Stages Of Cirrhosis Research Articles

Low ADAMTS13 Activity in Patients with Liver Disease- Thrombotic Thrombocytopenic Purpura or Not?

Introduction: Patients with liver injury have hemostatic defects including reduced ADAMTS13 (A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13). Severe deficiency of ADAMTS13 (ADMS13) activity (< 10%) is pathognomonic for thrombotic thrombocytopenic purpura (TTP), a rare thrombotic microangiopathy (TMA). Differentiating TTP from severe liver injury is complex for multiple reasons including 1) low baseline ADMS13 2) concomitant coagulopathies complicating differentiation from disseminated intravascular coagulation (DIC) 3) ADMS13 activity (ADMS13:AC) assay interference (hyperbilirubinemia (>30mg/dL) can cause artifactual reduction of ADMS13:AC). Here we sought to characterize the clinical presentation, management, and outcomes of patients with liver injury presenting with thrombocytopenia (TCP), microangiopathic hemolytic anemia (MAHA) and low ADMS13:AC at our institution. Methods: In this retrospective study, after IRB approval, electronic medical records (EMR) of institutional patients who had ADMS13:AC and inhibitor profile performed in our special coagulation laboratory between 2018 and July 17, 2023, were reviewed. Eligible patients had ADMS13:AC ≤20% were ≥ 18 years and had evidence of liver injury at time of ADMS13. Liver injury was defined as ALT or AST elevations greater than two times the upper level of normal within one month prior to ADMS13:AC testing, history of end stage liver disease or cirrhosis, or liver transplant with evidence of graft dysfunction. Details regarding clinical presentation, management and outcomes were extracted from the EMR. PLASMIC and ISTH DIC scores were retrospectively calculated. Results: 70 patients had at least one ADMS13:AC < 20% during the study period. 28/70 patients met liver injury inclusion criteria and 20/28 had TCP and MAHA. Of those 20 patients, median age at initial ADMS13:AC was 56.5 years (29-85). Most patients (n=14) had ADMS13:AC of 10-20%. ADMS13:AC was < 5% and 5-10% in 3 patients each. Eleven patients had a positive inhibitor with a median Bethesda titer of 1.85 BU (0.5-3.9). Etiology of liver included: ischemic hepatopathy (n=8), liver graft failure (n=4), liver metastasis (n=3), cirrhosis (n=2), alcoholic hepatitis (n=1), unknown (n=2). Median hemoglobin and platelet (plt) count at time of ADMS13 was 7 g/dL (6.4-13.2) and 30 x10 9/L (3-98), respectively. 7/20 patients had a PLASMIC score of ≥5; PLASMIC score was ≥5, in 2/6 patients with ADMS13:AC <10%. 16/18 patients had an ISTH DIC score ≥5. 18/20 patients had a creatinine > 2 mg/dL or were receiving renal replacement therapy the time of ADMS13: AC. 7/20 patients had total or direct bilirubin of >30mg/dL. Eight/20 patients were treated with plasma exchange (PEX) for a median duration of 7 days (2-13). 66.7% of pts with ADMS13:AC <10% received PEX. Glucocorticoids and Rituximab were used with the intent to treat TTP in 7 and 3 patients, respectively. Caplacizumab was used in 2 patients. 3/8 (37.5%) patients receiving PEX demonstrated normalization of MAHA. One of these patients demonstrated improvement but not normalization of plts (Table 1B, case 5). All patients had recurrence of hematologic abnormalities after PEX was stopped. One patient was treated with plasma infusion with stabilization in plt count. There were 13 and 15 deaths within 1 and 6 months of first ADMTS13:AC, respectively. One death was potentially attributable to management of TTP (Table 1B, case 1). There was no difference in time to death or mortality with the use of PEX. Repeat ADMS13:AC remote from PEX, TCP and MAHA was available for 1/5 surviving patients. This patient (Table1, case 2) had normalization of ADMS:AC after undergoing liver transplant. Conclusion: The differential diagnosis of TCP and MAHA in patients with liver injury includes hepatic dysfunction, DIC and TMA. In the current cohort, 89% of evaluable patients met criteria for overt DIC per ISTH criteria. Due to a low ADMTS13:AC, 40% of patients underwent a trial of PEX with 37.5% demonstrating improvement in MAHA that was not sustained upon discontinuation of PEX due to persistent liver dysfunction. Six-month mortality was 75% and use of PEX did not affect mortality. Given the high mortality, further studies evaluating which patients with TMA and liver injury are more likely to benefit from therapies typically used to treat TTP are necessary.

Abstract 17801: Age-Specific Normal Values for Myocardial Blood Flow on 82rb Positron Emission Tomography

Introduction: Positron emission tomography (PET) myocardial perfusion imaging (MPI) is utilized to evaluate ischemia along with myocardial blood flow (MBF). The ability to adequately augment blood flow, measured by myocardial blood flow reserve (MBFR), is a measure of overall health of the coronary circulation and associated with lower major adverse cardiovascular events (MACE) and all-cause mortality. The age-specific ranges of MBFR in patients without demonstrable coronary artery disease (CAD) has not been well established. Hypothesis/Aim: To determine the effect of age on MBF and MBFR in a cohort of patients without demonstrable CAD. Methods: Patients who underwent PET MPI studies from 2012-2022 on Siemens PET/CT cameras were included if Summed Stress Score=0, coronary calcium score=0, and left ventricular ejection fraction ≥50%. Those with prior history of MI or coronary intervention, heart/kidney/liver transplant, cirrhosis, or CKD stage IV+ were excluded. MBF was calculated using a net retention model (ImagenQ, Cardiovascular Imaging Technologies, Kansas City, MO) and multivariable linear regression models were developed to predict MBF. Results: Among 3,235 patients (age 59.5+/-12.6 years, 24.2% male) with median rest MBF 0.74 [0.61-0.92] and stress MBF 1.71 [1.41-2.10], MBFR was 2.28 [1.93-2.72]. With increasing age, rest MBF remained fairly stable while stress MBF and MBFR decreased, such that for every 10 years of age, stress MBF decreased by 0.07 [95% CI 0.05-0.08] mL/min/g and MBFR decreased by 0.12 [95% CI 0.11-0.14] after multivariable adjustment. Age-specific predicted MBFR values are documented in the Table. Conclusions: In patients without demonstrable CAD, the MBFR decreases with age. Abnormal MBFR values under 2.0 may be seen in a significant number of older patients.

Tumor Necrosis Factor-Alpha and Adiponectin in Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma.

Nonalcoholic fatty liver disease (NAFLD) is emerging as an important risk factor for hepatocellular carcinoma (HCC), whose prevalence is rising. Although the mechanisms of progression from NAFLD to HCC are not fully elucidated, tumor necrosis factor-α (TNF-α) and adiponectin, as well as their interplay, which seems to be antagonistic, may contribute to the pathophysiology of NAFLD-associated HCC. TNF-α initially aims to protect against hepatocarcinogenesis, but during the progression of NAFLD, TNF-α is increased, thus probably inducing hepatocarcinogenesis in the long-term, when NAFLD is not resolved. On the other hand, adiponectin, which is expected to exert anti-tumorigenic effects, is decreased during the progression of the disease, a trend that may favor hepatocarcinogenesis, but is paradoxically increased at end stage disease, i.e., cirrhosis and HCC. These observations render TNF-α and adiponectin as potentially diagnostic biomarkers and appealing therapeutic targets in the setting of NAFLD-associated HCC, possibly in combination with systematic therapy. In this regard, combination strategy, including immune checkpoint inhibitors (ICIs) with anti-TNF biologics and/or adiponectin analogs or medications that increase endogenous adiponectin, may warrant investigation against NAFLD-associated HCC. This review aims to summarize evidence on the association between TNF-α and adiponectin with NAFLD-associated HCC, based on experimental and clinical studies, and to discuss relevant potential therapeutic considerations.

HMGB2 is a potential diagnostic marker and therapeutic target for liver fibrosis and cirrhosis.

High mobility group proteins 1 and 2 (HMGB1 and HMGB2) are 80% conserved in amino acid sequence. The function of HMGB1 in inflammation and fibrosis has been extensively characterized. However, an unaddressed central question is the role of HMGB2 on liver fibrosis. In this study, we provided convincing evidence that the HMGB2 expression was significantly upregulated in human liver fibrosis and cirrhosis, as well as in several mouse liver fibrosis models. The carbon tetrachloride (CCl4) induced liver fibrosis mouse model was used. AAV8-Hmgb2 was utilized to overexpress Hmgb2 in the liver, while Hmgb2-/- mice were used for loss of function experiments. The HMGB2 inhibitor inflachromene and liposome-shHMGB2 (lipo-shHMGB2) were employed for therapeutic intervention. The serum HMGB2 levels were also markedly elevated in patients with liver fibrosis and cirrhosis. Deletion of Hmgb2 in Hmgb2-/- mice or inhibition of HMGB2 in mice using a small molecule ICM slowed the progression of CCl4-induced liver fibrosis despite constant HMGB1 expression. In contrast, AAV8-mediated overexpression of Hmgb2 enchanced CCl4-incuded liver fibrosis. Primary hepatic stellate cells (HSCs) isolated from Hmgb2-/- mice showed significantly impaired transdifferentiation and diminished activation of α-SMA, despite a modest induction of HMGB1 protein. RNA-seq analysis revealed the induction of top 45 CCl4-activated genes in multiple signaling pathways including integrin signaling and inflammation. The activation of these genes by CCl4 were abolished in Hmgb2-/- mice or in ICM-treated mice. These included C-X3-C motif chemokine receptor 1 (Cx3cr1) associated with inflammation, cyclin B (Ccnb) associated with cell cycle, DNA topoisomerase 2-alpha (Top2a) associated with intracellular component, and fibrillin (Fbn) and fibromodulin (Fmod) associated with extracellular matrix. We conclude that HMGB2 is indispensable for stellate cell activation. Therefore, HMGB2 may serve as a potential therapeutic target to prevent HSC activation during chronic liver injury. The blood HMGB2 level may also serve as a potential diagnostic marker to detect early stage of liver fibrosis and cirrhosis in humans.

The Impact of Clinical Prognosis of Viral Hepatitis in Head and Neck Cancer Patients Receiving Concurrent Chemoradiotherapy.

This study evaluated the clinical characteristics of head and neck cancer (HNC) patients with hepatitis B (HBV) or hepatitis C (HCV) who underwent concurrent chemoradiotherapy (CCRT) and examined the prognostic impact of antiviral therapies. In a 19-year retrospective analysis of 8224 HNC patients treated with CCRT, 29.8% (2452) were diagnosed with HBV or HCV, of whom 714 received antiviral therapy. For non-metastatic HNC patients on CCRT, factors such as gender, Charlson Comorbidity Index (CCI), liver cirrhosis markers (Fibrosis-4, APRI), and initial tumor stage were significant determinants of their overall survival. However, the presence of HBV or HCV and the administration of antiviral treatments did not yield distinct survival outcomes. In summary, antiviral therapy for HBV or HCV did not affect the 5-year survival rates of non-metastatic HNC patients undergoing CCRT, while gender, tumor stage, CCI, and liver cirrhosis were notable prognostic indicators.

Diagnostic role of transient elastography in patients with autoimmune liver diseases: A systematic review and meta-analysis.

Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy. However, previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease. The diagnostic value of transient elastography for autoimmune liver diseases (AILDs) is worth studying. To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD. The PubMed, Cochrane Library and EMBASE databases were searched. Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs [autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)] were included. The summary area under the receiver operating characteristic curve (AUROC), diagnostic odds ratio, sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis. A total of 60 articles were included in this study, and the number of patients with AIH, PBC and PSC was 1594, 3126 and 501, respectively. The summary AUROC of transient elastography in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis in patients with AIH were 0.84, 0.88 and 0.90, respectively, while those in patients with PBC were 0.93, 0.93 and 0.91, respectively. The AUROC of cirrhosis for patients with PSC was 0.95. However, other noninvasive indices (aspartate aminotransferase to platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, fibrosis-4 index) had corresponding AUROCs less than 0.80. Transient elastography exerts better diagnostic accuracy in AILD patients, especially in PBC patients. The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.

Antimitochondrial antibody associated with liver cirrhosis in patients with primary biliary cholangitis.

Antimitochondrial antibody (AMA) serves as a serological marker for diagnosing primary biliary cholangitis (PBC). However, the association between AMA and prognosis for PBC patients remains unclear. The objective of this study was to investigate the relationship between AMA and cirrhosis in PBC patients. This retrospective study enrolled 225 PBC patients, including 127 with liver cirrhosis and 98 without cirrhosis. AMA was tested by indirect immunofluorescence (IIF) with rat kidney as the substrate. AMA-M2 and M2-3E were detected by line immunoassay (LIA). The overall positivity rate for AMA detection in PBC patients was 80.9%. The positivity rates of IIF-AMA, AMA-M2, and M2-3E were significantly higher in patients with liver cirrhosis than in those without cirrhosis (73.2% vs. 52.0%, 74.0% vs. 51.0%, and 80.3% vs. 60.2%, respectively). In multivariate logistic regression, IIF-AMA (OR: 3.05, 95% CI: 1.59-5.87), AMA-M2 (OR: 3.11, 95% CI: 1.61-6.01), and M2-3E (OR: 3.29, 95% CI: 1.63-6.66) remained significantly associated with an increased incidence of liver cirrhosis. Moreover, in multinomial logistic regression, IIF-AMA (compensated cirrhosis, OR: 3.55, 95% CI: 1.49-8.44; decompensated cirrhosis, OR: 2.86, 95% CI: 1.32-6.18), AMA-M2 (compensated cirrhosis, OR: 4.74, 95% CI: 1.94-11.58; decompensated cirrhosis, OR: 2.51, 95% CI: 1.19-5.33), and M2-3E (compensated cirrhosis, OR: 4.92, 95% CI: 1.74-13.96; decompensated cirrhosis, OR: 2.91, 95% CI: 1.28-6.64) were all found to be associated with different stages of liver cirrhosis. AMA was found to be associated with the occurrence of liver cirrhosis in PBC patients. Additionally, AMA was also related to different stages of liver cirrhosis, including compensated and decompensated cirrhosis.

Extracellular Vesicles as Therapeutic and Diagnostic Tools for Chronic Liver Diseases.

Chronic liver diseases can lead to fibrotic changes that may progress to the development of cirrhosis, which poses a significant risk for morbidity and increased mortality rates. Metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and viral hepatitis are prevalent liver diseases that may lead to cirrhosis. The advanced stages of cirrhosis can be further complicated by cancer development or end-stage liver disease and liver failure. Hence, early detection and diagnosis of liver fibrosis is crucial for preventing the progression to cirrhosis and improving patient outcomes. Traditionally, invasive liver biopsy has been considered the gold standard for diagnosing and staging liver fibrosis. In the last decade, research has focused on non-invasive methods, known as liquid biopsies, which involve the identification of disease-specific biomarkers in human fluids, such as blood. Among these alternative approaches, extracellular vesicles (EVs) have emerged as promising diagnostic and therapeutic tools for various diseases, including chronic liver diseases. EVs are released from stressed or damaged cells and can be isolated and quantified. Moreover, EVs facilitate cell-to-cell communication by transporting various cargo, and they have shown the potential to reduce the expression of profibrogenic markers, making them appealing tools for novel anti-fibrotic treatments. This review focuses on the impact of EVs in chronic liver diseases and exploring their potential applications in innovative therapeutic and diagnostic approaches.

Recent Advances in the Pathogenesis and Clinical Evaluation of Portal Hypertension in Chronic Liver Disease.

In chronic liver disease, hepatic stellate cell activation and degeneration of liver sinusoidal endothelial cells lead to structural changes, which are secondary to fibrosis and the presence of regenerative nodules in the sinusoids, and to functional changes, which are related to vasoconstriction. The combination of such changes increases intrahepatic vascular resistance and causes portal hypertension. The subsequent increase in splanchnic and systemic hyperdynamic circulation further increases the portal blood flow, thereby exacerbating portal hypertension. In clinical practice, the hepatic venous pressure gradient is the gold-standard measure of portal hypertension; a value of ≥10 mm Hg is defined as clinically significant portal hypertension, which is severe and is associated with the risk of liver-related events. Hepatic venous pressure gradient measurement is somewhat invasive, so evidence on the utility of risk stratification by elastography and serum biomarkers is needed. The various stages of cirrhosis are associated with different outcomes. In viral hepatitis-related cirrhosis, viral suppression or elimination by nucleos(t)ide analog or direct-acting antivirals results in recompensation of liver function and portal pressure. However, careful follow-up should be continued, because some cases have residual clinically significant portal hypertension even after achieving sustained virologic response. In this study, we reviewed the current and future prospects for portal hypertension.

New insights into the pathogenesis of primary biliary cholangitis asymptomatic stage.

Primary biliary cholangitis (PBC) is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in adults. Damage to cholangiocytes triggers the development of intrahepatic cholestasis, which progresses to cirrhosis in the terminal stage of the disease. Accumulating data indicate that damage to biliary epithelial cells [(BECs), cholangiocytes] is most likely associated with the intracellular accumulation of bile acids, which have potent detergent properties and damaging effects on cell membranes. The mechanisms underlying uncontrolled bile acid intake into BECs in PBC are associated with pH change in the bile duct lumen, which is controlled by the bicarbonate (HCO3-) buffer system "biliary HCO3- umbrella". The impaired production and entry of HCO3- from BECs into the bile duct lumen is due to epigenetic changes in expression of the X-linked microRNA 506. Based on the growing body of knowledge on the molecular mechanisms of cholangiocyte damage in patients with PBC, we propose a hypothesis explaining the pathogenesis of the first morphologic (ductulopenia), immunologic (antimitochondrial autoantibodies) and clinical (weakness, malaise, rapid fatigue) signs of the disease in the asymptomatic stage. This review focuses on the consideration of these mechanisms.

Segmental analysis of liver cirrhosis with different etiologies: a study based on iodine mixed imaging in port-venous phase.

Computed tomography (CT) in port-venous phase can display the intra-hepatic vessels, and may provide the possibility for segment function evaluation for cirrhosis. To assess the value of iodine mixed imaging of dual-source dual-energy CT in port-venous phase in segmental evaluation of liver cirrhosis with different etiologies. Patients diagnosed with liver cirrhosis were enrolled. Patients without cirrhosis were included as a control group. Each patient underwent iodine-contrast enhanced multi-phase dual-energy CT scanning. Parameters were analyzed by SPSS, version 22.0, and Medcalc. In total, 256 patients were investigated, including 114 Child-Pugh A, 51 Child-Pugh B, 41 Child-Pugh C and 50 control patients. Total iodine content (ICt)/body surface area (BSA) in the cirrhosis group was significantly lower than the control group (P < 0.05) and the standardized-iodine parameter (SI) of each segment decreased with cirrhosis progression. In Child-Pugh A and B, SI increased more significantly in the caudal and lateral segment in A (alcholism) than in the V (virus-related) and N (non-alcoholic steatohepatitis) groups (P < 0.001). ICt/BSA showed the best diagnosis power of cirrhosis with an area under the curve of 0.765, sensitivity of 76.0% and specificity of 71.8%. Blood flow compensated in the left lateral and caudal lobe in the early stage of liver cirrhosis. The compensation in alcoholism in the middle and early stages is significantly higher than that of V and N cirrhosis. Iodine mixed imaging in portal phase may provide the possibility of an incremental value in segmented blood flow perfusion and functional evaluation of liver cirrhosis on a morphological basis.

CfDNA and associated risk factors in the early diagnosis of cancers in Côte d’Ivoire: The case of primary liver cancer related to viral hepatitis B

Introduction: In Côte d'Ivoire (CI), according to Globocan 2020 primary liver cancer (PLC) had an incidence of 10.1/1.0E+05 inhabitants in men (2nd rank) and 5.5/1.0E+05 inhabitants among women (4th rank). This situation has so far been favored by late diagnosis and ignorance of the risk factors responsible for the tumor in people at risk. Objective: To detect free circulating DNA (cfDNA) and evaluate its possible diagnostic role in order to contribute to the prevention of PLC in CI. Methodology: Prospective experimental study carried out at the Institut Pasteur in CI in patients coming for alfa-fetoprotein assay. Sociodemographic, clinical, paraclinical and epidemiological data were collected. A blood sample was taken for biological analysis. Data collected in Excel and processed with the GraphPad Prism 5. Results: 142 predominantly male patients with an average age of 45 were included. More than 50% had the same dietary habits including the consumption of tap water, rice, cassava, plantain, millet, maize and yam and 18% regularly consumed alcohol. 66.66% were carriers of chronic viral hepatitis B (HVB) including 2.81% at the cirrhosis stage and 0.70% at the PLC stage. 20% had a history of familial hepatitis and 9.6% a notion of familial cancer. The cfDNA concentration ranged from 38ng/ml to 10763ng/ml for an average of 571ng/ml. The elevation of AFP and transaminase levels was related to the presence of HBsAg (P˂0.001; P=0.02). In addition, the concentration of cDNA was strongly linked to HBsAg carriage as well as to other factors including the notion of familial cancer (P=0.03), and consumption of alcohol (p =0.04) and/or tobacco (p=0.02). Conclusion: HVB remains the predominant risk factor that can lead to PLC. The dosage of cfDNA and the monitoring of food and life hygiene in a chronic carrier of HVB could contribute to the prevention of PLC in the latter.

Portal vein thrombosis after cetuximab and 5-fluorouracil therapy in a patient with advanced colon cancer and decompensated cirrhosis: a case report and review of the literature

BackgroundTreatment options for advanced colon cancer are mainly combinations of chemotherapy and targeted drugs. However, poor physical health and medication intolerance limit the choice of anticancer drugs. Colon cancer with cirrhosis is a particular patient group that poses a challenge to clinical treatment.Case presentationThis article presents a case of a patient in the decompensated stage of cirrhosis who was diagnosed with advanced colon cancer. The initial presentation was a nodule on his navel named the Sister Mary Joseph’s nodule, which was later confirmed by biopsy and PET-CT as one of the metastases of colon cancer. The patient was treated with cetuximab and 5-fluorouracil at a below-guideline dose; however, portal vein thrombosis developed and led to death. This entire process, from diagnosis to death, occurred within a span of three months.ConclusionCancers with cirrhosis are a special group that deserves more attention. There is no unified treatment guideline for these patients, especially those with extrahepatic primary tumors. We should be more cautious when choosing treatment for such patients in the future. Both chemotherapy and targeted treatment may potentially induce portal vein thrombosis, which appears to have a higher incidence and worse prognosis than cancers without cirrhosis.

Diagnostic performance of circulating biomarkers for non-alcoholic steatohepatitis.

There are no approved diagnostic biomarkers for at-risk non-alcoholic steatohepatitis (NASH), defined by the presence of NASH, high histological activity and fibrosis stage ≥2, which is associated with higher incidence of liver-related events and mortality. FNIH-NIMBLE is a multi-stakeholder project to support regulatory approval of NASH-related biomarkers. The diagnostic performance of five blood-based panels was evaluated in an observational (NASH CRN DB2) cohort (n = 1,073) with full spectrum of non-alcoholic fatty liver disease (NAFLD). The panels were intended to diagnose at-risk NASH (NIS4), presence of NASH (OWLiver) or fibrosis stages >2, >3 or 4 (enhanced liver fibrosis (ELF) test, PROC3 and FibroMeter VCTE). The prespecified performance metric was an area under the receiver operating characteristic curve (AUROC) ≥0.7 and superiority over alanine aminotransferase for disease activity and the FIB-4 test for fibrosis severity. Multiple biomarkers met these metrics. NIS4 had an AUROC of 0.81 (95% confidence interval: 0.78-0.84) for at-risk NASH. The AUROCs of the ELF test, PROC3 and FibroMeterVCTE for clinically significant fibrosis (≥stage 2), advanced fibrosis (≥stage 3) or cirrhosis (stage 4), respectively, were all ≥0.8. ELF and FibroMeter VCTE outperformed FIB-4 for all fibrosis endpoints. These data represent a milestone toward qualification of several biomarker panels for at-risk NASH and also fibrosis severity in individuals with NAFLD.

Implementing Better Standard Instruments for Detecting Cirrhosis in Hepatitis C Patients.

An increasing number of hepatitis C diagnoses in the younger population could partly be due to the rising opioid epidemic and intravenous drug use. Using hepatic venous portal gradient (HVPG) and liver stiffness tests, this study investigates better early diagnostic markers in identifying cirrhosis-related complications compared to percutaneous liver biopsy in hepatitis C patients. Scholarly journal articles were surveyed using PubMed and MeSH terms. Articles published more than 15 years ago were excluded. Various databases from the New England Journal of Medicine and the Centers for Disease Control and Prevention were also referenced to support the hypothesis. There is substantial affirmation from cohort and clinical studies that transient elastography and HVPG can indicate advancing chronic inflammatory and fibrotic stages of cirrhosis in comparison to liver biopsy. Additionally, they are helpful in predicting overall mortality from complications such as esophageal varices. The use of liver stiffness measurements and HVPG appears to be equivalent and/or superior to liver biopsy in assessing advancing cirrhosis. As hepatitis C cases continue to rise, it is crucial to search for alternative methods to better suit the needs of the patients and to improve their overall prognosis and potential treatments. Liver biopsy as the gold standard for cirrhosis assessment is questionable when less invasive instrumental tools are available in practice that have been shown to predict progressing fibrosis.

GPU accelerated volumetric lattice Boltzmann model for image-based hemodynamics in portal hypertension

We are developing a new technique for monitoring portal hypertension by the pressure gradient between the portal vein and the inferior vena cava (PPG) based on non-invasive measurements (MRI images). Massive parametrization and classification are required to investigate the underlying relationship between the porosity and the stages of liver cirrhosis numerically, and the hepatic-portal venous system is a multi-scale system. Both of them need high computational costs. The suitability of the lattice Boltzmann method for GPU (Graphics Processing Unit) parallel computation provides an opportunity to overcome it. In this paper, we perform GPU parallelization and optimization for the volumetric lattice Boltzmann method with arbitrary geometry based on images. Three application cases, including pipe flow, hemodynamics in the portal venous system, and hemodynamics in a simple hepatic-portal venous system, are employed to prove the method can be applied in the hepatic-portal venous system based on accuracy and efficiency. The reliability of the model is qualitatively validated by the analytical solution of velocity and pressure difference distribution of pipe flow and quantitatively confirmed by the pulsatility of velocity and pressure difference that can be neglected in the portal venous system. The performance of the application cases is examined with Intel Broadwell E5-2683 v3@ 2.30 GHz (CPU) and NVIDIA Tesla V100 16GB (GPU). It shows the GPU algorithm for sparse geometry (SPARSE) has a similar speed to the regular GPU algorithm for dense geometry (DENSE) when the fluid volume fraction (q) is close to 1. And SPARSE speeds up to 2.2 times compared with DENSE when q is in the range of 0.19∼0.27. Meanwhile, the saving ratio of memory cost depends on q. For a numerical case in the hepatic-portal venous system, i.e., a large-scale system, parallel execution can be converged around half an hour with SPARSE, while the memory spills the limitation with DENSE with a single GPU. Hence, multi-GPU implementation is applied to release the limitation, and it can improve performance by increasing the number of GPU cards. In summary, the method presented in the paper is feasibility applied in the hepatic-portal venous system, laying the foundation of the new technique development.

Correlation between Severity of Liver Disease According to CHILD &amp; MELD Scores and Degree of Cardiac Impairment

Abstract Background Cirrhosis is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcoholism. The prevalence of cirrhosis has nearly doubled over the last decade, and the number of hospitalizations has similarly increased. Objective To detect correlation between severity of liver disease according to Child and MELD scores and degree of cardiac impairment such as systolic and diastolic functions and ECG changes. To elucidate this aim 60 cases were included in the current study. Patients and Methods Type of Study: Cross-sectional Study. Study Setting: This study was carried out in El-Demerdash Hospital-Ain Shams University and El-Qabbary Hospital - Alexandria. Study Period 6 months Results In the current study, there was statistically significant increase in age of positive ECG cases than negative ECG cases; also the percentage of males in positive ECG cases was found higher than those of negative ECG cases. There was statistically significant increase in child B and C in positive ECG group than negative ECG group. There was statistically significant increase in the level of Meld score, T. bilirubin and D. bilirubin in positive ECG group than negative ECG group; and statistically significant decrease in the level of albumin and NA in positive ECG group than negative ECG group. That there was statistically significant positive correlation found between MELD score and AST, ALT, total biliruibn, direct bilirubin, PT, INR and creatinine and also negative correlation found between meld score and albumin and NA levels. Conclusion There was statistically significant relation found between child score, MELD.S (the severity of cirrhosis) and ECG results. There was a high statistically significant difference in between ECHO and MELD.S but no statistically significant difference in between ECHO and CHILD.S, therefore, in order to prepare the best post-procedural management of cirrhotic patients, echocardiography is required for all patients before any interventional procedure or liver transplantation regardless of the stage of cirrhosis. The mechanism of cardiac involvement in patients with cirrhosis seems to be complex and multifactorial.

Evaluation of Left Ventricular Diastolic Function Using a Tissue-Doppler Imaging Based Algorithm According to 2016 Ase/Eacvi Guidelines in Patients with Decompensated Liver Cirrhosis: A Prospective Observational Study

Abstract Background Cirrhosis is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcoholism. The prevalence of cirrhosis has nearly doubled over the last decade, and the number of hospitalizations has similarly increased. Aim of the Work We aimed to correlate between the severity of liver cirrhosis using new MELD score and left ventricle diastolic dysfunction using tissue doppler imaging. Patients and Methods A prospective observational study in ICU of Theodor Bilharz Research Institute Hospital and Ain Shams University Hospitals for 6 months from June 2021 till end of November 2021 on hepatic patients who were admitted to ICU of Theodor Bilharz Research Institute Hospital and Ain Shams University Hospitals. Results In the studied group, the mean age was 53.13±9.44 years with males constituting more than half of them (57.8%). The mean MELD score was 24.08±6.01, and the mean left ventricular ejection fraction (LVEF %) was 60.43±5.49%. There were 5 patients (5.6%) with normal LV diastolic function and 85 patients (94.4%) with abnormal LV diastolic dysfunction. Out of the 90 patients, 5 patients were normal, 44 patients (48.9%) had a grade I LVDD, 28 patients (31.1%) had a grade II LVDD and 13 patients (14.4%) had a grade III LVDD. There was a highly statistically significant positive association between the grades of left ventricular diastolic dysfunction according to ALT, AST, T.Bilirubin, D.Bilirubin, INR and Creatinine. Additionally, there was a highly statistically significant negative association between grading of left ventricular diastolic dysfunction according to platelet count and sodium levels. Conclusion There was a statistically significant correlation found between the severity of liver cirrhosis represented by the new MELD score and the grade of left ventricular diastolic dysfunction. Therefore, in order to prepare the best post-procedural management of cirrhotic patients, echocardiography is required for all patients before any interventional procedure or liver transplantation regardless of the stage of cirrhosis. The mechanism of cardiac involvement in patients with cirrhosis seems to be complex and multifactorial.

Diagnostic Accuracy of Indocyanine Green Clearance Test for Different Stages of Liver Fibrosis and Cirrhosis.

(1) Background: This study aimed to correlate the indocyanine green clearance (ICG) test with histopathological grades of liver fibrosis and liver cirrhosis to assess its diagnostic accuracy in differentiating normal liver parenchyma from liver fibrosis and liver cirrhosis. (2) Methods: A total of 82 patients who received a histopathological liver examination, imaging, and ICG test within three months were included in this retrospective study. The histopathological level of fibrosis was graded using the Ishak scoring system, and the patients were divided into five categories: no liver fibrosis (NLF), mild liver fibrosis (MLF), advanced liver fibrosis (ALF), severe liver fibrosis (SLF), and liver cirrhosis (LC). The non-parametric Kruskal-Wallis test with post hoc pairwise comparison utilizing Mann-Whitney U tests and Bonferroni adjustment was used to analyze differences in the ICG test results between the patient groups. Cross correlation between the individual fibrosis/cirrhosis stages and the score of the ICG test was performed, and the sensitivity, specificity, and positive and negative predictive values were calculated for each model predicting liver fibrosis/cirrhosis. (3) Results: A significant difference (p ≤ 0.001) between stages of NLF, LF, and LC was found for the ICG parameters (ICG plasma disappearance rate (ICG-PDR) and ICG retention percentage at 15 min (ICG-R15)). The post hoc analysis revealed that NLF significantly differed from SLF (ICG-PDR: p = 0.001; ICG-R15: p = 0.001) and LC (ICG-PDR: p = 0.001; ICG-R15: p = 0.001). ALF also significantly differed from SLF (ICG-PDR: p = 0.033; ICG-R15: p = 0.034) and LC (ICG-PDR: p = 0.014; ICG-R15: p = 0.014). The sensitivity for detection of an initial stage of liver fibrosis compared to no liver fibrosis (Ishak ≥ 1) was 0.40; the corresponding specificity was 0.80. The differentiation of advanced liver fibrosis or cirrhosis (Ishak ≥ 4) compared to other stages of liver fibrosis was 0.75, with a specificity of 0.81. (4) Conclusions: This study shows that the ICG test, as a non-invasive diagnostic test, is able to differentiate patients with no liver fibrosis from patients with advanced liver fibrosis and liver cirrhosis. The ICG test seems to be helpful in monitoring patients with liver fibrosis regarding compensation levels, thus potentially enabling physicians to both detect progression from compensated liver fibrosis to advanced liver fibrosis and cirrhosis and to initiate antifibrotic treatment at an earlier stage.

Longitudinal Study of Cirrhosis Development in STAM and carbon tetrachloride Mouse Models Using Fourier Transform Infrared Spectral Imaging

Animal models of cirrhosis are of great interest to investigate the pathological process leading to the final stage of cirrhosis. The aim of this study was to analyze the different steps involved in the progressive development of cirrhosis using Fourier transform infrared spectral histology in 2 mouse models of cirrhosis, the STAM model of metabolic cirrhosis, and the carbon tetrachloride–induced cirrhosis model. Formalin-fixed, paraffin-embedded liver samples were obtained from 3 mice at 5 time points in each model to analyze the course of hepatic lesions up to the formation of cirrhosis. For each time point, adjacent 3-μm–thick liver sections were obtained for histologic stains and spectral histology. Fourier transform infrared acquisitions of liver sections were performed at projected pixel sizes of 25 μm × 25 μm and 6.25 μm × 6.25 μm. Spectral images were then preprocessed with an extended multiplicative signal correction and analyzed with common k-means clustering, including all stages in each model. In both models, the 2- and 4-class common k-means clustering in the 1000 to 1350 cm−1 range showed that spectral classes characterized by higher absorbance peaks of glycogen were predominant at baseline, then decreased markedly in early stages of hepatic damage, and almost disappeared in cirrhotic tissues. Concomitantly, spectral classes characterized by higher absorbance peaks of nucleic acids became progressively predominant during the course of hepatic lesions. These results were confirmed using k-means clustering on the peaks of interest identified for glycogen and nucleic acid content. Our study showed that the glycogen depletion previously described at the stage of cirrhosis is an early event in the pathological process, independently of the cause of cirrhosis. In addition, there was a progressive increase in the nucleic acid content, which may be linked to increased proliferation and polyploidy in response to cellular lesions.