Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy.

BACKGROUND & AIMS: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. METHODS: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.453.25), respectively group 1,2,3. RESULTS: At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.453.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.453.25 (42.3%, group 3). CONCLUSIONS: FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

Bystander Effects and Profibrotic Interactions in Hepatic Stellate Cells during HIV and HCV Coinfection.

This study aims to explore the influence of coinfection with HCV and HIV on hepatic fibrosis. A coculture system was set up to actively replicate both viruses, incorporating CD4 T lymphocytes (Jurkat), hepatic stellate cells (LX-2), and hepatocytes (Huh7.5). LX-2 cells' susceptibility to HIV infection was assessed through measurements of HIV receptor expression, exposure to cell-free virus, and cell-to-cell contact with HIV-infected Jurkat cells. The study evaluated profibrotic parameters, including programed cell death, ROS imbalance, cytokines (IL-6, TGF-ß, and TNF-α), and extracellular matrix components (collagen, α-SMA, and MMP-9). The impact of HCV infection on LX-2/HIV-Jurkat was examined using soluble factors released from HCV-infected hepatocytes. Despite LX-2 cells being nonsusceptible to direct HIV infection, bystander effects were observed, leading to increased oxidative stress and dysregulated profibrotic cytokine release. Coculture with HIV-infected Jurkat cells intensified hepatic fibrosis, redox imbalance, expression of profibrotic cytokines, and extracellular matrix production. Conversely, HCV-infected Huh7.5 cells exhibited elevated profibrotic gene transcriptions but without measurable effects on the LX-2/HIV-Jurkat coculture. This study highlights how HIV-infected lymphocytes worsen hepatic fibrosis during HCV/HIV coinfection. They increase oxidative stress, profibrotic cytokine levels, and extracellular matrix production in hepatic stellate cells through direct contact and soluble factors. These insights offer valuable potential therapies for coinfected individuals.

Microinvasion in hepatocellular carcinoma: predictive factor and application for definition of clinical target volume for radiotherapy.

BACKGROUND: To investigate the correlation between microinvasion and various features of hepatocellular carcinoma (HCC), and to clarify the microinvasion distance from visible HCC lesions to subclinical lesions, so as to provide clinical basis for the expandable boundary of clinical target volume (CTV) from gross tumor volume (GTV) in the radiotherapy of HCC. METHODS: HCC patients underwent hepatectomy of liver cancer in our hospital between July 2019 and November 2021 were enrolled. Data on various features and tumor microinvasion distance were collected. The distribution characteristics of microinvasion distance were analyzed to investigate its potential correlation with various features. Tumor size compared between radiographic and pathologic samples was analyzed to clarify the application of pathologic microinvasion to identify subclinical lesions of radiographic imaging. RESULTS: The average microinvasion distance was 0.6 mm, with 95% patients exhibiting microinvasion distance less than 3.0 mm, and the maximum microinvasion distance was 4.0 mm. A significant correlation was found between microinvasion and liver cirrhosis (P = 0.036), serum albumin level (P = 0.049). Multivariate logistic regression analysis revealed that HCC patients with cirrhosis had a significantly lower risk of microinvasion (OR = 0.09, 95%CI = 0.02 ~ 0.50, P = 0.006). Tumor size was overestimated by 1.6 mm (95%CI=-12.8 ~ 16.0 mm) on radiographic size compared to pathologic size, with a mean %Δsize of 2.96% (95%CI=-0.57%~6.50%). The %Δsize ranged from - 29.03% to 34.78%. CONCLUSIONS: CTV expanding by 5.4 mm from radiographic GTV could include all pathologic microinvasive lesions in the radiotherapy of HCC. Liver cirrhosis was correlated with microinvasion and were independent predictive factor of microinvasion in HCC.

Oxidative stress promotes liver fibrosis by modulating the microRNA-144 and SIN3A-p38 pathways in hepatic stellate cells.

Background & Aims: Reactive oxygen species (ROS) act as modulators triggering cellular dysfunctions and organ damage including liver fibrosis in which hepatic stellate cell (HSC) activation plays a key role. Previous studies suggest that microRNA-144 (miR-144) acts as a pro-oxidant molecule; however, whether and how miR-144 affects HSC activation and liver fibrosis remain unknown. Methods: Carbon tetrachloride (CCl4) and bile duct ligation (BDL)-induced experimental liver fibrosis models were used. Hepatic miR-144 expression was analyzed by miRNA in situ hybridization with RNAscope probe. The in vivo effects of silencing or overexpressing miR-144 were examined with an adeno-associated virus 6 (AAV6) carrying miR-144 inhibitor or mimics in fibrotic mouse experimental models. Results: In this study, we demonstrated that ROS treatment significantly upregulated miR-144 in HSCs, which further promoted HSC activation in vitro. Interestingly, miR-144 was preferentially elevated in HSCs of experimental liver fibrosis in mice and in human liver fibrotic tissues. Furthermore, in vivo loss or gain-of-function experiments via AAV6 carrying miR-144 antagomir or agomir revealed that blockade of miR-144 in HSCs mitigated, while overexpression of miR-144 in HSCs accelerated the development of experimental liver fibrosis. Mechanistically, SIN3 transcription regulator family member A (SIN3A), a transcriptional repressor, was identified to be the target of miR-144 in HSCs. MiR-144 downregulated Sin3A, and in line with this result, specific knockdown of Sin3a in HSCs remarkedly activated p38 MAPK signaling pathway to promote HSC activation, eventually exacerbating liver fibrosis. Conclusions: Oxidative stress-driven miR-144 fuels HSC activation and liver fibrogenesis by limiting the SIN3A-p38 axis. Thus, a specific inhibition of miR-144 in HSCs could be a novel therapeutic strategy for the treatment of liver fibrosis.

Prevalence and predictors of multidrug-resistant bacteremia in liver cirrhosis.

BACKGROUND/AIMS: Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. METHODS: This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022. Local epidemiology and antibiotic resistance patterns and the determinants of MDR bacteremia were analyzed using logistic regression analysis. RESULTS: The most frequently isolated bacteria, from the bloodstream, were Escherichia coli (n = 45, 31.7%) and Klebsiella spp. (n = 35, 24.6%). Thirty-four isolates (23.9%) were MDR, and extended-spectrum beta-lactamase E. coli (52.9%) and methicillin-resistant Staphylococcus aureus (17.6%) were the most commonly isolated MDR bacteria. When Enterococcus spp. were cultured, the majority were MDR (MDR 83.3% vs. 16.7%, p = 0.003), particularly vancomycin-susceptible Enterococcus faecium. Antibiotics administration within 30 days and/or nosocomial infection was a significant predictor of MDR bacteremia (OR: 3.40, 95% CI: 1.24-9.27, p = 0.02). MDR bacteremia was not predicted by sepsis predictors, such as positive systemic inflammatory response syndrome (SIRS) or quick Sequential Organ Failure Assessment (qSOFA). CONCLUSION: More than 70% of strains that can be treated with a third-generation cephalosporin have been cultured. In cirrhotic patients, antibiotic administration within 30 days and/or nosocomial infection are predictors of MDR bacteremia; therefore, empirical administration of broad-spectrum antibiotics should be considered when these risk factors are present.

The diagnostic utility of FIB-4 as a non-invasive tool for liver fibrosis scoring among NAFLD patients: a retrospective cross-sectional study.

OBJECTIVE: Liver biopsy is the gold standard method to evaluate patients with non-alcoholic fatty liver disease (NAFLD). However, due to its several limitations and complications, a reliable and non-invasive marker is required to assess liver fibrosis. In this study, we compared the performance of the FIB-4 index [based on age, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels and platelets count] with the Scheuer scoring system of liver biopsies to evaluate the diagnostic utility of FIB-4 among NAFLD patients with different liver fibrosis severities. PATIENTS AND METHODS: A cross-sectional study was conducted at An-Najah National University Hospital (NNUH) in Palestine. The FIB-4 index was calculated using laboratory data for 128 NAFLD patients who underwent liver biopsies between November 2014 and July 2022. The results of FIB-4 were compared with the Scheuer scoring system of liver biopsies (using F0, F1+F2, F3+F4) to determine the sensitivity and specificity of FIB-4 in detecting and staging liver fibrosis. RESULTS: Out of 128 patients involved in our study, 49 of them had advanced fibrosis according to liver biopsy (F3+F4), where their FIB-4 indices showed 87% sensitivity at 1.45 cut off point and 87% specificity at 3.25 cut off point. CONCLUSIONS: The FIB-4 index may be used as a screening tool in the primary care setting. To raise awareness of liver diseases, this non-invasive, inexpensive, simple, and quick marker could identify people in need of further liver fibrosis evaluation and diagnosis.

[Arbutin ameliorates liver fibrosis in mice by inhibiting macrophage recruitment and regulating the Akt/NF-κB and Smad signaling pathways].

OBJECTIVE: To investigate the protective effect of arbutin against CCl4-induced hepatic fibrosis in mice and explore the underlying mechanisms. METHODS: Twenty-four C57BL/6 mice were randomly divided into control group, model group, and low- and high-dose arbutin treatment (25 and 50 mg/kg, respectively) groups. Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4, and arbutin was administered daily via gavage for 6 weeks. After the treatments, serum biochemical parameters of the mice were tested, and liver tissues were taken for HE staining, Sirius Red staining and immunohistochemical staining. RT-qPCR was used to detect the mRNA levels of α-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-a, and Western blotting was performed to detect α-SMA protein expression in the liver tissues. In the cell experiment, the effect of arbutin treatment for 24 h on THP-1 and RAW264.7 cell migration and recruitment was examined using Transwell migration assay and DAPI staining; The changes in protein levels of Akt, p65, Smad3, p-Akt, p-p65, p-Smad3 and α-SMA in arbutintreated LX-2 cells were detected with Western blotting. RESULTS: Arbutin treatment significantly lowered serum alanine aminotransferase and aspartate aminotransferase levels, alleviated liver tissue damage and collagen deposition, and reduced macrophage infiltration and α-SMA protein expression in the liver of the mouse models (P < 0.05 or 0.001). Arbutin treatment also significantly reduced CCl4-induced elevation of a-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-a mRNA levels in mice (P < 0.05). In the cell experiment, arbutin treatment obviously inhibited migration and recruitment of THP-1 and RAW264.7 cells and lowered the phosphorylation levels of Akt, p65 and Smad3 and the protein expression level of α-SMA in LX-2 cells. CONCLUSION: Arbutin ameliorates liver inflammation and fibrosis in mice by inhibiting hepatic stellate cell activation via reducing macrophage recruitment and infiltration and suppressing activation of the Akt/NF-κB and Smad signaling pathways.

Using the FIB-4, automatically calculated, followed by the ELF test in second line to screen primary care patients for liver disease.

The objective of our work was to evaluate the screening of hepatic fibrosis in primary care using the FIB-4 score, automatically calculated. When the FIB-4 was ≥ 1.3, it was defined as positive, and ELF Test was performed. FIB-4 positivity was confirmed when ELF Test was ≥ 9.8 indicating an advanced fibrosis. Among the 3427 patients included, 869 (25%) had a positive FIB-4 score, 784 (22.5%) at intermediate (FIB-4: 1.3-2.67), and 85 (2.5%) at high risk of fibrosis (FIB-4 > 2.67). 509 (59%) of the FIB-4 positive were confirmed by the ELF Test. The percentage of confirmation was significantly higher in patients over 65 years (83 vs. 57%), with FIB-4 > 2.67 (80 vs. 56%), BMI > 25 (47 vs. 37%), and diabetes (24 vs. 14%), p = 0.001). In patients without known liver disease (92%), the practitioner identified a cause of disease in 27% of cases: mainly NAFLD and alcohol. Liver fibrosis was suspected on FIB-4 in 25% of patients in primary care. The ELF Test, performed as a second-line, improves the screening of liver fibrosis, particularly for FIB-4 intermediate results. A positive FIB-4 test allows physicians to recognize a liver disease, providing an opportunity for timely intervention.Clinical trial registration: Comité de protection des personnes du sud-ouest et outre-mer SI18.00832.201865-MS04-IDRCB 2018-A01571-54.

CLINICAL CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH SEVERE COVID-19 AND CIRRHOSIS OR LIVER TRANSPLANT IN A BRAZILIAN QUATERNARY CENTER.

BACKGROUND: Specific associations between liver cirrhosis and liver transplant with poorer outcomes in COVID-19 are still not completely clear. OBJECTIVE: We aimed to evaluate the clinical characteristics and outcomes of patients with severe COVID-19 and cirrhosis or liver transplant in Sao Paulo, Brazil. METHODS: A retrospective observational study was conducted in a quaternary hospital. Patients with COVID-19 and liver cirrhosis or liver transplant were selected. The clinical and demographic characteristics, as well as the outcomes, were assessed using electronic records. RESULTS: A total of 46 patients with COVID-19 and liver condition were included in the study. Patients with liver cirrhosis had significantly more endotracheal intubation and a higher relative risk of death than liver transplant recipients. Patients with higher MELD-Na scores had increased death rates and lower survival probability and survival time. CONCLUSION: Patients with liver cirrhosis, especially those with higher MELD-Na scores, had poorer outcomes in COVID-19. Liver transplant recipients do not seem to be linked to poorer COVID-19 outcomes.

SPONTANEOUS REGRESSION OF HEPATOCELLULAR CARCINOMA: FOCUSING IN THE ASSOCIATED RISK FACTORS.

BACKGROUND: Spontaneous regression (SR) is defined as the partial or complete disappearance of a tumor, in the absence of a specific treatment. Evidence of the SR in hepatocellular carcinoma (HCC) is rare. OBJECTIVE: The authors aimed to review all the cases of SR of HCC in two reference centers of Southern Brazil, highlighting the main characteristics. METHODS: Data of all patients with HCC were retrospectively reviewed looking for the occurrence of SR in patients from two tertiary centers in Southern Brazil, in the last five years. The diagnosis of cirrhosis was established according to clinical, laboratory and imaging data, as well as upper endoscopy or histopathological examination when necessary. The diagnosis of HCC was based on typical findings according to radiologic criteria (LIRADS) or histopathological examination. Spontaneous regression was defined as a partial or complete involution of a HCC in the absence of a specific therapy. RESULTS: From all cases of HCC in the last 5 years (n=433), there were five cases of SR. Three (60%) were men, the mean age was 62.6 (50.0-76.0) years, and the etiology was HCV in 3 (60%). Complete regression was observed in three patients (60%), one patient (20%) presented partial regression, and one (20%) relapesed and died. The time of follow-up varied between 12 and 21 months. In this presentation, it was highlighted one case of SR observed after COVID-19 infection in a patient with cirrhosis. The possible mechanisms involved in this situation were reviewed, emphasizing the most common like hypoxia and immunological. There were also one patient submitted to a surgical procedure as a possible fator involved and three patients without obvious risk factors. CONCLUSION: This phenomenon will possibly contribute to a better understanding of the pathophysiological mechanisms of HCC.

The value of APGA score, fibrosis index for diagnosing liver fibrosis in patients with chronic hepatitis B.

Background: Various non-invasive methods have been studied for assessing the fibrosis stage in patients with chronic hepatitis B. However, the performance of APGA, Fibrosis index in diagnosing liver fibrosis remains unclear globally and specifically in Vietnam. Methods: An analytical cross-sectional study was performed among 242 patients treated at Thong Nhat Hospital. Results: Both the APGA index and Fibrosis index showed good accuracy in diagnosing significant fibrosis (≥ F2), advanced liver fibro-sis (≥ F3), and cirrhosis (F4) with an area under the curve (AUROC) greater than 0.7. AUROC value of APGA index, Fibrosis index for diagnosing signifcant fibrosis (≥ F2) were 0.828, 0.767 respectively. AUROC value of APGA index, Fibrosis index for diagnosing advanced liver fibrosis (≥ F3) were 0.784, 0.755 respectively. AUROC value of APGA index, Fibrosis index for diagnosing cirrhosis (F4) were 0.736, 0.782 respectively. APGA index and the Fibrosis index were significantly positively correlated with the fibrosis stage (p < 0.001), with the APGA index showing the strongest correlation (r = 0.51, p < 0.001). Conclusions: The APGA values of 6.23, 7.88, and 8.99 can serve as cutoff points for the diagnosis of significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis (F4) when combined with ARFI data.

Application of metagenomic next-generation sequencing in optimizing the diagnosis of ascitic infection in patients with liver cirrhosis.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) is an emerging technique for the clinical diagnosis of infectious disease that has rarely been used for the diagnosis of ascites infection in patients with cirrhosis. This study compared mNGS detection with conventional culture methods for the on etiological diagnosis of cirrhotic ascites and evaluated the clinical effect of mNGS. METHODS: A total of 109 patients with ascites due to cirrhosis were included in the study. We compared mNGS with conventional culture detection by analyzing the diagnostic results, pathogen species and clinical effects. The influence of mNGS on the diagnosis and management of ascites infection in patients with cirrhosis was also evaluated. RESULTS: Ascites cases were classified into three types: spontaneous bacterial peritonitis (SBP) (16/109, 14.7%), bacterascites (21/109, 19.3%) and sterile ascites (72/109, 66.1%). In addition, 109 patients were assigned to the ascites mNGS-positive group (80/109, 73.4%) or ascites mNGS-negative group (29/109, 26.6%). The percentage of positive mNGS results was significantly greater than that of traditional methods (73.4% vs. 28.4%, P < 0.001). mNGS detected 43 strains of bacteria, 9 strains of fungi and 8 strains of viruses. Fourteen bacterial strains and 3 fungal strains were detected via culture methods. Mycobacteria, viruses, and pneumocystis were detected only by the mNGS method. The mNGS assay produced a greater polymicrobial infection rate than the culture method (55% vs. 16%). Considering the polymorphonuclear neutrophil (PMN) counts, the overall percentage of pathogens detected by the two methods was comparable, with 87.5% (14/16) in the PMN ≥ 250/mm3 group and 72.0% (67/93) in the PMN < 250/mm3 group (P > 0.05). Based on the ascites PMN counts combined with the mNGS assay, 72 patients (66.1%) were diagnosed with ascitic fluid infection (AFI) (including SBP and bacterascites), whereas based on the ascites PMN counts combined with the culture assay, 37 patients (33.9%) were diagnosed with AFI (P < 0.05). In 60 (55.0%) patients, the mNGS assay produced positive clinical effects; 40 (85.7%) patients had their treatment regimen adjusted, and 48 patients were improved. The coincidence rate of the mNGS results and clinical findings was 75.0% (60/80). CONCLUSIONS: Compared with conventional culture methods, mNGS can improve the detection rate of ascites pathogens, including bacteria, viruses, and fungi, and has significant advantages in the diagnosis of rare pathogens and pathogens that are difficult to culture; moreover, mNGS may be an effective method for improving the diagnosis of ascites infection in patients with cirrhosis, guiding early antibiotic therapy, and for reducing complications related to abdominal infection. In addition, explaining mNGS results will be challenging, especially for guiding the treatment of infectious diseases.

Impact of an Automated Population-Level Cirrhosis Screening Program Using Common Pathology Tests on Rates of Cirrhosis Diagnosis and Linkage to Specialist Care (CAPRISE): Protocol for a Pilot Prospective Single-Arm Intervention Study.

BACKGROUND: People with compensated cirrhosis receive the greatest benefit from risk factor modification and prevention programs to reduce liver decompensation and improve early liver cancer detection. Blood-based liver fibrosis algorithms such as the Aspartate Transaminase-to-Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) index are calculated using routinely ordered blood tests and are effective screening tests to exclude cirrhosis in people with chronic liver disease, triaging the need for further investigations to confirm cirrhosis and linkage to specialist care. OBJECTIVE: This pilot study aims to evaluate the impact of a population screening program for liver cirrhosis (CAPRISE [Cirrhosis Automated APRI and FIB-4 Screening Evaluation]), which uses automated APRI and FIB-4 calculation and reporting on routinely ordered blood tests, on monthly rates of referral for transient elastography, cirrhosis diagnosis, and linkage to specialist care. METHODS: We have partnered with a large pathology service in Victoria, Australia, to pilot a population-level liver cirrhosis screening package, which comprises (1) automated calculation and reporting of APRI and FIB-4 on routinely ordered blood tests; (2) provision of brief information about liver cirrhosis; and (3) a web link for transient elastography referral. APRI and FIB-4 will be prospectively calculated on all community-ordered pathology results in adults attending a single pathology service. This single-center, prospective, single-arm, pre-post study will compare the monthly rates of transient elastography (FibroScan) referral, liver cirrhosis diagnosis, and the proportion linked to specialist care in the 6 months after intervention to the 6 months prior to the intervention. RESULTS: As of January 2024, in the preintervention phase of this study, a total of 120,972 tests were performed by the laboratory. Of these tests, 78,947 (65.3%) tests were excluded, with the remaining 42,025 (34.7%) tests on 37,872 individuals meeting inclusion criteria with APRI and FIB-4 being able to be calculated. Of these 42,025 tests, 1.3% (n=531) had elevated APRI>1 occurring in 446 individuals, and 2.3% (n=985) had elevated FIB-4>2.67 occurring in 816 individuals. Linking these data with FibroScan referral and appointment attendance is ongoing and will continue during the intervention phase, which is expected to commence on February 1, 2024. CONCLUSIONS: We will determine the feasibility and effectiveness of automated APRI and FIB-4 reporting on the monthly rate of transient elastography referrals, liver cirrhosis diagnosis, and linkage to specialist care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000295640; https://tinyurl.com/58dv9ypp. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56607.

Effect of branched-chain amino acid supplementation and exercise on quadriceps muscle quantity and quality in patients with cirrhosis as assessed by ultrasonography: A randomized controlled trial.

BACKGROUND/AIM: Sarcopenia and myosteatosis are common in patients with cirrhosis. The study aimed to evaluate efficacy of ultrasound to monitor muscle status during branched-chain amino acid (BCAA) supplementation and/or muscle exercise interventional approaches. PATIENTS AND METHODS: A randomized controlled study, included 220 liver cirrhosis patients with Child- Pugh B and C, randomized into a control group (55 patients) received only the standard care, and interventional groups (165 patients) equally distributed into three subgroups, in addition to standard care, they received BCAA, programmed exercise, or BCAA and programmed exercise. At baseline and after 28 days, all participants were subjected to ultrasound-measured quadriceps muscle thickness and echo-intensity, muscle strength using handgrip, performance using short physical performance battery (SPPB), Model for End-Stage Liver Disease (MELD) score and nutritional assessment using 7- point Subjective Global Assessment Score (SGA) and laboratory assessment. RESULTS: All interventional groups showed a significant improvement in the ultrasound detected quadriceps muscle thickness (p = 0.001) and echo intensity, in addition to muscle strength, muscle performance, and SGA. Hematological parameters (hemoglobin and platelet count), biochemical parameters (ALT, AST, bilirubin, creatinine, urea and INR) and MELD score were also improved in the interventional groups. In Child-Pugh B patients BCAA combined with exercise showed an add-on effect. CONCLUSION: BCAA supplements, programed muscle exercise and both are useful interventional methods in improving muscle quality and quantity in cirrhosis patients, which can be monitored by ultrasound. The best results can be achieved by combined intervention in Child-Pugh B, while in Child-Pugh C single intervention may lead to an acceptable improvement. The trial was registered retrospectively in the Clinical Trials Registry (registration number NCT06088550).

Outcomes and Recurrence Rate of Esophageal Varices after Endoscopic Treatment in Patients with Alcoholic Cirrhosis and Viral Cirrhosis.

BACKGROUND: The incidence of alcoholic liver cirrhosis (ALC) is increasing. However, few reports have focused on ALC-derived esophageal varices (EV). We retrospectively examined differences in overall survival (OS) and EV recurrence rate in patients after endoscopic injection sclerotherapy (EIS) for ALC and hepatic B/C virus liver cirrhosis (B/C-LC). METHODS: We analyzed data from 215 patients (B/C-LC, 147; ALC, 68) who underwent EIS. The primary endpoints were OS and EV recurrence in patients with unsuccessful abstinence ALC and those with uncontrolled B/C-LC, before and after propensity score matching (PSM) to unify the patients' background. The secondary endpoints were predictors associated with these factors, as determined by multivariate analysis. RESULTS: The observation period was 1,430 ± 1,363 days. In the analysis of all patients, OS was significantly higher in the ALC group than in the B/C-LC group (p = 0.039); however, there was no difference in EV recurrence rate (p = 0.502). Ascites and history of hepatocellular carcinoma (HCC) (p = 0.019 and p < 0.001, respectively) predicted OS, whereas age and EV size predicted recurrence (p = 0.011 and 0.024, respectively). In total, 96 patients without an HCC history were matched by PSM, and there was no significant difference in OS or EV recurrence rate (p = 0.508 and 0.246, respectively). CONCLUSION: When limited to patients without a history of HCC, OS and the EV recurrence rate were comparable in patients with ALC who continued to consume alcohol and those with B/C-LC without viral control.

[Liver cirrhosis as a multisystem disease]. / Die Leberzirrhose als Multisystemerkrankung.

In recent years, the pathophysiological concept of decompensated liver cirrhosis has undergone significant changes. Until a few years ago, the focus of pathophysiological considerations was on the hyperdynamic circulation resulting from portal hypertension. In recent years, emerging data suggests that increased bacterial translocation leading to systemic inflammation plays an important role in patients with decompensated liver cirrhosis. This inflammation affects a variety of extrahepatic organs. Nowadays, liver cirrhosis is considered not only a condition confined to the liver but rather an inflammatory-triggered multisystem disease. The existing inflammation serves as the common pathophysiological explanation for the diverse impact of liver cirrhosis on several extrahepatic organs. It plays a significant role in the development of conditions such as hepatorenal syndrome, cirrhotic cardiomyopathy, hepatopulmonary syndrome, hepatic encephalopathy, and even in the emergence of cirrhosis-associated relative adrenal insufficiency. These new pathophysiological insights hold clinical significance as they influence the prophylaxis and treatment of patients with decompensated liver cirrhosis.

A Novel Approach to Orthotopic Hepatocyte Transplantation Engineered With Liver Hydrogel for Fibrotic Livers, Enhancing Cell-Cell Interaction and Angiogenesis.

Hepatocyte transplantation (HCT) is a potential bridging therapy or an alternative to liver transplantation. Conventionally, single-cell hepatocytes are injected via the portal vein. This strategy, however, has yet to overcome poor cell engraftment and function. Therefore, we developed an orthotopic HCT method using a liver-derived extracellular matrix (L-ECM) gel. PXB cells (flesh mature human hepatocytes) were dispersed into the hydrogel solution in vitro, and the gel solution was immediately gelated in 37°C incubators to investigate the affinity between mature human hepatocyte and the L-ECM gel. During the 3-day cultivation in hepatocyte medium, PXB cells formed cell aggregates via cell-cell interactions. Quantitative analysis revealed human albumin production in culture supernatants. For the in vivo assay, PXB cells were encapsulated in the L-ECM gel and transplanted between the liver lobes of normal rats. Pathologically, the L-ECM gel was localized at the transplant site and retained PXB cells. Cell survival and hepatic function marker expression were verified in another rat model wherein thioacetamide was administered to induce liver fibrosis. Moreover, cell-cell interactions and angiogenesis were enhanced in the L-ECM gel compared with that in the collagen gel. Our results indicate that L-ECM gels can help engraft transplanted hepatocytes and express hepatic function as a scaffold for cell transplantation.

Development and validation of a nomogram for predicting in-hospital death in cirrhotic patients with acute kidney injury.

BACKGROUND: The purpose of this study was to develop a nomogram for predicting in-hospital mortality in cirrhotic patients with acute kidney injury (AKI) in order to identify patients with a high risk of in-hospital death early. METHODS: This study collected data on cirrhotic patients with AKI from 2008 to 2019 using the Medical Information Mart for Intensive Care IV. Multivariate logistic regression was used to identify confounding factors related to in-hospital mortality, which were then integrated into the nomogram. The concordance index (C-Index) was used to evaluate the accuracy of the model predictions. The area under the curve (AUC) and decision curve analysis (DCA) was used to assess the predictive performance and clinical utility of the nomogram. RESULTS: The final study population included 886 cirrhotic patients with AKI, and 264 (29.8%) died in the hospital. After multivariate logistic regression, age, gender, cerebrovascular disease, heart rate, respiration rate, temperature, oxygen saturation, hemoglobin, blood urea nitrogen, serum creatinine, international normalized ratio, bilirubin, urine volume, and sequential organ failure assessment score were predictive factors of in-hospital mortality. In addition, the nomogram showed good accuracy in estimating the in-hospital mortality of patients. The calibration plots showed the best agreement with the actual presence of in-hospital mortality in patients. In addition, the AUC and DCA curves showed that the nomogram has good prediction accuracy and clinical value. CONCLUSIONS: We have created a prognostic nomogram for predicting in-hospital death in cirrhotic patients with AKI, which may facilitate timely intervention to improve prognosis in these patients.