in Cirrhosis: Experience from Clinical Trials

Update current knowledge of the use of hepatic venous pressure gradient (HVPG) as a predictor of clinical events and of efficacy of therapy for portal hypertension. HVPG is a good predictor of clinical events. Decrease in HVPG during therapy is accompanied by a decreased incidence of complications from portal hypertension and improved survival. HVPG measurements are a valuable tool in the management of portal hypertension in cirrhosis. In addition of detecting and grading the severity of portal hypertension, HVPG measurements provide robust prognostic information on the risk of complications, disease progression/regression, and survival. Changes in HVPG in response to therapy predict the effects on clinical outcomes, both during treatment with beta-blockers and when treating HCV-related cirrhosis with specific antivirals. This has led to suggest that HVPG can be used as a surrogate for clinical events when developing new therapies for portal hypertension. Limitations of this approach are discussed.

Successful surgical treatment for intrahepatic arterioportal fistula with severe portal hypertension: a case report

BackgroundIntrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension. Interventional radiology (IVR) is generally selected as the first-line therapeutic option. Surgical treatment for IAPF is required in refractory cases of IVR. As the treatment success rate with IVR is high, cases requiring surgical treatment are extremely rare.Case presentationA 54-year-old man was admitted to another hospital complaining of hematemesis due to rupture of the esophageal varices. A computed tomography revealed ascites and arterioportal fistula in the left lobe of the liver. Transcatheter arterial embolization (TAE) was performed to occlude the fistula; however, it could not reach complete occlusion. Thereafter, there were a total of four hematemeses, and six endoscopic variceal ligations were required. The second TAE also failed to reach complete occlusion. He was transferred to our hospital for further treatment. Because liver function was low due to frequent hematemeses and there was also uncontrollable ascites, it was confirmed that hepatectomy could not be performed safely at this time. Therefore, we ligated the left portal branch and ligated and dissected the left gastric vein to decrease portal vein pressure. However, on the 5th day after surgery, the esophageal varices reruptured. As the disappearance of ascites was observed in the postoperative course and the general condition also improved, left hepatectomy was performed to remove IAPF. There was no recurrence of portal hypertension for 1 year and 3 months since hepatectomy.ConclusionsThis case was difficult to treat with IVR and required surgical treatment. Our experience in the present case suggests that hepatectomy to remove arterioportal fistula was considered effective for improving portal hypertension due to IAPF. However, careful treatment selection according to the patient’s overall condition and clinical course is necessary for IAPF presenting with severe portal hypertension.

FRI-117-The gain of function mutation of SerpinB3 (SCCA-PD) is associated with the severity of portal hypertension and complications onset in patients with advanced liver disease

FRI-117-The gain of function mutation of SerpinB3 (SCCA-PD) is associated with the severity of portal hypertension and complications onset in patients with advanced liver disease

LBO-01-Multicenter, double-blind, placebo-controlled, randomized trial of emricasan in subjects with NASH cirrhosis and severe portal hypertension

LBO-01-Multicenter, double-blind, placebo-controlled, randomized trial of emricasan in subjects with NASH cirrhosis and severe portal hypertension

Endoscopic injection sclerotherapy for pediatric bleeding esophageal varices complicated by gastric vein, main portal vein, splenic mesenteric junction, and splenic vein occlusion: a case report

BackgroundEndoscopic injection sclerotherapy (EIS) is a life-saving procedure for pediatric patients with bleeding gastric varices (GV) associated with advanced liver cirrhosis and severe portal hypertension. Because of the lack of an endoscopic banding ligation device for pediatric patients, EIS is usually performed for bleeding esophageal varices (EV) in infants with congenital biliary atresia.Case presentationWe present a case of a 15-month-old female infant with type I biliary atresia with jaundice (total serum bilirubin, 22.2 mg/dL), hypoalbuminemia (serum albumin level, 2.58 g/dL), coagulopathy (prothrombin time > 20 s compared with that of a normal control), ascites, splenomegaly, portal hypertension (portal vein velocity, 3.9–5.6 cm/sec of hepatopetal flow), and repeated bleeding of the varices after receiving three doses of intravascularly administered Histoacryl 1 ampoule mixed with Lipiodol UF 8 mL in the EV. Prominent GV and EV were occluded by EIS. The sclerosing agent was also present in the main portal vein, splenic mesenteric junction, and splenic vein, causing an engorged inferior mesenteric vein. The patient underwent total hepatectomy and living donor liver transplantation (LDLT) by left lateral segment graft (segments 2, 3, and 4 of the middle hepatic vein trunk) and left portal vein graft to the recipient inferior mesenteric vein anastomosis. Portal vein stent placement via segment 4 of the portal vein stump was performed from the inferior mesenteric vein to the umbilical portion of the left portal vein. The patient is still alive and doing well after the LDLT.ConclusionsEIS is a life-saving procedure in cases involving bleeding EV complicated by gastric, main portal vein, splenic mesenteric junction, and splenic vein occlusions; hence, it should be kept in mind as a treatment for EV complications in pediatric patients.