Hepatobiliary conditions represent important etiologies of both chronic and acute illness. This edition of FP EssentialsTM will update family physicians on the evaluation and management of four hepatobiliary conditions: chronic viral hepatitis, cirrhosis, nonalcoholic steatohepatitis, and biliary stone disease.
The FP EssentialsTM monograph should be approximately 10,000 words in length, divided into four sections of approximately 2,500 words each, plus a preface, key practice recommendations, a maximum of 15 tables and figures, recommended readings, and references. The monograph should focus on what’s new in each topic and should answer the key questions listed for each section. Each section should begin with an illustrative case, similar to the examples provided, with modifications to emphasize key points. The references listed below include information that should be considered in preparation of this edition of FP EssentialsTM. However, these references are only a useful starting point that should be used to identify additional information to review.
Hepatobiliary Conditions
Section One: New Strategies in the Diagnosis and Management of Chronic Viral Hepatitis
Example case: Oliver, a 48-year-old white man, presents to your office for fatigue. He is a former intravenous drug user, but has not used for 25 years. Upon testing, he is found to have an alanine aminotransferase (ALT) level of 93 IU/L. Further testing reveals a positive antibody to hepatitis C virus.
Key questions to consider:
Key questions to consider:
- What is the recommended diagnostic evaluation for patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection? What are the best indicators of viral replication? Which patients should be referred for liver biopsy?
- How do ALT levels, viral load, hepatitis B e antigen (HbeAg), viral genotype, and staging by liver biopsy inform treatment decisions in HBV and HCV?
- What pharmacologic regimens are recommended for initial treatment of HBV and HCV?
- Which patients with HBV should be treated with antiretroviral drugs such as adefovir (Hepsera), telbivudine (Tyzeka), or tenofovir?
- What are HCV protease inhibitors (telaprevir, boceprevir) and polymerase inhibitors? Could the addition of these agents to standard combination therapy improve sustained virologic response rates in patients with HCV? What other specific targeted antiviral therapies for HCV (eg, STAT-C) hold promise for the future?
- What options are available after failed initial therapy?
- Are any nonprescription therapies beneficial for individuals with chronic viral hepatitis?
- What effect does coffee consumption have on the progression of HCV?
Initial references to consider:
- Dienstag JL, McHutchison JG. American Gastroenterological Association medical position statement on the management of hepatitis C. Gastroenterology. 2006;130(1):225-230. Erratum in: Gastroenterology. 2006;130(3):1018. Gastroenterology. 2006;131(3):979.
- Ferenci P, Laferl H, Scherzer TM, et al; Austrian Hepatitis Study Group. Peginterferon alfa-2a and ribavirin for 24 weeks in hepatitis C type 1 and 4 patients with rapid virological response. Gastroenterology. 2008 Aug;135(2):451-8.
- Freedman ND, Everhart JE, Lindsay KL, et al; HALT-C Trial Group. Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C. Hepatology. 2009 Jul 13. [Epub ahead of print]
- Ghany MG, Strader DB, Thomas DL, et al; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335-74. Also available at http://www.aasld.org/practiceguidelines/Pages/ViralHepatitis.aspx. Accessed September 2009.
- Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al; Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006 Dec;131(6):1743-1751.
- Hézode C, Forestier N, Dusheiko G, et al; PROVE2 Study Team. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med. 2009;360(18):1839-1850.
- Jensen DM, Marcellin P, Freilich B, et al. Re-treatment of patients with chronic hepatitis C who do not respond to peginterferon-alpha2b: a randomized trial. Ann Intern Med. 2009 Apr 21;150(8):528-540.
- Lai CL, Gane E, Liaw YF, et al; Globe Study Group. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med. 2007;357(25):2576-2588.
- Thompson AJ, McHutchison JG. Antiviral resistance and specifically targeted therapy for HCV (STAT-C). J Viral Hepat. 2009;16(6):377-387.
Section Two: New Strategies for the Management of Cirrhosis?
Example case: David, a 56-year-old man with a history of alcohol-induced cirrhosis, is hospitalized for exacerbation of chronic lung disease. Examination of the abdomen reveals shifting dullness to percussion, and ultrasound demonstrates the presence of ascites. He has no fever or abdominal pain.
Key questions to consider:
Key questions to consider:
- What conditions are emerging as the most important causes of cirrhosis?
- What drugs can help alleviate portal hypertension?
- What is the role of antibiotic prophylaxis for spontaneous bacterial peritonitis? When should patients undergo paracentesis?
- Which patients are most at risk for bleeding or death due to acute variceal hemorrhage? How can that risk be minimized?
- What is eltrombopag? Can it be used in patients with thrombocytopenia resulting from cirrhosis?
- What options are available for patients with advanced disease? What role is there, if any, for transjugular intrahepatic portosystemic shunt? Which patients are candidates for liver transplantation?
Initial references to consider:
- Abraldes JG, Albillos A, Bañares R. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology. 2009;136(5):1651-1658.
- Bambha K, Kim WR, Pedersen R. Predictors of early re-bleeding and mortality after acute variceal haemorrhage in patients with cirrhosis. Gut. 2008;57(6):814-820.
- Chavez-Tapia NC, Soares-Weiser K, Brezis M, et al. Antibiotics for spontaneous bacterial peritonitis in cirrhotic patients. Cochrane Database Syst Rev. 2007;(2):CD002232.
- Fernández J, Navasa M, Planas R, et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 2007;133(3):818-824.
- Gonzalez R, Zamora J, Gomez-Camarero J, et al. Meta-analysis: Combination endoscopic and drug therapy to prevent variceal rebleeding in cirrhosis. Ann Intern Med. 200815;149(2):109-122.
- McHutchison JG, Dusheiko G, Shiffman ML, et al; TPL102357 Study Group. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med. 2007;357(22):2227-2236.
- Ripoll C, Groszmann R, Garcia-Tsao G, et al; Portal Hypertension Collaborative Group. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology. 2007;133(2):481-488.
- Runyon BA; AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009;49(6):2087-2107. Also available at http://www.aasld.org/practiceguidelines/Pages/default.aspx. Accessed September 2009.
- Salerno F, Cammà C, Enea M, et al. Transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis of individual patient data. Gastroenterology. 2007;133(3):825-834. Erratum in: Gastroenterology. 2007;133(5):1746.
Section Three: Diagnosis and Management of Nonalcoholic Steatohepatitis
Example case: Kimberly, a 45-year-old woman, is found to have several abnormal liver enzymes on routine laboratory tests. She has central obesity and hyperlipidemia that is controlled with pravastatin. She does not use alcohol. Viral hepatitis panel is negative, and transferrin saturation is normal. Computerized tomography scan reveals diffuse fatty infiltration of the liver with no dominant mass.
Key questions to consider:
Key questions to consider:
- What are nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease? Are they the same or different conditions? How are they related to obesity and insulin resistance?
- What is the recommended diagnostic evaluation for patients suspected to have NASH? Which patients should be referred for liver biopsy? Is NASH evaluated differently in children?
- How effective is weight loss in the management of NASH?
- What role, if any, do insulin-sensitizing agents such as pioglitazone have in treating NASH?
- What is probucol, and is it beneficial for patients with NASH?
Initial references to consider:
- Aithal GP, Thomas JA, Kaye PV, et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology. 2008;135(4):1176-1184.
- Angelico F, Burattin M, Alessandri C, et al. Drugs improving insulin resistance for non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005166.
- Merat S, Aduli M, Kazemi R, et al. Liver histology changes in nonalcoholic steatohepatitis after one year of treatment with probucol. Dig Dis Sci. 2008;53(8):2246-2250.
- Patton HM, Lavine JE, Van Natta ML, et al; Nonalcoholic Steatohepatitis Clinical Research Network. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology. 2008;135(6):1961-1971.e2.
- Ratziu V, Giral P, Jacqueminet S, et al; LIDO Study Group. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology. 2008;135(1):100-110.
Section Four: Current Concepts in the Diagnosis and Management of Biliary Stone Disease
Example case: Elena, a 38-year-old woman who is 6 weeks postpartum, presents to your office with right-upper-quadrant abdominal pain, nausea, and vomiting for 3 hours. The pain began 30 minutes after eating. She had a similar episode 2 weeks ago that resolved spontaneously.
Key questions to consider:
Key questions to consider:
- How do newer imaging techniques, such as endoscopic ultrasound and magnetic resonance cholangiopancreatography, compare with conventional ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) in the diagnostic evaluation of biliary stone disease?
- Is ezetimibe or ursodeoxycholic acid helpful for preventing or managing gallstones?
- Should asymptomatic gallstones or common duct stones (detected incidentally on imaging for other problems) be treated?
- When might an endoscopic approach be preferable to surgical management of ductal gallstones? Is small-incision cholecystectomy superior to laparoscopic cholecystectomy? Does ERCP improve outcomes when used as a preoperative or postoperative adjunct to surgery?
- What is the optimal timing of cholecystectomy for acute cholecystitis?
- Is cholecystectomy an effective way to treat symptomatic patients who do not have gallstones but who have positive hepatobiliary iminodiacetic acid scans?
Initial references to consider:
- Clayton ES, Connor S, Alexakis N, et al. Meta-analysis of endoscopy and surgery versus surgery alone for common bile duct stones with the gallbladder in situ. Br J Surg. 2006;93(10):1185-1191 [Review].
- Keus F, Werner JE, Gooszen HG, et al. Randomized clinical trial of small-incision and laparoscopic cholecystectomy in patients with symptomatic cholecystolithiasis: primary and clinical outcomes. Arch Surg. 2008;143(4):371-377; discussion 377-378 [Review].
- Mahid SS, Jafri NS, Brangers BC, et al. Meta-analysis of cholecystectomy in symptomatic patients with positive hepatobiliary iminodiacetic acid scan results without gallstones. Arch Surg. 2009 Feb;144(2):180-187.
- Martin DJ, Vernon DR, Toouli J. Surgical versus endoscopic treatment of bile duct stones. Cochrane Database Syst Rev. 2006;(2):CD003327.
- Siddiqui T, MacDonald A, Chong PS, et al. Early versus delayed laparoscopic cholecystectomy for acute cholecystitis: a meta-analysis of randomized clinical trials. Am J Surg. 2008;195(1):40-47.
- Wang HH, Portincasa P, Mendez-Sanchez N, et al. Effect of ezetimibe on the prevention and dissolution of cholesterol gallstones. Gastroenterology. 2008;134(7):2101-2110.
- Williams EJ, Green J, Beckingham I, et al; British Society of Gastroenterology. Guidelines on the management of common bile duct stones (CBDS). Gut. 2008 Jul;57(7):1004-1021 [Review].
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