Liver Biopsy Evaluation Research Articles

NAFLD: Reporting Histologic Findings in Clinical Practice.

The role of liver biopsy in NASH has evolved along with the increased recognition of the significance of this disease, and the unmet medical need it presents. Drug development and clinical trials are rapidly growing, as are noninvasive tests for markers of steatosis, inflammation, injury, and fibrosis. Liver biopsy evaluation remains necessary for both drug development and clinical trials as the most specific means of diagnosis and patient identification for appropriate intervention. This White Paper, sponsored by the American Association for the Study of Liver Disease NASH Task Force, is a focused review of liver biopsy evaluation in fatty liver disease in subjects with presumed NAFLD for practicing clinical hepatologists and pathologists. The goal is to provide succinct and specific means for reporting the histopathologic elements of NASH, distinguishing NASH from nonalcoholic fatty liver without steatohepatitis, and from alcohol-associated steatohepatitis when possible. The discussion includes the special situations of NASH in advanced fibrosis or cirrhosis, and in the pediatric population. Finally, there is discussion of semiquantitative methods of evaluation of lesions of "disease activity" and fibrosis. Tables are presented for scoring and a suggested model for final reporting. Figures are presented to highlight the histopathologic elements of NASH.

Magnetic resonance quantitative susceptibility mapping in the evaluation of hepatic fibrosis in chronic liver disease: a feasibility study.

Noninvasive methods for the early diagnosis and staging of hepatic fibrosis are needed. The present study aimed to investigate the alteration of magnetic susceptibility in the liver of patients with various fibrosis stages and to evaluate the feasibility of using susceptibility to stage hepatic fibrosis. A total of 30 consecutive patients with chronic liver diseases (CLDs) underwent magnetic resonance imaging (MRI) and liver biopsy evaluation of hepatic fibrosis, necroinflammatory activity, iron load, and steatosis. Quantitative susceptibility mapping (QSM), R2* and proton density fat fraction (PDFF) images were postprocessed from the same gradient-echo data for quantitative tissue characterization using region of interest (ROI) analysis. The differences for MRI measurements between cohorts of non-significant (Ishak-F <3) and significant fibrosis (Ishak-F ≥3) and the correlation of MRI measurements with fibrosis stages and necroinflammatory activity grades were tested. Receiver operating characteristic (ROC) analysis was also performed. There was a significant difference in liver susceptibility between the cohorts of significant and non-significant fibrosis (Z=-2.880, P=0.004). A moderate negative correlation between the stages of liver fibrosis and liver susceptibility was observed (r=-0.471, P=0.015). Liver magnetic susceptibility differentiated non-significant from significant hepatic fibrosis with an area under the receiver operating curve (AUC) of 0.836 (P=0.004). A highly sensitive diagnostic performance with an AUC of 0.933 was obtained using magnetic susceptibility and PDFF together (P<0.001). A noninvasive liver QSM-based evaluation promises an accurate assessment of significant fibrosis in patients with CLDs.

Role of Liver Biopsy in Assessment of Radiologically Identified Liver Masses.

Despite improvements in imaging techniques that have enhanced the ability to diagnose hepatocellular carcinoma (HCC), histopathological evaluation of many other types of liver masses is critical. To evaluate the utility of liver biopsy in patients with radiologically undiagnosed liver masses. We retrospectively analyzed 293 consecutive patients who had a liver biopsy for evaluation of an undiagnosed liver mass between January 2014 and January 2018. Out of 293 biopsies, 246 patients were found to have malignancy (84%), including 210 (72%) patients with metastatic malignancy and 36 with primary hepatic malignancies (20 HCC and 16 others). In the 47 patients without malignancy, 17 patients had necrotic abscess/granuloma, 16 patients had normal histology, eight patients had hepatic fibrosis/cirrhosis without malignant foci, and six patients had benign tumors. The most common primary lesion in patients with liver metastasis was breast carcinoma (32/293, 11%), followed by colon and pancreas (31 (each)/293, 11%), and lung (9%) adenocarcinomas. Histopathological analysis confirmed the presence of metastasis in 165/200 (83%) patients with a history of oncological malignancy and in 45/93 (48%) patients who had no malignancy history. In patients with a radiologically identified liver mass of unclear etiology, liver biopsy/histology made a diagnosis in 95% (277/293) of patients, including 84% (246/293) found to have an oncological malignancy. Liver biopsy/histology also identified malignancy in a high proportion of patients without known underlying cancer. We conclude that liver biopsy is valuable for evaluation of radiologically identified liver masses of unclear etiology.

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

BACKGROUNDAbnormal 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. AIMTo evaluate the diagnostic performance of ERCP and LB in patients with non-vascular post-LT complications.METHODSThis 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. RESULTSOf 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). CONCLUSIONIn 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.

Liver biopsy evaluation in chronic hepatitis b infection: ‘Back to basics’ - re-visiting semi-quantitative scoring systems

Context: Despite advances in understanding into the pathophysiology of chronic hepatitis B, liver biopsy evaluation on H&E stained sections has stood the test of time. There is therefore, a need to re-visit the most commonly used scoring systems with an aim to look for an ideal semi-quantitative system which is objective, simple to apply and versatile enough to incorporate newer advances. Aims: To compare various semi-quantitative scoring systems with a view to (a) look for consistency in reporting, (b) assess usefulness in follow-up and (c) recommend a scoring system that is practical and easy to apply. Settings and Design: Chronic hepatitis B was defined as HBsAg positive status for at least six months. All liver biopsies were evaluated using semi-quantitative scoring systems viz the Knodell, Ishak’s modified HAI and Scheuer systems. Materials and Methods: Baseline biopsies were assessed for intra- and inter-observer variation in order to find the system best suited for routine use. The observer variation was also calculated separately for portal, peri-portal and lobular inflammation as well as for fibrosis. Statistical Analysis used: A Kappa analysis up to 95% confidence interval was done to look for statistical significance of inter- and intra-observer agreement between the three scoring systems. Results: On multivariate Kappa analysis, it was found that both inter- and intra-observer agreement were comparable in the Knodell and Ishak systems, and was significantly better with the Scheuer system. Further, agreement was better with fibrosis than with necro-inflammatory scores. Conclusions: The authors recommend Ishak’s modified system as it conveyed the most relevant and exhaustive information. Keywords: Chronic hepatitis B, Ishak’s system, Knodell’s system, Liver biopsy, Scheuer system, Semi-quantitative scoring systems.

Comparative evaluation of fibroscan, liver biopsy and non-invasive serum markers for assessment of hepatic fibrosis in chronic liver disease

Introduction: Chronic liver disease is a disease of the liver that lasts over a period of six months or more, involving a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis.In this study, we have compared three main tools to assess liver fibrosis including fibroscan, liver biopsy and non-invasive biomarkers. Materials and Methods: Inthis prospective study, a total of 30 cases of chronicliver disease were included. Fibrosis stage was assessed using fibroscan. In liver biopsy, Grading of fibrosis was done by modified activity grading system and staging was done using Ishak staging system. Serum markers were analysed using various scoring systems including AST/ALT ratio (AAR), AST/platelet ratio index (APRI), FIB-4 index and Forn Index. The obtained results were analyzed and evaluated using chi square test and area under receiver operator characteristic curve (AUROC) using SPSS version 20. Results: A significant association was found between fibroscan and Ishak fibrosis stage (p 0.049), fibroscan and APRI (p 0.02) and FIB-4 and liver biopsy (p 0.03). AAR and Forn index did not have any significant association with either fibroscan (p 0.969 and 0.889) or liver biopsy (p 2.56 and 0.98). Conclusion: The accuracy of fibroscan in evaluating fibrosis is comparable to that of liver biopsy. Thus, liver biopsy can be replaced with fibroscan in the future. Though, the non-invasive biomarkers are useful in assessing fibrosis, a combination of these markers may perform better than each alone. Keywords: Chronic liver disease, Liver biopsy, Fibroscan, Non invasive biomarkers.

S1808 Gastrointestinal Manifestation of Hypereosinophilic Syndrome

INTRODUCTION: Hypereosinophilic syndrome (HES) is a rare disorder of eosinophil accumulation that can affect any organ leading to heterogeneous presentations. Diagnosis is often delayed due to nonspecific symptoms. The authors present a rare case of hypereosinophilia with recurrent gastrointestinal (GI) symptoms. CASE DESCRIPTION/METHODS: A 45-year-old Vietnamese female with history of asthma initially noted four months of dyspnea, lower extremity edema, abdominal distension, and transient rash. She then presented to the ER with persistent abdominal pain, nausea, vomiting, and diarrhea. Serology was notable for WBC 11.1 × 103/uL with 36.8% eosinophils, albumin 2.3 g/dL, total bilirubin 2.9 mg/dL. CT was significant for moderate hepatomegaly, abdominal ascites, diffuse intestinal wall thickening. Peritoneal fluid had 44% eosinophils, SAAG of 0.9 g/dL. ESR, CRP, and serum immune-electrophoresis were elevated, but autoimmune and stool studies for malabsorption and infections were negative. Ascites, hypoalbuminemia and hyperbilirubinemia suggested infiltrative hepatic disease, but liver chemistries were normal and she declined liver biopsy for further evaluation. Endoscopic exam found erosions, erythema and friability in the entire duodenum and terminal ileum. Random biopsies showed focal eosinophilic crypt abscess. Treatment with prednisone was delayed due to suspicion of lymphatic filariasis (filaria antibody 5.94, positive IgG4). Unfortunately, patient was lost to follow up and was re-admitted a few months later for continued abdominal symptoms and fluid overload. Incidental observation of “jellied” blood prompted evaluation of serum viscosity, notably elevated at 15.5. Despite plasma exchange, she developed unilateral paralysis with diffuse multifocal arterial and venous thrombi. Further work up with bone marrow biopsy, cytogenetics with fluorescent in-situ hybridization were negative for alternative causes of eosinophilia. DISCUSSION: Over 10 months, the patient developed multisystem idiopathic HES with components of atypical eosinophilic granulomatosis with polyangiitis. Serology improved with corticosteroid and rituxan. She ultimately made a full recovery on prednisone. This case describes the multifarious presentations of eosinophil deposition within the GI tract. Given its nonspecific presentation and potential to progress to debilitating systemic manifestations, a high index of suspicion for HES is advised when hypereosinophilia is observed peripherally and at other sites.Figure 1.: CT abdomen and pelvis. Patient had mild to moderate hepatomegaly, mild ascites, diffuse wall thickening involving small and large bowel loops which may be related to infectious/inflammatory process, mildly enlarged retroperitoneal mesenteric lymph node that are reactive.Figure 2.: Endoscopic image of duodenal bulb. Endoscopies showed diffuse moderate inflammation with edema, erythema, erosions, and friability.Figure 3.: Random colon biopsy with H&E stain, 400x A single eosinophilic crypt abscess can be seen. Note surrounding eosinophilia in the lamina propria (arrows).

S3523 Rare Complication of Liver Biopsy

INTRODUCTION: Bleeding from the hepatobiliary tract is an unusual cause of the acute upper gastrointestinal bleed. Liver biopsy is deemed a safe and highly effective procedure to diagnose numerous liver conditions. Since its introduction at the end of the 19th century, modern imaging methods, special needles, and clinical experience have significantly reduced the rate of complications associated with liver biopsy. Hemoperitoneum, sub-capsular hematoma, pneumothorax, sepsis, and haemobilia are rare complications associated with liver biopsy. We are presenting a case of haemobilia, which resulted as a complication of liver biopsy and its management. CASE DESCRIPTION/METHODS: A 62-year-old male presented after an episode of hematemesis, severe right upper abdominal pain, jaundice, and melena after transjugular liver biopsy for evaluation of autoimmune hepatitis. Abdominal ultrasound showed dilated common bile duct (CBD), indicating biliary obstruction. Upper endoscopy, however, showed no signs of ongoing or old bleeding. These findings were followed by endoscopic retrograde cholangiopancreatography (ERCP) with discovery of blood clots in the CBD, revealing the diagnosis of haemobilia. The blood clots were removed and followed by placement of a plastic stent in the CBD. The patient, however, underwent a repeat ERCP with replacement of CBD stent as he continues to have melena requiring multiple blood transfusions. After the deployment of metal stent, patient's abdominal pain started to improve and his hemoglobin level stabilized. The third ERCP was performed 4 days later, which confirmed the resolution of haemobilia. The patient's symptoms continued to improve and was discharged after 29 days of hospitalization. DISCUSSION: Percutaneous or transjugular liver biopsies are performed very frequently for evaluation of causes of liver conditions in a safe and effective way. Complications associated with liver biopsy are uncommon, but severe complications do occur. Our case illustrates a distinctive way of managing such rare complication with advanced techniques like biliary stenting.

Evaluation of the Hepatorenal B-Mode Ratio and the "Controlled Attenuation Parameter" for the Detection and Grading of Steatosis.

The aim of this study was to evaluate the hepatorenal index ratio of Supersonic Imagine (B-mode ratio) and the controlled attenuation parameter (CAP) of FibroScan for the noninvasive diagnosis and grading of steatosis. Two centers prospectively included patients who underwent liver biopsy, B-mode ratio and CAP evaluation all on the same day between June 2017 and July 2019. MRI and histological morphometry were also performed in center 1. Histology (classic semiquantitative score and morphometry) was used as the reference. Concerning the B-mode ratio, the AUROCs for ≥ S1, ≥ S2 and ≥ S3 were respectively 0.896 ± 0.20, 0.775 ± 0.30 and 0.729 ± 0.39 with the best cut-off values being 1.22 for ≥ S1 (Se = 76.4 %, Sp = 93.2 %), 1.42 for ≥ S2 (Se = 70.2 %, Sp = 71.2 %) and 1.54 for ≥ S3 (Se = 68.4 %, Sp = 69.8 %). The correlation between the B-mode ratio and morphometry was moderate (Rs = 0.575, p < 0.001) and the correlation between the B-mode ratio and MRI was good (Rs = 0.613, p < 0.001). Concerning the CAP, the AUROCs for ≥ S1, ≥ S2 and ≥ S3 were 0.926 ± 0.18, 0.760 ± 0.30 and 0.701 ± 0.40, respectively, with the best cut-off values being 271 dB/m for ≥ S1 (Se = 84 %, Sp = 88.2 %), 331 dB/m for ≥ S2 (Se = 64.5 %, Sp = 74.7 %) and 355 dB/m for ≥ S3 (Se = 55.3 %, Sp = 75.1 %). The correlation between the CAP and morphometry and between the CAP and MRI was moderate in both cases (Rs = 0.526, p < 0.001 and Rs = 0.397, p < 0.001, respectively). The B-mode ratio was better at ruling in and the CAP was better at ruling out the disease. B-mode ratio and CAP show similar and good performance for the diagnosis of steatosis (≥ S1). However, both techniques are limited with respect to differentiating mild to moderate (≥ S2) or severe (≥ S3) steatosis.

Deep learning quantification of percent steatosis in donor liver biopsy frozen sections.

BackgroundPathologist evaluation of donor liver biopsies provides information for accepting or discarding potential donor livers. Due to the urgent nature of the decision process, this is regularly performed using frozen sectioning at the time of biopsy. The percent steatosis in a donor liver biopsy correlates with transplant outcome, however there is significant inter- and intra-observer variability in quantifying steatosis, compounded by frozen section artifact. We hypothesized that a deep learning model could identify and quantify steatosis in donor liver biopsies.MethodsWe developed a deep learning convolutional neural network that generates a steatosis probability map from an input whole slide image (WSI) of a hematoxylin and eosin-stained frozen section, and subsequently calculates the percent steatosis. Ninety-six WSI of frozen donor liver sections from our transplant pathology service were annotated for steatosis and used to train (n = 30 WSI) and test (n = 66 WSI) the deep learning model.FindingsThe model had good correlation and agreement with the annotation in both the training set (r of 0.88, intraclass correlation coefficient [ICC] of 0.88) and novel input test sets (r = 0.85 and ICC=0.85). These measurements were superior to the estimates of the on-service pathologist at the time of initial evaluation (r = 0.52 and ICC=0.52 for the training set, and r = 0.74 and ICC=0.72 for the test set).InterpretationUse of this deep learning algorithm could be incorporated into routine pathology workflows for fast, accurate, and reproducible donor liver evaluation.FundingMid-America Transplant Society

The Relevance of Noninvasive Tools To Assess Fibrosis in Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver diseases worldwide, involving about 25% of people. NAFLD incorporates a large spectrum of pathological conditions, from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and its complications include hepatic decompensation and hepatocellular carcinoma (HCC). This progression occurs, over many years, in an asymptomatic way, until advanced fibrosis appears. Thus, the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis are key issues. To date, the histological assessment of fibrosis with liver biopsy is the gold standard, but obviously, invasiveness is the greater threshold. In addition, rare but potentially life-threatening complications, poor acceptability, sampling variability and cost maybe restrict its use. Furthermore, due to the epidemic of NAFLD worldwide and several limitations of liver biopsy evaluation, noninvasive assessment tools to detect fibrosis in NAFLD patients are needed.

Use of Artificial Intelligence as an Innovative Method for Liver Graft Macrosteatosis Assessment.

The worldwide implementation of a liver graft pool using marginal livers (ie, grafts with a high risk of technical complications and impaired function or with a risk of transmitting infection or malignancy to the recipient) has led to a growing interest in developing methods for accurate evaluation of graft quality. Liver steatosis is associated with a higher risk of primary nonfunction, early graft dysfunction, and poor graft survival rate. The present study aimed to analyze the value of artificial intelligence (AI) in the assessment of liver steatosis during procurement compared with liver biopsy evaluation. A total of 117 consecutive liver grafts from brain-dead donors were included and classified into 2 cohorts: ≥30 versus <30% hepatic steatosis. AI analysis required the presence of an intraoperative smartphone liver picture as well as a graft biopsy and donor data. First, a new algorithm arising from current visual recognition methods was developed, trained, and validated to obtain automatic liver graft segmentation from smartphone images. Second, a fully automated texture analysis and classification of the liver graft was performed by machine-learning algorithms. Automatic liver graft segmentation from smartphone images achieved an accuracy (Acc) of 98%, whereas the analysis of the liver graft features (cropped picture and donor data) showed an Acc of 89% in graft classification (≥30 versus <30%). This study demonstrates that AI has the potential to assess steatosis in a handy and noninvasive way to reliably identify potential nontransplantable liver grafts and to avoid improper graft utilization.

Approach to the patient with acute severe autoimmune hepatitis.

SummaryAutoimmune hepatitis is associated with varied clinical presentations and natural history, as well as somewhat unpredictable treatment responses. Understanding how to stratify patients who require further escalation of therapy will help clinicians manage these patients. The presentation of acute severe autoimmune hepatitis (AS-AIH) is relatively uncommon, although its prevalence is potentially greater than currently perceived. Previous studies consist of small retrospective single-centre series and are not directly comparable due to the diversity of presentations, disease definitions and non-standardised treatment regimens. We define AS-AIH as those who present acutely with AIH and are icteric with an international normalised ratio ≥1.5 and no evidence of hepatic encephalopathy. Those with hepatic encephalopathy should be defined as having AS-AIH with acute liver failure. In this review, we provide a structured practical approach for diagnosing and managing this unique group of patients.

Suboptimal reliability of liver biopsy evaluation has implications for randomized clinical trials

Liver biopsies are a critical component of pivotal studies in non-alcoholic steatohepatitis (NASH), constituting inclusion criteria, risk stratification factors and endpoints. We evaluated the reliability of NASH Clinical Research Network scoring of liver biopsies in a NASH clinical trial. Digitized slides of 678 biopsies from 339 patients with paired biopsies randomized into the EMMINENCE study - examining a novel insulin sensitizer (MSDC-0602K) in NASH - were read independently by 3 hepatopathologists blinded to treatment code and scored using the NASH CRN histological scoring system. Various endpoints were computed from these scores. Inter-reader linearly weighted kappas were 0.609, 0.484, 0.328, and 0.517 for steatosis, fibrosis, lobular inflammation, and ballooning, respectively. Inter-reader unweighted kappas were 0.400 for the diagnosis of NASH, 0.396 for NASH resolution without worsening fibrosis, and 0.366 for fibrosis improvement without worsening NASH. In the current study, 46.3% of the patients included in the study based on 1 hepatopathologist's qualifying reading were deemed not to meet the study's histologic inclusion criteria by at least 1 of the 3 hepatopathologists. The MSDC-0602K treatment effect was lowest for those histologic features with lower inter-reader reliability. Simulations show that the lack of reliability of endpoints and inclusion criteria can drastically reduce study power - from >90% in a well-powered study to as low as 40%. The reliability of hepatopathologists' liver biopsy evaluation using currently accepted criteria is suboptimal. This lack of reliability may affect NASH pivotal studies by introducing patients who do not meet NASH study entry criteria, misclassifying fibrosis subgroups, and attenuating apparent treatment effects. Since liver biopsy analysis plays such an important role in clinical studies of non-alcoholic steatohepatitis, it is important to understand the reliability of hepato-pathologist readings. We examined both inter- and intra-reader variability in a large data set of paired liver biopsies froma clinical trial. We found very poor inter-reader and modest intra-reader variability. This result has important implications for entry criteria, fibrosis stratification, and the ability to measure a treatment effect in clinical trials.

Occult hepatitis B virus infection predicts non-alcoholic steatohepatitis in severely obese individuals from Italy.

Obesity is associated withnon-alcoholic fatty liver (NAFL), which may progress towards non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B virus infection (OBI) may contribute to hepatic damage in patients withchronic liver diseaseof different aetiologies (egHCV, alcohol). However, information on the prevalence and clinical impact of OBI in obese individuals is lacking. The aims of this study were to investigate NASH prevalence and risk factors in obese people who underwent bariatric surgery. Two-hundred and twenty-six subjects (160 females; mean age 42.9years ±10.8SD) without evidence of any further cause of liver disease consecutively underwent bariatric surgery in two Italian liver centers. During surgery, all patients underwent liver biopsy for histological evaluation and molecular studies. Liver DNA extracts were tested for PNPLA3, TM6SF2, MBOAT7, IRGM polymorphisms and for OBI. Univariate and multivariate analyses were used to identify predictors of NASH. Histology showed NASH in 115 (50.9%) and NAFL in 111 cases (49.1%). Twenty-nine/226 (12.8%) cases had OBI, 24 (82.8%) of whom had NASH and 5 (17.2%) NAFL, whereas among the 197 OBI-negative cases, 91 (46.2%) had NASH and 106 (53.8%) NAFL (P=.0002). Multivariate analysis showed that older age (P=.03, OR 1.034), alanine aminotransferase values (P=.005, OR 1.023), insulin resistance/diabetes (P=.02, OR 2.257), TM6SF2 polymorphism (P=.04, OR 3.168) and OBI (P=.004, OR 5.503) were independent predictors of NASH. NASH is highly prevalent in obese individuals undergoing bariatric surgery. OBI is one of the strongest risk factors of NASH in these patients.

Comparison of the severity of non-alcoholic fatty liver disease in diabetic and non-diabetic obese patients.

nonalcoholic fatty liver disease presents a broad spectrum of histopathological alterations, from steatosis to liver cirrhosis. Patients with diabetes mellitus (DM) present increased incidence and severity of NAFLD. determine the prevalence and severity of NAFLD in diabetic and non-diabetic obese patients undergoing bariatric surgery. the evaluation of liver biopsies was carried out through NAFLD activity score (NAS) in order to evaluate degree of hepatic steatosis, presence of ballooning, inflammatory activity and degree of fibrosis. a total of 154 patients who have undergone bariatric surgery with intraoperative biopsy were observed and divided into two BMI ranges: from 35 to 44.9 and from 45 to 54.9. 32 (20.8%) from 154 patients were diabetic and 122 (79.2%) were non-diabetic. Patients with DM were significantly older than patients without the disease, presenting 41.29 ± 9.40 years vs 36.71 ± 10.13 years in the group with BMI of 35 to 44.9 (p=0.049); and 45.13 ± 7.10 years vs 37.00 ± 9.24 years in the group with BMI of 45 to 54.9 (p=0.024). In the histological evaluation, patients with DM from the BMI group of 35 to 44.9 had a strong association with higher prevalence and severity of steatosis, balloning, inflammation, fibrosis and steatohepatitis. the present study confirms the high prevalence of NAFLD in patients with Morbid Obesity. Prevalence and severity increase proportionally to BMI and who have DM as comorbidity.

Role of Leptin in Neoplastic and Biliary Tree Disease.

Leptin is a small hormone of protein nature, it is strongly involved in the regulation of lipid metabolism and its functioning mechanism is not yet well known or whether or not it is actually secreted by cholangiocytes, nor if the biliary tree expresses its receptors. In the past, various studies have tried to correlate leptin levels with certain neoplasms. The aim of this study was to demonstrate that serum leptin values can become a new sensitive and specific serum marker for cholangiocarcinoma. Seventy-two patients with gallbladder stones, hepatolithiasis with benign biliary stenosis, cholangiocarcinoma, and a group of patients without hepato-biliary diseases were enrolled in the study. In all cases blood and bile samples were collected for evaluation of leptin levels and liver biopsies were performed to confirm diagnosis. In all patients, both ultrasound and cholangio-magnetic resonance imaging (MRI) were performed to complete the diagnostic procedure. Twenty-two patients were affected by cholangiocarcinoma, 50 by benign biliary disease (35 cholelithiasis and 6 hepatolithiasis and 9 by inflammatory biliary stenosis). The mean values of serum leptin in patients with cholangiocarcinoma were 19.28±8.76 ng/ml, significantly higher than those observed in non-neoplastic biliary diseases. Serum leptin levels might be a useful marker to differentiate patients with cholangiocarcinoma from those with biliary lithiasis and inflammatory stenosis.

Retrospective study of the outcome of liver transplantation in Egyptian patients with chronic hepatitis C virus infection

Aim To assess the outcome of living-related-donor liver transplantation for chronic hepatitis C infection in Egyptian patients including hepatitis C recurrence, fibrosis progression, and improved survival. Patients and methods This retrospective study included 104 adult Egyptian patients with chronic liver disease due to chronic hepatitis C, who underwent living-donor liver transplantation at Wadi El-Neel Hospital, Cairo, Egypt, during the period from January 2005 to January 2014. All data regarding comprehensive history taking, clinical examination, laboratory evaluation, model for end-stage liver disease score, fibrosis-4 score, liver biopsy, histopathology examination, and radiological evaluation before and after transplant were collected and analyzed. Moreover, the data of regimen of immunosuppression and regimen of antiviral therapy after transplant were collected and analyzed. Results There were 75 males and 29 females. Their ages ranged from 30 to 74 years, with an average of 51.62 years old. Of 104 cases, 90 were of class C, whereas 13 cases of class B, and only one case was class A Pugh–Child classification. Of 104 cases, 31 missed follow-up owing to follow-up in another hospital within their city. Recurrence of hepatitis C virus infection after liver transplantation occurred in 73 (70.19%) cases. Sustained virological response was observed in 40 (54.79%) cases, and relapse was observed in 33 (31.73%) cases after antiviral treatment. Second relapse after treatment occurred in 33 (31.73%) of 73 cases and received antiviral therapy course again, with sustained virological response in 15 (45.45%) cases out of 33, relapse again was seen in seven (21.21%) of 33 cases, and 11 (42.4%) of 33 cases were nonresponders. According to clinical outcomes in the studied cases, eight (7.7%) died, five (4.8%) cases had decompensated liver disease, five (4.8%) cases underwent retransplantation, two (19%) cases had liver fibrosis, and one case (0.96%) had hepatocellular carcinoma.

Outcomes and Toxicology of Herbal Drugs in Alcoholic Hepatitis - A Single Center Experience from India.

Background and Aims: We aimed to study clinical outcomes and liver biopsy features of alcoholic hepatitis (AH) patients on complementary and alternative medicines (CAMs) and to analyze the retrieved drugs for chemical and toxic components linked to drug-induced liver injury. Methods: We retrospectively assessed clinical, biochemical and liver biopsy features of AH patients on CAM with drug-induced liver injury (AH-CAM, n = 27) and compared them to a control group (classical AH, n = 29) on standard of care. Patients without liver biopsy evaluation and other causes for liver disease were excluded. Samples of the CAMs (n = 42) from patients were retrieved and assessed for chemical and toxins. Results: All were males, and significantly worse clinical presentation, biochemical severity, and liver disease scores were notable in patients with AH-CAM. Traditional Ayurvedic-polyherbal formulations were the most commonly used CAM. On liver histology, varying grades of severe-necrosis, severe hepatocellular, canalicular, cholangiolar cholestasis with predominant lymphocytic-portal-inflammation and varying grades of interface-hepatitis were noted in AH-CAM. Analysis of CAMs revealed presence of heavy metals up to 100,000 times above detectable range and adulterants, such as antibiotics, chemotherapy agents, nonsteroidal anti-inflammatory drugs, alcohols, antidepressants, anxiolytics, and recreational drugs. On follow up, a significantly higher number of patients with AH on CAM died at end of 1, 3- and-6-months compared to controls (37% vs. 83%, 29% vs. 62%, 18% vs. 52% respectively; p < 0.001). Conclusions: Patients with AH and CAM-related drug-induced liver injury have extremely poor short-term survival in the absence of liver transplantation compared to those patients with AH on evidence-based management. Early transplant referral and educating on and curbing of CAM use in severe liver disease through strict monitoring of unregulated traditional health practices can help ease the burden of liver-related death.

Fatty Liver Disease: A Practical Approach.

Fatty liver disease is now one of the most commonly encountered entities in the practice of liver pathology. Distinguishing simple steatosis from steatohepatitis is critical because the latter requires follow-up because of long-term risks that include cirrhosis and hepatocellular carcinoma. An organized approach for evaluating liver biopsies with steatosis is recommended to capture all of the relevant features: (1) degree of steatosis, (2) presence or absence of ballooning degeneration, (3) lobular inflammation, and (4) fibrosis. Herein, we provide a stepwise approach that readers can use to evaluate liver biopsies with steatosis, including examples, pitfalls, differential diagnostic considerations, and suggested diagnostic phrasing. To provide a stepwise approach for the evaluation of liver biopsies showing significant steatosis (involving ≥5% of liver parenchyma). Biopsies demonstrating fatty liver disease encountered in our daily practice were examined as well as recent literature. Effective evaluation of liver biopsies with steatosis requires careful histologic examination and correlation with clinical history, particularly regarding medications, nutrition status, and alcohol use. Examples of uniform reporting, including appropriate use of the nonalcoholic steatohepatitis Clinical Research Network Activity Score, are provided.