FibroScan-aspartate transaminase:A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)with hepatic histological NAFLD activity score≥4 and fibrosis stage F≥2 is regarded as“at risk”non-alcoholic steatohepatitis(NASH).Based on an international consensus,NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH),respectively;hence,we introduced the term“high-risk MASH”.Diagnostic values of seven non-invasive models,including FibroScan-aspartate transaminase(FAST),fibrosis-4(FIB-4),aspartate transaminase to platelet ratio index(APRI),etc.for high-risk MASH have rarely been studied and compared in MASLD.AIM To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH.METHODS A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital,between January 2012 and December 2020.After screening for MASLD and the exclusion criteria,279 patients wereincluded and categorized into high-risk and non-high-risk MASH groups.Utilizing threshold values of each model,sensitivity,specificity,positive predictive value(PPV),and negative predictive values(NPV),were calculated.Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve(AUROC).RESULTS MASLD diagnostic criteria were met by 99.4%patients with NAFLD.The MASLD population was analyzed in two cohorts:Overall population(279 patients)and the subgroup(117 patients)who underwent liver transient elastography(FibroScan).In the overall population,FIB-4 showed better diagnostic efficacy and higher PPV,with sensitivity,specificity,PPV,NPV,and AUROC of 26.9%,95.2%,73.5%,72.2%,and 0.75.APRI,Forns index,and aspartate transaminase to alanine transaminase ratio(ARR)showed moderate diagnostic efficacy,whereas S index and gamma-glutamyl transpeptidase to platelet ratio(GPR)were relatively weaker.In the subgroup,FAST had the highest diagnostic efficacy,its sensitivity,specificity,PPV,NPV,and AUROC were 44.2%,92.3%,82.1%,67.4%,and 0.82.The FIB-4 AUROC was 0.76.S index and GPR exhibited almost no diagnostic value for high-risk MASH.CONCLUSION FAST and FIB-4 could replace liver biopsy as more effectively diagnostic methods for high-risk MASH compared to APRI,Forns index,ARR,S index,and GPR;FAST is superior to FIB-4.

Exploring non-invasive diagnostics for metabolic dysfunctionassociated fatty liver disease

The population with metabolic dysfunction-associated fatty liver disease(MAFLD)is increasingly common worldwide.Identification of people at risk of progression to advanced stages is necessary to timely offer interventions and appropriate care.Liver biopsy is currently considered the gold standard for the diagnosis and staging of MAFLD,but it has associated risks and limitations.This has spurred the exploration of non-invasive diagnostics for MAFLD,especially for steatohepatitis and fibrosis.These non-invasive approaches mostly include biomarkers and algorithms derived from anthropometric measurements,serum tests,imaging or stool metagenome profiling.However,they still need rigorous and widespread clinical validation for the diagnostic performance.

Ensemble for evaluating diagnostic efficacy of non-invasive indices in predicting liver fibrosis in untreated hepatitis C virus population

BACKGROUND Hepatitis C virus(HCV)infection progresses through various phases,starting with inflammation and ending with hepatocellular carcinoma.There are several invasive and non-invasive methods to diagnose chronic HCV infection.The invasive methods have their benefits but are linked to morbidity and complications.Thus,it is important to analyze the potential of non-invasive methods as an alternative.Shear wave elastography(SWE)is a non-invasive imaging tool widely validated in clinical and research studies as a surrogate marker of liver fibrosis.Liver fibrosis determination by invasive liver biopsy and non-invasive SWE agree closely in clinical studies and therefore both are gold standards.AIM To analyzed the diagnostic efficacy of non-invasive indices[serum fibronectin,aspartate aminotransferase to platelet ratio index(APRI),alanine aminotransferase ratio(AAR),and fibrosis-4(FIB-4)]in relation to SWE.We have used an Artificial Intelligence method to predict the severity of liver fibrosis and uncover the complex relationship between non-invasive indices and fibrosis severity.METHODS We have conducted a hospital-based study considering 100 untreated patients detected as HCV positive using a quantitative Real-Time Polymerase Chain Reaction assay.We performed statistical and probabilistic analyses to determine the relationship between non-invasive indices and the severity of fibrosis.We also used standard diagnostic methods to measure the diagnostic accuracy for all the subjects.RESULTS The results of our study showed that fibronectin is a highly accurate diagnostic tool for predicting fibrosis stages(mild,moderate,and severe).This was based on its sensitivity(100%,92.2%,96.2%),specificity(96%,100%,98.6%),Youden’s index(0.960,0.922,0.948),area under receiver operating characteristic curve(0.999,0.993,0.922),and Likelihood test(LR+>10 and LR-<0.1).Additionally,our Bayesian Network analysis revealed that fibronectin(>200),AAR(>1),APRI(>3),and FIB-4(>4)were all strongly associated with patients who had severe fibrosis,with a 100% probability.CONCLUSION We have found a strong correlation between fibronectin and liver fibrosis progression in HCV patients.Additionally,we observed that the severity of liver fibrosis increases with an increase in the non-invasive indices that we investigated.

Functional near-infrared spectroscopy in non-invasive neuromodulation

Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.

Non-coding RNA as future target for diagnose and treatment of perineural invasion in cancers

Perineural invasion(PNI),a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread,has the capacity to extend well beyond the primary tumor site,infiltrating distant regions devoid of lymphatic or vascular structures.PNI often heralds a decrease in patient survival rates and is recognized as an indicator of an unfavorable prognosis across a variety of cancers.Despite its clinical significance,the underlying molecular mechanisms of PNI remain elusive,complicating the development of specific and efficacious diagnostic and therapeutic strategies.In the realm of cancer research,non-coding RNAs(ncRNAs)have attracted considerable attention due to their multifaceted roles and cancer-specific expression profiles,positioning them as promising candidates for applications in cancer diagnostics,prognostics,and treatment.Among the various types of ncRNAs,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)have emerged as influential players in PNI.Their involvement is increasingly recognized as a contributing factor to tumor progression and therapeutic resistance.Our study synthesizes and explores the diverse functions and mechanisms of ncRNAs in relation to PNI in cancer.This comprehensive review aims to shed light on cutting-edge perspectives that could pave the way for innovative diagnostic and therapeutic approaches to address the challenges posed by PNI in oncology.

Recent developments in non-invasive methods for assessing metabolic dysfunction-associated fatty liver disease

The prevalence of metabolic dysfunction-associated fatty liver disease(MAFLD)is increasing,affecting over one-third of the global population and contributing to significant morbidity and mortality.Diagnosing MAFLD,especially with advan-ced fibrosis,remains challenging due to the limitations of liver biopsy,the current gold standard.Non-invasive tests are crucial for early detection and management.Among these,the fibrosis-4 index(Fib-4)is widely recommended as a first-line test for screening for liver fibrosis.Advanced imaging techniques,including ultrasound-based elastography and magnetic resonance elastography,offer high accuracy but are limited by cost and availability.Combining biomarkers,such as in the enhanced liver fibrosis score and FibroScan-AST score,enhances diagnostic precision and is recommended to further stratify patients who are considered to be intermediate or high risk from the Fib-4 score.We believe that the future lies in the combined use of biomarkers to improve diagnostic accuracy.

Advances in the Research Application of Ultrasound Non-Invasive Stress-Strain Loop Technology in Cardiovascular Diseases

The ultrasound pressure-strain loop (PSL) technique is a non-invasive method of examining myocardial work, which takes into account the effect of cardiac afterload on deformation and combines the overall longitudinal strain force of the left ventricle with the changes in the left ventricular pressure, allowing earlier detection of possible subclinical cardiac damage in patients, and a more accurate and non-invasive assessment of the patient’s myocardial work performance. In this article, we will discuss the progress of PSL applications in cardiovascular diseases.

A Study on Near-Infrared Non-Invasive Blood Glucose Concentration Regression Prediction Based on PSO-MKL-SVR

To improve the accuracy of predicting non-invasive blood glucose concentration in the near-infrared spectrum, we utilized the Particle Swarm Optimization (PSO) algorithm to optimize hyperparameters for the Multi-Kernel Learning Support Vector Machine (MKL-SVR). With these optimized hyperparameters, we established a non-invasive blood glucose regression model, referred to as the PSO-MKL-SVR model. Subsequently, we conducted a comparative analysis between the PSO-MKL-SVR model and the PSO-SVR model. In a dataset comprising ten volunteers, the PSO-MKL-SVR model exhibited significant precision improvements, including a 16.03% reduction in Mean Square Error and a 0.29% increase in the Squared Correlation Coefficient. Moreover, there was a 0.14% higher probability of the Clark’s Error Grid Analysis falling within Zone A. Additionally, the PSO-MKL-SVR model demonstrated a faster operational speed compared to the PSO-SVR model.

Observation on the Effect of Non-Invasive Ventilator Combined with Conventional Therapy in the Treatment of Chronic Obstructive Pulmonary Disease Complicated with Respiratory Failure

Objective:To explore the clinical effect of a non-invasive ventilator combined with conventional therapy in the treatment of patients with chronic obstructive pulmonary disease(COPD)combined with respiratory failure.Methods:68 patients with COPD combined with respiratory failure treated in our hospital from September 2021 to October 2023 were selected as the research subjects.Using the random number table method,they were divided into a control group and an experimental group of 34 cases each.The control group received conventional symptomatic treatment,and the experimental group received non-invasive ventilator treatment based on the control group.The clinical effects,blood gas indicators(partial pressure of carbon dioxide(PaCO_(2)),partial pressure of oxygen(PaO_(2)),arterial oxygen saturation(SaO_(2))),lung function(forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),6 min walking distance),complications,and inflammatory factor levels(c-reactive protein(CRP),interleukin-6(IL-6),neutrophil-to-lymphocyte ratio(NLR))of the two groups of patients were observed.Results:(1)The clinical efficacy of the patients in the experimental group(33/97.06%)was more significant as compared with the control group(25/73.53%)(P<0.05);(2)After treatment,the clinical efficacy of the two groups of patients in terms of FEV1,FEV1/FVC,6-minute walking distance,PaO_(2)and SaO_(2)all increased in the experimental group as compared to that of the control group(P<0.05);(3)After treatment,the PaCO_(2),CRP,IL-6,and NLR of the two groups of patients decreased,and the decrease in the experimental group was higher than that of the control group(P<0.05);(4)The patients’complication rate in the experimental group(2/5.88%)was lower as compared to that of the control group(9/26.46%)(P<0.05).Conclusion:Non-invasive ventilators combined with conventional therapy achieved good clinical results in treating patients with COPD and respiratory failure.

Analysis of the Effect of Non-Invasive Positive Pressure Ventilation in Emergency Treatment of Severe Bronchial Asthma with Respiratory Failure

Objective:This study aims to evaluate the clinical efficacy of non-invasive positive pressure ventilation(NIPPV)in patients with severe bronchial asthma combined with respiratory failure.Methods:90 patients with severe bronchial asthma combined with respiratory failure between September 2022 and December 2023 were selected for the study and randomly divided into the experimental group(NIPPV-assisted treatment)and the control group.The differences between the two groups were compared in terms of total effective rate of treatment,days of clinical symptom disappearance,days of hospitalization,lung function indexes,incidence of adverse reactions,and quality of life.Results:Patients in the experimental group had a significantly higher total effective rate of treatment(97.78%)than the control group(75.56%).In terms of pulmonary function indexes,patients in the experimental group showed significant improvement after treatment,especially the increase in forced expiratory volume and forced vital capacity,while these improvements were not as obvious in the control group.In addition,the incidence of adverse reactions was significantly lower in the experimental group than in the control group,suggesting that the application of NIPPV is relatively safe.Quality of life assessment also showed that patients in the experimental group had significantly better quality of life than the control group after treatment.Conclusion:This study demonstrated the effectiveness of NIPPV as an adjunctive treatment for severe bronchial asthma combined with respiratory failure.NIPPV can improve lung function,reduce the incidence of adverse effects,increase the overall effectiveness of the treatment,and contribute to the improvement of patients'quality of life.Therefore,NIPPV should be regarded as an effective and safe treatment in clinical management,especially in patients with severe bronchial asthma combined with respiratory failure,where its application has potential clinical significance.

Relationship Between Gene-Phenotype and Clinical Manifestations of Chromosomal Copy Number Variations Indicated by Non-Invasive Prenatal Testing

Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.

Non-Invasive Approach to Early Diagnosis of the Formation of Oncological Neoplasms

The currently developed instrumental approaches for detecting pathological changes in the body have a number of disadvantages. The most important of them is that the equipment is sensitive to the detection of diseases only from a certain threshold level of destructive changes in the body. The present article discusses the possibility of using the new instrumental complex “Bioscope” for early and non-invasive diagnosis of the beginning of the formation of ontological neoplasm’s in the body.

Perivascular epithelioid cell tumors of the liver misdiagnosed as hepatocellular carcinoma:Three case reports

BACKGROUND Hepatic perivascular epithelioid cell neoplasms(PEComas)are rare.Diagnostic and treatment experience with hepatic PEComa remains insufficient.CASE SUMMARY Three hepatic PEComa cases are reported in this paper:One case of primary malignant hepatic PEComa,one case of benign hepatic PEComa,and one case of hepatic PEComa with an ovarian mature cystic teratoma.During preoperative imaging and pathological assessment of intraoperative frozen samples,patients were diagnosed with hepatocellular carcinoma(HCC),while postoperative pathology and immunohistochemistry subsequently revealed hepatic PEComa.Patients with hepatic PEComa which is misdiagnosed as HCC often require a wider surgical resection.It is easy to mistake them for distant metastases of hepatic PEComa and misdiagnosed as HCC,especially when it’s combined with tumors in other organs.Three patients eventually underwent partial hepatectomy.After 1-4 years of follow-up,none of the patients experienced recurrence or metastases.CONCLUSION A clear preoperative diagnosis of hepatic PEComa can reduce the scope of resection and prevent unnecessary injuries during surgery.

Emerging role of non-invasive and liquid biopsy biomarkers in pancreatic cancer

A global increase in the incidence of pancreatic cancer(PanCa)presents a major concern and health burden.The traditional tissue-based diagnostic techniques provided a major way forward for molecular diagnostics;however,they face limitations based on diagnosis-associated difficulties and concerns surrounding tissue availability in the clinical setting.Late disease development with asymptomatic behavior is a drawback in the case of existing diagnostic procedures.The capability of cell free markers in discriminating PanCa from autoimmune pancreatitis and chronic pancreatitis along with other precancerous lesions can be a boon to clinicians.Early-stage diagnosis of PanCa can be achieved only if these biomarkers specifically discriminate the non-carcinogenic disease stage from malignancy with respect to tumor stages.In this review,we comprehensively described the non-invasive disease detection approaches and why these approaches are gaining popularity for their early-stage diagnostic capability and associated clinical feasibility.

Non-invasive model for predicting high-risk esophageal varices based on liver and spleen stiffness

BACKGROUND Acute bleeding due to esophageal varices(EVs)is a life-threatening complication in patients with cirrhosis.The diagnosis of EVs is mainly through upper gastrointestinal endoscopy,but the discomfort,contraindications and complications of gastrointestinal endoscopic screening reduce patient compliance.According to the bleeding risk of EVs,the Baveno VI consensus divides varices into high bleeding risk EVs(HEVs)and low bleeding risk EVs(LEVs).We sought to identify a non-invasive prediction model based on spleen stiffness measurement(SSM)and liver stiffness measurement(LSM)as an alternative to EVs screening.AIM To develop a safe,simple and non-invasive model to predict HEVs in patients with viral cirrhosis and identify patients who can be exempted from upper gastrointestinal endoscopy.METHODS Data from 200 patients with viral cirrhosis were included in this study,with 140 patients as the modelling group and 60 patients as the external validation group,and the EVs types of patients were determined by upper gastrointestinal endoscopy and the Baveno Ⅵ consensus.Those patients were divided into the HEVs group(66 patients)and the LEVs group(74 patients).The effect of each parameter on HEVs was analyzed by univariate and multivariate analyses,and a noninvasive prediction model was established.Finally,the discrimination ability,calibration ability and clinical efficacy of the new model were verified in the modelling group and the external validation group.RESULTS Univariate and multivariate analyses showed that SSM and LSM were associated with the occurrence of HEVs in patients with viral cirrhosis.On this basis,logistic regression analysis was used to construct a prediction model:Ln[P/(1-P)]=-8.184-0.228×SSM+0.642×LSM.The area under the curve of the new model was 0.965.When the cut-off value was 0.27,the sensitivity,specificity,positive predictive value and negative predictive value of the model for predicting HEVs were 100.00%,82.43%,83.52%,and 100%,respectively.Compared with the four prediction models of liver stiffness-spleen diameter to platelet ratio score,variceal risk index,aspartate aminotransferase to alanine aminotransferase ratio,and Baveno VI,the established model can better predict HEVs in patients with viral cirrhosis.CONCLUSION Based on the SSM and LSM measured by transient elastography,we established a non-invasive prediction model for HEVs.The new model is reliable in predicting HEVs and can be used as an alternative to routine upper gastrointestinal endoscopy screening,which is helpful for clinical decision making.

Non-invasive diagnosis of liver fibrosis and cirrhosis

The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect; even according to its proponents, it is only "the best" among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future.

Non-invasive diagnosis of gastric mucosal atrophy in an asymptomatic population with high prevalence of gastric cancer

AIM: To validate a non-invasive method to detect gastric mucosal atrophy in a Chilean population with high prevalence of gastric cancer and a poor survival rate. METHODS: We first determined the optimal cut-off level of serum pepsinogen (PG)-1, PG-1/PG-2 ratio and 17-gastrin in 31 voluntary symptomatic patients (mean age: 66.1 years), of them 61% had histologically confirmed gastric atrophy. Then, in a population-based sample of 536 healthy individuals (209 residents in counties with higher relative risk and 327 residents in counties with lower relative risk for gastric cancer), we measured serum anti-H pylori antibodies, PG and 17-gastrin and estimated their risk of gastric cancer. RESULTS: We found that serum PG-1 < 61.5 μg/L, PG-1/PG-2 ratio < 2.2 and 17-gastrin > 13.3 pmol/L had a high specificity (91%-100%) and a fair sensitivity (56%-78%) to detect corpus-predominant atrophy. Based on low serum PG-1 and PG-1/PG-2 ratio together as diagnostic criteria, 12.5% of the asymptomatic subjects had corpus-predominant atrophy (0% of those under 25 years and 20.2% over 65 years old). The frequency of gastric atrophy was similar (12% vs 13%) but H pylori infection rate was slightly higher (77% vs 71%) in the high-risk compared to the low-risk counties. Based on their estimated gastric cancer risk, individuals were classified as: low-risk group (no H pylori infection and no atrophy; n = 115; 21.4%); moderate-risk group(H pylori infection but no atrophy; n = 354, 66.0%); and high-risk group (gastric atrophy, with or without H pylori infection; n = 67, 12.5%). The high-risk group was significantly older (mean age: 61.9 ± 13.3 years), more frequently men and less educated as compared with the low-risk group. CONCLUSION: We propose to concentrate on an upper gastrointestinal endoscopy for detection of early gastric cancer in the high-risk group. This intervention model could improve the poor prognosis of gastric cancer in Chile.

Non-invasive diagnosis of alcoholic liver disease

Alcoholic liver disease(ALD)is the most common liver disease in the Western world.For many reasons,it isunderestimated and underdiagnosed.An early diagnosis is absolutely essential since it(1)helps to identify patients at genetic risk for ALD;(2)can trigger efficient abstinence namely in non-addicted patients;and(3)initiate screening programs to prevent life-threateningcomplications such as bleeding from varices,spontaneous bacterial peritonitis or hepatocellular cancer.The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis(AH).The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on acombination of laboratory,clinical and imaging findings.It is not widely conceived that conventional screeningtools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca.40%of manifest alcoholic liver cirrhosis.Non-invasive methods such as transient elastography(Fibroscan),acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholiccirrhosis.Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca.95%of patients.The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels.Other non-invasive methods such as controlled attenuation parameter,serum levels of M30 or M65,susceptometry or breath tests are under current evaluation to assess the degree of steatosis,apoptosis and iron overload in these patients.Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH.

Invasive and non-invasive diagnosis of cirrhosis and portal hypertension

With advances in the management and treatment of advanced liver disease,including the use of antiviral therapy,a simple,one stage description for advanced fibrotic liver disease has become inadequate.Although refining the diagnosis of cirrhosis to reflect disease heterogeneity is essential,current diagnostic tests have not kept pace with the progression of this new paradigm.Liver biopsy and hepatic venous pressure gradient measurement are the gold standards for the estimation of hepatic fibrosis and portal hypertension(PHT),respectively,and they have diagnostic and prognostic value.However,they are invasive and,as such,cannot be used repeatedly in clinical practice.The ideal noninvasive test should be safe,easy to perform,inexpensive,reproducible as well as to give numerical and accurate results in real time.It should be predictive of long term outcomes related with fibrosis and PHT to allow prognostic stratification.Recently,many types of noninvasive alternative tests have been developed and are under investigation.In particular,imaging and ultrasound based tests,such as transient elastography,have shown promising results.Although most of these noninvasive tests effectively identify severe fibrosis and PHT,the methods available for diagnosing moderate disease status are still insufficient,and further investigation is essential to predict outcomes and individualize therapy in this field.

Non-invasive diagnosis of advanced fibrosis and cirrhosis

Liver cirrhosis is a common and growing public health problem globally.The diagnosis of cirrhosis portends an increased risk of morbidity and mortality.Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis.However,despite its universal use,liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks.In order to overcome the limitations of liver biopsy,a number of non-invasive techniques have been investigated for the assessment of cirrhosis.This review will focus on currently available non-invasive markers of cirrhosis.The evidence behind the use of these markers will be highlighted,along with an assessment of diagnostic accuracy and performance characteristics of each test.Non-invasive markers of cirrhosis can be radiologic or serum-based.Radiologic techniques based on ultrasound,magnetic resonance imaging and elastography have been used to assess liver fibrosis.Serum-based biomarkers of cirrhosis have also been developed.These are broadly classified into indirect and direct markers.Indirect biomarkers reflect liver function,which may decline with the onset of cirrhosis.Direct biomarkers,reflect extracellular matrix turnover,and include molecules involved in hepatic fibrogenesis.On the whole,radiologic and serum markers of fibrosis correlate well with biopsy scores,especially when excluding cirrhosis or excluding fibrosis.This feature is certainly clinically useful,and avoids liver biopsy in many cases.