Liver biopsy in the post-hepatitis C virus era in Japan

In Japan,liver biopsies were previously crucial in evaluating the severity of hepatitis caused by the hepatitis C virus(HCV)and diagnosing HCV-related hepatocellular carcinoma(HCC).However,due to the development of effective antiviral treatments and advanced imaging,the necessity for biopsies has significantly decreased.This change has resulted in fewer chances for diagnosing liver disease,causing many general pathologists to feel less confident in making liver biopsy diagnoses.This article provides a comprehensive overview of the challenges and potential solutions related to liver biopsies in Japan.First,it highlights the importance of considering steatotic liver diseases as independent conditions that can coexist with other liver diseases due to their increasing prevalence.Second,it emphasizes the need to avoid hasty assumptions of HCC in nodular lesions,because clinically diagnosable HCCs are not targets for biopsy.Third,the importance of diagnosing hepatic immune-related adverse events caused by immune checkpoint inhibitors is increasing due to the anticipated widespread use of these drugs.In conclusion,pathologists should be attuned to the changing landscape of liver diseases and approach liver biopsies with care and attention to detail.

Endoscopic ultrasound guided liver biopsy: Recent evidence

Liver biopsy(LB)is an essential tool in diagnosing,evaluating and managing various diseases of the liver.As such,histopathological results are critical as they establish or aid in diagnosis,provide information on prognosis,and guide the appropriate selection of medical therapy for patients.Indications for LB include evaluation of persistent elevation of liver chemistries of unclear etiology,diagnosis of chronic liver diseases such as Wilson's disease,autoimmune hepatitis,small duct primary sclerosing cholangitis,work up of fever of unknown origin,amyloidosis and more.Traditionally,methods of acquiring liver tissue have included percutaneous LB(PCLB),transjugular LB(TJLB)or biopsy taken surgically via laparotomy or laparoscopy.However,traditional methods of LB may be inferior to newer methods.Additionally,PCLB and TJLB carry higher risks of adverse events and complications.More recently,endoscopic ultrasound guided LB(EUS-LB)has evolved as an alternative method of tissue sampling that has proven to be safe and effective,with limited adverse events.Compared to PC and TJ routes,EUS-LB may also have a greater diagnostic yield of tissue,be superior for a targeted approach of focal lesions,provide higher quality images and allow for greater patient comfort.These advantages have contributed to the increased use of EUS-LB as a technique for obtaining liver tissue.Herein,we provide a review of the recent evidence of EUS-LB for liver disease.

Update on endoscopic ultrasound-guided liver biopsy

Endoscopic ultrasound guided liver biopsy(EUS-LB)has emerged as a minimally-invasive alternative to the traditional(percutaneous or transjugular)liver biopsy techniques for the diagnosis of liver parenchymal diseases.Potentially,EUS-LB combines the advantages of percutaneous and transjugular liver biopsy in addressing focused sampling in addition to measuring portal pressure.Additionally,EUS-LB facilitates access to both the lobes of the liver which is not considered with the traditional percutaneous liver biopsy.Multiple studies have compared EUS-LB with conventional liver biopsy and reported comparable diagnostic yield,increased acquisition of complete portal tracts,and longer specimen length as compared to the traditional approaches.EUS-LB is associated with lesser post-procedural pain and shorter recovery time,while providing lower risk of complications when compared to traditional liver biopsy.Innovations in needle types,needle sizes and suction techniques have aimed at further optimizing the EUS-LB technique.This review article updates current literature with focus on the variations in the technique and equipment used for EUS-LB,and compares EUS-LB with traditional methods of liver biopsy.

Metabolomics in liver diseases: A novel alternative for liver biopsy?

Hepatitis C virus(HCV)remains a significant public health problem as it can cause acute and chronic hepatitis.Chronic HCV infection is a major cause of liver fibrosis,and evaluation of liver fibrosis is essential because the prognosis of patients with chronic HCV infection is closely related to the stage of fibrosis.Liver fibrosis is traditionally evaluated based on pathological analysis of biopsy specimens,which is considered the gold standard.Nevertheless,liver biopsy is invasive and susceptible to sampling error and inter-and intraobserver variation in pathological interpretation;it is also costly.Therefore,noninvasive diagnostic investigations have been developed,including the use of fibrotic markers,scoring systems based on routine blood tests,and transient elastography with magnetic resonance imaging or ultrasonography.Recently,metabolomics,an emerging technology,has been used to detect the fibrosis stage.In this editorial,I comment on the article titled“Metabolomics in chronic hepatitis C:Decoding fibrosis grading and underlying pathways”by Ferrasi et al published in the recent issue of the World Journal of Hepatology.I discuss previous studies on the use of metabolome analysis for the diagnosis of HCV-related liver fibrosis and the potential development of biopsy-free diagnostic techniques.

Major complications after ultrasound-guided liver biopsy:An annual audit of a Chinese tertiary-care teaching hospital

BACKGROUND As ultrasound-guided percutaneous liver biopsy(PLB)has become a standard and important method in the management of liver disease in our country,a periodical audit of the major complications is needed.AIM To determine the annual incidence of major complications following ultrasoundguided PLB and to identify variables that are significantly associated with an increased risk of major complications.METHODS A total of 1857 consecutive cases of PLB were included in our hospital from January 2021 to December 2021.The major complication rate and all-cause 30-d mortality rate were determined.Multivariate analyses were performed by logistic regression to investigate the risk factors associated with major complications and all-cause 30-d mortality following ultrasound-guided PLB.RESULTS In this audit of 1857 liver biopsies,10 cases(0.53%)of major complications occurred following ultrasound-guided PLB.The overall all-cause mortality rate at 30 d after PLB was 0.27%(5 cases).Two cases(0.11%)were attributed to major hemorrhage within 7 d after liver biopsy.Fibrinogen less than 2 g/L[odds ratio(OR):17.226;95%confidence interval(CI):2.647-112.102;P=0.003],post-biopsy hemoglobin level(OR:0.963;95%CI:0.942-0.985;P=0.001),obstructive jaundice(OR:6.698;95%CI:1.133-39.596;P=0.036),application of anticoagulants/antiplatelet medications(OR:24.078;95%CI:1.678-345.495;P=0.019)and age(OR:1.096;95%CI:1.012-1.187;P=0.025)were statistically associated with the incidence of major complications after PLB.CONCLUSION In conclusion,the results of this annual audit confirmed that ultrasound-guided PLB can be performed safely,with a major complication rate within the accepted range.Strict patient selection and peri-biopsy laboratory assessment are more important than procedural factors for optimizing the safety outcomes of this procedure.

Protocol liver biopsy is the only examination that can detect mid-term graft fibrosis after pediatric liver transplantation

AIM: To assessed the clinical significance of protocol liver biopsy (PLB) in pediatric liver transplantation (LT).

Endoscopic retrograde cholangiopancreatography and liver biopsy in the evaluation of elevated liver function tests after liver transplantation

BACKGROUND Abnormal liver function tests(LFTs)in post-liver transplant(LT)patients pose a challenge in the timing and selection of diagnostic modalities.There are little data regarding the accuracy of endoscopic retrograde cholangiopancreatography(ERCP)and liver biopsy(LB)in diagnosing post-transplant complications.AIM To evaluate the diagnostic performance of ERCP and LB in patients with nonvascular post-LT complications.METHODS This single-center retrospective study evaluated patients undergoing both ERCP and LB for evaluation of elevated LFTs within 6 mo of LT from 2000 to 2017.Diagnostic operating characteristics including accuracy,sensitivity and specificity for various diagnoses were calculated for ERCP and LB.The R factor(ratio of alkaline phosphatase to alanine aminotransferase)was also calculated for each patient.RESULTS Of the 1284 patients who underwent LT,91 patients(74.7%males,mean age of 51)were analyzed.Anastomotic strictures(AS,24.2%),acute cellular rejection(ACR,11%)and concurrent AS/ACR(14.3%)were the most common diagnoses.ERCP carried an accuracy of 79.1%(95%CI:69.3-86.9),LB had an accuracy of 93.4%(95%CI:86.2-97.5),and the combination of the two had an accuracy of 100%(95%CI:96-100).There was no difference between patients with AS and ACR in mean R factor(AS:1.9 vs ACR:1.1,P=0.24).Adverse events did not differ between the two tests(ERCP:3.1%vs LB:1.1%,P=0.31).CONCLUSION In patients with abnormal LFTs after LT without vascular complications,the combination of LB and ERCP carries low risk and improves diagnostic accuracy over either test alone.

Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

It is estimated that 30% of the adult population in Japan is affected by nonalcoholic fatty liver disease (NAFLD). Fatty changes of the liver are generally diagnosed using imaging methods such as abdominal ultrasonography (US) and computed tomography (CT), but the sensitivity of these imaging techniques is low in cases of mild steatosis. Alanine aminotransferase levels may be normal in some of these patients, warranting the necessity to establish a set of parameters useful for detecting NAFLD, and the more severe form of the disease, nonalcoholic steatohepatitis (NASH). Although liver biopsy is currently the gold standard for diagnosing progressive NASH, it has many drawbacks, such as sampling error, cost, and risk of complications. Furthermore, it is not realistic to perform liver biopsies on all NAFLD patients. Diagnosis of NASH using various biomarkers, scoring systems and imaging methods, such as elastography, has recently been attempted. The NAFIC score, calculated from the levels of ferritin, fasting insulin, and type IV collagen 7S, is useful for the diagnosis of NASH, while the NAFLD fibrosis score and the FIB-4 index are useful for excluding NASH in cases of advanced fibrosis. This article reviews the limitations and merits of liver biopsy and noninvasive diagnostic tests in the diagnosis of NAFLD/NASH.

Role of liver biopsy in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the “gold standard” for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease.

Comparison of the liver stiffness measurement by transient elastography with the liver biopsy

AIM: To compare the liver stiffness (LS) measurement by transient elastography (TE) to the liver biopsy (LB)-considered the "gold standard" in the evaluation of patients with chronic hepatitis C. METHODS: During a period of 12 mo, we evaluated 199 consecutive patients with chronic hepatitis due to hepatitis C virus (HCV), in which LB and LS assessments (by means of TE) were performed during the same session. RESULTS: Out of 199 patients, a valid measurement of the LS could not be obtained in 8. The mean value of LS in the cohort of 191 valid measurements was 8.45 ± 4.96 kPa, ranging from 2.3 to 38 kPa. The mean value of LS in patients with signifi cant fi brosis at biopsy (161 patients with F ≥ 2 according to Metavir) was 9.02 ± 5.15 kPa, significantly higher than in patients with no or mild fi brosis (30 patients with F < 2 Metavir): 5.39 ± 1.81 kPa (P < 0.0001). For a cut- off value of 6.8 kPa, the LS had a PPV of 98%, a NPV of 30.1%, a sensitivity of 59.6% and a specificity of 93.3% for the presence of signifi cant fi brosis (at least F2 Metavir), with a diagnostic performance of 77.3% (AUROC 0.773). Using this cut-off value, we reached the best discrimination between absence of fibrosis/ mild fibrosis (F < 2 Metavir) and the presence ofmoderate to severe fi brosis (F ≥ 2 Metavir). CONCLUSION: In patients with chronic hepatitis due to HCV, a cut-off value of 6.8 kPa measured by TE can differentiate between significant fibrosis and absent or mild fi brosis, with a PPV of 98%, a NPV of 30.1%, a sensitivity of 59.6%, a specificity of 93.3%, and a diagnostic performance of 77.3%.

Comparison of a new aspiration needle device and the Quick-Core biopsy needle for transjugular liver biopsy

AIM: To evaluate sample adequacy, safety, and needle passes of a new biopsy needle device compared to the Quick-Core biopsy needle for transjugular liver biopsy in patients affected by liver disease. METHODS: Thirty consecutive liver-disease patients who had major coagulation abnormalities and/or relevant ascites underwent transjugular liver biopsy using either a new needle device (18 patients) or the Quick-Core biopsy needle (12 patients). The length of the specimens was measured before fixation. A pathologist reviewed the histological slides for sample adequacy and pathologic diagnoses. The two methods’ specimen adequacy and complication rates were assessed. RESULTS: Liver biopsies were technically successful in all 30 (100%) patients, with diagnostic histological core specimens obtained in 30 of 30 (100%) patients, for an overall success rate of 100%. With the new device, 18 specimens were obtained, with an average of 1.1 passes per patient. Using the Quick-Core biopsy needle, 12 specimens were obtained, with an average of 1.8 passes per patient. Specimen length was significantly longer with the new needle device than with the Quick- Core biopsy needle (P < 0.05). The biopsy tissue was not fragmented in any of the specimens with the new aspiration needle device, but tissue was fragmented in 3 of 12 (25.0%) specimens obtained using the Quick-Core biopsy needle. Complications included cardiac arrhythmia in 3 (10.0%) patients, and transient abdominal pain in 4 (13.3%) patients. There were no cases of subcapsular hematoma, hemoperitoneum, or sepsis, and there was no death secondary to the procedure. In particular, no early or delayed major procedure-related complications were observed in any patient.CONCLUSION: Transjugular liver biopsy is a safe and effective procedure, and there was significant difference in the adequacy of the specimens obtained using the new needle device compared to the Quick- Core biopsy needle. Using the new biopsy needle device, the specimens showed no tissue fragmentation and no increment in major procedure-related complications was observed.

Recurrent gastrointestinal bleeding and hepatic infarction after liver biopsy

Hepatic artery pseudoaneurysms(HAP)are rare events,particularly after liver biopsy,but can be associated with serious complications.Therefore a high suspicion is necessary for timely diagnosis and appropriate treatment.We report on a case of HAP that potentially formed after a liver biopsy in a patient with sarcoidosis.The HAP in our case was virtually undetectable initially by angiography but resulted in several complications including recurrent gastrointestinal bleeding,hemorrhagic cholecystitis and finally hepatic infarction with abscess formation until it became detectable at a size of 5-mm.The patient remains asymptomatic over a year after endovascular embolization of the HAP.In this report,we demonstrate that a small HAP can avoid detection by angiography at an early stage while being symptomatic for a prolonged course.A high clinical suspicion with a close clinical/radiological follow-up is needed in symptomatic patients with history of liver biopsy despite initial negative work up.Once diagnosed,HAP can be safely and effectively treated by endovascular embolization.

Gastric ulcer penetrating to liver diagnosed by endoscopic biopsy

Liver penetration is a rare but serious complication of peptic ulcer disease.Usually the diagnosis is made by operation or autopsy.Clinical and laboratory data were no specific.A 64-year-old man was admitted with upper gastrointestinal bleeding.Hepatic penetration was diagnosed as the cause of bleeding.Endoscopy showed a large gastric ulcer with a pseudotumoral mass protruding from the ulcer bed.Definitive diagnosis was established by endoscopic biopsies of the ulcer base.

Biopsy of solid liver tumors:adverse consequences

BACKGROUND:Percutaneous radiologically-guided liver biopsy is used routinely worldwide in all secondary- level hospital centers.While it has an undoubted role in the investigation and management of acute and chronic inflammatory conditions of the liver,its role in hepatic oncology is doubtful and probably dangerous. METHOD:We report on two patients who underwent preoperative biopsy of potentially resectable liver tumors. RESULTS:At the time of surgery,there was evidence of seeding at the biopsy site in both cases.In case 1,potentially curative liver resection was rendered incurable because of gross peritoneal carcinomatosis lying adjacent to the site of liver biopsy.In case 2,the patient underwent curative liver resection,but there was histopathological evidence of peritoneal disease beyond the liver capsule along the falciform ligament at the site of the previous biopsy. CONCLUSIONS:No patient with a suspicious liver tumor which is thought to be malignant and has any possibility of being a potential candidate for liver surgery,should be subjected to pre-operative diagnostic biopsy in a non- specialist center.

Endoscopic ultrasound-guided tissue acquisition for the diagnosis of focal liver lesion

In patients with liver tumors,the histopathology examination can assist in diagnosis,staging,prognosis,and therapeutic management strategy.Endoscopic ultrasound(EUS)-guided tissue acquisition using fine needle aspiration(FNA)or more newly fine needle biopsy(FNB)is a well-developed technique in order to evaluate and differentiate the liver masses.The goal of the EUS-FNA or EUS-FNB is to provide an accurate sample for a histopathology examination.Therefore,malignant tumors such as hepatocarcinoma,cholangiocarcinoma and liver metastasis or benign tumors such as liver adenoma,focal hyperplastic nodular tumors and cystic lesions can be accurately diagnosed using EUS-guided tissue acquisition.EUS-FNB using 19 or 22 Ga needle provide longer samples and a higher diagnostic accuracy in patients with liver masses when compared with EUS-FNA.Few data are available on the diagnostic accuracy of EUS-FNB when compared with percutaneously,ultrasound,computer tomography or transjugulary-guided liver biopsies.This review will discuss the EUS-guided tissue acquisition options in patients with liver tumors and its efficacy and safety in providing accurate samples.The results of the last studies comparing EUS-guided liver biopsy with other conventional techniques are presented.The EUS-guided tissue acquisition using FNB can be a suitable technique in suspected liver lesions in order to provide an accurate histopathology diagnosis,especially for those who require endoscopy.

Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy

AIM:To characterize development of diet-induced nonalcoholic steatohepatitis(NASH)by performing live biopsy in wild-type and genetically obese mice.METHODS:Male wild-type C57BL/6J(C57)mice(DIO NASH)and male Lep ob/Lep ob(ob/ob)mice(ob/ob-NASH were maintained on a diet high in trans-fat(40%)fructose(22%)and cholesterol(2%)for 26 and 12 wk respectively.A normal chow diet served as control in C57 mice(lean chow)and ob/ob mice(ob/ob chow)After the diet-induction period,mice were liver biopsied and a blinded histological assessment of steatosis and fibrosis was conducted.Mice were then stratified into groups counterbalanced for steatosis score and fibrosi stage and continued on diet and to receive daily PO dosing of vehicle for 8 wk.Global gene expression in liver tissue was assessed by RNA sequencing and bioin formatics.Metabolic parameters,plasma liver enzyme and lipids(total cholesterol,triglycerides)as well a hepatic lipids and collagen content were measured b biochemical analysis.Non-alcoholic fatty liver disease activity score(NAS)(steatosis/inflammation/ballooningdegeneration)and fibrosis were scored.Steatosis and fibrosis were also quantified using percent fractional area.RESULTS:Diet-induction for 26 and 12 wk in DIONASH and ob/ob-NASH mice,respectively,elicited progressive metabolic perturbations characterized by increased adiposity,total cholesterol and elevated plasma liver enzymes.The diet also induced clear histological features of NASH including hepatosteatosis and fibrosis.Overall,the metabolic NASH phenotype was more pronounced in ob/ob-NASH vs DIO-NASH mice.During the eight week repeated vehicle dosing period,the metabolic phenotype was sustained in DIO-NASH and ob/ob-NASH mice in conjunction with hepatomegaly and increased hepatic lipids and collagen accumulation.Histopathological scoring demonstrated significantly increased NAS of DIO-NASH mice(0 vs4.7±0.4,P<0.001 compared to lean chow)and ob/ob-NASH mice(2.4±0.3 vs 6.3±0.2,P<0.001compared to ob/ob chow),respectively.Furthermore,fibrosis stage was significantly elevated for DIO-NASH mice(0 vs 1.2±0.2,P<0.05 compared to lean chow)and ob/ob NASH(0.1±0.1 vs 3.0±0.2,P<0.001compared to ob/ob chow).Notably,fibrosis stage was significantly(P<0.001)increased in ob/ob-NASH mice,when compared to DIO-NASH mice.CONCLUSION:These data introduce the obese dietinduced DIO-NASH and ob/ob-NASH mouse models with biopsy-confirmed individual disease staging as a preclinical platform for evaluation of novel NASH therapeutics.

Is liver biopsy mandatory in children with chronic hepatitis C?

Liver biopsy is considered the most accurate means to estimate the necroinflammatory activity and the extent of fibrosis. However, histology evaluation is an invasive procedure associated with risk to the patient, risk of sampling error and diagnostic inconsistencies due to inter- and intra-observer error. On the basis of histological studies performed so far, chronic hepatitis C in children appears morphologically benign in the majority of cases. At the Pediatric Liver Unit of our university, a total of 67 children with chronic hepatitis C underwent liver biopsy. Liver biopsy was repeated 5.5 years after the initial histological evaluation in 21 children. On a total number of 88 liver biopsies, micronodular cirrhosis was detected only in one genotype 1b-infected obese child. Since liver histology investigation of a child with chronic hepatitis C has few chances to highlight severe lesions, we question how liver biopsy helps in the management of children with chronic hepatitis C.

Metrically measuring liver biopsy:A chronic hepatitis B and C computer-aided morphologic description

AIM： To describe a quantitative analysis method for liver biopsy sections with a machine that we have named ＂Dioguardi Histological Metriser＂ which automatically measures the residual hepatocyte mass （including hepatocytes vacuolization）, inflammation, fibrosis and the loss of liver tissue tectonics.METHODS： We analysed digitised images of liver biopsy sections taken from 398 patients, The analysis with Dioguardi Histological Metriser was validated by comparison with semi-quantitative scoring system.RESULTS： The method provides： （1） the metrical extension in two-dimensions （the plane） of the residual hepatocellular set, including the area of vacuoles pertinent to abnormal lipid accumulation; （2） the geo- metric measure of the inflammation basin, which distinguishes intra-basin space and extra-basin dispersed parenchymal leukoo/tes; （3） the magnitude of collagen islets, （which were considered truncated fractals and classified into three degrees of magnitude）; and （4） the tectonic index that quantifies alterations （disorders） in the organization of liver tissue. Dioguardi Histological Metriser machine allows to work at a speed of 0.1 mm^2/s, scanning a whole section in 6-8 min.CONCLUSION： The results are the first standardized metrical evaluation of the geometric properties of the parenchyma, inflammation, fibrosis, and alterations in liver tissue tectonics of the biopsy sections. The present study confirms that biopsies are still valuable, not only for diagnosing chronic hepatitis, but also for quantifying changes in the organization and order of liver tissue structure.

Checkpoint inhibitor-induced hepatotoxicity:Role of liver biopsy and management approach

Immunological checkpoint inhibitors(ICIs)have revolutionized therapy of many different malignanices.Concomitant immune-mediated adverse effects are common and can affect many organs such as the skin,lungs,gastrointestinal and endocrine organs as well as the liver.Liver injury has been reported in 3%-8%of patients with grade III-IV hepatitis in retrospective studies.The liver injury is characterized by hepatocellular injury resembling autoimmune hepatitis biochemically but not immunologically as patients with ICI induced hepatoxicity rarely have auto-antibodies or IgG elevation.The role for liver biopsy(LB)in patients with suspected liver injury due to ICIs is controversial and it is not clear whether results of a LB will change clinical management.LB can be helpful when there is diagnostic uncertainty and pre-existing liver disease is suspected.Although there are no distinctive histological features,the finding of granulomas and endothelitis may suggest a specific type of hepatitis induced by ICIs.The natural history of hepatotoxicity of ICI therapy is not well known.Recent studies have demonstrated that 33%-50%of patients improve spontaneously with discontinuation of ICIs.In patients with jaundice and/or coagulopathy corticosteroids are used.The high doses of corticosteroids with 1-2 mg/kg/d of methylprednisolone recommended by the oncological societies are controversial.Recently it has shown that initial treatment with 1 mg/kg/d provided similar liver tests improvement which was also associated with a reduced risk of steroid-induced adverse effects in comparison with higher-dose regimens.Secondary immunosuppression mostly with mycophenolate mofetil has been reported to be helpful.

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.