Need For Liver Biopsy Research Articles

Elast PQ Ultrasound - a Noninvasive, Reproducible, Easily Performed Method and a New Era in Liver Fibrosis Assessment

Liver fibrosis represents the repair mechanism in liver injury and is a feature of most chronic liver diseases. The degree of liver fibrosis in chronic viral hepatitis infection has major clinical implications and presence of advanced fibrosis or cirrhosis determines prognosis. Treatment initiation for viral hepatitis is indicated in most cases of advanced liver fibrosis and diagnosis of cirrhosis entails hepatology evaluation for specialized clinical care. Liver biopsy is an invasive technique and has been the standard of care of fibrosis assessment for years; however, it has several limitations and procedure related complications. Recently, several methods of noninvasive assessment of liver fibrosis have been developed which require either serologic testing or imaging of liver. Imaging based noninvasive techniques are reviewed here and their clinical use is described. Some of the imaging based tests are becoming widely available, and collectively they are shown to be superior to liver biopsy in important aspects. Clinical utilization of these methods requires understanding of performance and quality related parameters which can affect the results and provide wrong assessment of the extent of liver fibrosis. Familiarity with the strengths and weakness of each modality is needed to correctly interpret the results in appropriate clinical content. A new technique called Elast PQ uses ultrasound shear wave elastography to provide a noninvasive, reproducible, easily performed method of assessing liver fibrosis. It can easily combine a routine ultrasound imaging exam of the liver anatomy with targeted tissue stiffness values, assess liver fibrosis in patient with clinically suspected disease even before abnormalities are detected with ultrasound imaging, evaluate and obtain a baseline stiffness value in patients with chronic liver disease, follow up patients under treatment to monitor progression, stabilization or regression of liver disease and help avoid the need for liver biopsies when elastography results are consistent with other clinical findings. Both the prognosis and potential treatment of chronic liver diseases greatly depend on the progression of liver fibrosis, which is the ultimate outcome of chronic liver damage. Historically, liver biopsy has been instrumental in adequately assessing patients allows clinicians both to obtain diagnosis information and initiate adequate therapy. However, the technique is not exempt of deleterious effects. Multiple diagnostic tests have been developed for the staging of fibrosis using noninvasive methods, most of them in the setting of chronic hepatitis C. The goal of this paper is to review available data on the staging and assessment of liver fibrosis with two methods: serum markers & transient elastography (FibroScan).Faridpur Med. Coll. J. Jan 2018;13(1): 44-46

Transient Elastography in Healthy Children and Children with Cystic Fibrosis

Background: Transient Elastography (TE) is a point-of-care test, which has revolutionised the management of liver disease in adults and reduced the need for liver biopsy. TE has been used in a variety of liver diseases in children. However studies to evaluate its repeatability and reproducibility are limited. Aims to (i) evaluate the normal range, (ii) repeatability of TE in healthy children, (iii) determine if TE could facilitate early diagnosis and monitor disease progression in children with cystic fibrosis liver disease (CFLD). Methods: Healthy children had two measurements of liver stiffness to determine the upper limit of normal (ULN). The repeatability and reproducibility of TE was examined using Repeatability Coefficient (RC), Bland and Altman plots and Lin's Concordance Correlation Coefficient (CCC). 128 participants with CF, classified as (i) clinically significant liver disease (CSCFLD, n=20), (ii) nonspecific changes (NSCFLD, n=43) and (iii) no evidence of liver disease (NOCFLD, n=65), had TE measurements. Findings: 235/257 (91·4%) volunteers had two valid measurements (mean age 11·7years, SD2·51, 45·3% male). The normal range of TE in healthy children was 2·88-6·52k Pa. The mean difference between paired measurements was -0.044 kPa, SD 0.414 with a normal distribution (Shapiro-Wilk test W= 0·99 p 1 kPa between measurements in 61/235 (25.9%) of healthy children. In CF, TE could distinguish children with advanced liver disease from those with no liver disease, but the repeatability of TE was also poor in CFLD. Interpretation: TE is not repeatable or reproducible in healthy children. This variability in TE performance indicates that TE does not have acceptable diagnostic accuracy in children. Funding Statement: This study was funded by the Health Research Board (HRA-POR-662) Declaration of Interests: None of the authors have any conflicts of interest to declare. Ethics Approval Statement: The study was approved by the Ethics Committees of Our Lady’s Children’s Hospital Crumlin (sports club volunteers and patients), The National Children’s Hospital, The Children’s University Hospital Temple Street, and St Vincent’s University Hospital Dublin. Signed consent to participate in the study was obtained from parents or guardians of both healthy volunteer children and CF participants.

Dual-energy computed tomography for non-invasive staging of liver fibrosis: Accuracy of iodine density measurements from contrast-enhanced data.

To investigate whether iodine density measurements from contrast-enhanced dual-energy computed tomography (CT) data can non-invasively stage liver fibrosis. This single-center, prospective study was approved by our IRB with written informed consent. Forty-seven consecutive patients (26 men and 21 women; mean age, 63.1years) with chronic liver disease underwent contrast-enhanced dual-energy CT of the liver (non-contrast, arterial, portal venous, and equilibrium phase images), followed by liver biopsy. Iodine density of liver and aorta were obtained by two independent observers. Iodine uptake of the liver (Δ Liver), representing the difference in iodine density between equilibrium phase and non-contrast images, was calculated and normalized by aorta (Δ Liver/Aorta). We accounted for contrast agent distribution volume by using hematocrit level. Accuracy of iodine density measurements for staging liver fibrosis was assessed by using receiver operating characteristic (ROC) curves. Multivariate linear regression analysis was used to assess the impact of independent variables (liver fibrosis stage and patient-related confounders) on iodine uptake. The Δ Liver/Aorta significantly increased and moderately correlated with METAVIR liver fibrosis stage (ρ = 0.645, P < 0.001). Areas under the ROC curve ranged from 0.795 to 0.855 for discriminating each liver fibrosis score (≥F1-F4). METAVIR fibrosis stage was the most significant independent factor associated with Δ Liver (P = 0.005) and Δ Liver/Aorta (P < 0.001). Hepatic extracellular volume fraction with contrast-enhanced dual-energy CT can non-invasively stage liver fibrosis in chronic liver diseases. This technique could prove useful for monitoring disease progression and treatment response, potentially reducing the need for liver biopsy.

Well-controlled autoimmune hepatitis treatment withdrawal may be safely accomplished without liver-biopsy guidance.

BackgroundAutoimmune hepatitis may flare up after treatment withdrawal, especially in those who had not achieved histological remission but had normal liver enzymes. The European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Disease (AASLD) Guidelines recommend performing liver biopsy before treatment withdrawal. The aim of the study is to define the outcome of treatment withdrawal in adults with well-controlled disease for 2 years with and without liver-biopsy guidance.MethodsA retrospective observational study was conducted on biopsy-proven autoimmune hepatitis patients who were treated for 2 years and with persistently normal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) or nearly so for 6 months prior to treatment withdrawal. Exclusions were: juvenile onset autoimmune hepatitis and prior treatment or use of agents other than corticosteroids and azathioprine. The primary endpoint was to define freedom from flare-ups for 1 year after treatment withdrawal.ResultsThirty-four consecutive subjects meeting study criteria were identified. Treatment withdrawal was accomplished in 24 subjects without liver-biopsy guidance and 10 had pre-treatment withdrawal liver biopsy. Demographics, immunosuppressive usage, pre-treatment cirrhosis and pre-treatment liver enzymes were similar between the two groups, and 25% had an enzyme flare-up within 12 months after treatment withdrawal, which was similar in the two groups (20.8 vs 30.0%, P = 0.57).ConclusionsAdults with autoimmune hepatitis and excellent response to therapy for 2 years are candidates for treatment withdrawal without the need for liver biopsy.

Routine indexes for cirrhosis and significant fibrosis detection in patients with compensated chronic hepatitis B

Background and aimFibrosis index based on the four factors (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) were not well validated in patients with chronic hepatitis B (CHB). The aim of this study was to validate the performances of these indexes and construct novel indexes for liver fibrosis assessment. MethodsA total of 1438 consecutive antivirus treatment-naïve patients with CHB were analysed, and two novel indexes (named HeBCI and HeBFI) were derived for cirrhosis and significant fibrosis detection. ResultsFor cirrhosis, the area under receiver operating characteristic curves (AUROCs) were 0.841 for HeBCI, 0.708 for FIB-4 and 0.623 for APRI in the model set, and 0.779, 0.690, 0.595 in the validation set. For significant fibrosis, the AUROCs were 0.781 for HeBFI, 0.693 for APRI and 0.641 for FIB-4 in the model set, and 0.776, 0.729, 0.641 in the validation set. HeBCI determined 750 (52.2%) patients as having cirrhosis or non-cirrhosis with an accuracy of 86%. HeBFI detected 673 (46.8%) patients with or without significant fibrosis with an accuracy of 76.6%. ConclusionsAs economical and convenient indexes, HeBCI and HeBFI are suitable to serve as outpatient tools for detecting significant fibrosis and cirrhosis to reduce the need of liver biopsy significantly in resource-limited settings.

Prediction of hepatic necroinflammatory activity in patients with chronic hepatitis B by a simple noninvasive model

BackgroundA model was constructed using clinical and serum variables to discriminate between chronic hepatitis B (CHB) patients with and without significant necroinflammatory activity (score 4–18 vs. score 0–3).MethodsConsecutive CHB patients who underwent liver biopsy were divided into two sequential groups: a training group (n = 401) and a validation group (n = 401). Multivariate analysis identified alanine aminotransferase, γ-glutamyltransferase, prothrombin time and albumin as independent predictors of necroinflammatory activity.ResultsThe area under the receiver operating characteristic curve was 0.826 for the training group and 0.847 for the validation group. Using a cut-off score of H ≤ 0.375, significant necroinflammatory activity (score 4–18) was excluded with high accuracy [78.2% negative predictive value (NPV), 72% positive predictive value (PPV), and 90.8% sensitivity] in 238 (59.4%) of 401 patients in the training group and with the same certainty (88.1% NPV, 61.2% PPV, and 95.1% sensitivity) among 204 (50.9%) of 401 patients in the validation group. Similarly, applying a cut-off score of H > 0.720, significant necroinflammatory activity was correctly identified with high accuracy (90.8% PPV, 57.7% NPV, and 92.0% specificity) in 150 (37.4%) of 401 patients in the training group and with the same certainty (91.8% PPV, 64.6% NPV, and 95.4% specificity) in 188 (46.9%) of 401 patients in the validation group.ConclusionsA predictive model based on easily accessible variables identified CHB patients with and without significant necroinflammatory activity with a high degree of accuracy. This model may decrease the need for liver biopsy for necroinflammatory activity grading in 72.1% of CHB patients.

Noninvasive Biomarkers in Assessment of Liver Fibrosis in Patients with HBeAg Negative Chronic Hepatitis B.

BACKGROUND:Liver biopsy for evaluation of liver fibrosis has several adverse effects, for which reason noninvasive tests have been developed.AIM:To evaluate the usefulness of noninvasive biomarkers, qHBsAg and HBV DNA levels in predicting liver fibrosis in patients with hepatitis Be antigen (HBeAg) negative chronic hepatitis B (CHB).MATERIAL AND METHODS:This prospective study included 50 patients with HBeAg negative CHB. All patients underwent laboratory and serology testing, quantification of HBV DNA and HBs antigen. The liver stiffness was measured with elastography. The patients were analysed for APRI and FIB-4, quantitative hepatitis Bs antigen and HBV DNA.RESULTS:Logistic regression analysis showed that greatest significance in predicting liver fibrosis has FIB-4 (Wald = 3.24, P = 0.07), followed by HBV DNA ≥ 2 000 IU/ml ≤ 20 000 IU/ml (Wald = 2.86, P = 0.09), qHBsAg (Wald = 2.17, P = 0.14), HBV DNA > 20 000 IU/ml (Wald = 0.58, P = 0.45), APRI (Wald = 0.04, P = 0.84).CONCLUSION:the FIB-4 index has the greatest value in predicting liver fibrosis while APRI has the lowest; the more advanced liver disease is associated with lower serum level of quantitative HBs antigen. Combination of noninvasive blood biomarkers and imaging tests can provide better diagnostic accuracy and exclude the need for liver biopsy.

Practical Diagnosis and Staging of Nonalcoholic Fatty Liver Disease: A Narrative Review

As the rates of obesity increase worldwide, the prevalence of nonalcoholic fatty liver disease (NAFLD) has risen and it is now the most common cause of liver disease in the developed world. A significant proportion of patients with NAFLD develop nonalcoholic steatohepatitis and progressive liver fibrosis, which can lead to cirrhosis and its complications. NAFLD should be suspected in individuals who have central obesity and metabolic risk factors. A diagnosis of NAFLD can be made when patients have evidence of steatosis on imaging or if they have raised liver enzymes with a background of metabolic risk factors, provided other causes of liver disease and excessive alcohol consumption are excluded. Making a specific diagnosis of NAFLD is important so that affected individuals can receive specific treatment and be monitored for its complications. The stage of liver fibrosis is the most important prognostic factor so must be assessed in all patients; a number of simple blood tests and imaging modalities allow accurate fibrosis staging without the need for liver biopsy. The aim of this narrative review is to provide a practical overview relating to the diagnosis and staging of NAFLD using noninvasive tests that are widely available in primary and secondary care.

Diagnostic Accuracy of Aspartate Aminotransferase to Platelet Ratio Index and Fibrosis 4 Scores in Predicting Advanced Liver Fibrosis in Patients with End-stage Renal Disease and Chronic Viral Hepatitis: Experience from Pakistan.

The aim was to assess the diagnostic accuracy of APRI and FIB-4 in assessing the stage of liver fibrosis in end stage renal disease (ESRD) patients with chronic viral hepatitis and to compare the two tests with standard tru-cut liver biopsy. The study was conducted at Sindh Institute of Urology and Transplantation Karachi (SIUT) from May 2010 to May 2014. All ESRD patients, being considered as candidates for renal transplantation and in whom liver biopsy was performed were included. Fibrosis stage was assessed on liver biopsy using Ishak scoring system. The serum transaminases and platelet counts were used to calculate APRI and FIB-4 scores. Out of 109 patients, hepatitis C and B virus infections were present in 104 (95.4%) and 3(2.8%), respectively, while 2 (1.8%) patients had both infections. The mean Ishak fibrosis score was 1.95 ± 2. Advanced fibrosis was noted in 37 (34%) patients. Univariate analysis showed that advanced liver fibrosis was associated with lower platelets counts (P=0.001) and higher aspartate aminotransferase (AST) (P=0.001), alanine aminotransferase (ALT) (P=0.022), APRI score (P=0.001) and FIB-4 score (P=0.001). On logistic regression analysis, only APRI score (P < 0.001) was found to be the independent variable associated with advanced liver fibrosis. APRI score cutoff ≥1 indicating advanced fibrosis showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 91.9%, 90.3%, 82.9%, 95.6%, respectively with area under the curve (AUC) of 0.97. Similarly, a FIB-4 score cutoff ≥1.1 had sensitivity, specificity, PPV and NPV of 70.27%, 66.67%, 52% and 81.36%, respectively with AUC of 0.74. APRI is more accurate noninvasive test for assessing advanced liver fibrosis in ESRD patients as compared to FIB-4. It can be used to obviate the need for liver biopsy in this high risk population.

A radiofrequency device for tract ablation after liver biopsy: a single-institution human feasibility study.

The need for liver biopsy has been increasing because genetic testing of specimens has become important for determining prognosis and management in patients with hepatic malignancy. We evaluated the feasibility of a device for biopsy tract ablation in patients with hepatic masses. This prospective single-center pilot study was approved by our institutional review board and patients provided written informed consent. Between September 2015 and March 2016, 10 patients (6 males and 4 females, 35-66-years-old) who had hepatic masses and normal range of platelet count and prothrombin time were enrolled. After percutaneous ultrasound-guided biopsy, the biopsy tract was ablated with the device which consists of an insulation sheath and a radiofrequency applicator. Complications were evaluated with Doppler ultrasound immediately after the biopsy, with noncontrast abdominopelvic CT the day after the biopsy, and with a telephone interview 7 days after the biopsy. Tract ablation did not cause any pain in seven patients and caused minimal pain in three3 patients. Tract ablation was performed for a mean of 4.8 s (range, 4-6 s). No adverse events occurred during the procedure. Bleeding through the biopsy tract was not apparent on Doppler ultrasound, and abnormal fluid was not detected in the abdominal cavity on CT. Procedure-related complications were not reported on telephone interview. Biopsy tract ablation with the device is technically feasible. If the device is used appropriately considering its potential advantages, it may help to reduce the risk of complications associated with liver biopsy. Advances in knowledge: It is technically feasible to perform biopsy tract ablation with the radiofrequency ablation device after liver biopsy.

Can negligible hepatic steatosis determined by magnetic resonance imaging–proton density fat fraction obviate the need for liver biopsy in potential liver donors?

The purpose of this study is to determine whether magnetic resonance (MR)-proton density fat fraction (PDFF) estimate of negligible hepatic fat percentage (<5%) can exclude significant hepatic steatosis (≥10%) in living liver donor candidates obviating the need for liver biopsy and to perform intraindividual comparisons between MR-PDFF techniques for hepatic steatosis quantification. In an ethics-approved retrospective study, 144 liver donor candidates with magnetic resonance spectroscopy (MRS) and 6-echo Dixon magnetic resonance imaging (MRI) between 2013 and 2015 were included. A subset of 32 candidates underwent liver biopsy. Hepatic fat percentage was determined using MR-PDFF and histopathology-determined fat fraction as the reference standard. A receiver operating characteristic analysis with positive predictive value, negative predictive value (NPV), sensitivity, and specificity was performed to discriminate between clinically significant steatosis (≥10%) or not (<10%) at MRS-PDFF and MRI-PDFF thresholds of 5% and 10%. Pearson correlation and Bland-Altman analyses between MRS-PDFF and MRI-PDFF were performed for intraindividual comparison of hepatic steatosis estimation. There was significant association between MRS-PDFF and MRI-PDFF with HP-FP. High NPV of 95% (95% confidence interval [CI], 78%-99%) and 100% (95% CI, 76%-100%) as well as an area under the curve of 0.90 (95% CI, 0.79-1.0) and 0.93 (95% CI, 0.84-1.0) were obtained with a cutoff threshold of 5% MRI-PDFF and MRS-PDFF, respectively, to exclude clinically significant steatosis (≥10%). Intraindividual comparison between MRS-PDFF and MRI-PDFF showed a Pearson correlation coefficient of 0.83. Bland-Altman analysis showed a mean difference of 1% with 95% limits of agreement between -1% and 3%. MR-PDFF estimate of negligible hepatic fat percentage (<5%) has sufficient NPV for excluding clinically significant hepatic steatosis (≥10%) in living liver donor candidates obviating the need for liver biopsy. It may be sufficient to acquire only the multiecho Dixon MRI-PDFF for hepatic steatosis estimation. Liver Transplantation 24 470-477 2018 AASLD.

VITAMIN D DEFICIENCY, A NONINVASIVE MARKER OF STEATOHEPATITIS IN PATIENTS WITH OBESITY AND BIOPSY PROVEN NONALCOHOLIC FATTY LIVER DISEASE.

Nonalcoholic fatty liver disease (NAFLD) includes simple steatosis, steatohepatitis (NASH) which can evolve with progressive fibrosis, cirrhosis and hepatocellular carcinoma. As liver biopsy cannot be used as a screening method, noninvasive markers are needed. The aim of this study was to test if there is a significant association between vitamin D deficit and the severity of NAFLD. The patients were divided into two groups (vitamin D insufficiency/deficiency) and statistical analyses were performed on the correlation of clinical and biochemical characteristics with histopathological hepatic changes. We prospectively studied 64 obese patients referred for bariatric surgery between 2014 and 2016 to our Surgical Unit. Anthropometric, clinical measurements, general and specific biological balance were noted. NAFLD diagnosis and activity score (NAS) were evaluated on liver biopsies. Increased serum fibrinogen was correlated with NASH (p=0.005) and higher NAS grade. T2DM was positively correlated with liver fibrosis (p=0.002). 84.37% of the patients had vitamin D deficit and 15.62% were vitamin D insufficient. Lobular inflammation correlated with vitamin D deficit (p=0.040). Fibrosis (p=0.050) and steatohepatitis (p=0.032) were independent predictors of low vitamin D concentration. Vitamin D status in conjunction with other parameters - such as T2DM - or serum biomarkers - namely fibrinogen level and PCR level - may point out the aggressive forms of NAFLD and the need for liver biopsy for appropriate management.

Progress in non-invasive detection of liver fibrosis.

Liver fibrosis is an important pathological precondition for hepatocellular carcinoma. The degree of hepatic fibrosis is positively correlated with liver cancer. Liver fibrosis is a series of pathological and physiological process related to liver cell necrosis and degeneration after chronic liver injury, which finally leads to extracellular matrix and collagen deposition. The early detection and precise staging of fibrosis and cirrhosis are very important for early diagnosis and timely initiation of appropriate therapeutic regimens. The risk of severe liver fibrosis finally progressing to liver carcinoma is >50%. It is known that biopsy is the gold standard for the diagnosis and staging of liver fibrosis. However, this method has some limitations, such as the potential for pain, sampling variability, and low patient acceptance. Furthermore, the necessity of obtaining a tissue diagnosis of liver fibrosis still remains controversial. An increasing number of reliable non-invasive approaches are now available that are widely applied in clinical practice, mostly in cases of viral hepatitis, resulting in a significantly decreased need for liver biopsy. In fact, the non-invasive detection and evaluation of liver cirrhosis now has good accuracy due to current serum markers, ultrasound imaging, and magnetic resonance imaging quantification techniques. A prominent advantage of the non-invasive detection and assessment of liver fibrosis is that liver fibrosis can be monitored repeatedly and easily in the same patient. Serum biomarkers have the advantages of high applicability (>95%) and good reproducibility. However, their results can be influenced by different patient conditions because none of these markers are liver-specific. The most promising techniques appear to be transient elastography and magnetic resonance elastography because they provide reliable results for the detection of fibrosis in the advanced stages, and future developments promise to increase the reliability and accuracy of the staging of hepatic fibrosis. This article aims to describe the recent progress in the development of non-invasive assessment methods for the staging of liver fibrosis, with a special emphasize on computer-aided quantitative and deep learning methods.

Liver histology in asymptomatic Hepatitis-C virus positive blood donors.

Objective:To assess the Histological alteration of liver in asymptomatic HCV PCR positive family blood donors.Methods:This is a prospective cross sectional study carried out at Blood Transfusion Services, Clinical & Molecular Laboratory and Pakistan Health Research Council, Jinnah Postgraduate Medical Centre, Karachi from January 2011 to December 2016. One hundred thirteen (113) Anti HCV and HCV RNA positive family blood donors with normal or slightly raised ALT during three consecutive bimonthly visits were included. After taking consent liver biopsy was done to see the histopathological changes in these study participants. The software program SPSS for windows (Ver.19) was utilized for all statistical analysis.Results:One hundred thirteen blood donors who were Anti HCV and HCV RNA positive were included. Ninety eight were male and 15 Female with a mean age of 32.3±6.94 years. Nineteen (16.8%) had significant inflammation of grade 2-3. Nine (8.0%) had significant fibrosis and steatosis was seen in 65 (57.5%) cases. Cirrhosis or advanced liver disease was not found in this series.Conclusion:HCV infected individual with normal ALT level having good physical health, without any sign of advanced liver disease on ultrasonography and routine laboratory investigation like AST, Gamma GT, Alkaline Phosphatase, serum albumin, A/G ratio, platelet count and PT, INR might be highly helpful to predict mild or progressive liver disease. Ultimately it reduces the need of liver biopsy, an invasive procedure having significant complications.

Prediction of histologic alcoholic hepatitis based on clinical presentation limits the need for liver biopsy.

The clinical presentation of alcoholic hepatitis (AH) can be mimicked by other alcoholic liver diseases. The aim of this study was to identify clinical features that predict AH on liver biopsy. Biopsies from patients hospitalized for presumed severe AH were used to identify a derivation cohort (101 patients) and validation cohort (71 patients). Using histologic scores for hepatocyte ballooning, Mallory‐Denk bodies, and lobular inflammation, 95 patient biopsies (55%) were classified as definite AH, 55 (32%) as possible AH, and 22 (13%) as no AH. Survival was similar among the groups, but mortality was significantly increased for patients with fatty change ≤50% on initial liver biopsy. An analysis limited to uninfected patients with definite AH or no AH in the derivation cohort identified a greater leukocyte count at admission and radiographic evidence of liver surface nodularity as independent predictors of definite AH on biopsy (P < 0.05). In the derivation cohort, the leukocyte count thresholds for ensuring 100% specificity for diagnosing definite AH were 10 × 109/L if the liver surface was nodular and 14 × 109/L if the liver surface was smooth, with a sensitivity of 76% and an area under the receiver operator characteristic curve of 0.88. In the validation cohort, these thresholds had a specificity of 86%, a sensitivity of 59%, and an area under the receiver operator characteristic curve of 0.72. Conclusion: The combination of an elevated leukocyte count and a nodular liver surface in the absence of active infection retrospectively identified patients with a high likelihood of histologic AH for whom liver biopsy may not be necessary. For patients with suspected severe AH who do not fulfill these criteria, liver biopsy is important to exclude other variants of alcoholic liver disease. (Hepatology Communications 2017;1:1070–1084)

Specialty considerations in management of hepatitis C

Abstract Objective To provide an update on chronic hepatitis C virus (HCV) infections and the challenges of HCV management, using clinical case vignettes. Data sources Clinical guidelines from the American Association for the Study of Liver Diseases/Infectious Diseases Society of America, U.S. prescribing information, PubMed articles, and patient advocacy websites. Study selection At the authors' discretion based on relevance of information presented. Summary Despite the availability of curative therapies, chronic HCV infections pose a substantial health care burden. Interest in chronic HCV management increased with new drug approvals; however, concerns about cost of therapy continue to limit patient access to treatment. Criteria used to determine HCV treatment candidacy, including staging of liver disease and need for liver biopsy, alcohol and substance abuse screening, ability to use short-course therapy, challenges of geno-type 3 infection, and the potential pitfalls of strict restrictions during HCV therapy, are examined using clinical case scenarios. Although access to HCV therapy is improving nationally, restrictions continue to vary by state and payer. Conclusion Despite increasing options for highly effective HCV therapy, the HCV treatment landscape remains a dynamic challenge. Pharmacists need to be familiar with current treatment guidelines to successfully navigate patients into treatment and ultimately, to cure HCV infections.

Assessment of Liver Fibrosis Using Real-time Shear-wave Elastography for Patients with Hepatitis B e Antigen-negative Chronic Hepatitis B and Alanine Transaminase &lt;2 Times the Upper Limit of Normal

We assessed liver fibrosis using real-time shear-wave elastography (SWE) combined with liver biopsy (LB) for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) and alanine transaminase < 2 times the upper limit of normal and hepatitis B virus DNA < 2000 IU/ml. A total of 107 patients met the inclusion criteria. Real- ime SWE and ultrasoundassisted liver biopsies were consecutively performed. Fibrosis was staged according to the METAVIR scoring system. Analyses of receiver operating characteristic curve were performed to calculate the optimal area under the receiver operating characteristic curve for F0-F1 versus F2-F4, F0-F2 versus F3-F4, and F0-F3 versus F4 for real-time SWE. The most concurrent liver fibrosis degrees were between F1 and F2 for these HBeAg-negative CHB patients. Liver stiffness increased in parallel with the degree of liver fibrosis using SWE measurements. The area under the receiver operating characteristic curves was 0.881 (95% confidence interval [CI]: 0.704-1.000) for SWE (p = 0.004); 0.912 (95% CI: 0.836-0.987) for SWE (p = 0.000); 0.981 (95% CI: 0.956-1.000) for SWE (p = 0.000); 0.974 (95% CI: 0.936-1.000) for SWE (p = 0.000) when comparing F0 versus F1-F4, F0-F1 versus F2-F4, F0-F2 versus F3-F4, and F0-F3 versus F4, respectively. SWE has the advantage of providing an image of liver stiffness in real-time. As an alternative to LB, the development of all these noninvasive methods for dynamic evaluation of liver fibrosis will decrease the need for LB, making clinical care safer and more convenient for patients with liver diseases.

Performance of transient elastography and serum fibrosis biomarkers for non-invasive evaluation of recurrent fibrosis after liver transplantation: A meta-analysis.

Recurrent fibrosis after liver transplantation (LT) impacts on long-term graft and patient survival. We performed a meta-analysis to compare the accuracy of non-invasive methods to diagnose significant recurrent fibrosis (stage F2-F4) following LT. Studies comparing serum fibrosis biomarkers, namely AST-to-platelet ratio index (APRI), fibrosis score 4 (FIB-4), or transient elastography (TE) with liver biopsy in LT recipients were systematically identified through electronic databases. In the meta-analysis, we calculated the weighted pooled odds ratio and used a fixed effect model, as there was no significant heterogeneity between studies. Eight studies were included for APRI, four for FIB-4, and twelve for TE. The mean prevalence of significant liver fibrosis was 37.4%. The summary odds ratio was significantly higher for TE (21.17, 95% CI confidence interval 14.10–31.77, p = 1X10-30) as compared to APRI (9.02, 95% CI 5.79–14.07; p = 1X10-30) and FIB-4 (7.08, 95% CI 4.00–12.55; p = 1.93X10-11). In conclusion, TE performs best to diagnose recurrent fibrosis in LT recipients. APRI and FIB-4 can be used as an estimate of significant fibrosis at centres where TE is not available. Longitudinal assessment of fibrosis by means of these non-invasive tests may reduce the need for liver biopsy.

O-39 Tacrolimus intra-patient variability is an independent factor associated with the need for liver biopsy in paediatric liver transplant recipients

Background The intra-patient variability in tacrolimus exposure (TAC-IPV) after paediatric liver transplantation and its impact on patient outcomes has been poorly studied. The present study aims to investigate whether there is a trend in TAC-IPV during the first 5 years post transplantation, which variables influence IPV and wheth-er the IPV during the first year is associated with liver transplantation outcomes in paediatric patients. Methods We conducted a single centre retrospective study including 41 living paediatric patients transplanted between January 2003 and September 2016 at the Ghent University Hospital. The intra-patient variability in the dose-adjusted tacrolimus pre-dose concentrations was calculated yearly during the first five years following trans-plantation, expressed as coefficient of variation (CV%1–5) The difference in CV% in the years following transplanta-tion was analysed using the Friedman test. A linear uni-variate and multivariate regression analysis was applied to identify factors associated with TAC-IPV. The following parameters were tested: age, gender, origin, the number of missed clinic appointments as a surrogate marker for ther-apy adherence, the total number of medications, concom-itant medications potentially interfering with TAC metabo-lism-CYP3A4/A5 inductors or inhibitors and biochemical parameters. Logistic and linear regression models were fit-ted to test an association of TAC-IPV with patient outcomes: need for biopsy during year 1, 3 and 5; hypertension and renal function at 1, 3 and 5 years; acute rejection and CMV/EBV viremia during year 1 post-transplantation. Results We identified a significant decrease in TAC-IPV during the first 3 years after transplantation with the me-dian CV%1=39,4%; CV%2=30,9%; CV%3=28,5% (p=0,004), after which the CV% reaches a plateau (CV%4=23,6% en CV%5=28,9%). Multivariate analysis showed that serum albumin in the first year (p=0,029), haematocrit in the third year (p=0,019) and the number of missed clin-ic appointments in the fifth year after transplantation (p=0,009) were associated with TAC-IPV.in the 1 st, 3rd and 5th year, respectively. Univariate analysis showed that CV%1 was significantly associated with the need for bi-opsy during the first year post-transplantation (p=0.036) and the occurrence of one or more episodes of acute al-lograft rejection during the first year post-transplantation (p=0.031). In univariate analysis a trend was observed for association with hypertension one year after transplan-tation (p=0,085). Multivariate logistic regression analysis confirmed that CV%1 was an independent factor associ-ated with the need for liver biopsy in the first year follow-ing liver transplantation. (p=0.05; Exp(B)=1.045). Conclusion As expected, tacrolimus intra-patient vari-ability is higher during the first two years after transplantation. Our results suggest that while albumin and hae-matocrit are associated with TAC-IPV in the first 3 years, therapy adherence expressed as the number of missed clinic appointments is associated with TAC-IPV after a longer follow-up. A high TAC-IPV during the first year was an independent factor associated with the need for liver biopsy. Our results therefore highlight the importance of monitoring the variability of the tacrolimus trough levels.

Clinical Application of Vibration Controlled Transient Elastography in Patients with Chronic Hepatitis B.

Evaluation of the extent and progression of liver fibrosis and cirrhosis is of critical importance in the management and prognosis of patients with chronic hepatitis B. Due to the limitation of liver biopsy, non-invasive methods, especially liver stiffness measurement (LSM) by vibration controlled transient elastography, have been developed and widely applied for liver fibrosis assessment. LSM aims to reduce, but not to substitute, the need for liver biopsy for fibrosis/cirrhosis diagnosis. While LSM may have potential utility in monitoring treatment response, its applications in prediction of liver complications in terms of portal hypertension and esophageal varices, as well as disease prognosis, have been gradually validated. Here, we review the latest clinical applications of LSM in patients with chronic hepatitis B.