Modulation of the gut microbiome could favorably alter the hepatic venous pressure gradient (HVPG) in cirrhosis and portal hypertension (PH).
This meta-analysis was to evaluate the effects of microbiome-targeted therapies (MTTs) on HVPG in persons with cirrhosis and PH.
PubMed, The Cochrane Library, Embase, Web of Science and Scopus were searched for randomized clinical trials (RCTs) analyzing the effects on HVPG in people with cirrhosis who received MTTs. Clinical outcomes were pooled using RevMan5.3 software. A trial sequential analysis was applied to calculate the required information size and evaluate the credibility of the meta-analysis results.
A total of six studies were included. MTTs were associated with a reduction of 1.22 mm Hg in HVPG (95% CI: -2.31, -0.14 mmHg, P = 0.03). Subgroup analysis showed a greater reduction with longer duration (-1.88 mmHg;95% CI: -3.23, -0.53; P = 0.006). In the trial sequential analysis of HVPG reduction, the cumulative Z curve crossed the traditional significance boundary without the achievement of required information size (330).
MTTs may be associated with a reduction in HVPG in patients with cirrhosis and PH. Microbiome-targeted therapies merit additional large-sample studies to define the efficacy of HVPG.
PROSPERO 2020: CRD4202021609.

OBJECTIVE: Liver stiffness measurement using transient elastography (TE-LSM) is a promising noninvasive alternative to hepatic venous pressure gradient (HVPG) for diagnosing clinically significant portal hypertension (CSPH). However, previous studies have yielded conflicting results. We evaluated the correlation between TE-LSM and HVPG and the performance of TE-LSM in diagnosing CSPH (HVPG ≥ 10 mmHg).
METHODS: We conducted a systematic review and meta-analysis by searching PubMed and Scopus databases for relevant literature evaluating the clinical usefulness of TE for diagnosing CSPH in patients with chronic liver disease.
RESULTS: Twenty-six studies (4337 patients with valid TE and HVPG) met our inclusion criteria. The median correlation coefficient of TE with HVPG was 0.70 (range 0.36-0.86). The weighted mean of optimal cut-off of liver stiffness value for diagnosing CSPH was 22.8 kPa (95% CI 22.7-23.0 kPa). The summary sensitivity and specificity were 79% (95% CI 74-84%) and 88% (95% CI 84-91%), respectively. The area under the hierarchical summary receiver operating characteristic (HSROC) curve was 0.91 (95% CI 0.88-0.93) according to the bivariate model. One limitation of the study was significant heterogeneity in the results of summary sensitivity and specificity (I2 83 and 74%, respectively). The heterogeneity could be explained by the variable liver stiffness cut-offs used in studies. The meta-regression plot revealed that as the optimal cut-off increased, the sensitivity decreased, the specificity increased, and vice versa.
CONCLUSIONS: Liver stiffness measurement using TE correlates well with HVPG, and a liver stiffness cut-off value of 22.8 kPa shows a high accuracy for diagnosing CSPH. Thus, use of TE should be integrated into clinical practice for noninvasive diagnosis of CSPH.

Introduction: Small-for-size graft and consequently small-for-size syndrome (SFSS) is an important issue for adult living donor liver transplantation (LDLT). The optimal intra- and postoperative prevention and management strategies for SFSS remain unclear. We aimed to analyse and compare the existing strategies of portal inflow modulation (PIM) and conduct a meta-analysis of studies comparing various PIMs. The primary outcome was the incidence SFSS. Methods: The Google Scholar, Embase, PubMed, and Cochrane Library databases were systematically searched. Both fixed-and random-effects models were used to perform the meta-analysis. Results: Twenty-five studies were selected from a pool of 830 studies, of which 13 compared available surgical techniques between cohorts with and without PIM, and 12 reported outcomes of patients who underwent LDLT and developed SFSS. The incidence rate of SFSS was significantly lower in the PIM cohort than in the non-portal inflow modulation (NPIM) cohort. One-year overall survival (OS) and the re-transplantation rate were significantly better in the PIM cohort than in the NPIM cohort. Conclusion: In LDLT patients diagnosed during the reperfusion period with increased portal venous pressure and/or flow, application of PIM significantly decreased the incidence rate of SFSS and demonstrated significantly better one-year OS.

BACKGROUND: The small-for-size syndrome (SFSS) is characterized by prolonged hyperbilirubinemia, coagulopathy, and/or encephalopathy caused by a small liver graft that cannot sustain the metabolic demands of the recipient after a partial liver transplant (PLT). Models of PLT in pigs are excellent for studying this syndrome. This review aimed to identify the different porcine models of SFSS in the literature and compare their technical aspects and therapeutics methods focused on portal inflow modulation (PIM).
METHODS: We performed a systematic review of the porcine experimental model and SFSS. The MEDLINE-PubMed, EMBASE, Cochrane Library, LILACS, and SciELO databases were electronically searched and updated until June 20, 2021. The MeSH terms used were \'\'ORGAN SIZE\'\' AND \'\'LIVER TRANSPLANTATION\".
RESULTS: Thirteen SFSS porcine models were reported. Four were performed with portocaval shunt to PIM and 3 with mesocaval shunt to PIM. A few studies focused on clinical therapeutics to PIM; a study described somatostatin infusion to avoid SFSS. Initially, studies on PIM showed its potentially beneficial effects without mentioning the minimum portal flow that permits liver regeneration. However, an excessive portal diversion could be detrimental to this process.
CONCLUSIONS: The use of porcine models on SFSS resulted in a better understanding of its pathophysiology and led to the establishment of various types of portal modulation, surgical techniques with different complexities, and pharmaceutical strategies such as somatostatin, making clear that without reducing the portal vein pressure the outcomes are poor. With the improvement of these techniques, SFSS can be avoided.

Centers for the research of patients with pulmonary hypertension (PH) usually perform right cardiac catheterization (RHC) to document this hemodynamic condition; traditionally, the procedure is performed by the interventional cardiologist, while the interventional radiologist generally conducts the study of hepatic hemodynamics. In our center, where the leading cause of catheterization of the hepatic veins is orthotopic liver transplantation, the cardio-pulmonologist performs the procedure to diagnose the possibility of porto-pulmonary hypertension and its implications. Routine measurement of the hepatic venous pressure gradient (HVPG) during RHC is not recommended but is performed to confirm the diagnosis of portal hypertension (PoH). Our objective in this review was to graphically describe the technique of hemodynamic recording of suprahepatic veins in patients with chronic liver disease and PoH who are in liver transplant protocol. The concepts included in this manuscript are measuring portal pressure, the definition of the hepatic venous pressure gradient (HVPG), procedures for a correct measurement of the HVPG, techniques associated with a suprahepatic vein catheterization, contraindications, and complications of HVPG, and clinical applications of HVPG. Clinically significant PoH is defined as an increase in GPVH ≥10 mmHg. HVPG measurement is currently the best available method for assessing the presence and severity of PoH. The RHC is the standard gold method for diagnosing PoPH that confirms its existence and provides additional data to exclude other causes of PAH in liver transplant candidates.

Portal inflow modulation (PIM) aimed at reducing portal hyperperfusion is commonly used in living donor liver transplantation (LDLT) to reduce the risk of small-for-size syndrome (SFSS). Many different techniques, both pharmacological and surgical have been used for this purpose. There is, however, little consensus on the best method of PIM, its exact role in preventing SFSS and on early post-LDLT recovery.
To identify whether modifications of portal pressures and flows enhance recovery after LDLT and to provide international expert panel recommendations.
Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central.
Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel.
CRD42021260997.
Five hundred and ninety four articles were identified through databases\' search. Of the 24 included for a final review by the working group (WG), there were five randomized control trials, four prospective studies and 15 retrospective series. Six outcome measures which were likely to influence early recovery after LDLT, especially in small-for-size grafts (SFSG) were shortlisted. These included acute kidney injury, SFSS, morbidity including sepsis, length of ICU and hospital stay, morbidity of the PIM technique and overall mortality. The WG noted that PIM in this subset of LDLT recipients had a beneficial effect on all the outcomes measures.
Considering all decision domains, the panel recommends pre- and intraoperative actual graft weight validation, portal pressure/flow measurements, and a comprehensive donor evaluation for the determination of potentially small-for-size/ small-for-flow grafts as mandatory. (Quality of Evidence: Moderate | Grade of Recommendation: Strong) Pharmacological PIM helps improve early renal function in LDLT recipients. (Quality of Evidence: High | Grade of Recommendation: Strong) In selected patients with SFSG, PIM helps reduce SFSS/EAD and sepsis. (Quality of Evidence: Moderate | Grade of Recommendation: Strong) PIM in the form of splenectomy has increased morbidity compared to splenic artery ligation (SAL). (Quality of Evidence: Low | Grade of Recommendation: Strong) In LDLT recipients with SFSG, PIM may help reduce morbidity/mortality. (Quality of Evidence: Low | Grade of Recommendation: Strong) In LDLT recipients with SFSG, modification of portal pressures and flows enhances recovery after LDLT. (Quality of Evidence: Moderate | Grade of Recommendation: Strong).

Portal hypertension (PH) is one of the most severe complications of chronic liver diseases. It is defined as an increase in pressure in the portal venous system which results in a portosystemic gradient >5 mmHg. In the western world, cirrhosis is the most frequent cause of PH, mainly due to nonalcoholic fatty liver disease and alcoholic liver disease. Patients with PH have esophageal varices in 68-73% of cases, portal hypertensive gastropathy in 51-73% and hyperplastic polyps (HPs) in 0.9-2%. Recent studies have shown that HPs found in PH patients are different from classical HPs. They constitute a new entity called portal hypertensive polyps (PHPs). The main difference between sporadic HPs and PHP is the presence of larger and more numerous vascular capillaries in the lamina propria. The clinical course of PHPs is unknown. Their physiopathology seems different from HPs: the increased congestion caused by higher portal pressure in the stomach may induce capillaries proliferation and neoangiogenesis. PHPs may be responsible for symptoms, such as pyloric obstruction, iron deficiency and anemia. Their prevalence in portal hypertensive and cirrhotic patients is from 1% to 8%. PHPs can be single or numerous, in the antrum or the gastric corpus. Their size ranges from 2 to 3 cm. PHPs seem to disappear or shrink with the treatment of PH. They should be resected in case of symptom and if >10 mm, after Helicobacter pylori eradication if present. However, their recurrence is frequent (40-79%), thus surveillance endoscopy is mandatory, at the same time as esophageal varices.

Background-Objectives: It has been reported, that high posthepatectomy portal vein pressure (PVP) has deleterious effect on the liver parenchyma and causes posthepatectomy liver failure (PHLF) and increased 90-day mortality. Terlipressin, is widely used to mitigate the effects of portal hyper-tension. Randomised clinical trials (RCTs) demonstrated encouraging results of use of terlipressin for modulation of increased posthepatectomy PVP. The aim of the present study was to evaluate the effectiveness of the pharmacological modulation of the increased posthepatectomy PVP after major hepatectomy. Methods: Systematic literature searches of electronic databases in accordance with PRISMA was conducted. Meta-analysis was conducted using both fixed- and random-effects models. Results: Three randomised controlled trials (RCTs) comparing terlipressin versus placebo including 284 patients of pooled 60 studies were selected. Placebo cohort patients were significantly younger by 5 years compared to terlipressin cohort. However, the terlipressin cohort demonstrated significantly shorter intensive care unit (ICU) stay compared to placebo cohort. Conclusions: The first meta-analysis demonstrated that terlipressin cohort patients although significantly older by 5 years had significantly shorter ICU stay compared to placebo cohort. Furthermore, though statistically nonsignificant only 6% of terlipressin patients needed inotropic support compared to 16.4% of placebo cohort.

There are evolving data correlating elevated post-hepatic resection portal vein pressure (PVP) with risk of developing post-resection liver failure (PLF) and other complications. As a consequence, modulation of PVP presents a potential strategy to improve outcomes following liver resection (LR). The primary aim of this study was to review the existing evidence regarding the impact of post-resection PVP on clinical outcomes in patients undergoing a LR.
Systematic literature searches of electronic databases in accordance with PRISMA were conducted. Changes in PVP and clinical outcomes following liver resection were defined according to the existing literature.
Ten studies, consisting of 712 patients with a median age 61 (52-68) years, were identified that met the inclusion criteria. Of those, 77% (n = 550) underwent a major LR and 27% (n = 195) of patients had cirrhosis. Following LR, the median (range) PVP increased from 11.4 mmHg (median baseline, range 7.3-16.4) to 15.9 mmHg (7.9-19). The overall median incidence of PLF was 19%. Six of the ten studies found an elevated PVP after LR predicted PLF. One study found elevated PVP after LR predicted mortality after LR.
Elevated PVP following hepatic resection was associated with increased rates of PLF. It was not possible to define a specific threshold PVP for predicting PLF. Modulation of PVP therefore presents a potential strategy to mitigate the incidence of LR. Future studies should standardize on reporting liver remnant and haemodynamics to better characterize clinical outcomes following LR.

The effects of poorly/non-absorbable antibiotics on hepatic venous pressure gradient (HVPG) are debated.
To analyze the effects of rifaximin or norfloxacin on HVPG and on markers of bacterial translocation and proinflammatory cytokines.
We performed a systematic search of randomized clinical trials (RCTs) involving patients with cirrhosis and portal hypertension, assessing the effect of rifaximin or norfloxacin vs control on HVPG. Pooled analyses were based on random-effects models, heterogeneity was assessed by Cochran\'s Q, I2 statistic and subgroup analyses.
Five studies (215 patients) were included. Risk of bias was high in three. We found no significant differences using antibiotics versus control. The summary mean difference in HVPG was of -0.55 mmHg (95%CI:-1.52, 0.42; P = 0.27), with moderate heterogeneity (P = 0.15; I2 = 40%). RCTs with longer therapy (60-90 days) used non-selective-beta-blockers (NSBB) in both antibiotics and control arms. Subgroup analysis showed a significantly greater reduction in HVPG in the combination arm over controls (mean difference -1.46 mmHg [95%CI: -2.63, -0.28; P = 0.01]) with no heterogeneity (P = 0.46; I2 = 0%). Serum lipopolysaccharide-binding protein (LBP) significantly decreased with antibiotics, but with high heterogeneity (P < 0.001; I2 = 92%).
Rifaximin or norfloxacin did not significantly reduce HVPG in patients with cirrhosis and portal hypertension. Studies using antibiotic for longer periods on top of NSBB showed a significant decrease in HVPG.