[Thrombosis of portal cavernoma]. / Thrombose du cavernome porte.

Portal cavernoma thrombosis is a complication of portal cavernoma. We describe the case of a 74-year-old patient who presented to the emergency department with abdominal pain. The computed tomography scan showed a mass from the head of the pancreas to the hepatic hilum not enhanced after injection of iodinated contrast. There was no dilatation of the bile ducts. Abdominal magnetic resonance ruled out a tumour and confirmed a portal cavernoma thrombosis. In 50 % of cases the etiology of the portal cavernoma is unknown. It is often asymptomatic. It may be discovered in case of complications of portal hypertension. In rare cases the portal cavernoma can compress the bile ducts. To our knowledge, portal cavernoma thrombosis has only been described in one article. It is important to search for a thrombophilic disorder when such a complication is found. We share this case report in order to raise awareness in the medical community about this rare complication.

La thrombose de cavernome portal est une complication du cavernome porte. Nous décrivons le cas d'un patient de 74 ans qui s'est présenté aux urgences pour des douleurs abdominales. La tomodensitométrie montrait un syndrome de masse de la tête du pancréas jusqu'au hile hépatique non rehaussé après injection de produit de contraste iodé. Il n'y avait pas de dilatation des voies biliaires. Une imagerie par résonance magnétique abdominale a permis d'infirmer l'hypothèse d'une masse tumorale et d'affirmer une thrombose du cavernome porte. Dans 50 % des cas, l'étiologie du cavernome portal est inconnue. Il est souvent asymptomatique. Il peut être découvert en cas de complications à la suite d'une hypertension portale. Dans de rares cas, le cavernome portal peut comprimer les voies biliaires. À notre connaissance, la thrombose de cavernome portal n'a été décrite que dans un seul article. Il est important de rechercher un désordre thrombophilique quand une telle complication est retrouvée. Nous partageons ce cas clinique afin de sensibiliser la communauté médicale à cette rare complication.

Carvedilol to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by liver stiffness: study protocol for a randomied, double-blind, placebo-controlled, multicentre trial in China.

INTRODUCTION: Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%-6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy. METHODS AND ANALYSIS: This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committees of the Sixth People's Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073864.

Management of liver disease and portal hypertension in cystic fibrosis: a review.

INTRODUCTION: Cystic fibrosis (CF)-associated liver disease can significantly affect the quality of life and survival of people with CF. The hepatobiliary manifestations in CF are various, with focal/multilobular biliary cirrhosis more common in children and porto-sinusoidal vascular disease (PSVD) in young adults. Portal hypertensive complications, particularly bleeding from esophagogastric varices and hypersplenism are common, while liver failure is rarer and mainly linked to biliary disease. AREAS COVERED: This review explores current therapeutic options for CF-associated liver disease, presenting ongoing studies and new insights into parthenogenesis for potential future therapies. EXPERT OPINION: Monitoring for signs of portal hypertension is essential. Limited evidence supports ursodeoxycholic acid (UDCA) efficacy in halting CF liver disease progression. The effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on liver outcomes lacks definitive data, since patients with CF-related liver disease were excluded from trials due to potential hepatotoxicity. A proposed approach involves using UDCA and modulators in early stages, along with anti-inflammatory agents, with further therapeutic strategies awaiting randomized trials. Prevention of portal hypertensive bleeding includes endoscopic sclerotherapy or ligation of esophageal varices. Nonselective beta-blockers may also prevent bleeding and could be cautiously implemented. Other non-etiological treatments require investigation.

Advancing hepatic recompensation: Baveno VII criteria and therapeutic innovations in liver cirrhosis management.

The Baveno VII criteria redefine the management of decompensated liver cirrhosis, introducing the concept of hepatic recompensation marking a significant departure from the conventional view of irreversible decline. Central to this concept is addressing the underlying cause of cirrhosis through tailored therapies, including antivirals and lifestyle modifications. Studies on alcohol, hepatitis C virus, and hepatitis B virus-related cirrhosis demonstrate the efficacy of these interventions in improving liver function and patient outcomes. Transjugular intrahepatic portosystemic shunt (TIPS) emerges as a promising intervention, effectively resolving complications of portal hypertension and facilitating recompensation. However, optimal timing and patient selection for TIPS remain unresolved. Despite challenges, TIPS offers renewed hope for hepatic recompensation, marking a significant advancement in cirrhosis management. Further research is needed to refine its implementation and maximize its benefits. In conclusion, TIPS stands as a promising avenue for improving hepatic function and patient outcomes in decompensated liver cirrhosis within the framework of the Baveno VII criteria.

Low-dose alcohol exacerbates hyperdynamic circulation and shunting in non-alcoholic cirrhotic rats.

BACKGROUND: Portal hypertension affects hepatic, splanchnic and portosystemic collateral systems. Although alcohol is a well-known risk factor for liver cirrhosis, it also affects vascular contractility. However, the relevant effects on portal hypertension have not been evaluated in non-alcoholic cirrhosis. The present study aimed to investigate the impacts of low-dose alcohol on portal hypertension-related derangements in non-alcoholic cirrhotic rats. METHODS: Sprague-Dawley rats received bile duct ligation to induce cirrhosis or sham operation as controls. The chronic or acute effects of low-dose alcohol (2.4 g/kg/day, oral gavage, approximately 1.3 drinks/day in humans) were evaluated. RESULTS: The chronic administration of low-dose alcohol did not precipitate liver fibrosis in the sham or cirrhotic rats; however, it significantly increased splanchnic blood inflow (P=0.034) and portosystemic collaterals (P=0.001). Mesenteric angiogenesis and pro-angiogenic proteins were up-regulated in the alcohol-treated cirrhotic rats, and poorer collateral vasoresponsiveness to vasoconstrictors (P<0.001) was noted. Consistently, acute alcohol administration reduced splenorenal shunt resistance. Collateral vasoresponsiveness to vasoconstrictors also significantly decreased (P=0.003). CONCLUSIONS: In non-alcoholic cirrhosis rats, a single dose of alcohol adversely affected portosystemic collateral vessels due to vasodilatation. Long-term alcohol use precipitated splanchnic hyperdynamic circulation, in which mesenteric angiogenesis played a role. Further studies are warranted to evaluate the benefits of avoiding low-dose alcohol consumption in patients with non-alcoholic cirrhosis.

Cholestasis after Kasai operation predicts portal hypertension in native liver survivors of biliary atresia: a multicenter study.

PURPOSE: This study evaluated portal hypertension (PHT) and its predictors among native liver survivors (NLS) of biliary atresia (BA) after Kasai portoenterostomy (KPE). METHODS: This was a multicenter study using prospectively collected data. The subjects were patients who remained transplant-free for 5 years after KPE. Their status of PHT was evaluated and variables that predicted PHT were determined by regression analysis and receiver operating characteristic (ROC) curve. RESULTS: Six centers from East Asia participated in this study and 320 subjects with KPE between 1980 to 2018 were analyzed. The mean follow-up period was 10.6 ± 6.2 years. At the 5th year after KPE, PHT was found in 37.8% of the subjects (n = 121). Patients with KPE done before day 41 of life had the lowest percentage of PHT compared to operation at older age. At 12 months after KPE, PHT + ve subjects had a higher bilirubin level (27.1 ± 11.7 vs 12.3 ± 7.9 µmol/L, p = 0.000) and persistent jaundice conferred a higher risk for PHT (OR = 12.9 [9.2-15.4], p = 0.000). ROC analysis demonstrated that a bilirubin level above 38 µmol/L at 12 months after KPE predicted PHT development (sensitivity: 78%, specificity: 60%, AUROC: 0.75). CONCLUSIONS: In BA, early KPE protects against the development of PHT among NLSs. Patients with persistent cholestasis at one year after KPE are at a higher risk of this complication. They should receive a more vigilant follow-up. LEVEL OF EVIDENCE: Level III.

[Porto sinusoidal vascular disease: an unusual cause of digestive bleeding]. / Enfermedad vascular porto sinusoidal: una causa inusual de sangrado digestivo.

Portal hypertension (PHT) is defined as an increase in pressure at the level of the portal vein above 5 mmHg, the most common cause being liver cirrhosis. Among the presinusoidal intrahepatic causes of PHT with portal venular involvement, what was traditionally known as idiopathic non-cirrhotic portal hypertension (NCIH) is described, with the requirements of excluding those patients who did not present PHT, as well as those with the presence of liver cirrhosis and thrombosis. portal venous vein (PVT). Currently, the diagnostic criteria for this entity have been reconsidered, and its name, being known as porto-sinusoidal vascular disease (PSVD), also does not exclude patients with PHT or the presence of underlying liver disease. Liver biopsy continues to be the gold standard for diagnosis. The clinical manifestations are derived from PHT and the management is similar to the complications that occur in patients with liver cirrhosis. The case of a male patient is presented who presents with symptoms of digestive bleeding, with findings of esophageal varices in upper endoscopy in addition to a study of viral, autoimmune liver disease and negative deposits, with a conclusive liver biopsy of porto-sinusoidal vascular disease.

Portal vein thrombosis: diagnosis, management, and endpoints for future clinical studies.

Portal vein thrombosis (PVT) refers to the development of a non-malignant obstruction of the portal vein, its branches, its radicles, or a combination. This Review first provides a comprehensive overview of all aspects of PVT, namely the specifics of the portal venous system, the risk factors for PVT, the pathophysiology of portal hypertension in PVT, the interest in non-invasive tests, as well as therapeutic approaches including the effect of treating risk factors for PVT or cause of cirrhosis, anticoagulation, portal vein recanalisation by interventional radiology, and prevention and management of variceal bleeding in patients with PVT. Specific issues are also addressed including portal cholangiopathy, mesenteric ischaemia and intestinal necrosis, quality of life, fertility, contraception and pregnancy, and PVT in children. This Review will then present endpoints for future clinical studies in PVT, both in patients with and without cirrhosis, agreed by a large panel of experts through a Delphi consensus process. These endpoints include classification of portal vein thrombus extension, classification of PVT evolution, timing of assessment of PVT, and global endpoints for studies on PVT including clinical outcomes. These endpoints will help homogenise studies on PVT and thus facilitate reporting, comparison between studies, and validation of future studies and trials on PVT.

Portal thrombosis after surgical treatment of schistosomatic portal hypertension.

OBJECTIVE: Several studies have investigated the correlation between the effects of different surgical treatments and laboratory exams for schistosomal portal hypertension, especially concerning portal system thrombosis. The etiopathogenic factors of this thrombosis are not fully understood. In this study, the correlation between surgical treatment for schistosomal portal hypertension and the occurrence of postoperative portal system thrombosis was investigated. METHODS: A total of 61 patients who underwent surgical treatment for schistosomal portal hypertension were distributed into four groups: Patients in Group 1 (n=12) underwent portal variceal disconnection associated with splenic artery ligation and spleen preservation. Patients in Group 2 (n=20) underwent portal variceal disconnection and total splenectomy. Patients in Group 3 (n=20) underwent portal variceal disconnection with subtotal splenectomy, preserving the upper splenic pole supplied by the splenogastric vessels. Patients in Group 4 (n=9) underwent portal variceal disconnection with total splenectomy and autogenous splenic implants on the greater omentum. Late postoperative portal vein thrombosis was diagnosed using Doppler ultrasound. RESULTS: Over the 10-year follow-up, portal vein thrombosis occurred in 26 operated patients (42.6%), with no significant difference observed among the four surgical groups (p=0.217). Most of the thrombi only partially occluded the portal system veins. All the patients presented with a thrombus inside the portal vein. There was no difference in hematological and biochemical tests between groups with or without portal vein thrombosis. CONCLUSIONS: Portal vein thrombosis is often observed in the late postoperative period, irrespective of the surgical treatment employed, and is not associated with patient characteristics or any hematological and biochemical tests.

Transjugular intrahepatic portosystemic shunt for recompensating decompensated cirrhosis?

Transjugular intrahepatic portosystemic shunt (TIPS) is a medical procedure that has been used to manage variceal bleeding and ascites in patients with cirrhosis. It can prevent further decompensation and improve the survival of high-risk decompensated patients. Recent research indicates that TIPS could increase the possibility of recompensation of decompensated cirrhosis when it is combined with adequate suppression of the causative factor of liver disease. However, the results of the studies have been based on retrospective analysis, and further validation is required by conducting randomized controlled studies. In this context, we highlight the limitations of the current studies and emphasize the issues that must be addressed before TIPS can be recommended as a potential recompensating tool.

A novel surgical scheme for hepatectomy in hepatocellular carcinoma patients with clinically significant portal hypertension.

OBJECTIVE: Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH. BACKGROUNDS: Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC. METHODS: Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram. RESULTS: This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR. CONCLUSION: This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.

The Pathophysiology of Portal Hypertension.

This article reviews the pathophysiology of portal hypertension that includes multiple mechanisms internal and external to the liver. This article starts with a review of literature describing the cellular and molecular mechanisms of portal hypertension, microvascular thrombosis, sinusoidal venous congestion, portal angiogenesis, vascular hypocontractility, and hyperdynamic circulation. Mechanotransduction and the gut-liver axis, which are newer areas of research, are reviewed. Dysfunction of this axis contributes to chronic liver injury, inflammation, fibrosis, and portal hypertension. Sequelae of portal hypertension are discussed in subsequent studies.

Radiological and Surgical Treatments of Portal Hypertension.

Interventions for portal hypertension are continuously evolving and expanding beyond the realm of medical management. When complications such as varices and ascites persist despite conservative interventions, procedures including transjugular intrahepatic portosystemic shunt creation, transvenous obliteration, portal vein recanalization, splenic artery embolization, surgical shunt creation, and devascularization are all potential interventions detailed in this article. Selection of the optimal procedure to address the underlying cause, treat symptoms, and, in some cases, bridge to liver transplantation depends on the specific etiology of portal hypertension and the patient's comorbidities.

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.

Noninvasive Assessment of Portal Hypertension.

The progressive use of noninvasive tests (NITs) has changed the way hepatologists diagnose and manage patients with chronic liver disease, mainly because of their easiness to use and the ability to be repeated during follow-up. Liver stiffness measurement is the NIT with more scientific evidence. NITs have demonstrated to be useful to detect not only liver fibrosis but also the presence of clinically significant portal hypertension. Moreover, current evidence supports they can also be useful to evaluate the prognosis of patients with chronic liver disease.

Pharmacologic Treatment of Portal Hypertension.

Portal hypertension is the key mechanism driving the transition from compensated to decompensated cirrhosis. In this review, the authors described the pathophysiology of portal hypertension in cirrhosis and the rationale of pharmacologic treatment of portal hypertension. We discussed both etiologic and nonetiologic treatment of portal hypertension and the specific clinical scenarios how nonselective beta-blocker can be used in patients with cirrhosis. Finally, the authors summarized the evidence for emerging alternatives for portal hypertension in patients with cirrhosis.