Porto-sinusoidal Vascular Disease and Portal Hypertension.

Porto-sinusoidal vascular disease (PSVD) is the medical diagnosis for a patient who has portal hypertension in the absence of cirrhosis on liver biopsy. There are several specific histologic findings for PSVD, including obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal fibrosis. Epidemiologic reports vary widely among regions; PSVD comprises less than 10% of causes of portal hypertension in Western countries but incidence has been found to be as high as 48% in India. There is an expansive list of etiologies that have been reported to cause PSVD.

Pulmonary Complications of Portal Hypertension.

Portopulmonary hypertension (POPH), hepatopulmonary syndrome, and hepatic hydrothorax constitute significant complications of portal hypertension, with important implications for management and liver transplantation (LT) candidacy. POPH is characterized by obstruction and remodeling of the pulmonary resistance arterial bed. Hepatopulmonary syndrome is the most common pulmonary vascular disorder, characterized by intrapulmonary vascular dilatations causing impaired gas exchange. LT may improve prognosis in select patients with POPH. LT is the only effective treatment of hepatopulmonary syndrome. Hepatic hydrothorax is defined as transudative pleural fluid accumulation that is not explained by primary cardiopulmonary or pleural disease. LT is the definitive cure for hepatic hydrothorax.

Bleeding Complications of Portal Hypertension.

In portal hypertension, acute variceal bleed is the cause of 2/3rd of all upper gastrointestinal bleeding episodes. It is a life-threatening emergency in patients with cirrhosis. Nonselective beta-blockers by decreasing the hepatic venous pressure gradient are the mainstay of medical therapy for the prevention of variceal bleeding and rebleeding. Evaluation of the severity of bleed, hemodynamic resuscitation, prophylactic antibiotic, and intravenous splanchnic vasoconstrictors should precede the endoscopy procedure. Endoscopic band ligation is the recommended endotherapy. Rescue transjugular intrahepatic port-systemic shunt (TIPS) is recommended for variceal bleed refractory to endotherapy. In patients with a high risk of failure of combined pharmacologic and endoscopic therapy, pre-emptive TIPS may improve the outcome. For gastric varices, "Sarin classification" is universally applied as it is simple and has therapeutic implication. For IGV1 and GOV2, injection cyanoacrylate glue is considered the endotherapy of choice. Endoscopic ultrasound is a useful modality in the management of gastric varices.

Infectious Complications of Portal Hypertension.

Patients with cirrhosis and clinically significant portal hypertension are at high risk of developing bacterial infections (BIs) that are the most common trigger of acute decompensation and acute-on-chronic liver failure. Furthermore, after decompensation, the risk of developing BIs further increases in an ominous vicious circle. BIs may be subtle, and they should be ruled out in all patients at admission and in case of deterioration. Timely administration of adequate empirical antibiotics is the cornerstone of treatment. Herein, we reviewed current evidences about pathogenesis, clinical implications and management of BIs in patients with cirrhosis and portal hypertension.

Renal Complications in Portal Hypertension.

Acute kidney injury (AKI) is a common complication among patients with decompensated cirrhosis and its development is associated with worse prognosis in terms of survival. Patients with decompensated cirrhosis may develop a unique type of AKI, known as hepatorenal syndrome (HRS-AKI), characterized by marked impairment of kidney function due to haemodynamic changes that occur in late stages of liver cirrhosis. Besides, patients with cirrhosis also may develop chronic alterations of kidney function (chronic kidney disease, CKD), the incidence of which is increasing markedly and may be associated with clinical complications. The aim of this review is to provide the reader with an update of the most relevant aspects of alterations of kidney function in patients with cirrhossi that may be useful for theri clinical practice.

Cerebral Aspects of Portal Hypertension: Hepatic Encephalopathy.

Portal hypertension has cerebral consequences via its causes and complications, namely hepatic encephalopathy (HE), a common and devastating brain disturbance caused by liver insufficiency and portosystemic shunting. The pathogenesis involves hyperammonemia and systemic inflammation. Symptoms are disturbed personality and reduced attention. HE is minimal or grades I to IV (coma). Bouts of HE are episodic and often recurrent. Initial treatment is of events that precipitated the episode and exclusion of nonhepatic causes. Specific anti-HE treatment is lactulose. By recurrence, rifaximin is add-on. Anti-HE treatment is efficacious also for prophylaxis, but emergence of HE marks advanced liver disease and a dismal prognosis.

Congenital hepatic fibrosis with negative endoscopic evaluation of esophageal and gastric varices: A case report.

RATIONAL: Congenital hepatic fibrosis (CHF) is a rare autosomal recessive genetic disease, which is often diagnosed in children and young adults. The clinical manifestations of CHF were lack of specificity, mainly including portal hypertension related symptoms and signs, and normal or mildly abnormal liver function. When no obvious varices are indicated under endoscope, it can easily lead to misdiagnosis or missed diagnosis. We report this case in the hope of raising awareness of this disease. PATIENT CONCERNS: A 31 years old male patient with major clinical manifestations of unexplained thrombocytopenia for 5 years. DIAGNOSES: Results of ultrasound, magnetic resonance imaging (MRI) and computed tomography portal venography (CTV) showed that patient had liver cirrhosis with portal hypertension and liver biopsy revealed CHF. INTERVENTION: Patient received ursodeoxycholic acid tablets, fuzheng huayu capsule, ganshuang granule, etc for liver protection treatment. OUTCOMES: The condition of patient stabilized after symptomatic treatment. Spleen resection will be considered during follow-up. LESSONS: This case reminds us that in case of patients with negative endoscopic evaluation, ultrasonic, computed tomography (CT) and MRI examination should be performed at the same time to determine whether patients have portal hypertension. When patients with normal or mildly abnormal liver function had unexplained liver cirrhosis complicated with portal hypertension, the possibility of CHF should be considered.

Portal hypertension and its prognostic implications in patients with Wilson's disease.

BACKGROUND AND AIMS: Wilson's disease may progress to cirrhosis and clinically significant portal hypertension (CSPH). We aimed to assess the prevalence and prognostic impact of CSPH-related features on hepatic decompensation and transplant-free survival in patients with Wilson's disease. METHODS AND RESULTS: About 137 patients with Wilson's disease (Leipzig score ≥4), followed for a median observation period of 9.0 (3.9-17.7) years at the Vienna General Hospital, were included in this retrospective study. Overall, 49 (35.8%) developed features of CSPH: 14 (10.2%) varices, 40 (29.2%) splenomegaly, 20 (14.6%) ascites, 18 (13.1%) hepatic encephalopathy and 3 (2.2%) experienced acute variceal bleeding. Overall, 8 (5.8%) patients died, including three deaths caused by CSPH-related complications. Within 10 years, compensated patients with features of CSPH developed more decompensation events (8.3% vs. 1.5% in patients without CSPH, p = 0.3) and had worse transplant-free-survival (91.7% vs. 98.6%), which further declined in patients with hepatic decompensation (26.7%, log-rank: p < 0.0001). Patients with liver stiffness <15 kPa and normal platelets (≥150 G/L) were less likely to decompensate within 10 years (2.6% vs. 8.4%, p = 0.002) and had a better 10-year transplant-free-survival (97.7% vs. 83.9%, p = 0.006). CONCLUSIONS: Patients with Wilson's disease developing features of CSPH are at an increased risk for hepatic decompensation and liver-related mortality, warranting for regular screening and timely initiation of effective CSPH-directed treatments.

Outcomes of bariatric surgery in the setting of compensated advanced chronic liver disease associated with clinically significant portal hypertension: a multicenter, retrospective, cohort study on feasibility and safety.

BACKGROUND: The obesity epidemic has led to an increase in the proportion of patients with chronic liver disease due to metabolic associated steatosic liver disease and in the prevalence of obesity in patients with cirrhosis. Metabolic and bariatric surgery (MBS) has been proven to determine weight loss, obesity-related medical problems remission, and liver steatosis, inflammation, and fibrosis improvement. However, cirrhosis and portal hypertension are well-known risk factors for increased morbidity and mortality after surgery. The aim of this study is to evaluate the safety of MBS in patients with compensated advanced chronic liver disease (cALCD) and clinically significant portal hypertension (CSPH). MATERIAL AND METHODS: This is an international, multicentric, retrospective study on 63 individuals affected by obesity with cALCD and CSPH who underwent MBS in tertiary referral centers with experts hepatobiliary surgeons between January 2010 and October 2022. The primary endpoint was postoperative mortality at 90 days. The secondary endpoints included postoperative weight loss at last follow-up and postoperative complication rate. In addition, the authors performed subgroup analyses of Child-Pugh (A vs. B) score, MELD (≤9 vs. >9) score, and type of surgery. RESULTS: One patient (1.6%) experienced gastric leakage and mortality. There were three (5%) reported cases of portal vein thrombosis, two (3%) postoperative acute renal failure, and one (1.6%) postoperative encephalopathy. Child-Pugh score A resulted to be a protective factor for intraoperative bleeding requiring transfusion at univariate analysis (OR: 0.73, 95% CI: 0.55-0.97, P =0.046) but not at multivariate analysis. MELD>9 score and the type of surgery did not result to be a risk factor for any postoperative complication. CONCLUSION: MBS is safe in patients with cALCD and CSPH performed in tertiary bariatric referral centers with hepatobiliary expert surgeons. Larger, prospective studies with longer follow-up periods are needed to confirm these results.

Effect of Probiotics on Portal Hypertension (PH) with Cirrhosis: A Systematic Review and Meta-Analysis.

INTRODUCTION: There are many options for the reduction of portal hypertension (pH) in cirrhotic patients, but all the current ones have side effects. Probiotics are a new approach for ameliorating the hyperdynamic circulation of cirrhotic patients. The aim of this study is to measure the effect of probiotics on pH in cirrhosis for the first time. METHODS: A search was conducted across four electronic databases (PubMed, Scopus, Web of Science, Cochrane) for English-language records evaluating probiotic effects on pH in cirrhotic patients. Quality assessment used the Cochrane Collaboration's tool, employing a random-effects model in statistical analysis with Stata software version 1. RESULTS: A search yielded 1,251 articles, which were narrowed down to 5 through screening. These studies, involving 158 participants across Canada, India, Spain, and Russia, focused on probiotic interventions in cirrhotic patients. Meta-analysis of two RCTs (66 participants) indicated a significant decrease in hepatic venous pressure gradient (HVPG) (SMD: -0.60 [-1.09, -0.12]). In single-arm analysis, four studies (58 participants) showed a substantial reduction in HVPG with probiotic use compared to the control (SMD: -2.55 [-3.42, -1.68]). CONCLUSION: In summary, it showcased a notable reduction in HVPG compared to the control group, indicating a potential advantage of probiotics in decreasing pH in cirrhotic patients. Further research with larger samples and robust designs is warranted.

Does depressurization of the portal vein before liver transplantation affect the recurrence of HCC? A nested case-control study.

BACKGROUND: Portal hypertension (PHT) has been proven to be closely related to the development of hepatocellular carcinoma (HCC). Whether PHT before liver transplantation (LT) will affect the recurrence of HCC is not clear. METHODS: 110 patients with depressurization of the portal vein (DPV) operations (Transjugular Intrahepatic Portosystemic Shunt-TIPS, surgical portosystemic shunt or/and splenectomy) before LT from a HCC LT cohort, matched with 330 preoperative non-DPV patients; this constituted a nested case-control study. Subgroup analysis was based on the order of DPV before or after the occurrence of HCC. RESULTS: The incidence of acute kidney injury and intra-abdominal bleeding after LT in the DPV group was significantly higher than that in non-DPV group. The 5-year survival rates in the DPV and non-DPV group were 83.4% and 82.7% respectively (P = 0.930). In subgroup analysis, patients in the DPV prior to HCC subgroup may have a lower recurrence rate (4.7% vs.16.8%, P = 0.045) and a higher tumor free survival rate (88.9% vs.74.4%, P = 0.044) after LT under the up-to-date TNMI-II stage, while in TNM III stage, there was no difference for DPV prior to HCC subgroup compared with the DPV after HCC subgroup or the non-DPV group. CONCLUSION: Compared with DPV after HCC, DPV treatment before HCC can reduce the recurrence rate of HCC after early transplantation (TNM I-II). DPV before LT can reduce the recurrence of early HCC.

Non-Invasive Diagnostic Tests for Portal Hypertension in Patients with HBV- and HCV-Related Cirrhosis: A Comprehensive Review.

Clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease indicates an increased risk of decompensation and death. While invasive methods like hepatic venous-portal gradient measurement is considered the gold standard, non-invasive tests (NITs) have emerged as valuable tools for diagnosing and monitoring CSPH. This review comprehensively explores non-invasive diagnostic modalities for portal hypertension, focusing on NITs in the setting of hepatitis B and hepatitis C virus-related cirrhosis. Biochemical-based NITs can be represented by single serum biomarkers (e.g., platelet count) or by composite scores that combine different serum biomarkers with each other or with demographic characteristics (e.g., FIB-4). On the other hand, liver stiffness measurement and spleen stiffness measurement can be assessed using a variety of elastography techniques, and they can be used alone, in combination with, or as a second step after biochemical-based NITs. The incorporation of liver and spleen stiffness measurements, alone or combined with platelet count, into established and validated criteria, such as Baveno VI or Baveno VII criteria, provides useful tools for the prediction of CSPH and for ruling out high-risk varices, potentially avoiding invasive tests like upper endoscopy. Moreover, they have also been shown to be able to predict liver-related events (e.g., the occurrence of hepatic decompensation). When transient elastography is not available or not feasible, biochemical-based NITs (e.g., RESIST criteria, that are based on the combination of platelet count and albumin levels) are valid alternatives for predicting high-risk varices both in patients with untreated viral aetiology and after sustained virological response. Ongoing research should explore novel biomarkers and novel elastography techniques, but current evidence supports the utility of routine blood tests, LSM, and SSM as effective surrogates in diagnosing and staging portal hypertension and predicting patient outcomes.

Hyponatremia in the Context of Liver Disease.

Hyponatremia is common in patients with liver disease and is associated with increased mortality, morbidity, and a reduced quality of life. In liver transplantation, the inclusion of hyponatremia in organ allocation scores has reduced waitlist mortality. Portal hypertension and the resulting lowering of the effective arterial blood volume are important pathogenetic factors, but in most patients with liver disease, hyponatremia is multifactorial. Treatment requires a multifaceted approach that tries to reduce electrolyte-free water intake, restore urinary dilution, and increase nonelectrolyte solute excretion. Albumin therapy for hyponatremia is a peculiarity of advanced liver disease. Its use appears to be increasing, while the vaptans are currently only given in selected cases. Osmotic demyelination is a special concern in patients with liver disease. Serial checks of serum sodium concentrations and urine volume monitoring are mandatory.

Outcomes of endoscopic sclerotherapy for jejunal varices at the site of choledochojejunostomy (with video): Three case reports.

BACKGROUND: Hemorrhage associated with varices at the site of choledochojejunostomy is an unusual, difficult to treat, and often fatal manifestation of portal hypertension. So far, no treatment guidelines have been established. CASE SUMMARY: We reported three patients with jejunal varices at the site of choledochojejunostomy managed by endoscopic sclerotherapy with lauromacrogol/α-butyl cyanoacrylate injection at our institution between June 2021 and August 2023. We reviewed all patient records, clinical presentation, endoscopic findings and treatment, outcomes and follow-up. Three patients who underwent pancreaticoduodenectomy with a Whipple anastomosis were examined using conventional upper gastrointestinal endoscopy for suspected hemorrhage from the afferent jejunal loop. Varices with stigmata of recent hemorrhage or active hemorrhage were observed around the choledochojejunostomy site in all three patients. Endoscopic injection of lauromacrogol/α-butyl cyanoacrylate was carried out at jejunal varices for all three patients. The bleeding ceased and patency was observed for 26 and 2 months in two patients. In one patient with multiorgan failure and internal environment disturbance, rebleeding occurred 1 month after endoscopic sclerotherapy, and despite a second endoscopic sclerotherapy, repeated episodes of bleeding and multiorgan failure resulted in eventual death. CONCLUSION: We conclude that endoscopic sclerotherapy with lauromacrogol/α-butyl cyanoacrylate injection can be an easy, effective, safe and low-cost treatment option for jejunal varicose bleeding at the site of choledochojejunostomy.

Association of Cardiopulmonary Hemodynamics and Mortality in Veterans With Liver Cirrhosis: A Retrospective Cohort Study.

BACKGROUND: Portopulmonary hypertension (PoPH), associated with increased mortality, can limit treatment options for liver diseases. Data on the continuum of clinical risk related to cardiopulmonary hemodynamics in PoPH are lacking. METHODS AND RESULTS: As part of the United States national Veterans Affairs Clinical Assessment, Reporting, and Tracking database, we performed a retrospective cohort study of adults with cirrhosis undergoing right heart catheterization between October 1, 2017, and September 30, 2022. Pulmonary hypertension (mean pulmonary arterial pressure [mPAP] >20 mm Hg without PoPH) and PoPH (mPAP >20 mm Hg+pulmonary artery wedge pressure ≤15 mm Hg+pulmonary vascular resistance ≥3 WU) were defined by right heart catheterization hemodynamics. Multivariable Cox proportional hazards using natural splines for hemodynamic variables were used to evaluate the association between cardiopulmonary hemodynamics and mortality following right heart catheterization. A total of 4409 patients were included in the final analysis, predominantly men (96.3%), with a mean age of 68.5 years. Pulmonary hypertension and PoPH were observed in 71.6% and 10.2% of the cohort, respectively. Compared with a reference cardiac index of 2.5 L/min per m2, the hazard for mortality increased progressively with decreasing cardiac index, even after adjustment for mPAP and pulmonary vascular resistance. The minority of patients with PoPH (N=65, 14.5%) were prescribed pulmonary vasodilator therapy. CONCLUSIONS: These data suggest that pulmonary hypertension and PoPH are prevalent in veterans with chronic liver disease, but low use of targeted PoPH therapy persists. Cardiac function discriminated mortality risk across a wide range of mPAP and pulmonary vascular resistance values and may diagnose and clarify prognosis in this patient population.

Prospective evaluation of patients with non-cirrhotic portal hypertension: A single centre study.

BACKGROUND: Non-cirrhotic portal hypertension (NCPH) is a spectrum of liver diseases, including porto-sinusoidal vascular disorder, with portal hypertension (PH) in the absence of cirrhosis. The natural history and diagnostic approach to NCPH are not well understood. AIM: We aimed to evaluate disease progression and outcomes in NCPH. METHODS: Patients with or at risk for NCPH were enrolled in a single centre prospective study; two groups were formed based on the presence of specific features of PH, such as varices, collaterals, portal hypertensive gastropathy or portal hypertensive bleeding. All participants underwent a baseline liver biopsy. Liver stiffness measurement (LSM), and imaging were repeated every 6-12 months. RESULTS: Fifteen patients without specific features of PH (Group I), and 35 patients with specific features (Group II) were enrolled. The median follow-up time was 50 months. Group II had higher hepatic venous pressure gradients, non-invasive measures of PH and a lower platelet count (PLT) when compared to Group I. Rates of survival and decompensation were similar in both groups. Patients with PLT ≤100 K/mcL had lower survival compared to those with PLT >100 K/mcL. Patients with LSM ≥10 kPa had lower survival and survival without decompensation when compared to patients with LSM <10 kPa. CONCLUSIONS: Patients irrespective of specific features of PH had similar survival or survival without decompensation. Patients without specific features are at risk for disease progression and should be monitored closely. Thrombocytopenia and increased LSM are associated with severe forms of liver disease, which are strongly associated with outcomes.