MANAGEMENT OF LIVER CIRRHOSIS

By ANNOY MALLICK

9TH SEMESTER

Guided by: Dr. N. K. Sundaray

Dr. S.K. Barad

Cirrhosis is a consequence of chronic liver disease characterised 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.

Manifestations of Liver Cirrhosis

PREVENTION

• Eliminating alcohol abuse could prevent 75–80% of all cases of cirrhosis.

• Maintaining a healthy diet that includes whole foods and grains, vegetable, and fruits.

• Obtaining counseling or other treatment for alcoholism.

• Taking precautions (practicing safe sex, avoiding dirty needles) to prevent hepatitis.

• Getting immunizations against hepatitis(A and B), pneumococcus and influenza if a person is in a high-risk group .

• receiving appropriate medical treatment quickly when diagnosed with hepatitis B or hepatitis C.

• Having blood drawn at regular intervals to rid the body of excess iron from hemochromatosis.

• Wearing protective clothing and following product directions when using toxic chemicals at work, at home, or in the garden.

GUIDELINES FOR MANAGEMENT

The major goals of treating the cirrhotic patient include:

1. Slowing or reversing the progression of liver disease2. Preventing superimposed insults to the liver3. Preventing and treating the complications4. Determining the appropriateness and optimal timing for liver

transplantation

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

1. GENERAL MANAGEMENT

• Good nutrition

• Low salt diet

• Alcohol abstinence

• Avoid NSAID and sedatives & opiates

• Cholestyramine for pruritus

• Avoiding hepatotoxic drugs

2. SPECIFIC MANAGEMENT

AETIOLOGY OF CIRRHOSIS

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

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

• 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) or pegylated Interferon alpha-2b once in a week ; lamivudine 100mg once daily until HBeAg becomes negative ; entecavir, tenofovir, adefovir dipivoxil or telbivudine can also be tried.

2. Patients with chronic hepatitis C infection must receive pegylated Interferon alpha-2b and ribavirin.

3. In a case of both hepatitis B and D co-infection, pegylated Interferon alpha-2b has been found effective.

• Drug induced cirrhosis- methotrexate, methyldopa, isoniazid, phenylbutazone, sulphonamides

TREATMENT BASED ON AETIOLOGY contd.• Biliary cirrhosis-

1. Ursodeoxycholic acid(10-15mg/kg)

2. Steroids

3. Azathioprine, colchicine, methotrexate or cyclosporine

4. Limit fat intake

5. Monthly injections of vitamin K

• NASH-

1. Control of weight, Diabetes and hyperlipidemia

2. Metformin, pioglitazone, UDCA, pentoxyfylline and atorvastatin might be helpful

• Hemochromatosis-

1. Weekly venesection of 500ml of blood until serum iron is normal

2. Chelation therapy with desferrioxamine(40-80mg/kg/day)

3. Treatment for diabetes, CHF.

TREATMENT BASED ON AETIOLOGY contd.• 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. or tetrathiomolybdate

3. Liver transplantation in advanced cases

• Hepatic outflow tract obstruction-

1. Predisposing causes should treated

2. TIPSS for opening hepatic veins

3. Streptokinase followed by heparin and warfarin in case of thrombosis

4. Percutaneous balloon angioplasty

5. Liver transplantation in advanced cases

3. MANAGEMENT OF COMPLICATIONS

MAJOR COMPLICATIONS

1. Ascites

2. Spontaneous bacterial peritonitis

3. Hepatic encephalopathy

4. Portal hypertension

5. Variceal bleeding

6. Renal failure

7. Portal vein thrombosis

8. Hepatocellular carcinoma

9. Hemorrhagic manifestations

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; triamterene and

amiloride can also be tried. Frusemide can be added to the above therapy

• daily weight chart weight loss <1/2 kg/day

• Diuretics should be stopped if there is severe hyponatremia

• therapeutic paracentesis+ concomitant albumin infusion(6-8gm/L fluid removed)

• TIPSS; Le Veen shunt- fluid to internal jugular vein; Side to side portocaval shunt; liver

transplantation

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. Albumin along with antibiotics

reduces risk of hepatic encephalopathy

• Prophylaxis- ciprofloxacin 750mg or cotrimoxazole 960mg once weekly.

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

• Oral Neomycin 0.5-1g 6 hourly; metronidazole and rifaximin can also be used; mannitol iv can be used for cerebral oedema

• Haemoperfusion and liver transplantation are other options

Hepatorenal syndrome

1. Avoid overuse of diuretics, protein

2. IV albumin with/without haemodialysis

3. Terlipressin(vasopressin analogue) and alpha-adrenergic agonists(norepinephrine+midodrine+octreotide) along with

albumin

4. TIPPS if vasoconstriction fails

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)

3. Balloon tamponade

4. Endoscopic sclerotherapy and endoscopic band ligation

5. TIPSS

Portal hypertension-6. Non selective beta-blockers(propranolol and nadolol)

7. Nitrates(nitroglycerine and isosorbide dinitrate)

MANAGEMENT OF COMPLICATIONS contd.

Hepatocellular carcinoma-

• Curative therapy(lesions 1-3 in number and ,5cm in size, no metastasis)- surgical removal; percutaneous ethanol or acetic acid acid injection; percutaneous radiofrequency thermal ablation

• Palliative therapy-PEI and acetic acid injection; transcatheter arterial chemoembolization; percutaneous radiofrequency thermal ablation; chemotherapy using sorafenib(multikinase inhibitor)

• Liver transplant in presence of a localized tumour and underlying advanced liver disease

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

SIGNS OF LIVER INSUFFIENCY POINTING TO THE NEED FOR LIVER TRANSPLANT

• 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

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

CONTRAINDICATIONS

• Sepsis

• Multi-organ failure

• AIDS

• Extra-hepatic malignancy

• Active alcohol and other substance abuse

• Marked cardiorespiratory dysfunction

• Renal insufficiency

• >65yrs age

PROGNOSIS OF CIRRHOSIS

• Overall prognosis is poor

25% survive 5 years from diagnosis

• If liver function is good,

50% survive for 5 years

25% upto 10 years

POOR PROGNOSTIC FACTORS

• Deteriorating liver function

• Falling albumin <2.5g/dL

• Serum bilirubin >20g/L

• Marked hyponatremia <120mmol/L

• Prolonged PT

• Encephalopathy

• Rising serum creatinine

Health is wealth…eat well, stay well and sleep well

Thank you