CIRRHOSIS

2. CIRRHOSIS ASSIT.PROF. ZAHERTARIK IBRAHIM AMANY MOHAMAD IBRAHIM

3. Cirrhosis is a condition in which the liver slowly deteriorates and malfunctions due to chronic injury. Scar tissue replaces healthy liver tissue, partially blocking the flow of blood through the liver. Scarring also impairs the liver’s ability to: • 1-control infections • 2-remove bacteria and toxins from the blood • 3-prosecc nutrients, hormones, and drugs • 4- make proteins that regulate blood clotting • 5-produce bile to help absorb fats—including cholesterol—and fat-soluble vitamins • A healthy liver is able to regenerate most of its own cells when they become damaged. With end-stage cirrhosis, the liver can no longer effectively replace damaged cells. A healthy liver is necessary for survival.

4. Definition: Cirrhosis results from the necrosisof liver cells followed by fibrosis and nodule formation the liver architecture is diffusely abnormal and this interferes with liver blood flow and function: 1-Portal hypertension 2 - impaird liver function

5. Causes of cirrhosis • 1- HepatitisB &Hepatitis C • 2- Cystic fibrosis • 3-Fat that accumulates in the liver (nonalcoholic fatty liver disease) • 4-Hardening and scarring of the bile ducts (primary sclerosing cholangitis) • 5- Inability to process sugars in milk (galactosemia) • 6-Too much copper accumulated in the liver (Wilson's disease)

6. 7 -Liver disease caused by your body's immune system (autoimmune hepatitis) • 8-Poorly formed bile ducts in babies (biliary atresia) • 9- Iron build up in the body (hemochromatosis) • 10-Destruction of the bile ducts (primary biliary cirrhosis) • ohol

7. 11-Budd-Chiari syndrome • 12-Veno-occlusive disease • 13-Drugs (methotrexate) • 14-α1-Antitrypsin deficiency • 15-Hepatic venous congesion • 16-Idiopathic (cryptogenic) • 17-Alcohol • 18-Other viruses :  -

8. Pathogenesis: Chronic injury to the liver results in inflammation, necrosis and, eventually, fibrosis. Fibrosis is initiated by activation of the stellate cells.Kupffer cells, damaged hepatocytes and activated also platelets are probably involved. Stellate cells are activated by many cytokines and their receptors, reactive oxygen signals. In the early stage of activation the stellate cells become swollen and lose retinoids with upregulation of receptors for proliferative and fibrogenic cytokines, such as platelet-derived growth factor (PDGF), and transforming growth factor β1 (TGF-β1). TGF-β1 is the most potent fibrogenic mediator identified.

9. Inflammatory cells contribute to fibrosis via cytokine secretion, in the space of Disse, the normal matrix is replaced by collagens, predominantly types 1 and 3, and fibronectin. Subendothelial fibrosis leads to loss of the endothelial fenestrations (ports), and this impairs liver function. Collagenases (matrix metalloproteinases, MMPs) are able to degrade this collagen but are inhibited by tissue inhibitors of metalloproteinases (TIMPs), which are increased in human liver fibrosis. There is accumulating evidence that in the early stages liver fibrosis is reversible, particularly when inflammation is reduced, e.g. by suppressing or eliminating viruses.

12. Pathology:The characteristic features of cirrhosis are regenerating nodules separated by fibrous septa and loss of the normal lobular architecture within the nodules two types of cirrhosis are present: Micronodularcirrhosisnodules are usually less than 3 mm in size and the liver is involved uniformly. This type is often caused by ongoing alcohol damage or biliary tract disease • Macronodular cirrhosis the nodules are of variable size and normal acini may be seen within the larger nodules. This type is often seen following chronic viral hepatitis. • A mixed picture with small and large nodules is sometimes seen.

13. SYMPTOMS • Patients may be asymptomatic or complain of non-specific symptoms, particularly fatigue. Specific symptoms include:: • Right hypochondrial pain due to liver distension- • Abdominal distension due to ascites- • Ankle swelling due to fluid retention- • -Haematemesis and melaena from gastrointestinal haemorrhage • -Pruritus due to cholestasis - this is often an early symptom of primary biliary cirrhosis • -Breast swelling (gynaecomastia), loss of libido and amenorrhoea due to endocrine dysfunction • -Confusion and drowsiness due to neuropsychiatric complications (portosystemic encephalopathy • -fever-loss of body weight-

14. Signs:1-general signs • jaundice-fever-loss of bodyhair-LOSSof body weight-pallor-cacheexia • Spider navi :Vascular lesions consisting of a central arteriole surrounded by many smaller vessels because of an increase in estradiol. These occur in about 1/3 of cases • Palmar erythema:Exaggerationsof normal speckled mottlingof the palm, because of altered sex hormone metabolism. • Ecchymosis(1to 3cm)-purpura(3m to1cm) • or petechia (<3mm) • Scratch marks (pruritus):due to bile salt deposite in skin • Nail changes : clubbing-terry nail -leuchonychia • Oedema of the lower limb • Xanthelasmas-parotid enlargement

29. 2- local signs: • Abdominal enlargment –full flankes-umblical hernia • Dilated viens-divercation of recti • Venous hum:heard in epigastric region (on examination by stethoscope) because of collateral connections between portal system and the remnant of the umbilical vein in portal hypertension • . • Caput medusa:In portal hypertension, the umbilical vein may open. Blood from the portal venous system may be shunted through the periumbilical veins into the umbilical vein and ultimately to the abdominal wall veins, manifesting as caput medusa. • . • ). • Liver :enlarged –normal or shranked

30. Splenomegalyincrease in size of the spleen). Caused by congestion of the red pulp as a result of portal hypertension). Liver size:enlarged-normalor shranked Neurological signs: (disorientation-drowsy-hepatic coma) : hepatic encephalopathy : Asterixis Bilateral asynchronous flapping of outstretched, dorsiflexed hands Fetor hepaticus : Musty odor in breath as a result of increaseddimethyl sulfide

31. Ascites:Accumulation of fluid in the peritoneal cavity giving rise to flank dullness (needs about 1500 mL to detect flank dullness). causes of ascites according to serum-ascites albumin gradient :

32. Investigations • These are performed to assess the severity and type of cirrhosis • . Liver function : Serum albumin and prothrombin time are the best indicators of liver function: the outlook is poor with an albumin level below 28 g/L. The prothrombin time is prolonged commensurate with the severity of the liver disease • Bilirubin

33. Liver biochemistry :elevation in the serum Alanine aminotransferase ALP) and serum Aspartateaminotransferase (AST). In decompensated cirrhosis all biochemistry is deranged • Total proteins. • Alkaline phosphatase. • Serum electrolytes:A low sodium indicates severe liver disease due to a defect in free water clearance or to excess diuretic therapy • Serum creatinine:An elevated concentration >130 μmol/L is a marker of worse prognosis • In addition, serum α-fetoprotein if >200 ng/mL is strongly suggestive of the presence of a hepatocellular carcinoma. This can be determined

34. . Lab to detect cause of cirrhosis: • 1-viral marker • 2-serum autoantibodies : • -Anti-mitochondrial antibody(primary biliary cirrhosis) • -anti- nuclear,smooth muscle(actin),liver/kidney microsomal antibody(AUTOIMMUNAHEPATITIS) • 3- serum immunoglobulins: • -IgG (AUTOIMMUNA HEPATITIS ) • -IgM (primary biliary cirrhosis • 4-iron indices • 5- copper and caeruloplasmin • 6-alpha 1 antitrypsin • 7- MARKER OF LIVER CIRRHOSIS • 8-Anti-nuclear cytoplasmic antibodies • 9-Genetic analyses

35. . Ultrasound examinationThis can demonstrate changes in size and shape of the liver. Fatty change and fibrosis produce a diffuse increased echogenicity. In established cirrhosis there may be marginal nodularity of the liver surface and distortion of the arterial vascular architecture. The patency of the portal and hepatic veins can be evaluated. It is useful in detecting hepatocellular carcinoma-ascites. Elastography is being used in diagnosis and follow-up to avoid liver biopsy. • CT SCAN : hepatosplenomegaly, and dilated collaterals are seen in chronic liver disease. Arterial phase-contrast-enhanced scans are useful in the detection of hepatocellular carcinoma.

36. Endoscopy is performed for the detection and treatment of varices, and portal hypertensive gastropathy. Colonoscopy is occasionally performed for colopathy. • .MRI scan: This is useful in the diagnosis of benign tumours such as haemangiomas. MR angiography can demonstrate the vascular anatomy and MR cholangiography the biliary tree. • Liver biopsy

37. Scoring system in cirrhosis(a)Modified Child – Pugh classification

38. Sursurvival % for patient score above

39. (b)Model 0f end stage- liver disease (MELD)score • 3.8 ×LN (bilirubin in mg/dl)+9.6 × LN(creatinine in mg/ dl)+11.2 ×LN (INR)+ 6.4 • To convert • bilirubin from μmol/L to mg/dL divide by 17 • creatinine from μmol/L to mg/dL divide by 88.4 • LN, natural logarithm; INR, international normalized ratio. • MELD scores (with no complications): 1-year survival 97% (score <10); 70% (score 30-40) • ).

40. management • Generally, liver damage from cirrhosis cannot be reversed, but treatment could stop or delay further progression and reduce complications. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. Close follow-up is often necessary. Antibiotics will be prescribed for infections, and various medications can help with itching.

41. Preventing further liver damage: • Regardless of underlying cause of cirrhosis, there are drugs known as hepato-toxic effect (high dose of paracetamol-alcohol-Halothane-Steroid-contraceptive pills-erythromycin-oral hypoglycaemics.,etc), avoid this drugs is very important in hepatic patients. • Vaccination of susceptible patients should be considered for prevention of chronic liver diseasesHepatitis AandHepatitis B.

42. Treating underlying causes: • . early treatment should be considered for Hepatitis C,B (interferon-ribavirin-lamivudine) • interferon for viral hepatitis and corticosteroids for autoimmune hepatitis. Cirrhosis caused byWilson's disease, in which copper builds up in organs, is treated withchelation therapy (e.g., penicillamine) to remove the copper • Stop alcohol intake in alcohilic cirrhosis

43. Tretment of complications • ascites : Salt restriction-diurietics • Esophageal variceal bleeding: • For portal hypertensionpropranolol is a commonly used agent to lower blood pressure over the portal system. In severe complications from portal transjugular intrahepatic portosystemic shuntingis occasionally indicated to relieve pressure on the portal vein. As this can worsen encephalopathy, it is reserved for those at low risk of encephalopathy, and is generally regarded only as a bridge to liver transplantation or as a palliative measure.

44. : Hepatic encephalopathy • Restriction protien diet-enema-lactulose • :Hepatorenal syndrome • Is defined as urine sodium <10mmol and serum creatinine >1.5 mg/dl after trial of volume expansion without diuretics treatment by Terlipressin or noradrenaline with intravenous albumin improve function in 30% of cases • Spontaneous bacterial peritonitis(SBP): Symptoms include fevers, chills, nausea, vomiting, abdominal tenderness and general malaisePatients may complain of abdominal pain and worsening ascites.Thirteen percent of patients have no signs or Hepatic encephalopathy • Diagnosis necessitates paracentesis (needle drainage of the ascitic fluid) and laboratory confirmation of ascitic neutrophils > 250/mm³.[1]

45. Treatment of SBP: • Antibiotics • After confirmation of SBP, patients need hospital admission for intravenous antibiotics (most often cefotaxime 2g IV Q8-12H for at least 5 days or ceftriaxone 2g IV Q24H). They will often also receive intravenous albumin. A repeat paracentesis in 48 hours is sometimes performed to ensure control of infection. Once patients have recovered from SBP, they require regular prophylactic antibiotics (e.g. Septra DS 1 tab 5 times/week, Ciprofloxacin 750mg PO Q1W, norfloxacin 400mg Q24H) as long as they still have ascites. • Intravenous albumin • A randomized controlled trial found that intravenous albumin on the day of admission and on hospital day 3 can reduce renal impairment • liver transplantation

46. Poor prognostic indicators in cirrhosis • Blood tests • Low albumin (< 28 g/L • Low serum sodium(<125mmol/L): • Prolonged prothrombin time > 6 seconds • Raisedcreatinine >130 um/L • Clinical: • Persistent jaundice • Persistent hypotension • Haemorrhage from varices, particularly with poor liver function_ • Ascites • Neuropsychiatric complications developing with progressive liver • Small liver • Aetiology (e.g. alcoholic cirrhosis,if patient continue drinking) • Failure of response to treatment

47. Thank You