-
International Journal of Surgery... Feb 2024Although surgery is the standard curative modality for hepatocellular carcinoma, more than two-thirds experience intrahepatic recurrence. Since no standard perioperative... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Although surgery is the standard curative modality for hepatocellular carcinoma, more than two-thirds experience intrahepatic recurrence. Since no standard perioperative treatment has been established, the authors performed a meta-analysis to evaluate the benefits of perioperative radiotherapy (RT).
METHODS
The PubMed, MEDLINE, EMBASE, and Cochrane Library were searched until May 2023. Randomized or propensity-matched studies evaluating at least five major clinical factors investigating benefit of perioperative RT, were included. The main effect measure were the pooled odds ratios (OR) regarding the benefit of perioperative RT using 2-year overall survival (OS) and 1-year disease-free survival (DFS) data.
RESULTS
Seven studies (five randomized and two propensity-matched studies) involving 815 patients were included. The pooled ORs for 1-year DFS and 2-year OS were 0.359 (95% CI: 0.246-0.523) and 0.371 (95% CI: 0.293-0.576), respectively, favoring perioperative RT, with very low heterogeneity. In the subgroup analyses, the benefits of OS and DFS were consistent between the two subgroups [portal vein thrombosis (PVT) and narrow resection margin (RM) groups]. In the PVT subgroup, the pooled OS rates at both 1-year and 2-year (75.6 vs. 36.9%, P <0.001; 25.6 vs. 9.9%, P =0.004) and DFS rates at both 1-year and 2-year (25.2 vs. 10.3%, P =0.194; 11.9 vs. 3.0%, P =0.022) were higher in the perioperative RT group. In the narrow RM subgroup, the surgery and RT groups showed higher pooled OS rates for both 1-year and 2-year (97.3 vs. 91.9%, P =0.042; 90.4 vs. 78.7%, P =0.051) and DFS (88.1 vs. 72.6%, P <0.001; 70.1 vs. 51.7%, P <0.001). Grade 5 toxicity was not reported, and three studies reported grade ≥3 or higher liver function test abnormalities, ranging from 4.8-19.2%.
CONCLUSION
The present study supports the oncological benefits of perioperative RT, for cases with high-risk of recurrence. Oncologic outcomes between subgroups differed according to clinical indications.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Disease-Free Survival; Randomized Controlled Trials as Topic
PubMed: 38000053
DOI: 10.1097/JS9.0000000000000914 -
Annals of Palliative Medicine Nov 2023A number of therapeutic treatment strategies exist for patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT). The aim of this review is to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A number of therapeutic treatment strategies exist for patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT). The aim of this review is to provide a current understanding of treatment options and determine the relative effectiveness of treatment options in preventing mortality over 24 months.
METHODS
A search was conducted in PubMed, EMBASE and Cochrane CENTRAL from 2007 to 2022. Articles were screened to identify those that reported on all-cause mortality among treated, non-palliative patients with HCC and PVT. Study quality was assessed using the Cochrane Risk of Bias in Non-Randomized Studies of Interventions tool (ROBINS-1). Mortality rates at prespecified timepoints between 6 and 24 months were extracted and summarized using a random-effects DerSimonian-Laird model. This review was registered a priori on PROSPERO (CRD42022290708).
RESULTS
When comparing radiotherapy (RT) to sorafenib and combined transarterial chemoembolization (TACE), there was a trend that RT yields better survival at 6 months [odds ratio (OR) 0.70, 95% confidence interval (CI): 0.28-1.76]. When comparing sorafenib to Y90 and RT, sorafenib was associated with higher odds for mortality at 6 months (OR 2.20, 95% CI: 1.11-4.39). No significant differences were noticed from 12 to 24 months.
CONCLUSIONS
Future strategies for HCC with PVT should look at the combination of radiation and systemic treatments either concurrently or sequentially.
Topics: Humans; Carcinoma, Hepatocellular; Sorafenib; Liver Neoplasms; Portal Vein; Chemoembolization, Therapeutic; Treatment Outcome; Venous Thrombosis
PubMed: 37953217
DOI: 10.21037/apm-23-463 -
Journal of Thrombosis and Haemostasis :... Feb 2024Limited evidence is available on management of splanchnic vein thrombosis (SVT). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Limited evidence is available on management of splanchnic vein thrombosis (SVT).
OBJECTIVES
This study aimed to evaluate safety and efficacy of direct oral anticoagulants (DOACs) for SVT treatment.
METHODS
Studies were systematically searched in the PubMed, Web of Science, and Scopus databases according to PRISMA guidelines. We assessed any recanalization, full recanalization, recurrence, mortality, and major bleeding as outcomes of interest. Results were reported as weighted mean prevalence (WMP) with 95% CI. Subgroup analyses and meta-regressions have been performed to address heterogeneity and adjust for potential confounders.
RESULTS
We included a total of 16 studies (17 datasets) on 648 patients with SVT treated with DOACs. We found any recanalization in 60.3% (95% CI: 41.8%-76.3%; I = 84.9%; P < .001) and full recanalization in 51.7% (95% CI: 36.0%-67.0%; I = 87.4%; P < .001). Recurrent venous thromboembolism occurred in 2.8% (95% CI: 1.4%-5.9%; I = 0%; P = .787) and death in 3.4% (95% CI: 1.6%-7.3%; I = 13.2%; P = .318) of patients. Major bleeding was reported by 5.8% (95% CI: 3.7%-8.9%; I = 29.2%; P = .125) of patients. Results were consistent when separately analyzing prospective studies, retrospective studies, studies on cirrhotic patients, and studies enrolling patients with portal vein thrombosis. Meta-regression analyses showed that an increasing age and cancer impacted the rate of recanalization. Cirrhosis was associated with a higher rate of major bleeding and mortality.
CONCLUSION
The results of the present study, mostly based on observational studies, suggest good safety and efficacy profiles of DOACs in patients with SVT. Randomized studies are needed to corroborate our findings.
Topics: Humans; Anticoagulants; Prospective Studies; Retrospective Studies; Venous Thrombosis; Hemorrhage; Venous Thromboembolism; Splanchnic Circulation
PubMed: 37926192
DOI: 10.1016/j.jtha.2023.10.023 -
Asian Journal of Andrology Oct 2023To evaluate the relationship between testosterone replacement therapy (TRT) and arterial and/or venous thrombosis in patients with pre-treatment total testosterone (TT)...
To evaluate the relationship between testosterone replacement therapy (TRT) and arterial and/or venous thrombosis in patients with pre-treatment total testosterone (TT) <12 nmol l-1, we performed a meta-analysis following the Population Intervention Comparison Outcome model. Population: men with TT <12 nmol l-1 or clear mention of hypogonadism in the inclusion criteria of patients; intervention: TRT; comparison: placebo or no therapy; outcomes: arterial thrombotic events (stroke, myocardial infarction [MI], upper limbs, and lower limbs), VTE (deep vein thrombosis [DVT], portal vein thrombosis, splenic thrombosis, and pulmonary embolism), and mortality. A total of 2423 abstracts were assessed for eligibility. Twenty-four studies, including 14 randomized controlled trials (RCTs), were finally included, with a total of 4027 and 310 288 hypotestosteronemic male patients, from RCTs and from observational studies, respectively. Based on RCT-derived data, TRT did not influence the risk of arterial thrombosis (odds ratio [OR] = 1.27, 95% confidence interval [CI]: 0.47-3.43, P = 0.64), stroke (OR = 1.34, 95% CI: 0.09-18.97, P = 0.83), MI (OR = 0.51, 95% CI: 0.11-2.31, P = 0.39), VTE (OR = 1.42, 95% CI: 0.22-9.03, P = 0.71), pulmonary embolism (OR = 1.38, 95% CI: 0.27-7.04, P = 0.70), and mortality (OR = 0.70, 95% CI: 0.20-2.38, P = 0.56). Meanwhile, when only observational studies are considered, a significant reduction in the risk of developing arterial thrombotic events, MI, venous thromboembolism, and mortality was observed. The risk for DVT remains uncertain, due to the paucity of RCT-based data. TRT in men with TT <12 nmol l-1 is safe from the risk of adverse cardiovascular events. Further studies specifically assessing the risk of DVT in men on TRT are needed.
PubMed: 37921515
DOI: 10.4103/aja202352 -
European Journal of Radiology Nov 2023The morphometry of the hepatic portal vein is of clinical importance, particularly in pre-operative assessments, surgical management, and diagnoses of liver conditions.... (Meta-Analysis)
Meta-Analysis
PURPOSE
The morphometry of the hepatic portal vein is of clinical importance, particularly in pre-operative assessments, surgical management, and diagnoses of liver conditions. This systematic review and meta-analysis aimed to characterize the morphometry of the normal portal vein in both pediatric and adult patients.
METHODS
The study, conducted using the PRISMA guidelines and registered with PROSPERO, utilized the MEDLINE, EMBASE, SCOPUS and Web of Science databases up to May 2020, and updated to May 2023. All studies reporting extractable data on diameter, length, and cross-sectional area (CSA) of the main, left, and right portal veins (PV, LPV, RPV, respectively) were included. The AQUA Tool was used to assess the quality of the included studies. Data analysis included subgroup analyses based on geographical location, sex, age, and imaging modality.
RESULTS
A total of 122 studies with 11,637 subjects were eligible for inclusion. Overall, the pooled mean diameter of the PV (PVD) was 10.09 mm (95% CI: 9.56-10.62). Significant differences in diameter were found between pediatric (6.60 mm; 95% CI: 5.38-7.82) and adult (10.72 mm; 95% CI: 10.25-11.19) subjects. Additionally, there was a significantly larger PVD measurement from computed tomography (CT) than other imaging modalities: CT, 13.28 mm (95% CI: 11.71-14.84); magnetic resonance imaging (MRI), 10.50 mm (95% CI: 9.35-11.66) and ultrasound (US), 9.81 mm (95% CI: 9.47-10.16). The mean diameters of the LPV and RPV were 8.27 mm (95% CI: 6.78-9.77) and 8.33 mm (95% CI: 6.70-9.95), respectively. Mean PV length in adults is 48.63 mm (95% CI: 35.63-61.64). Mean CSA of the PV was 1.09 cm.
CONCLUSIONS
The study obtained aim to improve the understanding of portal vein anatomy, especially with relevance to surgical interventions of the liver in both pediatric and adult patients. Measurements from ultrasound imaging closely approximates the generated pooled PVD mean for pediatric and adult patients. CT imaging, however, significantly exceeded the established 13 mm threshold for adults. For pediatric patients, a threshold of 8 mm is proposed as a diagnostic upper limit for a normal PVD. Although not significant, the PVD decreased from the portal confluence towards its bifurcation.
Topics: Humans; Adult; Child; Portal Vein; Liver Diseases; Tomography, X-Ray Computed; Magnetic Resonance Imaging
PubMed: 37742371
DOI: 10.1016/j.ejrad.2023.111016 -
United European Gastroenterology Journal Oct 2023Transjugular intrahepatic portosystemic shunts (TIPS) in patients with hepatocellular carcinoma (HCC) may improve access to curative therapies, treat portal hypertension...
BACKGROUND/AIMS
Transjugular intrahepatic portosystemic shunts (TIPS) in patients with hepatocellular carcinoma (HCC) may improve access to curative therapies, treat portal hypertension (PH)-related complications without worsening liver function, and increase overall survival. Data on the efficacy and safety of TIPS to treat PH complications in HCC patients, as well as the HCC treatment response, were evaluated.
METHODS
Studies reporting efficacy in controlling bleeding/ascites or response to HCC therapy, safety, and survival in patients with HCC and TIPS were searched systematically on PubMed and Embase. An extraction of articles using predefined data fields and quality indicators was used.
RESULTS
We selected 19 studies and found 937 patients treated for ascites/bleeding and 177 evaluating HCC treatment response. Over half were under 5 cm and solitary lesions, and most studies included tumours with portal vein thrombosis. Regarding PH studies, TIPS resolved bleeding/ascites in >60% of patients, more effective for bleeding. There were no lethal complications reported and procedural bleeding occurred in <5%. Hepatic encephalopathy occurred in 15%-30% within three months. In the HCC treatment-response studies, major complication rates were low with no mortality. In the studies that evaluated the response to transarterial chemoembolization, complete response rate of patients with TIPS varied from 16% to 75%. Liver transplantation rate varied from 8% to 80%, with >40% rate in half of the studies.
CONCLUSIONS
In the published studies, TIPS is effective in treating PH complications in patients with HCC. Prospective studies on TIPS placement in patients with HCC are urgently needed to evaluate the efficacy and safety of TIPS in this setting.
Topics: Humans; Carcinoma, Hepatocellular; Portasystemic Shunt, Transjugular Intrahepatic; Liver Neoplasms; Ascites; Prospective Studies; Esophageal and Gastric Varices; Treatment Outcome; Chemoembolization, Therapeutic; Hypertension, Portal
PubMed: 37736854
DOI: 10.1002/ueg2.12454 -
Obstetric Medicine Sep 2023Concerned studies with respect to the outcome of pregnant patients with non-cirrhotic portal hypertension are limited. Thus, a systematic review and meta-analysis of the...
BACKGROUND
Concerned studies with respect to the outcome of pregnant patients with non-cirrhotic portal hypertension are limited. Thus, a systematic review and meta-analysis of the available literature was conducted.
METHODS
A literature search was conducted from 1999 to December 2021 for studies evaluating pregnancy outcomes in patients with non-cirrhotic portal hypertension.
RESULTS
Twelve studies were included in the meta-analysis. The pooled rate of variceal bleeding, ascites and severe anemia requiring blood transfusion were 9.6%, 2.3%, and 14.9%, respectively. The pooled rate of spontaneous miscarriage, gestational hypertension, delivery by cesarean section, and postpartum hemorrhage were 11.9%, 4.5%, 36.7%, and 4.7%, respectively. The pooled stillbirth rate was 2.5% and among the live births, the pooled rates of preterm birth, low birth weight, intensive care unit admission, and neonatal mortality were 21.6%, 18.7%, 15.5%, and 1.8%, respectively.
CONCLUSION
Pregnancy in patients with non-cirrhotic portal hypertension is associated with increased maternal & fetal morbidity but mortality remains low.
PubMed: 37719996
DOI: 10.1177/1753495X221143864 -
The Cochrane Database of Systematic... Sep 2023Liver transplantation is the only chance of cure for people with end-stage liver disease and some people with advanced liver cancers or acute liver failure. The... (Review)
Review
BACKGROUND
Liver transplantation is the only chance of cure for people with end-stage liver disease and some people with advanced liver cancers or acute liver failure. The increasing prevalence of these conditions drives demand and necessitates the increasing use of donated livers which have traditionally been considered suboptimal. Several novel machine perfusion preservation technologies have been developed, which attempt to ameliorate some of the deleterious effects of ischaemia reperfusion injury. Machine perfusion technology aims to improve organ quality, thereby improving outcomes in recipients of suboptimal livers when compared to traditional static cold storage (SCS; ice box).
OBJECTIVES
To evaluate the effects of different methods of machine perfusion (including hypothermic oxygenated machine perfusion (HOPE), normothermic machine perfusion (NMP), controlled oxygenated rewarming, and normothermic regional perfusion) versus each other or versus static cold storage (SCS) in people undergoing liver transplantation.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 10 January 2023.
SELECTION CRITERIA
We included randomised clinical trials which compared different methods of machine perfusion, either with each other or with SCS. Studies comparing HOPE via both hepatic artery and portal vein, or via portal vein only, were grouped. The protocol detailed that we also planned to include quasi-randomised studies to assess treatment harms.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. overall participant survival, 2. quality of life, and 3. serious adverse events. Secondary outcomes were 4. graft survival, 5. ischaemic biliary complications, 6. primary non-function of the graft, 7. early allograft function, 8. non-serious adverse events, 9. transplant utilisation, and 10. transaminase release during the first week post-transplant. We assessed bias using Cochrane's RoB 2 tool and used GRADE to assess certainty of evidence.
MAIN RESULTS
We included seven randomised trials (1024 transplant recipients from 1301 randomised/included livers). All trials were parallel two-group trials; four compared HOPE versus SCS, and three compared NMP versus SCS. No trials used normothermic regional perfusion. When compared with SCS, it was uncertain whether overall participant survival was improved with either HOPE (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.42 to 1.98; P = 0.81, I = 0%; 4 trials, 482 recipients; low-certainty evidence due to imprecision because of low number of events) or NMP (HR 1.08, 95% CI 0.31 to 3.80; P = 0.90; 1 trial, 222 recipients; very low-certainty evidence due to imprecision and risk of bias). No trials reported quality of life. When compared with SCS alone, HOPE was associated with improvement in the following clinically relevant outcomes: graft survival (HR 0.45, 95% CI 0.23 to 0.87; P = 0.02, I = 0%; 4 trials, 482 recipients; high-certainty evidence), serious adverse events in extended criteria DBD liver transplants (OR 0.45, 95% CI 0.22 to 0.91; P = 0.03, I = 0%; 2 trials, 156 participants; moderate-certainty evidence) and clinically significant ischaemic cholangiopathy in recipients of DCD livers (OR 0.31, 95% CI 0.11 to 0.92; P = 0.03; 1 trial, 156 recipients; high-certainty evidence). In contrast, NMP was not associated with improvement in any of these clinically relevant outcomes. NMP was associated with improved utilisation compared with SCS (one trial found a 50% lower rate of organ discard; P = 0.008), but the reasons underlying this effect are unknown. We identified 11 ongoing studies investigating machine perfusion technologies.
AUTHORS' CONCLUSIONS
In situations where the decision has been made to transplant a liver donated after circulatory death or donated following brain death, end-ischaemic HOPE will provide superior clinically relevant outcomes compared with SCS alone. Specifically, graft survival is improved (high-certainty evidence), serious adverse events are reduced (moderate-certainty evidence), and in donors after circulatory death, clinically relevant ischaemic biliary complications are reduced (high-certainty evidence). There is no good evidence that NMP has the same benefits over SCS in terms of these clinically relevant outcomes. NMP does appear to improve utilisation of grafts that would otherwise be discarded with SCS; however, the reasons for this, and whether this effect is specific to NMP, is not clear. Further studies into NMP viability criteria and utilisation, as well as head-to-head trials with other perfusion technologies are needed. In the setting of donation following circulatory death transplantation, further trials are needed to assess the effect of these ex situ machine perfusion methods against, or in combination with, normothermic regional perfusion.
Topics: Humans; Liver Transplantation; Quality of Life; Perfusion; End Stage Liver Disease
PubMed: 37698189
DOI: 10.1002/14651858.CD014685.pub2 -
Journal of Crohn's & Colitis Mar 2024Inflammatory bowel disease [IBD] comprises an immune-mediated group of chronic gastrointestinal disorders. Patients with IBD may experience extraintestinal... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Inflammatory bowel disease [IBD] comprises an immune-mediated group of chronic gastrointestinal disorders. Patients with IBD may experience extraintestinal manifestations, such as hepatobiliary complications. This meta-analysis aims to assess the prevalence of different hepatic manifestations in IBD patients.
METHODS
For this systematic review and meta-analysis, PubMed, Scopus, Web of Science, and Embase were searched until July 20, 2022, by specifying keywords for IBD, hepatic manifestations, and study type. Full texts of cohort studies in English that examined the prevalence of different hepatic manifestations were included in this study. The primary outcome was the overall prevalence of hepatic manifestations in IBD patients. For the statistical analysis, a proportion by random effect model meta-analysis was performed. The registration number for the protocol of this study in PROSPERO is CRD42022369595.
RESULTS
From the 4421 articles retrieved from the primary search, 118 met the inclusion criteria and were included in the final analysis. After a pooled analysis of 1 729 128 patients, the overall prevalence of hepatic manifestations was 3.49% (95% confidence interval [CI]: 3.31-3.68%; I2: 99.55%). The pooled prevalence of non-alcoholic fatty liver disease in 228 216 patients was 26.1% [95% CI: 22.1-30.2%; I2: 99.018%]. After pooled analysis of 9642 patients, the prevalence of primary sclerosing cholangitis was 1.67% [95% CI: 1.47-1.88%; I2: 99.10%]. The pooled prevalence of biliary stones was 4.1% [95% CI: 3.6-4.7%; I2: 97.43%]. Autoimmune hepatitis (0.51% [95% CI: 0.26-0.75%]; I2: 85.36%) and portal vein thrombosis (0.21% [95% CI: 0.08-0.33%]; I2: 97.95%) are considered as rare manifestations.
CONCLUSION
This study summarizes the prevalence and importance of different hepatic manifestations in IBD patients. These findings are crucial for the management of extraintestinal manifestations, especially hepatic manifestations, in IBD patients.
Topics: Humans; Inflammatory Bowel Diseases; Prevalence; Research Design; Liver Diseases
PubMed: 37695111
DOI: 10.1093/ecco-jcc/jjad157 -
Indian Journal of Gastroenterology :... Oct 2023Both Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT) have been linked to various prothrombotic (PT) conditions. The PT profile in Asians is different from... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Both Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT) have been linked to various prothrombotic (PT) conditions. The PT profile in Asians is different from the west and there are no nationwide epidemiological surveys from India. Hence, the present meta-analysis was aimed at analyzing the prevalence of acquired and hereditary thrombophilia among Indian patients with non-cirrhotic PVT and BCS.
METHODS
A comprehensive literature search of Embase, Medline and Scopus was conducted from January 2000 to February 2022 for studies evaluating the prevalence of various PT conditions in Indian patients with PVT and BCS. Pooled prevalence rates across studies were expressed with summative statistics.
RESULTS
Thirty-five studies with 1005 PVT patients and 1391 BCS patients were included in the meta-analysis. At least one PT condition was seen in 46.2% (28.7-63.7) of the PVT patients and 44.9% (37.3-60.7) of the BCS patients. Multiple PT conditions were seen in 13.0% (4.2-21.8) of the PVT patients and 7.9% (3.5-12.4) of the BCS patients. Among PVT patients, hyperhomocysteinemia was the commonest prothrombotic condition (21.6%) followed by protein C (PC) deficiency (10.7%), Janus kinase 2 (JAK-2) mutation (8.5%) and antiphospholipid antibodies (APLA) (7.5%). Among patients with BCS, PC deficiency was the commonest prothrombotic condition (10.6%) followed by methylenetetrahydrofolate reductase (MTHFR) mutation (9.8%), APLA (9.7%) and JAK-2 mutation (9.1%).
CONCLUSION
The PT profile in Indian patients with abdominal vein thrombosis is different from that of the western data with a lower prevalence of PT conditions in patients with BCS.
Topics: Humans; Budd-Chiari Syndrome; Portal Vein; Venous Thrombosis; Thrombosis; Mutation
PubMed: 37610562
DOI: 10.1007/s12664-023-01400-5