CIRRHOSIS BY DR WAQAR M.B.B.S., M.R.C.P. ASST. PROFESSOR (MEDICINE) MAAREFA MEDICAL COLLEGE

CIRRHOSIS It is a condition where there is necrosis(death) of liver cells, followed by “fibrosis” and “nodule” formation. So, the liver structure gets damaged. It is a slowly developing process ( months to years) and causes disturbed liver functions. *Any “chronic” liver disease can lead to cirrhosis *Cirrhosis is irreversible

Nodular liver in cirrhosis

ETIOLOGIES Any chronic liver damage can lead to cirrhosis Alcohol Chronic Hep B & C most common Non alcoholic fatty liver disease causes(1,2,3) Primary biliary cirrhosis Autoimmune hepatitis ( can cause acute or chronic liver disease) Hemochromatosis ( excess iron deposition in the liver) Drugs Wilson’s disease ( excess copper deposition in the liver)

9) Cardiac cirrhosis: Due to right heart failure & liver congestion 10) Alpha 1 antitrypsin deficiency : Hereditary condition. Patients have COPD also. 11) Idiopathic ( no known cause) * Also called cryptogenic cirrhosis * Many patients have this

CLINICAL FEATURES OF CIRRHOSIS May be asymptomatic Weakness, anorexia, nausea, wt. loss Thin & chronically ill looking, cachexia 4) May be drowsy, slurred speech, disoriented ( due to hepatic encephalopathy) 4) Eyes: * Jaundice * Anemia 5) Breath: “Sweet” smell called fetor hepaticus

Clinical features contd. 7) Chest: * Gynecomastia in males ( due to high estrogen in blood) * Spider nevi ( spider shaped blood vessels on the skin). They blanch with pressure. (this testing is called diascopy) Spider nevi occur on the chest, face, neck or arms.

SPIDER NEVI GYNECOMASTIA

Clinical Features (contd) 8) Axilla: Loss of hair ( due to high estrogens) 9) Hands: * Clubbing * White nails ( due to low albumin) * Palmar erythema( redness of plams) * Dupuytren’s contracture (fibrosis in the palm) causing contractures of fingers) * Asterixis (flapping tremor) 10) Skin: * Jaundice * Scratch marks * Petechiae

DUPUYTREN’S CONTRACTURE

Clinical features contd. 11) Abdomen: * Usually distended ( ascites) * Umbilicus usually bulging * Dilated veins around the umbilicus ( called caput medusae) * Liver enlarged or “small” (in late stages) * Splenomegaly * Shifting dullness & fluid thrill ( ascites)

12) Testicular atrophy ( due to estrogens) 13) Pedal edema Estrogens are normally destroyed in the liver so in liver disease, can not be destroyed levels are high

INVESTIGATIONS CBC: * Thrombocytopenia ( due to splenomegaly) * Later, anemia & low WBC 2) LFTs: * AST usually high * ALT BUT * Alk. Phos. may be normal * Bilirubin The levels of these do not tell us about the severity of the liver disease. Cirrhosis may be very advanced but the enzymes may be minimally high.

Investigations(contd) 3) High P.T. & INR: This is due to decreased synthesis of clotting factors 4) Low albumin : Due to decreased synthesis. P.T./INR & serum albumin show severity of cirrhosis 5) High creatinine : ? Hepatorenal syndrome. 6) Serum alpha fetoprotein (AFP) * Normally, AFP is found in fetal blood & disappears after birth. * Levels rise in cirrhosis & very high in liver carcinoma * AFP levels are used as a screening test for liver cancer

Contd. 7) Ultrasound: Shows fibrous tissue in the liver. Other conditions like carcinoma of liver, if present, can also be seen. 8) Liver biopsy: Gold standard but not done in every patient 9) Paracentesis : Done if ascites is present

MANAGEMENT Cirrhosis is irreversible and the liver can not become normal. We just treat the complications as they arise. General Steps Good nutrition. Multivitamins Treat the cause ( eg Hep B or C, stop alcohol) Avoid certain medicines: Panadol, sleeping pills, diazepam etc. ( adjust doses of many medicines) Screen for hepatocellular carcinoma by: * ultrasound & alpha fetoprotein levels every 6 months

Management (contd) 5) Annual flu vaccine, pneumovac 6) In some cases, liver transplant

COMPLICATIONS OF CIRRHOSIS & THEIR MANAGEMENT Ascites Portal HTN (& its consequences) Encephalopathy Hepato-renal syndrome Liver carcinoma Infections Malnutrition/Osteoporosis

Portal HTN Increased pressure in the portal system due to compression by cirrhosis (there are also other causes of portal HTN). The dilated portal vein can be seen in ultrasound

Etiologies of Portal HTN Cirrhosis ( most common cause) Portal vein thrombosis Chronic pancreatitis ( compression of portal vein) 4) Schistosomiasis ( bilharziasis) 5) Budd-Chiari syndrome ( thrombosis of hepatic veins)

EFFECTS OF PORTAL HTN Esophageal & gastric varices: * Dilated vessels at the esophagogastric junction & gastric fundus ( called varices) * Varices can rupture & bleed. This can be life threatening. * Varices can be seen at endoscopy * Propranolol is given to prevent rupture & bleeding (by causing vasoconstriction) * Treatment of acute bleeding is : a) i.v. Octreotide ( causes vasoconstriction)

Varices contd. b) Endoscopic treatment ( sclerotherapy, banding, balloon tamponade). After an initial bleeding episode, there is a high chance of rebleeding. So, propranolol is given for prophylaxis & continued for ever.

Effects of portal HTN contd. 2) Splenomegaly 3) Ascites 4) Caput Medusae ( dilated abdominal wall veins

Complications of Cirrhosis Hepatic Encephalopathy It is “mental status changes & psychiatric disturbance secondary to liver failure.” It occurs in cirrhosis & also in acute liver failure, if that is severe Occurs due to accumulation of ammonia (NH3) & other toxins which can not be removed from the blood by the diseased liver Divided into grades, depending on severity

Encephalopathy contd. Grade 1: Mild confusion, asterixis, changed sleep pattern( sleep during day & awake at night) Grade 2: More confusion, asterixis, lethargy Grade 3: Severe confusion, increased sleep, aggressive behavior Grade 4: Coma ( Other metabolic problems can also cause these symptoms of encephalopathy)

Encephalopathy (contd) Factors which can precipitate Encephalopathy in a cirrhosis patient: GI bleed b) Constipation c) Hypokalemia High protein diet e) Infection f) Sedatives g) Progressive worsening of cirrhosis h) SBP (spontaneous bacterial peritonitis) TREATMENT (of encephalopathy) Aim is to decrease NH3 production, & increase its excretion in the stool. This is done as follows:

Contd. Laxatives Lactulose syrup or enema Antibiotics They kill the NH3 producing bacteria in the G.I.T. ( Rifaximin, Flagyl, Neomycin) 3) Treat the pptating factor 4) Hold dietary proteins for few days ( excess proteins more NH3 is produced) 5) i.v. ptoton pump inhibitors ( for GI bleed)

Hepatorenal Syndrome Renal Failure secondary to liver disease Occurs due to renal vasoconstriction Renal tissue is normal ( no renal pathology) Treatment is: * Dialysis * Liver transplant Poor prognosis wthout treatment (In ascites, too much removal of fluid , more than 7 liters at a time can cause hepato-renal syndr.)

PROGNOSIS OF CIRRHOSIS Prognosis is very variable and depends on the etiology, severity of liver disease & presence of complications. There is a classification or grading system for cirrhosis, called CHILD-PUGH classification, in which we grade the severity of cirrhosis according to : * Bilirubin * Albumin level * Ascites B A A * P.T./ INR * Presence of Encephalopathy P E Points are given for each of the above & total score is calculated According to this, cirrhosis can be Class A, B or C High score Poor prognosis Low score Better prognosis Overall, the 5 yr. survival is 50%

Primary Biliary Cirrhosis (PBC) POINTS: It is mostly seen in middle aged females. There is antibody mediated destruction of intrahepatic bile ducts which causes chole- -stasis (bile flow is decreased) 3) Ultimately, it leads to cirrhosis

S/S of PBC Pruritus : Due to accumulation of bile salts Jaundice & fatigue 3) Xanthelasma: These are cholesterol plaques on the eyes. ( Blood cholesterol is high in PBC) 1) & 2) are the most common symptoms.

Xanthelasma

INVESTIGATIONS Antimitochondrial antibody in the blood ( A.M.A. Diagnostic) 2) LFTs: * Alk.Phos. & bilirubin are very high * AST & ALT may be high 2) High serum Cholesterol 4) Liver Biopsy: Shows destruction of the intra- - hepatic bile ducts.

Treatment of P.B.C. There is no cure of this disease. Treatment controls the symptoms and slows the progression. Urso-deoxy-cholic acid Liver transplant ( in advanced disease) Symptomatic treatment for pruritus (cholestyramine, antihistamines, Rifampicin) Vit A, D & E supplements ( fat soluble vitamins) PROGNOSIS It progresses slowly and can lead to liver failure.

HEMOCHROMATOSIS A genetic disorder in which excess iron is absorbed from the GIT & deposited in various tissues including liver, pancreas, joints, heart, brain, testes etc.

S/S Cirrhosis If you see these DM S/S, think of Skin discoloration hemochromatosis Cardiomypathy Joint pains

DIAGNOSIS Serum ferritin is high Transferrin saturation is high Genetic analysis ( presence of C282 Y mutation ) Liver biopsy ( gold standard)

TREATMENT OF HEMOCHRO. Repeated phlebotomy to remove blood Iron chelation therapy with Deferoxamine First choice treatment is phlebotomy ( forever). If phlebotomy is contraindicated chelation therapy Always screen family members of the patient

THANK YOU & KEEP SMILING BECAUSE LIFE IS BEAUTIFUL