Liver cirrhosis Management

Management of Liver Cirrhosis.

1. Liver Cirrhosis S. Arunkumar , IVth Pharm.D ., J.K.K. Nattraja College of Pharmacy, Kumarapalayam .

2. Definition Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrous scar tissue as well as regenerative nodules (lumps that occur as a result of a process in which damaged tissue is regenerated) leading to progressive loss of liver function.

3. C o n t d . Scarring also impairs the liver's In ability to: control infections remove bacteria and toxins from the blood process nutrients, hormones, and drugs make proteins that regulate blood clotting produce bile to help absorb fats — including cholesterol — and fat-soluble vitamins

4. Manifestations of Liver Cirrhosis

5. Causes of Cirrhosis ( P ercentage wise) 1. Fatty liver 60- 70% 2. Viral hepatitis 10 % 3. Billiary disease 5-10 % Primary hemochromatosis 5% Cryp t o g enic cirr h osi s 1 - 15 %

6. Clinical cirrhosis:

7. GUIDELINES FOR MANAGEMENT The major goals of treating the cirrhotic patient include: Slowing or reversing the progression of liver disease Preventing superimposed insults to the liver Preventing and treating the complications Determining the appropriateness and optimal timing for liver transplantation

8. MANAGEMENT There is no specific drug therapy for cirrhosis Drugs are used to treat symptoms and complications of advanced liver disease General management Specific treatments Treatment of complications of cirrhosis liver transplantation

9. 1. GENERAL MANAGEMENT Good nutrition Low salt diet Alcohol abstinence Avoid NSAID and sedatives & opiates Cholestyramine for pruritus Avoiding hepatotoxic drugs

10. 2. SPECIFIC MANAGEMENT

11. ETIOLOGY OF CIRRHOSIS Alcoholic cirrhosis Post viral cirrhosis( Hepatitis B, Hepatitis C ) Drug induced cirrhosis Biliary cirrhosis NASH Chronic autoimmune hepatitis Hemochromatosis Wilson’s disease Alpha1- antitrypsin deficiency Hepatic outflow tract obstruction and Idiopathic cirrhosis

12. TREATMENT BASED ON AETIOLOGY Alcoholic cirrhosis- Complete abstinence from alcohol Nutritional support (>3000kcal/day) along with multivitamins Prednisolone and Pentoxifylline in severe case s. Pentoxifylline is a hemorrheologic agent, Anti-inflammatory agent. ADR of Pentoxifylline :- Cyto -toxic effect in Preclinical studies[1]. The findings suggest that the administration of 40 mg of  prednisolone  daily for 1 month may have a beneficial effect on short-term mortality but not on the medium-term or long-term outcome of  alcoholic cirrhosis .[2]`

13. Post viral cirrhosis- For chronic hepatitis B infection, Interferon alpha-2b (5 million units daily s.c . or 10 million units thrice a week for 4-6 months); lamivudine 100mg once daily until HBeAg becomes negative ; entecavir , tenofovir , adefovir dipivoxil or telbivudine can also be tried. The combination of  tenofovir  and efavirenz with either  lamivudine  or  emtricitabine  (TELE) has proved to be highly effective in clinical trials for first-line treatment of HIV-1 infection[3]. Lamivudine , entecavir , tenofovir , adefovir dipivoxil or telbivudine comes under Anti-retroviral nucleoside Reverse Transcriptase Inhibitor Major ADR is NRTI is Thrombocytopenia (decreased level of Platelet) Management of Thrombocytopenia:- Blood transfusion to temporarily increase platelet levels in your blood. .. And prescribe the steroids[6].

14. Drug induced cirrhosis- Drug induced Cirrhosis: Methotrexate , 5-flurouracil, mercaptopurine Methyldopa, Isoniazid , Sulphonamides 7. Patients with chronic hepatitis C infection must receive pegylated Interferon alpha-2b and ribavirin . 8. In a case of both hepatitis B and D co-infection, pegylated Interferon alpha-2b has been found effective.

15. TREATMENT BASED ON AETIOLOGY contd. Biliary cirrhosis- Ursodeoxycholic acid (10-15mg/kg) MOA:- Reduce absorption of Cholestereol ADR:- Severe right-sided upper abdominal pain Skin rash, both are common Management of ADR:- Prescribe the NSAID for Pain like Aspirin. For Skin rash to prescribe Anti-histamine drugs like citrezine . 2. Steroids

16. Azathioprine (50mg tab), colchicine (500 microgram tab), methotrexate  3.3 mg/m2/day orally  or cyclosporine 600mg BD are immunosuppresant . Among them Immunosuppresent , Azathioprine have more efficacy compared to other drugs[7]. 4. Limit fat intake 5. Monthly injections of vitamin K 6. NASH (Non alcoholic steatohepatitis ) Control of weight, Diabetes and hyperlipidemia Metformin 500 mg BD, pioglitazone 15 mg Tab, UDCA, pentoxyfylline and atorvastatin might be helpful

17. TREATMENT BASED ON AETIOLOGY contd. Wilson’s disease :- Chelating agents like penicillamine (1g/day) or trientine hydrochloride (1.2-2.4g/day), Zinc acetate can be added to the therapy Patients with neurologic involvement can be given dimercaprol i.m . (100mg/2ml) or tetrathiomolybdate Hepatic outflow tract obstruction :- Predisposing causes should treated TIPSS for opening hepatic veins

18. Streptokinase(15 lac IU/1 hr) followed by heparin and warfarin in case of thrombosis, MOA:- Circulate the plasminogen to form complex that activate plasminogen to plasmin . ADR:- Hypotension, Management of ADR:- Hypertensive agents like high sodium intake, and prescribe adrenaline injection are prescribed. Percutaneous balloon angioplasty Liver transplantation in advanced cases

19. TIPPS A shunt is an artificial passage which allows fluid to move from one part of your body to another. A transjugular intrahepatic portosystemic shunt (TIPS) connects the vein which brings blood from your gastrointestinal tract and intra-abdominal organs to your liver, and the vein from your liver to the right part of your heart.

20. 3. MANAGEMENT OF COMPLICATIONS

21. MAJOR COMPLICATIONS Ascites Spontaneous bacterial peritonitis Hepatic encephalopathy Portal hypertension Variceal bleeding

22. MANAGEMENT OF COMPLICATIONS Ascites :- B ed rest L ow salt diet (4-6g of salt) A void NSAIDs F luid restriction to 1-1.5L/24 hr S pironolactone 25mg/6 hr orally and increase dose every 48 hr to 400mg/24hr ; triamterene and amiloride can also be tried , but Spironolactone is more efficacy[4 ] . Frusemide can be added to the above therap y. Diuretics should be stopped if there is severe hyponatremia

23. MANAGEMENT OF COMPLICATIONS contd. Spontaneous bacterial peritonitis I.V cefotaxime 2g 8 hourly for 5 days; alternate therapy includes amoxicillin/clavulanate (1.2g iv 8 hourly followed by 625mg orally) or ciprofloxacin(200 mg iv 12 hourly followed by 500mg BID) or ofloxacine(400mg twice daily) in patients with hepatic encephalopathy . Efficacy - Albumin along with antibiotics reduces risk of hepatic encephalopathy [5]. Prophylaxis- ciprofloxacin 750mg or cotrimoxazole 960mg once weekly.

24. MANAGEMENT OF COMPLICATIONS contd. Hepatic encephalopathy Reduce protein intake (0.8-1g/kg of protein per day) and maintain correct electrolyte balance and calorie intake(300g glucose/day) In gastrointestinal bleeds-ryles tube aspiration and repeated bowel wash Lactulose 15-30mL TDS orally and dose increased till there is 2-3 loose stools per day. Lactitol is better compared to lactulose

25. MANAGEMENT OF COMPLICATIONS contd. Variceal bleeding :- Vasopressin (20 units in 100mL of 5% glucose iv for 10 mins, repeated 3-4hourly if needed) with nitroglycerine (0.4g) or terlipressin(2mg iv 6 hourly till bleeding stops and then 1mg 6 hourly for 24 hours ) . Somatostatin(250µg/hr for 2-5 days) and octreotide(50µg bolus and then 50µg/hr for 2-3 days ) , this combination is more efficient when compare to L anreotide. Balloon T amponade Endoscopic S clerotherapy and E ndoscopic B and L igation TIPSS

26. Balloon tamponade Balloon tamponade  usually refers to the use of  balloons  inserted into the esophagus, stomach or uterus, and inflated to alleviate or stop refractory bleeding.

27. Portal hypertension- Non selective beta-blockers propranolol (ADULTS: PO 10 to 30 mg 3 to 4 times/day before meals and at bedtime) and nadolol ( PO Initiate with 40 mg/day) are more efficient when compare to other drugs, MOA:- Act by causing vasoconstriction, thereby decreasing  portal  blood flow. ADR:- Hypotension. Management - Nitrates(nitroglycerine( PO 2.5 or 2.6 mg (sustained-release form) tid to qid initially) and isosorbide dinitrate ( PO (oral tablets) 5 to 40 mg q 6 hr). MOA:- bRelaxation of smooth muscle of venous and arterial vasculatar

28. INDICATIONS FOR LIVER TRANSPLANTATION Fulminant hepatic failure Hepato-renal syndrome Biliary atresia Hepatocellular carcinoma with no single lesion >5cm or no more than 3 lesions with the largest being less than equal to 3cm Alcoholic cirrhosis Cirrhosis due to hepatitis C Alpha1Antitrypsin deficiency Glycogen storage disorder

29. SIGNS OF LIVER INSUFFIENCY POINTING TO THE NEED FOR LIVERTRANSPLANT Sustained or increased jaundice Ascites Hepatic encephalopathy not responding to medical therapy Hypoalbuminaemia <30g/l Fatigue and lethargy affecting the quality of life Intractable itching Recurrent variceal bleeding

30. LIVER TRANSPLATATION contd . 5 year survival is almost 75% Orthotopic liver transplantation- implantation of a donor organ after removal of the native organ in the same anatomical location; most common Auxiliary Orthotopic liver transplantation- native liver is removed and replaced with either the respective left or right lobe of a graft Living donor liver transplantation- a portion of healthy person’s liver is removed and used Bioartificial liver- cultured hepatocytes are used as bridge in patients with acute liver failure till donor liver becomes available

31. CONTRAINDICATIONS Sepsis Multi-organ failure AIDS Extra-hepatic malignancy Active alcohol and other substance abuse Marked cardiorespiratory dysfunction Renal insufficiency >65yrs age

32. AFP(American Family Physician) Guidelines

33. REFERENCE:- Crabb , D.W., Im , G.Y., Szabo , G., Mellinger , J.L. and Lucey , M.R. (2020), Diagnosis and Treatment of Alcohol‐Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases. Hepatology , 71: 306-333. doi: 10.1002/hep.30866 Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis.  N Engl J Med . 2015;372(17):1619-1628. doi:10.1056/NEJMoa1412278 Swartz JE, Vandekerckhove L, Ammerlaan H, et al. Efficacy of tenofovir and efavirenz in combination with lamivudine or emtricitabine in antiretroviral-naive patients in Europe.  J Antimicrob Chemother . 2015;70(6):1850-1857. doi:10.1093/ jac /dkv033 Campra JL, Reynolds TB. Effectiveness of high-dose spironolactone therapy in patients with chronic liver disease and relatively refractory ascites .  Am J Dig Dis . 1978;23(11):1025-1030. doi:10.1007/BF01263103. 5. Bernardi M, Ricci CS, Zaccherini G. Role of human albumin in the management of complications of liver cirrhosis.  J Clin Exp Hepatol . 2014;4(4):302-311. doi:10.1016/j.jceh.2014.08.007

34. REFERENCE:- 6. Izak M, Bussel JB. Management of thrombocytopenia.  F1000Prime Rep . 2014;6:45. Published 2014 Jun 2. doi:10.12703/P6-45. 7. https :// www.slideshare.net/annoy007/management-of-liver-cirrhosis https :// www.slideshare.net/NikhilVaishnav3/liver-cirrhosis-126216985 https :// www.slideshare.net/mahendradebbarma/management-of-cirrhosis-for-improving-survival https :// www.slideshare.net/jagdishsamabd/liver-cirrhosis-90356960 https ://www.slideshare.net/DevRamSunuwar/cirrhosis-of-liver-final-pptx-83199340