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.

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.

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.

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.

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%.

Role of liver biopsy in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (&#x0003e; 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 &#x0201c;gold standard&#x0201d; 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.

Hemobilia and other complications caused by percutaneous ultrasound-guided liver biopsy

Hemobilia accounts for approximately 3%of all major percutaneous liver biopsy complications,and rarely results from arterioportal fistula.We report a patient who suffered from four complications over 11 d after ultrasound-guided percutaneous liver biopsy:hemobilia,acute pancreatitis,acute cholecystitis,and multiple stomach ulcers.Digital subtraction angiography was done after consultation with doctors,and showed obvious arteriovenous fistula of the right liver.The hepatic artery was selected and embolized by spring orbs.The active bleeding was stopped after embolization of the hepatic artery.The patient was discharged home on day 12 after embolization and remained well.

Why,who and how should perform liver biopsy in chronic liver diseases

Chronic viral hepatitis is a common disease in the general population.During chronic hepatitis,the prognosis and clinical management are highly dependent on the extent of liver fibrosis.The fibrosis evaluation can be performed by FibroTest(using serological markers),by Elastography or FibroScan(a noninvasive percutaneous technique using the elastic properties of the hepatic tissue) and by liver biopsy(LB),considered to be the "gold standard".Currently,there are three techniques for performing LB:percutaneous,transjugular and laparoscopic.The percutaneous LB can be performed blind,ultrasound(US) guided or US assisted.There are two main categories of specialists who perform LB:gastroenterologists(hepatologists) and radiologists,and the specialty of the individual who performs the LB determines if the LB is performed under ultrasound guidance or not.There are two types of biopsy needles used for LB:cutting needles(Tru-Cut,Vim-Silverman) and suction needles(Menghini,Klatzkin,Jamshidi).The rate of major complications after percutaneous LB ranges from 0.09% to 2.3%,but the echo-guided percutaneous liver biopsy is a safe method for the diagnosis of chronic diffuse hepatitis(cost-effective as compared to blind biopsy) and the rate of complications seems to be related to the experience of the physician and the type of the needle used(Menghini type needle seems to be safer).Maybe,in a few years we will use non-invasive markers of fibrosis,but at this time,most authorities in the field consider that the LB is useful and necessary for the evaluation of chronic hepatopathies,despite the fact that it is not a perfect test.

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).

Checkmate to liver biopsy in chronic hepatitis C?

Liver biopsy (LB) has traditionally been considered the gold standard for pretreatment evaluation of liver fibrosis in patients with chronic hepatitis C (CHC). However, LB is an invasive procedure with several shortcomings (intra-and interobserver variability of histopathological interpretation, sampling errors, high cost) and the risk of rare but potentially life-threatening complications. In addition, LB is poorly accepted by patients and it is not suitable for repeated evaluation. Further-more, the prevalence of CHC makes LB unrealistic to be performed in all patients with this disease who are candidates for antiviral therapy. The above-mentioned drawbacks of LB have led to the development of non-invasive methods for the assessment of liver fibrosis. Several noninvasive methods, ranging from serum marker assays to advanced imaging techniques, have proved to be excellent tools for the evaluation of liver fibrosis in patients with CHC, whereas the value of LB as a gold standard for staging fibrosis prior to antiviral therapy has become questionable for clinicians. Despite significant resistance from those in favor of LB, noninvasive methods for pretreatment assessment of liver fibrosis in patients with CHC have become part of routine clinical practice. With protease inhibitors-based triple therapy already available and substantial improvement in sustained virological response, the time has come to move forward to noninvasiveness, with no risks for the patient and, thus, no need for LB in the assessment of liver fibrosis in the decision making for antiviral therapy in CHC.

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.

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.

Percutaneous liver biopsy complicated by hemobilia-associated acute cholecystitis

Liver biopsy is generally considered a safe and highly useful procedure. It is frequently performed in an outpatient setting for diagnosis and follow-up in numerous liver disorders. Since its introduction at the end of the 19th century, broad experience, new imaging techniques and special needles have significantly reduced the rate of complications associated with liver biopsy. Known complications of percutaneous biopsy of the liver include hemoperitoneum, subcapsular hematoma, hypotension, pneumothorax and sepsis. Other intra-abdominal complications are less common. Hemobilia due to arterio-biliary duct fistula has been described, which has only rarely been clinically expressed as cholecystitis or pancreatitis. We report a case of a fifteen year-old boy who developed severe acute cholecystitis twelve days after a percutaneous liver biopsy performed in an outpatient setting. The etiology was clearly demonstrated to be hemobilia-associated, and the clinical course required the performance of a laparoscopic cholecystectomy. The post operative course was uneventful and the patient was discharged home. Percutaneous liver biopsy is a safe and commonly performed procedure. However, severe complications can occasionally occur. Both medical and surgical options should be evaluated while dealing with these rare incidents.

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.

Gallbladder polyp as a manifestation of hemobilia caused by arterial-portal fistula after percutaneous liver biopsy: A case report

Outpatient percutaneous liver biopsy is a common practice in the differential diagnosis and treatment of chronic liver disease. The major complication and mortality rate were about 2-4% and 0.01-0.33% respectively. Arterio-portal fistula as a complication of percutaneous liver biopsy was infrequently seen and normally asymptomatic. Hemobilia, which accounted for about 3% of overall major percutaneous liver biopsy complications, resulted rarely from arterio-portal fistula We report a hemobilia case of 68 years old woman who was admitted for abdominal pain after liver biopsy. The initial ultrasonography revealed a gallbladder polypoid tumor and common bile duct (CBD) dilatation. Blood clot was extracted as endoscopic retrograde cholangiopancreatography (ERCP) showed hemobilia. The patient was shortly readmitted because of recurrence of symptoms. A celiac angiography showed an intrahepatic arterio-portal fistula. After superselective embolization of the feeding artery, the patient was discharged uneventfully. Most cases of hemobilia caused by percutaneous liver biopsy resolved spontaneously. Selective angiography embolization or surgical intervention is reserved for patients who failed to respond to conservative treatment.

Delayed hemorrhage from hepatic artery after ultrasound-guided percutaneous liver biopsy: A case report

Percutaneous liver biopsy is considered one of the most important diagnostic tools to evaluate diffuse liver diseases. Pseudoaneurysm of hepatic artery is an unusual complication after ultrasound-guided percutaneous liver biopsy. Delayed hemorrhage occurs much less frequently. We report a case of pseudoaneurysm of the hepatic artery of a 46-year-old man who was admitted for abdominal pain after 4 d of liver biopsy. The bleeding was controlled initially by angiographic embolization. However, recurrent bleeding could not be controlled by repeat angiography, and the patient died 4 d after admission from multiorgan failure. The admittedly rare possibility of delayed hemorrhage should be considered whenever a liver biopsy is performed.

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.

Liver biopsy in a district general hospital:Changes over two decades

AIM： To study liver biopsy practice over two decades in a district general hospital in the United Kingdom.METHODS： We identified all patients who had at least one liver biopsy between 1986 and 2006 from the databases of the radiology and gastroenterology departments. Subjects with incomplete clinical data were excluded from the study.RESULTS： A total of 103 liver biopsies were performed. Clinical data was available for 88 patients, with 95 biopsies. Between 1986 and 1996, 18 （95%） out of the 19 liver biopsies performed were blind and 6 （33%） were for primary biliary cirrhosis. Between 1996 and 2006, 14 （18%） out of 76 biopsies were blind; and the indications were abnormal liver tests （33%）, hepatitis C （12%） and targeted-biopsies （11%）. Liver biopsies were unhelpful in 5 （50） subjects. Pain was the most common complication of liver biopsy （5%）. No biopsy-related mortality was reported. There was a trend towards more technical failures and complications with the blind biopsy technique.CONCLUSION： Liver biopsies performed in small district hospitals are safe and useful for diagnostic and staging purposes. Abnormal liver tests, non-alcoholic fatty liver disease and targeted biopsies are increasingly common indications. Ultrasound-guided liver biopsies are now the preferred method and are associated with fewer complications.

Staging liver fibrosis with various diffusion-weighted magnetic resonance imaging models

BACKGROUND Diffusion-weighted imaging(DWI)has been developed to stage liver fibrosis.However,its diagnostic performance is inconsistent among studies.Therefore,it is worth studying the diagnostic value of various diffusion models for liver fibrosis in one cohort.AIM To evaluate the clinical potential of six diffusion-weighted models in liver fibrosis staging and compare their diagnostic performances.METHODS This prospective study enrolled 59 patients suspected of liver disease and scheduled for liver biopsy and 17 healthy participants.All participants underwent multi-b value DWI.The main DWI-derived parameters included Mono-apparent diffusion coefficient(ADC)from mono-exponential DWI,intravoxel incoherent motion model-derived true diffusion coefficient(IVIM-D),diffusion kurtosis imaging-derived apparent diffusivity(DKI-MD),stretched exponential model-derived distributed diffusion coefficient(SEM-DDC),fractional order calculus(FROC)model-derived diffusion coefficient(FROC-D)and FROC model-derived microstructural quantity(FROC-μ),and continuous-time random-walk(CTRW)model-derived anomalous diffusion coefficient(CTRW-D)and CTRW model-derived temporal diffusion heterogeneity index(CTRW-α).The correlations between DWI-derived parameters and fibrosis stages and the parameters’diagnostic efficacy in detecting significant fibrosis(SF)were assessed and compared.RESULTS CTRW-D(r=-0.356),CTRW-α(r=-0.297),DKI-MD(r=-0.297),FROC-D(r=-0.350),FROC-μ(r=-0.321),IVIM-D(r=-0.251),Mono-ADC(r=-0.362),and SEM-DDC(r=-0.263)were significantly correlated with fibrosis stages.The areas under the ROC curves(AUCs)of the combined index of the six models for distinguishing SF(0.697-0.747)were higher than each of the parameters alone(0.524-0.719).The DWI models’ability to detect SF was similar.The combined index of CTRW model parameters had the highest AUC(0.747).CONCLUSION The DWI models were similarly valuable in distinguishing SF in patients with liver disease.The combined index of CTRW parameters had the highest AUC.