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.

5. Contd
.• Scarring also impairs the liver's Inability 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

6. Manifestations of Liver Cirrhosis

8. Causes of Cirrhosis
(Percentagewise)
1. Fatty liver 60- 70%
2. Viral hepatitis 10 %
3. Billiary disease 5-10 %
4. Primary hemochromatosis 5%
5. Cryptogenic cirrhosis 10-15%

9. Clinical cirrhosis:

10. GUIDELINES FOR MANAGEMENT

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

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

13. 2. SPECIFIC MANAGEMENT

14. 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

15. TREATMENT BASED ON AETIOLOGY
• Alcoholic cirrhosis-
1. Complete abstinence from alcohol
2. Nutritional support(>3000kcal/day) along with multivitamins
3. Prednisolone and Pentoxifylline in severe cases.
4. Pentoxifylline is a hemorrheologic agent, Anti-inflammatory agent.
5. ADR of Pentoxifylline:-
Cyto-toxic effect in Preclinical studies[1].
6. 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]`

16. • Post viral cirrhosis-
1. 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);
2. lamivudine 100mg once daily until HBeAg becomes negative ; entecavir,
tenofovir, adefovir dipivoxil or telbivudine can also be tried.
3. 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].
4. Lamivudine, entecavir, tenofovir, adefovir dipivoxil or telbivudine comes under
Anti-retroviral nucleoside Reverse Transcriptase Inhibitor
5. Major ADR is NRTI is Thrombocytopenia (decreased level of Platelet)
6. Management of Thrombocytopenia:- Blood transfusion to temporarily increase
platelet levels in your blood. .. And prescribe the steroids[6].

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

18. TREATMENT BASED ON AETIOLOGYcontd.
• Biliary cirrhosis-
1. 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:-
(i) Prescribe the NSAID for Pain like Aspirin.
(ii) For Skin rash to prescribe Anti-histamine drugs like
citrezine.
2. Steroids

19. 3. 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)
(i) Control of weight, Diabetes and hyperlipidemia
(ii) Metformin 500 mg BD, pioglitazone 15 mg Tab, UDCA,
pentoxyfylline and atorvastatin might be helpful

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

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

23. 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.

24. 3. MANAGEMENT OF COMPLICATIONS

25. MAJOR COMPLICATIONS
1. Ascites
2. Spontaneous bacterial peritonitis
3. Hepatic encephalopathy
4. Portal hypertension
5. Variceal bleeding

26. MANAGEMENT OF COMPLICATIONS
Ascites:-
• Bed rest
• Low salt diet (4-6g of salt)
• Avoid NSAIDs
• Fluid restriction to 1-1.5L/24 hr
• Spironolactone 25mg/6 hr orally and increase dose every 48 hr to
400mg/24hr; triamtereneand amiloride can also be tried, but Spironolactone
is more efficacy[4] . Frusemide can be added to the abovetherapy.
• Diuretics should be stopped if there is severe hyponatremia

27. 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.

28. 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

29. MANAGEMENT OF COMPLICATIONS contd.
Variceal bleeding:-
1. 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).
2. 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 Lanreotide.
3. Balloon Tamponade
4. Endoscopic Sclerotherapy and Endoscopic Band Ligation
5. TIPSS

30. 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.

34. Portal hypertension-
1. 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 -
1. 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).
2. MOA:- bRelaxation of smooth muscle of venous and arterial vasculatar

35. 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 Alcoholiccirrhosis
• Cirrhosis due to hepatitis C
• Alpha1Antitrypsin deficiency
• Glycogen storage disorder

36. 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

37. 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

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

39. AFP(American Family Physician) Guidelines

40. REFERENCE:-
1. 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
2. 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
3. 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
4. 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

41. 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
8. https://www.slideshare.net/NikhilVaishnav3/liver-cirrhosis-126216985
9. https://www.slideshare.net/mahendradebbarma/management-of-
cirrhosis-for-improving-survival
10. https://www.slideshare.net/jagdishsamabd/liver-cirrhosis-90356960
11. https://www.slideshare.net/DevRamSunuwar/cirrhosis-of-liver-final-
pptx-83199340