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.

Future Therapies of Hepatic Encephalopathy.

Hepatic encephalopathy, either covert or overt, affects more than half of patients with cirrhosis and has lasting effects even after portal hypertension is corrected. Unfortunately, the current therapeutic options still result in high rates of relapse and progression, in part owing to cost barriers and side effects, leading to poor adherence. This review summarizes emerging treatment options, which could take advantage of alternative disease pathways to improve future care of those with hepatic encephalopathy.

Combined Spontaneous Portosystemic Shunt Embolization and Transjugular Intrahepatic Portosystemic Shunt Creation for Treatment of Hepatic Encephalopathy.

This retrospective case series assessed the early effectiveness of combined spontaneous portosystemic shunt (SPSS) embolization and preemptive transjugular intrahepatic portosystemic shunt (TIPS) creation for alleviation of medically refractory hepatic encephalopathy (HE) and prevention of portal hypertension complications in patients with liver cirrhosis. Eight patients with liver cirrhosis (5 men and 3 women; mean age, 61 years [SD ± 10]) and HE (overt [West-Haven Grade 2-4], n = 7; covert [West-Haven Grade 1], n = 1) refractory to lactulose and rifaximin therapy who underwent concurrent or staged SPSS embolization and TIPS creation between 2018 and 2022 were included in this study. The primary outcomes were 3-month improvement in HE and postprocedural HE-related hospitalizations. HE improvement was achieved in 7 (87.5%) of 8 cases. Among all patients, there was 1 HE-related hospitalization within 90 days that responded to repeat embolization with no further admissions. No patients developed new ascites, variceal hemorrhage, or other portal hypertension complications within 3 months.

Portal hypertension in patients with nonalcoholic fatty liver disease: Current knowledge and challenges.

Portal hypertension (PH) has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease (NAFLD). However, recent studies have provided evidence that PH may develop in earlier stages of NAFLD, suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis. The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning, leading to the compression of liver sinusoids. External compression and intra-luminal obstacles cause mechanical forces such as strain, shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways, resulting in endothelial dysfunction and the development of fibrosis. The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD. Thus, current diagnostic methods such as hepatic venous pressure gradient (HVPG) measurement tend to underestimate portal pressure (PP) in NAFLD patients, who might decompensate below the HVPG threshold of 10 mmHg, which is traditionally considered the most relevant indicator of clinically significant portal hypertension (CSPH). This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients. In theory, the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component, but more investigations are needed to test its clinical utility for this indication. Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment. Lifestyle change remains the cornerstone of the treatment of PH in NAFLD, together with correcting the components of metabolic syndrome, using nonselective beta blockers, whereas emerging candidate drugs require more robust confirmation from clinical trials.

Management of Sinistral Portal Hypertension after Pancreaticoduodenectomy.

BACKGROUND: Sinistral, or left-sided, portal hypertension (SPH) is a rare cause of upper gastrointestinal (GI) hemorrhage resulting from obstruction of the splenic vein. Venous drainage from the spleen via collaterals can result in venous hemorrhage into both the retroperitoneal and intra-abdominal spaces due to increased venous blood pressure in peripancreatic and gastroduodenal vasculature. SPH can occur secondary to pancreatitis with thrombosis of the splenic vein. Another possible cause is the surgical ligation of the splenic vein as part of pancreaticoduodenectomy (PD). Although splenectomy has been traditionally considered as the treatment of choice to relieve venous hypertension, individual concepts for each patient have to be developed. Considering the venous collateral drainage pathways, a comprehensive approach involving surgical, endoscopic, and interventional radiology interventions may be necessary to address the underlying cause of variceal bleeding. Among these approaches, splenic artery embolization (SAE) has demonstrated efficacy in mitigating the adverse effects associated with elevated venous outflow pressure. SUMMARY: This review summarizes key imaging findings in SPH patients after PD and highlights the potential of minimally invasive embolization for curative treatment of variceal hemorrhage. KEY MESSAGES: (i) SPH is a potential consequence after major pancreas surgery. (ii) Collateral flow can lead to life-threatening abdominal bleeding. (iii) Depending on the origin and localization of the bleeding, a dedicated management is required, frequently involving interventional radiology techniques.

Managing cirrhosis with limited resources: perspectives from sub-Saharan Africa.

Cirrhosis represents the end stage of chronic liver disease. Sub-Saharan Africa, a resource-constrained region, has a high burden of chronic liver disease, with causes including chronic viral hepatitis, excessive alcohol use, and metabolic dysfunction-associated steatotic liver disease (MASLD), the risk of which is burgeoning. The development of liver cirrhosis predicts for morbidity and mortality, driven by both liver dysfunction and the consequences of portal hypertension. Compensated cirrhosis portends a better prognosis than decompensated cirrhosis, highlighting the need for the early diagnosis of cirrhosis and its causes. With resource challenges, the diagnosis and management of cirrhosis is demanding, but less costly and less invasive interventions with substantial benefits, ranging from simple blood tests to transient elastography, are feasible in such settings. Simple interventions are also available to manage the complex manifestations of decompensation, such as ß blockers in variceal bleeding prophylaxis, salt restriction and appropriate diuretic use in ascites, and lactulose and generic rifaximin in hepatic encephalopathy. Ultimately, managing the underlying causative factors of liver disease is key in improving prognosis. Management demands expanded policy interventions to increase screening and treatment for hepatitis B and C and reduce alcohol use and the metabolic factors driving MASLD. Furthermore, the skills needed for more specialised interventions, such as transjugular intrahepatic portosystemic shunt procedures and even liver transplantation, warrant planning, increased capacity, and support for regional centres of excellence. Such centres are already being developed in sub-Saharan Africa, demonstrating what can be achieved with dedicated initiatives and individuals.

Endoscopic procedures in hepatology: Current trends and new developments.

Gastrointestinal endoscopy has long been a reliable backbone in the diagnosis and management of hepatobilary disorders and their complications. However, with evolving non-invasive testing, personalised medicine has reframed the utility and necessity of endoscopic screening. Conversely, the growing interest and use of endoscopic ultrasound (EUS) and advanced endoscopy within gastrointestinal units has also opened novel diagnostic and therapeutic avenues for patients with various hepatobiliary diseases. The integration of "advanced endoscopy" within the practice of hepatology is nowadays referred to as "endo-hepatology". In essence, endo-hepatology consists of two pillars: one focusing primarily on disorders of the liver parenchyma, vascular disorders, and portal hypertension, which is mainly captured via EUS, while the other targets the hepatobiliary tract via endoscopic retrograde cholangiopancreatography and advanced imaging. Applications under the umbrella of endo-hepatology include, amongst others, EUS-guided liver biopsy, EUS-guided portal pressure gradient measurement, coil and glue embolisation of gastric varices as well as cholangioscopy. As such endo-hepatology could become an attractive concept wherein advanced endoscopy might reinforce the medical management of patients with hepatobiliary disorders and their complications after initial basic work-up. In this review, we discuss current trends and future developments within endo-hepatology and the remaining hurdles to overcome.

Perioperative proximal splenic artery embolization in cirrhotic patients with splenomegaly.

INTRODUCTION: The purpose of this study was to determine the effect of proximal splenic artery embolization (SAE) in cirrhotic patients with splenomegaly who underwent surgical laparotomy. MATERIAL AND METHODS: This retrospective observational study included 8 cirrhotic patients with splenomegaly. They underwent proximal SAE before- (n = 6) or after (n = 2) laparotomy. Vascular plugs or coils were placed in the proximal splenic artery. The diameter of the portal vein and the splenic volume were recorded. Clinical outcome assessments included platelet counts, the model for end-stage liver disease (MELD) score, and complications. RESULTS: After embolization, the portal venous diameter was significantly smaller (pre: 13.6 ± 2.7 mm, post: 12.5 ± 2.3 mm, p = 0.023), the splenic volume was significantly decreased (pre: 463.2 ± 145.7 ml, post: 373.3 ± 108.5 ml, p = 0.008) and the platelet count was significantly higher (pre: 69.6 ± 30.8 × 103/µl, post: 86.8 ± 27.7 × 103/µl, p = 0.035). Before embolization, the median MELD score was 12; after embolization, it was 11 (p = 0.026). No patient developed post-treatment complications after embolization. CONCLUSIONS: The reduction of hypersplenism by perioperative proximal SAE may be safe and reduce the surgical risk in cirrhotic patients with splenomegaly.

Portal hypertension and variceal bleeding in patients with liver cancer: Evidence gaps for prevention and management.

BACKGROUND AND AIMS: Portal hypertension (PHT) and HCC are 2 major complications of cirrhosis that often coexist in the same patient and impact the prognosis, especially in patients with acute variceal bleeding. In this review, we aim to discuss the best strategy for PHT screening and primary prophylaxis, as well as the management of acute variceal bleeding, to improve the management of PHT in HCC patients. RESULTS: Recent therapeutic advances observed in the management of HCC, notably through the advent of immunotherapy, have led to a clear improvement in the survival of patients. The prevention of complications related to underlying cirrhosis, such as PHT and acute variceal bleeding, is now part of the management of HCC patients. The Baveno VII conference recently redefined screening and prophylaxis in patients with cirrhosis. However, data regarding the applicability of these criteria in patients with HCC have been sparse. From our point of view, the Baveno criteria are not appropriate to exclude high-risk esophageal varices (EV) in HCC patients, and endoscopy should be performed except in HCC patients with a liver stiffness measurement (LSM) ≥25 kPa, who should benefit from nonselective beta-blockers (NSSBs) without performing endoscopy. We are also in favor of using NSBBs as primary prophylaxis in patients with EV regardless of the size and with gastric varices since these patients display clinically significant PHT. CONCLUSIONS: Appropriate evaluation and treatment of PHT remain major issues in improving the outcomes of HCC patients. Many questions remain unanswered, opening the field to many areas of research.

Outcomes of Transjugular Intrahepatic Portosystemic Shunt and Gastric Coronary Vein Embolization for Variceal Bleeding in Cirrhotic Portal Hypertension.

Purpose: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with gastric coronary vein embolization (GCVE) for cirrhotic portal hypertensive variceal bleeding and compare outcomes of first-line with second-line treatment, coil with glue, and single-covered with double stents.Methods: Fifteen patients received TIPS plus GCVE as the first-line treatment for secondary prophylaxis of variceal bleeding, and 45 received it as second-line treatment. Preoperative and postoperative quantitative variables were compared using a paired t test. The incidence of survival rate, re-bleeding, hepatic encephalopathy, and shunt dysfunction were analyzed using the Kaplan-Meier method.Results: The portal venous pressure was significantly decreased from 39.0 ± 5.0 mm Hg to 22.5 ± 4.4 mm Hg (P≤0.001) after TIPS treatment. After 1, 3, 6, 12, 18, and 24 months re-bleeding rates were 1.6%, 3.3%, 6.6%, 13.3%, 0%, and 0%, respectively. Shunt dysfunction rates were 5%, 0%, 10%, 16.6%, 1.6%, and 5%, respectively. Hepatic encephalopathy rates were 3.3%, 1.6%, 3.3%, 6.6%, 0%, and 0%, respectively. And survival rates were 100%, 100%, 100%, 96.6%, 93.3%, and 88.3% respectively. In comparative analysis, statistically significant differences were seen in re-bleeding between the first-line and second-line treatment groups (26.6% vs 24.4%, log-rank P=0.012), and survival rates between single-covered and double stent (3.7% vs 16.1%, log-rang (P=0.043).Conclusion: The results suggest that TIPS combined with GCVE is effective and safer in the treatment of cirrhotic portal hypertensive variceal bleeding. The use of TIP plus GCVE as first-line treatment, may be preferable for high-risk re-bleeding, and more than 25 mm Hg portal venous pressure with repeated variceal bleeding. However, the sample size was small. Therefore, large, randomized, controlled, multidisciplinary center studies are needed for further evaluation.

Long-Term Impact of Direct-Acting Antivirals on Liver Fibrosis and Survival in HCV-Infected Liver Transplant Recipients.

(1) Background: Little is known about the long-term impact of sustained virological response (SVR) on fibrosis progression and patient survival in liver transplantation (LT) recipients treated with direct-acting antivirals (DAAs). We investigated liver fibrosis evolution and patient survival in hepatitis C virus (HCV)-infected patients receiving DAAs after LT. (2) Methods: All consecutive HCV-infected patients treated with DAAs after LT between May 2014 and January 2019 were considered. The clinical and virological features were registered at the baseline and during the follow-up. The liver fibrosis was assessed by liver biopsy and/or transient elastography (TE) at the baseline and at least 1 year after the end of treatment (EoT). (3) Results: A total of 136 patients were included. The SVR12 was 78% after the first treatment and 96% after retreatment. After the SVR12, biochemical tests improved at the EoT and remained stable throughout the 3-year follow-up. Liver fibrosis improved after the SVR12 (p < 0.001); nearly half of the patients with advanced liver fibrosis experienced an improvement of an F ≤ 2. The factors associated with lower survival in SVR12 patients were the baseline platelet count (p = 0.04) and creatinine level (p = 0.04). (4) Conclusions: The long-term follow-up data demonstrated that SVR12 was associated with an improvement in hepatic function, liver fibrosis, and post-LT survival, regardless of the baseline liver fibrosis. The presence of portal hypertension before the DAAs has an impact on patient survival, even after SVR12.

Management of Portal Hypertension in Patients with Acute-on-Chronic Liver Disease.

Portal hypertension is central to the pathogenesis of complications of cirrhosis, including acute-on-chronic liver failure (ACLF). Both nonselective beta-blockers and preemptive transjugular portal-systemic stent shunt can lower portal pressure, reducing the risk of variceal bleeding, a known trigger for ACLF. However, in patients with advanced cirrhosis, both could potentially induce ACLF by causing hemodynamic instability and hepatic ischemia, respectively, and therefore must be used with caution. Lowering portal pressure with vasoconstrictor such as terlipressin can reverse the kidney failure but careful patient selection is key for success, with careful monitoring for complications.

Austrian consensus on the diagnosis and management of portal hypertension in advanced chronic liver disease (Billroth IV).

The Billroth IV consensus was developed during a consensus meeting of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) and the Austrian Society of Interventional Radiology (ÖGIR) held on the 26th of November 2022 in Vienna.Based on international recommendations and considering recent landmark studies, the Billroth IV consensus provides guidance regarding the diagnosis and management of portal hypertension in advanced chronic liver disease.

Clinical manifestations and approach to the management of patients with common variable immunodeficiency and liver disease.

Purpose: The clinical spectrum of common variable immunodeficiency (CVID) includes predisposition to infections, autoimmune/inflammatory complications and malignancy. Liver disease is developed by a proportion of patients with CVID, but limited evidence is available about its prevalence, pathogenesis and prognostic outcome. This lack of evidence leads to the absence of guidelines in clinical practice. In this study, we aimed at defining the characteristics, course and management of this CVID complication in Spain. Methods: Spanish reference centers were invited to complete a cross-sectional survey. Thirty-eight patients with CVID-related liver disease from different hospitals were evaluated by a retrospective clinical course review. Results: In this cohort, abnormal liver function and thrombocytopenia were found in most of the patients (95% and 79% respectively), in keeping with the higher incidence of abnormal liver imaging and splenomegaly. The most common histological findings included nodular regenerative hyperplasia (NRH) and lymphocytic infiltration, which have been associated with portal hypertension (PHTN) leading to a poorer prognosis. Autoimmune/inflammatory complications occurred in 82% of the CVID patients that developed liver disease and 52% of the patients treated with immunomodulators showed a reduction in the liver function tests' abnormalities during treatment. Among the experts that conducted the survey, there was 80% or more consensus that the workup of CVID-related liver disease requires liver profile, abdominal ultrasound and transient elastography. The majority agreed that liver biopsy should be essential for diagnosis. There was 94% consensus that endoscopic studies should be performed in the presence of PHTN. However, there was 89% consensus that there is insufficient evidence on the management of these patients. Conclusion: Liver disease varies in severity and may contribute substantially to morbidity and mortality in patients with CVID. Hence the importance of close follow-up and screening of this CVID complication to prompt early targeted intervention. Further research is needed to evaluate the pathophysiology of liver disease in patients with CVID to identify personalized treatment options. This study emphasizes the urgent need to develop international guidelines for the diagnosis and management of this CVID complication.

Large left varicocele in a patient with portal hypertension treated via transjugular intrahepatic portosystemic shunt placement and both variceal and varicocele embolization.

BACKGROUND: Scrotal swelling from varicocele is a common complaint in adult men. Varicocele due to portosystemic collaterals is a rare presentation of portal hypertension. Imaging workup and intervention for varicocele in this case is more complex than varicocele due to absent or incompetent valves in the testicular veins and pampiniform plexus. CASE PRESENTATION: We present the case of a 53-year-old man with alcohol-related cirrhosis presented with persistent left scrotal heaviness, pain, and swelling found to have a large left varicocele. Given his history of cirrhosis, a contrast-enhanced CT of the abdomen and pelvis was obtained showing that the varices were supplied by a vessel arising from the splenic vein and draining into the left renal vein as well as gastric varices. Varicocele embolization alone is not sufficient in this case, and we treated with transjugular intrahepatic portosystemic shunt, variceal and varicocele embolization. CONCLUSION: In patients presenting with a varicocele with a history of cirrhosis/portal hypertension, cross sectional imaging of the abdomen and pelvis should be obtained prior to treatment to evaluate for the presence of varices which may be pressured by varicocele embolization. If present, consideration should be given to referral to an interventional radiologist for possible concurrent variceal embolization and TIPS placement.

Attach importance to the individualized treatment of adult portal hypertension based on etiology and pathogenesis: A review.

There are many factors that can cause portal hypertension and secondary symptoms such as ascites, splenomegaly, and variceal hemorrhage, can seriously affect patients' quality of life and even threaten their lives. In this paper, we summarize various causes of portal hypertension based on etiology and pathogenesis and give individualized treatment strategies in order to remind clinicians to pay attention to the identification of different causes and select corresponding treatment, so that patients are provided with the optimal treatment strategies and benefit from them.

Liver Cirrhosis and Portal Hypertension: How to Deal with Esophageal Varices?

The understanding of pathogenesis of portal hypertension in patients with liver cirrhosis continues to evolve. In addition to progressive fibrosis, cirrhosis is characterized by parenchymal extinction and vascular remodelling, causing architectural distortion. Existence of prothrombotic state and more recently, intestinal bacterial dysbiosis are recently described in the pathogenesis of portal hypertension. Clinically significant portal hypertension (CSPH) is an important prognostic milestone in patients with liver cirrhosis. This is a pre-symptomatic phase that predicts the development of varices, ascites and importantly increased risk of Hepatocellular carcinoma (HCC). CSPH is associated with significantly reduced survival. Endoscopic surveillance is necessary in these patients. Non-selective Beta-blocker is the preferred therapy for primary prophylaxis in the management of portal hypertension. Patients with acute variceal bleed should be resuscitated appropriately, followed by vasoactive drugs and endoscopic therapy. Early TIPS should be considered in those with refractory bleed or in endoscopic treatment failure. Application of artificial intelligence and machine learning may be useful in future for identifying patients at risk of variceal hemorrhage.

Cirrhosis and Portal Hypertension: How Do We Deal with Ascites and Its Consequences.

Ascites is the most common complication of cirrhosis, with 5-year mortality reaching 30%. Complications of ascites (ie, spontaneous bacterial peritonitis, hepatorenal syndrome, recurrent/refractory ascites, and hepatic hydrothorax) further worsen survival. The development of ascites is driven by portal hypertension, systemic inflammation, and splanchnic arterial vasodilation. Etiologic treatment and nonselective beta-blockers can prevent ascites in compensated cirrhosis. The treatment of ascites is currently based on the management of fluid overload (eg, diuretics, sodium restriction, and/or paracenteses). In selected patients, long-term albumin use, norfloxacin prophylaxis, and transjugular intrahepatic portosystemic shunt reduce the risk of further decompensation and improve survival.