Gastrointestinal varices medical therapy

Jump to navigation Jump to search

Gastrointestinal varices Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Gastrointestinal varices from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Guidelines for Management

Case Studies

Case #1

Gastrointestinal varices medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Gastrointestinal varices medical therapy

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Gastrointestinal varices medical therapy

CDC on Gastrointestinal varices medical therapy

Gastrointestinal varices medical therapy in the news

Blogs on Gastrointestinal varices medical therapy

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for Gastrointestinal varices medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Overview

Medical therapy in cases of gastrointestinal varices includes goal-directed management of the cause of portal hypertension along with specific management of varices after their development. The treatment is aimed at optimizing portal venous inflow, portal pressure and portal resistance. The pharmacological therapy includes vasoconstrictors (beta blockers) and venodilators (nitrates). These therapies may be employed alone or in combination with endoscopic variceal ligation/sclerotherapy and transjugular intrahepatic shunt (TIPS) therapy depending upon the condition of the patient.

Medical Therapy

Medical therapy for gastrointestinal varices should include management of the underlying cause of portal hypertension and specific therapy for varices after they have developed.

Treatment of underlying causes

Alcoholic liver disease

For a detailed description for treatment of alcoholic liver disease, click here.

Hepatitis C

For a detailed description for treatment of Hepatitis C, click here[1][2][3][4][5][6]

Genotypes HCV 1 and 4

  • Preferred regimen (1): Peginterferon plus ribavirin for 48 weeks. The dose for peginterferon alfa-2a is 180 µg subcutaneously per week together with ribavirin using doses of 1,000 mg for those <75 kg in weight and 1,200 mg for those >75 kg; the dose for peginterferon alfa-2b is 1.5 µg/kg subcutaneously per week together with ribavirin using doses of 800 mg for those weighing <65 kg; 1,000 mg for those weighing >65 kg to 85 kg, 1,200 mg for >85 kg to 105 kg, and 1,400 mg for >105 kg.[7]

Genotypes HCV 2 and 3

Hepatitis B

For a detailed description for treatment of Hepatitis B, click here[9][10][11][12][13][14][15][16][17][18][13]
a. ALT greater than 2 times normal or moderate/severe hepatitis on biopsy, and HBV DNA >20,000 IU/mL - treatment may be initiated with any of the 7 approved antiviral medications, but pegIFN-α, tenofovir or entecavir are preferred.
b. ALT persistently normal or minimally elevated (<2 times normal) - should not be initiated on treatment.
c. Children with elevated ALT greater than 2 times normal - treatment may be initiated with IFN-α or lamivudine if ALT levels remain elevated at this level for longer than 6 months.

Autoimmune hepatitis

For a detailed description for treatment of autoimmune hepatits, click here.

Primary biliary cirrhosis

For a detailed description for treatment of primary biliary cirrhosis, click here.

Primary sclerosing cholangitis

For a detailed description for treatment of primary sclerosing cholangitis, click here.

Wilson's disease

For a detailed description for treatment of Wilson's disease, click here.

Treatment of Esophageal Varices

General considerations and disease stratification

The management of gastrointestinal varices in chronic liver disease should be tailored according to the clinical stage of liver disease and cirrhosis. The following table outlines the key stages of chronic liver disease and the treatment goals for the respective stage:

Disease stage HPVG Varices Complications of portal hypertension Management goals
Compensated liver disease Less than 10 mmHg - -
Greater than equal to 10 mmHg - - Prevent decompensation
Greater than equal to 10 mmHg + - Prevent decompensation
Decompensated liver disease Greater than equal to 12 mmHg + Acute variceal bleed Control bleeding, prevent early rebleeding and death
Greater than equal to 12 mmHg + Previous variceal hemorrhage without ascites or encephalopathy Prevent further decompensation (further bleeding, ascites and encephalopathy)
Greater than equal to 12 mmHg + Prior variceal hemorrhage with ascites and/or encephalopathy Prevent further decompensation and death

Goal-directed management

The management of gastrointestinal varices is aimed at optimizing the following:[23][24]

This is achieved through the following pharmacological therapies:[25][23]

The following table shows the major mechanism affected by the various pharmacological therapies used in the management of varices:[26][27][28][23][25]

Major pharmacological therapy Portal flow Portal resistance Portal pressure
Vasoconstrictors (e.g. β-blockers) ↓↓
Venodilators (e.g. nitrates)
Endoscopic therapy
TIPS/Shunt therapy ↓↓↓ ↓↓↓

1 Small non-bleeding varices

  • 1.1 Adult
    • 1.1.1 Child-Pugh B and C or increased risk of bleeding
      • Preferred regimen (1): Propranolol immediate-release initial dose of 20 mg BID; adjust to maximal tolerated dose
      • Alternative regimen (1): Nadolol initial dose of 40 mg once daily; adjust to maximal tolerated dose
    • 1.1.2 No increased risk of bleeding
      • Preferred regimen (1): Propranolol immediate-release initial dose of 20 mg BID; adjust to maximal tolerated dose
      • Alternative regimen (1): Nadolol initial dose of 40 mg once daily; adjust to maximal tolerated dose
    • 1.1.3 No previous use of beta blockers
      • Preferred regimen (1): EGD should be repeated in 2 years
    • 1.1.4 Hepatic decompensation
      • Preferred regimen (1): EGD should be done at that time and repeated annually

2 Large non-bleeding varices[29][30][31][32][33][34][35][36][37]

2.1 Adult

  • 2.1.1 Child-Pugh B and C or increased risk of bleeding
    • Preferred regimen (1): Propranolol immediate-release initial dose of 20 mg BID; adjust to maximal tolerated dose
    • Preferred regimen (2): Endoscopic variceal ligation
    • Alternative regimen (1): Nadolol initial dose of 40 mg once daily; adjust to maximal tolerated dose
  • 2.1.2 No increased risk of bleeding
    • Preferred regimen (1): Propranolol immediate-release initial dose of 20 mg BID; adjust to maximal tolerated dose
    • Preferred regimen (2): Endoscopic variceal ligation
    • Alternative regimen (1): Nadolol initial dose of 40 mg once daily; adjust to maximal tolerated dose
  • 2.1.3 No previous use of beta blockers
    • Preferred regimen (1): EGD should be repeated in 2 years
    • Preferred regimen (2): Endoscopic variceal ligation
  • 2.1.4 Hepatic decompensation
    • Preferred regimen (1): EGD should be done at that time and repeated annually
    • Preferred regimen (2): Endoscopic variceal ligation

3 Acute hemorrhage[38][39][40]

  • 3.1 Adult
    • Preferred regimen (1): Endoscopy (sclerotherapy or endoscopic variceal ligation) within 12 hours of bleed plus octreotide initial IV bolus of 50 µg followed by a continuous infusion of 50 µg/hour (should be continued for 3-5 days after confirmation of diagnosis) plus norfloxacin 400 mg PO BID for 7 days
    • Preferred regimen (2): Vasopressin continuous IV infusion of 0.2–0.4 units/minute that can be increased to a maximal dose of 0.8 units/minute. It should always be accompanied by IV nitroglycerin at a starting dose of 40 µg/minute, which can be increased to a maximum of 400 µg/minute, adjusted to maintain a systolic blood pressure >90 mmHg
    • Preferred regimen (3): Endoscopy within 12 hours of bleed plus telipressin initial dose of 2 mg IV every 4 hours and can be titrated down to 1 mg IV every 4 hours once hemorrhage is controlled (should be continued for 3-5 days after confirmation of diagnosis) plus norfloxacin 400 mg PO BID for 7 days
    • Alternative regimen (1): Endoscopy (sclerotherapy or endoscopic variceal ligation) within 12 hours of bleed plus octreotide initial IV bolus of 50 µg followed by a continuous infusion of 50 µg/hour (should be continued for 3-5 days after confirmation of diagnosis) plus ciprofloxacin 400 mg PO BID for 7 days
  • 3.1.1 Adult (Child-Pugh B and C)
    • Preferred regimen (1): Endoscopy (sclerotherapy or endoscopic variceal ligation) within 12 hours of bleed plus octreotide initial IV bolus of 50 µg followed by a continuous infusion of 50 µg/hour (should be continued for 3-5 days after confirmation of diagnosis) plus IV ceftriaxone 1 g/day
  • 3.1.2 Adult (Bleeding despite pharmacological plus endoscopic therapy)
  • 3.1.3 Adult (Temporary measure- in case of planned TIPS or endoscopy)

Treatment of Gastric Varices

The following treatment options may be employed for the treatment of bleeding gastric varices:

1 Fundic varices

  • 1.1 Adult
    • Preferred regimen (1): Endoscopic variceal obturation using tissue adhesives such as cyanoacrylate

References

  1. Lai MY, Kao JH, Yang PM, Wang JT, Chen PJ, Chan KW, Chu JS, Chen DS (1996). "Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C". Gastroenterology. 111 (5): 1307–12. PMID 8898645.
  2. Everson GT (2005). "Management of cirrhosis due to chronic hepatitis C". J. Hepatol. 42 Suppl (1): S65–74. doi:10.1016/j.jhep.2005.01.009. PMID 15777574.
  3. Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, Ling MH, Albrecht J (2002). "Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C". Gastroenterology. 122 (5): 1303–13. PMID 11984517.
  4. Poynard T, McHutchison J, Manns M, Myers RP, Albrecht J (2003). "Biochemical surrogate markers of liver fibrosis and activity in a randomized trial of peginterferon alfa-2b and ribavirin". Hepatology. 38 (2): 481–92. doi:10.1053/jhep.2003.50319. PMID 12883493.
  5. McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, McNair L, Alam J, Muir AJ (2009). "Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection". N. Engl. J. Med. 360 (18): 1827–38. doi:10.1056/NEJMoa0806104. PMID 19403902.
  6. Poordad F, McCone J, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP (2011). "Boceprevir for untreated chronic HCV genotype 1 infection". N. Engl. J. Med. 364 (13): 1195–206. doi:10.1056/NEJMoa1010494. PMC 3766849. PMID 21449783.
  7. Vierling JM, Zeuzem S, Poordad F, Bronowicki JP, Manns MP, Bacon BR, Esteban R, Flamm SL, Kwo PY, Pedicone LD, Deng W, Dutko FJ, DiNubile MJ, Koury KJ, Helmond FA, Wahl J, Bruno S (2014). "Safety and efficacy of boceprevir/peginterferon/ribavirin for HCV G1 compensated cirrhotics: meta-analysis of 5 trials". J. Hepatol. 61 (2): 200–9. doi:10.1016/j.jhep.2014.03.022. PMID 24747798.
  8. "Medscape Log In".
  9. Perrillo RP (1990). "Factors influencing response to interferon in chronic hepatitis B: implications for Asian and western populations". Hepatology. 12 (6): 1433–5. PMID 1701755.
  10. Hoofnagle JH, di Bisceglie AM (1997). "The treatment of chronic viral hepatitis". N. Engl. J. Med. 336 (5): 347–56. doi:10.1056/NEJM199701303360507. PMID 9011789.
  11. Dienstag JL, Perrillo RP, Schiff ER, Bartholomew M, Vicary C, Rubin M (1995). "A preliminary trial of lamivudine for chronic hepatitis B infection". N. Engl. J. Med. 333 (25): 1657–61. doi:10.1056/NEJM199512213332501. PMID 7477217.
  12. Dienstag JL, Goldin RD, Heathcote EJ, Hann HW, Woessner M, Stephenson SL, Gardner S, Gray DF, Schiff ER (2003). "Histological outcome during long-term lamivudine therapy". Gastroenterology. 124 (1): 105–17. doi:10.1053/gast.2003.50013. PMID 12512035.
  13. 13.0 13.1 Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J (2004). "Lamivudine for patients with chronic hepatitis B and advanced liver disease". N. Engl. J. Med. 351 (15): 1521–31. doi:10.1056/NEJMoa033364. PMID 15470215.
  14. Lok AS, McMahon BJ (2004). "Chronic hepatitis B: update of recommendations". Hepatology. 39 (3): 857–61. doi:10.1002/hep.20110. PMID 14999707.
  15. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Arterburn S, Xiong S, Currie G, Brosgart CL (2005). "Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B". N. Engl. J. Med. 352 (26): 2673–81. doi:10.1056/NEJMoa042957. PMID 15987916.
  16. Chang TT, Gish RG, Hadziyannis SJ, Cianciara J, Rizzetto M, Schiff ER, Pastore G, Bacon BR, Poynard T, Joshi S, Klesczewski KS, Thiry A, Rose RE, Colonno RJ, Hindes RG (2005). "A dose-ranging study of the efficacy and tolerability of entecavir in Lamivudine-refractory chronic hepatitis B patients". Gastroenterology. 129 (4): 1198–209. doi:10.1053/j.gastro.2005.06.055. PMID 16230074.
  17. Schiff ER, Lai CL, Hadziyannis S, Neuhaus P, Terrault N, Colombo M, Tillmann HL, Samuel D, Zeuzem S, Lilly L, Rendina M, Villeneuve JP, Lama N, James C, Wulfsohn MS, Namini H, Westland C, Xiong S, Choy GS, Van Doren S, Fry J, Brosgart CL (2003). "Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post-liver transplantation patients". Hepatology. 38 (6): 1419–27. doi:10.1016/j.hep.2003.09.040. PMID 14647053.
  18. "EASL Clinical Practice Guidelines: Management of chronic hepatitis B virus infection - Journal of Hepatology".
  19. Lai CL, Leung N, Teo EK, Tong M, Wong F, Hann HW, Han S, Poynard T, Myers M, Chao G, Lloyd D, Brown NA (2005). "A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B". Gastroenterology. 129 (2): 528–36. doi:10.1016/j.gastro.2005.05.053. PMID 16083710.
  20. Manolakopoulos S, Triantos C, Theodoropoulos J, Vlachogiannakos J, Kougioumtzan A, Papatheodoridis G, Tzourmakliotis D, Karamanolis D, Burroughs AK, Archimandritis A, Raptis S, Avgerinos A (2009). "Antiviral therapy reduces portal pressure in patients with cirrhosis due to HBeAg-negative chronic hepatitis B and significant portal hypertension". J. Hepatol. 51 (3): 468–74. doi:10.1016/j.jhep.2009.05.031. PMID 19616339.
  21. Villeneuve JP, Condreay LD, Willems B, Pomier-Layrargues G, Fenyves D, Bilodeau M, Leduc R, Peltekian K, Wong F, Margulies M, Heathcote EJ (2000). "Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B". Hepatology. 31 (1): 207–10. doi:10.1002/hep.510310130. PMID 10613747.
  22. Fontana RJ, Hann HW, Perrillo RP, Vierling JM, Wright T, Rakela J, Anschuetz G, Davis R, Gardner SD, Brown NA (2002). "Determinants of early mortality in patients with decompensated chronic hepatitis B treated with antiviral therapy". Gastroenterology. 123 (3): 719–27. PMID 12198698.
  23. 23.0 23.1 23.2 Blei AT, Garcia-Tsao G, Groszmann RJ, Kahrilas P, Ganger D, Morse S, Fung HL (1987). "Hemodynamic evaluation of isosorbide dinitrate in alcoholic cirrhosis. Pharmacokinetic-hemodynamic interactions". Gastroenterology. 93 (3): 576–83. PMID 3301517.
  24. Reichen J, Le M (1986). "Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver". J. Clin. Invest. 78 (2): 448–55. doi:10.1172/JCI112596. PMC 423578. PMID 3734100.
  25. 25.0 25.1 Kong DR, Ma C, Wang M, Wang JG, Chen C, Zhang L, Hao JH, Li P, Xu JM (2013). "Effects of propranolol or propranolol plus isosorbide-5-mononitrate on variceal pressure in schistosomiasis". World J. Gastroenterol. 19 (26): 4228–33. doi:10.3748/wjg.v19.i26.4228. PMC 3710427. PMID 23864788.
  26. D'Amico G, Pagliaro L, Bosch J (1999). "Pharmacological treatment of portal hypertension: an evidence-based approach". Semin. Liver Dis. 19 (4): 475–505. doi:10.1055/s-2007-1007133. PMID 10643630.
  27. Calés P, Oberti F, Payen JL, Naveau S, Guyader D, Blanc P, Abergel A, Bichard P, Raymond JM, Canva-Delcambre V, Vetter D, Valla D, Beauchant M, Hadengue A, Champigneulle B, Pascal JP, Poynard T, Lebrec D (1999). "Lack of effect of propranolol in the prevention of large oesophageal varices in patients with cirrhosis: a randomized trial. French-Speaking Club for the Study of Portal Hypertension". Eur J Gastroenterol Hepatol. 11 (7): 741–5. PMID 10445794.
  28. Merkel C, Marin R, Angeli P, Zanella P, Felder M, Bernardinello E, Cavallarin G, Bolognesi M, Donada C, Bellini B, Torboli P, Gatta A (2004). "A placebo-controlled clinical trial of nadolol in the prophylaxis of growth of small esophageal varices in cirrhosis". Gastroenterology. 127 (2): 476–84. PMID 15300580.
  29. Abraczinskas DR, Ookubo R, Grace ND, Groszmann RJ, Bosch J, Garcia-Tsao G, Richardson CR, Matloff DS, Rodés J, Conn HO (2001). "Propranolol for the prevention of first esophageal variceal hemorrhage: a lifetime commitment?". Hepatology. 34 (6): 1096–102. doi:10.1053/jhep.2001.29305. PMID 11731997.
  30. Garcia-Tsao, Guadalupe; Sanyal, Arun J.; Grace, Norman D.; Carey, William (2007). "Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis". Hepatology. 46 (3): 922–938. doi:10.1002/hep.21907. ISSN 0270-9139.
  31. Khuroo MS, Khuroo NS, Farahat KL, Khuroo YS, Sofi AA, Dahab ST (2005). "Meta-analysis: endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleeding". Aliment. Pharmacol. Ther. 21 (4): 347–61. doi:10.1111/j.1365-2036.2005.02346.x. PMID 15709985.
  32. Li L, Yu C, Li Y (2011). "Endoscopic band ligation versus pharmacological therapy for variceal bleeding in cirrhosis: a meta-analysis". Can. J. Gastroenterol. 25 (3): 147–55. PMC 3076033. PMID 21499579.
  33. Jutabha R, Jensen DM, Martin P, Savides T, Han SH, Gornbein J (2005). "Randomized study comparing banding and propranolol to prevent initial variceal hemorrhage in cirrhotics with high-risk esophageal varices". Gastroenterology. 128 (4): 870–81. PMID 15825071.
  34. Boyer TD (2005). "Primary prophylaxis for variceal bleeding: are we there yet?". Gastroenterology. 128 (4): 1120–2. PMID 15825093.
  35. de Franchis R (2006). "Endoscopy critics vs. endoscopy enthusiasts for primary prophylaxis of variceal bleeding". Hepatology. 43 (1): 24–6. doi:10.1002/hep.21026. PMID 16374843.
  36. Lo GH, Chen WC, Chen MH, Lin CP, Lo CC, Hsu PI, Cheng JS, Lai KH (2004). "Endoscopic ligation vs. nadolol in the prevention of first variceal bleeding in patients with cirrhosis". Gastrointest. Endosc. 59 (3): 333–8. PMID 14997127.
  37. Schepke M, Kleber G, Nürnberg D, Willert J, Koch L, Veltzke-Schlieker W, Hellerbrand C, Kuth J, Schanz S, Kahl S, Fleig WE, Sauerbruch T (2004). "Ligation versus propranolol for the primary prophylaxis of variceal bleeding in cirrhosis". Hepatology. 40 (1): 65–72. doi:10.1002/hep.20284. PMID 15239087.
  38. D'Amico G, De Franchis R (2003). "Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators". Hepatology. 38 (3): 599–612. doi:10.1053/jhep.2003.50385. PMID 12939586.
  39. Carbonell N, Pauwels A, Serfaty L, Fourdan O, Lévy VG, Poupon R (2004). "Improved survival after variceal bleeding in patients with cirrhosis over the past two decades". Hepatology. 40 (3): 652–9. doi:10.1002/hep.20339. PMID 15349904.
  40. Chalasani N, Kahi C, Francois F, Pinto A, Marathe A, Bini EJ, Pandya P, Sitaraman S, Shen J (2003). "Improved patient survival after acute variceal bleeding: a multicenter, cohort study". Am. J. Gastroenterol. 98 (3): 653–9. PMID 12650802.