Advanced Liver Cirrhosis Research Articles

Diagnostic accuracy of red blood cell distribution width to platelet ratio for predicting liver fibrosis in patients with chronic hepatitis B: A meta-analysis

ObjectiveThis study aims to systematically review the performance of red blood cell distribution width to platelet ratio (RPR) in the diagnosis of significant or advanced fibrosis, and cirrhosis associated with hepatitis B virus (HBV). MethodsThe relevant studies were comprehensively searched in English databases such as Web of Science, PubMed, EMBASE, Cochrane Library, as well as Chinese databases such as China National Knowledge Infrastructure, Wanfang Data from the inception to March 2021. Accuracy of RPR in diagnosing significant or advanced fibrosis and liver cirrhosis was assessed by area under the curve (AUC), pooled sensitivity and specificity, as well as positive and negative likelihood ratios. Stata 15.0 software was applied to analyze the data. ResultsIn total, 13 literature met the requirements, including patients with significant fibrosis (n=1890), advanced fibrosis (n=645), and cirrhosis (n=499). The prevalence rates of significant fibrosis, advanced fibrosis and cirrhosis were 49.31% (range: 17.25–84.21%), 37.07% (range: 9.60–58.20%) and 2.18% (range: 2.78–44.19%), respectively. The AUCs for predicting significant fibrosis, advanced fibrosis, and cirrhosis by RPR were 0.73 (95%CI: 0.69–0.76), 0.80 (95%CI: 0.77–0.84) and 0.80 (95%CI: 0.76–0.83), respectively. ConclusionRPR is of some diagnostic value to the prediction of HBV-related significant fibrosis, advanced fibrosis and cirrhosis. This conclusion is urgently needed to be verified by further multi-center studies of large sample size and rigorous design.

Liver fibrosis assessment: MR and US elastography.

Elastography has emerged as a preferred non-invasive imaging technique for the clinical assessment of liver fibrosis. Elastography methods provide liver stiffness measurement (LSM) as a surrogate quantitative biomarker for fibrosis burden in chronic liver disease (CLD). Elastography can be performed either with ultrasound or MRI. Currently available ultrasound-based methods include strain elastography, two-dimensional shear wave elastography (2D-SWE), point shear wave elastography (pSWE), and vibration-controlled transient elastography (VCTE). MR Elastography (MRE) is widely available as two-dimensional gradient echo MRE (2D-GRE-MRE) technique. US-based methods provide estimated Young's modulus (eYM) and MRE provides magnitude of the complex shear modulus. MRE and ultrasound methods have proven to be accurate methods for detection of advanced liver fibrosis and cirrhosis. Other clinical applications of elastography include liver decompensation prediction, and differentiation of non-alcoholic steatohepatitis (NASH) from simple steatosis (SS). In this review, we briefly describe the different elastography methods, discuss current clinical applications, and provide an overview of advances in the field of liver elastography.

Accuracy of AST to platelet ratio for predicting liver fibrosis in patients with chronic HCV infection after viral eradication

Determining the stage of fibrosis is an essential element of chronic hepatitis C (HCV) management. This study aims to evaluate aminotransferase to platelet ratio (APRI) score in comparison with Vibration-Controlled Transient Elastography (VCTE) for assessing the severity of liver disease in HCV-infected patients. Material and methods: We retrospectively enrolled 293 HCV-infected patients with different stages of fibrosis who achieved sustained virological response (SVR) after direct-acting antivirals (DAAs) therapy, which have been evaluated by VCTE from 1st September 2020 to 30th July 2021. Results: Two hundred and ninety-three patients (72.7% females, mean age of 61.75 ± 10.87 years, and mean BMI of 27.85 ± 4.63 kg/m2) were evaluated. As estimated by VCTE, 44 (15%) of patients were without liver fibrosis (F0), 80 (27.3%) with F1 (mild), 39 (13.3%) with F2 (significant), 43 (14.7%) with F3 (advanced) liver fibrosis, and 87 (29.7%) with F4 (cirrhosis), with a mean value of liver stiffness measurements (LSM) of 10.17 ± 7.42 kPa. The APRI score has a positive correlation with the LSM score (p=0.047), predicting severe liver disease adequately. The optimal receiver operator curve (ROC) for predicting advanced fibrosis was > 1.15 (area under the curve [AUC] 0.79, 95% CI 0.71-0.83; p < 0.001) with a sensitivity (Ss) of 82.5%, specificity (Sp) 28%, a positive predictive value (PPV) of 72%, and negative predictive value (NPV) of 81%. Conclusions: APRI score can predict well the advanced liver fibrosis and cirrhosis and can be a useful non-invasive biochemical marker for resource-limited management of HCV-infected patients.

Peripheral Angioinvasive Aspergillosis in the Setting of End-Stage Liver Disease

Invasive aspergillosis of the peripheral arteries is a rare complication in vascular surgery. Angioinvasion can compromise vascular wall integrity, leading to local and systemic complications. We report the case of peripheral angioinvasive aspergillosis of the common femoral artery (CFA) and superficial femoral artery in a patient with decompensated alcoholic liver cirrhosis. We reviewed the electronic medical records for the patient's medical history, diagnostic imaging, operative reports, and in-hospital course. All information was de-identified. A 58-year-old man with advanced alcoholic liver cirrhosis had presented to our tertiary care center for orthotopic liver transplant evaluation. A part of the workup included coronary angiography, which was performed through a 6F femoral sheath access. Subsequently, the patient developed right groin hematoma with a CFA pseudoaneurysm and evidence of femoral nerve compression. He underwent hematoma evacuation and CFA repair that required endarterectomy. His postoperative course was complicated by a recurring surgical site hematoma requiring transfusions, several groin reexplorations, and creation of a sartorius flap to provide coverage of the femoral vascular bundle. A vacuum-assisted closure device was used for wound dressing. During the ensuing days, sartorius flap necrosis developed, and the patient experienced acute arterial bleeding. On reexploration, the CFA was noted to have sieve-like bleeding with complete disintegration of the arterial wall. Ligation of the CFA, profunda femoris, and superficial femoral artery as lifesaving measures was required. The patient's condition continued to worsen, with liver failure and right leg ischemia. After the goals of care were discussed with the family, they decided for terminal extubation, after which the patient died. Evaluation of samples of the femoral vessels obtained during surgery returned positive for the presence of Aspergillus species on fungal stains within the arterial wall, with large fungal bodies protruding into the vessel segment lumen (Fig). Distorted vessel wall anatomy was also observed with dense infiltration and hyphae and evidence of vessel microperforation. The presence of invasive aspergillosis was most likely responsible for the arterial wall disintegration. Peripheral angioinvasive aspergillosis is a rare infectious complication in vascular surgery and can occur in patients with end-stage liver disease. Angioinvasion is difficult to treat and can result in vascular wall compromise, presenting as life-threatening hemorrhage.

Genotype-specific versus pangenotypic regimens in patients infected with hepatitis C virus genotype 1b in real-world settings.

Introduction: The introduction of direct-acting antivirals (DAAs) has provided us with hope to eliminate hepatitis C virus (HCV) infection as a significant public health problem in the coming years. Objective: Our study aimed to compare the effectiveness and safety of genotype-specific and pangenotypic regimens in genotype 1b–infected patients treated in real-world settings. Patients and methods: Patients were selected from 990 HCV-infected individuals treated with DAAs in the Department of Infectious Diseases in Kielce, Poland, who had the therapy initiated between July 1, 2015 and December 31, 2020. Results: A total of 795 genotype 1b–infected patients with a median age of 51 years, female predominance (55%), and a 21.1% rate of cirrhosis were included in the analysis. A total of 69.9% of patients were treated with genotype-specific regimens. Those patients were significantly older, more often were treatment experienced, and had advanced liver fibrosis and cirrhosis compared with patients assigned to pangenotypic regimens. An overall sustained virologic response rate of 97.9% in the intention-to-treat (ITT) analysis and 99% after excluding nonvirologic nonresponders was achieved, with no significant difference between patients in the 2 treatment arms. Significantly higher proportions of men (P = 0.001) and DAA-experienced patients (P = 0.049) were documented among virologic nonresponders. Conclusions: We confirmed very high effectiveness and a good safety profile of both genotype-specific and pangenotypic regimens used in patients with genotype 1b HCV infection, and we found no differences between these 2 generations of medications. Male sex and previous treatment with DAAs were identified as negative predictors for therapy effectiveness.

Impact of Branched Chain Amino Acid on Muscle Mass, Muscle Strength, Physical Performance, Combined Survival, and Maintenance of Liver Function Changes in Laboratory and Prognostic Markers on Sarcopenic Patients With Liver Cirrhosis (BCAAS Study): A Randomized Clinical Trial.

Background: This study aimed to investigate the long-term effects of branched-chain amino acids (BCAAs) supplementations on the parameters associated with improved prognosis in sarcopenic patients with liver cirrhosis (LC) and evaluate its impact on cirrhotic-related events.Methods: A 24-week, single-center, randomized, open-label, controlled, two cohort parallel-group intervention study was carried out by comparing the efficacy of BCAAs against lactoalbumin (L-ALB) on 106 sarcopenic patients with LC. The BCAA (intervention) group was treated with 7.2 g BCAA per dose, whereas the L-ALB group was treated with 6.3 g of L-ALB. The primary outcome was to assess the effect of BCAA on the parameters of sarcopenia, such as muscle mass, muscle strength, and physical performance. The secondary outcomes were to study the combined survival and maintenance of liver function changes in laboratory and prognostic markers over the duration of 6 months.Results: The treatment with BCAA leads to the significant improvement in sarcopenic parameters, such as muscle strength, muscle function, and muscle mass. The total cirrhotic-related complications and cumulative event-free survival occurred fewer in the BCAA group than in the L-ALB group. In addition, prognostic markers improved significantly in the study.Conclusion: The current study demonstrated that long-term BCAAs supplementation improved sarcopenia and prognostic markers in patients with advanced LC.

P-75 UPDATE OF CLINICO-EPIDEMIOLOGICAL CHARACTERISTICS OF PRIMARY BILIAR CHOLANGITIS IN URUGUAY

Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease of increasing prevalence, female-predominant, and usually diagnosed in the fifth decade of life. To update the description of clinico-epidemiological characteristics of a series of Uruguayan patients diagnosed with PBC. Descriptive, multi-centric study including Uruguayan patients diagnosed with PBC (at least two of the following criteria: biochemical cholestasis, autoantibodies —AMA, antinuclear with anticentromere, sp100, or gp210 patterns— and compatible liver biopsy). Age, sex, symptoms, associated diseases, laboratory, imaging, histological and elastography parameters were recorded in the diagnosis. One hundred twenty-nine patients (81 belonging to the first report), 93% female, with an average age of 57 years old (23 - 81) were included. Sixty-nine percent had at least one symptom and 59% had pruritus. Eighty-three percent were AMA-positive and in 41% of patients one or more associated diseases were confirmed. (Table). Histological studies were available in 40 patients (31%), 26 (65%) of which had advanced liver fibrosis or cirrhosis. Elastography was available in 6 patients, 2 of which (33%) were diagnosed with cirrhosis. Six patients (5%) were diagnosed with cirrhosis due to presence of ascites. The global survival rate was 84%. Survival depending on the presence or absence of symptoms was 251 months (95% CI, 229 - 274) and 241 months (95% CI, 238 - 275) respectively (p>0.05). Median survival for cirrhotic patients was 201 months (CI 95%, 160 – 242) versus 191 (CI 95%, 172 – 210) for non-cirrhotics (p>0.05). As previously reported, female prevalence and frequent association with other diseases –mainly autoimmune– remain. The presence of symptoms or cirrhosis showed no association with survival.

Portal hypertension is the main driver of liver stiffness in advanced liver cirrhosis.

Liver stiffness (LS) is a novel non-invasive parameter widely used in clinical hepatology. LS correlates with liver fibrosis stage in non-cirrhotic patients. In cirrhotic patients it also shows good correlation with Hepatic Venous Pressure Gradient (HVPG). Our aim was to assess the contribution of liver fibrosis and portal hypertension to LS in patients with advanced liver cirrhosis. Eighty-one liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG and LS measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France). Liver collagen content was assessed in the explanted liver as collagen proportionate area (CPA) and hydroxyproline content (HP). The studied cohort included predominantly patients with Child-Pugh class B and C (63/81, 77.8%), minority of patients were Child-Pugh A (18/81, 22.2%). LS showed the best correlation with HVPG (r=0.719, p< 0.001), correlation of LS with CPA (r=0.441, p< 0.001) and HP/Amino Acids (r=0.414, p< 0.001) was weaker. Both variables expressing liver collagen content showed good correlation with each other (r=0.574, p<0.001). Multiple linear regression identified the strongest association between LS and HVPG (p < 0.0001) and weaker association of LS with CPA (p = 0.01883). Stepwise modelling showed minimal increase in r2 after addition of CPA to HVPG (0.5073 vs. 0.5513). The derived formula expressing LS value formation is: LS = 2.48 + (1.29 x HVPG) + (0.26 x CPA). We conclude that LS is determined predominantly by HVPG in patients with advanced liver cirrhosis whereas contribution of liver collagen content is relatively low.

Epidemiology and Clinical Outcomes of Metabolic (Dysfunction)-associated Fatty Liver Disease.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is currently the most common chronic liver disease and affects at least a quarter of the global adult population. It has rapidly become one of the leading causes of hepatocellular carcinoma and cirrhosis in Western countries. In this review, we discuss the nomenclature and definition of MAFLD as well as its prevalence and incidence in different geographical regions. Although cardiovascular disease remains the leading cause of death in MAFLD patients, the proportion of patients dying from hepatic complications increases sharply as the disease progresses to advanced liver fibrosis and cirrhosis. In addition, patients with MAFLD are at increased risk of various extrahepatic cancers. Although a causal relationship between MAFLD and extrahepatic cancers has not been established, clinicians should recognize the association and consider cancer screening (e.g., for colorectal cancer) as appropriate.

Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Shift in the Microbial Pattern? A Retrospective Analysis

Introduction: Over the last decade, a shift in the spontaneous bacterial peritonitis (SBP) microbial pattern toward an increasing incidence of gram-positive and multidrug-resistant (MDR) bacteria has been reported. Systematic surveillance of the local microbiological scenario and antibiotic resistance is crucial to SBP treatment success. The main objective of this study was to evaluate the microbiological profile and bacterial resistance of SBP pathogens in a Portuguese cohort to allow selection of the most appropriate empirical antibiotics. Methods: This is a single-center retrospective study including 63 adult cirrhotic patients with culture-positive SBP. Patients were identified using a hospital general diagnostic database and searching for all SBP events (neutrophil count in ascitic fluid ≥250/mm³) from January 1, 2012, to December 31, 2017. Patients were excluded if they had culture-negative SBP, secondary peritonitis, peritoneal dialysis, a liver transplant, or immunodeficiency. The site of SBP acquisition was classified as nosocomial if it was diagnosed 48 h or longer after hospitalization or as nonnosocomial if it was diagnosed within the first 48 h. MDR bacteria were those with an acquired resistance to at least 1 agent in 3 or more antimicrobial categories. All statistical analyses were carried out using IBM SPSS Statistics software version 22 (IBM, New York, USA). Results: The study cohort comprised 53 (84.1%) men. The mean age of the patients was 60.6 ± 11.2 years. Alcohol was the most common etiology (88.9%) and most patients had advanced liver cirrhosis (87.1%, Child C). Gram-negative bacteria were slightly more frequent than gram-positive bacteria (56.9 vs. 43.1%). Escherichia coli was the most common pathogen (33.8%). Nineteen (31.7%) bacteria were classified as MDR. Resistance to third-generation cephalosporins, quinolones, piperacillin-tazobactam, and carbapenems was found in 31.7, 35, 26.7, and 18.3% of the cases, respectively. The rates of gram-positive bacteria were similar between nosocomial and nonnosocomial episodes (45 vs. 42.2%; p = 0.835). MDR bacteria were more common in the nosocomial group (50 vs. 23.8%; p = 0.046). Resistance to third-generation cephalosporins (50 vs. 23.8%; p = 0.046), piperacillin-tazobactam (44.4 vs. 19.1%; p = 0.041), and carbapenems (33.3 vs. 11.9%; p = 0.049) occurred more frequently in nosocomial episodes. Resistance to first-line antibiotic occurred in 29.3% of the patients, being more common in the nosocomial group (44.4 vs. 22.5%; p = 0.089). Conclusion: Although gram-negative bacteria remain the most common causative microorganisms, our results emphasize the shift in SBP microbiological etiology, as almost half of the isolated microorganisms were gram positive. The emergence of bacteria resistant to traditionally recommended empirical antibiotics underlines the importance of basing this choice on local flora and antibiotic susceptibility data, allowing a more rational and successful use of antibiotics.

Long-standing effect of cholecystectomy in patients with metabolic-associated fatty liver disease.

The role of cholecystectomy as a risk factor in patients with metabolic-associated fatty liver disease (MAFLD) remains unclear. This study aimed to investigate if long-standing cholecystectomy is associated with advanced liver fibrosis and cirrhosis in patients with recently diagnosed MAFLD. A retrospective observational study was performed in four hospitals in Mexico including patients with recently diagnosed MAFLD and a history of cholecystectomy. Subjects were divided into those with cholecystectomy ≥6 months before MAFLD diagnosis (ChBM), and those with cholecystectomy at the time of MAFLD diagnosis (ChAM). Odds ratios (OR) for the association of advanced liver fibrosis and cirrhosis with the timing of cholecystectomy were calculated. Mean age of 211 participants was 49.06 ± 15.12 years and the majority were female (72.5%). Patients from the ChBM (n = 70) group were significantly older (53.14 vs. 47.03 years; P = 0.003), had higher BMI (30.54 vs. 28.52 kg/m2; P = 0.011) and lower platelet count (236.23 vs. 266.72 × 103/µL; P = 0.046) compared with patients from ChAM group (n = 141). In multivariable-adjusted analysis, age (OR = 2.37; P = 0.024), dyslipidemia (OR = 4.28; P = 0.005) and severe liver fibrosis (OR = 4.68; P = 0.0) were independent risk factors associated with long-standing cholecystectomy. Patients with long-standing cholecystectomy (≥6 months) are at increased risk of severe liver fibrosis and cirrhosis at the time of MAFLD diagnosis compared to those with recently done cholecystectomy. Advanced age (>50 years) and dyslipidemia are also commonly found in these subjects.

Hepatic Hydrothorax in a Patient with Liver Cirrhosis: a Case Report

Hepatic hydrothorax is a transudative pleural effusion which presents in 5-10% patients with liver cirrhosis. Although fairly uncommon, it is associated with higher morbidity and lower survival rate. The mechanism is yet to be understood fully, but the most widely accepted pathogenesis involves the presence of portal hypertension, diaphragmatic defects, and negative intrathoracal pressure, all of which lead to the formation of unidirectional passage of ascitic fluid from peritoneal cavity into pleural space. Due to its origin, the pleural effusion has similar characteristics to ascitic fluid. We herein report the case of a 60-year-old woman with advanced liver cirrhosis and right-sided moderate hepatic hydrothorax. Treatment given to the patient includes diuretics, sodium restriction, and repeated thoracentesis. Subsequent evaluation of the patient revealed improvement both clinically and radiologically.

The Combination of Age, International Standardized Ratio, Albumin and γ-Glutamyl Transpeptidase (AIAG), Tumor Size and Alpha Fetoprotein (AFP) Stage as the Prognostic Model for Hepatitis B-Related Hepatocellular Carcinoma.

BackgroundAdvanced liver fibrosis can lead to cirrhosis, portal hypertension and liver failure. Besides, advanced liver fibrosis and cirrhosis are the major risk factors for hepatocellular carcinoma (HCC). Almost all patients with HCC also have liver cirrhosis. This study aims to predict the survival rate of hepatitis B-related hepatocellular carcinoma (HCC) by age, international standardized ratio, albumin and γ-glutamyl transpeptidase (AIAG), an indicator measuring the degree of cirrhosis.MethodsA total of 501 hepatitis B-related HCC patients experiencing radical surgery were analyzed, retrospectively. General data about demographics and labs were collected at the date of diagnosis to calculate AIAG [age, international standardized ratio (INR), albumin and gamma-glutamyl transferase (GGT)]. The Kaplan–Meier curves and Cox analysis were used to evaluate overall survival (OS) and recurrence-free survival (RFS). The C-index was calculated in R software (version 4.0.3) to evaluate the accuracy of the prognostic model.ResultsDuring a median follow-up period of 30 months, 31.1% (156/501) of the patients died, and 34.3% (172/501) experienced the recurrence of HCC. Compared with patients with lower AIAG score, patients with higher AIAG score had higher Child-Pugh grade and were at higher Barcelona Clinic Liver Cancer (BCLC) stage (both P<0.05). Multivariate analysis suggested that GGT, alpha fetoprotein (AFP), tumor size, BCLC stage and AIAG grade were independent predictors of OS and RFS. Furthermore, the combined use of tumor size, AFP and AIAG stage could predict survival significantly better (C-index=0.710, 95% CI: 0.669–0.751) than BCLC stage.ConclusionAIAG is significantly associated with survival of HCC patients, and provides additional prognostic information for patients with HCC. Our findings suggest that the combination of AIAG, tumor size and AFP stage has a better predictive value for the prognosis of patients with hepatitis B-related hepatocellular carcinoma. However, it is necessary for more external evidences to determine clinical utility.

Role of the S100 protein family in liver disease (Review).

Liver disease is a significant health challenge worldwide and comprises liver fibrosis and cirrhosis, viral hepatitis, fatty liver, non‑alcoholic fatty liver disease, alcoholic liver disease and hepatocellular carcinoma (HCC). Due to the lack of effective treatments, the prognosis of end‑stage liver disease (including advanced liver cirrhosis and HCC) is often poor. S100 proteins are a type of Ca2+ binding protein, which are expressed in a cell‑specific manner in vertebrates. These proteins are involved in numerous functions, such as serving as intracellular Ca2+ sensors, transduction of Ca2+ signals and regulation of extracellular factors that affect cellular activity by binding to a range of membrane receptors. Evidence has shown that S100 proteins serve key roles in the occurrence and development of liver disease and can be used as potential therapeutic targets or diagnosis markers. For example, certain studies have suggested that blocking S100 protein expression may be an innovative treatment strategy. The present review focuses on the functions of the S100 protein family in liver disease.

To turn weakness into a strength-preoperative future liver remnant (FLR) augmentation with special focus on local tumor control and in-situ immunization for patients with advanced hepatocellular carcinoma (HCC) and liver cirrhosis (LC)

Portal vein embolization (PVE) provokes tumor progression. LC decreases FLR regeneration capacity doubling the risk for patient dropout. Our aim was to develop method of FLR augmentation that convert aggressive tumor into safe vaccine and prolonged waiting period for FLR regeneration into effective In situ immunization period. 3 initially unresectable patients due to small FLR with advanced hepatocellular carcinoma (HCC) and LC were treated. Selective transarterial chemoembolization with short term biodegradable starch microspheres (DSM-TACE), into tumor bearing liver to be resected, was followed by simultaneous PVE of latter. Upon completion of PVE selective intratumoral immunotherapy (HIT-IT) with antiPD-L1 (atezolizumab 1,200 mg) into restored after DSM-TACE tumor arterial feeders (for selective connection with PD-L1 ligands located on tumor cells but not on normal human tissues) was done. DSM-TACE and HIT-IT was repeated one more time in all patients after postzenith decrease of T-cytotoxic cells. Predominantly T and NK cells response was observed. All patients had successfully underwent major liver resection upon sufficient FLR regeneration. In all 3 cases we had achieved effective local tumor control via total or subtotal HCC necrosis, even more, in 1 (33%) case planned amount of liver resection was decreased due to achieved tumor downsizing. There were no severe morbidity or Immune-related adverse events (irAEs). Herein we had proposed new aggressive but safe method of FLR augmentation for patients with HCC and LC that could potentially preclude drop out of patients during anticipated prolonged waiting period of FLR augmentation and possible improves long-term outcomes by means of tumor downsizing and HCC immunoscore conversion.

Current impact of viral hepatitis on liver cancer development: The challenge remains.

Chronic infections due to hepatitis B and hepatitis C viruses are responsible for most cases of hepatocellular carcinoma (HCC) worldwide, and this association is likely to remain during the next decade. Moreover, viral hepatitis-related HCC imposes an important burden on public health in terms of disability-adjusted life years. In order to reduce such a burden, some major challenges must be faced. Universal vaccination against hepatitis B virus, especially in the neonatal period, is probably the most relevant primary preventive measure against the development of HCC. Moreover, considering the large adult population already infected with hepatitis B and C viruses, it is also imperative to identify these individuals to ensure their access to treatment. Both hepatitis B and C currently have highly effective therapies, which are able to diminish the risk of development of liver cancer. Finally, it is essential for individuals at high-risk of HCC to be included in surveillance programs, so that tumors are detected at an early stage. Patients with hepatitis B or C and advanced liver fibrosis or cirrhosis benefit from being followed in a surveillance program. As hepatitis B virus is oncogenic and capable of leading to liver cancer even in individuals with early stages of liver fibrosis, other high-risk groups of patients with hepatitis B are also candidates for surveillance. Considerable effort is required concerning these strategies in order to decrease the incidence and the mortality of viral hepatitis-related HCC.

Minimal hepatic encephalopathy may be present despite the absence of non-invasive and elastography evidence of cirrhosis in patients with primary biliary cholangitis

PurposeMinimal hepatic encephalopathy (MHE) is an important complication of chronic liver disease (CLD); however, MHE burden in patients with primary biliary cholangitis (PBC) has not been determined yet. Therefore, our study aimed to assess the prevalence of MHE in a typical cohort of middle-aged, patients with PBC suspicion of liver fibrosis and to investigate the relationship between MHE, basic laboratory tests and the stage of liver fibrosis. Patients and methodsFifty-one patients (38 with PBC and 13 controls), were prospectively enrolled. Portosystemic Encephalopathy-Syndrome test was used to diagnose MHE. Elastography point qualification (ElastPQ) and non-invasive markers (APRI and FIB-4) were used to assess liver fibrosis. The severity of CLD was assessed using the Model of End-Stage Liver Disease (MELD) and Child-Pugh score. ResultsMHE was diagnosed in 9 patients (24.3%) with PBC and none in the control group. As many as 44.4% of the patients with MHE had neither advanced fibrosis nor cirrhosis, as demonstrated using non-invasive markers of liver fibrosis or ElastPQ. The MELD score was the only predictor of MHE with cut-off value 8.5 [AUC ​= ​0.753, CI95% ​= ​0.569 to 0.938)] with sensitivity of 56%, specificity of 85% and accuracy of the test of 78%. Non-invasive markers of liver fibrosis and ElastPQ did not predict MHE. ConclusionsMHE may occur in PBC despite no evidence of advanced liver fibrosis or cirrhosis. The slightly elevated MELD score may indicate a substantially increased risk of MHE in patients with PBC.

Diagnostic Accuracy of Serum Hyaluronan for Detecting HCV Infection and Liver Fibrosis in Asymptomatic Blood Donors.

Background: The disease caused by hepatitis C virus (HCV) is asymptomatic, silent, and progressive liver disease. In HCV-infected patients the increase in serum HA is associated with the development of hepatic fibrosis and disease progression. Methods: HCV-RNA detection was performed in all serological samples of blood donors that tested positive using HCV Ultra ELISA. Determination of hyaluronan (HA) was performed in positive HCV samples using ELISA-like fluorometric method. The HA content was compared to HCV viral load, genotype of the virus, liver fibrosis as well as ALT and GGT liver biomarkers. Results: Persistently normal ALT (<40 U/L) and GGT (<50 U/L) serum levels were detected in 75% and 69% of the HCV-Infected blood donors, respectively. Based on ROC analysis, the HA value < 34.2 ng/mL is an optimal cut-off point to exclude HCV viremia (specificity = 91%, NPV = 99%). Applying HA value ≥34.2 ng/mL significant liver fibrosis (≥F2) can be estimated in 46% of the HCV-infected blood donors. HA serum level (≥34.2 ng/mL) associated with a high ALT level (>40 U/mL) can correctly identify HCV infection and probable liver fibrosis (sensitivity = 96% and specificity = 90%) in asymptomatic blood donors. Conclusions: A high level of HA (≥34.2 ng/mL) in association with ALT (≥40 U/L) in serum can provide a good clinical opportunity to detect HCV-infected asymptomatic persons that potentially require a liver biopsy confirmation and antiviral treatment to prevent the development of advanced liver fibrosis or cirrhosis.

Reduced‑dose apixaban and dabigatran in patients with advanced liver cirrhosis and venous thromboembolism: a case series.

Reduced‑dose apixaban and dabigatran in patients with advanced liver cirrhosis and venous thromboembolism: a case series.

Hexa Histidine-Tagged Recombinant Human Cytoglobin Deactivates Hepatic Stellate Cells and Inhibits Liver Fibrosis by Scavenging Reactive Oxygen Species.

Background and AimsAntifibrotic therapy remains an unmet medical need in human chronic liver disease. We report the antifibrotic properties of cytoglobin (CYGB), a respiratory protein expressed in hepatic stellate cells (HSCs), the main cell type involved in liver fibrosis.Approach and Results Cygb‐deficient mice that had bile duct ligation–induced liver cholestasis or choline‐deficient amino acid–defined diet–induced steatohepatitis significantly exacerbated liver damage, fibrosis, and reactive oxygen species (ROS) formation. All of these manifestations were attenuated in Cygb‐overexpressing mice. We produced hexa histidine–tagged recombinant human CYGB (His‐CYGB), traced its biodistribution, and assessed its function in HSCs or in mice with advanced liver cirrhosis using thioacetamide (TAA) or 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC). In cultured HSCs, extracellular His‐CYGB was endocytosed and accumulated in endosomes through a clathrin‐mediated pathway. His‐CYGB significantly impeded ROS formation spontaneously or in the presence of ROS inducers in HSCs, thus leading to the attenuation of collagen type 1 alpha 1 production and α‐smooth muscle actin expression. Replacement the iron center of the heme group with cobalt nullified the effect of His‐CYGB. In addition, His‐CYGB induced interferon‐β secretion by HSCs that partly contributed to its antifibrotic function. Momelotinib incompletely reversed the effect of His‐CYGB. Intravenously injected His‐CYGB markedly suppressed liver inflammation, fibrosis, and oxidative cell damage in mice administered TAA or DDC mice without adverse effects. RNA‐sequencing analysis revealed the down‐regulation of inflammation‐ and fibrosis‐related genes and the up‐regulation of antioxidant genes in both cell culture and liver tissues. The injected His‐CYGB predominantly localized to HSCs but not to macrophages, suggesting specific targeting effects. His‐CYGB exhibited no toxicity in chimeric mice with humanized livers.ConclusionsHis‐CYGB could have antifibrotic clinical applications for human chronic liver diseases.