Percutaneous Needle Liver Biopsy Research Articles

S1701 Bile Leak: A Rare Complication of Percutaneous Liver Biopsy

Introduction: Percutaneous liver biopsy is a cornerstone in diagnosing various hepatobiliary disorders. It is generally a safe procedure. Bile leak is a very rare complication, with rates less than 0.001%. Case Description/Methods: A 79-year-old woman presented to the emergency department with severe right upper quadrant abdominal pain along with nausea and vomiting after undergoing an ultrasound-guided percutaneous liver biopsy for elevated liver enzymes. On examination, right upper quadrant tenderness was appreciated. Computed tomography (CT) and Magnetic resonance imaging (MRI) of the abdomen were suggestive of blood products within the gallbladder. She underwent Endoscopic retrograde cholangiopancreatography (ERCP) for increased bilirubin (Table). On Fluoroscopy, she was found to have a bile leak at the level of the common hepatic duct (Figure). A temporary plastic biliary stent was placed into the common bile duct (CBD). Discussion: There are guidelines by the American Association for the Study of Liver and the Society of Interventional Radiology to prevent complications after percutaneous needle biopsies and liver biopsies. Utilizing ultrasound can help avoid injury to the gall bladder and large bile ducts. A biopsy of at least 2-3 cm length and 16-gauge caliber is considered sufficient. Patients should be closely observed for at least 2-4 hours after the procedure. Keeping a low threshold for prompt evaluation with appropriate imaging modalities and timely intervention can help overcome this challenge and reduce morbidity and mortality.Figure 1.: Fluoroscopy demonstrates extravasation of contrast at the level of the common hepatic duct, suggestive of bile leak Table 1. - Trend of total bilirubin through the hospital course. Notice the 50% decrease after biliary stent placement Total Bilirubin (mg/dL) 0.8 3.6 6.2 6.7 7.4 3.1 2.7 2.2 0.9

Неінвазивна діагностика фіброзу печінки у хворих із неалкогольною жировою хворобою печінки

Актуальність. Неалкогольна жирова хвороба печінки (НАЖХП) — хронічна дифузна патологія печінки, що пов’язана з інсулінорезистентністю та метаболічними порушеннями, серед яких ожиріння, цукровий діабет 2 типу та дисліпідемія. НАЖХП охоплює простий стеатоз, який має доброякісний перебіг, неалкогольний стеатогепатит, що може прогресувати до цирозу та гепатоцелюлярної карциноми. Морфологічне дослідження печінки залишається золотим стандартом для оцінки ступеня стеатозу, печінкового запалення і фіброзу, однак все більший інтерес останнім часом викликають неінвазивні методи, серед яких оцінка різних індексів, заснованих на сироваткових маркерах. Мета. Оцінка показників діагностичної точності сироваткових маркерів та неінвазивних лабораторних індексів у визначенні морфологічних змін печінки у хворих на НАЖХП. Матеріали та методи. У дослідження включені 60 пацієнтів із НАЖХП, які проходили обстеження й лікування у відділенні захворювань печінки та підшлункової залози ДУ «Інститут гастроентерології НАМН України». Серед досліджених 26 (42,3 %) чоловіків та 34 (56,7 %) жінки, середнім віком (37,1 ± 12,4) та (44,3 ± 7,3) року відповідно. Усім пацієнтам була проведена черезшкірна пункційна трепан-біопсія печінки з подальшим морфологічним дослідженням пунктату; виконано визначення вмісту гіалуронової кислоти, a2-макроглобуліну, аполіпопротеїну А1, фібронектину, гаптоглобіну в сироватці крові, був проведений розрахунок неінвазивних маркерів фіброзу печінки: AAR, APRI, FIB-4. Результати. У хворих на НАЖХП встановлено високу діагностичну точність сироваткових маркерів фіброзу як при розмежуванні різних стадій фіброзу, так і при виключенні саме наявності фіброзу. Висновки. Визначення сироваткових маркерів має значення для вирішення питання про необхідність медикаментозного лікування та його тактику, а відповідність неінвазивних маркерів золотому стандарту — морфологічному дослідженню дозволяє уникати біопсії печінки як методу з потенційно можливими ускладненнями внаслідок своєї інвазивності.

Technical note: Extrapolation of hepatic glycogen concentration of the whole organ by performing a liver biopsy

Glycogen, a complex polysaccharide, is the form of storage of glucose in mammals that can be released rapidly when needed. Recent studies have mainly reported hepatic glycogen concentration for early-lactating cows, when the energy demand is higher than the energy supply from dry matter intake, driving the cow to use the energy stored as hepatic glycogen. Generally, liver samples are obtained through percutaneous needle biopsies in the right lobe of the liver. Our objective was to analyze the variation of glycogen concentration in the livers of Holstein and Jersey cows among different liver locations representing all lobes, to evaluate whether samples obtained by liver biopsies are representative of the whole organ. Liver from 10 culled lactating cows (5 Holstein and 5 Jersey cows) from 30 to 113 mo of age at slaughter were obtained. Each liver was sampled no more than 3 h after death on the following sites: 3 sites in the right lobe (1 to 3), 2 in the diaphragmatic surface of the left lobe (4 and 5), 3 in the visceral surface of the left lobe (6 to 8), 1 in the quadrate lobe (9), and 1 in the caudate lobe (10). Samples were snap frozen in liquid N2 and were then analyzed for glucose concentration after conversion of glycogen to glucose using amyloglucosidase (EC 3.2.1.3). Glycogen results are reported as grams of glucose per 100 g of wet weight of liver (i.e., percent of wet weight of liver). Liver weights averaged 5.1 [standard deviation (SD) 1.2, minimum 3.3, maximum 6.2] kg for Holstein and 6.0 (SD 1.8, minimum 4.7, maximum 8.9) kg for Jersey cows. Holstein cows [1.31, standard error of the mean (SEM) 0.05% of wet weight] had greater liver glycogen concentration than did Jersey cows (0.75, SEM 0.05% of wet weight). No significant difference was noted among the 10 liver locations regarding glycogen concentration and averaged, for both breeds, 1.03% of wet weight (SEM 0.10). These results suggest that, in dairy cows, percutaneous needle liver biopsy in the right lobe is an accurate technique to fairly extrapolate glycogen concentration of the whole organ.

Effectiveness of Sedoanalgesia in Percutaneous Liver Biopsy Premedication.

Aim:Percutaneous needle liver biopsy (PLB) is frequently associated with pain and anxiety. This may discourage the patients for biopsy, and rebiopsies, if needed. We planned a study to investigate the efficacy of additional analgesia or sedation for PLB.Materials and methods:The study has been designed as a single-center, prospective study. The PLB was planned for 18- to 65-year-old consecutive patients who were included in the study. The patients were divided into three premedication groups as control, Meperidine, and Midazolam. Hospital Anxiety and Depression Scale (HADS) was used to measure each subject’s anxiety level. Fifteen minutes before the biopsy, 1 mL 0.9% NaCl subcutaneously (sc), 1 mg/kg (max 100 mg) Meperidine sc, or 0.1 mg/kg (max 5 mg) Midazolam intravenously was administered to patients respectively. Then PLB was done with 16 G Menghini needle. The day after, the patients were asked about feelings regarding biopsy.Results:Groups were similar by gender and age. The HADS scores prior to PLB and on visual analog scale (VAS, 1-10 points) score during PLB were similar. In the three groups, 7, 12, and 7 patients, respectively, experienced no pain. Other patients explained pain as mild or moderate or severe. The number of patients who agreed for possible rebiopsy was higher in Meperidine and Midazolam groups than in the control group.Conclusion:Premedication with Meperidine or Midazolam in PLB would improve patients’ tolerance, comfort, and attitude against a possible repeat PLB.How to cite this article: Sezgin O, Yaras S, Ates F, Altintas E, Saritas B. Effectiveness of Sedoanalgesia in Percutaneous Liver Biopsy Premedication. Euroasian J Hepato-Gastroenterol 2017;7(2):146-149.

Generation of patient-derived xenografts from fine needle aspirates or core needle biopsy

Patient-derived xenografts have recently become a powerful tool for cancer research and may be used to guide personalized therapy. Thus far, patient-derived xenografts have been grown from tumor tissue obtained after operative resection; however, many cancer patients never undergo operative intervention for a variety of reasons. We hypothesized that xenograft tumors could be grown from smaller volumes of patient tissue, such as those obtained during diagnostic biopsies. Surgical specimens were obtained after resection of primary or metastatic lesions of the following cancers: pancreatic carcinoma, non-small cell lung cancer, bladder (urothelial) carcinoma, and melanoma. At least 10 cases of each cancer were included in this study. To mimic clinical biopsies, small fragments of the surgical specimens were biopsied with a 22-gauge needle, and the needle contents were injected subcutaneously in immunocompromised mice. The tumor fragment from which the biopsy was taken was also implanted subcutaneously in the contralateral side of the same mouse as a control. Success rates of the traditional method of xenograft implantation ranged from 27.3%-70%. Success rates of the fine needle aspirate technique ranged from 0%-36.4%. An attempt to engraft a percutaneous core needle liver biopsy of a metastatic pancreatic adenocarcinoma also was successful. We have found that it is possible to engraft fine needle aspirates and core biopsies of solid tumors in order to generate patient-derived xenografts. This may open up xenografting to a wider cancer patient population than previously possible.

Noncirrhotic Portal Hypertension in Perinatally HIV-infected Adolescents Treated With Didanosine-containing Antiretroviral Regimens in Childhood.

Noncirrhotic portal hypertension (NCPH) has been reported in HIV-infected adults. Antiretroviral drugs, as well as genetic and thrombophilic predisposition, have been suggested as possible etiologic factors. Clinical data were collected from 6 HIV-infected patients attending the Infectious Diseases Departments at respectively Emma Children's Hospital Academic Medical Centre in Amsterdam, The Thai Red Cross AIDS Research Centre, Bangkok, Imperial College Healthcare NHS Trust, London who were diagnosed with NCPH. All underwent extensive blood analysis, liver ultrasound, liver elastography, esophagogastroduodenoscopy and percutaneous needle liver biopsy for histological evaluation. We describe 6 perinatally HIV-infected adolescents, all female, who developed NCPH after prolonged exposure during childhood to a didanosine-containing antiretroviral regimen. Histology and electron microscopy showed periportal fibrosis and mitochondrial damage as key findings in their liver biopsies. One of these 6 patients required surgical intervention, the remainder have been managed conservatively to date. Thus, symptomatic NCPH may present in adolescence after perinatally acquired HIV-1 infection. In this case series, risk factors included female sex and prolonged exposure to antiretroviral regimens that included the nucleoside-analogue didanosine in childhood.

Hyaline droplets in Kupffer cells: a novel diagnostic clue for autoimmune hepatitis.

Pediatric autoimmune hepatitis (AIH) is relatively common and has a characteristic but relatively nonspecific histopathology with a usually prominent lymphoplasmacytic infiltrate. Herein, we describe for the first time the presence of characteristic hyaline droplets in the cytoplasm of Kupffer cells on routine hematoxylin and eosin (H&E) sections in AIH. The medical records and pathologic material over a 20-year period (1992 to 2012) were reviewed from children with AIH (n=30), hepatitis B virus (n=30), and hepatitis C virus (n=30) from the pathology files at Boston Children's Hospital. All children had percutaneous needle liver biopsies. We reviewed sections stained with H&E, PAS, and PAS with diastase for the presence of hyaline droplets in all 90 biopsies. We also performed immunohistochemical analysis for IgG, IgA, and IgD in 6 biopsies with AIH. Hyaline droplets were identified in Kupffer cells throughout the lobules in 15 of 30 biopsies (easily found in 13 and rare in 2); conversely, no droplets were identified in 15. Droplets were identified in 10 AIH type 1 biopsies, 1 in AIH type 2, 3 in overlap syndrome, and 1 in unclassified. Serum IgG levels, when available, were correlated with biopsy findings. Seventeen patients had serum IgG levels available for review. The average IgG level in patients without droplets in their biopsies was 1364 mg/dL, in contrast to 3424 mg/dL in patients with droplets (P=0.021). Immunohistochemical analysis performed in 6 biopsies revealed that droplets were nearly always positive for IgG, occasionally for IgA, and rarely for IgD. None of the biopsies in patients with hepatitis C contained hyaline droplets. One biopsy of a patient with hepatitis B revealed hyaline droplets; this biopsy had an unusually prominent plasmacytic infiltrate, and the patient was found to have an elevated IgG serum level and antibodies to smooth muscle actin. As far as we are aware, hyaline droplets in Kupffer cells on routine H&E sections have never been described. They should be distinguished from the nonspecific granular lysosomal structures frequently found in Kupffer cells in a variety of chronic liver diseases and from erythrophagocytosis. Hyaline droplets may occur in AIH regardless of the type and correlate with a >2-fold increase in serum level of IgG as compared with patients without droplets in their biopsies. Identification of hyaline droplets in Kupffer cells provides a useful diagnostic clue to distinguish AIH from other forms of chronic hepatitis.

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

Sonography-Guided Percutaneous Liver Biopsies in Children

The purpose of this study was to evaluate the safety and efficacy of sonography-guided percutaneous core needle liver biopsy in infants and children. We conducted a retrospective analysis of all patients who underwent sonography-guided percutaneous core needle liver biopsies over a 7.5-year period by pediatric interventionalists at a single tertiary center. A total of 597 procedures were performed in 470 patients (270 male and 200 female), with a mean age of 10.5 years (age range, 1 month-21 years). The main indications for biopsies were abnormal liver enzymes (n=129, 21.6%), grading and staging of chronic hepatitis B or C (n=105, 17.6%), evaluation of transplanted liver (n=111, 18.6%), iron overload (n=73, 12.2%), miscellaneous other diffuse parenchymal abnormalities (n=124, 20.7%), and focal hepatic lesions (n=55, 9.2%). The procedures were performed either under sedation (n=311, 52.1%) or general anesthesia (n=286, 47.9%). Diagnostic yield was obtained in 596 biopsies (99.8%) from an average of 2.4 cores in patients with diffuse disease (n=541, 90.6%) and 6.5 cores in patients with focal disease (n=55, 9.2%). Ten patients (1.7%) experienced a major complication, including pneumothorax (n=1, 0.2%), abdominal wall pseudoaneurysm (n=1, 0.2%), and symptomatic bleeding (n=8, 1.3%). Five of these children required transfusion, two were only admitted for observation, and one required surgical evacuation. There were no procedure-related deaths. Minor complications (n=49, 8.2%) included a symptomatic subcapsular hematoma (n=35) and stable small hemoperitoneum (n=9). Sonography-guided percutaneous core liver biopsy is a safe and effective procedure in children that has a high diagnostic yield and very low complication rate.

Multicenter validation of spin‐density projection‐assisted R2‐MRI for the noninvasive measurement of liver iron concentration

PurposeMagnetic resonance imaging (MRI)-based techniques for assessing liver iron concentration (LIC) have been limited by single scanner calibration against biopsy. Here, the calibration of spin-density projection-assisted (SDPA) R2-MRI (FerriScan®) in iron-overloaded β-thalassemia patients treated with the iron chelator, deferasirox, for 12 months is validated.MethodsSDPA R2-MRI measurements and percutaneous needle liver biopsy samples were obtained from a subgroup of patients (n = 233) from the ESCALATOR trial. Five different makes and models of scanner were used in the study.ResultsLIC, derived from mean of MRI- and biopsy-derived values, ranged from 0.7 to 50.1 mg Fe/g dry weight. Mean fractional differences between SDPA R2-MRI- and biopsy-measured LIC were not significantly different from zero. They were also not significantly different from zero when categorized for each of the Ishak stages of fibrosis and grades of necroinflammation, for subjects aged 3 to <8 versus ≥8 years, or for each scanner model. Upper and lower 95% limits of agreement between SDPA R2-MRI and biopsy LIC measurements were 74 and −71%.ConclusionThe calibration curve appears independent of scanner type, patient age, stage of liver fibrosis, grade of necroinflammation, and use of deferasirox chelation therapy, confirming the clinical usefulness of SDPA R2-MRI for monitoring iron overload. Magn Reson Med 71:2215–2223, 2014. © 2013 Wiley Periodicals, Inc.

Biliary Atresia: A Challenging Diagnosis

Abstract: Biliary atresia (BA) constitutes about one third of all neonatal cholestasis (NC) and the most common indication (up to 50%) of liver transplantation (LTx) in children. Despite extensive studies, its etiopathogenesis has not been clearly revealed. Treatment is primarily surgical based on reinstitution of bile flow by Kasai portoenterostomy, the success of which is largely dependent on the early diagnosis before 60 days of age. If portoenterostomy is not successful or not performed, LTx is the only life-saving alternative. Accurate diagnosis of BA, particularly distinguishing it from other causes of liver injury in the neonatal period, is challenging as there is a high degree of overlap in clinical, biochemical, imaging, and histological characteristics. There is no single preoperative investigation that enables the diagnosis of BA to be made with certainty. Liver biochemistry assessment, biliary radionuclide excretion scanning, magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), percutaneous needle liver biopsy, and laparoscopy can all be helpful, but their results are not individually diagnostic. The current review presents an overview of BA with emphasis on the recent diagnostic modalities.

Su1291 How Should Be Applied the Premedication in Percutanous Liver Biopsy? : The Roles of Analghesics and Sedatives

AIM:Percutaneous needle liver biopsy (PLB) is important for diagnosis of liver disease and is frequently associated with pain and anxiety. This may discourage patients for further biopsies, if needed. Procedure is performed under local anesthesia(LA). No concencus are available on premedication. Some reports suggested benefits of sedation and analghesia, while others, possibility of interferance with patient's cooperation. We use LA and sometimes add Meperidine (Me) or Midazolam (Mi) for PLB premedication. We planned a study to investagate the efficacy of analghesia and sedation for PLB. MATERIALS-METHODS: This was a prospective, randomized, double-blinded, double dummy study. Approval received from local ethic committe. PLB planned, 18-65 years old patients included in study. Written informed consent was obtained. Patients randomized into three premedication groups as placebo (P), Me and Mi and requested to complete the Hospital Anxiety and Depression Scale (HADS) before biopsy. Biopsy site was located with ultrasonography. Then, 15 minutes before biopsy, 1ml %0,9 NaCl sc, 1 mg/kg (max100mg)Me sc, and 0.1 mg/kg (max5mg) Mi iv administered to P, Me and Mi patients, respectively. PLBs were performed by the same skilled operator (SY) for all, placed supine position. After local disinfection, LA with Prilocaine HCL 10 ml apllied to skin and periton beneath. Then PLB applied with 16 G Menghini needle.The patient, then lied on right side or supine, monitored in order to detect complications for 4 hours, then discharged. The day after, the patient asked about biopsy.Visual analog scale (VAS) was used to grade the intensity of the subjects' pain. RESULTS: Each of 3 groups as 30, total 90 patients included in study (62 male, 28 female, mean age 41,6 years). Groups were similar by gender, age, PLB indications, HADS scores prior to PLB (5, 4 and 4,respectively, p:0.735), and VAS score during PLB (4.5, 3, 4,respectively p:0.567). In 3 groups 7,12 and 7 patients (respectively) explained no pain (p:0.412). Other patients explained pain as mild or moderate 63%, 40%, and 66% (respectively, p:0.412). Mean length of liver specimen achieved with PLB was 23±9 mm, and pain level didn't related with (p:0.835). 80/90 patients (88.8%) defined PLB as easy, with all groups similar. PLB defined as uneasy by 20%, 6.7%, and 6.6% patients respectively; there was numeric but not stastical difference (p:0.256). There was difference between P group and other two about the attitude for re-biopsy. Patients agreeing rebiopsy without doubt were 33%,53% and 50% (p,0.035) while anxious about 50%, 30% and 33% (p,0.035) respectively. Patients refusing re-biopsy were 13.3% in P, 6.7% in Me and none in Mi groups. CONCLUSION: Premedication with Me or Mi in PLB would improve tolerance, comfort and attitude against a new PLB, and there is no increased risk related to these agents.

Chemotherapy Toxicity Related to Non-Alcoholic Fatty Liver Disease (NAFLD) in an Adolescent with Pre-B Cell Acute Lymphoblastic Leukemia

Abstract 4303The incidence of obesity and metabolic syndrome is on the rise. NAFLD is a chronic liver condition characterized by hepatic fat accumulation not due to other causes. NAFLD can progress to include a spectrum of inflammation, necrosis, fibrosis, and in some cases, cirrhosis. In its most extreme form, non-alcoholic steatohepatitis (NASH) and other liver dysfunction syndromes can cause significant toxicity and complicate the treatment of cancer patients receiving chemotherapy. Here we describe the complications of NAFLD transitioning to NASH acutely during induction therapy in an obese adolescent male with newly diagnosed pre-B ALL.A 15 year-old Hispanic male presented with a one-week history of lymphadenopathy. His past medical history included hypertension and NAFLD. No hepatosplenomegaly was noted at diagnosis. The initial laboratory evaluation revealed mild anemia, elevated LDH and uric acid as well as normal AST and ALT. Subsequent work-up including a bone marrow aspiration/biopsy revealed Pre-B ALL. The patient was started on induction therapy on a high-risk protocol receiving vincristine, daunorubicin, prednisone, and asparaginase. On Day 14 of induction, he complained of right upper quadrant pain, and leg paresthesias. Physical examination revealed jaundice, hepatomegaly, and loss of deep tendon reflexes in the lower extremities. Laboratory results revealed transaminitis and cholestatic jaundice with hyponatremia. Vincristine and daunorubicin were held. The patient was found to have SIADH and Grade IV peripheral neuropathy attributable to vincristine toxicity. Abdominal ultrasound showed diffuse fatty infiltration of the liver. Percutaneous needle liver biopsy revealed NASH with 70% pan-lobular steatosis, marked degeneration, mild cannalicular cholestasis, and stage 2–3/4 fibrosis.The patient completed 28 days of prednisone but did not receive any subsequent doses of vincristine during induction. The Day 14 bone marrow evaluation showed the patient to be in remission, and this was sustained through Day 29 despite only receiving 2 doses of vincristine (1.5mg/m2/dose) and daunorubicin (25mg/m2/dose), one dose of asparaginase (2500 IU/m2), and 28 days of prednisone (60mg/m2/day). The transaminitis resolved over the next month, as did the SIADH and neuropathy. It was hypothesized that the patient's baseline fatty liver was exacerbated by the prednisone diminishing hepatic metabolic capacity and enhancing chemotherapy related toxicities. He was removed from the study protocol and is being treated with 50% dose-reduced vincristine and avoidance of other hepatotoxic chemotherapies. He has liver biopsies performed after each cycle of chemotherapy to assess the degree of steatosis.Pediatric obesity is a growing problem. It is estimated that about 10% of children are affected by NAFLD/NASH. Higher rates are seen in Hispanics, obese populations, and type 2 diabetics. Serologic markers and imaging techniques have not proven to be effective at screening patients at risk for NAFLD/NASH. The gold standard for diagnosis is biopsy of liver tissue but may not be practical for all patients. Proven treatment strategies for NAFLD/NASH are similarly limited to lifestyle changes involving diet and exercise.Chemotherapy agents used in leukemia therapy consist of multiple agents that either rely on hepatic function for metabolic activation (cyclophosphamide, cytarabine, methotrexate) or elimination (vincristine, daunorubicin, mercaptopurine). Others including the antimetabolites (mercaptopurine, methotrexate, asparaginase, prednisone) have direct toxic effects on the liver. Limitations in the use of these standard agents severely hamper the therapeutic options for oncologists treating patients with leukemia.Although this is the only case report to our knowledge that describes chemotherapy inducing progression to NASH, clinicians are likely to continue to experience complications related to obesity, fatty liver, and metabolic syndrome as their incidence continues to rise worldwide. An essential component of leukemia therapy, corticosteroids have been shown to induce fat accumulation in the liver. This patient previously carried a diagnosis of fatty liver prior to treatment, but the rapid progression to NASH and subsequent hepatic dysfunction contributed significantly to his toxicities and future chemotherapeutic treatment options. Disclosures:Assanasen:Vidacare Corporation: Research Funding. Falcon:Vidacare Corporation: Research Funding.

NEEDLE BIOPSY FOR HEPATIC VITAMIN A LEVELS IN LIONS (PANTHERA LEO)

Hypovitaminosis A (HA)-related skull malformations resulting in neurologic abnormalities and death have been, and still are, reported in captive lions (Panthera leo) worldwide. Liver vitamin A (VA) concentration is the most reliable indicator of animals' VA status, and its assessment is essential in prevention and treatment of HA in lions. A percutaneous needle liver biopsy using high-performance liquid chromatography ultraviolet retinoid analysis for VA concentration measurement was validated. It was first assessed in vitro using chicken liver. Later, the safety and feasibility of ultrasound-guided percutaneous needle liver biopsy was assessed in living lions. Hepatic VA concentrations in lion liver were measured using the above laboratory method. Mean chicken hepatic VA concentration in needle biopsy (NB) and wedge biopsy (WB) of the same liver lobes were 108.66 and 60.89 microg/g wet tissue, respectively, and were significantly (P = 0.03) correlated (r = 0.74). The calculated linear regression for predicting VA concentration in WB using NB VA for chicken liver was 25.194 + 0.3234x NB (microg/g). Four ultrasound-guided percutaneous needle liver biopsies were obtained from each of the four lions under general anesthesia. Mean hepatic VA concentration was 8.25 microg/g wet tissue (range 1.43-25.29 microg/g). Mean serum VA concentration, measured in these four lions was 1,011.1 nmol/L with a standard deviation of 337.91 nmol/L (range 590.26-1,077.2 nmol/L). The lions recovered uneventfully, and no complications were observed during a 4-yr follow-up period. In conclusion, the percutaneous needle liver biopsy technique is a reliable, practical, safe tool for obtaining liver tissue samples antemortem for assessment of the VA status in lions and can be used in future studies.

Effects of percutaneous needle liver biopsy on dairy cow behaviour

In cattle, percutaneous needle liver biopsy is used for scientific examination of liver metabolism. The impact of the biopsy procedure is, however, poorly investigated. Our aim was to examine the behaviour of dairy cows during and after liver biopsy.Data were collected from 18 dry cows. Percutaneous needle liver biopsies (after administration of local anaesthesia (2% Procaine)) and blood samples were taken during restraining. During the control treatment, animals were restrained and blood sampled.During the biopsy procedure, cows showed increased restlessness (P=0.008), frequency of head shaking (P=0.016), and decreased rumination (P=0.064). After biopsies, tail pressing (P=0.016) and time spent perching (P=0.058) increased. Time spent upright (P=0.10) and number of leg movements (P=0.033) increased during the night as compared to controls. Thus, liver biopsy induced behavioural changes for up to 19h – and particularly for behaviour previously associated with pain.Even though the exact welfare impact of percutaneous needle liver biopsies in cows is not known, and the magnitude of the behavioural changes was limited, pain always has negative effects on animal welfare. Therefore, if the present biopsy procedure – involving several biopsy passes – is to be used, improvement of the anaesthetic protocol as well as the inclusion of analgesics should be considered.

Preactivation of the interferon signalling in liver is correlated with nonresponse to interferon alpha therapy in patients chronically infected with hepatitis B virus

Interferon alpha (IFN-α) therapy is widely used to treat patients with chronic hepatitis B (CHB) but the sustained response rate is low, and the molecular mechanisms for the ineffectiveness of IFN-α treatments are not known. We screened differentially expressed genes between responders (Rs) and nonresponders (NRs) in patients with CHB treated with IFN-α to explore the molecular basis for treatment failure. Expression profiling was performed on percutaneous needle liver biopsy specimens taken before therapy. Gene expression levels were compared between seven patients who did not respond to therapy (NR) and six who did respond (R). Gene ontology category and KEGG pathway were analysed for differentially expressed genes, and the selected differentially expressed genes were confirmed using real-time polymerase chain reaction. We identified 3592 genes whose expression levels differed significantly between all Rs and NRs (P < 0.05); many of these genes are IFN-stimulated genes (ISGs) and immune-related genes. The ISGs were more highly expressed, while immune-related genes were inhibited in NRs before IFN-α treatment. Two ISGs (CEB1 and USP18) that are linked in an IFN inhibitory pathway are highly expressed in NRs, and a potential antiviral gene ISG20 was inhibited in NRs, suggesting a possible rationale for treatment nonresponse. Patients who do or do not respond to IFN have different liver gene expression profiles before IFN-α treatment. Preactivation of the IFN signalling pathway leading to the increased expression of inhibitory ISGs and inhibition of immune response in the pretreatment livers was associated with treatment failure.

Multicenter Validation of Spin-Density Projection-Assisted R2-MRI for the Non-Invasive Measurement of Liver Iron Concentration

AbstractAbstract 2053▪Several MRI based techniques for assessing liver iron concentration (LIC) have been proposed. A limitation of most of these techniques is that they have been calibrated against biopsy using only a single scanner. The spin-density-projection assisted (SDPA) R2-MRI (FerriScan®) technique was calibrated from data from 5 different scanners (St Pierre et al. Blood 2005;105:855–61) on 105 subjects (hereditary hemochromatosis (23); β-thalassemia (9); β-thalassemia/HbE (41); hepatitis C (29); alcohol induced (2) and drug induced (1) hepatitis) none of whom had been chelated with deferasirox (Exjade®). The aim of this new study was to validate the SDPA R2-MRI technique in a multicenter study with 5 scanners different from the original 5 used in the calibration and with a group of regularly transfused (including severely iron loaded) β-thalassemia subjects treated with deferasirox. Methods:SDPA R2-MRI measurements and percutaneous needle liver biopsy samples (>0.5 mg dw) were obtained from 233 subjects after 12 months of treatment with deferasirox at 7 different clinics involved in the ESCALATOR trial. Samples were fixed in buffered neutral formalin and were then embedded in paraffin. Histological examination of the biopsies and quantitative measurement of LIC by atomic absorption spectrometry (AAS) were carried out in a single laboratory (Rennes University Hospital, France). Non-invasive measurements of LIC were made using the SDPA R2-MRI technique on 5 MRI scanners (Philips NT Intera [82 subjects]; Philips Gyroscan [102 subjects]; Siemens Sonata [18 subjects]; Siemens Symphony [11 subjects]; GE Signa Excite [20 subjects]). All data were analyzed at a single laboratory (Resonance Health Analysis Services Pty Ltd, Australia). Analysts were blinded to the AAS results. Significance is quoted at á = 0.05 level. Results:LIC values (mean of MRI and biopsy derived values) ranged from 0.7 to 50.1 mg Fe/g dry tissue. Histological examination yielded the following distribution of Ishak fibrosis stages; 0 (15), 1 (43), 2 (68), 3 (33), 4 (20), 5 (26), 6 (25), unavailable (3). The mean percentage difference between the SDPA R2-MRI and biopsy LIC measurements for each MRI scanner (defined as [SDPA R2-MRI LIC – Biopsy LIC] × 100/mean of the two measurements) was not significantly different from zero indicating that the original calibration curve was applicable to this new patient group on different MRI scanners. Thirty nine subjects were between 3 and 8 years of age (8 years being the minimum age subject involved in the original calibration). The mean percentage difference in LIC between MRI and biopsy for these children was not significantly different from zero indicating that the same calibration can be used in very young children. Furthermore, the variances of the percentage differences between the biopsy and R2-MRI derived LIC measurements for the 5 scanners were not significantly different (Bartlett's test for equal variances) indicating that the precision of LIC measurement was not significantly different between scanners. The upper and lower 95% limits of agreement between the SDPA R2-MRI and biopsy measurements of LIC were 74 and -71%, respectively. These limits are slightly greater than those observed in the original calibration study. Greater limits of agreement may reflect the generally higher stages of fibrosis observed in the population in this study compared with those observed in the original calibration study. The standard deviation of percentage differences between the MRI and biopsy derived LIC values was found to be higher for subjects with higher stages of fibrosis (stage 0, 30%; stage 1–2, 37%; stage 3–4, 38%; stage 5–6, 39%) but mean differences for each stage were not significantly different from zero. Higher stages of fibrosis are known to increase needle biopsy sampling error (Emond et al. Clin Chem 1999;45:340–6). Conclusions:The calibration curve for the SDPA R2-MRI technique appears to be robust, with no statistically significant deviations observed in the current study of 233 β-thalassemia subjects measured on 5 different scanners. No statistically significant differences in accuracy or precision of LIC measurements between the 5 scanners were observed. No detectable change in the calibration curve is caused by the use of deferasirox, the presence of fibrosis, or use in very young children. These findings confirm the clinical usefulness of SDPA R2-MRI as a monitoring tool for iron overload. Disclosures:St Pierre:Resonance Health: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Habr:Novartis: Employment. Kriemler-Krahn:Novartis: Employment. Taher:Novartis: Honoraria, Research Funding.

Bioelectrical Impedance Analysis for Evaluation of Donor Hepatic Steatosis in Living-Donor Liver Transplantation

Objective To assess whether bioelectrical impedance analysis (BIA) can be used to evaluate the degree of hepatic steatosis in potential living liver donors. Material and Methods From May 2008 to April 2009, BIA was measured in 302 living donor candidates. Correlations among body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), total fatty changes at percutaneous needle liver biopsy, and BIA-derived fat composition were assessed. Results The median (range) BIA-derived fat proportion was 19.4% (4.8%–35.3%), BMI was 24 (17–39), and hepatic steatosis at liver biopsy was 2% (0%–75%). Crude correlations were observed between BIA-derived fat proportion and hepatic steatosis ( r 2 = 0.14; P = .000), between BMI and hepatic steatosis ( r 2 = 0.27; P = .000), and between BMI and BIA-derived fat proportion ( r 2 = .25; P = .000). Receiver operating characteristic curve analysis revealed that the area under the curve of BIA-derived fat proportion was smaller than that of BMI, and no significant cutoff value was identified. Conclusions These results suggest that BIA-derived fat composition alone cannot be used to accurately determine the degree of hepatic steatosis. However, a combination of BMI and BIA-derived fat composition may increase clinical ability to assess hepatic steatosis.

Histopathological Findings In Liver Biopsies And Clinical Correlation At Kano, Nigeria

Background: Proper evaluation of liver disease requires histological diagnosis of liver biopsy specimens which form the basis for rational treatment and monitoring, as well as assessment of disease severity and progression. We report the histological findings in liver biopsy specimens obtained by percutaneous blind needle biopsy in Kano, Nigeria over a two year period (February 2002-April 2004). Materials and methods: Percutaneous blind needle liver biopsy (PBNLB) was performed in 37 consecutive patients with clinical, laboratory and ultrasonographically established liver disease using the Menghini suction needle after observing necessary precautions. Liver tissues obtained were processed and stained with Haematoxylin and Eosin (H&E), reticulin and Masson's trichrome stains before being reported on by a Histopathologist. Results: Adequate liver tissues were obtained in 36 patients with one reported as inadequate sample for histological assessment giving a failure rate of 0.027% for this study. The Commonest histological finding was chronic hepatitis accounting for 15 (40.5%) followed by PLCC in 10 (27%) of the patients. The other findings were cirrhosis in 5 (13.5%), extra hepatic biliary obstruction in 2 (5.4%) normal histology in 2 (5.4%), cholestatic hepatitis in 1 (2.7%), while reactive changes and inadequate sample were each reported in 1(2.7%) of the patients. Thirty two (86.5%) and 1 (2.7%) of the patients were positive for HBV and HCV respectively. The prevalence of HBV in cirrhosis, PLCC and chronic hepatitis were 100%, 90% and 86.7% respectively. One patient (2.7%) who was a case of PLCC tested positive for HCV antibody and this patient was positive for HBV as well. Conclusion: HBV related liver diseases (chronic hepatitis, cirrhosis and PLCC) are prevalent in this environment despite the almost totally preventable nature of the virus. It is therefore recommended that screening and vaccination for HBV should be encouraged and that those found positive for HBV be referred to a specialist early for proper evaluation and follow up. These measures will no doubt reduce the morbidity and mortality associated with HBV infection in this environment. Sahel Medical Journal Vol. 11 (1) 2008: pp. 20-23

Migration of Gelfoam to the gallbladder after liver biopsy

Liver biopsy is a common procedure, with an inherent risk of bleeding. There are different ways to help avoid hemorrhage, including biopsy through a transjugular venous route or embolization of the tract with liquid or solid materials. We describe an image-guided percutaneous core needle liver biopsy with tract embolization using thick Gelfoam slurry in a pediatric oncology patient. Imaging studies acquired after the biopsy indicated that the Gelfoam mixture had likely migrated to the gallbladder and common bile duct. We report this rare occurrence with its striking imaging in order to make those performing biopsies aware of this possibility.