Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors.

BACKGROUND: Patients with liver cancer complicated by portal hypertension present complex challenges in treatment. AIM: To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition. METHODS: Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group (n = 50) and a control group (n = 50) according to the treatment regimen. The research group received radiofrequency ablation (RFA) in combination with sorafenib, and the control group only received RFA. The short-term efficacy of both the research and control groups was observed. Liver function and portal hypertension were compared before and after treatment. Alpha-fetoprotein (AFP), glypican-3 (GPC-3), and AFP-L3 levels were compared between the two groups prior to and after treatment. The occurrence of adverse reactions in both groups was observed. The 3-year survival rate was compared between the two groups. Basic data were compared between the survival and non-surviving groups. To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension, multivariate logistic regression analysis was employed. RESULTS: When comparing the two groups, the research group's total effective rate (82.00%) was significantly greater than that of the control group (56.00%; P < 0.05). Following treatment, alanine aminotransferase and aspartate aminotransferase levels increased, and portal vein pressure decreased in both groups. The degree of improvement for every index was substantially greater in the research group than in the control group (P < 0.05). Following treatment, the AFP, GPC-3, and AFP-L3 levels in both groups decreased, with the research group having significantly lower levels than the control group (P < 0.05). The incidence of diarrhea, rash, nausea and vomiting, and fatigue in the research group was significantly greater than that in the control group (P < 0.05). The 1-, 2-, and 3-year survival rates of the research group (94.00%, 84.00%, and 72.00%, respectively) were significantly greater than those of the control group (80.00%, 64.00%, and 40.00%, respectively; P < 0.05). Significant differences were observed between the survival group and the non-surviving group in terms of Child-Pugh grade, history of hepatitis, number of tumors, tumor size, use of sorafenib, stage of liver cancer, histological differentiation, history of splenectomy and other basic data (P < 0.05). Logistic regression analysis demonstrated that high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, no use of sorafenib, liver cancer stage IIIC, and previous splenectomy were independent risk factors for poor prognosis in patients with liver cancer complicated with portal hypertension (P < 0.05). CONCLUSION: Patients suffering from liver cancer complicated by portal hypertension benefit from the combination of RFA and sorafenib therapy because it effectively restores liver function and increases survival rates. The prognosis of patients suffering from liver cancer complicated by portal hypertension is strongly associated with factors such as high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, lack of sorafenib use, liver cancer at stage IIIC, and prior splenectomy.

Hepatic recompensation according to Baveno VII criteria via transjugular intrahepatic portosystemic shunt.

Transjugular intrahepatic portosystemic shunt is a therapeutic modality done through interventional radiology. It is aimed to decrease portal pressure in special situations for patients with decompensated liver disease with portal hypertension. It represents a potential addition to the therapeutic modalities that could achieve hepatic recompensation in those patients based on Baveno VII criteria.

Gut-Liver Axis Dysregulation in Portal Hypertension: Emerging Frontiers.

Portal hypertension (PH) is a complex clinical challenge with severe complications, including variceal bleeding, ascites, hepatic encephalopathy, and hepatorenal syndrome. The gut microbiota (GM) and its interconnectedness with human health have emerged as a captivating field of research. This review explores the intricate connections between the gut and the liver, aiming to elucidate how alterations in GM, intestinal barrier function, and gut-derived molecules impact the development and progression of PH. A systematic literature search, following PRISMA guidelines, identified 12 original articles that suggest a relationship between GM, the gut-liver axis, and PH. Mechanisms such as dysbiosis, bacterial translocation, altered microbial structure, and inflammation appear to orchestrate this relationship. One notable study highlights the pivotal role of the farnesoid X receptor axis in regulating the interplay between the gut and liver and proposes it as a promising therapeutic target. Fecal transplantation experiments further emphasize the pathogenic significance of the GM in modulating liver maladies, including PH. Recent advancements in metagenomics and metabolomics have expanded our understanding of the GM's role in human ailments. The review suggests that addressing the unmet need of identifying gut-liver axis-related metabolic and molecular pathways holds potential for elucidating pathogenesis and directing novel therapeutic interventions.

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.

Optimizing nutrition in hepatic cirrhosis: A comprehensive assessment and care approach.

Cirrhosis is considered a growing cause of morbidity and mortality, which represents a significant public health problem. Currently, there is no effective treatment to reverse cirrhosis. Treatment primarily centers on addressing the underlying liver condition, monitoring, and managing portal hypertension-related complications, and evaluating the potential for liver transplantation in cases of decompensated cirrhosis, marked by rapid progression and the emergence of complications like variceal bleeding, hepatic encephalopathy, ascites, malnutrition, and more. Malnutrition, a prevalent complication across all disease stages, is often underdiagnosed in cirrhosis due to the complexities of nutritional assessment in patients with fluid retention and/or obesity, despite its crucial impact on prognosis. Increasing emphasis has been placed on the collaboration of nutritionists within hepatology and Liver transplant teams to deliver comprehensive care, a practice that has shown to improve outcomes. This review covers appropriate screening and assessment methods for evaluating the nutritional status of this population, diagnostic approaches for malnutrition, and context-specific nutrition treatments. It also discusses evidence-based recommendations for supplementation and physical exercise, both essential elements of the standard care provided to cirrhotic patients.

A new computational fluid dynamics based noninvasive assessment of portacaval pressure gradient.

Accurate assessment of portacaval pressure gradient (PCG) in patients with portal hypertension (PH) is of great significance both for diagnosis and treatment. This study aims to develop a noninvasive method for assessing PCG in PH patients and evaluate its accuracy and effectiveness. This study recruited 37 PH patients treated with transjugular intrahepatic portosystemic shunt (TIPS). computed tomography angiography was used to create three dimension (3D) models of each patient before and after TIPS. Doppler ultrasound examinations were conducted to obtain the patient's portal vein flow (or splenic vein and superior mesenteric vein). Using computational fluid dynamics (CFD) simulation, the patient's pre-TIPS and post-TIPS PCG was determined by the 3D models and ultrasound measurements. The accuracy of these noninvasive results was then compared to clinical invasive measurements. The results showed a strong linear correlation between the PCG simulated by CFD and the clinical invasive measurements both before and after TIPS (R2 = 0.998, P < 0.001 and R2 = 0.959, P < 0.001). The evaluation accuracy of this noninvasive method reached 94 %, and the influence of ultrasound result errors on the numerical accuracy was found to be marginal if the error was less than 20 %. Furthermore, the information about the hemodynamic environment in the portal system was obtained by this numerical method. Spiral flow patterns were observed in the portal vein of some patients. In a conclusion, this study proposes a noninvasive numerical method for assessing PCG in PH patients before and after TIPS. This method can assist doctors in accurately diagnosing patients and selecting appropriate treatment plans. Additionally, it can be used to further investigate potential biomechanical causes of complications related to TIPS in the future.

Beta-blockers or Placebo for Primary Prophylaxis (BOPPP) of oesophageal varices: study protocol for a randomised controlled trial.

BACKGROUND: Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality. It remains uncertain whether administering a non-selective beta-blocker (NSBB), specifically carvedilol, at an earlier stage, i.e. when oesophageal varices are small, can prevent VH and reduce all-cause decompensation (ACD). METHODS/DESIGN: The BOPPP trial is a pragmatic, multicentre, placebo-controlled, triple-blinded, randomised controlled trial (RCT) in England, Scotland, Wales and Northern Ireland. Patients aged 18 years or older with cirrhosis and small oesophageal varices that have never bled will be recruited, subject to exclusion criteria. The trial aims to enrol 740 patients across 55 hospitals in the UK. Patients are allocated randomly on a 1:1 ratio to receive either carvedilol 6.25 mg (a NSBB) or a matched placebo, once or twice daily, for 36 months, to attain adequate power to determine the effectiveness of carvedilol in preventing or reducing ACD. The primary outcome is the time to first decompensating event. It is a composite primary outcome made up of variceal haemorrhage (VH, new or worsening ascites, new or worsening hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, an increase in Child-Pugh grade by 1 grade or MELD score by 5 points, and liver-related mortality. Secondary outcomes include progression to medium or large oesophageal varices, development of gastric, duodenal, or ectopic varices, participant quality of life, healthcare costs and transplant-free survival. DISCUSSION: The BOPPP trial aims to investigate the clinical and cost-effectiveness of carvedilol in patients with cirrhosis and small oesophageal varices to determine whether this non-selective beta-blocker can prevent or reduce hepatic decompensation. There is clinical equipoise on whether intervening in cirrhosis, at an earlier stage of portal hypertension, with NSBB therapy is beneficial. Should the trial yield a positive result, we anticipate that the administration and use of carvedilol will become widespread with pathways developed to standardise the administration of the medication in primary care. ETHICS AND DISSEMINATION: The trial has been approved by the National Health Service (NHS) Research Ethics Committee (REC) (reference number: 19/YH/0015). The results of the trial will be submitted for publication in a peer-reviewed scientific journal. Participants will be informed of the results via the BOPPP website ( www.boppp-trial.org ) and partners in the British Liver Trust (BLT) organisation. TRIAL REGISTRATION: EUDRACT reference number: 2018-002509-78. ISRCTN reference number: ISRCTN10324656. Registered on April 24 2019.

[Research progress on pseudocirrhosis].

Presently, pseudocirrhosis occurs in most patients with liver metastases from malignant tumors and can exhibit clinical manifestations related to portal hypertension, such as edema, ascites, and gastrointestinal bleeding. Imaging features include malignant tumor liver metastasis, the appearance of nodules accompanied with or without hepatic contour, segmental liver volume reduction, and caudate lobe enlargement. Histology shows the typical pathological manifestations of liver cirrhosis, such as diffuse tumor cell infiltration, fibrosis around the infiltrating lesion, hepatic sinus vascular thrombosis, nodular hyperplasia, non-accompanied bridging necrosis, bridging fibrosis, and pseudolobule formation. The possible pathogenesis of pseudocirrhosis is tumor cell infiltration and toxic reactions of tumor cells and liver cells to chemotherapy. The presence of pseudocirrhosis in patients diagnosed with malignant tumors is one of the challenges affecting their survival cycle and shortening the median survival time. The relationship between its onset, tumor type and metastasis, and the use of chemotherapy drugs is still unclear. The atypical clinical manifestations and imaging characteristics bring about great challenges for clinicians and patients. Thus, based on the existing case reports, observational studies, and meta-analysis results, this article reviews the research progress on the prevalence, etiology, pathogenesis, diagnosis, treatment, and prognosis of pseudocirrhosis.

Serum proteomic profiling of patients with compensated advanced chronic liver disease with and without clinically significant portal hypertension.

INTRODUCTION: Portal hypertension (PH) drives the progression of liver cirrhosis to decompensation and death. Hepatic venous pressure gradient (HVPG) measurement is the standard of PH quantification, and HVPG≥10 mmHg defines clinically significant PH (CSPH). We performed proteomics-based serum profiling to search for a proteomic signature of CSPH in patients with compensated advanced chronic liver disease (cACLD). MATERIALS AND METHODS: Consecutive patients with histologically confirmed cACLD and results of HVPG measurements were prospectively included. Serum samples were pooled according to the presence/absence of CSPH and analysed by liquid chromatography-mass spectrometry. Gene set enrichment analysis was performed, followed by comprehensive literature review for proteins identified with the most striking difference between the groups. RESULTS: We included 48 patients (30 with, and 18 without CSPH). Protein CD44, involved in the inflammatory response, vascular endothelial growth factor C (VEGF-C) and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), both involved in lymphangiogenesis were found solely in the CSPH group. Although identified in both groups, proteins involved in neutrophil extracellular traps (NET) formation, as well as tenascin C, autotaxin and nephronectin which mediate vascular contractility and lymphangiogenesis were more abundant in CSPH. DISCUSSION AND CONCLUSION: We propose that altered inflammatory response, including NET formation, vascular contractility and formation of new lymph vessels are key steps in PH development. Proteins such as CD44, VEGF-C, LYVE-1, tenascin C, Plasminogen activator inhibitor 1, Nephronectin, Bactericidal permeability-increasing protein, Autotaxin, Myeloperoxidase and a disintegrin and metalloproteinase with thrombospondin motifs-like protein 4 might be considered for further validation as potential therapeutic targets and candidate biomarkers of CSPH in cACLD.

Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis.

BACKGROUND: For compensated advanced chronic liver disease (cACLD) patients, the first decompensation represents a dramatically worsening prognostic event. Based on the first decompensation event (DE), the transition to decompensated advanced chronic liver disease (dACLD) can occur through two modalities referred to as acute decompensation (AD) and non-AD (NAD), respectively. Clinically Significant Portal Hypertension (CSPH) is considered the strongest predictor of decompensation in these patients. However, due to its invasiveness and costs, CSPH is almost never evaluated in clinical practice. Therefore, recognizing non-invasively predicting tools still have more appeal across healthcare systems. The red cell distribution width to platelet ratio (RPR) has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). However, its predictive role for the decompensation has never been explored. AIM: In this observational study, we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients. METHODS: Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up (FUP) semiannually for 3 years. At baseline, biochemical, clinical, and Liver Stiffness Measurement (LSM), Child-Pugh (CP), Model for End-Stage Liver Disease (MELD), aspartate aminotransferase/platelet count ratio index (APRI), Fibrosis-4 (FIB-4), Albumin-Bilirubin (ALBI), ALBI-FIB-4, and RPR were collected. During FUP, DEs (timing and modaities) were recorded. CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines. RESULTS: Of 150 MASLD-related cACLD patients, 43 (28.6%) progressed to dACLD at a median time of 28.9 months (29 NAD and 14 AD). Baseline RPR values were significantly higher in cACLD in comparison to controls, as well as MELD, CP, APRI, FIB-4, ALBI, ALBI-FIB-4, and LSM in dACLD-progressing compared to cACLD individuals [all P < 0.0001, except for FIB-4 (P: 0.007) and ALBI (P: 0.011)]. Receiving operator curve analysis revealed RPR > 0.472 and > 0.894 as the best cut-offs in the prediction respectively of 3-year first DE, as well as its superiority compared to the other non-invasive tools examined. RPR (P: 0.02) and the presence of baseline-CSPH (P: 0.04) were significantly and independently associated with the DE. Patients presenting baseline-CSPH and RPR > 0.472 showed higher risk of decompensation (P: 0.0023). CONCLUSION: Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.

HCC portal hypertension imaging score derived from CT predicts re-bleeding and mortality after acute variceal bleeding.

BACKGROUND/PURPOSE: Risk factors for re-bleeding and death after acute variceal bleeding (AVB) in cirrhotic HCC patients are not fully understood.We aimed to (1) explore how the combination of high-risk esophageal varices, HCC status, and portal vein tumor thrombus (i.e., HCC Portal Hypertension Imaging Score [HCCPHTIS]) helps predict increased risk of variceal re-bleeding and mortality; (2) assess predictability and reproducibility of the identified variceal re-bleeding rules. METHODS: This prospective study included 195 HCC patients with first-time AVB and liver cirrhosis, and conducted multivariable Cox regression analysis and Kaplan-Meier analysis. Receiver operating characteristic curve analysis was calculated to find the optimal sensitivity, specificity, and cutoff values of the variables. The reproducibility of the results obtained was verified in a different but related group of patients. RESULTS: 56 patients (28.7%) had re-bleeding within 6 weeks; HCCPHTIS was an independent risk factor for variceal re-bleeding after AVB (Odd ratio, 2.330; 95% confidence interval: 1.728-3.142, p < 0.001). The positive predictive value of HCCPHTIS cut off value > 3 was 66.2%, sensitivity 83.9%, and specificity 82.3%. HCCPHTIS area under the curve was higher than Child-Pugh score (89% vs. 75%, p < 0.001). 74(37.9%) death occurred within 6 weeks; HCCPHTIS > 4 was associated with increased risk of death within 6 weeks after AVB (p < 0.001). CONCLUSION: HCCPHTIS > 3 is a strong predictor of variceal re-bleeding within the first 6 weeks. However, patients with HCCPHTIS > 4 were at increased risk of death within 6 weeks.

Noninvasive assessment of liver fibrosis and portal hypertension.

PURPOSE OF REVIEW: The result of ongoing liver injury - and disease, regardless of cause - is fibrosis, and fibrosis appears to be a critically important result of ongoing injury. Further, in a number of different liver diseases, the presence of fibrosis has prognostic value. Therefore, the assessment of fibrosis is of critical clinical importance. Given the importance of fibrosis, there has been a rapid evolution in the use of noninvasive liver tests. This review highlights a number of the core principles surrounding. RECENT FINDINGS: The use of noninvasive test has progressed rapidly over the last decade and data are rapidly accumulating. New terminology has been adapted by the American Association for the Study of Liver Disease (AASLD) for noninvasive assessment of liver disease and termed 'NILDA' (Non-Invasive Liver Disease Assessment). Blood based such as APRI and or FIB-4 and imaging tests such as liver stiffness measurement (LSM) have moderate to high degrees of accuracy for detection of advanced liver fibrosis (≥ F2) and even higher accuracy for detection of severe fibrosis (F4 or cirrhosis). NILDA are particularly effective at the ends of the liver disease spectrum. For example, a very low LSM (less than 7 kPa) essentially excludes significant fibrosis or portal hypertension, and a very high LSM (> 25 kPa) makes significant fibrosis with portal hypertension (cirrhosis) highly likely. SUMMARY: NILDA are currently front and center in terms of assessment of the severity of liver disease. In all patients with known or suspected liver disease, noninvasive blood tests, including APRI and or FIB-4, should be the initial choice to assess the severity of liver fibrosis and/or portal hypertension. In most patients, these tests should be followed with imaging evaluation. The most commonly available imaging is LSM, which appears to be more accurate in predicting fibrosis severity, and is superior to blood tests in the assessment of portal hypertension. In situations in which there is diagnostic uncertainly, liver biopsy with or without HVPG remains an important consideration.

Efficacy and safety of atezolizumab plus bevacizumab in patients with portal hypertension for unresectable hepatocellular carcinoma.

AIM: Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is used as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). Serious adverse events (AEs), including rupture of esophagogastric varices, have been seen during treatment. Therefore, the relationships of efficacy, safety, and portal hypertension (PH) were analyzed. METHODS: A total of 146 patients with u-HCC and Child-Pugh Scores of 5-7 received Atezo + Beva. Prophylactic treatment for varices was performed for patients with the risk of rupture of varices before the start of Atezo + Beva. A propensity score-matched cohort was created to minimize the risk of potential confounders. Efficacy was assessed in 41 propensity score-matched pairs. AEs were assessed between patients without PH (n = 80) and with PH (n = 66). RESULTS: In patients without PH and with PH, median overall survival was 18.4 months and 18.8 months (p = 0.71), and median progression-free survival was 8.6 months and 5.8 months (p = 0.92), respectively. On the best radiological response evaluation for Response Evaluation Criteria in Solid Tumors, the objective response rate was 31.7% and 26.8% (p = 0.81), respectively. Variceal rupture occurred in three patients with PH, but there were no significant differences in the occurrence of variceal rupture (p = 0.090) and Grade 3-4 AEs between patients without and with PH. CONCLUSIONS: No significant differences in efficacy and safety were observed with PH. Prophylactic treatment for varices before the start of Atezo + Beva would allow treatment to continue relatively safely.

[Trends in endovascular treatment and prevention of portal bleeding]. / Tendentsii v rentgenendovaskulyarnom lechenii i profilaktike portal'nykh krovotechenii (obzor literatury).

Bleeding from esophageal and gastric varices is a major factor of mortality in patients with portal hypertension. The gold standard for diagnosis of portal hypertension is hepatic venous pressure gradient determining the treatment algorithms and risk of recurrent bleeding. Combination of endoscopic methods and therapy is limited by varix localization and not always effective. In these cases, endovascular bypass and decoupling techniques are preferred. Early endovascular treatment of portal bleeding is effective for hemostasis and higher transplantation-free survival of patients. Early transjugular intrahepatic portosystemic bypass should be associated with 8-mm covered stents of controlled dilation. Combination of endovascular techniques reduces the complications of each technique and potentiates their positive effect. Endovascular treatment and prevention of portal bleeding should be determined by anatomical features of portal venous system.

Surgery for a symptomatic massive liver haemangioma.

Liver haemangiomas are the most common benign hepatic tumours, but secondary portal hypertension resulting from haemangiomas is exceedingly uncommon. We present a case of a man in his 50s who presented with a progressively enlarging mass in the right upper abdomen. CT of the liver revealed a large hypodense lesion involving the right lobe, with two smaller lesions in the left lobe. The portal vein was compressed by the tumour, causing portal hypertension. The patient underwent right hepatectomy. Postoperatively, the patient had an uneventful course, and a 3-month follow-up demonstrated resolution of the oesophageal varices, portal gastropathy, with hypertrophy of the left lobe. This case report highlights the successful surgical management of a rare massive hepatic haemangioma causing portal hypertension with surgical resection, emphasising the potential benefits of surgical intervention with minimal complications.

Gynura segetum induces hepatic sinusoidal obstruction syndrome in a child: A case report.

RATIONALE: Hepatic sinusoidal obstruction syndrome (HSOS), which includes hepatic stasis and portal hypertension, is a rare vascular disorder of the liver. It is often associated with hematopoietic stem cell transplantation. It is also possible to treat this disease using Chinese herbal medicines that contain pyrrolizidine alkaloids (PAs). This disease is extremely rare in children and poses a serious threat to their health. To our knowledge, this is the first case of HSOS in a child with PAs. PATIENT CONCERNS: We report a 4-year-old boy suffering from abdominal pain, hepatomegaly, massive ascites, elevated liver enzyme level, and severe portal hypertension as a result of the consumption of Gynura segetum (also known as Tusanqi in Chinese, a traditional herbal medicine containing PAs). DIAGNOSES: The child was finally diagnosed with PA-HSOS based on pathological diagnosis and imaging examination. INTERVENTION: With active symptomatic and supportive care and sequential anticoagulation therapy, the abdominal distension and liver function improved in the patient. OUTCOMES: The patient was eventually recovered. The levels of liver enzymes, hemoglobin, and bilirubin were normal, and the international normalized ratio fluctuated between 2.0 and 3.0 during 1-year follow-up after discharge. LESSONS: This case report emphasizes the prevention of Chinese herb-induced liver injury in children and the importance of active long-term sequential anticoagulant therapy to reduce the progressive damage of PA-HSOS in the liver.

Attitudes towards transjugular intrahepatic portosystemic shunt (TIPS) in Australia: a national survey of TIPS centres.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive therapeutic option to treat the sequelae of portal hypertension. It is unclear whether current international recommendations are reflected in current clinical practice across Australia and the extent of variations in care. This study aimed to address this gap in knowledge and benchmark the current landscape of TIPS services in Australia against international guidelines. METHODS: We designed a 42-item questionnaire according to practice-based recommendations and standards of international guidelines to investigate current landscape of TIPS service across four key domains: (1) service provision, (2) patient selection and indications, (3) best procedure practice, and (4) postoperative care. RESULTS: Gastroenterologist/hepatologists from 23 major liver centres (67.6%) across Australia currently performing TIPS completed the questionnaire. Between 2017 and 2020, there were 456 elective TIPS insertions. Units offering TIPS service had a low median number of TIPS insertions (n=7 per annum). More than half of respondents (56.5%) did not have institutional clinical practice protocols. There was marked variation in practices across institutions in terms of TIPS indications and patient selection. Despite variations, the success rate of elective TIPS was high at 91.7% (79-100%), with 86.6% (29-100%) for rescue TIPS. There was significant variation in postoperative follow-up and care. CONCLUSION: Current TIPS practice in Australia varies significantly across institutions. There is a need for a national consensus clinical practice guidelines to improve access and minimise unwarranted variation. A national registry for TIPS could measure, monitor, and report on quality of clinical care and patient outcomes.

Tofogliflozin Delays Portal Hypertension and Hepatic Fibrosis by Inhibiting Sinusoidal Capillarization in Cirrhotic Rats.

BACKGROUND: Liver cirrhosis leads to portal hypertension (PH) with capillarization of liver sinusoidal endothelial cells (LSECs), although drug treatment options for PH are currently limited. Sodium glucose transporter 2 inhibitors, which are antidiabetic agents, have been shown to improve endothelial dysfunction. We aimed to elucidate the effect of tofogliflozin on PH and liver fibrosis in a rat cirrhosis model. METHODS: Male-F344/NSlc rats repeatedly received carbon tetrachloride (CCl4) intraperitoneally to induce PH and liver cirrhosis alongside tofogliflozin (10 or 20 mg/kg). Portal hemodynamics and hepatic phenotypes were assessed after 14 weeks. An in vitro study investigated the effects of tofogliflozin on the crosstalk between LSEC and activated hepatic stellate cells (Ac-HSC), which are relevant to PH development. RESULTS: Tofogliflozin prevented PH with attenuated intrahepatic vasoconstriction, sinusoidal capillarization, and remodeling independent of glycemic status in CCl4-treated rats. Hepatic macrophage infiltration, proinflammatory response, and fibrogenesis were suppressed by treatment with tofogliflozin. In vitro assays showed that tofogliflozin suppressed Ac-HSC-stimulated capillarization and vasoconstriction in LSECs by enhancing the antioxidant capacity, as well as inhibited the capilliarized LSEC-stimulated contractive, profibrogenic, and proliferative activities of Ac-HSCs. CONCLUSIONS: Our study provides strong support for tofogliflozin in the prevention of liver cirrhosis-related PH.