Liver Biopsy Research Articles

Development and validation of MRI PDFF Cut-offs for living liver donor eligibility assessment.

Hepatic steatosis (HS) criteria for living donor liver transplantation (LDLT) donor eligibility should be based on large droplet fat as per Banff consensus recommendations. We aimed to establish MRI PDFF cut-offs for HS assessment in potential LDLT donors. This retrospective study included consecutive potential LDLT donors who underwent MRI and liver biopsy between 2013 and 2023 at two tertiary institutions, each as development (n=3062; 2015 men; median [interquartile range] age of 32 [25-38] years) and external validation (n=472; 287 men; 35 [26-44] years) datasets. PDFF was measured using dedicated MRI sequences. Histologic HS defined as large droplet fat fraction was used as the reference standard. Dual PDFF cut-offs aimed at 95% sensitivity or 95% specificity, for diagnosing histologic HS of ≥10%, ≥20%, ≥30%, and ≥40%, were determined in the development dataset using ten-fold cross validation. The cut-offs were then validated in the external validation dataset. Equation for estimating histologic HS from PDFF was also derived using linear regression. The PDFF cut-offs for histologic HS of ≥10%, ≥20%, ≥30%, and ≥40%, targeting 95% sensitivity, were 3.7%, 5.5%, 8.0%, and 10.0%, respectively. External validation demonstrated high sensitivities ≥ 97.9% with specificities ranging from 60.9% to 95.1%. The PDFF cut-offs targeting 95% specificity were 6.3%, 8.0%, 9.1%, and 10.1%, respectively. External validation rendered high specificities ranging from 88.5% to 95.3% with sensitivities ranging from 76.6% to 100%. For diagnosing histologic HS ≥30%, which is the most prevalently used threshold for LDLT donor eligibility assessment, the PDFF cut-offs achieved sensitivities and specificities of both over 90%. The equation of (Histologic HS=-2.95 + 1.93 * PDFF) was derived.

Preoperative nonalcoholic steatohepatitis and resolution of metabolic comorbidities after bariatric surgery

BackgroundMost patients undergoing bariatric surgery demonstrate elements of the metabolic syndrome (MetS) and can therefore be diagnosed with metabolically unhealthy obesity (MUO). Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) as hepatic manifestations of the MetS occur in many patients with obesity, but their leverage on postoperative improvement to Metabolic Health (MH), defined as absence of any metabolic comorbidity, remains unclear. ObjectivesThe aim of this study was to assess the influence of liver health status, operative procedure, and sex on postoperative switch from a MUO to an MH phenotype. Secondary objective was weight loss to MH. SettingUniversity Hospital, Germany. MethodsPatients who underwent either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at our obesity surgery center were included in this retrospective study. Liver biopsy was taken and evaluated for presence of NAFLD/NASH. For diagnosis of MH, blood pressure and laboratory values referring to the MetS were assessed preoperatively and at 3, 6, 12, and 24 months’ postoperatively. ResultsOne hundred thirty-three patients (73% female) with a mean body mass index of 52.0 kg/m2 and mean age of 43 years were included in this study. A total of 55.6% underwent RYGB and 44.4% underwent SG. NAFLD was found in 51.1% of patients and NASH in 33.8%. All patients were diagnosed MUO at baseline. Postoperatively, 38.3% patients (n = 51) switched to a MH condition. Mean time to MH was 321 days and mean excess body mass index loss to MH was 63.8%. There were no differences regarding liver health status, operative procedure, or sex. ConclusionsBariatric surgery can resolve MUO independent of liver health status, operative procedure, and sex. However, patients should be closely monitored to ensure sustainable long-term outcomes following the switch to the MH condition.

MRI-serum-based score accurately identifies patients undergoing liver transplant without rejection avoiding the need for liver biopsy: A multisite European study.

Serum liver tests (serum tests) and histological assessment for T-cell-mediated rejection are essential for post-liver transplant monitoring. Liver biopsy carries a risk of complications that are preferably avoided in low-risk patients. Multiparametric magnetic resonance imaging (mpMRI) is a reliable noninvasive diagnostic method that quantifies liver disease activity and has prognostic utility. Our aim was to determine whether using mpMRI in combination with serum tests could noninvasively identify low-risk patients who underwent liver transplants who are eligible to avoid invasive liver biopsies. In a multicenter prospective study (RADIcAL2), including 131 adult and pediatric (children and adolescent) patients with previous liver transplants from the Netherlands, Portugal, and the United Kingdom, concomitant mpMRI and liver biopsies were performed. Biopsies were centrally read by 2 expert pathologists. T-cell-mediated rejection was assessed using the BANFF global assessment. Diagnostic accuracy to discriminate no rejection versus indeterminate or T-cell-mediated liver transplant rejection was performed using the area under the receiver operating characteristic curve. In this study, 52% of patients received a routine (protocol) biopsy, while 48% had a biopsy for suspicion of pathology. Thirty-eight percent of patients had no rejection, while 62% had either indeterminate (21%) or T-cell-mediated rejection (41%). However, there was a high interobserver variability (0 < Cohen's Kappa < 0.85) across all histology scores. The combined score of mpMRI and serum tests had area under the receiver operating characteristic curve 0.7 (negative predictive value 0.8) to identify those without either indeterminate or T-cell-mediated rejection. Combining both imaging and serum biomarkers into a composite biomarker (imaging and serum biomarkers) has the potential to monitor the liver graft to effectively risk stratify patients and identify those most likely to benefit from a noninvasive diagnostic approach, reducing the need for liver biopsy.

Human Liver Organoids to Predict the Outcome of Kasai Portoenterostomy

BackgroundKasai portoenterostomy (KPE) remains the primary intervention for biliary atresia (BA), but its outcomes are highly variable. Reliable prognostic biomarkers remain elusive, complicating the management and prediction of postoperative progression. MethodLiver biopsies from BA patients taken at and after KPE (post-KPE) were used to generate organoids for RNA-sequencing analysis. Control organoids were derived from non-BA livers. Differential gene expression and enrichment analyses were performed to assess post-KPE transcriptomic changes between native liver survivors (NLS) and patients who eventually became liver transplant recipients (LTR). ResultsOrganoid datasets: 70 from liver biopsies at KPE (10 patients), 112 from post-KPE livers (13 livers; 12 patients), and 47 from control livers (9 patients). At KPE, BA organoids displayed mainly hepatocyte expression, a trait notably reduced in control organoids. Similarly, post-KPE organoids from NLS revealed a significant decrease in hepatocyte expression features and an overall increase in cholangiocyte expression features. A similar hepatocyte-to-cholangiocyte expression transition was evidenced in paired liver organoids (at- and post-KPE) generated from an NLS. In contrast, post-KPE organoids from LTR maintained a high level of hepatocyte expression features. ConclusionOur study demonstrated that an elevated expression of hepatocyte features in KPE organoids may indicate aberrant cholangiocyte development in BA livers. In contrast, a post-KPE hepatocyte-to-cholangiocyte expression transition in NLS may imply effective biliary recovery. The lack of this transition in LTR organoids indicates ongoing disease progression, highlighting the potential for organoid-based transcriptomic profiling to inform KPE success and guide BA management. Level of EvidenceLevel III.

Optimal cut-offs of vibration-controlled transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis.

Opinions differ regarding vibration-controlled transient elastography and magnetic resonance elastography (VCTE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of VCTE and MRE for diagnosing AF. Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating VCTE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for VCTE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated. A total of 19,199 patients from 63 studies using VCTE showed diagnostic AUC of 0.83 (95% confidence interval: 0.80-0.86), 0.83 (0.80-0.86), 0.87 (0.84-0.90), and 0.94 (0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89 (0.86-0.92), 0.92 (0.89-0.94), 0.89 (0.86-0.92), and 0.94 (0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. The diagnostic AUC for AF using VCTE was highest at 0.90 with a cut-off of 7.1-7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62-3.8 kPa. VCTE (7.1-7.9 kPa) and MRE (3.62-3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.

Liver Biopsy Technique for Analysis of Hepatic Content during Pregnancy and Early Lactation in Dairy Goats.

Biopsy techniques in dairy goats are currently limited. This study aimed to describe a liver biopsy technique in dairy goats and to evaluate liver triglyceride levels and glycogen content. Sixty-nine dairy goats in the final stage of pregnancy and early lactation period were selected. Fifty goats were selected randomly for hepatic biopsy (HB) according to gestational period and were characterized according to fetus number (single: n = 16, multiple: n = 34), supplementation with propylene glycol (diet: n = 23, diet+PG: n = 27), and milk production levels (high: 3.0 ± 0.4 L/day, n = 15; low: 1.4 ± 0.4 L/day, n = 26). Liver tissue samples were obtained through biopsy on days -30, -20, -15, -10, -5, and 15 days after calving. Hepatic triglyceride and glycogen were quantified. The results were analyzed using the F-test at a 5% significance level and a comparison of means using the Tukey test. The liver biopsies did not influence dry matter intake, body weight, or milk yield. Hepatic glycogen concentration was lower 15 days after calving than it was prior to calving, except on day -20. Goats that generated high levels of milk production had lower triglyceride levels than goats that generated low levels of milk production. The biopsy technique is a safe method for obtaining tissue and evaluating liver content in dairy goats. The milk production level and days relative to parturition influence the hepatic triglyceride and glycogen content in dairy goats.

Intrinsic Causes of Nonfibrotic Portal Hypertension-A Clinicopathologic Review of 56 Patients.

Aim: The differential diagnosis of intrinsic nonfibrotic conditions that may lead to portal hypertension include hepatoportal sclerosis (HPS), nodular regenerative hyperplasia (NRH), and sinusoidal obstruction syndrome (SOS). In this article, we characterize the clinical features and outcome of these lesions when they manifest as portal hypertension. Methods: Data was collected through retrospective patient medical records. Results: Patients (HPS: 28, NRH: 17, SOS: 11) were identified more frequently in recent years. All groups presented with signs and symptoms of portal hypertension. All patients had complex medical histories. An elevated serum alkaline phosphatase occurred in all groups and an elevated bilirubin with SOS. Imaging of the liver with HPS and NRH suggested cirrhosis, which was not seen with SOS. 11%, 12%, and 9% of patients in the HPS, NRH, and SOS respectively, underwent transjugular intrahepatic portosystemic shunt placement to manage the complications of portal hypertension, while 43%, 24%, and 36% of patients respectively, received a liver transplant. Conclusions: Patients with HPS, NRH, and SOS had complex medical histories, likely contributing to the development of these lesions. They are recognized more frequently now. In contrast to HPS and NRH, SOS occurred in liver transplant recipients, was associated with elevated serum bilirubin, and imaging did not suggest the presence of advanced fibrosis/cirrhosis. Liver transplantation appeared to be a viable treatment for complications related to HPS and NRH. Retransplantation for SOS yielded mixed results. HPS, SOS, and NRH should be considered when evaluating liver specimens from patients with unexplained nonfibrotic portal hypertension. Key message: Intrinsic nonfibrotic causes of portal hypertension appear to be increasing in frequency. The differential diagnosis includes NRH, HPS, and SOS. These conditions are associated with complex diseases and possibly due to treatments. Pathologists need to be aware of this differential diagnosis when presented with liver biopsies performed to assess portal hypertension.

MiR-106b-5p protects against drug-induced liver injury by targeting vimentin to stimulate liver regeneration.

Understanding the endogenous mechanism of adaptive response to drug-induced liver injury (arDILI) may discover innovative strategies to manage DILI. To gain mechanistic insight into arDILI, we investigated exosomal miRNAs in the adaptive response to toosendanin-induced liver injury (TILI) of mice. Exosomal miR-106b-5p was identified as a specific regulator of arDILI by comprehensive miRNA profiling. Outstandingly, miR-106b-5p agomir treatment alleviated TILI and other DILI by inhibiting apoptosis and promoting hepatocyte proliferation. Conversely, antagomir treatments had opposite effects, indicating that miR-106b-5p protects mice from liver injury. Injured hepatocytes released miR-106b-5p-enriched exosomes taken up by surrounding hepatocytes. Vim (encodes vimentin) was identified as an important target of miR-106b-5p by dual luciferase reporter and siRNA assays. Furthermore, single-cell RNA-sequencing analysis of toosendanin-injured mouse liver revealed a cluster of Vim + hepatocytes; nonetheless declined following miR-106b-5p cotreatment. More importantly, Vim knockout protected mice from acetaminophen poisoning and TILI. In the clinic, serum miR-106b-5p expression levels correlated with the severity of DILI. Indeed, liver biopsies of clinical cases exposed to different DILI causing drugs revealed marked vimentin expression among harmed hepatocytes, confirming clinical relevance. Together, we report mechanisms of arDILI whereby miR-106b-5p safeguards restorative tissue repair by targeting vimentin.

Diagnostic accuracy of vibration-controlled transient elastography for staging liver fibrosis in autoimmune liver diseases: A systematic review and meta-analysis.

The assessment of liver fibrosis is crucial for managing autoimmune liver diseases such as primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). However, data on the efficacy of noninvasive tests for these diseases are limited. This meta-analysis evaluated the diagnostic accuracy of vibration-controlled transient elastography (VCTE) for staging fibrosis in patients with autoimmune liver disease. Searches were conducted in PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases to assess the diagnostic accuracy of VCTE against histology as the reference standard in adult patients with autoimmune liver disease. The summary area under the curve (sAUC) and diagnostic odds ratio were calculated for significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis, according to liver biopsy. Fourteen articles were included, comprising 559 PBC patients from six studies, 388 AIH patients from five studies, and 151 PSC patients from three studies. VCTE demonstrated good performance for fibrosis staging in PBC, AIH, and PSC. In PBC, sAUCs of VCTE were 0.87, 0.89, and 0.99 for staging SF, AF, and cirrhosis, respectively. In AIH, the sAUCs were 0.88, 0.88, and 0.92, respectively, while in PSC, they were 0.88, 0.95, and 0.92, respectively. The cutoff values for AF were 7.5-17.9 kPa in PBC, 8.18-12.1 kPa in AIH, and 9.6 kPa in PSC. VCTE shows high diagnostic accuracy for staging liver fibrosis in patients with autoimmune liver diseases. This non-invasive method serves as a valuable tool for the evaluation and monitoring of fibrosis in these lifelong diseases.

Differences in the course of hepatocellular carcinoma depending on the DAA treatment

Background and aims: 58 million people live with chronic hepatitis C virus (HCV) infection which can lead to liver cirrhosis and hepatocellular carcinoma (HCC). Currently, a non-interferon therapy based on direct-acting antivirals (DAA) is the standard treatment of HCV infection. This study aimed to assess the occurrence of HCC after treatment with DAA and evaluate whether the course of the disease and liver function is different in patients treated with DAA compared to those who did not receive such therapy. Materials and methods: We studied the population of adult patients from the 2015-2021 period and analyzed the demographic and clinical data, including alcohol abuse, liver enzymes, Child-Pugh and model for end-stage liver disease scores, imaging tests, liver biopsy and elastography, if performed. The Mann-Whitney U and the McNemar’s tests were used. The p-value was set at 0.05. Results: The study included n=34 patients with HCC. In this group n=22 patients (61%) were diagnosed with a chronic HCV infection and n=11 (50%) were receiving DAA treatment. Patients who were receiving DAA developed multiple HCC significantly less often compared to patients not treated with DAA (45.5% vs. 69.6%). We also observed a significantly less common occurrence of portal vein thrombosis (8.7% vs. 18.2%) and distant metastases (0.0% vs. 13.0%) in patients with HCC receiving DAA. Patients with HCC who underwent DAA therapy had significantly lower levels of serum liver enzymes in comparison with patients diagnosed with HCC and not receiving DAA. Conclusions: HCC occurring in patients treated with DAA was more often associated with lymphadenopathy, multiple tumors, portal vein thrombosis and distant metastases probably due to restricted treatment qualification criteria. DAA treatment led to a decrease in the inflammatory activity in the liver. It is important to adjust qualification protocols so that all patients suffering from chronic HCV infection could receive the treatment as soon as possible.

Diagnostic performance of liver stiffness as marker of liver involvement in systemic immunoglobulin light chain (AL) amyloidosis.

To investigate the diagnostic performance of liver stiffness for detecting liver involvement in immunoglobulin light chain (AL) amyloidosis. Liver stiffness was measured using transient elastography in 71 patients with systemic AL amyloidosis and 18 patients with wild type transthyretin (ATTRwt) amyloidosis with cardiomyopathy. Both non-invasive consensus criteria and serum amyloid P component (SAP) scintigraphy were used as substitute standards instead of liver biopsy for establishing liver involvement. Liver stiffness was higher in AL amyloidosis patients with liver involvement than in those without: this was observed using both consensus criteria (median 14.4kPa vs. 8.1kPa; p = 0.001) and SAP scintigraphy (median 20.9kPa vs. 6.2kPa; p < 0.001). Liver stiffness was also higher in AL amyloidosis patients with liver involvement compared to AL and ATTRwt amyloidosis patients with cardiac involvement. Based on receiver operating characteristic (ROC) curves a cut-off value of 14.4kPa for stiffness was optimal to indicate liver involvement, providing sensitivity and specificity of 50% and 74%, respectively, using the consensus criteria and 63% and 90%, respectively, using SAP scintigraphy as standard. Liver stiffness is a promising tool to establish liver involvement in AL amyloidosis having potential to become part of updated criteria for liver involvement.

Lymphangiogenesis in the liver of biliary atresia

BackgroundLymphatic vessels (LVs) play a crucial role in immune reactions by serving as the principal conduits for immune cells. However, to date, no study has analyzed the morphological changes in the LVs of patients with biliary atresia (BA). In this study, we aimed to determine the morphological changes in the LVs irrigating the liver in patients with BA, elucidate their correlations with the morphology of the portal vein (PV) branches, and discuss their etiopathogenetic significance.MethodsMorphometric analyses of liver biopsy specimens from patients treated between 1986 and 2016 were performed. The parameters measured were as follows: the whole liver area of the specimen, fibrotic area, number of LVs, LVs without patent lumen (designated as Ly0) and PV branches, and diameters of the LVs with patent lumen and the PVs.ResultsThe numbers of LVs, Ly0, and PV branches per unit area of the whole liver specimen were significantly higher in patients with BA than in control participants with liver disease and those with normal livers. However, no correlation was observed between the fibrotic area and the average diameter of LVs or PVs, and between the fibrotic area and the number of LVs or PV branches. Furthermore, no correlation was observed between the total number of LVs and the number of PV branches.ConclusionsThe present study showed a significant increase in the number of total LVs and Ly0, characterized by a high Ly0 to total LVs ratio, suggesting that lymphangiogenesis occurs in the liver of patients with BA.

Non-alcoholic fatty liver disease and heart failure: A comprehensive bioinformatics and Mendelian randomization analysis.

Heart failure (HF) and non-alcoholic fatty liver disease (NAFLD) are significant global health issues with a complex interrelationship. This study investigates their shared biomarkers and causal relationships using bioinformatics and Mendelian randomization (MR) approaches. We analysed NAFLD and HF datasets from the Gene Expression Omnibus (GEO). The GSE126848 dataset included 57 liver biopsy samples [14 healthy individuals, 12 obese subjects, 15 NAFL patients and 16 non-alcoholic steatohepatitis (NASH) patients]. The GSE24807 dataset comprised 12 NASH samples and 5 healthy controls. The GSE57338 dataset included 313 cardiac muscle samples [177 HF patients (95 ischaemic heart disease patients and 82 idiopathic dilated cardiomyopathy patients) and 136 healthy controls]. The GSE84796 dataset consisted of 10 end-stage HF patients and 7 healthy hearts procured from organ donors. We identified differentially expressed genes (DEGs) and constructed a protein-protein interaction (PPI) network. Functional pathways were elucidated through enrichment analyses using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneMANIA annotation. Single nucleotide polymorphism (SNP) data for HF and NAFLD were sourced from genome-wide association studies (GWAS). The HF dataset included 486160 samples (14262 experimental and 471898 control), and the NAFLD dataset comprised 377988 samples (4761 experimental and 373227 control). MR analysis investigates the causal interrelations. Our analysis revealed 4032 DEGs from GSE126848 and 286 DEGs from GSE57338. The top 10 hub genes (CD163, VSIG4, CXCL10, FCER1G, FPR1, C1QB, CCR1, C1orf162, MRC1 and CD38) were significantly enriched in immune response, calcium ion concentration regulation and positive regulation of monocyte chemotaxis. CIBERSORT analysis indicated associations between these hub genes and natural killer (NK) cells and macrophages. Transcription factor (TF) target prediction for CD38, CXCL10 and CCR1 highlighted related TFs. A two-sample MR analysis confirmed a bidirectional causal relationship between NAFLD and HF. The main method [inverse variance weighted (IVW)] demonstrated a significant positive causal relationship between NAFLD and HF [P=0.037; odds ratio (OR)=1.024; 95% confidence interval (CI): 1.001 to 1.048]. Similarly, HF was associated with an increase in the risk of NAFLD (P<0.001; OR=1.117; 95% CI: 1.053 to 1.185). Our findings reveal novel molecular signatures common to NAFLD and HF and confirm their bidirectional causality, highlighting the potential for targeted therapeutic interventions and prompting further investigation into their intricate relationship.

Fighting Fatty Liver Disease: Pathogenesis and Therapeutic Approaches

FLD is a burgeoning international ailment closely associated with the increasing rates of obesity, type II diabetes mellitus and physical inactivity. This review focuses on the various aspects of FLD pathophysiology including genetic susceptibility, metabolic disturbances, inflammation, oxidative stress, and environmental factors. Diagnostic tests can be simple and non-invasive such as imaging and biomarkers and can be relatively invasive, such as liver biopsies. Currently the treatment focus is made on drug and surgical interventions with lifestyle changes, and besides, gene and stem cell therapies remain an experimental method with fewer evidences. The article points to the problems of patient compliance, adequate diagnostics, and effectiveness of the treatment, the necessity of working on the concept of individualized medicine, new therapeutic strategies, and prevention. A statically and working knowledge and a combination and complex strategy are required to approach and decrease the burden of FLD worldwide.

Acute presentation of autoimmune hepatitis -from acute hepatitis to ALF and ACLF.

Acute presentation of autoimmune hepatitis (AIH) occurs in 22-43% of all AIH cases, and is not a rare condition. Rather than constituting a single disease entity, it represents a clinical spectrum characterized by considerable variability in severity and the presence of preexisting chronic AIH. This spectrum ranges from acute AIH and acute severe AIH to AIH presenting as acute liver failure (ALF) or as acute-on-chronic liver failure (ACLF), contingent upon factors such as coagulopathy, hepatic encephalopathy, and underlying liver disease. Diagnosing acute presentation of AIH can be particularly challenging due to the frequent absence of classical serologic signatures such as autoantibodies and elevated IgG levels. Histopathological examination remains essential for diagnosis, typically necessitating percutaneous or transjugular liver biopsy. Corticosteroids (CS) are recommended for the management of acute AIH and acute severe AIH with coagulopathy. However, the therapeutic response to CS should be meticulously monitored. If a poor response is anticipated, liver transplantation (LT) should be promptly considered. For AIH presenting as ALF with encephalopathy or ACLF with advanced underlying liver disease, LT is generally advised. Nonetheless, there is potential for a trial of CS therapy in cases of ALF with low MELD scores or ACLF without encephalopathy. This review provides an overview of the latest findings concerning the definition, diagnosis, and management of acute presentation of AIH.

Does liver cirrhosis affect outcomes in non-metastatic esophageal squamous cell carcinoma (ESCC) undergoing radiotherapy-based treatment?

89 Background: Liver cirrhosis frequently coexists with esophageal squamous cell carcinoma (ESCC), as both conditions share alcohol consumption as a common etiological factor. Surgical intervention is often contraindicated or associated with significant morbidity in patients with non-metastatic ESCC and liver cirrhosis. Consequently, radiotherapy-based therapy is commonly employed. This study aims to investigate prognostic factors for overall survival in such patients undergoing radiotherapy-based therapy. Additionally, we will evaluate predictors for the 90-day mortality rate, proposed as a measure to mitigate treatment-related toxicity and prevent unwarranted or excessive medical interventions. Methods: From January 2001 to December 2021, we conducted a retrospective review of the medical records of 1298 patients diagnosed with esophageal squamous cell carcinoma (ESCC). Within this cohort, we identified 103 patients with concomitant liver cirrhosis, diagnosed through abdominal ultrasonography, computerized tomography, and/or liver biopsy, as appropriate. Of these individuals, 78 patients with non-metastatic ESCC and liver cirrhosis were included in our analysis. We collected clinicopathologic parameters and examined their correlation with overall survival and the 90-day mortality rate. Results: Univariate analysis revealed several factors significantly associated with inferior overall survival: Child-Pugh classification B/C (P&lt;0.001, compared to A), radiotherapy alone (P=0.03, compared to chemoradiotherapy), prothrombin time prolonged by ≥2 seconds (P=0.024), albumin levels ≤3.5g/dl (P&lt;0.001), controlled/refractory ascites (P=0.01, compared to no ascites), and total bilirubin levels ≥1.5mg/dl (P=0.004). In multivariate analyses, albumin levels ≤3.5g/dl (P=0.001, odds ratio: 2.500) and total bilirubin levels ≥1.5mg/dl (P=0.019, odds ratio: 2.012) were identified as independent prognostic factors. Among the 78 patients receiving radiotherapy-based therapy, the 90-day mortality rate was 10.3% (n=8). Clinical 8th AJCC stage IVA (P=0.02), clinical T classification T3/4 (P=0.049), prothrombin time prolonged by ≥4 seconds (P=0.009), and albumin levels ≤3.5g/dl (P=0.027) were significantly correlated with higher 90-day mortality rate. The logistic model indicated that albumin levels ≤3.5g/dl (P=0.015, odds ratio: 16.129) and clinical 8th AJCC stage IVA (P=0.012, odds ratio: 17.544) were independently associated with higher 90-day mortality rate. Conclusions: In patients undergoing radiotherapy-based therapy for non-metastatic esophageal squamous cell carcinoma (ESCC) and liver cirrhosis, pretreatment hypoalbuminemia has been associated with increased 90-day mortality and unfavorable prognosis.

Frequency of Peptic Ulcer Disease in Patients with Chronic Liver Disease Presenting with Upper Gastrointestinal Bleeding

Background: Peptic ulcer disease (PUD) is a significant cause of morbidity and mortality worldwide, particularly in patients with chronic liver disease (CLD). The occurrence of upper gastrointestinal bleeding (UGIB) in CLD patients presents a serious complication, often requiring urgent medical intervention. Objective: The main objective of this study was to determine the frequency of peptic ulcer disease in patients with chronic liver disease presenting with upper gastrointestinal bleeding. Methods: This retrospective observational study was conducted at Ayub Teaching Hospital, Abbottabad, from 2021 to 2023. Data were collected from 105 patients diagnosed with chronic liver disease who presented with symptoms of upper gastrointestinal bleeding. The diagnosis of CLD was confirmed through clinical evaluation, biochemical tests, imaging studies, and/or liver biopsy. Patients included were aged 18 years and above and presented with UGIB evidenced by hematemesis, melena, or both. Exclusion criteria were individuals with bleeding disorders unrelated to CLD and those who did not undergo endoscopic evaluation. Data collection involved demographic information, clinical history, duration and etiology of CLD, comorbid conditions, and UGIB presentation. Upper gastrointestinal endoscopy was performed on all patients to identify the source of bleeding. Statistical analysis was performed using SPSS version 25, with a p-value of less than 0.05 considered statistically significant. Results: The study included 105 patients, with a mean age of 55.3±3.27 years; 65 (61.9%) were male, and 40 (38.1%) were female. The etiologies of CLD were viral hepatitis (42.9%), alcoholic liver disease (28.6%), non-alcoholic fatty liver disease (19.0%), and other causes (9.5%). Clinical presentations of UGIB included hematemesis (66.7%), melena (23.8%), and both (9.5%). Endoscopic findings revealed that 35 patients (33.3%) had peptic ulcer disease, with 20 (57.1%) having duodenal ulcers and 15 (42.9%) having gastric ulcers. Other sources of UGIB included esophageal varices (38.1%), gastric varices (14.3%), erosive gastritis (9.5%), and malignancies (4.8%). Associated risk factors for PUD included NSAID use (42.9%), smoking (28.6%), and coexisting portal hypertension (71.4%). The mean size of ulcers was 10.2 mm. Endoscopic therapy was utilized in 71.4% of cases, with pharmacological treatment primarily including proton pump inhibitors (85.7%). Complications included rebleeding within 7 days (14.3%) and the need for surgical intervention (5.7%). The mean hospital stay was 7.8 days, and in-hospital mortality was observed in 8.6% of patients. Conclusion: Peptic ulcer disease represents a substantial yet manageable complication in patients with chronic liver disease presenting with upper gastrointestinal bleeding. Prompt recognition and targeted therapeutic interventions are crucial for optimizing outcomes in this high-risk population.

Quantification of liver fat using non-invasive MRI-PDFF technique versus guided biopsy in potential liver donor

IntroductionSignificant hepatic steatosis affects the outcome of surgery when living donors are transplanted. The gold standard for diagnosing and evaluating hepatic steatosis is hepatic imaging-guided biopsy. Hepatic steatosis assessment using MR spectroscopy and the proton density fat fraction (MR-PDFF) method has produced positive findings.ObjectivesIs to compare the pre-operative assessment of liver fat quantification using MRI-PDFF methods, a non-invasive method, with histopathology.Subjects and methodsA 42 potential donors were then operated surgically for liver transplantation, consequently, were available for the assessment of the efficiency and sensitivity of the radiological findings MRI-PDFF procedures and imaging-guided liver biopsy. This radiological workup of these donors was done through a period of 7 months.ResultsIn many liver transplantations centers, liver imaging-guided biopsy histopathological examination is the gold standard. The study examined the MR proton density fat fraction modality, a recently developed test for hepatic steatosis measurement. The findings indicate 86.8% sensitivity, 50% specificity, 94.2% PDV, 28.5% NPV, 83.3% accuracy, and 0.684 AUC. On analyzing the fat percent, we found that the recorded fat percent using liver imaging-guided biopsy ranges between 1 and 10% with a median of 3. On the other hand, the recorded fat percent using MRI ranged between 2 and 15% with a median of 5.ConclusionThe non-invasive magnetic resonance hepatic proton density fat fraction approach using IDEAL sequence is a reliable and accurate means of quantitatively evaluating hepatic steatosis with excellent sensitivity, specificity, and accuracy.

Association between primary hypothyroidism and metabolic dysfunction-associated steatotic liver disease: an updated meta-analysis

ObjectiveEpidemiological studies have reported an association between primary hypothyroidism and metabolic dysfunction-associated steatotic liver disease (MASLD). However, the magnitude of the risk and whether this risk changes with the severity...

Clinical significance of transjugular liver biopsy in acute liver failure – a real-world analysis

BackgroundHistopathological characterization obtained by transjugular liver biopsy (TJLB) may theoretically contribute to clarification of the exact aetiology of acute liver failure (ALF). It's unclear whether the histopathological information from TJLB, due to the small specimen size, significantly contributes to diagnosing ALF causes, guiding therapy decisions, or predicting overall prognosis. This retrospective study aimed to analyse safety and clinical significance of TJLB in patients with ALF.MethodsThis retrospective, monocentric study investigated safety and efficacy of TJLB in patients with ALF over a ten-year period at a tertiary care transplant-center. The predictive value of various clinical and laboratory characteristics as well as histopathological findings obtained by TJLB on 28-day liver-transplant-free survival were evaluated by calculating uni- and multivariate Cox-proportional hazard regression models. Additional univariate logistic regression analyses were performed to explore the influence of degree of intrahepatic necrosis on the secondary endpoints intensive-care-unit (ICU) admission, need for endotracheal intubation, renal replacement therapy and high-urgency listing for LTX.ResultsA total of 43 patients with ALF receiving TJLB were included into the study. In most cases (n = 39/43 cases) TJLB confirmed the initially already clinically presumed ALF aetiology and the therapeutic approach was unchanged by additional histological examination in the majority of patients (36/43 cases). However, in patients with a high suspicion for aetiologies potentially treatable by medical immunosuppression (e.g. AIH, GvHD), TJLB significantly influenced further treatment planning and/or adjustment. While the degree of intrahepatic necrosis showed significance in the univariate analysis (p = 0.04), it did not demonstrate a significant predictive effect on liver transplant-free survival in the multivariate analysis (p = 0.1). Only consecutive ICU admission was more likely with higher extent of intrahepatic necrosis (Odds ratio (OR) 1.04 (95% CI 1–1.08), p = 0.046).ConclusionsPerformance of TJLB in ALF led to a change in suspected diagnosis and to a significant change in therapeutic measures only in those patients with a presumed high risk for aetiologies potentially responsive to immunosuppressive therapy. Clinical assessment alone was accurate enough, with additional histopathological examination adding no significant value, to predict overall prognosis of patients with ALF.