Viral Cirrhosis Research Articles

Association of TGF-β1 Polymorphism and TGF-β1 Levels With Chronic Hepatitis C and Cirrhosis: A Systematic Review and Meta-Analysis.

Despite the extensive research conducted on the relationship between transforming growth factor-beta 1 (TGF-β1) polymorphisms and levels and the onset and development of liver disease, there are still certain gaps that need to be addressed. To address these gaps and provide a comprehensive overview of the current knowledge, this review aimed to identify relevant published research on TGF-β1/TGF-β1 polymorphism, TGF-β1/TGF-β1 levels, and their associations with cirrhosis and hepatitis C. The synthesis of available data was performed to further enhance our understanding in this area. Adopting the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a search strategy was implemented across several online databases to search for relevant articles as per the defined selection criterion. Eight studies were selected after the completion of the search strategy. Of the eight studies, five revealed a considerably high level of TGF-β1 in patients who had hepatitis C virus (HCV) and liver cirrhosis caused by hepatocellular carcinoma (HCC). The forest plot analysis showed a statistically significant impact of TGF-β1polymorphism and levels on the incidence of hepatic cirrhosis and hepatitis C, with an odds ratio (OR) of 0.65 and a risk ratio (RR) of 0.76. The heterogeneity test showed a high level of heterogeneity at 94% and 95% for OR and RR, respectively, but the overall effect was significant with P< 0.01 for both measures.According to the results obtained, the authors concluded that TGF-β1 polymorphism and its associated levels should be taken into account while developing preventive and therapeutic approaches for hepatic cirrhosis and hepatitis C.

Bacteremia Caused by a Serotype Ob5 Vibrio cholerae Strain in a Cirrhotic Patient in China.

The increasing incidence of non-O1/non-O139 Vibrio cholerae (NOVC) has been observed worldwide. However, septicemia caused by NOVC remains a rare condition that has received limited attention. Currently, there are no established treatment guidelines for bloodstream infections caused by NOVC, and the understanding of this condition mainly relies on individual case reports. Although NOVC bacteremia can be fatal in a small percentage of cases, knowledge about its microbiological features remains limited. Here, we present a case of V. cholerae septicemia caused by NOVC in a 46-year-old man with chronic viral hepatitis and liver cirrhosis. The isolated strain, named V. cholerae VCH20210731 and classified as a new sequence type (ST), ST1553, was found to be susceptible to most of the antimicrobial agents tested. O-antigen serotyping of V. cholerae VCH20210731 revealed that it belonged to serotype Ob5. Interestingly, the ctxAB genes, which are typically associated with V. cholerae, were absent in VCH20210731. However, the strain possessed 25 other potential virulence genes, such as hlyA, luxS, hap, and rtxA. The resistome of V. cholerae VCH20210731 included several genes, including qnrVC4, crp, almG, and parE. Nevertheless, susceptibility testing demonstrated that the isolate was susceptible to most of the antimicrobial agents tested. Phylogenetic analysis indicated that the closest strain to VCH20210731 was strain 120 from Russia, differing by 630 single-nucleotide polymorphisms (SNPs). Our findings contribute to the understanding of the genomic epidemiological characteristics and antibiotic resistance mechanisms of this invasive bacterial pathogen. IMPORTANCE This study highlights the discovery of a novel ST1553 V. cholerae strain in China, providing valuable insights into the genomic epidemiology and global transmission dynamics of V. cholerae. It is important to note that clinical presentations of NOVC bacteremia can vary significantly, and the isolates demonstrate genetic diversity. Consequently, health care professionals and public health experts should remain vigilant about the potential for infection with this pathogen, particularly considering the elevated prevalence of liver disease in China.

Biomarkers for Hepatocellular Carcinoma: From Origin to Clinical Diagnosis.

The incidence of hepatocellular carcinoma (HCC) and HCC-related deaths has increased over the last few decades. There are several risk factors of HCC such as viral hepatitis (B, C), cirrhosis, tobacco and alcohol use, aflatoxin-contaminated food, pesticides, diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), and metabolic and genetic diseases. Diagnosis of HCC is based on different methods such as imaging ultrasonography (US), multiphasic enhanced computed tomography (CT), magnetic resonance imaging (MRI), and several diagnostic biomarkers. In this review, we examine the epidemiology of HCC worldwide and in Egypt as well as risk factors associated with the development of HCC and, finally, provide the updated diagnostic biomarkers for the diagnosis of HCC, particularly in the early stages of HCC. Several biomarkers are considered to diagnose HCC, including downregulated or upregulated protein markers secreted during HCC development, circulating nucleic acids or cells, metabolites, and the promising, recently identified biomarkers based on quantitative proteomics through the isobaric tags for relative and absolute quantitation (iTRAQ). In addition, a diagnostic model used to improve the sensitivity of combined biomarkers for the diagnosis of early HCC is discussed.

Viral hepatitis in Asia-Pacific: a post-COVID-19 reset

Viral hepatitis in Asia-Pacific: a post-COVID-19 reset

Comprehensive DNA methylation profiling of COVID-19 and hepatocellular carcinoma to identify common pathogenesis and potential therapeutic targets

Background & aimsThe effects of SARS-CoV-2 infection can be more complex and severe in patients with hepatocellular carcinoma (HCC) as compared to other cancers. This is due to several factors, including pre-existing conditions such as viral hepatitis and cirrhosis, which are commonly associated with HCC.MethodsWe conducted an analysis of epigenomics in SARS-CoV-2 infection and HCC patients, and identified common pathogenic mechanisms using weighted gene co-expression network analysis (WGCNA) and other analyses. Hub genes were identified and analyzed using LASSO regression. Additionally, drug candidates and their binding modes to key macromolecular targets of COVID-19 were identified using molecular docking.ResultsThe epigenomic analysis of the relationship between SARS-CoV-2 infection and HCC patients revealed that the co-pathogenesis was closely linked to immune response, particularly T cell differentiation, regulation of T cell activation and monocyte differentiation. Further analysis indicated that CD4+ T cells and monocytes play essential roles in the immunoreaction triggered by both conditions. The expression levels of hub genes MYLK2, FAM83D, STC2, CCDC112, EPHX4 and MMP1 were strongly correlated with SARS-CoV-2 infection and the prognosis of HCC patients. In our study, mefloquine and thioridazine were identified as potential therapeutic agents for COVID-19 in combined with HCC.ConclusionsIn this research, we conducted an epigenomics analysis to identify common pathogenetic processes between SARS-CoV-2 infection and HCC patients, providing new insights into the pathogenesis and treatment of HCC patients infected with SARS-CoV-2.

Circulating liver cancer stem cells and their stemness-associated MicroRNAs as diagnostic and prognostic biomarkers for viral hepatitis-induced liver cirrhosis and hepatocellular carcinoma.

Liver cancer stem cells (LCSCs) are a subpopulation of tumor cells that can drive cancer initiation and relapses. Because of their significance, researchers are looking for biomarkers that characterize or regulate LCSCs so that they can be used as targets for the diagnosis and treatment of chronic liver diseases and hepatocellular carcinoma (HCC). Six groups of patients having hepatitis C virus (HCV), HCV+cirrhosis, HCV+HCC, hepatitis B virus (HBV), HBV+cirrhosis, or HBV+HCC, in addition to a control group, were subjected to the measurement of LCSCs levels and analysis of miR-1290 and miR-1825 expression. The percentages of the CD133/EpCAM-expressing LCSCs were increased in viral hepatitis and cirrhosis groups, compared to the control group. HCC patients had the highest percentages of LCSCs. CD133/EpCAM-expressing cells showed significant correlations with stemness-associated miRNAs; miR-1290 and miR-1825. Also, the miR-1290 and miR-1825 were significantly up-regulated in viral hepatitis-associated cirrhosis and HCC groups. Moreover, in HCV+HCC, miR-1290 and miR-1825 expression was significantly positively correlated with tumor size and number. However, only miR-1825 could distinguish between HCV- and HBV-associated HCC groups. MiR-1290 exhibited the highest sensitivity and specificity for detecting HCC, followed by miR-1825 and CD133/EpCAM-expressing LCSCs. These findings indicate the relevance of CD133/EpCAM-expressing cells in the pathogenesis of liver cirrhosis and HCC developed as a consequence of either chronic HCV or HBV infection. Accordingly, CD133/EpCAM-expressing cells, miR-1290, and miR-1825, could serve as promising diagnostic and prognostic biomarkers as well as therapeutic targets in patients suffering from liver cirrhosis or HCC.

The impact of high body mass index on hepatocellular carcinoma in viral hepatitis and cirrhosis.

10537 Background: The impact of a high body mass index (BMI) on hepatocellular carcinoma (HCC) has been unclear in patients with viral hepatitis and liver cirrhosis (LC). Our aim is to investigate the association between BMI and HCC in patients with viral hepatitis and LC. Methods: We conducted a population-based cohort study. In total, 156,143 Korean adults who underwent routine health examinations during 2003-2006 were followed up until December 2019 via linkage to the national hospital discharge records. Multivariable-adjusted hazard ratios (HRs) per each 5 kg/m2 increase in BMI for HCC risk were calculated using Cox proportional hazard models. Results: BMI was positively associated with HCC in hepatitis B virus (HBV) patients with BMI range of 27.5~29.9 kg/m² and BMI ≥30 kg/m² and LC patients with a BMI range of 27.5~29.9 kg/m². Assuming linear associations, HRs were 1.17 for HBV, 1.08 for hepatitis C virus (HCV), and 1.11 for LC. In the subgroup analysis for the LC, the HR were 1.19 in the HBV-LC, 1.38 in the HCV-LC, 1.36 in the alcoholic LC, and 1.59 in the fatty liver LC. Women showed stronger positive associations between BMI and HCC than men in the HBV (HR, 1.45 vs 1.06) and LC (1.27 vs. 1.02). The positive association seemed to be stronger in younger age ( &lt; 65 years) in HBV (1.17 vs 1.05) and HCV (1.33 vs 0.77) patients compared to older age ( &gt; 65 years). Conclusions: In the BMI range of ≥25 kg/m2, a higher BMI was associated with an increased risk of HCC in LC and HBV. The associations between BMI and HCC risk are different according to liver disease, sex and age.

Spleen size change after hepatitis C treatment: a simple parameter to predict clinical outcomes.

Portal hypertension contributes to splenomegaly in cirrhotic patients. Reduction in spleen size may represent improvement in portal hypertension. The goal was to determine whether reduction in spleen size following sustained virologic response (SVR) in patients with hepatitis C virus (HCV) cirrhosis is associated with lower risk of liver-related adverse outcomes. A retrospective cohort study was performed regarding HCV-infected patients treated with direct-acting antiviral agents at the Iowa City Veterans Administration Medical Center between 2014 and 2019. Patients with cirrhosis and splenomegaly on baseline ultrasound were included. Spleen size, platelet counts, decompensations, hepatocellular carcinoma (HCC) status, and mortality were recorded through July 31, 2021. Decrease in spleen size ≥1.5 cm was regarded as significant. Intergroup comparisons were performed on SPSS 28. Eighty patients with cirrhosis and splenomegaly before SVR were identified. Spleen sizes decreased significantly after SVR in 31 patients over a median of 1 year (Group A), whereas 49 patients did not meet this endpoint (Group B). Lack of spleen size reduction was associated with the presence of varices before SVR (odds ratio (OR): 5.3, p < 0.01). Group A had significantly greater increases in platelet count after SVR than did Group B. Patients in Group B had greater risk of HCC (OR: 9.7, CI: 1.2-79; p = 0.03) and death (OR: 3.6, CI: 1.1-12; p = 0.04). Reduced spleen size in patients with HCV cirrhosis after SVR is associated with greater increment in platelet count, decreased risk of HCC, and reduced mortality compared to patients whose spleen size does not decrease.

Analysis of Short-Term and Long-Term Outcomes of Living Donor Liver Transplantation for Patients with a High Model for End-Stage Liver Disease Score

The Model of End-Stage Liver Disease (MELD) scoring system can predict short-term survival among patients awaiting liver transplantation and is used to allocate organs prioritizing liver transplantation. Patients with high MELD scores have been reported to have worse early graft dysfunction and survival. However, recent studies have shown that patients with high MELD scores had satisfactory graft survival, although they showed more postoperative complications. In this study, we examined the effect of the MELD score on the short-term and long-term prognosis of living donor liver transplantation (LDLT). This study included 102 patients who underwent LDLT in our institution between 2005 and 2020. The patients were divided into 3 groups according to MELD score (low MELD group: ≤20, moderate MELD group: 21-30, and high MELD group: ≥31). Perioperative factors were compared among the 3 groups, and cumulative overall survival rates were calculated using the Kaplan-Meier method. The patients' characteristics were comparable, and the median age was 54 years. Hepatitis C virus cirrhosis was the most common primary disease (n=40), followed by hepatitis B virus (n=11). The low MELD group consisted of 68 patients (median score: 16, 10-20); the moderate MELD group, 24 patients (median score: 24, 21-30); and the high MELD group, 10 patients (median score: 35, 31-40). The mean operative time (1241 min versus 1278 min versus 1158 min, P=.19) and mean blood loss (7517 mL vs 11162 mL vs 8808 mL, P=.71) were not significantly different among the 3 groups. The vascular and biliary complication rates were similar. The periods of intensive care unit and hospital stay tended to be longer in the high MELD group, but the difference was insignificant. The 1-year postoperative survival rate (85.3 % vs 87.5 % vs 90.0 %, P=.90) and overall survival rate were also not significantly different among the 3 groups. Our study showed that LDLT patients with high MELD scores do not have a worse prognosis than those with low scores.

Abstract 1516: Bulk and spatial single-cell transcriptomic characterization of fibrolamellar hepatocellular carcinoma

Abstract Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer affecting adolescents and young adults, with no gender or ethnicity predilection and without history of underlying viral hepatitis, cirrhosis, or other known risk factors. Almost all FLC patients present a somatic heterozygous deletion in chromosome 19p13.12, DNAJB1::PRKACA, which is sufficient to drive FLC in mice. A few studies comparing FLC tumors with adjacent non-transformed liver (normal) samples revealed many transcriptional differences. However, there were done in very small datasets and analyzed using different bioinformatic methods, resulting in just 18-47% agreement between them. This study aims to comprehensively characterize the transcriptome of FLC at bulk and spatial single-cell resolution. The whole transcriptome of 109 FLC frozen patient samples, the largest RNA-seq dataset of FLC to date, was sequenced using different library preparation and ribosomal depletion methods. Only paired tumor and normal tissue samples resected from the same patient were used and divided into two groups: exploration (3 datasets, 67 samples) and testing (2 datasets, 17 samples). Additionally, as external validation datasets, RNA-seq samples from previously published studies were collected, including Sorenson et al. (FLC: 26, normal: 9, paired: 8), the TCGA-LIHC study (FLC: 6, normal: 1, paired: 1), Hirsch et al. (FLC: 15, normal: 3, paired: 0) and Francisco et al. (FLC: 27, normal: 10, paired: 9). All were reanalyzed using state-of-the-art bioinformatic methods: mapped to the Human Genome GRCh38.103 and transcripts quantified using Salmon 1.6.0, unsupervised clustering exploration using PCA, tSNE and UMAP, differential expression calculated using DESeq2 1.28.1, and checking for detectability and consistency among datasets. We found 857 up- and 988 down-regulated genes presenting the same dysregulation in the exploration datasets and confirmed in the testing and external datasets. We call these genes the transcriptional FLC signature. The FLC signature was further characterized by comparing it with the genes differentially expressed in other liver cancers: hepatocellular carcinoma (41 paired samples), hepatoblastoma (22 paired samples), and cholangiocarcinoma (27 paired samples). We found 276 up- and 352 down-regulated genes altered in other liver cancers as well as FLC, but 156 up- and 68 down-regulated only in FLC. The 112 genes with the strongest dysregulation (56 up and 56 down) were used for a MERFISH screening, providing for the first time a single-cell spatial transcriptomic characterization of FLC. This showed clear differential expression patterns in tumor, normal, stromal, and infiltrating immune cells, allowing the identification of how different cell types contribute to the transcriptional FLC signature. Citation Format: David Requena, Aldhair Medico, Luis F. Soto, Mahsa Shirani, James A. Saltsman, Gadi Lalazar, Michael P. LaQuaglia, Sanford M. Simon. Bulk and spatial single-cell transcriptomic characterization of fibrolamellar hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1516.

Sonographic gallbladder wall thickness measurement and the prediction of esophageal varices among cirrhotics.

Acute variceal bleeding in patients with liver cirrhosis and portal hypertension (PHT) is the most serious emergency complication among those patients and could have catastrophic ‎outcomes if not timely managed. ‎Early screening by esophago-gastro-duodenoscopy (EGD) for the presence of esophageal varices (EVs) is ‎‎currently recommended by the practice guidelines for all cirrhotic patients. Meanwhile, EGD is not readily accepted or preferred by many patients. The literature is rich in ‎studies to investigate and validate ‎ non-invasive markers of EVs prediction aiming at reducing the unneeded endoscopic procedures. Gallbladder (GB) wall thickness (GBWT) ‎measurement has been found promising in many published research ‎articles. We aim to highlight the validity of sonographic GBWT measurement in the ‎prediction of EVs based on the available evidence.‎ We searched databases including Cochrane library, PubMed, Web of Science and many others for relevant articles. GBWT is associated with the presence of EVs in cirrhotic patients with PHT of different etiologies. The cut-off of GBWT that can predict the presence of EVs varied in the literature and ranges from 3.1 mm to 4.35 mm with variable sensitivities of 46%-90.9% and lower cut-offs in viral cirrhosis compared to non-viral, however GBWT > 4 mm in many studies is associated with acceptable sensitivity up to 90%. Furthermore, a relation was also noticed with the degree of varices and portal hypertensive gastropathy. Among cirrhotics, GBWT > 3.5 mm predicts the presence of advanced (grade III-IV) EVs with a sensitivity of 45%, the sensitivity increased to 92% when a cut-off ≥ 3.95 mm was used in another cohort. Analysis of these results should carefully be revised in the context of ascites, hypoalbuminemia and other intrinsic GB diseases among cirrhotic patients. The sensitivity for prediction of EVs improved upon combining GBWT measurement with other non-invasive predictors, e.g., platelets/GBWT.

Gamma-glutamyl transferase and risk of all-cause and disease-specific mortality: a nationwide cohort study

Population-based data regarding the prognostic implication of gamma-glutamyl transferase (GGT) have been inconsistent. We examined the association of GGT with all-cause and disease-specific mortality. Using the Korean nationwide database, we included 9,687,066 subjects without viral hepatitis or cirrhosis who underwent a health examination in 2009. Subjects were classified into three groups by sex-specific tertile of serum GGT levels. The underlying causes of death were classified by 10th Revision of the International Classification of Diseases codes. During the median follow-up period of 8.3 years, 460,699 deaths were identified. All-cause mortality increased as serum GGT levels became higher (hazard ratio [HR], 95% confidence interval [CI] 1.05, 1.04–1.05 in the middle tertile, and 1.33, 1.32–1.34 in the high tertile) compared to the low tertile of serum GGT levels. Similar trends were observed for cardiovascular disease (CVD) (HR, 95% CI 1.07, 1.05–1.09 in the middle tertile, 1.29, 1.26–1.31 in the high tertile), cancer (HR, 95% CI 1.08, 1.07–1.10 in the middle tertile, 1.38, 1.36–1.39 in the high tertile), respiratory disease (HR, 95% CI 1.10, 1.08–1.13 in the middle tertile, 1.39, 1.35–1.43 in the high tertile), and liver disease mortality (HR, 95% CI 1.74, 1.66–1.83 in the middle tertile, 6.73, 6.46–7.01 in the high tertile). Regardless of smoking, alcohol consumption and history of previous CVD and cancer, a higher serum GGT levels were associated with a higher risk of mortality. Serum GGT levels may be useful for risk assessment of all-cause and disease-specific mortality in general population.

Prevalence of Spontaneous Bacterial Peritonitis (SBP) in Hepatitis B (HBV), and Hepatitis C (HCV) Liver Cirrhosis: A Systematic Review and Meta-Analysis.

Spontaneous bacterial peritonitis (SBP) is a common infection in liver cirrhosis. This systematic review and meta-analysis provide detailed information on the prevalence of SBP among hepatitis B virus (HBV) and hepatitis C virus (HCV)-related liver cirrhosis globally. A systematic search for articles describing the prevalence of SBP in HBV and HCV-related cirrhosis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Our search returned ten (10) eligible articles involving 1713 viral cirrhosis cases representing eight (8) countries. A meta-analysis was performed on our eligible studies using the random effect model. A protocol was registered with PROSPERO (CRD42022321790). The pooled prevalence of SBP in HBV-associated cirrhosis had the highest estimate [8.0% (95% CI, 2.7-21.0%; I2 = 96.13%; p &lt; 0.001)], followed by SBP in HCV-associated liver cirrhosis [4.0% (95% CI, 1.3%-11.5%; I2 = 88.99%; p &lt; 0.001)]. China (61.8%, CI: 57.1-66.3%), the USA (50.0%, CI: 34.6-65.4%), and Holland (31.1%, CI: 21.6-42.5%) had the highest estimate for SBP in HBV associated liver cirrhosis, SBP in HCV associated liver cirrhosis and SBP in HBV + HCV associated liver cirrhosis respectively. There was a significant difference in the prevalence of SBP in viral hepatitis-associated liver cirrhosis with the year of sampling and method of SBP detection at P &lt; 0.001. There was an increase in SBP incidence at the beginning of 2016 across the liver cirrhosis in this study. The findings of this review revealed a rise in the incidence of SBP in viral hepatitis over the last decade. The latter indicates a possible future rise in the global prevalence of SBP among HBV and HCV-related liver cirrhosis.

Impact of Race and Neighborhood Socioeconomic Characteristics on Liver Cancer Diagnosis in Patients with Viral Hepatitis and Cirrhosis

Concerning data have revealed that viral hepatitis and hepatocellular carcinoma (HCC) disproportionally impact non-White patients and those from lower socioeconomic status. A recent study found that HCC clusters were more likely to be in high poverty areas in New York City. We aim to investigate the impacts of neighborhood characteristics on those with viral hepatitis and cirrhosis, particularly with advanced HCC diagnosis. Patients with cirrhosis and viral hepatitis admitted to a New York City health system between 2012 and 2019 were included. Those with prior liver transplants were excluded. Neighborhood characteristics were obtained from US Census. Our primary outcome was HCC and advanced HCC diagnosis. This study included 348 patients; 209 without history of HCC, 20 with early HCC, 98 with advanced HCC, and 21 patients with HCC but no staging information. Patients with advanced HCC were more likely to be older, male, Asian, history of HBV, and increased mortality. They were more likely to live in areas with more foreign-born, limited English speakers, and less than high school education. After adjusting for age, sex, and payor type, Asian race and low income were independent risk factors for advanced HCC. Neighborhood factors were not associated with mortality or readmissions. We observed that in addition to age and sex, Asian race, lower household income, lower education, and lower English proficiency were associated with increased risk of advanced HCC. These disparities likely reflect suboptimal screening programs and linkage to care among vulnerable populations. Further efforts are crucial to validate and address these concerning disparities.

Liver disease among patients with psoriasis: the Malaysian Psoriasis Registry.

Therapeutic options may be limited for patients with psoriasis who have concomitant liver disease (PsL). We aimed to report the frequency of liver disease among patients with psoriasis, and describe the clinical features, treatment modalities and quality of life. This was a multicentre cross-sectional study of patients with psoriasis notified to the Malaysian Psoriasis Registry (MPR) from January 2007 to December 2018. Of 21 735 patients with psoriasis, 174 (0.8%) had liver disease. The three most common liver diseases were viral hepatitis (62.1%), fatty liver (14.4%) and liver cirrhosis (10.9%). The male-to-female ratio was 3.8 : 1. Mean age (SD) of onset of psoriasis was higher in those with liver disease vs. those without [37.25 years (13.47) vs. 33.26 years (16.96), P < 0.001]. Patients with PsL, compared with those without liver disease, had a higher rate of dyslipidaemia (27.5% vs. 16.4%, P < 0.001), hypertension (33.9% vs. 23.7%, P = 0.002), diabetes mellitus (22.4% vs. 15.9%, P = 0.021) and HIV infection (5.3% vs. 0.4%, P < 0.001). Those with PsL were also more likely than those without liver disease to have severe disease [body surface area > 10% and/or Dermatology Life Quality Index (DLQI) > 10] (59.3% vs. 49.9%, P = 0.027), psoriatic arthropathy (21.1% vs. 13.0%, P = 0.002) and nail involvement (78.2% vs. 56.1%, P < 0.001). Also significantly higher in the group with PsL were the use of phototherapy (8.4% vs. 2.6%, P < 0.001), acitretin (7.3% vs. 2.8%, P < 0.001) and ciclosporin (3.0% vs. 0.7%, P < 0.001). Mean DLQI was similar in both groups [9.69 (7.20) vs. 9.62 (6.75), P = 0.88]. The frequency of patients with PsL in the MPR was 0.8%. Patients with PsL were more likely to be male, had a higher rate of comorbidities, severe disease, and nail and joint involvement than those without liver disease.

Role of microvesicles as markers of inflammation and adverse clinical outcomes in orthotopic liver transplantation

Microvesicles (MV) are intracellular transmitters that participate in both physiological and pathological conditions, such as inflammatory processes. During orthotopic liver transplantation (OLT), the abrupt exacerbation of inflammatory response contributes to adverse transplant outcomes. Our hypothesis is that MVs are released due to the OLT-associated inflammatory response and may serve as biomarkers of OLT short-term prognosis. In this context, the aim of this study was to evaluate changes in MV marker levels during OLT and their association with adverse outcomes. Blood samples of patients submitted to OLT were collected on three occasions: pretransplant, reperfusion phase and end of hospitalization. The following MVs markers were quantified by flow cytometry: CD41A+-MV, CD162+-MV, CD31+-MV, CD9+-MV and CD81+-MV. ANOVA with repeated measures, Spearman correlation and regression models were performed for data analysis. Ninety patients were included with a median age of 60 years; most of them had viral or alcoholic cirrhosis. The levels of all MV markers increased from the pretransplant to the liver reperfusion phase and returned to their basal levels before hospital discharge. During reperfusion, the levels of CD162+-MV (r 0.703; P = 0.034) were correlated with prothrombin time, and the levels of CD41A+-MV (r 0.220; P = 0.047) and CD81+-MV (r 0.332; P = 0.002) were correlated with serum lactate. Increased levels of MVs expressing CD162 (OR = 2.34; 95% CI 1.23 – 4.47; P = 0.01) and CD31 (OR = 2.00; 95% CI 1.01 – 3.99; P = 0.05) in the reperfusion phase were associated with an increased risk of death. Increased levels of CD162+-MV were also associated with the risk of infection during hospitalization (OR = 1.59; 95% CI 1.06 - 2.39; P = 0.03). Our results suggest that MV expressing platelet-endothelium and leukocyte-platelet adhesion antigens are released after ischemia‒reperfusion injury and are associated with the risk of infectious complications and death during OLT.

Upper gastrointestinal bleeding in patients with liver cirrhosis

Upper gastrointestinal bleeding (UGIB) is a potentially life-threatening emergency that remains a common cause of admission to hospital for cirrhotic patients. This re­tro­s­pec­tive study included 230 patients, over a period of two years, who presented with UGIB and underwent emer­gen­cy gastroscopy at the County Emergency Clinical Hos­pi­tal Târgu-Mureş. The patients were divided into two groups (patients with variceal bleeding versus non-variceal ble­eding, and alcoholic cirrhosis versus viral cirrhosis). Com­­pa­ri­sons were made to identify the sources of digestive ble­eding, the risk factors and the clinical outcomes, such as mortality, need for transfusion and hemostasis. This study shows that esophageal varices are the main cause of UGIB in cirrhotic patients regardless the etiology, but al­most a half experience bleeding from a non-variceal source, the most common being peptic ulcer. Bleeding from a non-variceal source is as severe as variceal rupture, re­­quir­­ing the same number of transfusions, with a similar rate of rebleeding and mortality. Male young patients with al­co­ho­lic cirrhosis have a higher risk of UGIB and need more trans­fu­sions than in patients with viral cirrhosis. The large num­ber of patients requiring endoscopic hemostasis re­veals the importance of upper digestive endoscopy to specify the etio­lo­gy and establish the appropriate treat­ment.

Durable Stable Disease by Atezolizumab/Bevacizumab Can Provide Long-term Survival of Patients With Hepatocellular Carcinoma Lung Metastases.

Multiple bilateral lung metastases secondary to hepatocellular carcinoma (HCC) are mainly treated with molecular therapy. Atezolizumab plus bevacizumab can provide excellent long-term survival for patients with a good response. A 67-year-old woman underwent right hepatectomy for a primary solitary HCC, 11 cm in diameter, after portal embolization. After 2 years, she developed bilateral lung metastases with >100 nodules, <1 cm in size. She had no viral hepatitis or liver cirrhosis, and the Child-Pugh Grade was A (5 points). Lenvatinib (12 mg daily) was administered as a first-line treatment and continued for 18 months. The best response was stable disease (SD). Subsequently, intravenous atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) was administered once every three weeks. The best response was SD, which continued for 26 months. After that, cabozantinib treatment was initiated and discontinued after one cycle. Subsequently, dual immune checkpoint inhibitor treatment (durvalumab + tremelimumab) was administered. She has had multiple, but lung-only, metastases over four years. She has been well as an outpatient with the Child-Pugh Grade of A and a performance status of 0. Even if atezolizumab plus bevacizumab does not induce a good response, a durable SD could prolong survival in patients with metastatic HCC while maintaining liver function and a good quality-of-life.

Spleen stiffness determined by spleen-dedicated device accurately predicted esophageal varices in cirrhosis patients

Background: The advantages of spleen stiffness in prediction of high-risk varices (HRV) in cirrhosis patients have been confirmed. Recently, a new device utilizing a 100 Hz probe dedicated to spleen stiffness measurement (SSM) was developed. Objectives: To validate the clinical applicability of SSM@100 Hz in predicting HRV by comparing it with other non-invasive tests (NITs). Design: A prospective cohort study. Methods: A total of 171 cirrhosis patients who underwent esophagogastroduodenoscopy (EGD) examination were included in this study. SSM using a 100 Hz probe and liver stiffness measurement using a 50 Hz probe were performed. Additionally, 22 healthy controls underwent spleen stiffness evaluation using the 100 Hz probe. Results: The failure rates of spleen stiffness examination in patients with cirrhosis and in healthy controls were 2.9% and 4.5%, respectively. The means of SSM values were 56.4 ± 21.6 and 13.8 ± 6.7 kPa in cirrhosis and controls. SSM increased proportionally with the severity of esophageal varices. The area under receiver operating characteristic (ROC) for spleen stiffness in predicting HRV was 0.881 (95% confidence interval 0.829–0.934), with a cutoff value of 43.4 kPa. The accuracy, false negative rate and EGD spare rate were 86.5%, 2.5% and 24.3%, respectively. For HRV prediction, SSM was comparable to expanded Baveno VI and VII and superior to other NITs. As to viral versus non-viral cirrhosis and compensated versus decompensated cirrhosis, the cut-off and performance of SSM were different. Conclusion: SSM@100 Hz demonstrates high accuracy in predicting HRV with a low missed HRV rate. Our findings suggest that SSM@100 Hz can be used independently due to its simplicity and effectiveness. However, further studies are needed to determine appropriate cutoff values based on the cause of cirrhosis and liver function. Trail Registration: ChiCTR2300070270.

Osteoporosis Assessment among Adults with Liver Cirrhosis.

Osteopenic bone disease occurs frequently in patients with chronic liver cirrhosis, which most frequently presents with hepatic osteodystrophy. Thus, the relationship between nutritional status and bone mineral density has been poorly measured in liver cirrhosis. This single-center study consisted of a group of 70 patients diagnosed with liver cirrhosis. The nutritional status was evaluated with the Controlling Nutritional Status index, and volumetric vertebral bone mineral density was measured with quantitative computed tomography. Among the 70 patients included, osteopenia and osteoporosis were found in 71% and 24.3%, respectively. Malnutrition assessed with the Controlling Nutritional Status index was observed in 56 (80%) patients and was more frequent in alcoholic cirrhosis patients than viral cirrhosis patients (87.24% vs. 65.22%). Significant positive correlation with Controlling Nutritional Status score was found with Model for End-Stage Liver Disease (rho = 0.576, p-value < 0.0001), Child−Pugh score (rho = 0.670, p-value < 0.0001), International Normalized Ratio (rho = 0.517, p-value = 0.001), aspartate aminotransferase (rho = 0.293, p-value = 0.045), and bilirubin (rho =0.395, p-value = 0.02). Among the liver cirrhosis patients, 15 had osteoporosis and 49 had osteopenia at the lumbar spine (L1-L4 vertebrae), as determined by bone mass density via quantitative computed tomography. A non-significant relationship between Controlling Nutritional Status index-assessed nutritional status and bone mass density was documented. Regarding osteoporosis, no differences were found between the viral and alcohol types of liver cirrhosis patients (p-value = 0.870). Age, obesity, grade of varices, Child−Pugh score, and Model for End-Stage Liver Disease score were associated with osteoporosis in patients with liver cirrhosis.