Liver Biopsy Evaluation Research Articles

Optimized contrast-enhanced ultrasonography for characterization of focal liver lesions in cirrhosis: A single-center retrospective study.

Hepatocellular carcinoma (HCC) is the leading cause of death amongst cirrhotic patients. Its diagnosis and discrimination from non-HCC malignant lesions in cirrhosis includes contrast enhanced computed tomography (CECT), contrast enhanced magnetic resonance imaging (CEMRI), or, in selected cases, liver biopsy. The role of contrast-enhanced ultrasonography (CEUS) is still controversial. To evaluate whether, by selecting an appropriate 'time to wash-out' cut-off value, CEUS capability of discriminating between HCC and non-HCC malignancies in cirrhotic patients may be enhanced. We enrolled 282 cirrhotic patients who underwent CEUS at our institute, from January 2008 to January 2012, for focal liver lesions (FLLs) detected at ultrasound (US). We used liver biopsy and subsequent histological evaluation as the gold standard for correct classification of FLLs. We calculated the area under receiver operator characteristic curves for CEUS to distinguish patients with HCC from those with non-HCC malignancies. The best 'time to wash-out' cut-off values were selected. HISTOLOGICAL DIAGNOSIS OF FLLS WAS AS FOLLOWS: 34 benign lesions (i.e. 25 regenerative nodules and 9 dysplastic nodules) and 248 malignant lesions (223 well-to-moderately differentiated HCCs; 7 poorly-differentiated HCCs; 5 intrahepatic colangiocellular carcinomas (ICCs); 5 primary non-Hodgkin B-cell lymphomas (NHBLs); and 8 metastatic liver tumors). A time to wash-out > 55 s identified patients with HCC with the highest level of accuracy (92.7%). Similarly, a time to wash-out ≤ 55 s correctly identified the vast majority of the non-HCC malignancies (100% sensitivity, 98.2% specificity and diagnostic accuracy of 98.3%). CEUS is an accurate and safe procedure for discriminating FLLs in cirrhotic patients, especially when a cut-off time to wash-out of 55 s is chosen as a reference value.

Insulin-Like Growth Factor-I and -II Levels Are Associated with the Progression of Nonalcoholic Fatty Liver Disease in Obese Children

To correlate circulating levels of insulin-like growth factor (IGF)-I, IGF-II, and IGF binding protein (IGFBP)-3 in a population of obese children with biopsy-proven nonalcoholic fatty liver disease (NAFLD) with clinical, biochemical, and histological features. We conducted a cross-sectional study at the Hepatometabolic Unit of the Bambino Gesù Children's Hospital, Rome, Italy. Obese children (42 girls and 57 boys) underwent liver biopsy, anthropometry, biochemical assessment, and IGF system evaluation. Serum concentrations of IGF-I, IGF-II, and IGFBP-3 were measured. The liver biopsy features of each case were graded according to the NAFLD Activity Scoring system. The degrees of steatosis, inflammation, ballooning, and fibrosis were calculated. Nonalcoholic steatohepatitis was diagnosed in 14/99 obese subjects. Stepwise regression analysis revealed that IGF-I was the major predictor of ballooning (β = -0.463; P < .0001) and NAFLD activity score (β = -0.457; P < .0001), IGF-I/IGFBP-3 ratio was the major predictor of liver inflammation (β = -0.285; P = .005), and IGF-II was the major predictor of liver fibrosis (β = 0.343; P < .005). Circulating levels of IGF-I and IGF-II are associated with the histological stages of NAFLD and may represent novel markers of liver damage progression in obese children.

Pegylated IFN-α regulates hepatic gene expression through transient Jak/STAT activation

The use of pegylated interferon-α (pegIFN-α) has replaced unmodified recombinant IFN-α for the treatment of chronic viral hepatitis. While the superior antiviral efficacy of pegIFN-α is generally attributed to improved pharmacokinetic properties, the pharmacodynamic effects of pegIFN-α in the liver have not been studied. Here, we analyzed pegIFN-α-induced signaling and gene regulation in paired liver biopsies obtained prior to treatment and during the first week following pegIFN-α injection in 18 patients with chronic hepatitis C. Despite sustained high concentrations of pegIFN-α in serum, the Jak/STAT pathway was activated in hepatocytes only on the first day after pegIFN-α administration. Evaluation of liver biopsies revealed that pegIFN-α induces hundreds of genes that can be classified into four clusters based on different temporal expression profiles. In all clusters, gene transcription was mainly driven by IFN-stimulated gene factor 3 (ISGF3). Compared with conventional IFN-α therapy, pegIFN-α induced a broader spectrum of gene expression, including many genes involved in cellular immunity. IFN-induced secondary transcription factors did not result in additional waves of gene expression. Our data indicate that the superior antiviral efficacy of pegIFN-α is not the result of prolonged Jak/STAT pathway activation in hepatocytes, but rather is due to induction of additional genes that are involved in cellular immune responses.

Comparison of transient elastography, 13C-Methacetin meta-bolism, and liver biopsy for evaluation of fibrosis in chronic hepatitis C infection

Comparison of transient elastography, 13C-Methacetin meta-bolism, and liver biopsy for evaluation of fibrosis in chronic hepatitis C infection

Consensus on the histopathological evaluation of liver biopsies from patients following allogeneic hematopoietic cell transplantation

After allogeneic hematopoietic cell transplantation (alloHCT) liver biopsy is performed for enigmatic liver disorders when noninvasive diagnostic steps have failed in establishing a definitive diagnosis. This document provides an updated consensus on the prerequisites for proper evaluation of liver biopsies in alloHCT patients and the histological diagnostic criteria for liver graft-versus-host disease (GvHD). The Working Group's recommendations for the histological diagnosis of liver GvHD were derived from the peer-reviewed literature and from the consensus diagnosis of a total of 30 coded liver biopsies. Acceptance of the recommendations was tested by a survey distributed to all HCT centers in Austria, Germany and Switzerland. Consensus was achieved for biopsy indications, methods of sample acquisition and processing, reporting and interpretation of biopsy findings. As GvHD is variably treated and the treatment modalities have changed over time, the panel endorses the use of more frequent biopsies in clinical studies in order to improve the present challenging clinical and diagnostic situation.

Chronic viral hepatitis in patients with ultrasound-guided percutaneous cutting needle liver biopsy evaluation

Chronic viral hepatitis in patients with ultrasound-guided percutaneous cutting needle liver biopsy evaluation

Can aminotransferase-to-platelet ratio index and other non-invasive markers effectively reduce liver biopsies for renal transplant evaluation of hepatitis C virus-positive patients?

Advanced fibrosis or cirrhosis is still regarded as a contraindication for kidney transplantation alone by most centers. The value of aminotransferase to platelet ratio index (APRI) and other non-invasive markers has been less studied in hepatitis C virus (HCV)-positive patients with concurrent end-stage renal disease to predict hepatic fibrosis. Can these be used to effectively decrease the number of biopsies done in these patients being evaluated for transplantation? Our study population included 255 patients with liver biopsy data. All patient information was collected and reviewed from medical records. The diagnostic accuracy of the predictive models was analyzed by calculating sensitivity, specificity, positive predictive value and negative predictive value. The variables associated with F3-F4 were aspartate aminotransferase (P = 0.007), bilirubin (P ≤ 0.001), platelet count (P = 0.01) and APRI (P ≤ 0.001). The use of any one laboratory abnormality to predict liver biopsy scores did not show high positive predictive values (22.6-72.7%). Having abnormal liver findings or cirrhosis on imaging was associated with high specificities (92.0-97.8%) but low sensitivities (31.4-42.9%). Using APRI levels of ≥0.40 and ≤0.95 as an indication for liver biopsy, 50% of patients with F3-F4 would have correctly avoided having a biopsy. However, 33% of patients with F3-F4 would have been mislabeled and not be indicated for biopsy. Our data suggest that there may not currently be a simple and sufficiently accurate non-invasive test to replace liver biopsy in renal transplant workup for HCV-positive patients. The risks outweigh the benefits when it comes to using non-invasive markers like the APRI.

Urinary excretion of copper, zinc and iron with and without D-penicillamine administration in relation to hepatic copper concentration in dogs

Hereditary copper-associated hepatitis in dogs resembles Wilson’s disease, a copper storage disease in humans. Values for urinary copper excretion are well established in the diagnostic protocol of Wilson’s disease, whereas in dogs these have not been evaluated. The objectives of this study were to characterize both basal and D-penicillamine induced urinary copper, zinc and iron excretion in dogs in relation to hepatic copper concentration. Beagles, Beagle-Bedlington terrier cross-breeds homozygous for the COMMD1 gene mutation that causes copper toxicosis, and Labrador retrievers with normal or increased hepatic copper concentrations were investigated. The hepatic copper phenotype was determined by histological evaluation of liver biopsies and measurement of the hepatic copper concentration by instrumental neutron activation analysis. Urinary excretion of copper, iron and zinc was measured via inductively coupled plasma optical emission spectrometry under basal conditions and after oral administration of a single dose (20mg/kg bodyweight) of the chelator D-penicillamine.There was a rapid increase in urinary excretion of copper and zinc, but not iron after D-penicillamine administration. This increase was not different between dogs with high or normal hepatic copper concentrations. D-penicillamine-induced urinary copper excretion and the copper/creatinine ratio did not correlate with hepatic copper concentrations in the dogs studied, although basal urinary copper/zinc ratios did correlate with hepatic copper concentrations in Labrador retrievers. The latter parameter may be useful in diagnostic and follow-up protocols for copper-associated hepatitis in Labrador retrievers.

A Unifying Ontology to Integrate Histological and Clinical Observations for Drug-Induced Liver Injury

Drug-induced liver injury (DILI) may present any morphologic characteristic of acute or chronic liver disease with no standardized terminology in place. Defining lexemes of DILI histopathology would allow the development of advanced knowledge discovery and data mining tools for across comparisons of publicly available information. For these purposes, a DILI ontology (DILIo) was developed by using the Unified Medical Language System tool and the standardized terminology of the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT). The DILIo was entrained on findings of 114 US Food and Drug Administration-approved drugs by extracting all clinically DILI-related histopathologic descriptions for 1082 liver biopsy samples, which were then analyzed using the Unified Medical Language System MetaMap and subsequently mapped to the SNOMED CT. The DILIo provides a standard means to describe and organize liver injury induced by drugs, enabling comparative analysis of drugs within and across histopathologic terms. The analysis showed that flutamide, troglitazone, diclofenac, isoniazid, and tamoxifen were reported to have the most diverse histopathologic observations in liver biopsy. Necrosis, cholestasis, fatty degeneration, fibrosis, infiltrate, and hepatic necrosis were the most frequent terms used as descriptors of histopathologic features of DILI. In conclusion, DILIo entrains different algorithms for an efficient meta-analysis of published findings for an improved understanding of mechanisms and clinical characteristics of DILI.

Evaluation of Transjugular Liver Biopsy in the Diagnosis of Early Hepatic Dysfunction After Allogeneic Hematopoietic Cell Transplantation

Evaluation of Transjugular Liver Biopsy in the Diagnosis of Early Hepatic Dysfunction After Allogeneic Hematopoietic Cell Transplantation

Genetic Risk Factors for Drug-Induced Liver Injury in Rheumatoid Arthritis Patients Using Low-Dose Methotrexate

Low-dose methotrexate (MTX) is part of the mainstay of rheumatoid arthritis treatment. Hepatotoxicity is among the most feared side effects of low-dose MTX and is associated with increased morbidity. At present, histological evaluation of liver biopsies is the gold standard to retrospectively diagnose MTX-induced liver damage. Genetic markers present an interesting opportunity to preemptively identify patients at risk for MTX-induced hepatotoxicity. Here, we will review the literature on candidate genetic markers for the risk of MTX-induced hepatotoxicity. These candidate genetic markers include polymorphisms in the gene encoding the enzyme MTHFR.

Prospective Evaluation of Accuracy of Liver Biopsy Findings in the Identification of Chemotherapy-Associated Liver Injuries

OBJECTIVE To evaluate the accuracy of liver biopsy findings in preoperative assessment of chemotherapy-associated liver injuries (CALIs). DESIGN Prospective study. SETTING Tertiary care referral hospital. PATIENTS From July 1, 2007, to January 31, 2011, all patients with colorectal metastases receiving preoperative oxaliplatin- and/or irinotecan-based chemotherapy (≥4 cycles) were considered for the present study. Patients underwent parenchymal biopsy before liver resection. Blinded CALI evaluation was performed on biopsy and resection specimens. INTERVENTION Liver resection. MAIN OUTCOME MEASURES Sensitivity, specificity, and accuracy of liver biopsy in CALI evaluation. RESULTS We included 100 patients. At specimen analysis, grade 2or 3 steatosis was diagnosed in 30 patients; grade 2 or 3 sinusoidal dilatation, in 28; grade 2 hepatocellular ballooning, in 3; grade 2 or 3 lobular inflammation, in 25; and steatohepatitis in 19. Obesity was associated with grade 3 steatosis (20.8% vs 5.3%; odds ratio [OR], 4.74 [P=.03]) and steatohepatitis (33.3% vs 14.5%; OR, 2.96 [P=.04]). Oxaliplatin administration was associated with higher sinusoidal dilatation grade (P=.049). Mortality (2 cases) was increased among patients with steatohepatitis (10.5% vs 0; OR, 13.67 [P=.04]). Biopsy findings correctly predicted steatosis (sensitivity, 88.9%; accuracy, 93.0%) but had low sensitivity and accuracy for sinusoidal dilatation (21.4% and 63.0%, respectively), hepatocellular ballooning (16.0% and 69.0%, respectively), lobular inflammation (20.0% and 78.0%, respectively), and steatohepatitis (21.1% and 79.0%, respectively). Biopsy accuracy did not improve regarding specific chemotherapy regimens or prolonged treatments. CONCLUSIONS Liver biopsy cannot be considered a reliable tool in assessing CALIs except for steatosis. The procedure should not be recommended during preoperative workup.

Hepatorenal Index as an Accurate, Simple, and Effective Tool in Screening for Steatosis

The hepatorenal index has been reported to be a sensitive and noninvasive test to quantify steatosis, but it is cumbersome and time-consuming and requires specialized software. The aim of this study was to improve and simplify the hepatorenal index calculation and determine whether it is an effective tool for differentiating patients with steatosis from those without steatosis, thereby eliminating the need for biopsy in a large number of patients. One hundred one patients who had undergone ultrasound-guided percutaneous liver biopsy at our institution were selected from a patient database. Patients with renal disease, patients with liver masses, and patients whose liver and right kidney were not included on the same image were excluded. Images were acquired with high-resolution ultrasound, and the hepatorenal index was calculated using freeware based on comparison of hepatic and renal brightness. Of the 101 patients, 63 had 5% or less steatosis and 38 had more than 5% steatosis. Using freeware available online from the National Institutes of Health, we calculated hepatorenal index values for all patients. Our data showed a strong correlation between the hepatorenal index and percentage of fat (r = 0.71, p < 0.0001). A hepatorenal index of 1.28 or greater had a 100% sensitivity for identifying more than 5% fat, 54% specificity, 0.57 positive predictive value, and 1.0 negative predictive value. If this method had been used prospectively to select patients for biopsy in our sample, 34% of biopsies could have been avoided. The hepatorenal index is a simple, reliable, and cost-effective screening tool for identifying patients who should not undergo liver biopsy for evaluation of steatosis.

Real-time elastography as a noninvasive technique for quantification of fibrosis in patients with chronic viral liver disease: Preliminary findings

IntroductionReal-time elastography (RTE) is a novel technique for measuring tissue elasticity. The aims of this study were to prospectively measure liver stiffness with RTE in patients with chronic viral hepatitis and to evaluate the possible correlation between RTE data and the extent of fibrosis based on liver biopsy findings (Ishak score). Material and methodsBetween February and October 2011, 26 patients (18M, 8F, mean age 41 ± 13 [standard deviation], range 22–62) with chronic viral hepatitis were prospectively evaluated with ultrasonography (US) that included RTE. All patients then underwent US-guided percutaneous liver biopsy (right lobe) for evaluation of fibrosis. Examinations were performed with a iU22 scanner (Philips, Bothell, WA, USA); a convex transducer (C5-1) was used for the US examination, and a linear transducer (L12-5) for RTE. In the RTE images, relative tissue stiffness is expressed according to a color scale with soft areas represented in green/red and hard areas in blue. Patients were examined in the supine position in suspended normal respiration; three loops of 20 RTE frames were recorded for each case. For each patient, we calculated the mean strain ratio (MSR) for the 3 loops. The Spearman correlation coefficient was used to assess correlation between the ASR and fibrosis stage (F) reflected by the Ishak score. ResultsThe Spearman coefficient showed significant correlation between the MSR and F (Rho = 0.470, p = 0.015). ConclusionsRTE appears to be a useful tool for noninvasive evaluation of fibrosis in patients with chronic viral hepatitis although these findings need to be confirmed in larger case series.

Transient elastography and serum biomarkers: two-step screening methods for liver fibrosis in non-alcoholic fatty liver disease before liver biopsy

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease and nowadays it is recognized as one of main leading cause of liver fibrosis worldwide. Because of the high risk to develop cirrhosis and hepatocellular carcinoma, the early assessment of liver fibrosis is an important part of the management of NAFLD patients. To date, histological evaluation of liver biopsy represents the cornerstone for staging and grading liver fibrosis. However, due to the several drawbacks of this approach, during the last decade clinicians and researchers are dedicating their efforts to the identification of novel, safe and effective non-invasive tools to assess liver fibrosis. As due to their accuracy degree, transient elastography (TE) and serum biomarkers seem to be able to replace liver biopsy to determine at least the presence of significant liver fibrosis. The combination of these tools may greatly enhance their diagnostic power. Nevertheless, investigations of new imaging techniques and the molecular pathogenesis of NAFLD are necessary to develop reliable non-invasive alternative approaches to liver biopsy. Here, the authors discuss the salient aspects of diagnostic performance of TE and serum biomarkers available for detecting hepatic fibrosis in NAFLD and provide suggestions as to how these non-invasive techniques can be incorporated into diagnostic management of patients affected by this disease.

Ultrasonography as a non-invasive tool for detection of nonalcoholic fatty liver disease in overweight/obese Egyptian children

IntroductionLiver biopsy, although a gold standard in diagnosis of nonalcoholic fatty liver disease (NAFLD), is an invasive and expensive tool. AimTo assess the diagnostic accuracy of abdominal ultrasound in detecting NAFLD among a group of overweight/obese children having one or more liver abnormality (clinical hepatomegaly, raised ALT or echogenic liver parenchyma by ultrasound). MethodsSeventy-eight overweight/obese children were referred to the Pediatric Hepatology Unit, Cairo University Pediatric Hospital, Egypt, for assessment for hepatic abnormalities. Out of the 78 children, 34 had one or more abnormality in the form of clinical hepatomegaly, raised alanine aminotransferase (ALT) and/or echogenic liver parenchyma by ultrasound. All 34 cases underwent liver biopsy for evaluation for NAFLD. ResultsHistological NAFLD was detected in 15 cases; 8 simple steatosis and 7 nonalcoholic steatohepatitis (NASH). Sonographic evaluation of hepatic parenchymal echogenicity revealed: 11 with grade 1 echogenicity, 12 with grade 2 and 9 with grade 3 while only 2 had normal liver echopattern. Ultrasonography was 100% sensitive and 100% specific in detecting histological NAFLD, while the positive predictive value (PPV) was 47% and negative predictive value (NPV) was 11%. After consolidating the included children into 2 groups: the first including normal and grade 1 echogenicity and the second including grades 2 and 3, the sensitivity of ultrasonography in detecting histological NAFLD was still 100%, while negative predictive value increased to 100% with an accuracy of 82%. ConclusionWe conclude that ultrasonography is an important non invasive tool in assessment for NAFLD. Normal or grade 1 hepatic echogenicity can soundly exclude histological NAFLD and obviates the need for liver biopsy.

Widespread epithelioid angiosarcoma with ventricular wall involvement in a dog.

This paper reports on a canine angiosarcoma, presenting as an "undifferentiated metastasizing tumor". A 14-year-old female Cocker Spaniel was referred to the University of Extremadura Veterinary Clinic for clinical examination after suffering rapid deterioration, with chronic cough, anorexia and cachexia. One week after clinical examination, the dog died of right congestive heart failure and ventricular arrhythmia. Blood counts revealed lymphopenia and platelet depletion. The biochemistry profile was within normal limits, except for a drop in blood urea nitrogen. Cytological evaluation of liver and spleen biopsies revealed clustered anaplastic cells that lacked convincing tissue differentiation. Major findings at necropsy were enlarged spleen and multiple, beige to dark-red nodules ranging from 0.5 to 3 cm in diameter in the heart, lung, liver and spleen. At histological examination, multiple nests of anaplastic epithelioid cells were found in sections from all affected organs. Immunohistochemistry revealed widespread expression of CD31 and Factor VIII-related antigen. The neoplastic cells were negative for CD 18. The diagnosis of epithelioid angiosarcoma, localized in the myocardium, lung, liver and spleen was made. The primary site of the neoplasm could not be determined.

Nonalcoholic Fatty Liver Disease: Pathologic Patterns and Biopsy Evaluation in Clinical Research

Nonalcoholic fatty liver disease (NAFLD) results in histologically complex specific and nonspecific injury patterns. In clinical research of NAFLD, the liver biopsy evaluation provides a wealth of information on the architectural arrangement and severity of a variety of histologic changes, including steatosis, inflammation, cellular injury, and fibrosis. This information is summarized as an overall diagnostic category, such steatosis or steatohepatitis and the severity of the injury can be graded and staged. Histopathologic disease classification in NAFLD is related to but separate from evaluation of individual histologic lesions. The patient population under study may affect the prevalence of histologic findings and in particular, pediatric patients with NAFLD may show a higher prevalence of zone 1 steatosis and periportal fibrosis as compared with adult populations. For the purposes of clinical research, it is important to provide the pathologist with biopsies that are adequate to classify the disease process as well as to grade and stage the changes. A current understanding of NAFLD pathologic classification, as well as nuances of grading and staging, is presented in this review.

Longitudinal Analysis of Serial Liver Biopsies in Chronically Transfused Sickle Cell Disease

Abstract 1052▪▪This icon denotes a clinically relevant abstract Background:Chronic red cell transfusions are commonly used for the treatment and prevention of complications in sickle cell disease (SCD). Liver injury from transfusional iron overload is a recognized morbidity of chronic transfusion therapy, but little is known about the progression of liver injury over time in SCD. Methods:We conducted a retrospective cohort study of all chronically transfused people with SCD who had 2 or more serial liver biopsies at a single academic hospital. Subjects with viral hepatitis were excluded. Serum ferritin, serum ALT, chelation status, and transfusion volumes were extracted from the electronic record and validated against paper records in all subjects. Quantitative liver iron concentration (LIC) was determined at the time of biopsy by inductively coupled plasma-mass spectrometry. Core liver biopsy slides stained for iron and fibrosis were retrieved and scored in a blinded fashion by a hepatopathologist (RA) for total iron score (TIS, Deugnier, 2007) and fibrosis score (Ishak, 1995). Analyses evaluated how liver fibrosis changed over the first 2 biopsies and how changes in biomarkers correlated with changes in fibrosis. Cross sectional analyses assessed the relationship of biomarkers to the presence or absence of fibrosis. Ferritin was analyzed as an average of the 3 closest values ± 6 weeks of liver biopsy. Area under receiver operator characteristic curve (AUC) analysis, likelihood ratios for positive tests (LR+), and summary statistics were calculated using Stata v11.2. Results:26 people had at least 2 serial core liver biopsies for evaluation (n=70 biopsies total, range 2–7 biopsies per subject). Fibrosis was Ishak grade 0 or 1 in all biopsies. Median age at first biopsy was 13.3 years and median total transfusion duration was 9.4 years. The first 2 biopsies were obtained a median of 2.3 years apart. Evaluation of the first 2 biopsies showed that fibrosis was present in 7/26 initial biopsies and 3/26 second biopsies: fibrosis regressed in 6 subjects, developed in 2 subjects and persisted in 1 subject. Among non-chelated subjects at the time of first biopsy, 2/11 had fibrosis, as compared to 5/15 subjects who had received a mean of 3.7 years of chelation at the time of first biopsy (18% vs 33%, P=0.6). Eleven subjects had 3 or more serial biopsies performed during a median of 9.2 years of chronic transfusion. There was no consistent pattern of fibrosis development, nor was there an apparent association of fibrosis with LIC over time (Figure, asterisks indicate presence of fibrosis). On a cross-sectional basis, ALT performed better than ferritin in classifying fibrosis, with ALT having an AUC of 0.80 (95% CI 0.66–0.94) and ferritin having an AUC of 0.63 (95% CI 0.38–0.87). LIC performed poorly at discriminating fibrosis from no fibrosis (AUC 0.30; 95%CI 0.0–0.82). The highest positive likelihood ratios for fibrosis were for a ferritin cutoff of 5000 ng/mL (LR+ 5.7) and an ALT cutoff of 65 U/L (LR+ 5.2). Longitudinal analysis did not reveal any statistically significant relationship between changes in fibrosis status and changes in ferritin, ALT, LIC, TIS, and cumulative red cell transfusion volume. Summary:Among chronically transfused people with SCD, liver fibrosis most often does not persist or progress, as detected by serial core liver biopsies. On a cross-sectional basis, serum ALT >65 U/L and serum ferritin >5000 ng/mL are cutoffs associated with the highest likelihood of liver fibrosis. Cross-sectional or longitudinal measurements of LIC are not associated with fibrosis. Conclusion:The progression of liver fibrosis is minimal among people with SCD who receive chronic red cell transfusions for up to 17 years. Serum biomarkers may be used to inform when investigations for fibrosis are warranted. Disclosures:No relevant conflicts of interest to declare.

Liver Biopsies in Chronic Viral Hepatitis: Beyond Grading and Staging

Knowledge of the etiology and pathogenesis of chronic viral hepatitis has grown immensely during the past 50 years. The terminology used to assess liver biopsies with chronic viral hepatitis and the role of the liver biopsy itself have also evolved during this time. Although the focus of much discussion regarding diagnostic assessment of liver biopsies in patients with viral hepatitis has been on grading of activity and staging of fibrosis, each biopsy is also an opportunity to assess many other important features. To discuss opportunities provided by biopsies to assess features such as the presence of virus-associated premalignant or malignancy-related changes, and the presence of other concomitant diseases, including fatty liver disease of diverse causes, and hemochromatosis, hereditary or otherwise. The data were obtained from published literature and professional experience. The evaluation of liver biopsies with chronic viral hepatitis has evolved beyond grading and staging. Pathologists need to be aware of the other features that may have important clinical implications.