Non invasive fibrosis biomarkers reduce but not substitute the need for liver biopsy

Chronic liver diseases are very common worldwide, particularly those linked to viral hepatitis and to alcoholic and non-alcoholic fatty liver. Their natural history is variable and long-term evolution differs in individual patients. Optimised clinical management of compensated chronic liver diseases requires precise definition of the stage of liver fibrosis, the main determinant of prognosis and of most therapeutic decisions. Liver biopsy is the gold standard for assessment of hepatic fibrosis. However, it is invasive with possible complications, costly and prone to sampling errors. Many non-invasive markers of liver fibrosis have been recently proposed and assessed in the clinical setting as surrogates of liver biopsy. Direct markers are based on biochemical parameters directly linked to fibrogenesis while indirect markers use simple or more sophisticated parameters that correlate with liver fibrosis stages. Non-invasive markers of liver fibrosis have been tested in different forms of chronic liver disease and showed variable diagnostic performance, but accuracy rarely was above 75%-80%. Better results were obtained when markers were combined. On this line, we have recently proposed a set of algorithms that combine sequentially indirect non-invasive markers of liver fibrosis, reaching 90%-95% diagnostic accuracy with significant reduction in the need for liver biopsy. Based on available evidence, it can be anticipated that non-invasive markers of liver fibrosis and their combined use will soon become a most useful tool in the clinical management of many forms of chronic liver disease. However, their implementation is expected to reduce, but not to completely eliminate, the need for liver biopsy.

Is there a place for serum laminin determination in patients with liver disease and cancer?

Laminin is a glycoprotein which has an important role in the mechanism of fibrogenesis and is,thus,related to hepatic fibrosis in addition to presenting increased levels in several types of neoplasias. However,its determination is not routinely considered in the study of hepatic fibrosis. In this review,the authors critically comment on the role of this glycoprotein compared to other markers of fibrosis through non-invasive procedures(Fibroscan). They also consider its clinical investigational potential and believe that the continuation of these investigations might contribute to a better understanding of the fibrogenic mechanism,which could in turn either lead to the identification of patients at risk of developing fibrosis non-alcoholic fatty liver disease(NAFLD) and non-alcoholic steatohepatitis(NASH) or at least be used as an indicator for hepatic biopsy in such patients. Finally,the authors believe that serum laminin determination might contribute to the diagnosis of epithelial tumor metastasis and peritoneal carcinomatosis.

Usefulness of Mac-2 binding protein glycosylation isomer in noninvasive probing liver disease in the Vietnamese population

BACKGROUND Early diagnosis is critical for successful intervention before liver disease progresses to cirrhosis and hepatocellular carcinoma.AIM To examine a novel biomarker for probing early liver disease quickly using an automated immunology system.METHODS This was a cross-sectional study.140 patients at various stages of liver disease were randomly selected.The cohort consisted of patients who were treatment naïve and currently undergoing therapy.We included patients with diverse liver disease etiologies.Mac-2 binding protein glycosylation isomer(M2BPGi)levels in addition to different clinical parameters,co-morbidities and transient elastography results were collected and compared.RESULTS M2BPGi levels were significantly correlated with transient elastography for liver fibrosis staging across all disease etiologies.Statistically significant differences were observed in patients with F0-1;F2 and>F3 liver fibrosis.Further examination showed that M2BPGi levels were two-fold higher in F4 than F3 hepatitis C(HCV)patients.M2BPGi was observed to be etiology-specific and HCV patients had higher mean M2BPGi levels.We also observed significant correlations with aspartate aminotransferase to platelet ratio index and fibrosis-4 index as well as HBV DNA levels.Mean M2BPGi levels for HBV patients with a viral load lower than 2000 IU/mL was 1.75-fold lower than those with a viral load greater than 2000 IU/mL.CONCLUSION M2BPGi was observed to be a good indicator of early liver disease in patients with different etiologies.Our results provide reference cut-offs for different causes of liver disease and demonstrated the utility of this marker for early disease monitoring.This is useful for remote regions in developing countries.

Noninvasive Fibrosis Assessment in Chronic Hepatitis C Infection: An Update

Liver biopsy is historically the gold standard for liver fibrosis assessment of chronic hepatitis C patients.However,with the introduction and validation of noninvasive tests(NITs)to evaluate advanced fibrosis,and the direct-acting antiviral agents for treatment of chronic hepatitis C virus(HCV),the role of NITs have become even more complex.There is now need for longitudinal monitoring and elucidation of cutoff values for prediction of liver-related complication after sustained virological response.The aim of this report is to provide a critical overview of the various NITs available for the assessment of liver fibrosis in HCV patients.

Risk of hepatocellular carcinoma after hepatitis C virus cure

Hepatitis C virus(HCV)is a significant cause of hepatocellular carcinoma(HCC).The direct-acting antivirals marked a new era of HCV therapy and are associated with greater than 95%cure rate.Successful treatment of chronic hepatitis C greatly reduces the risk of HCC.A proportion of patients,especially those with pre-existing cirrhosis,remain at risk for HCC despite sustained virologic response(SVR).Diabetes mellitus,hepatic steatosis,alcohol consumption and lack of fibrosis regression are associated with risks of HCC after HCV cure.Noninvasive modalities such as aspartate aminotransferase to platelet ratio index and fibrosis-4 index and transient elastography have been used to monitor hepatic fibrosis.More recently,various fibrosis scores have been combined with clinical parameters and other novel biomarkers to predict risks of HCC for patients who achieved SVR.These models still need to be validated and standardized prior to applying to routine clinical care.

Practical Use of Transient Elastography in Screening for Nonalcoholic Steatohepatitis in a Japanese Population

Background and Aims:Fatty infiltration of liver may induce insulin resistance(IR),and a proportion of patients with nonalcoholic fatty liver disease(NAFLD)is diagnosed with nonalcoholic steatohepatitis.Transient elastography is gaining popularity as a means of non-invasively determining both liver stiffness(fibrosis level)and degree of fatty infiltration,expressed as controlled attenuation parameter(CAP)value.Methods:The aims of this study were to investigate the association between IR and level of fatty liver,and to identify the group at a greater risk of nonalcoholic steatohepatitis using transient elastography and other noninvasive fibrosis markers.A total of 169 patients without chronic hepatitis B and C were analyzed.Results:The CAP value was significantly associated with IR(HOMA-IR≥2.5;AUROC=0.81),and the optimal cut-off to discriminate IR was 264 dB/m.The liver stiffness measurement and aspartate aminotransferase-to-platelet ratio index values were significantly higher for CAP≥264 than in CAP<264.The 9 patients among the overall 169 patients(5.3%)and among the 102 NAFLD patients(8.8%)who showed≥264 dB and≥7.0 kPa in transient elastography could represent good candidates for liver biopsy.Conclusions:Evaluation of NAFLD based on CAP values was useful in diagnosing IR.About 9%of NAFLD patients in a Japanese outpatient clinic with a few metabolic complications might be considered good candidates for liver biopsy to confirm nonalcoholic steatohepatitis.