Introduction: Liver cirrhosis is a condition characterized by the gradual replacement of normal liver tissue with scar tissue, ultimately leading to liver failure. This slow and progressive disease begins with a chronic inflammatory process induced by a noxious agent. In its advanced stages, the disease lacks effective therapies. Research has demonstrated the significant involvement of the endocannabinoid system in the pathogenesis of this disease. This study evaluated the hepatoprotective effect of cannabidiol (CBD) in the progression of experimental hepatic cirrhosis induced by thioacetamide (TAA) in rats. Methods: A randomized experimental design was employed using Holtzman rats. Hepatic cirrhosis was induced by intraperitoneal administration of TAA at a dose of 150 mg/kg for 6 weeks, with treatment initiated additionally. The groups were as follows: Group 1: TAA + vehicle; Group 2: TAA + CBD 2 mg/kg; Group 3: TAA + CBD 9 mg/kg; Group 4: TAA + CBD 18 mg/kg; Group 5: TAA + silymarin 50 mg/kg; and Group 6: Healthy control. Serum biochemical analysis (total bilirubin, direct bilirubin, ALT, AST, alkaline phosphatase, and albumin) and hepatic histopathological study were performed. The Knodell histological activity index (HAI) was determined, considering periportal necrosis, intralobular degeneration, portal inflammation, fibrosis, and focal necrosis. Results: All groups receiving TAA exhibited an elevation in AST levels; however, only those treated with CBD at doses of 2 mg/kg and 18 mg/kg did not experience significant changes compared to their baseline values (152.8 and 135.7 IU/L, respectively). Moreover, ALT levels in animals treated with CBD showed no significant variation compared to baseline. The HAI of hepatic tissue was notably lower in animals treated with CBD at doses of 9 and 18 mg/kg, scoring 3.0 and 3.25, respectively, in contrast to the TAA + vehicle group, which recorded a score of 7.00. Animals treated with CBD at 18 mg/kg showed a reduced degree of fibrosis and necrosis compared to those receiving TAA alone (p ≤ 0.05). Conclusion: Our findings demonstrate that cannabidiol exerts a hepatoprotective effect in the development of experimental hepatic cirrhosis induced in rats.

BACKGROUND: The Baveno criteria for assessing advanced liver fibrosis were mainly determined by transient elastography (TE), and its pathology-based validation studies in two-dimensional shear wave elastography (2D-SWE) remain limited. We aimed to validate the Baveno criteria through use of 2D-SWE.
METHODS: Consecutive patients who underwent liver biopsies for various benign liver diseases were prospectively recruited. Liver stiffness measurement (LSM) was simultaneously evaluated by TE and 2D-SWE. The optimal cutoff value to predict advanced liver fibrosis was determined by the Youden Index, and the diagnostic performance was estimated using area under the receiver operating characteristic (AUROC) analysis.
RESULTS: A total of 101 patients were enrolled having a median age of 55.0 (IQR: 46.0-63.5) years, with 53 (52.48%) of them being male. Using <9 and >14 kPa as the optimal dual cutoffs, the AUROC values in TE and 2D-SWE were 0.92 (95% CI: 0.83-0.97) and 0.93 (95% CI: 0.84-0.98), respectively (p = 0.61). The sensitivity and specificity of LSM by TE/2D-SWE achieved rates of 94.44%/94.44% and 86.00%/88.00%, respectively. However, using the Baveno criteria, the AUROC values in TE and 2D-SWE could remain achieving 0.91 (95% CI: 0.82-0.97) and 0.93 (95% CI: 0.84-0.98), respectively (p = 0.36). The sensitivity and specificity in TE/2D-SWE were 88.24%/88.24% and 86.79%/90.57%, respectively.
CONCLUSIONS: This study establishes the compatibility of the Baveno dual cutoff criteria with 2D-SWE, positioning it as an easily used criteria in clinical practice and research.

An 82-year-old man with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) complicated by hepatocarcinoma was presented. Remission induction therapy of hyper-CVAD with half dose reduction achieved hematological complete remission (CR), but accompanied with elevated alanine aminotransferase and hyperbilirubinemia. The patient was thought intolerable for hyper-CVAD with half dose reduction due to liver toxicity, and treatment was switched to blinatumomab. Hematological CR was sustained after nine cycles of blinatumomab without exacerbation of liver dysfunction. After five courses of blinatumomab, hepatocarcinoma was treated successfully by trans-arterial chemoembolization. Two years after the diagnosis of ALL, the patient was alive in CR status of ALL.

UNASSIGNED: To investigate risk factors for portal venous thrombosis (PVT) after partial splenic artery embolization (PSE) in hepatic cirrhosis patients.
UNASSIGNED: The authors retrospectively analyzed 151 hepatic cirrhosis patients with hypersplenism who underwent partial splenic artery embolization between January 2020 and December 2021. The patients were divided into a PVT group and a non-PVT group according to whether they had PVT after PSE. Univariate analyses were performed to select risk factors for PVT after PSE, and multivariate analysis was used to analyze variates with a value of P less than 0.1 in univariate analysis.
UNASSIGNED: There were 151 patients enroled in the study, with 22 patients in the PVT group and 129 patients in the non-PVT group. There was no significant difference in terms of age, sex, smoking, hypertension, diabetes, Child-Pugh between two groups. White blood cell (WBC) and platelet counts after PSE were significantly higher than those before PSE in both the PVT group and non-PVT group. Univariate analysis showed that portal venous blood flow velocity, ligation of oesophageal varices and WBC after PSE were found to have a P value less than 0.1. Multivariate analysis showed that portal venous blood flow velocity was a factor associated with PVT after PSE.
UNASSIGNED: Portal venous blood flow velocity was a factor associated with PVT after PSE. Portal venous blood flow velocity should be considered before patients undergo PSE.

UNASSIGNED: The liver is the organ responsible for the metabolism of nutrients, some drugs, and the production of coagulation factors. According to the World Health Organization, approximately 23 million people worldwide are diagnosed with liver disease each year. As a result, it is common for dentists to encounter these patients on a daily basis in their practice. The objective of this review is to establish the dental management of patients with liver disease.
UNASSIGNED: A manual literature search was conducted using the indexed articles in PUBMED and EBSCO databases using the keywords \"oral surgery,\" AND \"liver disease,\" AND \"hepatic cirrhosis,\" AND \"dental management\".
UNASSIGNED: Patients with liver disease present important characteristics for the dentist, which must be recognized in order to perform procedures with the lowest risk of intraoperative and postoperative complications. A patient with poorly controlled underlying liver disease is more prone to infections and bleeding, which implies a high risk of morbidity.
UNASSIGNED: Dental care for patients with liver disease should be assessed according to the reason for consultation, control of the disease, the complexity of the procedure to be performed, and both intraoperative and postoperative hemostatic measures. All necessary hemostatic measures should be considered and dose adjustments should be considered in the use of NSAIDs.

BACKGROUND: The methylation SEPT9 (mSEPT9) appeared to be effective for hepatocellular carcinoma (HCC) detection. However, its performance in high-risk population has not been validated. We designed a pilot study and aimed to investigate the performance of mSEPT9, AFP, PIVKA-II and their combination in hepatic cirrhosis (HC) population.
METHODS: A training cohort was established including 103 HCC and 114 HC patients. 10 ml blood was collected from each patient with K2EDTA tubes, and 3-4 ml plasma was extracted for subsequent tests. The performance of mSEPT9, AFP, PIVKA-II and their combination was optimized by the training cohort. Test performance was prospectively validated with a validation cohort, including 51 HCC and 121 HC patients.
RESULTS: At the optimal thresholds in the training cohort, the sensitivity, specificity and area under curve (AUC) was 72.82%, 89.47%, 0.84, and 48.57%, 89.92%, 0.79, and 63.64%, 95.95%, 0.79 for mSEPT9, AFP and PIVKA-II, respectively. The combined test significantly increased the sensitivity to 84.47% (P < 0.05) at the specificity of 86.84% with an AUC of 0.91. Stage-dependent performance was observed with all single markers and their combination in plasma marker levels, positive detection rate (PDR) and AUC. Moderate correlation was found between mSEPT9 and AFP plasma levels (r = 0.527, P < 0.0001). Good complementarity was found between any two of the three markers, providing optimal sensitivity in HCC detection when used in combination. Subsequent validation achieved a sensitivity, specificity and AUC of 65.31%, 92.86%, 0.80, and 44.24%, 89.26%, 0.75, and 62.22%, 95.27%, 0.78 for mSEPT9, AFP and PIVKA-II, respectively. The combined test yielded a significantly increased sensitivity of 84.00% (P < 0.05) at 85.57% specificity, with an AUC at 0.89.
CONCLUSIONS: The performance was optimal by the combination of mSEPT9, AFP, PIVKA-II compared with any single marker, and the combination may be effective for HCC opportunistic screening in HC population.

UNASSIGNED: Diffuse parenchymal liver diseases are contributing substantially to global morbidity and represent major causes of deaths worldwide. The aim of our study is to assess whether established hepatic fat and iron quantitation and relaxometry-based quantification of hepatocyte-specific contrast material as surrogate for liver function estimation allows to evaluate liver fibrosis.
UNASSIGNED: Retrospective consecutive study. Seventy-two healthy patients (mean age: 53 years) without known liver disease, 21 patients with temporary elevated liver enzymes (mean: 65 years) and 109 patients with biopsy proven liver fibrosis or cirrhosis (mean: 61 years), who underwent liver magnetic resonance imaging (MRI) with a hepatocyte-specific contrast agent [gadoxetate disodium, gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), 0.25 mmol/mL Primovist, Bayer AG, Leverkusen, Germany] at 1.5 T (n=133) and at 3 T (n=69), were included. Fibrosis was classified using the histopathological meta-analysis of histological data in viral hepatitis (METAVIR) and the clinical Child-Pugh scores. Gd-concentration were quantified using T1 map-based calculations. Gd-concentration mapping was performed by using a Look-Locker approach prior to and 912±159 s after intravenous administration of hepatocyte specific contrast agent. Additionally, parenchymal fat fraction, R2*, bilirubin, gender and age were defined as predicting factors. Diagnostic accuracy was calculated in a monoparametric (linear regression, predictor: Gd-concentration) and multiparametric model (predictors: age, bilirubin level, iron overload, liver fat fraction, Gd concentration in the left and right liver lobe).
UNASSIGNED: Mean Gd-concentration in the liver parenchyma was significantly higher for healthy patients ([Gd] =0.51 µmol/L) than for those with liver fibrosis or cirrhosis ([Gd] =0.31 µmol/L; P<0.0001) and with acute liver disease ([Gd] =0.28 µmol/L), though there were no significant differences for the latter two groups. There was a significant moderate negative correlation for the mean Gd-concentration and the METAVIR score (ρ=-0.44, P<0.0001) as well as for the Child-Pugh stage (ρ=-0.35, P<0.0001). There was a significant strong correlation between the bilirubin concentration and the Gd-concentration (ρ=-0.61, P<0.0001). The diagnostic accuracy for the discrimination of healthy patients and patients with known fibrosis or cirrhosis was 0.74 (0.71/0.60 sensitivity/specificity) in a monoparametric and 0.76 (0.85/0.61 sensitivity/specificity) in a machine learning based multiparametric model.
UNASSIGNED: T1 mapping-based quantification of hepatic Gd-EOB-DTPA concentrations performed in a multiparametric model shows promising diagnostic accuracy for the detection of fibrotic changes. Liver biopsy might be replaced by imaging examinations.

Decreased circulating branched chain amino acids (BCAA) represent a prominent change in amino acid profiles in patients with end-stage liver disease (ESLD). These alterations are considered to contribute to sarcopenia and hepatic encephalopathy and may relate to poor prognosis. Here, we cross-sectionally analyzed the association between plasma BCAA levels and the severity of ESLD and muscle function in participants of the liver transplant subgroup of TransplantLines, enrolled between January 2017 and January 2020. Plasma BCAA levels were measured by nuclear magnetic resonance spectroscopy. Physical performance was analyzed with a hand grip strength test, 4 m walking test, sit-to-stand test, timed up and go test, standing balance test and clinical frailty scale. We included 92 patients (65% men). The Child Pugh Turcotte classification was significantly higher in the lowest sex-stratified BCAA tertile compared to the highest tertile (p = 0.015). The times for the sit-to-stand (r = -0.352, p < 0.05) and timed up and go tests (r = -0.472, p < 0.01) were inversely correlated with total BCAA levels. In conclusion, lower circulating BCAA are associated with the severity of liver disease and impaired muscle function. This suggests that BCAA may represent a useful prognostic marker in the staging of liver disease severity.

Methotrexate (MTX), an antifolate agent, is recommended as the first-line disease-modifying antirheumatic drug (DMARD). In this systematic review, our goals were to assess liver fibrosis in methotrexate-treated patients, evaluate liver fibrosis in relation to treatment duration and cumulative dose, and identify differences based on the underlying disease. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to perform the systematic review. We thoroughly searched PubMed, PubMed Central (PMC), and Cochrane library databases to identify relevant articles based on predefined selection criteria. Studies were selected based on the following predefined eligibility criteria: English language, papers from the last 20 years, systematic reviews, observational studies, randomized controlled trials (RCTs), and clinical trials, which included papers on MTX playing roles in the development of liver fibrosis with the derived data transferred to a template. Following that, quality was assessed using the appropriate assessment tool for each study. The initial search yielded 512 results. Following a thorough review, 10 studies were chosen for final consideration: eight observational studies and two systematic reviews. Liver enzyme (LE) elevations during MTX therapy are a common but transient problem. Serial abnormal LE tests may be associated with liver pathology, but fibrosis development is uncommon. However, it is unclear from the literature how therapy should be adjusted in the case of elevated LE and to what extent MTX is linked to liver toxicity; definitive conclusions cannot be drawn because more research is needed.

Since conducting a long-term randomised clinical trial is not logical and feasible to find the optimum dosage of salt intake in patients with cirrhosis, cohort studies are the best design to assess the long-term effects of dietary salt on the survival of cirrhotic patients. This cohort study aimed to evaluate the association between dietary intake of salt and mortality risk in cirrhotic patients. The present study was designed as a cohort in three referral hospitals in Iran in 2018. One hundred and twenty-one patients aged between 20 and 70 years with established cirrhosis were recruited. Dietary intakes, demographic data and disease severity were evaluated at the baseline. Participants were followed up annually. Crude survival was greater in patients with low-to-moderate salt consumption rather than in those with high consumption, and in non-consumers [34⋅26 (95 % CI 33⋅04, 35⋅49) v. 30⋅41 (95 % CI 27⋅13, 33⋅69) v. 32⋅72 (95 % CI 30⋅63, 34⋅80), P = 0⋅028; log-rank test]. Using the Cox proportional hazard model, it was shown that the risk of mortality in the high-salt consumption category was approximately 126 % higher than that of the reference category (non-consumers) [HR value 2⋅26, (95 % CI 0⋅91, 5⋅63)], while this risk for the low-to-moderate consumption group was about 28 % lower than the reference category [HR value 0⋅72, (95 % CI 0⋅26, 1⋅99), P-trend = 0⋅04]. In conclusion, a high daily dietary intake of salt might increase the rate of mortality and moderate salt restriction (instead of elimination of salt) decreases the risk of death.