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Hepatic Disorders

Features and Appropriate Management

  • Practical Therapeutics
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Summary

The spectrum of liver disease is extremely wide, with many of the underlying disorders having acute and chronic presentations. Most of the underlying pathogenetic mechanisms are accounted for by autoimmune disease, viral infection and toxic insult. The management strategy of any liver disease is a combination of treating the symptoms and complications that arise, as well as drug therapies relevant to the specific underlying diagnosis. Encephalopathy, ascites, spontaneous bacterial peritonitis, variceal bleeding and pruritus are the main complications at which drug therapy is directed, although in some cases it represents only 1 aspect of the overall management. Drug therapy per se is largely ineffective in acute liver failure with the possible exception of acetylcysteine, but many drugs are used in the management of the constituent components of this complex medical emergency. Treatments for specific liver conditions are expanding, especially in the areas of autoimmune and viral disease. The increasing availability and success of liver transplantation has tended to change the emphasis of management, and it is often not appropriate to exhaust the treatment options before referring the patient for transplantation. A comprehensive review of all liver disease is beyond the scope of this article, but hopefully the important principles of management and commonly occurring clinical decisions are discussed.

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References

  1. Jones EA, Bergasa NV. The pruritus of cholestasis: from bile acids to opiate antagonists. Hepatology 1990; 11 (5): 84–7

    Article  Google Scholar 

  2. Kaplan MM. Primary biliary cirrhosis. In: Schiff L, Schiff ER (eds). Diseases of the liver. 7th ed. Philadelphia: J.B. Lipincott Company, 1993: 377–410

    Google Scholar 

  3. Hoensh HP, Balzer K, Dylewicz P, et al. Effect of rifampicin treatment on hepatic drug metabolism and serum bile acids in patients with primary biliary cirrhosis. Eur J Glin Pharmacol 1985; 28(4) 475–7

    Article  Google Scholar 

  4. Bloomer JR, Boyer JL. Phenobarbital effects in cholestatic liver disease. Ann Intern Med 1975; 82 (3): 310–7

    CAS  PubMed  Google Scholar 

  5. Summerfield J. Naloxone modulates the perception of itch in man. Br J Clin Pharmacol 1980; 10: 180–2

    Article  CAS  PubMed  Google Scholar 

  6. Thornton JR, Losowsky MS. Opioid peptides and primary biliary cirrhosis. BMJ 1988; 297 (6662): 1501–4

    Article  CAS  PubMed  Google Scholar 

  7. Schworer H, Ramadori C. Treatment of pruritus: a new indication for serotonin type 3 antagonists. J Clin Invest 1993; 71: 659–62

    CAS  Google Scholar 

  8. Poupon RE, Poupon R, Balkau B. Ursodiol for the long-term treatment of primary biliary cirrhosis. N Engl J Med 1994; 330: 1342–7

    Article  CAS  PubMed  Google Scholar 

  9. Sungaila I, Bartle WR, Walter SE, et al. Spironolactone pharmacokinetics and pharmacodynamics in patients with cirrhotic ascites. Gastroenterology 1992; 102: 1680–5

    CAS  PubMed  Google Scholar 

  10. Runyon BA. Refractory ascites. Seminars in liver disease 1993; 13 (4): 343–51

    Article  CAS  PubMed  Google Scholar 

  11. Angeli P, Delia Pria M, De Bei E, et al. Randomized clinical study of the efficacy of amiloride and potassium canrenoate in nonazotemic cirrhotic patients with ascites. Hepatology 1994; 19 (1): 72–9

    Article  CAS  PubMed  Google Scholar 

  12. Gerbes AL, Bertheau-Reitha U, Faulkner C, et al. Advantages of the new loop diuretic torasemide over fursemide in patients with cirrhosis and ascites: a randomized, double-blind crossover trial. J Hepatol 1993: 17 (3): 353–8

    Article  CAS  PubMed  Google Scholar 

  13. Hagege H, Ink O, Ducreaux M, et al. Treatment of ascites in patients with liver cirrhosis without either hyponatraemia or renal insufficiency: results of a randomized study comparing diuretics and punctures compensated by albumin (in French). Gastroenterol Clin Biol 1992; 16: 751–5

    CAS  PubMed  Google Scholar 

  14. Fassio E, Terg R, Landeira G, et al. Paracentesis with Dextran 70 vs paracentesis with albumin in cirrhosis with tense ascites: results of a randomized study. J Hepatol 1992; 14: 310–6

    Article  CAS  PubMed  Google Scholar 

  15. Rossaro L, Graziotto A, Bonato, et al. Concentrated ascitic fluid reinfusion after cascade filtration in tense ascites. Dig Dis Sci 1993; 38 (5): 903–8

    Article  CAS  PubMed  Google Scholar 

  16. Wilde JT, Cooper P, Kennedy HJ, et al. Coagulation disturbances following ascites recirculation. J Hepatol 1990; 10 (2): 217–22

    Article  CAS  PubMed  Google Scholar 

  17. Gines P, Arroyo V, Vargas V, et al. Paracentesis with intravenous infusion of albumin as compared with peritoneovenous shunting in cirrhosis with refractory ascites. N Engl J Med 1991; 325 (12): 829–35

    Article  CAS  PubMed  Google Scholar 

  18. Sonyal AJ, Freedman AM, Shiffman ML, et al. Transjugular intrahepatic porto-systemic shunt for ascites: a preliminary report [abstract]. Am J Gastroenterol 1992; 87: 1305

    Google Scholar 

  19. Grange JD, Boudghene F, Dissaule JC, et al. Transjugular intrahepatic porto-systemic shunts (TIPS) in cirrhotic patients with refractory ascites: clinical efficacy and acute effects on aldosterone and atrial natriuretic factor [abstract]. Gastroenterology 1993; 104: A909

    Google Scholar 

  20. Ring EJ, Lake JR, Roberts JP, et al. Using transjugular portosystemic shunts to control variceal bleeding before liver transplantation. Ann Intern Med 1992; 116: 304–9

    CAS  PubMed  Google Scholar 

  21. Bar-Meir S, Lerner E, Conn HO. Analysis of ascitic fluid in cirrhosis. Dig Dis Sci 1979; 24: 136–44

    Article  CAS  PubMed  Google Scholar 

  22. Rimola A, Infections in Liver Disease. In: Mclntyre N, Benhemon J-P, Bircher J, et al. editors. Oxford Textbook of Hepatology. New York: Oxford University Press, 1991: 1271–84

    Google Scholar 

  23. Felisart J, Rimola A, Arroyo V, et al. Cefotaxime is more effective than is ampicillin-tobramycin in cirrhotics with severe infections. Hepatology 1985; 5: 457–62

    Article  CAS  PubMed  Google Scholar 

  24. Grange JD, Amiot X, Grange V, et al. Amoxicillin-clavulanic acid therapy of spontaneous bacterial peritonitis: a prospective study of twenty-seven cases in cirrhotic patients. Hepatology 1990; 11: 360–4

    Article  CAS  PubMed  Google Scholar 

  25. Mercarder J, Gomez J, Ruiz J, et al. Use of ceftriaxone in the treatment of bacterial infections in cirrhotic patients. Chemotherapy 1989; 35 Suppl. 2: 23–6

    Article  Google Scholar 

  26. Toledo C, Salmeron JM, Rimola A, et al. Spontaneous bacterial peritonitis in cirrhosis: predictive factors of infection resolution and survival in patients treated with cefotaxime. Hepatology 1993; 17: 251–7

    Article  CAS  PubMed  Google Scholar 

  27. Runyon BA. Low protein concentration ascitic tap is predisposed to spontaneous bacterial peritonitis. Gastroenterology 1986; 91: 1343–6

    CAS  PubMed  Google Scholar 

  28. Gines P, Rimola A, Planas R, et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. Hepatology 1990; 12: 716–24

    Article  CAS  PubMed  Google Scholar 

  29. Zenroli ML. Pathophysiology of hepatic encephalopathy. In: Rodes J, Arroyo V, editors. Therapy in liver diseases. Barcelona: Ediciones Doyma, 1992: 270–6

    Google Scholar 

  30. Weber Jr FI, Bonwell JG, Fresard KM, et al. Nitrogen in fecal, bacterial, fiber, and soluble fractions of patients with cirrhosis: effects of lactulose and lactulose plus neomycin. J Lab Clin Med 1987; 110: 259–63

    PubMed  Google Scholar 

  31. Camma C, Fiorello F, Trine F, et al. Lactitol in treatment of chronic hepatic encephalopathy: a meta-analysis. Dig Dis Sci 1993; 38 (5) 916–22

    Article  CAS  PubMed  Google Scholar 

  32. Blanc P, Daures JP, Rouillon JM, et al. Lactitol or lactulose in the treatment of chronic hepatic encephalopathy: results of a meta-analysis. Hepatology 1992; 15 (2): 222–8

    Article  CAS  PubMed  Google Scholar 

  33. Orlandi F, Freddara U, Candelaresi MT, et al. Comparison between neomycin and lactulose in 173 patients with hepatic encephalopathy. Dig Dis Sci 1981; 26: 498–506

    Article  CAS  PubMed  Google Scholar 

  34. Bucci L, Palmeri GC. Double-blind, double dummy comparison between treatment with rifaximin and lactulose in patients with medium to severe degree hepatic encephalopathy. Curr Med Res Opin 1993; 13 (2): 109–18

    Article  CAS  PubMed  Google Scholar 

  35. Tarao K, Ikeda T, Hayashi K, et al. Successful use of vancomycin hydrochloride in the treatment of lactulose resistant chronic hepatic encephalopathy. Gut 1990; 1 (6): 702–6

    Article  Google Scholar 

  36. Plauth M, Egberts EH, Hamster W, et al. Long-term treatment of latent porto-systemic encephalopathy with branched-chain amino acids: a double-blind placebo-controlled crossover study. J Hepatol 1993; 17 (3): 308–14

    Article  CAS  PubMed  Google Scholar 

  37. Marchesini G, Dioguardi FS, Bianchi GP, et al. Long-term oral branched-chain amino acid treatment in chronic hepatic encephalopathy: a randomized double-blind casein-controlled trial. J Hepatol 1990; 11 (1): 92–101

    Article  CAS  PubMed  Google Scholar 

  38. Pomier-Lagrargues G, Giguere JF, Lavoie J, et al. Flumazemil in cirrhotic patients in hepatic coma: a randomized doubleblind placebo-controlled crossover trial. Hepatology 1993;19 (1): 32–7

    Google Scholar 

  39. Van der Rijt CCD, Schalm SW, Meulstee J, et al. Flumazeril therapy for hepatic encephalopathy: a double-blind crossover study. Hepatology 1989; 10: 590

    Google Scholar 

  40. Gimson AES, Westaby D, Hegarty J, et al. A randomised trial of vasopressin and vasopressin plus nitroglycerin in the control of acute variceal haemorrhage. Hepatology 1986; 6: 410–3

    Article  CAS  PubMed  Google Scholar 

  41. Burroughs AK, McCormick PA, Hughes MD, et al. Randomised, double-blind placebo-controlled trial of somatostatin for variceal bleeding: emergency control and prevention of early variceal rebleeding. Gastroenterology 1990; 99: 1388–95

    CAS  PubMed  Google Scholar 

  42. Hwang S-J, Lin H-C, Chang C-F, et al. A randomised controlled trial comparing octreotide and vasopressin in the control of acute oesophageal bleeding. J Hepatol 1992; 16: 320–5

    Article  CAS  PubMed  Google Scholar 

  43. Jenkins SA, Shields R, Kingsnorth AN, et al. Octreotide in the control of post-injection sclerotherapy haemorrhage. Gut 1993; 34 Suppl. 1: S22

    Google Scholar 

  44. Ready J, Robertson A, Goff JS, et al. Assessment of the risk of bleeding from oesophageal varices by continuous monitoring of portal pressure. Gastroenterology 1991; 100: 1403–10

    CAS  PubMed  Google Scholar 

  45. Sung JY, Chung S, Lai CW, et al. Octreotide versus emergency sclerotherapy in the treatment of acute variceal haemorrhage: a prospective randomized study. Gastroenterology 1993; 109: A201

    Google Scholar 

  46. Terblanche J, Burroughs AK, Hobbs KEF. Controversies in the management of bleeding oesophageal varices. N Engl J Med 1989; 320: 1393–8

    Article  CAS  PubMed  Google Scholar 

  47. Ramand MJ, Valla D, Mosnier JF, et al. Successful endoscopic obliteration of gastric varices with butyl cyonacrylate. Hepatology 1989; 10: 488–93

    Article  Google Scholar 

  48. Williams SGJ, Peters RA, Westaby D. Thrombin — an effective treatment for fundal gastric varices? Gut 1993; 34 Suppl. 17: S48

    Google Scholar 

  49. Stiegman CV, Goff JS, Michaletz-Onody PA, et al. Endoscopic oesophageal sclerotherapy as compared with endoscopic ligation for bleeding oesophageal varices. N Engl J Med 1992; 326: 1527–32

    Article  Google Scholar 

  50. Panes J, Teres J, Bosch J, et al. Efficacy of balloon tamponade in the treatment of bleeding gastric and oesophageal varices: results in 151 consecutive episodes. Dig Dis Sci 1988; 33: 454–9

    Article  CAS  PubMed  Google Scholar 

  51. Sanyal AJ, Freedman AM, Shiffman ML, et al. Transjugular intrahepatic porto-systemic shunt (TIPS) for uncontrolled variceal haemorrhage in advanced cirrhotics at high risk for surgery: a prospective study. Gastroenterology 1993; 104: A985

    Google Scholar 

  52. Sellinger M, Haag K, Ochs A, et al. Factors influencing the incidence of hepatic encephalopathy in patients after transjugular intrahepatic portosystemic sten-shunt (TIPS) [abstract]. Hepatology 1992: 16: 122A

    Article  Google Scholar 

  53. Sanyal AJ, Freedman AM, Shiffman ML, et al. Portosystemic encephalopathy after transjugular portosystemic shunt: results of a prospective controlled study. Hepatology 1994; 20: 46–55

    CAS  PubMed  Google Scholar 

  54. Reynolds TB, Donovan AJ, Mikkelsen WP, et al. Results of a 12 year randomized trial of portocaval shunt in patients with alcoholic liver disease and bleeding varices. Gastroenterology 1981; 80: 1005–11

    CAS  PubMed  Google Scholar 

  55. Burroughs AK, Hamilton G, Phillips A, et al. A comparison of sclerotherapy with staple transection of the oesophagus for the emergency control of bleeding from oesophageal varices. N Engl J Med 1989; 321: 857–62

    Article  CAS  PubMed  Google Scholar 

  56. Pagliaro L, Burroughs AK, Sorenson T, et al. Therapeutic controversies and randomized controlled trials (RCT’s): prevention of bleeding and rebleeding in cirrhosis. Gastroenterol Int 1989; 2: 71–84

    Google Scholar 

  57. Garcia-Pagan JC, Feu F, Bosch J, et al. Propranolol compared with propanolol plus isosorbide for portal hypertension in cirrhosis: a randomized controlled study. Ann Intern Med 1991; 114: 869–73

    CAS  PubMed  Google Scholar 

  58. Jenkins SA, Ellenbogen S, Baxter JN, et al. Sandostatin in the long term management of portal hypertension: a preliminary prospective randomized controlled clinical trial. Gut 1991; 32:A838

    Article  Google Scholar 

  59. Orloff MJ, Orloff MS, Rambotti M, et al. Is portal-systemic shunt worthwhile in Child’s class C cirrhosis?. Ann Surg 1992; 216: 256–68

    Article  CAS  PubMed  Google Scholar 

  60. The Veterans Affairs Cooperative Variceal Sclerotherapy Group. Prophylactic sclerotherapy for oesophageal varices in men with alcoholic liver disease: a randomized, single-blind, multicenter clinical trial. N Engl J Med 1991; 324: 1779–84

    Article  Google Scholar 

  61. Pagliaro L, D’Amico G, Sorenson TIA, et al. Prevention of first bleeding in cirrhosis: a meta-analysis of randomized trials of non-surgical treatment. Ann Intern Med 1992; 117: 59–70

    CAS  PubMed  Google Scholar 

  62. Inokuchi K, Cooperative Study Group of Portal Hypertension of Japan. Improved survival after prophylactic portal nondecompression surgery for esophageal varices: a randomized clinical trial. Hepatology 1990; 12: 1–6

    Article  CAS  PubMed  Google Scholar 

  63. O’Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet 1993; 342: 273–5

    Article  PubMed  Google Scholar 

  64. European Association for the Study of the Liver. Randomised trial of steroid therapy in acute liver failure. Gut 1979; 20: 620–3

    Article  Google Scholar 

  65. Takahashi Y. Acute hepatic failure — in special relation to treatment. Jap J Med 1983; 22: 140–5

    Article  CAS  Google Scholar 

  66. Harrison PM, Hughes RD, Forbes A, et al. Failure of insulin and glucagon to stimulate liver regeneration in fulminant hepatic failure. J Hepatol 1990; 10: 332–6

    Article  CAS  PubMed  Google Scholar 

  67. Woolf GM, Redeker AG. Treatment of fulminant hepatic failure with insulin and glucagon; a randomised controlled trial. Dig Dis Sci 1991; 36; 92–6

    Article  CAS  PubMed  Google Scholar 

  68. Levin S, Hahn T. Interferon deficiency syndrome. Clin Exp Immunol 1985; 60: 267–73

    CAS  PubMed  Google Scholar 

  69. Sanchez-Tapias JM, Mas A, Costa J, et al. Recombinant a2c-interferon therapy in fulminant viral hepatitis. J Hepatol 1987; 5: 205–10

    Article  CAS  PubMed  Google Scholar 

  70. Sinclair SB, Greig PD, Blendis LM, et al. Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E. J Clin Invest 1989; 84: 1063–9

    Article  CAS  PubMed  Google Scholar 

  71. Bernuau J, Babany G, Bezeaud A, et al. Does prostaglandin El (PGE1) prevent further aggravation in severe, or early fulminant, hepatitis?: a preliminary open trial [abstract]. J Hepatol 1989; 9: S114

    Article  Google Scholar 

  72. Kramer DJ, Aggarwal S, Martin M, et al. Management options in fulminant hepatic failure. Trans Proc 1989; 23: 1895–8

    Google Scholar 

  73. Sheiner P, Sinclair S, Greig P, et al. A randomised control trial of prostaglandin E2 (PGE2) in the treatment of fulminant hepatic failure (FHF) [abstract]. Hepatology 1992; 16: 88A

    Google Scholar 

  74. Gimson AES, Braude S, Mellon PJ, et al. Earlier charcoal haemoperfusion in fulminant hepatic failure. Lancet 1982; 2: 681–3

    Article  CAS  PubMed  Google Scholar 

  75. O’Grady JG, Gimson AES, O’Brien CJ, et al. Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure. Gastroenterology 1988; 94; 1186–92

    PubMed  Google Scholar 

  76. Rozga J, Holzman M, Griffin DW, et al. Xenogeneic hybrid bioartificial liver [abstract]. Hepatology 1992; 16:46A

    Google Scholar 

  77. Harrison PM, Keays R, Bray GP, et al. Improved outcome of paracetamol induced fulminant hepatic failure by late administration of acetylcysteine. Lancet 1990; 335: 1572–73

    Article  CAS  PubMed  Google Scholar 

  78. Harrison PM, Wendon JA, Gimson AES, et al. Improvement by acetylcysteine of haemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med 1991; 324 (26): 1852–7

    Article  CAS  PubMed  Google Scholar 

  79. Rolando N, Harvey F, Brahm J, et al. Prospective study of bacterial infection in acute liver failure: an analysis of fifty patients. Hepatology 1990; 11: 49–53

    Article  CAS  PubMed  Google Scholar 

  80. Rolando N, Harvey F, Brahm J, et al. Fungal infection: a common unrecognised complication of acute liver failure. J Hepatol 1991; 12: 1–9

    Article  CAS  PubMed  Google Scholar 

  81. Selective Decontamination of the Digestive Tract Trialists’ Collaborative Group. Meta-analysis of randomised controlled trials of selective decontamination of the digestive tract. BMJ 1993; 307: 525–32

    Article  Google Scholar 

  82. Rolando N, Gimson H, Wade J, et al. Prospective controlled trial of selective parental and enteral antimicrobial regimen in fulminant liver failure. Hepatology 1993; 17: 196–201

    Article  CAS  PubMed  Google Scholar 

  83. Williams R, Gimson AES. Intensive liver care and management of acute hepatic failure. Dig Dis Sci 1991; 36: 820–6

    Article  CAS  PubMed  Google Scholar 

  84. Canalese J, Gimson AES, Davies C, et al. Controlled trial of dexamethasone and mannitol for the cerebral edema of fulminant hepatic failure. Gut 1982; 23: 625–9

    Article  CAS  PubMed  Google Scholar 

  85. Ede RJ, Gimson AES, Bihari DJ, Williams R. Controlled hyperventilation in the prevention of cerebral edema of fulminant hepatic failure. J Hepatol 1986; 2: 43–51

    Article  CAS  PubMed  Google Scholar 

  86. Forbes A, Alexander G, O’Grady JG, et al. Thiopental infusion in treatment of intracranial hypertension complicating fulminant hepatic failure. Hepatology 1989; 10: 306–10

    Article  CAS  PubMed  Google Scholar 

  87. Ringe R, Lubbe N, Kuse E, et al. Management of emergencies before and after liver transplantation by early total hepatectomy. Transplant Proc 1993; 25: 1090

    CAS  PubMed  Google Scholar 

  88. Wendon JA, Harrison PM, Keays R, et al. Effects of vasopressor agents and epoprostenol on systemic hemodynamics and oxygen transport in fulminant hepatic failure. Hepatology 1992; 15(6): 1067–71

    Article  CAS  PubMed  Google Scholar 

  89. O’Grady JG, Alexander GJM, Hayller KM, et al. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989; 97: 439–45

    PubMed  Google Scholar 

  90. O’Grady JG, Portmann B, Williams R. Fulminant hepatic failure. In: Schiff L, Schiff ER, editors. Diseases of the liver. Philadelphia: J.B. Lipincott Company, 1993: 1077–90

    Google Scholar 

  91. Neuberger JM, Gunson BK, Buckels JAC, et al. Referral of patients with primary biliary cirrhosis for liver transplantation. Gut 1990; 31: 1069–72

    Article  CAS  PubMed  Google Scholar 

  92. Stellon AJ, Davies A, Compston JE, et al. Osteoporosis in chronic cholestatic liver disease. Q J Med 1985; 57: 783–90

    CAS  PubMed  Google Scholar 

  93. McDonald JA, Dunstan CR, Dilworth P, et al. Bone loss after liver transplantation. Hepatology 1991; 14: 613–9

    Article  CAS  PubMed  Google Scholar 

  94. Poupon RE, Ouguerram K, Chretien K, et al. Cholesterol-lowering effect of ursodeoxyeholic acid in patients with primary biliary cirrhosis. Hepatology 1993; 17 (4): 577–82

    Article  CAS  PubMed  Google Scholar 

  95. Kurihara T, Akimoto M, Abe K, et al. Experimental use of pravastatin in patients with primary biliary cirrhosis associated with hypercholesterolaemia. Clin Ther 1993; 15 (5): 890–8

    CAS  PubMed  Google Scholar 

  96. Poupon RE, Poupon R, Balkau B, et al. Ursodiol for the longterm treatment of primary biliary cirrhosis. N Engl J Med 1994; 330: 1342–7

    Article  CAS  PubMed  Google Scholar 

  97. Floreani A, Zappala F, Mazzetto M, et al. Different response to ursodeoxyeholic acid (UDCA) in primary biliary cirrhosis according to severity of disease. Dig Dis Sci 1994; 39 (1): 9–14

    Article  CAS  PubMed  Google Scholar 

  98. Kneppelhaut JC, Mulder CJ, von Berge Henegouwen GP, et al. Ursodeoxyeholic acid treatment in primary biliary cirrhosis with the emphasis on late stage disease. Neth J Med 1992; 41 (1-2): 11–6

    Google Scholar 

  99. Lombard M, Portmann B, Neuberger J, et al. Cyclosporin A treatment in primary biliary cirrhosis: results of a long-term placebo controlled trial. Gastroenterology 1993; 104: 519–26

    CAS  PubMed  Google Scholar 

  100. Kaplan MM. Methotrexate after five years in primary biliary cirrhosis. Gastroenterology 1992; 102: A829

    Google Scholar 

  101. Kaplan MM, Ailing DW, Zimmerman HJ, et al. A prospective trial of colchicine for primary biliary cirrhosis. N Engl J Med 1986; 315: 1448–54

    Article  CAS  PubMed  Google Scholar 

  102. Mitchison HC, Palmer JM, Bassendine MF, et al. A controlled trial of prednisolone treatment in primary biliary cirrhosis: three year results. J Hepatol 1992; 15 (3): 336–44

    Article  CAS  PubMed  Google Scholar 

  103. Boyer JL. Definitive therapy for primary biliary cirrhosis — fact or fiction. Gastroenterology 1988; 95: 242–5

    CAS  PubMed  Google Scholar 

  104. Buscher HP, Zietzchmann Y, Gerok W. Positive responses to methotrexate and ursodeoxyeholic acid in patients with primary biliary cirrhosis responding insufficiently to ursodeoxyeholic acid alone. J Hepatol 1993; 18 (1): 9–14

    Article  CAS  PubMed  Google Scholar 

  105. Raedsch R, Stiehl A, Walker S, et al. Combined ursodeoxyeholic acid plus colchicine-treatment of primary biliary cirrhosis: results of a placebo-controlled double-blind study [German]. Z Gastroenterol 1992; 30 Suppl. 1: 55–7

    PubMed  Google Scholar 

  106. Shibata J, Fujiyama S, Handa Y, et al. Combination therapy with ursodeoxyeholic acid and colchicine for primary biliary cirrhosis. J Gastroenterol Hepatol 1992; 7 (3): 277–82

    Article  CAS  PubMed  Google Scholar 

  107. Beuers U, Spengler U, Kruis W, et al. Ursodeoxyeholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial. Hepatology 1992; 16 (3): 707–14

    Article  CAS  PubMed  Google Scholar 

  108. Knox TA, Kaplan MM, Treatment of primary sclerosing cholangitis with oral methotrexate. Am J Gastroenterol 1991; 86: 546–52

    CAS  PubMed  Google Scholar 

  109. Knox TA, Kaplan MM. A double-blind controlled trial of oralpulse methotrexate therapy in the treatment of primary sclerosing cholangitis. Gastroenterology 1994; 106: 494–9

    CAS  PubMed  Google Scholar 

  110. LaRusso NF, Wiesner RH, Ludwig J, et al. Prospective trial of penicillamine in primary sclerosing cholangitis. Gastroenterology 1988; 95: 1036–42

    CAS  PubMed  Google Scholar 

  111. Lombard M, Farrant M, Karani J, et al. Improving biliary-enteric drainage in primary sclerosing cholangitis: experience with endoscopic methods. Gut 1991; 32 (11): 1365–8

    Article  Google Scholar 

  112. Koff RS. Viral hepatitis. In: Schiff L, Schiff ER, editors. Diseases of the liver. 7th ed. Philadelphia: J.B. Lipincott Company, 1993: 492–577

    Google Scholar 

  113. Kirk AP, Jain S, Pocock S, et al. Late results of Royal Free Hospital controlled trial of prednisolone therapy in hepatitis B surface antigen negative chronic active hepatitis. Gut 1980; 21: 78–85

    Article  CAS  PubMed  Google Scholar 

  114. Schalm SW, Summerskill WH, Gitnik GL, et al. Contrasting features and responses to treatment of severe chronic active liver disease with and without hepatitis B surface antigen. Gut 1976; 17: 781

    Article  CAS  PubMed  Google Scholar 

  115. Summerskill WHJ, Karmann MG, Amman HV, et al. Prednisone for chronic active liver disease; dose titration, standard dose and combination with azathioprine compared. Gut 1975; 16: 876–83

    Article  CAS  PubMed  Google Scholar 

  116. Stellon AJ, Hegarty JE, Portmann B, et al. Randomised controlled trial of azathioprine withdrawal in autoimmune chronic active hepatitis. Lancet 1985; 1: 668

    Article  CAS  PubMed  Google Scholar 

  117. Paroli M, Franco I, Santilo C, et al. Cyclosporin A in the treatment of autoimmune chronic active hepatitis occurring with or without circulating antibodies against hepatitis C virus. Int J Immunother 1992; 8: 135–40

    Google Scholar 

  118. Hegarty JE, Nouri Aria KTN, Portmann B, et al. Relapse following treatment withdrawal in patients with autoimmune chronic active hepatitis. Hepatology 1993; 3: 685–9

    Article  Google Scholar 

  119. Czaja AJ, Wang KK, Shiels MT, et al. Oral pulse prednisone therapy after relapse of severe autoimmune chronic active hepatitis: a prospective randomized treatment trial evaluating clinical, biochemical and lymphocyte subset responses. J Hepatol 1993; 17 (2): 180–6

    Article  CAS  PubMed  Google Scholar 

  120. Rolandi E, Franceschini R, Cataldi A, et al. Effects of ursodeoxycholic acid (UDCA) on serum liver damage indices in patients with chronic active hepatitis: a double-blind controlled study. Eur J Clin Pharmacol 1991; 40 (5): 473–6

    Article  CAS  PubMed  Google Scholar 

  121. Crosignani A, Battezzati PM, Setchell KD, et al. Effects of ursodeoxycholic acid on serum liver enzymes and bile acid metabolism in chronic active hepatitis: a dose response study. Hepatology 1991; 13 (2): 339–44

    Article  CAS  PubMed  Google Scholar 

  122. Perillo RP, Schiff ER, Doris GL, et al. A randomized, controlled trial of Interferon Alpha-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. N Engl J Med 1990; 323: 295–301

    Article  Google Scholar 

  123. Dusheiko GM, Kassianides C, Song E, et al. Loss of hepatitis B surface antigen in three controlled trials of recombinant alpha interferon for treatment of chronic hepatitis B. In: Zuckerman AJ, editor. Viral hepatitis and liver disease. New York: Alan R Liss, 1988: 844–7

    Google Scholar 

  124. Wong DK, Cheung AM, O’Rourke K, et al. Effect of alpha interferon treatment in patients with hepatitis Be antigen-positive chronic hepatitis B: a meta-analysis. Ann Intern Med 1993; 119: 312–23

    CAS  PubMed  Google Scholar 

  125. Korenman J, Baker B, Waggoner J, et al. Long-term remission of chronic hepatitis B after alpha-interferon therapy. Ann Intern Med 1991; 114: 629–34

    CAS  PubMed  Google Scholar 

  126. Brook MG, Petrovic L. McDonald JA, et al. Evidence of histological improvement following anti-viral treatment in chronic hepatitis B virus carriers and identification of histological features that predict response. J Hepatol 1989; 8: 218–25

    Article  CAS  PubMed  Google Scholar 

  127. Wu PC, Lok AS, Lau JY, et al. Histologic changes in Chinese patients with chronic active hepatitis B virus infection after interferon-alpha therapy. Am J Clin Pathol 1992; 98 (4); 402–7

    CAS  PubMed  Google Scholar 

  128. Brunetto MR, Giavin M, Saracco G, et al. Hepatitis B virus unable to secrete e antigen and response to interferon in chronic hepatitis B. Gastroenterology 1993; 105 (3): 845–50

    CAS  PubMed  Google Scholar 

  129. Perillo RP, Regenstein FG, Roodman ST. Chronic hepatitis B in asymptomatic homosexual men with antibody to the human immunodeficiency virus. Ann Intern Med 1986; 105: 382–3

    Google Scholar 

  130. Lok AS, Lai CL, Wu PC, et al. Spontaneous hepatitis Be antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B infection. Gastroenterology 1987; 92: 1839–43

    CAS  PubMed  Google Scholar 

  131. Davis GL, Hoofnagle JH, Waggoner JG. Spontaneous reactivation of chronic hepatitis B virus infection. Gastroenterology 1984; 86: 230–5

    CAS  PubMed  Google Scholar 

  132. Hoofnagle JH, Di Bisceglie AM, Waggoner JG, et al. Interferon alpha for patients with clinical apparent cirrhosis due to chronic hepatitis B. Gastroenterology 1993; 104: 1116–21

    CAS  PubMed  Google Scholar 

  133. Catterall AP, King R, Lau JY, et al. Interferon-alpha therapy with and without interferon-alpha priming in patients with chronic hepatitis B infection. J Antimicrob Chemother 1993; 31 (5): 777–82

    Article  CAS  PubMed  Google Scholar 

  134. Matchmick MG, Appelman HD, Chung HT, et al. Thymosin treatment of chronic hepatitis B: a placebo-controlled pilot trial. Hepatology 1991; 14.(3): 409–15

    Article  Google Scholar 

  135. Janssen HL, Berk L, Heijtink RA, et al. Interferon alpha and zidovudine combination therapy for chronic hepatitis B results of a randomized, placebo-controlled trial. Hepatology 1993; 17 (3): 383–8

    Article  CAS  PubMed  Google Scholar 

  136. O’Grady JG, Smith M, Davies SE, et al. Hepatitis B virus reinfection after orthotopic liver transplantation: serological and clinical implications. J Hepatol 1992; 14: 104–11

    Article  PubMed  Google Scholar 

  137. Samuel D, Bismuth A, Mathieu D, et al. Passive im- munoprophylaxis after liver transplantation in HBsAg positive patients. Lancet 1991; 1: 813–5

    Article  Google Scholar 

  138. Di Bisceglie AM, Martin P, Kassiondes C, et al. Recombinant interferon alpha therapy for chronic hepatitis C: a randomized, double-blind, placebo controlled trial. N Engl J Med 1989; 321: 1506–10

    Article  PubMed  Google Scholar 

  139. Causse X, Godinot H, Chevallier M, et al. Comparison of 1 or 3 MU of interferon alpha-2b and placebo in patients with chronic non-A, non-B hepatitis. Gastroenterology 1991; 101: 497–502

    CAS  PubMed  Google Scholar 

  140. Marcellin P, Boyer N, Giostra E, et al. Recombinant human alpha-interferon in patients with chronic non-A, non-B hepatitis: a multicentre randomized controlled trial from France. Hepatology 1991; 13: 393–7

    Article  CAS  PubMed  Google Scholar 

  141. Liang TJ, Rustgi V, Galun E, et al. HCV RNA in patients with chronic hepatitis C treated with alpha interferon. J Med Virol 1993; 40 (10): 69–75

    Article  CAS  PubMed  Google Scholar 

  142. Battezzati PM, Podda M, Bruno S, et al. Factors predicting early response to treatment with recombinant interferon alpha-2a in chronic non-A, non-B hepatitis: preliminary report of a long term trial. Ital J Gastroenterol 1992; 24 (9): 481–4

    CAS  PubMed  Google Scholar 

  143. Yoshioka K, Kakamu S, Wakita T, et al. Detection of hepatitis C virus by polymerase chain reaction and response to interferon alpha therapy: relationship to genotypes of hepatitis C virus. Hepatology 1992; 16: 293–9

    Article  CAS  PubMed  Google Scholar 

  144. Tsubota A, Chayama K, Ikeda K, et al. Factors predictive of response to interferon alpha therapy in hepatitis C virus infection. Hepatology 1994; 19: 1088–94

    Article  CAS  PubMed  Google Scholar 

  145. Rakela J, Tong M, Shiffman M, et al. An open-label, randomized, parallel evaluation of one, three and six million units of interferon (IFN) alpha-2a in the sixth month treatment of patients with chronic non-a, non-B hepatitis (NANB). Gastroenterology 1993; 104: A976

    Google Scholar 

  146. Reichard O, Yun ZB, Sonnerborg A, et al. Hepatitis C viral RNA titers in serum prior to, during, and after treatment with ribavirin for chronic hepatitis C. J Med Virol 1993; 41 (2): 99–102

    Article  CAS  PubMed  Google Scholar 

  147. Di Bisceglie AM, Shindo M, Fong TL, et al. A pilot study of ribavirin for chronic hepatitis C. Hepatology 1992; 16 (3): 649–54

    Article  PubMed  Google Scholar 

  148. Ramond MJ, Paynard T, Rueff B, et al. A randomized trial of prednisolone in patients with severe alcoholic hepatitis. N Engl J Med 1992; 226 (8): 507–12

    Article  Google Scholar 

  149. Imperiale TF, McCullough AJ, Do corticosteroids reduce mortality from alcoholic hepatitis?: a meta-analysis of the randomized trials. Ann Intern Med 1990; 113 (4): 229–307

    Google Scholar 

  150. Halle P. Pare P, Kaptein E, et al. Double-blind, controlled trial of propylthiouracil in patients with severe acute alcoholic hepatitis. Gastroenterology 1982; 82: 925–31

    CAS  PubMed  Google Scholar 

  151. Orrego H, Blake J, Blendis L, et al. Long-term treatment of alcoholic liver disease with propylthiouracil. N Engl J Med 1987; 317: 1421

    Article  CAS  PubMed  Google Scholar 

  152. Kershenobich D, Vargas F, Garcia-Tsao G, et al. Colchicine in the treatment of cirrhosis of the liver. N Engl J Med 1988; 318: 1709–13

    Article  CAS  PubMed  Google Scholar 

  153. Mendemhall CL, Movitz TE, Roselle GA, et al. A study of oral nutritional support with oxandrolone in malnourished patients with alcoholic hepatitis: results of a Department of Veteran Affairs Cooperative Study. Hepatology 1993; 17: 564–76

    Article  Google Scholar 

  154. Plevris JN, Hayes PC, Bouchier IAD, et al. Ursodeoxycholic acid in the treatment of alcoholic liver disease. Eur J Gastroenterol Hepatol 1991; 3: 653–6

    Google Scholar 

  155. Bresci G, Piccinocchi M, Banti S. The use of reduced glutathi- one in alcoholic hepatopathy [Italian]. Minerva Med 1991; 82: (11): 753–5.

    CAS  PubMed  Google Scholar 

  156. Corsini G, Gelso E, Giuliano G. Effects of metadoxine on main biohumeral changes induced by chronic alcoholism [Italian]. ClinTer 1992; 140(3): 251–7

    CAS  Google Scholar 

  157. Muzes G, Deak G, Long I, et al. Effect of silymarin therapy on the anti-oxidant defense mechanism and lipid peroxidation in alcoholic liver disease (double-blind protocol) [Hungarian]. OrvHetil 1990; 131 (16): 863–6

    CAS  Google Scholar 

  158. Dubois RS, Rodgerson DO, Hambidige KM. Treatment of Wilson’s Disease with triethylene tetramine hydrochloride (trientine). J Pediatr Gastroenterol Nutr 1990; 10 (1): 77–81

    Article  CAS  PubMed  Google Scholar 

  159. Morita J, Yoshino M, Watari H, et al. Wilson’s disease treatment by triethylene tetramine dihydrochloride (trientine, 2HC1): long term observations. Dev Pharmacol Ther 1992; 19 (1): 6–9

    CAS  PubMed  Google Scholar 

  160. Brewer GJ, Yuzbasiyan-Gurkan V, Lee DY. Use of zinc-copper metabolic interactions in the treatment of Wilson’s disease. J Am Coll Nutr 1990; 9 (5): 487–91

    CAS  PubMed  Google Scholar 

  161. Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, et al. Treatment of Wilson’s disease with zinc: dose regimen requirements. Am J Med Sci 1993; 305 (4): 199–202

    Article  CAS  PubMed  Google Scholar 

  162. Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, et al. Treatment of Wilson’s disease with zinc: interaction with other anticopper agents. J Am Coll Nutr 1993; 12 (1): 26–30

    CAS  PubMed  Google Scholar 

  163. Danks DM. Copper and liver disease. Eur J Pediatr 1991 Jan; 150 (3): 142–8

    Article  CAS  PubMed  Google Scholar 

  164. Brewer GJ, Dick RD, Yuzbasiyan-Gurkan V, et al. Initial therapy of patients with Wilson’s disease with tetrathiomolybdate. ArchNeurol 1991; 48(1): 42–7

    CAS  Google Scholar 

  165. Brewer GJ, Yuzbasiyan-Gurkan V, Dick R, et al. Does vegetarian diet control Wilson’s disease? J Am Coll Nutr 1993 Oct; 12 (5): 527–30

    CAS  PubMed  Google Scholar 

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Aldersley, M.A., O’Grady, J.G. Hepatic Disorders. Drugs 49, 83–102 (1995). https://doi.org/10.2165/00003495-199549010-00007

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