Cirrhosis medical therapy: Difference between revisions

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==Medical Therapy==
==Medical Therapy==
* Treatment of [[cirrhosis]] is mostly directed towards the treatment of complications such as:
* Treatment of [[cirrhosis]] is mostly directed towards the treatment of complications such as:<ref name="pmid11179247">{{cite journal |vauthors=Garcia-Tsao G |title=Current management of the complications of cirrhosis and portal hypertension: variceal hemorrhage, ascites, and spontaneous bacterial peritonitis |journal=Gastroenterology |volume=120 |issue=3 |pages=726–48 |year=2001 |pmid=11179247 |doi= |url=}}</ref>
** [[ascites]]  
** [[ascites]]  
** [[hepatic encephalopathy]]
** [[hepatic encephalopathy]]
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===Hepatitis C===
===Hepatitis C===
:[[Hepatitis_C/Medical_Therapy|Hepatitis C Medical Therapy]]<ref name="pmid8898645">{{cite journal |vauthors=Lai MY, Kao JH, Yang PM, Wang JT, Chen PJ, Chan KW, Chu JS, Chen DS |title=Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C |journal=Gastroenterology |volume=111 |issue=5 |pages=1307–12 |year=1996 |pmid=8898645 |doi= |url=}}</ref>
:[[Hepatitis_C/Medical_Therapy|Hepatitis C Medical Therapy]]<ref name="pmid8898645">{{cite journal |vauthors=Lai MY, Kao JH, Yang PM, Wang JT, Chen PJ, Chan KW, Chu JS, Chen DS |title=Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C |journal=Gastroenterology |volume=111 |issue=5 |pages=1307–12 |year=1996 |pmid=8898645 |doi= |url=}}</ref><ref name="pmid15777574">{{cite journal |vauthors=Everson GT |title=Management of cirrhosis due to chronic hepatitis C |journal=J. Hepatol. |volume=42 Suppl |issue=1 |pages=S65–74 |year=2005 |pmid=15777574 |doi=10.1016/j.jhep.2005.01.009 |url=}}</ref><ref name="pmid11984517">{{cite journal |vauthors=Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, Ling MH, Albrecht J |title=Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C |journal=Gastroenterology |volume=122 |issue=5 |pages=1303–13 |year=2002 |pmid=11984517 |doi= |url=}}</ref><ref name="pmid12883493">{{cite journal |vauthors=Poynard T, McHutchison J, Manns M, Myers RP, Albrecht J |title=Biochemical surrogate markers of liver fibrosis and activity in a randomized trial of peginterferon alfa-2b and ribavirin |journal=Hepatology |volume=38 |issue=2 |pages=481–92 |year=2003 |pmid=12883493 |doi=10.1053/jhep.2003.50319 |url=}}</ref>


* Abstinence from alcohol as alcohol aggravates HCV associated [[fibrosis]], cirrhosis and makes [[liver cancer]] more likely.
* Abstinence from alcohol as alcohol aggravates HCV associated [[fibrosis]], cirrhosis and makes [[liver cancer]] more likely.
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===Hepatitis B===
===Hepatitis B===
:[[Hepatitis_B/Medical_Therapy|Hepatitis B Medical Therapy]]<ref name="pmid1701755">{{cite journal |vauthors=Perrillo RP |title=Factors influencing response to interferon in chronic hepatitis B: implications for Asian and western populations |journal=Hepatology |volume=12 |issue=6 |pages=1433–5 |year=1990 |pmid=1701755 |doi= |url=}}</ref><ref name="pmid9011789">{{cite journal |vauthors=Hoofnagle JH, di Bisceglie AM |title=The treatment of chronic viral hepatitis |journal=N. Engl. J. Med. |volume=336 |issue=5 |pages=347–56 |year=1997 |pmid=9011789 |doi=10.1056/NEJM199701303360507 |url=}}</ref><ref name="pmid7477217">{{cite journal |vauthors=Dienstag JL, Perrillo RP, Schiff ER, Bartholomew M, Vicary C, Rubin M |title=A preliminary trial of lamivudine for chronic hepatitis B infection |journal=N. Engl. J. Med. |volume=333 |issue=25 |pages=1657–61 |year=1995 |pmid=7477217 |doi=10.1056/NEJM199512213332501 |url=}}</ref>
:[[Hepatitis_B/Medical_Therapy|Hepatitis B Medical Therapy]]<ref name="pmid1701755">{{cite journal |vauthors=Perrillo RP |title=Factors influencing response to interferon in chronic hepatitis B: implications for Asian and western populations |journal=Hepatology |volume=12 |issue=6 |pages=1433–5 |year=1990 |pmid=1701755 |doi= |url=}}</ref><ref name="pmid9011789">{{cite journal |vauthors=Hoofnagle JH, di Bisceglie AM |title=The treatment of chronic viral hepatitis |journal=N. Engl. J. Med. |volume=336 |issue=5 |pages=347–56 |year=1997 |pmid=9011789 |doi=10.1056/NEJM199701303360507 |url=}}</ref><ref name="pmid7477217">{{cite journal |vauthors=Dienstag JL, Perrillo RP, Schiff ER, Bartholomew M, Vicary C, Rubin M |title=A preliminary trial of lamivudine for chronic hepatitis B infection |journal=N. Engl. J. Med. |volume=333 |issue=25 |pages=1657–61 |year=1995 |pmid=7477217 |doi=10.1056/NEJM199512213332501 |url=}}</ref><ref name="pmid12512035">{{cite journal |vauthors=Dienstag JL, Goldin RD, Heathcote EJ, Hann HW, Woessner M, Stephenson SL, Gardner S, Gray DF, Schiff ER |title=Histological outcome during long-term lamivudine therapy |journal=Gastroenterology |volume=124 |issue=1 |pages=105–17 |year=2003 |pmid=12512035 |doi=10.1053/gast.2003.50013 |url=}}</ref><ref name="pmid15470215">{{cite journal |vauthors=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 |title=Lamivudine for patients with chronic hepatitis B and advanced liver disease |journal=N. Engl. J. Med. |volume=351 |issue=15 |pages=1521–31 |year=2004 |pmid=15470215 |doi=10.1056/NEJMoa033364 |url=}}</ref><ref name="pmid14999707">{{cite journal |vauthors=Lok AS, McMahon BJ |title=Chronic hepatitis B: update of recommendations |journal=Hepatology |volume=39 |issue=3 |pages=857–61 |year=2004 |pmid=14999707 |doi=10.1002/hep.20110 |url=}}</ref><ref name="pmid15987916">{{cite journal |vauthors=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 |title=Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B |journal=N. Engl. J. Med. |volume=352 |issue=26 |pages=2673–81 |year=2005 |pmid=15987916 |doi=10.1056/NEJMoa042957 |url=}}</ref><ref name="pmid16230074">{{cite journal |vauthors=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 |title=A dose-ranging study of the efficacy and tolerability of entecavir in Lamivudine-refractory chronic hepatitis B patients |journal=Gastroenterology |volume=129 |issue=4 |pages=1198–209 |year=2005 |pmid=16230074 |doi=10.1053/j.gastro.2005.06.055 |url=}}</ref><ref name="pmid14647053">{{cite journal |vauthors=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 |title=Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post-liver transplantation patients |journal=Hepatology |volume=38 |issue=6 |pages=1419–27 |year=2003 |pmid=14647053 |doi=10.1016/j.hep.2003.09.040 |url=}}</ref>


* Patients with HBeAg-positive chronic hepatitis B
* Patients with HBeAg-positive chronic hepatitis B<ref name="pmid16083710">{{cite journal |vauthors=Lai CL, Leung N, Teo EK, Tong M, Wong F, Hann HW, Han S, Poynard T, Myers M, Chao G, Lloyd D, Brown NA |title=A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B |journal=Gastroenterology |volume=129 |issue=2 |pages=528–36 |year=2005 |pmid=16083710 |doi=10.1016/j.gastro.2005.05.053 |url=}}</ref>
:'''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.
:'''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.
:'''b.''' ALT persistently normal or minimally elevated (<2 times normal) - should not be initiated on treatment.
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* Patients with HBeAg-negative chronic hepatitis B (serum HBV DNA >20,000 IU/mL and elevated ALT >2 times normal) should be considered for treatment with [[pegIFN-α]], [[tenofovir]] or [[entecavir]].
* Patients with HBeAg-negative chronic hepatitis B (serum HBV DNA >20,000 IU/mL and elevated ALT >2 times normal) should be considered for treatment with [[pegIFN-α]], [[tenofovir]] or [[entecavir]].
* Patients with compensated cirrhosis - best treated with [[tenofovir]] or [[entecavir]].
* Patients with compensated cirrhosis - best treated with [[tenofovir]] or [[entecavir]].
* Patients with decompensated cirrhosis — [[Lamivudine]] or [[telbivudine]] may be used as initial treatment in combination with [[adefovir]] or [[tenofovir]] to reduce the risk of drug resistance.
* Patients with decompensated cirrhosis — [[Lamivudine]] or [[telbivudine]] may be used as initial treatment in combination with [[adefovir]] or [[tenofovir]] to reduce the risk of drug resistance.<ref name="pmid10613747">{{cite journal |vauthors=Villeneuve JP, Condreay LD, Willems B, Pomier-Layrargues G, Fenyves D, Bilodeau M, Leduc R, Peltekian K, Wong F, Margulies M, Heathcote EJ |title=Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B |journal=Hepatology |volume=31 |issue=1 |pages=207–10 |year=2000 |pmid=10613747 |doi=10.1002/hep.510310130 |url=}}</ref><ref name="pmid12198698">{{cite journal |vauthors=Fontana RJ, Hann HW, Perrillo RP, Vierling JM, Wright T, Rakela J, Anschuetz G, Davis R, Gardner SD, Brown NA |title=Determinants of early mortality in patients with decompensated chronic hepatitis B treated with antiviral therapy |journal=Gastroenterology |volume=123 |issue=3 |pages=719–27 |year=2002 |pmid=12198698 |doi= |url=}}</ref>


===Autoimmune Hepatitis===
===Autoimmune Hepatitis===
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==Treatment of Complications==
==Treatment of Complications==
===Ascites===
===Ascites===
:[[Ascites medical therapy|Ascites Treatment]]<ref name="pmid25954497">{{cite journal |vauthors=Pedersen JS, Bendtsen F, Møller S |title=Management of cirrhotic ascites |journal=Ther Adv Chronic Dis |volume=6 |issue=3 |pages=124–37 |year=2015 |pmid=25954497 |pmc=4416972 |doi=10.1177/2040622315580069 |url=}}</ref>
:[[Ascites medical therapy|Ascites Treatment]]<ref name="pmid25954497">{{cite journal |vauthors=Pedersen JS, Bendtsen F, Møller S |title=Management of cirrhotic ascites |journal=Ther Adv Chronic Dis |volume=6 |issue=3 |pages=124–37 |year=2015 |pmid=25954497 |pmc=4416972 |doi=10.1177/2040622315580069 |url=}}</ref><ref name="pmid15084697">{{cite journal |vauthors=Ginès P, Cárdenas A, Arroyo V, Rodés J |title=Management of cirrhosis and ascites |journal=N. Engl. J. Med. |volume=350 |issue=16 |pages=1646–54 |year=2004 |pmid=15084697 |doi=10.1056/NEJMra035021 |url=}}</ref>


* Abstinence from alcohol.
* Abstinence from alcohol.
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===Esophageal Variceal Bleeding===
===Esophageal Variceal Bleeding===
:[[Esophageal varices#Treatment|Esophageal Varices Treatment]]
:[[Esophageal varices#Treatment|Esophageal Varices Treatment]]<ref name="pmid15646423">{{cite journal |vauthors=de Franchis R, Dell'Era A, Iannuzzi F |title=Diagnosis and treatment of portal hypertension |journal=Dig Liver Dis |volume=36 |issue=12 |pages=787–98 |year=2004 |pmid=15646423 |doi=10.1016/j.dld.2004.08.001 |url=}}</ref>


*Patients with no varices and bleeding:
*Patients with no varices and bleeding:
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**Esophageal variceal ligation <ref name="pmid8101900">{{cite journal |vauthors=Gimson AE, Ramage JK, Panos MZ, Hayllar K, Harrison PM, Williams R, Westaby D |title=Randomised trial of variceal banding ligation versus injection sclerotherapy for bleeding oesophageal varices |journal=Lancet |volume=342 |issue=8868 |pages=391–4 |year=1993 |pmid=8101900 |doi= |url=}}</ref>
**Esophageal variceal ligation <ref name="pmid8101900">{{cite journal |vauthors=Gimson AE, Ramage JK, Panos MZ, Hayllar K, Harrison PM, Williams R, Westaby D |title=Randomised trial of variceal banding ligation versus injection sclerotherapy for bleeding oesophageal varices |journal=Lancet |volume=342 |issue=8868 |pages=391–4 |year=1993 |pmid=8101900 |doi= |url=}}</ref>
**Sclerotherapy <ref name="pmid17060770">{{cite journal |vauthors=Krige JE, Kotze UK, Bornman PC, Shaw JM, Klipin M |title=Variceal recurrence, rebleeding, and survival after endoscopic injection sclerotherapy in 287 alcoholic cirrhotic patients with bleeding esophageal varices |journal=Ann. Surg. |volume=244 |issue=5 |pages=764–70 |year=2006 |pmid=17060770 |pmc=1856595 |doi=10.1097/01.sla.0000231704.45005.4e |url=}}</ref><ref name="pmid9683971">{{cite journal |vauthors=Williams EJ, Iredale JP |title=Liver cirrhosis |journal=Postgrad Med J |volume=74 |issue=870 |pages=193–202 |year=1998 |pmid=9683971 |pmc=2360862 |doi= |url=}}</ref><ref name="pmid1579136">{{cite journal |vauthors=Stiegmann GV, Goff JS, Michaletz-Onody PA, Korula J, Lieberman D, Saeed ZA, Reveille RM, Sun JH, Lowenstein SR |title=Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices |journal=N. Engl. J. Med. |volume=326 |issue=23 |pages=1527–32 |year=1992 |pmid=1579136 |doi=10.1056/NEJM199206043262304 |url=}}</ref>
**Sclerotherapy <ref name="pmid17060770">{{cite journal |vauthors=Krige JE, Kotze UK, Bornman PC, Shaw JM, Klipin M |title=Variceal recurrence, rebleeding, and survival after endoscopic injection sclerotherapy in 287 alcoholic cirrhotic patients with bleeding esophageal varices |journal=Ann. Surg. |volume=244 |issue=5 |pages=764–70 |year=2006 |pmid=17060770 |pmc=1856595 |doi=10.1097/01.sla.0000231704.45005.4e |url=}}</ref><ref name="pmid9683971">{{cite journal |vauthors=Williams EJ, Iredale JP |title=Liver cirrhosis |journal=Postgrad Med J |volume=74 |issue=870 |pages=193–202 |year=1998 |pmid=9683971 |pmc=2360862 |doi= |url=}}</ref><ref name="pmid1579136">{{cite journal |vauthors=Stiegmann GV, Goff JS, Michaletz-Onody PA, Korula J, Lieberman D, Saeed ZA, Reveille RM, Sun JH, Lowenstein SR |title=Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices |journal=N. Engl. J. Med. |volume=326 |issue=23 |pages=1527–32 |year=1992 |pmid=1579136 |doi=10.1056/NEJM199206043262304 |url=}}</ref>
**[[Transjugular intrahepatic portosystemic shunt]] ([[TIPS]])<ref name="pmid10320885">{{cite journal |vauthors=Patel NH, Chalasani N, Jindal RM |title=Current status of transjugular intrahepatic portosystemic shunts |journal=Postgrad Med J |volume=74 |issue=878 |pages=716–20 |year=1998 |pmid=10320885 |pmc=2431632 |doi= |url=}}</ref><ref name="pmid24115809">{{cite journal |vauthors=Loffroy R, Estivalet L, Cherblanc V, Favelier S, Pottecher P, Hamza S, Minello A, Hillon P, Thouant P, Lefevre PH, Krausé D, Cercueil JP |title=Transjugular intrahepatic portosystemic shunt for the management of acute variceal hemorrhage |journal=World J. Gastroenterol. |volume=19 |issue=37 |pages=6131–43 |year=2013 |pmid=24115809 |pmc=3787342 |doi=10.3748/wjg.v19.i37.6131 |url=}}</ref><ref name="pmid7918921">{{cite journal |vauthors=McCormick PA, Dick R, Burroughs AK |title=Review article: the transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of portal hypertension |journal=Aliment. Pharmacol. Ther. |volume=8 |issue=3 |pages=273–82 |year=1994 |pmid=7918921 |doi= |url=}}</ref>
**[[Transjugular intrahepatic portosystemic shunt]] ([[TIPS]])<ref name="pmid12761727">{{cite journal |vauthors=Boyer TD |title=Transjugular intrahepatic portosystemic shunt: current status |journal=Gastroenterology |volume=124 |issue=6 |pages=1700–10 |year=2003 |pmid=12761727 |doi= |url=}}</ref><ref name="pmid10320885">{{cite journal |vauthors=Patel NH, Chalasani N, Jindal RM |title=Current status of transjugular intrahepatic portosystemic shunts |journal=Postgrad Med J |volume=74 |issue=878 |pages=716–20 |year=1998 |pmid=10320885 |pmc=2431632 |doi= |url=}}</ref><ref name="pmid24115809">{{cite journal |vauthors=Loffroy R, Estivalet L, Cherblanc V, Favelier S, Pottecher P, Hamza S, Minello A, Hillon P, Thouant P, Lefevre PH, Krausé D, Cercueil JP |title=Transjugular intrahepatic portosystemic shunt for the management of acute variceal hemorrhage |journal=World J. Gastroenterol. |volume=19 |issue=37 |pages=6131–43 |year=2013 |pmid=24115809 |pmc=3787342 |doi=10.3748/wjg.v19.i37.6131 |url=}}</ref><ref name="pmid7918921">{{cite journal |vauthors=McCormick PA, Dick R, Burroughs AK |title=Review article: the transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of portal hypertension |journal=Aliment. Pharmacol. Ther. |volume=8 |issue=3 |pages=273–82 |year=1994 |pmid=7918921 |doi= |url=}}</ref>
**[[Balloon tamponade]]: temporary measure to stop bleeding for 24 hours until one of the above procedures is initiated
**[[Balloon tamponade]]: temporary measure to stop bleeding for 24 hours until one of the above procedures is initiated
*Patients who have cirrhosis and have recovered from a variceal bleed:<ref name="pmid2029994">{{cite journal |vauthors=Conn HO, Grace ND, Bosch J, Groszmann RJ, Rodés J, Wright SC, Matloff DS, Garcia-Tsao G, Fisher RL, Navasa M |title=Propranolol in the prevention of the first hemorrhage from esophagogastric varices: A multicenter, randomized clinical trial. The Boston-New Haven-Barcelona Portal Hypertension Study Group |journal=Hepatology |volume=13 |issue=5 |pages=902–12 |year=1991 |pmid=2029994 |doi= |url=}}</ref>
*Patients who have cirrhosis and have recovered from a variceal bleed:<ref name="pmid2029994">{{cite journal |vauthors=Conn HO, Grace ND, Bosch J, Groszmann RJ, Rodés J, Wright SC, Matloff DS, Garcia-Tsao G, Fisher RL, Navasa M |title=Propranolol in the prevention of the first hemorrhage from esophagogastric varices: A multicenter, randomized clinical trial. The Boston-New Haven-Barcelona Portal Hypertension Study Group |journal=Hepatology |volume=13 |issue=5 |pages=902–12 |year=1991 |pmid=2029994 |doi= |url=}}</ref><ref name="pmid12648985">{{cite journal |vauthors=Bosch J, García-Pagán JC |title=Prevention of variceal rebleeding |journal=Lancet |volume=361 |issue=9361 |pages=952–4 |year=2003 |pmid=12648985 |doi=10.1016/S0140-6736(03)12778-X |url=}}</ref>
**Combination of esophageal variceal ligation (EVL) and non-selective [[beta blockers]]
**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
**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
Line 243: Line 243:


===Hepatorenal Syndrome===
===Hepatorenal Syndrome===
:[[Hepatorenal syndrome#Treatment|Hepatorenal Syndrome Treatment]]<ref name="pmid1435935">{{cite journal |vauthors=Epstein M |title=The hepatorenal syndrome--newer perspectives |journal=N. Engl. J. Med. |volume=327 |issue=25 |pages=1810–1 |year=1992 |pmid=1435935 |doi=10.1056/NEJM199212173272509 |url=}}</ref><ref name="pmid9683971">{{cite journal |vauthors=Williams EJ, Iredale JP |title=Liver cirrhosis |journal=Postgrad Med J |volume=74 |issue=870 |pages=193–202 |year=1998 |pmid=9683971 |pmc=2360862 |doi= |url=}}</ref>
:[[Hepatorenal syndrome#Treatment|Hepatorenal Syndrome Treatment]]<ref name="pmid1435935">{{cite journal |vauthors=Epstein M |title=The hepatorenal syndrome--newer perspectives |journal=N. Engl. J. Med. |volume=327 |issue=25 |pages=1810–1 |year=1992 |pmid=1435935 |doi=10.1056/NEJM199212173272509 |url=}}</ref><ref name="pmid9683971">{{cite journal |vauthors=Williams EJ, Iredale JP |title=Liver cirrhosis |journal=Postgrad Med J |volume=74 |issue=870 |pages=193–202 |year=1998 |pmid=9683971 |pmc=2360862 |doi= |url=}}</ref><ref name="pmid14654322">{{cite journal |vauthors=Ginès P, Guevara M, Arroyo V, Rodés J |title=Hepatorenal syndrome |journal=Lancet |volume=362 |issue=9398 |pages=1819–27 |year=2003 |pmid=14654322 |doi=10.1016/S0140-6736(03)14903-3 |url=}}</ref>


*[[Albumin]] infusion
*[[Albumin]] infusion

Revision as of 19:53, 4 December 2017

Cirrhosis Microchapters

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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]

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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:[3][4]

  • 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.[5]
  • 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.[6]
  • 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[7][8][9][10]
  • Abstinence from alcohol as alcohol aggravates HCV associated fibrosis, cirrhosis and makes liver cancer more likely.
  • Preferred regimen: Combination of the following produces normalization of LFTs, conjugated bilirubin, prothrombin time and and albumin levels in 12 weeks:
    • ABT-450 boosted with ritonavir
    • Dasabuvir plus ribavirin (3D + RBV)
    • Ombitasvir

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.[11]

Genotypes HCV 2 and 3

  • Preferred regimen (1): peginterferon plus ribavirin should be administered for 24 weeks, using a ribavirin dose of 800 mg.[12]
  • Alternative regimen (1): Triple therapy- peginterferon plus ribavirin along with an additional dose of 100mg of amantadine q12h.

Hepatitis B

Hepatitis B Medical Therapy[13][14][15][16][17][18][19][20][21]
  • Patients with HBeAg-positive chronic hepatitis B[22]
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.
  • Patients with HBeAg-negative chronic hepatitis B (serum HBV DNA >20,000 IU/mL and elevated ALT >2 times normal) should be considered for treatment with pegIFN-α, tenofovir or entecavir.
  • Patients with compensated cirrhosis - best treated with tenofovir or entecavir.
  • Patients with decompensated cirrhosis — Lamivudine or telbivudine may be used as initial treatment in combination with adefovir or tenofovir to reduce the risk of drug resistance.[23][24]

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.

Hemochromatosis

  • Phlebotomy

Treatment of Complications

Ascites

Ascites Treatment[25][26]
  • 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. [27]

Esophageal Variceal Bleeding

Esophageal Varices Treatment[28]
  • Patients with no varices and bleeding:
    • EGD should be performed at regular intervals.
  • Patients with small varices that have not bled:[29]
    • Non-selective beta blockers should be used to prevent the first variceal bleeding
    • 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:[30][31]
  • Patients who have cirrhosis and have recovered from a variceal bleed:[41][42]
    • 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: [43]

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.[44][45][46] 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.[47]
  • Antibiotics
  • Rifaximin
    • Dose of 400 mg taken orally 3 times a day was as effective as lactulose or lactilol at improving hepatic encephalopathy symptoms.[48] Similarly, rifaximin was as effective as neomycin and paromomycin.[49]
  • Benzodiazepines receptor agonists

Hepatorenal Syndrome

Hepatorenal Syndrome Treatment[50][35][51]

Other treatment modalities:

Spontaneous Bacterial Peritonitis

Spontaneous Bacterial Peritonitis Medical Therapy[53][54]

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. ↑ Giouleme OI, Vyzantiadis TA, Nikolaidis NL; et al. (2006). "Pathogenesis of osteoporosis in liver cirrhosis". Hepatogastroenterology. 53 (72): 938–43. PMID 17153457.
  3. ↑ Kondrup J, Nielsen K, Hamberg O (1993). "[Nutritional therapy in patients with liver cirrhosis]". Ugeskr. Laeg. (in Danish). 155 (29): 2248–51. PMID 8328092.
  4. ↑ Silk DB, O'Keefe SJ, Wicks C (1991). "Nutritional support in liver disease". Gut. Suppl: S29–33. PMC 1405219. PMID 1916467.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ "Medscape Log In".
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ Lok AS, McMahon BJ (2004). "Chronic hepatitis B: update of recommendations". Hepatology. 39 (3): 857–61. doi:10.1002/hep.20110. PMID 14999707.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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.
  24. ↑ 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.
  25. ↑ Pedersen JS, Bendtsen F, Møller S (2015). "Management of cirrhotic ascites". Ther Adv Chronic Dis. 6 (3): 124–37. doi:10.1177/2040622315580069. PMC 4416972. PMID 25954497.
  26. ↑ Ginès P, Cárdenas A, Arroyo V, Rodés J (2004). "Management of cirrhosis and ascites". N. Engl. J. Med. 350 (16): 1646–54. doi:10.1056/NEJMra035021. PMID 15084697.
  27. ↑ 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.
  28. ↑ 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.
  29. ↑ 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.
  30. ↑ 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.
  31. ↑ "Endoscopic management of acute esophageal variceal bleeding - Techniques in Gastrointestinal Endoscopy".
  32. ↑ Sung JJ, Chung SC, Lai CW, Chan FK, Leung JW, Yung MY, Kassianides C, Li AK (1993). "Octreotide infusion or emergency sclerotherapy for variceal haemorrhage". Lancet. 342 (8872): 637–41. PMID 8103145.
  33. ↑ Gimson AE, Ramage JK, Panos MZ, Hayllar K, Harrison PM, Williams R, Westaby D (1993). "Randomised trial of variceal banding ligation versus injection sclerotherapy for bleeding oesophageal varices". Lancet. 342 (8868): 391–4. PMID 8101900.
  34. ↑ Krige JE, Kotze UK, Bornman PC, Shaw JM, Klipin M (2006). "Variceal recurrence, rebleeding, and survival after endoscopic injection sclerotherapy in 287 alcoholic cirrhotic patients with bleeding esophageal varices". Ann. Surg. 244 (5): 764–70. doi:10.1097/01.sla.0000231704.45005.4e. PMC 1856595. PMID 17060770.
  35. ↑ 35.0 35.1 Williams EJ, Iredale JP (1998). "Liver cirrhosis". Postgrad Med J. 74 (870): 193–202. PMC 2360862. PMID 9683971.
  36. ↑ Stiegmann GV, Goff JS, Michaletz-Onody PA, Korula J, Lieberman D, Saeed ZA, Reveille RM, Sun JH, Lowenstein SR (1992). "Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices". N. Engl. J. Med. 326 (23): 1527–32. doi:10.1056/NEJM199206043262304. PMID 1579136.
  37. ↑ Boyer TD (2003). "Transjugular intrahepatic portosystemic shunt: current status". Gastroenterology. 124 (6): 1700–10. PMID 12761727.
  38. ↑ Patel NH, Chalasani N, Jindal RM (1998). "Current status of transjugular intrahepatic portosystemic shunts". Postgrad Med J. 74 (878): 716–20. PMC 2431632. PMID 10320885.
  39. ↑ Loffroy R, Estivalet L, Cherblanc V, Favelier S, Pottecher P, Hamza S, Minello A, Hillon P, Thouant P, Lefevre PH, Krausé D, Cercueil JP (2013). "Transjugular intrahepatic portosystemic shunt for the management of acute variceal hemorrhage". World J. Gastroenterol. 19 (37): 6131–43. doi:10.3748/wjg.v19.i37.6131. PMC 3787342. PMID 24115809.
  40. ↑ McCormick PA, Dick R, Burroughs AK (1994). "Review article: the transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of portal hypertension". Aliment. Pharmacol. Ther. 8 (3): 273–82. PMID 7918921.
  41. ↑ Conn HO, Grace ND, Bosch J, Groszmann RJ, Rodés J, Wright SC, Matloff DS, Garcia-Tsao G, Fisher RL, Navasa M (1991). "Propranolol in the prevention of the first hemorrhage from esophagogastric varices: A multicenter, randomized clinical trial. The Boston-New Haven-Barcelona Portal Hypertension Study Group". Hepatology. 13 (5): 902–12. PMID 2029994.
  42. ↑ Bosch J, García-Pagán JC (2003). "Prevention of variceal rebleeding". Lancet. 361 (9361): 952–4. doi:10.1016/S0140-6736(03)12778-X. PMID 12648985.
  43. ↑ Butterworth RF (1992). "Pathogenesis and treatment of portal-systemic encephalopathy: an update". Dig. Dis. Sci. 37 (3): 321–7. PMID 1346515.
  44. ↑ Kersh ES, Rifkin H (1973). "Lactulose enemas". Ann. Intern. Med. 78 (1): 81–4. PMID 4682313.
  45. ↑ Ratnaike RN, Hicks EP, Hislop IG (1975). "The rectal administration of lactulose". Australian and New Zealand journal of medicine. 5 (2): 137–40. PMID 240347.
  46. ↑ Uribe M, Campollo O, Vargas F; et al. (1987). "Acidifying enemas (lactitol and lactose) vs. nonacidifying enemas (tap water) to treat acute portal-systemic encephalopathy: a double-blind, randomized clinical trial". Hepatology. 7 (4): 639–43. PMID 3301614.
  47. ↑ Blei AT, Córdoba J (2001). "Hepatic Encephalopathy". Am. J. Gastroenterol. 96 (7): 1968–76. doi:10.1111/j.1572-0241.2001.03964.x. PMID 11467622.
  48. ↑ Bucci L, Palmieri GC (1993). "Double-blind, double-dummy comparison between treatment with rifaximin and lactulose in patients with medium to severe degree hepatic encephalopathy". Current medical research and opinion. 13 (2): 109–18. PMID 8325041.
  49. ↑ Pedretti G, Calzetti C, Missale G, Fiaccadori F (1991). "Rifaximin versus neomycin on hyperammoniemia in chronic portal systemic encephalopathy of cirrhotics. A double-blind, randomized trial". The Italian journal of gastroenterology. 23 (4): 175–8. PMID 1751811.
  50. ↑ Epstein M (1992). "The hepatorenal syndrome--newer perspectives". N. Engl. J. Med. 327 (25): 1810–1. doi:10.1056/NEJM199212173272509. PMID 1435935.
  51. ↑ Ginès P, Guevara M, Arroyo V, Rodés J (2003). "Hepatorenal syndrome". Lancet. 362 (9398): 1819–27. doi:10.1016/S0140-6736(03)14903-3. PMID 14654322.
  52. ↑ Ginés P, Arroyo V, Quintero E; et al. (1987). "Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study". Gastroenterology. 93 (2): 234–41. PMID 3297907.
  53. ↑ Toledo C, Salmerón JM, Rimola A, Navasa M, Arroyo V, Llach J, Ginès A, Ginès P, Rodés J (1993). "Spontaneous bacterial peritonitis in cirrhosis: predictive factors of infection resolution and survival in patients treated with cefotaxime". Hepatology. 17 (2): 251–7. PMID 8428722.
  54. ↑ Solà R, Andreu M, Coll S, Vila MC, Oliver MI, Arroyo V (1995). "Spontaneous bacterial peritonitis in cirrhotic patients treated using paracentesis or diuretics: results of a randomized study". Hepatology. 21 (2): 340–4. PMID 7843703.

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