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Cholestasis Post Liver Transplantation. IN: Lindor, K.; Talwalkar, J., eds. Cholestatic Liver Disease. Totowa, NJ: Humana Press. 2008. pp 171-182.
This chapter on cholestasis that occurs after liver transplantation is from a book that offers health care providers an overview of cholestatic liver disease; cholestasis is defined as a liver disorder characterized by impaired bile flow. The chapter covers biliary complications, preservation or reperfusion injury and ABO incompatibility, small-for-size syndrome, hepatic artery thrombosis, infectious complications, drug-induced acute cellular rejection, chronic rejection, and recurrent disease, including primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and viral hepatitis. The authors caution that cholestasis can occur anytime throughout the posttransplant period, may be intrahepatic or extrahepatic in origin, and has a very broad differential diagnosis. Careful diagnostic imaging of the biliary tree is an important first step in the workup, followed by liver biopsy if clinically indicated. 1 table. 50 references.
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Cholestatic Liver Disease. Totowa, NJ: Humana Press. 2008. 188 p.
This book offers health care providers an overview of cholestatic liver disease; cholestasis is defined as a liver disorder characterized by impaired bile flow. The text includes 10 chapters: the diagnosis of cholestasis, drug-induced cholestasis, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), overlap syndrome with autoimmune hepatitis, rare causes of cholestasis, cholestatic variants of viral disease and alcohol, cholestasis from systemic disorders, complications of cholestasis, and posttransplantation cholestasis. Specific topics include liver tests and antibodies, cross-sectional studies, liver biopsy, other diagnostic tests, endoscopic ultrasound, herbal remedies, the risk of colon cancer with inflammatory bowel disease (IBD), colon cancer posttransplant, and cholangiocarcinoma, genetic disorders, viral hepatitis, sarcoid disease, lymphoma, granulomatous disease, cystic fibrosis, rheumatologic diseases, osteoporosis, pruritus, hyperlipidemia, strictures, viral disease, and recurrent cholestatic liver disease. Each chapter begins with a brief outline and concludes with a summary and a list of references. The text concludes with a subject index.
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Cholestatic Variants of Viral Disease and Alcohol. IN: Lindor, K.; Talwalkar, J., eds. Cholestatic Liver Disease. Totowa, NJ: Humana Press. 2008. pp 119-134.
This chapter on cholestatic variants of viral disease and alcohol is from a book that offers health care providers an overview of cholestatic liver disease; cholestasis is defined as a liver disorder characterized by impaired bile flow. The chapter focuses on the cholestatic variants of viral hepatitis and of alcoholic liver disease. The authors note that hepatitis, or liver inflammation, of any etiology routinely presents with elevated transaminases. However, the presence of cholestasis does not necessarily rule out the presence of viral or alcoholic hepatitis. Specific diseases covered include hepatitis A, B, C, D, and E; cytomegalovirus; and Epstein-Barr virus. A careful clinical history, viral serologies, and in some cases, a liver biopsy can clarify and diagnose these disease states. The authors conclude that recognition of these variants may be crucial to the timely diagnosis and therapy of these disease states. 1 table. 134 references.
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Diagnosis and Treatment of Autoimmune Hepatitis. Gastroenterology Clinics of North America. 37(2): 461-478.June 2008.
This article about the diagnosis and treatment of autoimmune hepatitis is from an issue of Gastroenterology Clinics of North America that focuses on eosinophilic and autoimmune gastrointestinal disease. The authors describe autoimmune hepatitis (AIH) as a hepatitis of unknown cause, known as idiopathic, characterized by inflammation of the liver, presence of auto-antibodies, and evidence of increased gamma globulins in the serum. AIH is considered to be an interaction between the immune system, auto-antigens, and unknown triggering factors. The authors provide a brief summary of the diagnosis of AIH, epidemiologic factors, the natural history of AIH, an approach to the treatment and follow-up of AIH, and the role of liver transplantation in the treatment of AIH. This immune disease affecting the liver responds well to prednisone or a combination of prednisone and azathioprine; most patients can be brought into remission, although many will require maintenance therapy with low-dose levels of these drugs. The authors stress that not all patients with AIH need to be treated, even once the diagnosis is confirmed. Drug therapy should be considered in patients who have cirrhosis if biopsy demonstrates considerable inflammation. Liver transplantation should be considered in patients who have decompensated cirrhosis from AIH or in those patients who have severe fulminant hepatitis who fail to respond to initial therapy. 3 figures. 3 tables. 60 references.
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Diagnosis of Cholestasis. IN: Lindor, K.; Talwalkar, J., eds. Cholestatic Liver Disease. Totowa, NJ: Humana Press. 2008. pp 1-20.
This introductory chapter on diagnosis is from a book that offers health care providers an overview of cholestatic liver disease; cholestasis is defined as a liver disorder characterized by impaired bile flow. The chapter presents an approach to the diagnosis of cholestasis and discusses biochemical abnormalities, intrahepatic versus extrahepatic cholestasis, the use of cross-sectional imaging studies, the role of cholangiography in identifying the cause of extrahepatic cholestasis, and the role of laboratory studies and liver biopsy in identifying the causes of intrahepatic cholestasis. The author notes that an elevated serum alkaline phosphatase level is the hallmark of this disease and ultrasound is the most convenient way to differentiate between intrahepatic and extrahepatic cholestasis. Computerized tomography or magnetic resonance imaging (MRI) may be the initial test done, depending on the clinical setting. Cholangiography is the preferred method to determine the level of the obstruction. The author concludes that liver biopsy often remains the best way to determine or confirm the diagnosis of cholestasis. 1 figure. 5 tables. 49 references.
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Hepatitis C. Annals of Internal Medicine. 148(11): 1-16. June 2008.
This continuing education program, an In The Clinic supplement to the Annals of Internal Medicine, reviews the prevention, screening, diagnosis, and treatment of hepatitis C. The material presents the answers to common questions in each of these areas, supplemented by evidence from clinical studies that supports the implementation of best practices. Topics include the risk factors for hepatitis C virus (HCV) infection; how to reduce the risk of HCV transmission, particularly in the health care setting; screening and diagnostic tests for HCV infection; the symptoms of HCV, which range from asymptomatic individuals to chronic infection to liver cirrhosis; the indications for liver biopsy; the use of dietary and other lifestyle interventions in the management of HCV infection, including complementary and alternative medicine (CAM) approaches; when drug therapy for HCV is appropriate and the contraindications for drug therapy; treatment regimens and how to choose which drug regimen is appropriate for which patient; vaccinating patients with HCV; the clinical management of patients who do not respond to hepatitis C therapy or who relapse after an initial response; the side effects of hepatitis C drugs and strategies to minimize and manage side effects; how to evaluate the response to hepatitis C drug therapy; liver transplantation in patients with HCV infection; and the risks for hepatocellular carcinoma in patients with HCV infection, including the indications for routine screening for this cancer. A final section considers strategies for practice improvement. Appended to the instructional materials is a patient handout with basic information about hepatitis C, as well as a posttest with which readers can obtain continuing medical education (CME) credits. 1 figure. 4 tables. 53 references.
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Nonalcoholic Fatty Liver Disease. IN: Hauser, S., ed. Mayo Clinic Gastroenterology and Hepatology Board Review. 3rd ed. New York, NY: Informa Healthcare USA. 2008. pp 407-418.
This chapter on nonalcoholic fatty liver disease (NAFLD) is from a comprehensive textbook that provides an in-depth examination of essential knowledge in gastroenterology, hepatology, and the related areas of pathology, endoscopy, nutrition, and radiology. The author defines NAFLD as the accumulation of fat, mainly triglycerides, in hepatocytes that results from insulin resistance. NAFLD includes a wide range of disease, from bland hepatic steatosis, which is generally benign, to nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis and liver failure. The chapter covers clinical manifestations, imaging features, diagnosis, staging with liver biopsy, prognosis, drug therapy, treatment of associated conditions, and prevention strategies. The author cautions that weight gain and obesity resulting from an increased sedentary lifestyle and diets with a high content of fat and carbohydrates seem to be key factors in the development of insulin resistance and NAFLD. The chapter includes full-color and black-and-white illustrations. 4 figures. 4 tables. 20 references.
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Primary Sclerosing Cholangitis. IN: Lindor, K.; Talwalkar, J., eds. Cholestatic Liver Disease. Totowa, NJ: Humana Press. 2008. pp 67-84. Available from Humana Press. 999 Riverview Dr, Suite 208, Totowa, NJ 07512. Email: humana@humanapr.com. Website: www.humanapress.com. Price: $89.95.
This chapter on primary sclerosing cholangitis (PSC) is from a book that offers health care providers an overview of cholestatic liver disease; cholestasis is defined as a liver disorder characterized by impaired bile flow. Primary sclerosing cholangitis is a chronic, progressive cholestatic liver disease characterized by fibrosis of the intrahepatic and extrahepatic bile ducts. PSC is often associated with inflammatory bowel disease (IBD). The chapter covers diagnosis, pathogenesis, natural history, malignancy risk, and management of patients with PSC. The author notes that liver biopsy may be useful in helping establish the diagnosis of PSC, particularly if the patient’s cholangiograms are normal. PSC is a progressive disease that slowly advances over time and may shorten life expectancy. The most severe complication that can develop is bile duct cancer. No effective medical therapy is yet available for the underlying disease; however, liver transplantation is an option for patients with end-stage liver disease. 4 figures. 1 table. 91 references.
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Submassive Hepatic Necrosis in a Patient With AIDS. Practical Gastroenterology. 32(9): 54-62. September 2008.
This article reports the case of drug-induced hepatitis, resulting in submassive hepatic necrosis, in a patient with AIDS. The 43-year-old man presented with fever, chills, and a generalized rash of 2 weeks duration. He had chronic nonproductive cough and shortness of breath, generalized fatigue, malaise, and a 20-pound weight loss over 1 month. He had AIDS for 8 years, chronic hepatitis C infection, and previous hepatitis B infection. The patient had been taking nelfiniavir, zidovudine, and lamivudine for his HIV infection for 5 years. Three months before admission, the patient was started on dapsone for pneumonia prophylaxis. He was admitted to the hospital with a presumed diagnosis of adverse drug reaction to dapsone. The authors describe the diagnosis process that he underwent, with an explanation of a set of features suggesting adverse reaction to dapsone known as dapsone syndrome. Dapsone syndrome is a manifestation of the drug rash with eosinophilia and systemic symptoms (DRESS syndrome). The case exhibited most of the key features of dapsone syndrome, including exfoliative dermatitis, fever, hemolytic anemia, and hepatitis, as evidenced by liver biopsy and improvement in the patient’s condition after discontinuation of dapsone. 4 figures. 3 tables. 21 references.
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Anal Intraepithelial Neoplasia and Other Neoplastic Precursor Lesions of the Anal Canal and Perianal Region. Gastroenterology Clinics of North America. 36(4): 969-988. December 2007.
This article on anal intraepithelial neoplasia and other neoplastic precursor lesions found in the anal canal and perianal region is from a special issue of Gastroenterology Clinics of North America that focuses on the pathology and clinical relevance of neoplastic precursor lesions of the gastrointestinal tract, liver, and pancreaticobiliary system. The author notes that anal cancer is rare and thus anal preneoplastic conditions are poorly understood, especially with regard to their natural history and management. Anal intraepithelial neoplasia is closely linked to human papillomavirus infection and is particularly common in homosexuals and immunosuppressed patients, especially those with HIV/AIDS. Higher grades of anal intraepithelial neoplasia may not develop for long periods of time in patients with functioning immune systems, but those with HIV/AIDS show early and rapid transformation to cancer. The author concludes that most anal preneoplastic conditions are best diagnosed by biopsy and treated by surgical excision, although local recurrence is a problem. The chapter considers anal Paget’s disease, including its diagnosis and management. 9 figures. 1 table. 119 references.
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Chronic Hepatitis B: Who And How to Treat. Practical Gastroenterology. 31(11): 25-30, 35-40. November 2007.
This article reports on the use of drug therapies for hepatitis B and how to determine which patients can and should be treated. The author considers factors such as the natural history of hepatitis B, the variability in disease progression, variable individual patient response, and the advantages and disadvantages of each treatment modality. Patient selection is the key to having the best chance at a remission or cure with treatment. Specific topics include patient evaluation, the immune tolerant phase of the disease, the immune reactive phase of the disease, the inactive carrier phase, the e-antigen negative reactivation phase, treatment goals, treatment options currently approved by the Food and Drug Administration (FDA), and choosing a therapy for an individual patient. The six treatment approaches discussed are interferon alfa-2b, pegylated interferon alfa, lamivudine, adefovir dipivosil, entecavir, and L-deoxythymidine (telbivudine). The author concludes that the goal of treatment for chronic hepatitis B virus (HBV) is to prevent progressive liver disease, cirrhosis, and hepatocellular carcinoma. These goals are achieved through suppression of viral replication. An individual approach should be taken with each patient, and biopsy should be considered in some patients to evaluate for inflammation and fibrosis. 5 tables. 37 references.
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Hepatic Precancerous Lesions and Small Hepatocellular Carcinoma. Gastroenterology Clinics of North America. 36(4): 867-888. December 2007.
This article on the role of precancerous lesions in the liver and small hepatocellular carcinoma is from a special issue of Gastroenterology Clinics of North America that focuses on the pathology and clinical relevance of neoplastic precursor lesions of the gastrointestinal tract, liver, and pancreaticobiliary system. The authors describe the precancerous lesions that may be detected in chronically diseased, usually cirrhotic livers. These include clusters of hepatocytes with atypia and increased proliferative rate (dysplastic foci) that are usually found incidentally in biopsy or resection specimens and grossly evident lesions (dysplastic nodules) that may be detected on radiologic examination. The authors define small hepatocellular carcinoma (HCC) as HCC that measures less than 2 cm. This early form of HCC is well differentiated and has indistinct margins. In addition, there is a distinctly nodular small HCC, which is well or moderately differentiated and is usually surrounded by a fibrous capsule. They caution that precise diagnosis of precancerous and early cancerous lesions by imaging methods is often difficult or impossible. Detection of a dysplastic lesion in a biopsy specimen is a marker of increased risk for HCC development and warrants increased surveillance of the patient. 9 figures. 1 table. 105 references.
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Management of Alcoholic Hepatitis. Gastroenterology and Hepatology. 3(2): 97-99. February 2007.
This article answers common questions physicians may have about the management of alcoholic hepatitis. Topics covered include the pathophysiology of alcoholic hepatitis, the presenting symptoms and attributes of patients with alcoholic hepatitis, the typical course of treatment in these patients, the impact of cessation of drinking alcohol on the course and effects of alcoholic hepatitis, concerns regarding liver transplantation for patients with severe alcoholic hepatitis, and new research in this area. The hallmark of alcoholic hepatitis is jaundice. Most clinicians in the United States do not perform a liver biopsy to make the diagnosis; rather, they base diagnosis on a long history of alcohol use, elevated bilirubin, characteristic AST and ALT values, and no evidence of other liver diseases. The author cautions that approximately 20 to 50 percent of people who have alcoholic hepatitis also have chronic hepatitis C infection. After diagnosis, most patients are treated with oral prednisolone or pentoxifylline. Abstinence from alcohol is required for long-term survival. 6 references.
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Primary Hepatic Actinomycosis: Case Report and Literature Review. Practical Gastroenterology. 31(4): 92-100. April 2007.
This article presents a case report and literature review of primary hepatic actinomycosis. Actinomycosis is a spectrum of chronic, suppurative infections caused by anaerobic or microaerophilic, fungus-like bacteria. Actinomycosis is a rare cause of liver abscess and most commonly occurs as a consequence of prior infection or abdominal surgery. Primary hepatic actinomycosis accounts for less than 5 percent of all cases. The authors present a case of primary hepatic actinomycosis that occurred several years after endoscopic and surgical treatment of a hepatic artery pseudoaneurysm. The clinical presentation was suggestive of liver cancer. However, histologic evaluation of a fine-needle biopsy specimen demonstrated organisms consistent with Actinomyces. The authors presume that the previous interventions provided a portal of entry for the bacteria, leading to indolent abscess formation. After a prolonged course of antibiotic therapy, the patient’s symptoms resolved. Subsequent imaging tests demonstrated resolution of the liver abscesses. 5 figures. 19 references.
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Prospective Evaluation of FIBROSpect II for Fibrosis Detection in Hepatitis C and B Patients Undergoing Laparoscopic Biopsy. Gastroenterology and Hepatology. 3(5): 367-376. May 2007.
This article reports on a study undertaken to validate a serum marker of liver fibrosis through the use of laparoscopic biopsy, which decreases sampling error and increases the reliability of histopathologic assessment. The authors prospectively evaluated the FIBROSpect II serum marker test for viral liver fibrosis against laparoscopic biopsies by studying 145 patients with chronic hepatitis B or C who underwent laparoscopy in a tertiary care setting. Results showed that the FIBROSpect II test was able to rule in significant fibrosis (stages 2 to 4) with a likelihood rate of 2.6. The test correctly indicated absence of diseases in 74 percent of stages 0 to 1 patients and correctly predicted significant disease in 67 percent of stages 2 to 4 patients. Multiple biopsies from 52 percent of patients differed by at least one stage. In 13 patients (9 percent), cirrhosis was detected by laparoscopy but not histologically. The authors conclude that FIBROSpect II provides valuable additional information for assessing fibrosis. 3 figures. 4 tables. 26 references.
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Autoimmune Hepatitis. IN: Lichtenstein, G.; Reddy, K.R.; Faust, T., eds. Clinician’s Guide to Liver Disease. Thorofare, NJ: Slack Incorporated. 2006. pp 105-120.
This chapter about autoimmune hepatitis is from a user-friendly reference book that provides gastroenterologists with an overview of the management of acute and chronic liver disease. The author describes autoimmune hepatitis as a condition of unresolving liver inflammation, which primarily affects young women. The condition is characterized by elevated liver enzymes, hypergammaglobulinemia, serum autoantibodies, interface hepatitis, plasma cell infiltrates on liver biopsy, extrahepatic manifestations, and steroid responsiveness. The chapter provides a brief historical perspective and discussion of epidemiology. It discusses pathogenesis, natural history and prognosis, clinical features, diagnosis and diagnostic tests, complications, and treatment options including medial therapy and liver transplantation. The author cautions that diagnosis of autoimmune hepatitis requires a high index of clinical suspicion because several liver conditions can mimic the disease. Most patients respond to immunosuppressive medications with improvement in clinical symptoms, biochemical liver tests, hepatic histology, and patient survival; however, relapse is common. Up to 40 percent of patients progress to cirrhosis despite therapy. The chapter includes tables and a patient care algorithm and concludes with a list of references. 1 figure. 6 tables. 19 references.
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Benign Lesions of the Liver. Gastroenterology and Hepatology. 2(5): 325-326. May 2006.
This article describes benign lesions of the liver and patient care strategies for people who have these tumors. Benign lesions of the liver are generally of three types: hemangioma, focal nodular hyperplasia (FNH), and hepatic adenoma. Hemangiomas contain fibrous tissue and small blood vessels than can range in size from less than 1 centimeter in diameter to over 10 centimeters. FNH lesions are also solid with a typical central scar and nodule formation. Hepatic adenoma is an infrequently encountered, typically solitary lesion which carries a small risk of spontaneous rupture or malignancy. The author discusses indications for screening patients for these lesions, the interplay between liver lesions and oral contraceptive (OC) use, presenting symptoms that should prompt screening for these lesions, the lack of medical therapies for these lesions, surgical treatment (i.e., operative resection), the importance of differentiating between benign lesions and those that are potentially cancerous, the use of liver biopsy, and liver transplantation in patients with benign lesions (usually reserved only for those patients with other systemic diseases that also present with multiple hepatic adenomas). 5 references.
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Biliary Atresia. Bethesda, MD: National Digestive Diseases Information Clearinghouse. 2006. 6 p.
This fact sheet reviews the problem of biliary atresia, a serious but rare disease of the liver that affects newborn infants. Biliary atresia is defined as the loss or lack of the bile ducts that drain bile from the liver. Bile is made by the liver and passes through the bile ducts and into the intestines where it helps to digest food, fats, and cholesterol. The fact sheet reviews the symptoms, causes, diagnosis, surgical treatments, and postoperative care of biliary atresia. Diagnostic tests that may be used to confirm the condition include physical exam, ultrasound of the abdomen and liver, liver scans, and liver biopsy. The usual surgical correction for biliary atresia is the Kasai procedure (hepato-porto-enterostomy), in which a loop of intestine is brought up to replace the bile ducts and drain the liver. The benefits of this surgery make the early diagnosis of biliary atresia very important, preferably before the infant is several months old and has suffered permanent liver damage. Liver transplantation may be required in infants for whom the Kasai procedure is not effective or successful. The fact sheet concludes with a sidebar about current research studies on biliary atresia, a brief list of resource organizations for readers wanting additional information, and a description of the activities of the National Digestive Diseases Information Clearinghouse. 1 figure.
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Budd-Chiari Syndrome. EndoNurse. 6(3): 34. June- July 2006.
This brief article describes Budd-Chiari syndrome, a rare disorder that results from blood clots that completely or partially block the hepatic veins of the liver. Blood flow through the liver nourishes the liver, carries in substances that the liver will process, and carries away substances that the liver has produced. The author reviews the causes of the syndrome, common symptoms, diagnostic considerations, and treatment, which usually involves surgery. The most common symptom in Budd-Chiari syndrome is ascites (fluid accumulation) with accompanying pain in the upper right-hand portion of the abdomen. Blood accumulation in the liver raises the pressure in the portal vein, but the consequences may not develop for months. One consequence is the formation of dilated, twisted veins in the esophagus (esophageal varices). Diagnostic tests used to confirm Budd-Chiari syndrome include ultrasound and x-rays, liver biopsy, and hepatic vein catheterization. Surgery entails re-routing the blood flow around the clotted hepatic vein into the vena cava. If surgery is done before permanent liver damage sets in, long-term survival is possible. Liver transplantation can be an effective treatment; in some cases, however, the underlying condition that caused the syndrome excludes transplantation as an option. The author concludes that the best approach to prevention is to carefully control the blood disorders that can lead to Budd-Chiari syndrome. 3 references.
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Clinical Utility of Biomarkers of Liver Fibrosis. Gastroenterology and Hepatology. 2(1): 48-57. January 2006.
This article explores the clinical use of biomarkers of liver fibrosis. Liver fibrosis leads to impaired function, portal hypertension, and reduced survival. Thus an accurate evaluation of liver fibrosis in chronic liver disease is important to determine prognosis, therapy outcomes, and disease progression. The traditional method, needle liver biopsy, is an invasive procedure that is associated with small sample size and inaccurate staging, and provides only a semi-quantitative assessment of fibrosis. The authors review a number of simple and specific extracellular matrix biochemical markers that are predictive of fibrosis in patients with chronic liver disease. In patients with hepatitis C, serum HA has been shown to reflect virus response to therapy. Serum HA may also be predictive of severe complications in patients with compensated cirrhosis due to hepatitis C. Markers such as PIIINP and YKL-40 may also predict clinical outcomes in other chronic liver diseases such as primary biliary cirrhosis or alcoholic liver disease. The authors conclude by addressing concerns about overcoming the inherent issue of validation against a static and imperfect test such as liver biopsy; as with liver biopsy, noninvasive markers are imperfect. 4 tables. 78 references.
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Diagnosing and Misdiagnosing Patients with Hepatic Wilson's Disease. Copper Connection. p. 5. June 2006.
This brief newsletter article reports on the continuing difficulties of diagnosis for patients with hepatic Wilson’s disease (HWD). The author notes that the first barrier to diagnosis is failure to consider HWD in the differential diagnosis because it is rare. Misinformation about HWD may limit diagnostic testing and result in failure to diagnose. The author recommends testing for serum copper, serum ceruloplasmin, and 24 hour urine for total copper. Slip lamp evaluation for Kayser-Fleischer rings of the cornea is helpful when positive, but they are less often present in HWD, compared to their uniform presence in WD with neurological symptoms. Another barrier to an accurate diagnosis is a lack of familiarity with the spectrum of presentations of HWD and the wide age range of afflicted patients. The author provides guidelines for the testing of adults suspected of HWD, including the use of liver biopsy. 1 figure.
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Diagnostic Evaluation of Nonalcoholic Fatty Liver Disease. Journal of Clinical Gastroenterology. 40(Suppl 1): S34-S38. March 2006.
This article reviews the diagnostic evaluation of nonalcoholic fatty liver disease (NAFLD). The authors note that NAFLD should be considered in patients presenting with asymptomatic elevated amino-transaminases, patients with radiologic findings of hepatic fatty infiltration, or in patients with cryptogenic cirrhosis. The diagnosis of NAFLD requires evidence of fatty infiltration of the liver in the absence of excessive alcohol ingestion. Clinical evaluation should examine for metabolic risk factors, which include central obesity, glucose intolerance, hypertension, hypertriglyceridemia, and low HDL cholesterol. Secondary causes of NAFLD, such as medications and intestinal bypass surgery, must also be considered, as management of these conditions may differ. Confirmation of hepatic steatosis can usually be done by imaging studies, although occasionally liver biopsy is required. Liver biopsy is required to stage fibrosis and to distinguish between NAFLD and steatosis. This distinction is important to provide prognosis, to exclude other liver disease, and to monitor response to therapy and disease progression over time. The authors note that clinical features, particularly diabetes, obesity and older age, can aid in stratifying patients at risk for advanced fibrosis but are not sufficiently accurate to replace liver biopsy. 2 figures. 2 tables. 56 references.
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Evaluation of the Liver Patient. IN: Lichtenstein, G.; Reddy, K.R.; Faust, T., eds. Clinician’s Guide to Liver Disease. Thorofare, NJ: Slack Incorporated. 2006. pp 1-30.
This chapter about evaluation of the liver patient is from a user-friendly reference book that provides gastroenterologists with an overview of the management of acute and chronic liver disease. The author notes that although liver disease is often suspected after careful history-taking and physical examination, an increasing array of biochemical and serologic tests allows earlier diagnosis of liver disease, more accurate assessment of prognosis, and improved outcomes for some liver diseases. The chapter discusses patient history and symptoms to watch for, such as fatigue and malaise, nausea and vomiting, anorexia, weight loss and weight gain, abdominal pain, increased abdominal girth and edema, icterus and jaundice, dark urine, abnormal stool, pruritus, easy bruisability, sleep disturbance, change in mental status, and leg cramps. The physical examination should consider the presence of jaundice, skin findings, gynecomastia, lymphadenopathy, and abdominal examination. Laboratory evaluation and diagnosis includes tests that reflect hepatic and biliary injury, tests that measure the capacity for organic anion transport, tests of synthetic function, screening tests for specific liver diseases including hepatitis, hepatic imaging, and liver biopsy. The section about liver biopsy covers the indications for biopsy, requirements, contraindications, technical aspects, and complications. The chapter includes tables and reproductions of imaging studies and concludes with a list of references. 5 figures. 8 tables. 24 references.
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HIV-HCV Coinfection. Gastroenterology and Hepatology. 2(5): 357-365. May 2006.
Due to shared routes of transmission, coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common. Since the introduction of highly active antiretroviral therapy in the mid 1990s and the associated marked reduction in HIV-related mortality, the incidence of liver-related mortality in coinfected patients has risen significantly. This article reviews the epidemiology and evaluation of the coinfected patient and outlines the principles necessary for successful management of this challenging patient population. Topics include the natural history of the two diseases, the impact of HIV on HCV disease progression, the impact of antiretroviral therapy on the natural history and histologic spectrum of HCV, the impact of HCV on HIV disease progression, hepatotoxicity of HAART anti-viral therapy, evaluation of the coinfected patient, and treatment of HCV in the coinfected patient. The author concludes by calling for the screening of all HIV patients for HCV and then evaluated for disease severity and considered for therapy. Liver biopsy remains the gold standard for determining histologic severity. Pegylated interferon therapy combined with ribavirin therapy is superior to standard interferon combination therapy with acceptable, albeit lower sustained response rates in coinfected patients when compared to patients with HCV infection alone. The optimal duration of therapy in those coinfected is not clear and results of ongoing trials comparing 48 weeks to 72 weeks of therapy are anxiously awaited. 1 figure. 4 tables. 74 references.
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Liver Biopsies in the Treatment of Wilson’s Disease. Copper Connection. p 7. March 2006.
This brief newsletter article considers the role of liver biopsies in the treatment of Wilson's disease, a condition characterized by copper accumulation in the body. Liver biopsies can provide information about the amount of copper in the liver, if the samples are properly collected and analyzed. The biopsy can also provide a snapshot of the extent of scar tissue and inflammation in the liver. The author outlines the use and indications of liver biopsy, situations where repeated biopsies may not be recommended, and the possibility of a secondary illness that may cause liver damage. A final section reminds readers that zinc acetate is the only form of zinc salt approved by the United States FDA for use in the treatment of Wilson's disease.
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Nonalcoholic Fatty Liver Disease. IN: Lichtenstein, G.; Reddy, K.R.; Faust, T., eds. Clinician’s Guide to Liver Disease. Thorofare, NJ: Slack Incorporated. 2006. pp 121-138.
This chapter about nonalcoholic fatty liver disease (NAFLD) is from a user-friendly reference book that provides gastroenterologists with an overview of the management of acute and chronic liver disease. The authors define NAFLD as the presence of either steatosis or steatohepatitis on liver biopsy specimen in patients with little or no alcohol use. They define the complete clinicopathologic spectrum of NAFLD, review the important epidemiological data, and conclude with a discussion of practical approaches to the diagnosis and management of this disease. The major risk factors for NAFLD include diabetes mellitus, obesity, and hyperlipidemia, all of which predispose to hyperinsulinemia, insulin resistance, and fatty acid retention in liver cells. Symptoms, when present, include fatigue, malaise, and right upper quadrant discomfort. Liver biopsy remains the gold standard for diagnosis. Diet and exercise are the cornerstones of therapy; tight control of metabolic factors such as diabetes mellitus and hyperlipidemia should instituted. 2 figures. 6 tables. 36 references.
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Nonalcoholic Fatty Liver Disease: A Clinic Approach and Review. Canadian Journal of Gastroenterology. 20(5): 345-349. May 2006.
This article reviews advances in nonalcoholic fatty liver disease (NAFLD), the most common cause of incidental elevation of liver enzymes in North America and Europe. Risk factors for NAFLD include a body mass index of 25 or greater, central obesity, and diabetes mellitus. The spectrum of disease is wide, ranging from simple steatosis with benign prognosis to nonalcoholic steatohepatitis and cirrhosis, with associated increases in morbidity and mortality. Topics covered include epidemiology and risk factors, diagnosis, pathogenesis, and patient care management, notably drug therapy in NAFLD, bariatric surgery, and the role of liver biopsy. The first abnormality in NAFLD is insulin resistance leading to hepatic steatosis. The second problem involves multiple proinflammatory cytokines, resulting in nonalcoholic steatohepatitis. Treatment is aimed at aggressive risk factor control and weight loss. 1 figure. 3 tables. 38 references.
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Pathology of the Intrahepatic and Extrahepatic Bile Ducts and Gallbladder. IN: Clavien, P.; Baillie, J., eds. Diseases of the Gallbladder and Bile Ducts: Diagnosis and Treatment. 2nd ed. Williston, VT: Blackwell Publishing Inc. 2006. pp 21-57.
This chapter on pathology is from a textbook that provides a comprehensive and critical approach to both established and new diagnostic and therapeutic modalities for diseases of the gallbladder and bile ducts. The author focuses on the pathology of the intrahepatic and extrahepatic bile ducts and gallbladder. The chapter lists the characteristic morphologic features of primary biliary cirrhosis (PBC), with an emphasis on the florid duct lesion, and describes the histopathologic staging schemes for PBC and primary sclerosing cholangitis (PSC). Other topics include the morphologic features of acute cellular rejection in the hepatic allograft, use of grading schemas for rejection of a transplanted liver, the use of liver biopsy and the characteristic morphologic features of PSC, the secondary causes of sclerosing cholangitis, fibropolycystic diseases of the liver, the anatomic and gross features of cholangiocarcinoma, the staging systems used for gallbladder cancer, and the precursor lesions and etiologic factors in gallbladder cancer. The chapter includes a summary of objectives, a list of suggested readings, extensive references, and a set of self-test questions that focus on the material covered in the chapter. 25 figures. 10 tables. 122 references.
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Postoperative Jaundice. IN: Lichtenstein, G.; Reddy, K.R.; Faust, T., eds. Clinician’s Guide to Liver Disease. Thorofare, NJ: Slack Incorporated. 2006. pp 233-250.
This chapter about postoperative jaundice is from a user-friendly reference book that provides gastroenterologists with an overview of the management of acute and chronic liver disease. The authors note that abnormal liver chemistry tests (LCTs) are common after surgery. Evaluation of postoperative cholestasis requires a careful review of the medical record in combination with blood tests, noninvasive and invasive medical imaging, and liver biopsy when appropriate. The consultant should also review the surgical procedure performed, anesthetics administered, other medications used, and whether blood products were given during the perioperative and postoperative periods. The authors discuss postoperative jaundice subdivided into disorders associated with bilirubin overproduction, hepatocellular injury, intrahepatic or extrahepatic cholestasis, and miscellaneous conditions. They caution that there may be multiple mechanisms responsible for jaundice in a given patient. Two patient care algorithms are included. 2 figures. 1 table. 54 references.
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Hepatitis C Virus Infection and Type-2 Diabetes Mellitus in Renal Diseases and Transplantation. Alimentary Pharmacology and Therapeutics. 21(6): 623-632. March 2005.
This review article addresses the potential link between hepatitis C virus (HCV) infection and the development of type 2 diabetes mellitus in patients with renal disease and transplantation. The authors found that the unadjusted odds ratio for developing post-transplant diabetes mellitus in hepatitis C virus-infected renal transplant recipients ranged between 1.58 and 16.5 across the published studies. The rate of anti-hepatitis C virus antibody in serum was higher among dialysis patients with diabetes mellitus. Patients with type 2 diabetes-related glomerulonephritis had the highest anti-hepatitis C virus prevalence in a large cohort of Japanese patients who underwent renal biopsy. The authors contend that the link between HCV and diabetes mellitus may explain, in part, the detrimental role of HCV on patient and graft survival after liver transplantation or renal transplantation. The authors conclude that preliminary evidence suggests that anti-viral therapies prior to kidney transplantation and new immunosuppressive regimens may lower the occurrence of diabetes mellitus in HCV-infected patients after kidney transplantation.
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Hepatitis C Virus Infection and Type-2 Diabetes Mellitus in Renal Diseases and Transplantation. Alimentary Pharmacology and Therapeutics. 21(6): 623-632. March 2005.
This review article addresses the potential link between hepatitis C virus (HCV) infection and the development of type 2 diabetes mellitus in patients with renal disease and transplantation. The authors found that the unadjusted odds ratio for developing post-transplant diabetes mellitus in hepatitis C virus-infected renal transplant recipients ranged between 1.58 and 16.5 across the published studies. The rate of anti-hepatitis C virus antibody in serum was higher among dialysis patients with diabetes mellitus. Patients with type 2 diabetes-related glomerulonephritis had the highest anti-hepatitis C virus prevalence in a large cohort of Japanese patients who underwent renal biopsy. The authors contend that the link between HCV and diabetes mellitus may explain, in part, the detrimental role of HCV on patient and graft survival after liver transplantation or renal transplantation. The authors conclude that preliminary evidence suggests that anti-viral therapies prior to kidney transplantation and new immunosuppressive regimens may lower the occurrence of diabetes mellitus in HCV-infected patients after kidney transplantation.
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Liver Imaging and Biotechnology. IN: U.S. Department of Health and Human Services. Action Plan for Liver Disease Research. Bethesda, MD: National Digestive Diseases Information Clearinghouse. 2004. pp. 153-159.
The imaging technologies most commonly used in liver disease include computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US), which can be used alone or in combination. US and CT possess the sensitivity necessary to detect dilated intrahepatic or extrahepatic biliary ducts. These imaging techniques can be used to assess patients with suspected obstructive jaundice, to evaluate changes in liver texture (due to fat or fibrosis), as well as to guide liver biopsy and treatment of focal lesions. This chapter on liver imaging and biotechnology is from the Action Plan for Liver Disease Research that was developed to advance research on liver and biliary diseases. The Action Plan was undertaken to identify areas of scientific opportunity to help direct research resources at the National Institutes of Health (NIH) toward practical goals in the prevention, diagnosis, and management of liver and biliary diseases. In this chapter, the authors first review the advances in liver imaging and biotechnology, then outline recent research advances including positron emission tomography (PET) and combining imaging with other clinical tools. The authors provide specific research goals in the areas of standardization of liver disease imaging with existing technologies and the development of new technologies for liver imaging. A final section considers the steps that would assist in achieving these research goals. One chart summarizes the short (0 to 3 years), intermediate (4 to 6 years), and long-term (7 to 10 years) goals of research on these topics. 2 figures. 1 table.
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Update on Current Standards of Care in the Diagnosis and Management of Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatis (NASH): Diagnosis: Part 1. Practical Gastroenterology. 28(9): 70-88. September 2004.
Steatosis (fatty infiltration of the liver) also called non-alcoholic fatty liver disease (NAFLD), is increasingly recognized as a common cause of chronic liver disease. This disease ranges from the presence of fatty liver without inflammation to steatosis accompanied by inflammation and fibrosis. NAFLD is associated with obesity, hypertension (high blood pressure), hyperlipidemia (increased levels of blood fats), diabetes mellitus, and insulin resistance. These disorders are collectively known as the Metabolic Syndrome. This article reviews recommendations and the standard of care for the medical treatment of patients with NAFLD. The authors note that NAFLD is progressive and may lead to non-alcoholic steatohepatitis (NASH). NASH can, in turn, lead to cirrhosis (liver scarring) and end stage liver disease ultimately requiring liver transplantation. The authors review diagnostic tests, including liver chemistries, imaging studies, and the role of liver biopsy. NASH can be silent without any physical symptoms or lab abnormalities and may be associated with end stage 'cryptogenic' cirrhosis as well as hepatic (liver) cancer. For that reason, physicians must be alert in recognizing the clinical features of NASH so that earlier diagnosis, treatment, or at least monitoring, can be provided. The authors note that there is still no evidence-based definitive medical treatment of NASH. 5 tables. 125 references.
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