Cirrhosis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2] Sudarshana Datta, MD [3]

Overview

The change that cirrhosis causes to the liver is irreversible, therefore treatment is mostly centered on ameliorating the complications of cirrhosis. This entails treating pain, osteoporosis, hypogonadism, constipation, itching, malnutrition, as well as any identified underlying causes.

Medical Therapy

Pruritus

Hypogonadism

  • Males with cirrhosis sometimes complain of loss of libido due to hypogonadism.
  • Preferred regimen (1): Topical testosterone preparations
  • Preferred regimen (2): Growth hormone therapy

Osteoporosis

Pain management in Cirrhosis

  • Cirrhotic patients can develop pain from ascites (back and abdominal pain) and pain from gynecomastia (mastalgia).
  • Pain management in cirrhosis needs special consideration as many analgesic and anti-inflammatory drugs are metabolized by the liver and dosage regulations are required to prevent further liver damage and drug toxicity.
  • Drug dosages should be titrated as per the level of hepatic functioning in the patient.
  • Dosage changes are required in the follwing patients:
  • Non-selective NSAIDs should be avoided in patients with cirrhosis because of the following complications:
    • Increased bleeding from varices
    • Impaired renal function
    • Development of diuretic resistant ascites
    • Alternative regimen for pain in cirrhosis: celecoxib
  • Opioids should be used with caution in patients with cirrhosis because they are metabolized by the liver through oxidation and glucuronidation.
  • Patients with cirrhosis have reduced liver blood flow, protein binding and hepatic enzyme capacity,leading to drug accumulation and increased vulnerability to developing opiate toxicity.

Nutrition and exercise

The following points need to be kept in mind regarding nutrition in cirrhosis patients:[6][7][8][9]

  • Anorexia is common in cirrhosis patients with ascites due to the direct compression of the bowel by the ascitic fluid.
  • Adequate calories and proteins should be added to the diet of the patient.
  • Patients should consume a balanced diet and one multivitamin daily.
  • Vitamin D and K supplementation is recommended in patients with cholestasis.
  • Patients frequently benefit from the addition of commonly available liquid and powdered nutritional supplements to the diet.
  • Patients are encouraged to exercise regularly to prevent muscle wasting.
  • An exercise program under the direct supervision of a physical therapist may be proposed for patients.

Protein

  • The diet of cirrhosis patients should be adequately titrated for protein.
  • Excessive protein in the diet places the patient at risk for hepatic encephalopathy.
  • Low protein levels in the diet cause muscle wasting.
  • As per the guidelines by the American Association for the Study of Liver Diseases and the American College of Gastroenterology, cirrhosis patients with protein malnutrition require multiple feedings per day with breakfast and a nightly snack.[10][11][8]
  • Branched-chain amino acids (BCAA) can function as pharmacologic nutrients for patients with decompensated cirrhosis.

Zinc

  • Zinc deficiency is commonly observed in patients with cirrhosis.
  • Zinc supplementation can also help resolve muscle cramps.
  • Low dose Zn supplementation could prevent deterioration of the clinical status of cirrhosis and prevent excess Cu accumulation in non-alcoholic cirrhotic patients.
  • Zn supplementation produces metabolic effects and trends towards improvements in liver function, hepatic encephalopathy, and nutritional status.[12]
  • Preferred regimen: 220 mg Zinc po q12h may improve dysgeusia and also helps in stimulating the patient's appetite.

Vaccination

  • Patients with cirrhosis must be vaccinated against the following:
    • Hepatitis A
    • Pneumococci
    • Influenza

Treatment of Underlying Causes

Alcoholic Liver Disease

Alcoholic Liver Disease Medical Therapy
  • Mild to moderate alcoholic hepatitis:
    • Abstinence from alcohol
    • Preferred regimen (1): Aggressive enteral nutrition therapy
  • Severe Alcoholic hepatitis:
    • Preferred regimen (1): Four week course of prednisolone (40 mg/day for 28 days), typically followed by discontinuation or a 2-week taper (if no contraindications for steroid use).
    • Preferred regimen (2):Pentoxifylline therapy (400 mg orally 3 times daily for 4 weeks) is an alternative in severe disease, especially if there are contraindications to steroid therapy

Hepatitis C

Hepatitis C Medical Therapy[13][14][15][16][17][18]
  • Abstinence from alcohol as alcohol aggravates HCV associated fibrosis, cirrhosis and makes liver cancer more likely.

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.[19]

Genotypes HCV 2 and 3

  • Preferred regimen (1): peginterferon plus ribavirin should be administered for 24 weeks, using a ribavirin dose of 800 mg.[20]
  • Alternative regimen (1): Triple therapy- peginterferon plus ribavirin along with an additional dose of 100mg of amantadine q12h.

Hepatitis B

Hepatitis B Medical Therapy[21][22][23][24][25][26][27][28][29][30][25]
  • Patients with HBeAg-positive chronic hepatitis B[31]
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

Autoimmune Hepatitis Medical Therapy

Primary Biliary Cirrhosis

Primary Biliary Cirrhosis Medical Therapy
  • There is no known cure, but medication may slow the progression so that a normal lifespan and quality of life may be attainable.

Primary Sclerosing Cholangitis

Primary Sclerosing Cholangitis Medical Therapy
  • Standard treatment includes ursodiol which has been shown to lower elevated liver enzyme numbers in people with PSC.
  • Symptomatic treatment includes:
    • Anti-histaminics - for itching
    • Cholestyramine - bile acid sequestrant
    • Antibiotics - for infections
    • Vitamin supplemantation - Vitamin A, D and K.

Wilson's Disease

Wilson's Disease Medical Therapy
  • Avoid intake of foods and water with high concentrations of copper.
  • Initial treatment for symptomatic patients includes a chelating agent (D-penicillamine, trientine or zinc).
  • Patients with acute liver failure due to Wilson's disease, or unresponsive to chelation treatment - should be referred to liver transplantation.

Treatment of Complications

Ascites

Ascites Treatment[35][36][37][38][39][40][41]
  • Abstinence from alcohol.
  • Salt restriction to less than 2000 mg per day.
  • Fluid restriction unless the serum sodium is less than 120 - 125 mmol/L.
  • Diuretics are the first line drugs for the treatment of ascites.
  • Therapeutic paracentesis in tense ascites. Serial therapeutic paracentesis is a treatment option for refractory ascites.
  • Intravenous albumin infusion may also be considered in refractory cases. [42]
  • TIPS may be used in refractory cases of ascites.[43]

Esophageal Variceal Bleeding

Esophageal Varices Treatment[44][45]
  • Patients with no varices and bleeding:
    • EGD should be performed at regular intervals.
  • Patients with small varices that have not bled:[46][47][48][49][50][51]
    • Non-selective beta blockers should be used to prevent the first variceal bleeding[52][53][54]
    • Those not receiving beta blockers, should be followed up with EGD every 2 years
    • If the liver decompensates, EGD should be performed at that time and then annually
    • Those who recieve beta blockers may not require a regular follow up with EGD
  • Patients with medium/large varices that have not bled:
    • Esophageal variceal ligation or non-selective beta blockers may be used to prevent first variceal bleeding, as these patients are at a higher risk for bleeding with beta blockers being the first choice of treatment and esophageal variceal ligation reserved for those who are unable to tolerate the drugs
    • Nitrates, sclerotherapy and shunts alone are not used as primary prophylaxis to prevent bleeding
  • Patients with cirrhosis and an acute episode of variceal hemorrhage:[55][56]
  • Patients who have cirrhosis and have recovered from a variceal bleed:[68][69][70]
    • Combination of esophageal variceal ligation (EVL) and non-selective beta blockers
    • EVL should be repeated every 1-2 weeks until obliteration with first surveillance EVL performed 1-3 months and then every 6-12 months to check for recurrence
    • Refractory cases should be referred for transplantation.

Hepatic Encephalopathy

The treatment of hepatic encephalopathy in cirrhosis is as follows: [71]

Hepatic Encephalopathy Treatment

Prevention of hepatic encephalopathy:

  • Reduced protein intake
    • May lead to protein malnutrition and negative nitrogen balance
  • Correction of hypokalemia
  • Lactulose
    • Decreases absorption of ammonia from the gastrointestinal tract
    • Works as a laxative, increasing the transit time and reducing absorption of ammonia
    • Lactulose can be given rectally for patients who cannot take oral medications.[72][73][74] One regimen is 300 mL (200 gm) of lactulose syrup (10 gm/15 ml) in 1 L of water which is retained for 1 hour, with the patient in the Trendelenburg position.[75]
  • Antibiotics
  • Rifaximin[76][77]
    • Dose of 400 mg taken orally 3 times a day was as effective as lactulose or lactilol at improving hepatic encephalopathy symptoms.[78] Similarly, rifaximin was as effective as neomycin and paromomycin.[79][80]
  • Benzodiazepines receptor agonists

Hepatorenal Syndrome

Hepatorenal Syndrome Treatment[81][61][82]

Other treatment modalities:

Spontaneous Bacterial Peritonitis

Spontaneous Bacterial Peritonitis Medical Therapy[84][85][86]

Contraindicated medications

Cirrhosis is considered an absolute contraindication to the use of the following medications:

References

  1. ↑ Garcia-Tsao G (2001). "Current management of the complications of cirrhosis and portal hypertension: variceal hemorrhage, ascites, and spontaneous bacterial peritonitis". Gastroenterology. 120 (3): 726–48. PMID 11179247.
  2. ↑ Tsochatzis EA, Bosch J, Burroughs AK (2012). "New therapeutic paradigm for patients with cirrhosis". Hepatology. 56 (5): 1983–92. doi:10.1002/hep.25915. PMID 22729954.
  3. ↑ "Effects of ethanol consumption on hepatic hemodynamics in patients with alcoholic cirrhosis - Gastroenterology".
  4. ↑ "EASL clinical practical guidelines: management of alcoholic liver disease". J. Hepatol. 57 (2): 399–420. 2012. doi:10.1016/j.jhep.2012.04.004. PMID 22633836.
  5. ↑ Giouleme OI, Vyzantiadis TA, Nikolaidis NL; et al. (2006). "Pathogenesis of osteoporosis in liver cirrhosis". Hepatogastroenterology. 53 (72): 938–43. PMID 17153457.
  6. ↑ Kondrup J, Nielsen K, Hamberg O (1993). "[Nutritional therapy in patients with liver cirrhosis]". Ugeskr. Laeg. (in Danish). 155 (29): 2248–51. PMID 8328092.
  7. ↑ Silk DB, O'Keefe SJ, Wicks C (1991). "Nutritional support in liver disease". Gut. Suppl: S29–33. PMC 1405219. PMID 1916467.
  8. ↑ 8.0 8.1 Plank LD, Gane EJ, Peng S, Muthu C, Mathur S, Gillanders L, McIlroy K, Donaghy AJ, McCall JL (2008). "Nocturnal nutritional supplementation improves total body protein status of patients with liver cirrhosis: a randomized 12-month trial". Hepatology. 48 (2): 557–66. doi:10.1002/hep.22367. PMID 18627001.
  9. ↑ Plauth M, Cabré E, Riggio O, Assis-Camilo M, Pirlich M, Kondrup J, Ferenci P, Holm E, Vom Dahl S, Müller MJ, Nolte W (2006). "ESPEN Guidelines on Enteral Nutrition: Liver disease". Clin Nutr. 25 (2): 285–94. doi:10.1016/j.clnu.2006.01.018. PMID 16707194.
  10. ↑ O'Shea RS, Dasarathy S, McCullough AJ (2010). "Alcoholic liver disease". Am. J. Gastroenterol. 105 (1): 14–32, quiz 33. doi:10.1038/ajg.2009.593. PMID 19904248.
  11. ↑ Córdoba J, López-Hellín J, Planas M, Sabín P, Sanpedro F, Castro F, Esteban R, Guardia J (2004). "Normal protein diet for episodic hepatic encephalopathy: results of a randomized study". J. Hepatol. 41 (1): 38–43. doi:10.1016/j.jhep.2004.03.023. PMID 15246205.
  12. ↑ Somi MH, Rezaeifar P, Ostad Rahimi A, Moshrefi B (2012). "Effects of Low Dose Zinc Supplementation on Biochemical Markers in Non-alcoholic Cirrhosis: A Randomized Clinical Trial". Arch Iran Med. 15 (8): 472–6. PMID 22827782.
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  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ "Medscape Log In".
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  25. ↑ 25.0 25.1 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.
  26. ↑ Lok AS, McMahon BJ (2004). "Chronic hepatitis B: update of recommendations". Hepatology. 39 (3): 857–61. doi:10.1002/hep.20110. PMID 14999707.
  27. ↑ 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.
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  32. ↑ 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.
  33. ↑ 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.
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  41. ↑ Ginès P, Titó L, Arroyo V, Planas R, Panés J, Viver J, Torres M, Humbert P, Rimola A, Llach J (1988). "Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis". Gastroenterology. 94 (6): 1493–502. PMID 3360270.
  42. ↑ Moreau R, Asselah T, Condat B, de Kerguenec C, Pessione F, Bernard B, Poynard T, Binn M, Grangé JD, Valla D, Lebrec D (2002). "Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study". Gut. 50 (1): 90–4. PMC 1773081. PMID 11772973.
  43. ↑ Salerno F, Cammà C, Enea M, Rössle M, Wong F (2007). "Transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis of individual patient data". Gastroenterology. 133 (3): 825–34. doi:10.1053/j.gastro.2007.06.020. PMID 17678653.
  44. ↑ de Franchis R, Dell'Era A, Iannuzzi F (2004). "Diagnosis and treatment of portal hypertension". Dig Liver Dis. 36 (12): 787–98. doi:10.1016/j.dld.2004.08.001. PMID 15646423.
  45. ↑ Garcia-Tsao G, Bosch J (2010). "Management of varices and variceal hemorrhage in cirrhosis". N. Engl. J. Med. 362 (9): 823–32. doi:10.1056/NEJMra0901512. PMID 20200386.
  46. ↑ Merkel C, Marin R, Sacerdoti D, Donada C, Cavallarin G, Torboli P, Amodio P, Sebastianelli G, Bolognesi M, Felder M, Mazzaro C, Gatta A (2000). "Long-term results of a clinical trial of nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis". Hepatology. 31 (2): 324–9. doi:10.1002/hep.510310210. PMID 10655253.
  47. ↑ Gluud LL, Klingenberg S, Nikolova D, Gluud C (2007). "Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices: systematic review of randomized trials". Am. J. Gastroenterol. 102 (12): 2842–8, quiz 2841, 2849. doi:10.1111/j.1572-0241.2007.01564.x. PMID 18042114.
  48. ↑ Poynard T, Calès P, Pasta L, Ideo G, Pascal JP, Pagliaro L, Lebrec D (1991). "Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of data and prognostic factors in 589 patients from four randomized clinical trials. Franco-Italian Multicenter Study Group". N. Engl. J. Med. 324 (22): 1532–8. doi:10.1056/NEJM199105303242202. PMID 1674104.
  49. ↑ Bosch J (2010). "Carvedilol for portal hypertension in patients with cirrhosis". Hepatology. 51 (6): 2214–8. doi:10.1002/hep.23689. PMID 20513005.
  50. ↑ Tripathi D, Ferguson JW, Kochar N, Leithead JA, Therapondos G, McAvoy NC, Stanley AJ, Forrest EH, Hislop WS, Mills PR, Hayes PC (2009). "Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed". Hepatology. 50 (3): 825–33. doi:10.1002/hep.23045. PMID 19610055.
  51. ↑ "Primary prevention of variceal haemorrhage: A pharmacological approach - Journal of Hepatology".
  52. ↑ Abraldes JG, Tarantino I, Turnes J, Garcia-Pagan JC, Rodés J, Bosch J (2003). "Hemodynamic response to pharmacological treatment of portal hypertension and long-term prognosis of cirrhosis". Hepatology. 37 (4): 902–8. doi:10.1053/jhep.2003.50133. PMID 12668985.
  53. ↑ Villanueva C, Aracil C, Colomo A, Hernández-Gea V, López-Balaguer JM, Alvarez-Urturi C, Torras X, Balanzó J, Guarner C (2009). "Acute hemodynamic response to beta-blockers and prediction of long-term outcome in primary prophylaxis of variceal bleeding". Gastroenterology. 137 (1): 119–28. doi:10.1053/j.gastro.2009.03.048. PMID 19344721.
  54. ↑ Ge PS, Runyon BA (2014). "The changing role of beta-blocker therapy in patients with cirrhosis". J. Hepatol. 60 (3): 643–53. doi:10.1016/j.jhep.2013.09.016. PMID 24076364.
  55. ↑ Besson I, Ingrand P, Person B, Boutroux D, Heresbach D, Bernard P, Hochain P, Larricq J, Gourlaouen A, Ribard D (1995). "Sclerotherapy with or without octreotide for acute variceal bleeding". N. Engl. J. Med. 333 (9): 555–60. doi:10.1056/NEJM199508313330904. PMID 7623904.
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