CIRRHOSIS ASSIT PROF TARIK IBRAHIM ZAHER AMANY MOHAMAD

CIRRHOSIS ASSIT. PROF. TARIK IBRAHIM ZAHER AMANY MOHAMAD IBRAHIM

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 n 2 -remove bacteria and toxins from the blood n 3 -prosecc nutrients, hormones, and drugs n 4 - make proteins that regulate blood clotting n 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 n when they become damaged. With end-stage cirrhosis, the liver can no longer effectively replace damaged cells. A. healthy liver is necessary for survival n n

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: 2 - impaird liver function

Causes of cirrhosis 1 - Hepatitis. B & Hepatitis C n 2 - Cystic fibrosis n 3 -Fat that accumulates in the n 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) n n n

7 -Liver disease caused by your body's immune system (autoimmune hepatitis) 8 -Poorly formed bile ducts in n babies (biliary atresia) 9 - Iron build up in the body n (hemochromatosis) 10 -Destruction of the bile ducts (primary biliary cirrhosis) ohol . 1 n n

11 -Budd-Chiari syndrome n 12 -Veno-occlusive disease n 13 -Drugs (methotrexate) n 14 -α 1 -Antitrypsin deficiency n 15 -Hepatic venous congesion n 16 -Idiopathic (cryptogenic) n 17 -Alcohol n 18 -Other viruses n

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 β 1 (TGFβ 1). TGF-β 1 is the most potent fibrogenic mediator identified. n

Inflammatory cells contribute to fibrosis n 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.

Pathology: The characteristic features n Macronodular cirrhosis the nodules are n 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: Micronodular cirrhosis nodules are usually less than 3 mm in size and the liver is involved uniformly. This type is often caused by ongoing alcohol damage 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 n . nodules is sometimes seen

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

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

2 - local signs: n Abdominal enlargment –full flankes-umblical hernia Dilated viens-divercation of recti n Venous hum: heard in epigastric region (on n . n Caput medusa: In portal hypertension, the n n examination by stethoscope) because of collateral connections between portal system and the remnant of the umbilical vein in portal hypertension 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

Splenomegaly increase in size of the n spleen). Caused by congestion of the red pulp as a result of portal hypertension). er size: enlarged-normal or shranked n Neurological signs: (disorientation- n drowsy-hepatic coma) : alopathy : n Asterixis Bilateral asynchronous flapping of outstretched, dorsiflexed hands Fetor hepaticus : Musty odor in breath as a result of increased dimethyl sulfide n n

Ascites: Accumulation of fluid in the peritoneal cavity giving rise to flank dullness (needs about 1500 m. L to detect flank dullness). causes of ascites according to serum-ascites albumin gradient : High: >1. 1 g/dl -Cirrhosis -Chronic hepatic congestion Right sided hart failure Budd Chiari syndrom Constrictive Nephrotic syndrom Massive liver metastases- myxedema Low<1. 1 g/dl Peritoneal carcinomatosis -Peritonealtuberculosis - Pancreatic and biliary disease - Nephrotic syndrome

Investigations These are performed to assess the severity and type of cirrhosis Liver function : Serum albumin . and prothrombin time are the best n n 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 n

Liver biochemistry : elevation in the serum Alanine aminotransferase ALP) and serum Aspartate aminotransferase (AST). In decompensated cirrhosis all biochemistry is deranged . Total proteins n . Alkaline phosphatase n Serum electrolytes: A low sodium indicates n 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/m. L is strongly suggestive of the presence of a hepatocellular This can be determined. carcinoma n n

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

Ultrasound examination This can . n 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 n collaterals are seen in chronic liver disease. Arterial phase-contrast-enhanced scans are useful in the . detection of hepatocellular carcinoma

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

Scoring system in cirrhosis (a)Modified Child – Pugh classification Score Ascites Encephalopathy ubin (Umol/l) 1 2 None <34 Mild 34 -50 3 Modrate/sever Marked >50 bumin (g/l) . >35 28 -35 <28 othrombin time seconds over normal <4 4 -6 >6

Sursurvival % for patient score above Child A (<7) Child B (7 -9) Child C 1 year 82 5 year 45 10 year 25 62 20 7 42 20 0

(b)Model 0 f end stage- liver disease (MELD)score 3. 8 ×LN (bilirubin in mg/dl)+9. 6 × n LN(creatinine in mg/ dl)+11. 2 ×LN (INR)+ 6. 4 To convert n bilirubin from μmol/L to mg/d. L divide by n 17 creatinine from μmol/L to mg/d. L divide by 88. 4 LN, natural logarithm; INR, international n normalized ratio. MELD scores (with no complications): 1 - n year survival 97% (score <10); 70% n

management Generally, liver damage from cirrhosis n 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 followup is often necessary. Antibiotics will be prescribed for infections, and various medications can help with itching.

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

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

Tretment of complications ascites : Salt restriction-diurietics n Esophageal variceal bleeding: n propranolol is For portal hypertension n a commonly used agent to lower blood pressure over the portal system. In severe complications from portal transjugular intrahepatic portosystemic shunting is 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

Hepatic encephalopathy : n Restriction protien diet-enema-lactulose Hepatorenal syndrome : n n Is defined as urine sodium <10 mmol 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 n ous bacterial peritonitis(SBP): n Symptoms include fevers, chills, nausea, vomiting, abdominal tenderness and general malaise. Patients 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] n n

Treatment of SBP: n Antibiotics n After confirmation of SBP, patients need hospital admission for n intravenous antibiotics (most often cefotaxime 2 g IV Q 8 -12 H for at least 5 days or ceftriaxone 2 g IV Q 24 H). 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 750 mg PO Q 1 W, norfloxacin 400 mg Q 24 H) as long as they still have ascites. Intravenous albumin n A randomized controlled trial found that intravenous albumin on the day of admission and on hospital day 3 can reduce renal impairment liver transplantation n n

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