Search

Background: Patients with hepatocellular carcinoma (HCC) and cirrhosis can present with features of severe portal hypertension, which can be worsened further by portal vein tumoral thrombosis (PVTT). Due to the technical difficulties and short survival of these patients, HCC was traditionally considered a relative contra-indication for transjugular intrahepatic portosystemic shunt (TIPS). However, there is an increasing body of evidence, mainly from China, supporting the use of TIPS in HCC. The present study aimed at analyzing the efficacy and safety of TIPS in patients with HCC. Methods: From 2000 through May 2023, MEDLINE, Embase and Scopus were searched for studies analyzing the outcome of TIPS in HCC. Technical and clinical success, adverse events (AE) and mortality were the main outcomes assessed. With the use of a random effects model, the event rates were combined. Results: Total 19 studies with 1498 patients were included in the final analysis. The pooled technical and clinical success rates with TIPS in HCC were 98.8% (98.0–99.7) and 94.1% (91.2–97.0), respectively. After TIPS, ascites was controlled in 89.2% (85.1–93.3) of the cases, while rebleeding was observed in 17.2% (9.4–25.0) of cases on follow-up. The pooled incidence of overall AE, serious AE and post-TIPS hepatic encephalopathy (HE) was 5.2% (2.5–7.9), 0.1% (0.0–0.4) and 25.1% (18.7–31.5), respectively. On follow-up, 11.9% (7.8–15.9) of the patients developed shunt dysfunction requiring re-intervention. Conclusion: The present analysis supports the feasibility, safety and efficacy of TIPS in the management of portal hypertension in patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Primary sclerosing cholangitis (PSC) is an idiopathic cholestatic liver disease that may lead to biliary strictures and destruction. It is associated with p-ANCA positivity and inflammatory bowel disease, typically ulcerative colitis. The aim of this study is to investigate the trends of inpatient healthcare utilization and mortality from 2008 to 2017 in the United States. Methods: The Nationwide Inpatient Sample (NIS) was examined to identify adult patients diagnosed with PSC between 2008 and 2017. Data on patient demographics, resource utilization, mortality, and PSC-related complications were collected. STATA version 16.0 was employed to perform forward stepwise multivariate regression analysis, generating adjusted odds ratios for both primary and secondary outcomes. Primary outcomes included the inpatient mortality rate and healthcare resource utilization (length of stay, total charges, and trends over the study period). Secondary outcomes focused on trends in associated comorbidities and malignancies in patients with PSC. Results: The average total charge increased by 32.2% ± 2.12 from USD 61,873 ± 2567 in 2008 to USD 91,262 ± 2961 in 2017. Concurrently, the average length of stay declined from 8.07 ± 0.18 days in 2008 to 7.27 ± 0.13 days in 2017. The APR-DRG severity of illness and risk of death significantly increased (major or extreme) during the study period (2008 to 2017), with severity rising from 73.6% to 82.7% (coefficient: 0.21, 95% CI: 0.13–0.28) and risk of death from 45.3% to 60.9% (coefficient: 0.15, 95% CI: 0.08–0.23). The proportion of patients with HCC increased from 1.3% to 7.9% (coefficient: 2.13, 95% CI: 1.9–2.8). Conversely, the percentage of patients with cholangiocarcinoma (CCA) decreased from 5.1% to 2.8% (coefficient: −0.36, 95% CI: −0.25 to −0.46). Conclusions: There was rising mortality and healthcare resource utilization among patients with PSC from the years 2008 to 2017. These trends were paralleled by increasing rates of decompensated cirrhosis, HCC, and liver transplants. However, the incidence of CCA decreased during this time period. African American patients with PSC had worse inpatient mortality outcomes and healthcare utilization as compared to white patients. Further studies are warranted to investigate a possible causal link amongst these trends. [ABSTRACT FROM AUTHOR]

Cardiovascular complications are common in patients with severe liver disease and are an important cause of peri-operative and post-transplant morbidity and mortality. Cirrhotic cardiomyopathy (CCM), often found in advanced liver disease, is characterized by diastolic dysfunction, systolic dysfunction, and electrophysiological abnormalities. While CCM may not cause symptoms at rest, it can become evident during stressful activities, such as surgery. Liver transplantation, while being the definitive treatment for end-stage liver disease (ESLD), carries significant cardiovascular risks. Preoperative cardiac evaluation is essential for assessing these risks and planning appropriate management. Cardiac imaging, particularly echocardiography, plays a crucial role in evaluating liver transplant candidates, helping to identify conditions such as CCM, pulmonary hypertension, hepatopulmonary syndrome, and others. Currently, liver transplant anesthetists must acquire echocardiographic knowledge and skills to evaluate the cardiocirculatory conditions of the transplanted patient, especially in the pre-operative phase, but also intra-operatively and post-operatively. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Transjugular intrahepatic portosystemic shunt (TIPSS) is highly effective for treatment of variceal bleeding; however, factors contributing to rebleeding complications remain unclear.In this study, we aim to determine risk factors for recurrent portal hypertensive gastrointestinal bleeding following TIPSS.Utilising the Advancing Liver Therapeutic Approaches multicentre database, we retrospectively identified adult patients who underwent TIPSS for secondary prophylaxis of variceal bleeding and had a gastrointestinal rebleeding event within 1 year. We developed multivariable logistic regression models to identify clinical/procedural characteristics associated with rebleeding.We identified 476 patients, predominately middle‐aged (mean age 57), male (62%) and White (65%), with mean MELD‐Na 16. 16% (n = 77) had a rebleeding event; these patients were more likely to be male (p = 0.016), with higher serum creatinine (p = 0.005), MELD‐Na (p = 0.0002), portal hypertensive gastropathy on pre‐TIPSS upper endoscopy (p = 0.000) and with higher incidence of TIPSS revision (p = 0.000). There were no significant differences in type of TIPSS endoprosthesis, concurrent embolotherapy, and post‐TIPSS pressure gradients between those who experienced rebleeding and those who did not. After adjusting for TIPSS revision, multivariable analysis revealed MELD‐Na and presence of portal hypertensive gastropathy on pre‐TIPSS endoscopy were independently associated with rebleeding.In this retrospective analysis of a multicentre, nationally representative database, we found that apart from TIPSS‐related factors, high MELD‐Na and portal hypertensive gastropathy on pre‐TIPSS endoscopy were independent predictors of rebleeding within 1 year following TIPSS. These variables may be used to identify high‐risk patients who may require additional monitoring following TIPSS. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is one of the common complications of liver cirrhosis. It occurs in nearly 20% of patients with cirrhosis who are hospitalized. Prior literature demonstrated that the AKI occurrence in patients with cirrhosis is independently associated with higher mortality. However, there are data assessing predictors and outcomes of AKI resolution in hospitalized patients with cirrhosis. Therefore, the aim of the current study was to identify clinical predictors of AKI resolution among inpatients with cirrhosis that are easily obtained and to evaluate the clinical outcomes of those patients. Methods: The current study is a retrospective cohort of patients with cirrhosis who were hospitalized and had AKI between 2012 and 2020 at a tertiary referral center. Patients included in this study were identified using the International Classification of Diseases 9 codes and then they were manually verified by two independent chart reviewers. AKI was classified according to the AKI Network (AKIN) serum creatinine (Cr) criteria, with AKIN resolution defined as AKIN stage 1 or lower at the time of discharge, while unresolved AKIN was defined as AKIN stage 2 or 3 at the time of discharge. For univariate analysis, Fisher's exact and the two-sample T-test were utilized. For multivariable analysis, stepwise logistic regression was performed to evaluate variables associated with AKIN resolution. Survival curves were estimated and compared using the Kaplan–Meier method and Log-Rank Test. A p-value cutoff of 0.05 was used for statistical significance. Results: Between 2012 and 2020, there were 140 patients who were included (59% males). The majority of patients had viral hepatitis (54%) as the cirrhosis etiology with 80% of them having hepatitis C virus. Most patients had fluid-responsive AKI (49%), and stage 1 AKIN (69%). In terms of outcomes, the majority of patients (117 patients; 84%) had AKIN resolution at the time of discharge. In the multivariable analysis, after adjusting for clinical meaningful variables, our study shows that higher albumin value at the time of admission (adjusted Odds Ratio "aOR" = 3.28; p = 0.01) and non-metabolic dysfunction-associated steatotic liver disease (non-MASLD) cirrhosis (aOR = 9.43; p < 0.01) were variables associated with higher odds of AKIN resolution at the time of discharge. Conversely, we show that a higher Cr value at the time of admission was associated with lower odds of AKIN resolution at the time of discharge (aOR = 0.31; p < 0.01). When evaluating mortality, patients with unresolved AKIN at the time of discharge had higher rates of in-hospital mortality (p < 0.01) compared to those with resolved AKIN. Survival curve analyses using the Kaplan–Meier method indicated that patients with resolved AKIN experienced higher 90-day survival rates (p < 0.01). Additionally, those with resolved AKIN demonstrated greater transplant-free survival compared to patients with unresolved AKIN at both the 1-year (p = 0.04) and 3-year (p < 0.01) follow-ups. Conclusions: When evaluating clinical predictors of AKIN resolution in admitted patients with cirrhosis, our study showed that a higher admission albumin value and non-MASLD etiology of cirrhosis were associated with higher odds of AKIN resolution at the time of discharge. Conversely, a higher admission Cr value was associated with lower odds of AKIN resolution at the time of discharge. We also demonstrate that AKIN resolution during index admission was associated with improved short- and long-term transplant-free survival (up to 3 years). Our findings warrant external validation in larger cohorts to further evaluate the impact of inpatient AKI resolution on cirrhosis outcomes. Our findings can help clinicians predict AKIN outcomes and encourage more aggressive management of AKI, especially in high-risk patients, which can improve mortality. [ABSTRACT FROM AUTHOR]

Background and Aims: The role of histamine in advanced chronic liver disease (ACLD) is poorly understood. We investigated plasma histamine levels across ACLD stages and their prognostic value. Methods: We included patients with evidence of ACLD, defined by portal hypertension (hepatic venous pressure gradient [HVPG] ≥6 mmHg) and/or a liver stiffness measurement by transient elastography ≥10 kPa, who underwent HVPG measurement between 2017 and 2020. Acute‐on‐chronic liver failure (ACLF) and/or liver‐related death were defined as composite endpoint. Results: Of 251 patients, 82.5% had clinically significant portal hypertension (median HVPG: 17 mmHg [interquartile range (IQR) 12–21]) and 135 patients (53.8%) were decompensated at baseline. Median plasma histamine was 8.5 nmol/L (IQR: 6.4–11.5), 37.1% of patients showed elevated values (>9.9 nmol/L). Histamine levels did not differ significantly across Child‐Turcotte‐Pugh (CTP) stages nor strata of model for end‐stage liver disease (MELD) or HVPG. Histamine levels correlated with markers of circulatory dysfunction (i.e. sodium, renin and aldosterone). During a median follow‐up of 29.2 months, 68 patients developed ACLF or liver‐related death. In univariate as well as in multivariate analysis (adjusting for age, sex, HVPG as well as either MELD, clinical stage, and serum albumin or CTP and serum sodium), elevated histamine levels remained associated with the composite endpoint. CTP‐based multivariate model adjusted sub‐distribution hazard ratio (asHR): 1.010 (95% CI: 1.004–1.021), p <.001; MELD‐based multivariate model asHR: 1.030 (95% CI: 1.017–1.040), p <.001. Conclusion: High levels of histamine were linked to circulatory dysfunction in ACLD patients and independently associated with increased risks of ACLF or liver‐related death. Further mechanistic studies on the link between histamine signalling and development of hyperdynamic circulation and ACLF are warranted. [ABSTRACT FROM AUTHOR]

PURPOSE This meta-analysis aimed to evaluate the diagnostic accuracy of computed tomography (CT) for detecting gastroesophageal varices (GEVs) and identify high-risk GEVs in patients with cirrhosis. METHODS A comprehensive search of databases identified 28 studies reporting on CT-based diagnosis for GEVs confirmed via endoscopy. Meta-analyses were conducted to calculate pooled sensitivity (SEN) and pooled specificity (SPE), positive likelihood ratio (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC). RESULTS Based on the number of patients (or varices), the pooled SEN, SPE, PLR, NLR, DOR, and AUC of CTbased diagnosis were estimated at 0.91 (0.92), 0.81 (0.45), 4.82 (1.67), 0.11 (0.17), 42.47 (10.26), and 0.93 (0.94), respectively, for any GEV and at 0.89 (0.89), 0.90 (0.79), 8.86 (4.28), 0.12 (0.14), 75.71 (30.19), and 0.95 (0.85), respectively, for high-risk GEVs. Subgroup analyses indicated that CT had a higher diagnostic accuracy for esophageal varices compared with gastric varices (AUC: 0.93 vs. 0.89, P < 0.05), and the 64-slice CT yielded superior SEN compared with 16-slice and <16-slice CT (AUC: 0.97 vs. 0.92 and 0.82, respectively, P < 0.05). Prospective studies demonstrated higher diagnostic accuracy than retrospective studies (AUC: 0.95 vs. 0.90, P < 0.05). Regarding variceal size, a cut-off of 3 mm and 5 mm discriminated between low- and high-risk individuals, respectively, with high diagnostic accuracy (AUC: 0.992 vs. 0.997, P > 0.05). CONCLUSION CT demonstrates promising diagnostic accuracy for identifying gastroesophageal varices and distinguishing high-risk GEVs in patients with cirrhosis. Further research to validate optimal variceal size cut-offs is warranted to enhance clinical utility. CLINICAL SIGNIFICANCE Such a high diagnostic accuracy of CT scans for predicting varices is clinically meaningful for patients with cirrhosis accompanied by portal hypertension. If high-risk varices are identified at CT scans, early intervention would be helpful to reduce the risk of variceal bleeding. [ABSTRACT FROM AUTHOR]

Background: Portal vein pressure (PVP) is crucial in the diagnosis, treatment monitoring, and prognosis of portal hypertension (PHT). At present, the hepatic venous pressure gradient (HVPG) and the portal vein pressure gradient (PPG) are the main approaches for portal pressure measurement. However, HVPG and PPG are limited in application due to invasive operations and high requirements for medical conditions. A more convenient way to measure portal pressure is demanded. Objectives: To detect whether the endoscopic variceal pressure (EVP) could predict the PVP. Design: This is a single-center retrospective study that detects whether the EVP could predict the PVP. Methods: Thirty-six patients were considered eligible for pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) and were willing to accept the endoscopy-TIPS hybrid surgery (continuous operation within 24 h) from April 2023 to October 2023 retrospectively. EVP was measured in the procedure of the modified sandwich method. HVPG, PPG, and PVP were measured following TIPS operation. EVP was compared with HVPG, PPG, and PVP in groups divided by different sarin classifications and whether portal vein thrombosis (PVT) or not. Results: EVP was successfully measured and recorded in all. Totally, HVPG was lower than PPG, PPG was lower than PVP, and EVP manifested between PPG and PVP. In the PVT group, HVPG was lower than PPG, PPG was lower than EVP, and EVP manifested between PPG and PVP. In the non-PVT group, HVPG was lower than PPG, PPG was lower than PVP, and EVP manifested between PPG and PVP. In the gastroesophageal varices group, HVPG was lower than PPG, and PPG was lower than EVP. Conclusion: As a novel way for prediction, EVP measurement might be useful and convenient in PHT. Moreover, it might be closer to the PVP. [ABSTRACT FROM AUTHOR]

Hepatitis B and Hepatitis C are viral causes of Hepatitis that lead to significant worldwide mortality and morbidity through the sequelae of fibrosis and hepatocellular carcinoma. In this review, we have summarized recent studies that have examined the effects of antiviral therapy on the regression of fibrosis and the reduction in mortalities associated with the viruses. Antiviral therapy significantly decreases mortality and induces the regression of fibrosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) associated with portal vein thrombosis (PVT) represents an advanced stage of the tumor, with a subsequently poor prognosis and reduced therapeutic perspectives. These patients could present severe complications such as ascites, metastases, an increase in portal hypertension and potentially fatal gastrointestinal bleeding. The intricate molecular patterns at the basis of the development of TVP could also represent possible biomarkers in the early detection of patients at high risk of PVT. Hepatocellular carcinoma (HCC) represents the sixth most diagnosed cancer worldwide and is the second leading cause of cancer-related death in the world. The association of HCC and portal vein thrombosis (PVT) represents an advanced stage of the tumor. PVT has a prevalence of about 25–50% in HCC, determining poor prognosis and a remarkable reduction in therapeutic perspectives in these patients, leading to severe complications such as ascites, metastasis, an increase in portal hypertension and potentially fatal gastrointestinal bleeding. The aim of this review is to evaluate the molecular mechanisms that are at the basis of PVT development, trying to evaluate possible strategies in the early detection of patients at high risk of PVT. [ABSTRACT FROM AUTHOR]

Background Around 5% of patients with cirrhosis of the liver develop hepatic hydrothorax (HH). For patients with refractory HH (RHH), transjugular intrahepatic portosystemic shunt (TIPS) has been investigated in small studies. Hence, the present meta-analysis aimed to summarize the current data on the outcome of TIPS in patients with RHH. Methods From inception through June 2023, MEDLINE, Embase, and Scopus were searched for studies analyzing the outcome of TIPS in RHH. Clinical response, adverse events (AEs), mortality, and shunt dysfunction were the primary outcomes assessed. The event rates with their 95% confidence interval were calculated using a random-effects model. Results A total of 12 studies (n = 466) were included in the final analysis. The pooled complete and partial response rates were 47.2% (35.8–58.5%) and 25.5% (16.7–34.3%), respectively. The pooled incidences of serious AEs and post-TIPS liver failure after TIPS in RHH were 5.6% (2.1–9.0%) and 7.6% (3.1–12.1%), respectively. The pooled incidences of overall hepatic encephalopathy (HE) and severe HE nonresponsive to standard treatment after TIPS in RHH were 33.2% (20.0–46.4%) and 3.6% (0.4–6.8%), respectively. The pooled 1-month and 1-year mortality rates were 14.0% (8.3–19.6%) and 42.0% (33.5–50.4%), respectively. The pooled incidence of shunt dysfunction after TIPS in RHH was 24.2% (16.3–32.2%). Conclusion RHH has a modest response to TIPS in patients with cirrhosis, with only half having a complete response. Further studies are required to ascertain whether early TIPS can improve the outcome of patients with cirrhosis and HH. [ABSTRACT FROM AUTHOR]

Background and aims: The placement of Transjugular intrahepatic portosystemic shunt (TIPS) results in a sudden increase in central circulating blood volume, which requires proper regulation of the cardiovascular system. We aimed to investigate the impact of TIPS on cirrhotic cardiomyopathy (CCM). Method: A consecutive case series of patients with cirrhosis who underwent TIPS were evaluated by echocardiography and pressure measurements before, immediately after TIPS and 2–4 days later (delayed). Furthermore, all patients underwent a one-year follow-up. Results: In this study, 107 patients were enrolled, 38 (35.5%) with CCM. Echocardiography revealed an increase in postoperative left ventricular filling pressure accompanied by an elevation in left ventricular ejection fraction (LVEF). However, patients in the CCM group exhibited lower LVEF and mean arterial pressure (MAP) compared to the non-CCM group. Post-TIPS, CCM patients showed increased right atrium pressure (RAP) that normalized within 2–4 days, whereas non-CCM patients had lower RAP than baseline. Compared to patient without CCM, CCM patients revealed lower immediate (16.7 ± 4.4 vs. 18.9 ± 4.8, p = 0.022) and delayed 15.9 ± 3.7 vs. 17.7 ± 5.3, p = 0.044) portal vein pressures (PVP) and portal pressure gradients (PPG) (7.7 ± 3.4 vs. 9.2 ± 3.6, p = 0.032 and 10.1 ± 3.1 vs. 12.3 ± 4.9, p = 0.013). The 1-year mortality rates were 13.2% for CCM patients and 4.3% for non-CCM patients (log-rank test, p = 0.093), with MELD score, and preoperative RAP significantly associated with the mortality. Conclusion: Cirrhotic patients with CCM exhibit lower PVP and PPG immediately after TIPS and 2–4 days later, without significantly impacting one-year survival outcomes. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the differences between The balloon catheter method and End-hole Catheter Method in measuring hepatic venous pressure gradient (HVPG) among cirrhosis patients. Methods: From October 2017 to January 2024, patients who underwent HVPG measurements using both methods were consecutively included. HVPGs obtained from both methods were compared with the portal vein pressure gradient (PPG) obtained via transjugular intrahepatic portosystemic shunt (TIPS) using paired comparisons. Additionally, the consistency and predictive ability for bleeding risk of the two methods, as well as the impact of intrahepatic veno-venous shunt (IHVS), were analyzed. Results: The study enrolled 145 patients, each of whom had HVPG measured by both methods. PPG was measured in 61 patients. There was a statistically significant difference between the PPGs and HVPGs measured by both the balloon catheter method and the end-hole catheter method (P < 0.001), with the HVPG mean values obtained by the end-hole catheter method being closer to the PPGs. In the non-IHVS group, no significant statistical difference was found between the two methods (P = 0.071). In contrast, the IHVS group showed a significant difference (P < 0.001), with a mean difference of 2.98 ± 4.03 mmHg. When IHVS was absent, the measurement results from the end-hole catheter method and the balloon catheter method were found to be highly correlated. The end-hole catheter method has a higher screening capability for patients at risk of bleeding compared to the balloon catheter method (75.90% vs. 72.86%). Conclusion: HVPG measurements using either the balloon catheter method or end-hole catheter method showed significant difference with the PPG. The end-hole catheter method has a higher screening capability for patients at risk of bleeding, and IHVS could lead to lower HVPG measurements with The balloon catheter method. [ABSTRACT FROM AUTHOR]

Background Around 5% of patients with cirrhosis of the liver develop hepatic hydrothorax (HH). For patients with refractory HH (RHH), transjugular intrahepatic portosystemic shunt (TIPS) has been investigated in small studies. Hence, the present meta-analysis aimed to summarize the current data on the outcome of TIPS in patients with RHH.

Purpose The aim of this study was to evaluate the safety and efficacy of using a trans-splenic approach for transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with portal vein thrombosis. (PVT).

Transjugular intrahepatic portosystemic shunt (TIPS) has become essential in the treatment or prevention of portal hypertension‐related complications. In the early 1990s, the primary indication was refractory bleeding. It is now proposed for the treatment of ascites for the prevention of bleeding and in patients with vascular diseases of the liver. Thus, there are a growing number of patients being treated with TIPS all over the world. The broadening of indications, the involvement of multiple stakeholders, the need for an accurate selection, the positioning in relation to transplantation and the lack of standardization in pre‐therapeutic assessment, in the procedure itself and in the follow‐up have led the board of the French Association for the Study of the Liver to establish recommendations. [ABSTRACT FROM AUTHOR]

Purpose of this review: Aging is a process of physiological slowing, reduced regenerative capacity and inability to maintain cellular homeostasis. World Health Organisation declared the commencement of population aging globally, largely attributed to improvement in the healthcare system with early diagnosis and effective clinical management. Liver ages similar to other organs, with reduction in size and blood flow. In this review we aim to evaluate the effect of aging in liver disease. Recent findings: Aging causes dysregulation of major carbohydrate, fat and protein metabolism in the liver. Age is a major risk factor for liver fibrosis accelerated by sinusoidal endothelial dysfunction and immunological disharmony. Age plays a major role in patients with liver cirrhosis and influence outcomes in patients with portal hypertension. Transient elastography may be an useful tool in the assessment of portal hypertension. Hepatic structural distortion, increased vascular resistance, state of chronic inflammation, associated comorbidities, lack of physiological reserve in the older population may aggravate portal hypertension in patients with liver cirrhosis and may result in pronounced variceal bleed. Cut-offs for other non-invasive markers of fibrosis may differ in the elderly population. Non-selective beta blockers initiated at lower dose followed by escalation are the first line of therapy in elderly patients with cirrhosis and portal hypertension, unless contraindicated. Acute variceal bleed in the elderly cirrhotic patients can be life threatening and may cause rapid exsanguination due to poor reserve and associated comorbidities. Vasoactive drugs may be associated with more adverse reactions. Early endoscopy may be warranted in the elderly patients with acute variceal bleed. Role of TIPS in the elderly cirrhotics discussed. Summary: Management of portal hypertension in the older population may pose significant challenges to the treating clinician. [ABSTRACT FROM AUTHOR]

Simple Summary: Cirrhosis is the end-stage of chronic hepatitis, characterized by the replacement of hepatic parenchyma with fibrous tissue and regenerative nodules. In cirrhotic livers, reduced hepatic function and interference with portal blood flow cause sinusoidal portal hypertension, resulting in secondary complications such as varices, ascites, and hepatic encephalopathy. In human medicine, computed tomography (CT) is the most sensitive diagnostic imaging technique used to evaluate hepatic morphological change. However, there is limited information on the CT features of cirrhosis in dogs. This study aimed to describe the CT characteristics of histologically confirmed cirrhosis and to compare these characteristics between compensated and decompensated cirrhosis. The results of this study can aid clinicians in diagnosing cirrhosis and predicting the progression of cirrhosis to the decompensated phase. This study aimed to describe computed tomography (CT) characteristics of histologically confirmed cirrhosis and to compare these CT characteristics between compensated and decompensated cirrhosis. Sixteen dogs who underwent contrast CT and histopathological examinations were included; eleven dogs were assigned to the compensated group, and five dogs were assigned to the decompensated group. Irregular hepatic contours with a diffuse nodular distribution and hepatic lymph node enlargement are common concomitant features of cirrhotic livers on CT images. The enhancement patterns of the regenerative nodules and hepatic parenchyma were not significantly different from each other. Hypoattenuating areas with delayed contrast enhancement indicating fibrotic tissue were confirmed in 56.3% of cases. Hypoattenuating wedge-shaped area or nodule with minor or no contrast enhancement (histopathologically confirmed as focal necrosis) were confirmed in 37.5% of cases. Among CT variables, only normalized liver volume and portal vein-to-aorta ratio were significantly lower (p = 0.038 and 0.003, respectively) in the decompensated group. In conclusion, this study presented the CT features of cirrhosis and identified CT features that can discriminate between compensated and decompensated cirrhosis. Specifically, lower normalized liver volume and the portal vein-to-aorta ratio might be useful indicators for the progression of cirrhosis to the decompensated phase. [ABSTRACT FROM AUTHOR]

Rationale: Hepatopulmonary syndrome (HPS) is a severe complication of liver diseases characterized by abnormal dilation of pulmonary vessels, resulting in impaired oxygenation. Recent research highlights the pivotal role of liver-produced BMP-9 (bone morphogenetic protein-9) in maintaining pulmonary vascular integrity. Objectives: This study aimed to investigate the involvement of BMP-9 in human and experimental HPS. Methods: Circulating BMP-9 levels were measured in 63 healthy control subjects and 203 patients with cirrhosis with or without HPS. Two animal models of portal hypertension were employed: common bile duct ligation with cirrhosis and long-term partial portal vein ligation without cirrhosis. Additionally, the therapeutic effect of low-dose BMP activator FK506 was investigated, and the pulmonary vascular phenotype of BMP-9–knockout rats was analyzed. Measurements and Main Results: Patients with HPS related to compensated cirrhosis exhibited lower levels of circulating BMP-9 compared with patients without HPS. Patients with severe cirrhosis exhibited consistently low levels of BMP-9. HPS characteristics were observed in animal models, including intrapulmonary vascular dilations and an increase in the alveolar-arterial gradient. HPS development in both rat models correlated with reduced intrahepatic BMP-9 expression, decreased circulating BMP-9 level and activity, and impaired pulmonary BMP-9 endothelial pathway. Daily treatment with FK506 for 2 weeks restored the BMP pathway in the lungs, alleviating intrapulmonary vascular dilations and improving gas exchange impairment. Furthermore, BMP-9–knockout rats displayed a pulmonary HPS phenotype, supporting its role in disease progression. Conclusions: The study findings suggest that portal hypertension–induced loss of BMP-9 signaling contributes to HPS development. [ABSTRACT FROM AUTHOR]

\nIntroduction: Gastrointestinal varices rupture is considered to be prone to occur during atezolizumab and bevacizumab (Atez/Bev) treatment. This study aimed to investigate predictive factors affecting the increase in spleen volume (SpV) and the association of SpV variation with the clinical outcomes of Atez/Bev. Methods: A total of 164 HCC patients were included in this retrospective multicenter study. We measured SpV based on CT scans obtained before treatment and at evaluations. We used the inverse probability of treatment weight to address the imbalance between patient characteristics. Results: The median pretreatment SpV was 184 (130–257) cm3 and the median SpV variation was 27 (9–60) cm3. An increase in the SpV was observed in 140 patients (85.4%). Age <74 years (p = 0.03), mALBI grade 2b or 3 (p = 0.03), and pretreatment SpV ≥184 cm3 (p < 0.001) were significantly associated with increased SpV. There were no significant differences in progression-free survival (PFS) or overall survival (OS) between patients with SpV variation <25 cm3 and those with SpV variation ≥25 cm3 in the crude (p = 0.3 and 0.7) and IPTW-weighted cohorts (p = 0.08 and 0.8, respectively). Regarding pretreatment SpV, there were no significant differences in PFS or OS between patients with and without pretreatment spleen enlargement in the crude (both p = 0.3) and IPTW-weighted cohort (p = 0.6 and 0.3, respectively). Conclusion: Caution is warranted to detect the aggravation of portal hypertension when administering Atez/Bev to young patients or patients with an impaired liver function or pretreatment spleen enlargement. The impact of spleen modulation by Atez/Bev appears to be limited on clinical efficacy. Immunotherapy is now the standard of care for systemic therapy in hepatocellular carcinoma (HCC). The combination of atezolizumab and bevacizumab (Atez/Bev) is recommended for the first-line treatment, while gastrointestinal varices rupture is likely to be observed during Atez/Bev. Gastrointestinal varices rupture is a fatal event and developed due to portal hypertension. Spleen volume (SpV) plays an important role in portal hypertension based on previous studies, and we examined variation in SpV during Atez/Bev treatment and investigated predictive factors that affect the increase in SpV and the association of SpV variation and pretreatment SpV with the clinical outcome of Atez/Bev. The median pretreatment SpV was 184 (130–257) cm3 and the median SpV variation was 27 (9–60) cm3. An increase in the SpV was observed in 140 patients (85.4%). Age <74 years (p = 0.03), mALBI grade 2b or 3 (p = 0.03), and pretreatment SpV ≥184 cm3 (p < 0.001) were significantly associated with increased SpV. The present study revealed that there were no significant differences in progression-free survival and overall survival between patients with and without pretreatment spleen enlargement, as well as between patients with SpV variation ≥25 cm³ and those with SpV variation <25 cm³. In conclusion, caution is warranted to detect the aggravation of portal hypertension when administering Atez/Bev to young patients or those with an impaired liver function or pretreatment spleen enlargement. The impact of spleen modulation by Atez/Bev appears to be limited on clinical efficacy. [ABSTRACT FROM AUTHOR]

Background: Rebleeding is a significant complication of endoscopic injection of cyanoacrylate in gastric varices in cirrhotic patients. Aim: This systematic review and meta-analysis aimed to evaluate the efficiency of endoscopic cyanoacrylate injection and summarized the risk factors for rebleeding. Methods: Databases were searched for articles published between January 2012 and December 2022. Studies evaluating the efficiency of endoscopic injection of cyanoacrylate glue for gastric varices and the risk factors for rebleeding were included. Results: The final analysis included data from 24 studies. The hemostatic rates ranged from 65 to 100%. The pooled rate of gastric varices recurrence was 34% [95% CI 21–46, I2 = 61.4%], early rebleeding rate was 16% [95% CI 11–20, I2 = 37.4%], late rebleeding rate was 39% [95% CI 36–42, I2 = 90.9%], mild and moderate adverse events rate were 28% [95% CI 24–31, I2 = 91.6%], 3% [95% CI − 2 to 8, I2 = 15.3%], rebleeding-related mortality rate was 6% [95% CI 2–10, I2 = 0%], all-cause mortality rate was 17% [95% CI 12–22, I2 = 63.6%]. Independent risk factors for gastric variceal rebleeding included portal venous thrombosis, ascites, cyanoacrylate volume, fever/systemic inflammatory response syndrome, red Wale sign, previous history of variceal bleeding, active bleeding and paragastric veins. The use of proton pump inhibitors could be a protective factor. Conclusions: Endoscopic cyanoacrylate glue injection is an effective and safe treatment for gastric varices. Cirrhotic patients with the above risk factors may benefit from treatment aimed at reducing portal hypertension, antibiotic prophylaxis, and anticoagulation if they meet the indications. [ABSTRACT FROM AUTHOR]

Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH) require validation in patients with hepatitis D virus (HDV)-related compensated advanced chronic liver disease (cACLD). Therefore, we aimed to validate existing NIT algorithms for CSPH in this context. Patients with HDV-cACLD (LSM ≥10 kPa or histological METAVIR F3/F4 fibrosis) who underwent paired HVPG and NIT assessment at Medical University of Vienna or Hannover Medical School between 2013 and 2023 were retrospectively included. Liver stiffness measurement (LSM), von Willebrand factor to platelet count ratio (VITRO), and spleen stiffness measurement (SSM) were assessed. Individual CSPH risk was calculated according to previously published models (ANTICIPATE, 3P/5P). The diagnostic performance of Baveno VII criteria and refined algorithms (Baveno VII-VITRO, Baveno VII-SSM) was evaluated. The prognostic utility of NITs was investigated in the main cohort and an independent, multicenter, validation cohort. Fifty-one patients (HVPG ≥10 mmHg/CSPH prevalence: 62.7%, varices: 42.2%) were included. Patients with CSPH had significantly higher LSM (25.8 [17.2-31.0] vs. 14.0 [10.5-19.8] kPa; p <0.001), VITRO (n = 31, 3.5 [2.7-4.5] vs. 1.3 [0.6-2.0] %/[G/L]; p <0.001), and SSM (n = 20, 53.8 [41.7-75.5] vs. 24.0 [17.0-33.9] kPa; p <0.001). Composite CSPH risk models yielded excellent AUROCs (ANTICIPATE: 0.885, 3P: 0.903, 5P: 0.912). Baveno VII criteria ruled out CSPH with 100% sensitivity and ruled in CSPH with 84.2% specificity. The Baveno VII 'grey zone' (41.1%) was significantly reduced by Baveno VII-VITRO or Baveno VII-SSM algorithms, which maintained diagnostic accuracy. Hepatic decompensation within 2 years only occurred in patients who had CSPH or met Baveno VII rule-in criteria. The prognostic value of NITs was confirmed in the validation cohort comprising 92 patients. Standalone and composite NIT/diagnostic algorithms are useful for CSPH diagnosis in patients with HDV-cACLD. Thus, NITs may be applied to identify and prioritize patients with CSPH for novel antiviral treatments against chronic hepatitis D. Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH) have been developed to identify patients with compensated advanced chronic liver disease (cACLD) at risk of decompensation, but conflicting data has been published regarding the accuracy of liver stiffness measurement (LSM) for the staging of fibrosis in patients infected with hepatitis D virus (HDV). In our study, including 51 patients with HDV-cACLD, LSM- and lab-based NITs yielded high AUROCs for CSPH. Moreover, only patients with CSPH or high non-invasively assessed CSPH risk were at risk of decompensation within 2 years, with the prognostic value of NITs confirmed in a validation cohort. Thus, NITs should be applied and updated in yearly intervals in clinical routine to identify patients with HDV-cACLD at short-term risk of clinical events; NITs may also guide prioritization for novel antiviral treatment options. [Display omitted] • NITs for CSPH can be applied in HDV-cACLD with high accuracy. • NITs have similar ability to identify high-risk patients with HDV-cACLD as HVPG. • NITs may guide novel antiviral treatment prioritization and individualized prognostication. [ABSTRACT FROM AUTHOR]

The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the WFUMB Liver Elastography Guidelines Update released in 2018 and provides new evidence on the role of ultrasound elastography in chronic liver disease. The recommendations in this update were made and graded using the Oxford classification, including level of evidence (LoE), grade of recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [OCEBM] 2009). The guidelines are clinically oriented, and the role of shear wave elastography in both fibrosis staging and prognostication in different etiologies of liver disease is discussed, highlighting advantages and limitations. A comprehensive section is devoted to the assessment of portal hypertension, with specific recommendations for the interpretation of liver and spleen stiffness measurements in this setting. [ABSTRACT FROM AUTHOR]

Chronic liver injury leads to decreased liver function and increased fibrosis. Fibrosis is not only associated with the development of portal hypertension and carcinogenesis, but with the occurrence of events and a poor prognosis, highlighting the importance of non‐invasive fibrosis assessment in patients. In the present study, we searched for markers related to liver fibrosis via proteomic analysis of small extracellular vesicles (sEVs). In the discovery cohort, proteomic analysis was carried out in the sEVs extracted from the sera of 5 patients with decompensated cirrhosis, 5 patients with compensated cirrhosis, and 5 controls without liver disease. Interestingly, in this cohort, fibulin‐4 was significantly associated with cirrhosis while in the validation cohort [formed by 191 patients: 7 patients without disease, 16 patients without liver disease (other diseases), 38 patients with chronic liver disease (CLD), 75 patients with cirrhosis of Child–Pugh class A (36 without hepatocellular carcinoma [HCC], 29 with HCC), and 65 patients with cirrhosis of Child–Pugh class B–C (39 without HCC, 26 with HCC)], fibulin‐4/CD9 levels increased with cirrhosis progression. Furthermore, the fibulin‐4/CD9 ratio was significantly higher in patients with varices. Immunostaining also revealed strong fibulin‐4 expression in cholangiocytes within the fibrous areas and mesothelial cells in liver tissue blood vessels. Taken together, our results suggest that fibulin‐4, essential for lysyl oxidase activation, might be a new liver fibrosis marker found in the sEVs of patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Background: Propranolol, a non-selective beta-blocker, commonly used to prevent variceal bleed, but might precipitate circulatory dysfunction in severe ascites. Midodrine, an alpha-1 adrenergic agonist improves renal perfusion and systemic hemodynamics. Addition of midodrine might facilitate higher maximum tolerated dose (MTD) of propranolol, thereby less risk of variceal bleed in cirrhosis patients with severe ascites. Methods: 140 patients with cirrhosis and severe/refractory ascites were randomized- propranolol and midodrine (Gr.A,n = 70) or propranolol alone (Gr.B,n = 70). Primary outcome was incidence of bleed at 1 year. Secondary outcomes included ascites control, achievement of target heart rate (THR), HVPG response and adverse effects. Results: Baseline characteristics were comparable between two groups. Cumulative incidence of bleed at 1 year was lower in Gr.A than B (8.5%vs.27.1%,p-0.043). The MTD of propranolol was higher in Gr.A (96.67 ± 36.6 mg vs. 76.52 ± 24.4 mg; p-0.01) and more patients achieved THR (84.2%vs.55.7%,p-0.034). Significantly higher proportion of patients in Gr.A had complete resolution of ascites [17.1%vs.11.4%,p-0.014), diuretic tolerance (80%vs.60%,p-0.047) at higher doses(p-0.02) and lesser need for paracentesis. Patients in Gr.A also had greater reduction in variceal grade (75.7%vs.55.7%;p-0.01), plasma renin activity (54.4% from baseline) (p = 0.02). Mean HVPG reduction was greater in Gr.A than B [4.38 ± 2.81 mmHg(23.5%) vs. 2.61 ± 2.87 mmHg(14.5%),p-0.045]. Complications like post-paracentesis circulatory dysfunction and spontaneous bacterial peritonitis on follow-up were higher in Gr.B than A (22.8%vs.51.4%,p = 0.013 and 10%vs.15.7%, p = 0.03, respectively). Conclusion: Addition of midodrine facilitates effective use of propranolol in higher doses and greater HVPG reduction, thereby preventing first variceal bleed, reduced paracentesis requirements with fewer ascites- related complications in patients with cirrhosis with severe/refractory ascites. [ABSTRACT FROM AUTHOR]

Cirrhotic cardiomyopathy represents a syndrome of cardiac dysfunction associated with advanced liver disease. It is the result of complex pathophysiological processes that complicate the course of the disease, and is generally associated with a poor prognosis. Pathophysiologically, portal hypertension is the key factor leading to hyperdynamic circulation, via over-activation of the neurohumoral axis. Intestinal obstruction, subclinical inflammation and hepatocellular insufficiency, with defective synthesis or metabolism of several vasoactive mediators, are essential components of this process. Since it is usually unapparent at rest and only unmasked by an inadequate cardiac response to hemodynamic stress, the diagnosis of cirrhotic cardiomyopathy is challenging and demands a multimodal approach. There is currently no specific therapy, but there are prognostically effective drugs available to treat heart failure. Therefore, it is crucial to identify patients with chronic liver disease and heart failure in order to ameliorate their outcome. This article attempts to highlight the most important aspects of cirrhotic cardiomyopathy and draws attention to this condition. [ABSTRACT FROM AUTHOR]

Background & Aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is a non-invasive diagnostic biomarker of liver fibrosis. It is uncertain if LSM can predict risk for future liver-related outcomes in large, heterog-enous populations. Methods: This Swedish multi-centre cohort study included patients (n = 14414) from 16 sites who underwent LSM by VCTE between 2008 and 2020. Outcomes were ascertained from national registers. We investigated progression to cirrhosis with portal hypertension or hepatocellular carcinoma (HCC), separately. Cox regression was used to obtain hazard ratios (HRs). Harrel's C-index was used to measure discrimination of VCTE. Results: Included patients had a median age of 46 (interquartile range 34-57), median LSM of 5.9kPa (4.6-8.0), 59% were male, and the majority had hepatitis C (50.1%). During a median follow-up of 5.9 (4.3-8.0) years, 402 patients (2.7%) developed cirrhosis with portal hypertension. In patients with an LSM >25kPa, 28.7% developed cirrhosis with portal hypertension within 5years of follow-up, while only .6% of patients with an LSM <10 kPa did. This translated to a HR of 48.3 (95% confidence interval =37.6-62.0). VCTE had a high discriminative ability, with C-indices above .80 for most liver diseases, including .82 for MASLD. Similar findings were seen for incident HCC. Conclusions: Increased LSM by VCTE was associated with an increased risk of progression to both cirrhosis with portal hypertension, and to HCC, and had a high discriminative ability across different aetiologies of chronic liver diseases. These results support the use of VCTE to guide follow-up and treatment decisions. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to evaluate the safety and efficacy of using a trans-splenic approach for transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with portal vein thrombosis. (PVT). Material and Methods A retrospective review was performed on 36 consecutive patients with PVT who underwent TIPS using a trans-splenic approach from February 2018 to June 2021. Preprocedural data including demographic information and Model for End-Stage Liver Disease (MELD) scores were obtained. Outcomes measured included technical success, clinical success, complications, and survival. Results Technical success was achieved in 32 of 36 patients (89%). During the follow-up period, 16 of 32 (50%) required secondary TIPS interventions, most of which were planned as part of a staged procedure. 30/32 (94%) had stent patency on their most recent follow-up, with a median follow-up of 164 days. No patients had variceal bleeding following TIPS. 12 of 32 (38%) patients underwent successful transplant after TIPS. Anatomical portal vein end-to-end anastomosis was achieved in 11/12 (92%) patients. Conclusion The trans-splenic approach to TIPS is a reliable alternative to traditional TIPS in patients with PVT and provides high technical and clinical success rates. This technique can also be utilized to improve future liver transplant outcomes by facilitating anatomic portal vein end-to-end anastomoses. [ABSTRACT FROM AUTHOR]

The growing and evolving field of EUS and advanced hepatobiliary endoscopy has amplified traditional upper gastrointestinal endoscopy and unveiled novel options for remaining unsolved hepatobiliary issues, both diagnostically and therapeutically. This conceptually appealing and fascinating integration of endoscopy within the practice of hepatology is referred to as 'endo-hepatology'. Endo-hepatology focuses on the one hand on disorders of the liver parenchyma and liver vasculature and of the hepatobiliary tract on the other hand. Applications hanging under the umbrella of endohepatology involve amongst others EUS-guided liver biopsy, EUS-guided portal pressure measurement, EUS-guided portal venous blood sampling, EUS-guided coil & glue embolization of gastric varices and spontaneous portosystemic shunts as well as ERCP in the challenging context of (decompensated cirrhosis) and intraductal cholangioscopy for primary sclerosing cholangitis. Although endoscopic proficiency however does not necessarily equal in an actual straightforward end-solution for currently persisting (complex) hepatobiliary situations. Therefore, endohepatology continues to generate high-quality data to validate and standardize procedures against currently considered (best available) "golden standards" while continuing to search and trying to provide novel minimally invasive solutions for persisting hepatological stalemate situations. In the current review, we aim to critically appraise the status and potential future directions of endo-hepatology. [ABSTRACT FROM AUTHOR]

Summary: Decompensated cirrhosis has long been considered the irreversible end stage of liver disease, characterised by further decompensating events until death or liver transplantation. However, the observed clinical improvements after effective antiviral treatments for HBV and HCV and after sustained alcohol abstinence have changed this paradigm, leading to the concept of “recompensation” of cirrhosis. Recompensation of cirrhosis was recently defined by Baveno VII as (i) cure of the primary liver disease aetiology; (ii) disappearance of signs of decompensation (ascites, encephalopathy and portal hypertensive bleeding) off therapy; and (iii) stable improvement of liver function tests (bilirubin, international normalised ratio and albumin). Achieving these recompensation criteria is linked to a significant survival benefit. However, apart from aetiological therapies, no interventions/treatments that facilitate recompensation are available, the molecular mechanisms underlying recompensation remain incompletely understood, and early predictors of recompensation are lacking. Moreover, current recompensation criteria are based on expert opinion and may be refined in the future. Herein, we review the available evidence on cirrhosis recompensation, provide guidance on the clinical management of recompensated patients and discuss future challenges related to cirrhosis recompensation.

Background & Aims: Porto-sinusoidal vascular disorder (PSVD) is a rare and diagnostically challenging vascular liver disease. This study aimed to identify distinct metabolomic signatures in patients with PSVD or cirrhosis to facilitate non-invasive diagnosis and elucidate perturbed metabolic pathways. Methods: Serum samples from 20 healthy volunteers (HVs), 20 patients with histologically confirmed PSVD or 20 patients with cirrhosis were analyzed. Metabolites were measured using liquid chromatography-mass spectrometry. Differential abundance was evaluated with Limma’s moderated t-statistics. Artificial neural network and support vector machine models were developed to classify PSVD against cirrhosis or HV metabolomic profiles. An independent cohort was used for validation. Results: A total of 283 metabolites were included for downstream analysis. Clustering effectively separated PSVD from HV metabolomes, although a subset of patients with PSVD (n = 5, 25%) overlapped with those with cirrhosis. Differential testing revealed significant PSVD-linked metabolic perturbations, including pertubations in taurocholic and adipic acids, distinguishing patients with PSVD from both HVs and those with cirrhosis. Alterations in pyrimidine, glycine, serine, and threonine pathways were exclusively associated with PSVD. Machine learning models utilizing selected metabolic signatures reliably differentiated the PSVD group from HVs or patients with cirrhosis using only 4 to 6 metabolites. Validation in an independent cohort demonstrated the high discriminative ability of taurocholic acid (AUROC 0.899) for patients with PSVD vs. HVs and the taurocholic acid/aspartic acid ratio (AUROC 0.720) for PSVD vs. cirrhosis. Conclusions: High-throughput metabolomics enabled the identification of distinct metabolic profiles that differentiate between PSVD, cirrhosis, and healthy individuals. Unique alterations in the glycine, serine, and threonine pathways suggest their potential involvement in PSVD pathogenesis. Impact and implications:: Porto-sinusoidal vascular disorder (PSVD) is a vascular liver disease that can lead to pre-sinusoidal portal hypertension in the absence of cirrhosis, with poorly understood pathophysiology and no established treatment. Our study demonstrates that analyzing the serum metabolome could reveal distinct metabolic signatures in patients with PSVD, including alterations in the pyrimidine, glycine, serine and threonine pathways, potentially shedding light on the disease's underlying pathways. These findings could enable earlier and non-invasive diagnosis of PSVD, potentially reducing reliance on invasive procedures like liver biopsy and guiding diagnostic pathways.

BackgroundAlthough non-target puncture (NPT)-related complications are well known to clinicians performing TIPS, there is no NTP-focused study to assess the true clinical sequalae of NTP-related complications. In this study, the aim was to evaluate the incidence, safety, clinical outcomes and complications related to NTPs during the portal access of TIPS procedures.MethodsA retrospective review of 369 TIPS procedures from October 2007 to September 2019 was performed. We identified inadvertent NTPs, including biliary, hepatic artery, lymphatic and capsular punctures. Next, the medical records and images were reviewed and analyzed to assess the safety and clinical outcomes of these cohorts.ResultsA total of 71 NTPs were identified in 56 patients (15.18% of 369 patients). Of 369 TIPS patients, there were (1) 28 biliary punctures (7.6%), (2) 16 extracapsular punctures (4.3%), (3) 15 lymphatic punctures (4.1%) and (4) 12 hepatic artery punctures (3.3%). The overall complication rate was 2.2% (8/369). Based on the Clavien-Dindo classification, three patients (0.8%) had a minor complication. In addition, five patients (1.4%) experienced grade II-V major complications, such as symptomatic hemoperitoneum, arterio-biliary fistula or hemorrhagic shock leading to death. Mortality (0.5%) was only caused by extracapsular puncture combined with other NTP.ConclusionsNTPs during the portal access of TIPS procedures are associated with low complication risk. However, when extracapsular punctures are combined with other NTPs, a more severe complication, including mortality, can occur. Nevertheless, all patients with NTP should be closely monitored at a higher level of care after TIPS placement.

Objective To conduct a meta-analysis to assess the efficacy of intravascular ultrasound (IVUS) during transjugular intrahepatic portosystemic shunt (TIPS) creation. Methods MEDLINE and Embase databases were queried until July 2022 for comparative studies reporting procedure metrics for TIPS creation with or without IVUS guidance. Meta-analysis was performed with random-effects modelling for total procedural time, time to portal venous access, fluoroscopy time, iodinated contrast volume use, air kerma, dose area product, and number of needle passes. Intraoperative procedure-related complications were also reviewed. Results Of 95 unique records initially identified, 6 were eligible for inclusion. A total of 194 and 240 patients underwent TIPS with and without IVUS guidance. Pooled analyses indicated that IVUS guidance was associated with reduced total procedure time (SMD −0.76 [95% CI −1.02, −0.50] P  < .001), time to portal venous access (SMD −0.41 [95% CI −0.67, −0.15] P  = .002), fluoroscopy time (SMD, −0.54 [95% CI −1.02, −0.07]; P  = .002), contrast volume use (SMD, −0.89 [95% CI −1.16, −0.63]; P  < .001), air kerma (SMD, −0.75 [95% CI −1.11, −0.38]; P  < .001) and dose area product (SMD, −0.98 [95% CI −1.77, −0.20]; P  = .013). A total of 4.2 and 7.8 needle passes were required in the IVUS and non-IVUS group, respectively (SMD, −0.60 [95% CI −1.42, 0.21]; P  = .134). Pooled complication rates were 15.2% (12/79) and 21.4% (28/131), respectively. Conclusion IVUS guidance during TIPS creation improves procedural metrics including procedural time, contrast usage, and radiation exposure. Advances in Knowledge (1) The use of IVUS during TIPS is associated with shorter procedural time, lower contrast usage, and radiation exposure. (2)The use of IVUS is not associated with higher complication rates. [ABSTRACT FROM AUTHOR]

Background: Vascular plug-assisted retrograde transvenous obliteration (PARTO) obliterates the gastric varices and portosystemic shunt, thus resulting in a lower rebleeding rate than endoscopic glue/sclerotherapy. Aims: To evaluate the safety and efficacy of PARTO as salvage therapy in liver cirrhosis with gastric variceal bleed (GVB) after failed endotherapy. We assessed the clinical success rate and changes in liver function at 6- months. Materials and methods: Patients who underwent salvage PARTO after failed endotherapy for GVB (between December 2021 and November 2022) were searched and analyzed from the hospital database. Clinical success rate and rebleed rate were obtained at six months. Child–Pugh score (CTP) and Model for end-stage liver disease (MELD) score were calculated and compared between baseline and 6-month follow-up. Results: Fourteen patients (n = 14, Child–Pugh class A/B) underwent salvage PARTO. Nine had GOV-2, and five had IGV-1 varices. The mean shunt diameter was 11.6 ± 1.6 mm. The clinical success rate of PARTO was 100% (no recurrent gastric variceal hemorrhage within six months). No significant deterioration in CTP (6.79 ± 0.98 vs. 6.21 ± 1.52; p = 0.12) and MELD scores (11.5 ± 4.05 vs. 10.21 ± 3.19; p = 0.36) was noted at 6 months. All patients were alive at 6 months. One patient (n = 1, 7.1%) bled from esophageal varices after three days of PARTO and was managed with variceal banding. 21.4% (3/14) patients had progression of esophageal varices at 6 months requiring prophylactic band ligation. Three patients (21.4%) had new onset or worsening ascites and responded to low-dose diuretics therapy. Conclusions: PARTO is a safe and effective procedure for bleeding gastric varices without any deterioration in liver function even after six months. Patient selection is critical to prevent complications. Further prospective studies with larger sample size are required to validate our findings. [ABSTRACT FROM AUTHOR]

Cirrhosis has a high global incidence rate and serious harm. Numerous studies have shown that liver cirrhosis may cause cardiovascular abnormalities in patients, which are closely related to the severity of the condition and may have adverse effects on the prognosis of liver cirrhosis patients. Therefore, the pathogenesis and research progress in hyperdynamic circulation, portal hypertension pulmonary hypertension, cardiac systolic and diastolic dysfunction, cardiac electrophysiologic abnormalities, and cirrhotic cardiomyopathy are reviewed. To lay the foundation for further in-depth research on the prevention and treatment strategies of liver cirrhosis. [ABSTRACT FROM AUTHOR]

The renin–angiotensin system (RAS) is a complex homeostatic entity with multiorgan systemic and local effects. Traditionally, RAS works in conjunction with the kidney to control effective arterial circulation, systemic vascular resistance, and electrolyte balance. However, chronic hepatic injury and resulting splanchnic dilation may disrupt this delicate balance. The role of RAS in liver disease, however, is even more extensive, modulating hepatic fibrosis and portal hypertension. Recognition of an alternative RAS pathway in the past few decades has changed our understanding of RAS in liver disease, and the concept of opposing vs. "rebalanced" forces is an ongoing focus of research. Whether RAS inhibition is beneficial in patients with chronic liver disease appears to be context-dependent, but further study is needed to optimize clinical management and reduce organ-specific morbidity and mortality. This review presents the current understanding of RAS in liver disease, acknowledges areas of uncertainty, and describes potential areas of future investigation. [ABSTRACT FROM AUTHOR]

Objective: to establish how common Gastric Variceal bleeding is in Chronic liver Disease patients to alow them to be screened regularly and avoid morbidity and mortality. Study Design: Cross sectional study. Place and Duration of Study: Gastroenterology Department, Liaquat National Hospital and Medical Colege, Karachi Pakistan, from Jan to Dec 2020. Methodology: A total of 135 patients with history of melena, hematemesis and known diagnosis of Chronic liver Disease for more than six months who fulfiled the inclusion criteria were enroled in this study. Gastroscopy was carried out and dilated veins in the gastric fundus, either with active spurter or an overlying punctum, were labeled as Gastric Variceal bleeding. Results: This study included known Chronic Liver Disease patients for duration of 6 months or more with recent stigmata of upper Gastrointestinal Bleed. Out of 135 cases, 76(56.3%) were male and 59(43.7%) were female. Enroled patients' mean age was 51.0±5.2 years, and the mean duration of Chronic liver Disease was 4.9±2.6 years. Gastric Variceal bleeding in Chronic liver Disease patients who underwent endoscopy had a frequency of 18(13.3%) times. Conclusion: Gastric Variceal bleeding bleeding is rare but lethal complication of Chronic liver Disease, seen in patients in the age group of <50 years, female gender, hypertensive patients, and those with a duration of chronic liver disease <5 years. [ABSTRACT FROM AUTHOR]

The reader will come to appreciate that: • Severe cystic fibrosis liver disease (CLFD) commonly presents in early childhood years, and affects up to 10 % of people with cystic fibrosis by age 30 years. • United States CF Foundation (USCFF) guidelines have recently further defined CF hepatobiliary involvement (CFHBI) and advanced CF liver disease (aCFLD). • Familiarity with Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators monitoring guidelines is essential in clinical practice, particularly while their role in aCFLD is not established. Cystic fibrosis liver disease (CFLD) is characterised by a wide heterogenity of manifestations and severity. It represents a major cause of morbidity in people with cystic fibrosis (PwCF), which will be of increasing relevance as survival increases in the new era of cystic fibrosis care. No medical therapy currently available has evidence to treat or prevent progression of liver disease. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators may be transformative on pulmonary, nutritional and quality of life, but direct effect on long term liver disease outcomes is not yet established. Drug-associated hepatic adverse effects may be common, and clinician familiarity with drug-monitoring recommendations is essential. Longitudinal studies are required to understand the effect of CFTR modulators on the incidence and natural history of CFLD, including with early treatment initiation, in established advanced liver disease, and post liver transplantation. [ABSTRACT FROM AUTHOR]

This review explores the intricacies of evaluating cirrhotic patients for liver resection while exploring how to extend surgical intervention to those typically excluded by the Barcelona Clinic Liver Cancer (BCLC) criteria guidelines by focusing on the need for robust preoperative assessment and innovative surgical strategies. Cirrhosis presents unique challenges and complicates liver resection due to the altered physiology of the liver, portal hypertension, and liver decompensation. The primary objective of this review is to discuss the current approaches in assessing the suitability of cirrhotic patients for liver resection and aims to identify which patients outside of the BCLC criteria can safely undergo liver resection by highlighting emerging strategies that can improve surgical safety and outcomes. [ABSTRACT FROM AUTHOR]

Background and Objectives: Esophageal varices (EV) and variceal hemorrhages are major causes of mortality in liver cirrhosis patients. Detecting EVs early is crucial for effective management. Computed tomography (CT) scans, commonly performed for various liver-related indications, provide an opportunity for non-invasive EV assessment. However, previous CT studies focused on variceal diameter, neglecting the three-dimensional (3D) nature of varices and shunt vessels. This study aims to evaluate the potential of 3D volumetric shunt-vessel measurements from routine CT scans for detecting high-risk esophageal varices in portal hypertension. Methods: 3D volumetric measurements of esophageal varices were conducted using routine CT scans and compared to endoscopic variceal grading. Receiver operating characteristic (ROC) analyses were performed to determine the optimal cutoff value for identifying high-risk varices based on shunt volume. The study included 142 patients who underwent both esophagogastroduodenoscopy (EGD) and contrast-enhanced CT within six months. Results: The study established a cutoff value for identifying high-risk varices. The CT measurements exhibited a significant correlation with endoscopic EV grading (correlation coefficient r = 0.417, p < 0.001). A CT cutoff value of 2060 mm3 for variceal volume showed a sensitivity of 72.1% and a specificity of 65.5% for detecting high-risk varices during endoscopy. Conclusions: This study demonstrates the feasibility of opportunistically measuring variceal volumes from routine CT scans. CT volumetry for assessing EVs may have prognostic value, especially in cirrhosis patients who are not suitable candidates for endoscopy. [ABSTRACT FROM AUTHOR]

Background Endoscopic ultrasound-guided portal pressure gradient measurement (EUS-PPG) is a new modality where the portal pressure is measured by directly introducing a needle into the hepatic vein and portal vein. This is the first systematic review and meta-analysis to evaluate the efficacy and safety of EUS-PPG. Methods A comprehensive literature search was performed to identify pertinent studies. The primary outcomes assessed were the technical and clinical success of EUS-PPG. Technical success was defined as successful introduction of the needle into the desired vessel, while clinical success was defined as the correlation of the stage of fibrosis on the liver biopsy to EUS-PPG, or concordance of HVPG and EUS-PPG. The secondary outcomes were pooled rates for total and individual adverse events related to EUS-PPG. Pooled estimates were calculated using random-effects models with a 95% confidence interval (CI). Results Eight cohort studies with a total of 178 patients were included in our analysis. The calculated pooled rates of technical success and clinical success were 94.6% (95%CI 88.5-97.6%; P=<0.001; I² =0) and 85.4% (95%CI 51.5-97.0%; P=0.042; I² =70), respectively. The rate of total adverse events was 10.9% (95%CI 6.5-17.7%; P=<0.001; I² =4), and 93.7% of them were mild, as defined by the American Society for Gastrointestinal Endoscopy. Abdominal pain (11%) was the most common adverse event, followed by bleeding (3.6%). There were no cases of perforation or death reported in our study. Conclusions EUS-PPG is a safe and effective modality for diagnosing portal hypertension. Further randomized controlled trials are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Background and Aim: Statin use has shown a reduction in hepatic decompensation and portal hypertension. Its association with portal vein thrombosis (PVT) incidence is unknown. We aim to compare the incidence of PVT in patients with and without statin use. Methods: We excluded patients with a history of hepatocellular cancer, liver transplants, Budd–Chiari syndrome, and intra‐abdominal malignancies. Patients with cirrhosis were followed from their first hepatologist clinical encounter (January 1, 2016, to January 31, 2021) for 180 days to determine PVT incidence. We tested the association of statin use with PVT using 1:1 propensity score (PS) matching and Cox proportional hazard regression. Results: We analyzed 2785 patients with cirrhosis (mean age:61.0 ± 12.3 years, 44.3% female, 63.8% White, mean MELD‐Na score:11.7 ± 6.1, and statin use:23.1%). A total of 89 patients developed PVT during the follow‐up, which was lower in patients with statin use as compared to no statin use (1.3% vs 3.8%, P = 0.001, unadjusted HR:0.28, 95% CI: 0.13–0.62, P = 0.001). After matching for demographics, comorbidities, and hepatic decompensation events, patients with statin use had a lower risk of developing PVT in 180‐day follow‐up as compared to those without statin use (HR:0.24, 95% CI: 0.10–0.55, P = 0.001). Subgroup analysis showed that statin use was associated with lower PVT incidence in non‐NASH (HR: 0.20, 95% CI: 0.07–0.54, P = 0.002) and decompensated cirrhosis (HR: 0.12, 95% CI:0.03–0.53, P = 0.005) than no statin use. Conclusion: PVT incidence was lower in decompensated cirrhosis patients with statin use than in those with no statin use. However, this finding needs to be further tested in randomized control trials. [ABSTRACT FROM AUTHOR]

Non-invasive tests to assess the probability of clinically significant portal hypertension (CSPH) – including the ANTICIPATE±NASH models based on liver stiffness measurement and platelet count±BMI, and the von Willebrand factor antigen to platelet count ratio (VITRO) – have fundamentally changed the management of compensated advanced chronic liver disease (cACLD). However, their prognostic utility has not been compared head-to-head to the gold standard for prognostication in cACLD, i.e. the hepatic venous pressure gradient (HVPG). Patients with cACLD (liver stiffness measurement ≥10 kPa) who underwent advanced characterization via same-day HVPG/non-invasive test assessment from 2007-2022 were retrospectively included. Long-term follow-up data on hepatic decompensation was recorded. Four hundred and twenty patients with cACLD of varying etiologies, with a CSPH prevalence of 67.6%, were included. The cumulative incidence of hepatic decompensation at 1 and 2 years was 4.7% and 8.0%, respectively. HVPG, VITRO, and ANTICIPATE±NASH-CSPH-probability showed similar time-dependent prognostic value (AUROCs 0.683-0.811 at 1 year and 0.699-0.801 at 2 years). In competing risk analyses adjusted for MELD score and albumin, HVPG (adjusted subdistribution hazard ratio [aSHR] 1.099 [95% CI 1.054–1.150] per mmHg; p < 0.001), or VITRO (aSHR 1.134 [95% CI 1.062–1.211] per unit; p < 0.001), or ANTICIPATE±NASH-CSPH-probability (aSHR 1.232 [95% CI 1.094–1.387] per 10%; p < 0.001) all predicted first decompensation during follow-up. Previously proposed cut-offs (HVPG ≥10 mmHg vs. <10 mmHg, VITRO ≥2.5 vs. < 2.5, and ANTICIPATE-CSPH probability ≥60% vs. < 60%) all accurately discriminated between patients at negligible risk and those at substantial risk of hepatic decompensation. The prognostic performance of ANTICIPATE±NASH-CSPH-probability and VITRO is comparable to that of HVPG, supporting their utility for identifying patients who may benefit from medical therapies to prevent first hepatic decompensation. Non-invasive tests have revolutionized the diagnosis and management of clinically significant portal hypertension in patients with compensated advanced chronic liver disease (cACLD). However, limited data exists regarding the prognostic utility of non-invasive tests in direct comparison to the gold standard for prognostication in cACLD, i.e. the hepatic venous pressure gradient. In our study including 420 patients with cACLD, the ANTICIPATE±NASH model and VITRO yielded similar AUROCs to hepatic venous pressure gradient for hepatic decompensation within 1 to 2 years. Thus, non-invasive tests should be applied and updated in yearly intervals in clinical routine to identify patients at short-term risk, thereby identifying patients who may benefit from treatment aimed at preventing hepatic decompensation. [Display omitted] • Non-invasive tests have similar prognostic utility to the hepatic venous pressure gradient in patients with cACLD. • ANTICIPATE±NASH and VITRO identify patients at short-term risk of decompensation. • Non-invasive tests may be applied to individualize prognosis and treatment decisions in cACLD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Patients with cirrhosis often develop hyperdynamic circulation with increased cardiac output, heart rate, and redistribution of the circulating volume with expanded plasma volume (PV). PV determination is part of the evaluation of patients with cirrhosis, but gold-standard methods are invasive, expensive, and time-consuming. Therefore, other estimations of PV would be preferable, and the aim of this study was therefore to study if PV, as assessed by a simplified algorithm based on hematocrit and weight, can replace the gold-standard method. Methods: We included 328 patients with cirrhosis who had their PV assessed by the indicator dilution technique as the gold-standard method (PVI-125). Actual PV was estimated as PVa = (1 − hematocrit)·(a + (b·body weight)). Ideal PV was estimated as PVi = c · body weight, where a, b, and c are constants. Results: PVI-125, PVa, and PVi were 3.99 ± 1.01, 3.09 ± 0.54, and 3.01 ± 0.65 (Mean ± SD), respectively. Although PVI-125 correlated significantly with PVa (r = 0.72, p < 0.001), a Bland–Altman plot revealed wide limits of confidence. Conclusions: The use of simplified algorithms does not sufficiently estimate PV and cannot replace the indicator dilution technique. [ABSTRACT FROM AUTHOR]

Histologically cirrhosis is characterised by vascularised fibrosis septa that link portal tract with each other and with central veins leading to hepatocyte islands that are surrounded by fibrotic septa which are devoid of a central vein. The major clinical manifestations of cirrhosis are impaired hepatocyte function and increased intrahepatic resistance and development of portal hypertension and hepatocellular carcinoma. Liver has multiple functions including key role in metabolism, control of infection, elimination of toxins and byproducts of metabolism. This was a prospective study from 1st January 2023-31st December 2023 with a total of 100 deaths with presence of cirrhosis of liver detected during autopsy conducted in mortuary, Department of FMT, PMCH was analysed. Complete demographic, clinical details were obtained from accompanying relatives of the diseased, information sourced from police IO, inquest paper and medical records of the treatment furnished at the time of autopsy. Higher incidence of liver cirrhosis was found in age group 31-50 years, 74 percent of them were males, 30 percent were diabetic, alcohol was the etiological factor in 65 percent cases, NASH was etiological factor in 19%, hepatitis B and C was etiological factor in 12 % of the cases. [ABSTRACT FROM AUTHOR]

Background: Spleen stiffness measurement (SSM) correlates with the severity of portal hypertension. Aims: We investigated the utility of SSM in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) for detecting cirrhosis, esophageal varices (EV), and high-risk EV. Methods: 154 study participants with MASLD underwent simultaneous liver stiffness measurement (LSM) and SSM. 96 (62%) participants had an upper endoscopy (73 participants, i.e., 47% undergoing within a year). The diagnostic performance of SSM, as well as the BAVENO VII proposed SSM cutoffs (≥ 21 kPa, > 40 kPa, and > 50 kPa), was examined. Results: The failure rate for SSM was 19% compared to 5% for LSM. An invalid SSM was statistically significantly associated with a higher body mass index, a larger waist circumference, and a lower fibrosis stage. The area under the receiver operating characteristics for SSM to diagnose cirrhosis, EV, and high-risk EV was 0.78 (95% CI 0.70–0.85), 0.74 (95% CI 0.61–0.84), and 0.82 (95% CI 0.75–0.98), respectively. SSM ≥ 21 kPa cutoff had a sensitivity > 96% for all three outcomes, with a positive predictive value (PPV) of 88% for cirrhosis. In contrast, SSM > 40 kPa and SSM > 50 kPa cutoffs had better diagnostic abilities for identifying EV, particularly high-risk EV (sensitivity of 100% and 93% with NPV of 100% and 96%, respectively). Conclusion: SSM has a higher failure rate in individuals who are non-cirrhotic or have a higher BMI, or larger waist circumference. Although useful for diagnosing NASH cirrhosis, SSM is most reliable in excluding EV and high-risk EV. [ABSTRACT FROM AUTHOR]