Liver Cirrhosis PDF

Liver cirrhosis Prof. Dr. / Hany Shabana Professor of Internal Medicine , Hepatology & Gastroenterology Unit, Mansoura University CASE PRESENTATION A 50-year-old man is referred to the medical admission unit with 4-week history of increasing abdominal distensi...

Liver cirrhosis Prof. Dr. / Hany Shabana Professor of Internal Medicine , Hepatology & Gastroenterology Unit, Mansoura University CASE PRESENTATION A 50-year-old man is referred to the medical admission unit with 4-week history of increasing abdominal distension and anorexia, followed by2 weeks of jaundice. There has been no change in bowel habit or vomiting and he denies any weight loss. His wife has noticed him to be confused over the last 24 h. He takes no regular medication. He had used intravenous drugs once when he was aged 20. The patient has 5-6 spider naevi on his upper chest wall. Asterixis (flapping tremor) is demonstrated. He has a firm , sharp bordered, non-tender liver which is palpable 6 cm below the right costal margin at the midclavicular line. Ascites is confirmed on abdominal examination (shifting dullness).  CLINICAL SIGNS Jaundice Ascites  CLINICAL SIGNS Spider Navus Bilateral pitting oedema LL INVESTIGATIONS INVESTIGATIONS Ultrasound examination showed that the liver is enlarged and has a coarse texture; the spleen is also enlarged.There is no intrahepatic or common bile duct dilatation. No focal lesions are seen within the liver and the main portal vein is patent and dilated (16mm).Moderate ascites was detected. The virology screening tests indicated that the patient is hepatis is C antibody- positive. PCR for HCV RNA viral load was 2654000 iu/ml. Tapping of the ascitic fluid was done and biochemical and cytological examination revealed: WBCs count 1500/cmm with 90% neutrophils. Ascitic fluid albumin was 0.4 g/dl TREATMENT Spontaneous bacterial peritonitis(SBP) was the diagnosis Either intravenous cephalosporins or oral quinolones are effective and should be given while awaiting bacterial culture results. Secondary prophylaxis is then needed to reduce the risk of further infections. The mild hepatic encephalopathy will probably improve with treatment of the infection, but lactulose should also be given orally. Constipation is a common precipitant of hepatic encephalopathy, and if lactulose cannot be given orally because of reduced conscious level, then phosphate enemas are an alternative. An upper gastrointestinal endoscopy will be needed to look for varices, even though there is no history of bleeding, as ß-blocker prophylaxis will reduce the risk of bleeding from asymptomatic large varices. Treatment of the patient's hepatitis C will need to be considered when his liver function has improved. LIVER CIRRHOSIS DEFINITION : a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. It results in impairment of hepatic function which manifests as : Jaundice Portal hypertension Varices Ascites Spontaneous bacterial peritonitis Hepato-renal syndrome Hepatic encephalopathy Progressive hepatic failure CLASSIFICATION 1. Morphologic classification was historically used to classify cirrhosis as the following: Micronodular cirrhosis, with uniform nodules < 3 mm in diameter Macronodular cirrhosis, with nodular variation ≥3 mm in diameter Mixed cirrhosis, a combination of micronodular and macronodular cirrhosis. Micronodular cirrhosis frequently evolves into macronodular. This classification system has limited clinical utility. 2. Etiologic classification of cirrhosis is the most clinically useful. The two most common causes of cirrhosis in developed countries are excessive alcohol use and viral hepatitis. As the incidence of obesity and diabetes mellitus continues to rise; by the year 2030, NASH is will be one of the leading causes of cirrhosis. Most cases of cryptogenic cirrhosis are felt to be "burned out" NASH. Etiologic classification  Pathophysiology * The hepatocyte or liver cell has a variety of functions. The fenestrated sinusoids with absent intercellular junctions and basement membranes ensure close interactions between the sinusoidal blood and hepatocytes. Hepatic stellate cells, present in the space of Disse, are in close communication with the hepatocytes and the sinusoidal endothelial cells. *Injury to hepatocytes leads to the initiation of an inflammatory response with the release of cytokines. Hepatic stellate cells are transformed into cells with fibrinogenic, contractile, and proliferative properties. Extracellular matrix synthesis causes the fibrinogenic response and bridging fibrosis occurs, leading to "capillarization" of the hepatic sinusoids (a shift from a fenestrated sinusoid to a "non-fenestrated" capillary). Increased intrahepatic vasoconstrictors, such as endothelin, and decreased vasodilators, such as nitric oxide with increased stellate cell contractility, caused increased intrahepatic resistance and decreased sinusoidal blood flow.  Pathophysiology An abnormal proliferation of hepatocytes occurs, leading to a nodular pattern of regeneration within areas of fibrosis further decrease the intrahepatic blood flow This leads to an increase in the portal pressure and complications of portal hypertension caused by the formation of portosystemic collaterals, including the formation of gastroesophageal varices and splenomegaly. Portal hypertension leads to splanchnic arterial vasodilation caused by increased release of nitric oxide. Baroreceptors sensing of this arterial underfilling leads to the activation of the neurohormonal system causing vasoconstriction in non-splanchnic vascular beds by activation of the sympathetic nervous system (SNS), renin- angiotensin-aldosterone system (RAAS) and the arginine vasopressin system leads to a pattern of sodium retention, water retention, and renal vasoconstriction, leading to dilutional hyponatremia, ascites, peripheral edema, and , in severe cases, the hepatorenal syndrome. Ongoing destruction leads to a decrease in hepatic synthetic function, with coagulopathy, jaundice, hypoglycemia, and hepatic encephalopathy. PATHOLOGY Gross examination: The liver surface is irregular, with multiple yellowish nodules The liver may be enlarged because of multiple regenerating nodules, in the final stages, it becomes small and shrunken. Microscopic examination Nodularity (regenerative nodules) Fibrosis Abnormal hepatic architecture Abnormal Hepatocytes Importance of histologic examination(Liver biopsy) Establishment of the presence of cirrhosis Assessment of grade of histologic activity & degree of liver fibrosis Determination of the cause of cirrhosis in some cases. CLINICAL FEATURES Patients with cirrhosis may come to clinical attention in numerous ways: 1. Stigmata of chronic liver disease on physical examination (e.g., palmar erythema, spider naevi) 2. Abnormal investigation (high serum aminotransferases, alkaline phosphatase, high bilirubin, low albumin, prolonged prothrombin time, thrombocytopenia) 3. Imaging abnormalities (small, shrunken, nodular liver or evidence of portal hypertension). 4. Complications of decompensated cirrhosis (jaundice, ascites, variceal bleeding, hepatic encephalopathy). 5. Cirrhotic appearance of the liver at the time of laparotomy or laparoscopy. CLINICAL FEATURES À patient with cirrhosis may present with none, some, or all the following findings: 1. General: Fatigue Anorexia Malaise Sleep-wake reversal Weight loss Muscle wasting 2. Gastrointestinal: a. Parotid gland enlargement b. Diarrhea c. Cholelithiasis d. Gastrointestinal bleeding: due to ruptured esophageal, gastric, duodenal, rectal, and/or stomal varices, Portal hypertensive gastropathy, enteropathy, or colopathy. CLINICAL FEATURES 3. Hematological: a. Anemia b. Thrombocytopenia c. Leukopenia d. Impaired coagulation e. Disseminated intravascular coagulation g. Portal vein thrombosis 4. Pulmonary Hepatic hydrothorax Accumulation of fluid within the pleural space in association with cirrhosis Usually right sided (70%) Typically associated with clinically apparent ascites, but can be found in patients without obvious ascites Hepatopulmonary syndrome Characterized by dyspnea, platypnea, orthodeoxia, digital clubbing, and severe hypoxemia. Hepatopulmonary syndrome is characterized by intrapulmonary shunting. Shunts can be revealed by bubble contrast echocardiography and radionuclide scintigraphy scanning with technetium labeled albumin. Orthotopic liver transplantation is treatment of choice. 5. Cardiac: Hyperdynamic circulation, diastolic dysfunction 6. Renal: Secondary hyperaldosteronism leading to sodium and water retention Hepatorenal syndrome 7. Endocrinological: a. Hypogonadism Male patients: Loss of libido, testicular atrophy, impotence, decreased level of testosterone. Female patients: Infertility, dysmenorrhea, loss of secondary sexual characteristics. b. Feminization (acquisition of estrogen-induced characteristics) Spider naevi Palmar erythema Gynecomastia changes in body hair patterns c. Diabétes mellitus CLINICAL FEATURES 8. Neurological. a. Hepatic encephalopathy b. Peripheral neuropathy c. Asterixis 9. Musculoskeletal Reduction in muscle mass Hepatic osteodystrophy Muscle cramping Umbilical herniation 10. Dermatological a. Spider naevi b. Palmar erythema c. Jaundice d. Pruritus e. Dupuytren contractures f. Clubbing g. Paper money skin h. Caput medusa i. Easy bruising 11. Infections a. Spontaneous bacterial peritonitis b. Urinary tract infection C. Respiratory tract infection d. Bacteremia e. Cellulitis CLINICAL FEATURES CLINICAL FEATURES NATURAL HISTORY Compensated cirrhosis has a 10-year survival of 47%. Decompensated cirrhosis is characterized by jaundice, variceal hemorrhage, or uncontrolled ascites. Patients usually die from complications of hepatic dysfunction or portal hypertension. Patients develop decompensated cirrhosis at the rate of 7% to 10% per year. Ascites develops in approximately 35% to 50% of patients within 5 years. Varices develop in 5% to 10% of patients annually. There is a higher mortality rate seen in decompensated cirrhosis. DIAGNOSIS Clinical examination a. Stigmata of cirrhosis Spider naevi Palmar erythema Dupuytren contractures Gynecomastia Testicular atrophy b. Features of portal hypertension Ascites Splenomegaly Caput medusa Evidence of hyperdynamic circulation (e.g., resting tachycardia , water hammer pulse) Venous hum best auscultated in the epigastrium c. Features of hepatic encephalopathy Confusion Asterixis Fetor hepaticus d. Others Jaundice Parotid gland enlargement Scanty suprapubic, chest and axillary hair DIAGNOSIS Laboratory evaluation a. Tests of hepatocellular injury AST and ALT: Most forms of chronic hepatitis other than alcohol have an AST/ALT ratio < 1; however, as chronic hepatitis progresses to cirrhosis , the ratio of AST/ALT may reverse. b. Tests of cholestasis Serum bilirubin (conjugated and unconjugated) Alkaline phosphatase * Gamma- glutamyl-transpeptidase (GGT ), 5'-nucleotidase c. Tests of synthetic function Serum albumin Prothrombin time coagulation factors (II, V, VII, X) d. Tests for the cause e. Tumor marker for HCC: Serum alpha fetoprotein (AFP) level. DIAGNOSIS Radiological investigations a. Abdominal ultrasonography(US) Noninvasive, relatively inexpensive, assesses liver echotexture , border irregularity and size. Can easily detect ascites, biliary dilatation- Doppler ultrasonography can assess hepatic and portal vein patency, diameter and blood flow screening test for HCC.e.g., focal hepatic lesion(mass) b. Computed tomography (CT) more expensive than ultrasonography Often requires administration of potentially nephrotoxic contrast radiation exposure * confirms HCC diagnosis c. Magnetic resonance imaging (MRI) Noninvasive, high-expense imaging modality Excellent for evaluation of hepatic masses; can help differentiate other focal hepatic lesions eg hemangiomas from a possible HCC. Can easily assess hepatic vasculature without the need for nephrotoxic contrast agents; more reliable than Doppler ultrasonography. d. Magnetic resonance cholangio-pancreaticography (MRCP) is a noninvasive method to image the biliary tract. Abdominal ultrasonography DIAGNOSIS Endoscopic Esophagogastroduodenoscopy (EGD) to screen for gastro-esophageal varices DIAGNOSIS Noninvasive markers of hepatic fibrosis & cirrhosis 1- AST-to-platelet ratio index (APRI) score = [(AST/ULN) 100] / Platelets count. If the score was <.5, it denotes minimal or no fibrosis,.5 to 1.5, denotes significant fibrosis & >1.5, denotes cirrhosis. 2- FIB 4 score = Age (years) ×AST (U/L)/[PLT(109/L) ×ALT1/2 (U/L)] If the score was < 1.45, it denotes minimal or no fibrosis, 1.45 to 3.25, denotes significant fibrosis & >3.25, denotes cirrhosis 3-Transient elastography (fibroscan) TRANSIENT ELASTOGRAPHY DIAGNOSIS Liver biopsy A liver biopsy is often helpful for rare cases, such as Wilson's disease, autoimmune hepatitis, and hemochromatosis to diagnose the cause of liver cirrhosis. b. Usually performed percutaneously; occasionally obtained through a trans- jugular approach, EUS guided or at laparoscopy. c. Complications: Bleeding, infection, pneumothorax, pain DIAGNOSIS PROGNOSTIC SCORES 1-Child-Turcutte-Pugh score and class (CTP) DIAGNOSIS PROGNOSTIC SCORES TREATMENT Treatments of the cause of cirrhosis Avoidance of alcohol for alcohol-induced cirrhosis Antiviral therapy for chronic hepatitis C (Sofosbuvir, daclatasvir, ledipasvir) Antiviral agents for chronic hepatitis B (pegylated interferon, lamivudine, entecavir, tenofovir) Weight loss and risk factor modification in nonalcoholic fatty liver disease Phlebotomy for hemochromatosis Glucocorticoids for induction therapy and azathioprine for maintenance treatment of autoimmune hepatitis D-Penicillamine or trientine for Wilson disease. Ursodeoxycholic acid and/or obeticholic acid for primary biliary cholangitis (PBC). TREATMENT Treatment of complications (e.g., variceal hemorrhage, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis). Surveillance for HCC with ultrasonographic examinations and serum alpha fetoprotein(AFP) measurements every 6 months in patients with cirrhosis and in those with chronic hepatitis B. Vaccination of cirrhotic patients Vaccination against hepatitis A and B is recommended. Avoid hepatotoxins All cirrhotic patients should be advised to avoid alcohol and other hepato-toxins liver transplantation In end-stage cirrhosis, liver transplantation can be a lifesaving procedure if the patient is an appropriate candidate. Liver transplantation is indicated for patients with liver cirrhosis and a CTP class B/C or a MELD score of ≥15. HEPATIC ENCEPHALOPATHY Definition : Hepatic encephalopathy (HE) is a neuropsychiatric disorder associated with severe liver disease. Classification and grading: The type of HE is according the condition during which the manifestations appear.Its severity is graded according to the West Haven criteria. Types Type A (=acute) describes hepatic encephalopathy associated with acute liver failure, typically associated with cerebral oedema. Type B (= bypass) is caused by portal-systemic shunting without associated intrinsic liver disease. Type C (= cirrhosis) occurs in people with cirrhosis - this type is subdivided into minimal, episodic (if ≥ 2 attacks occur within 6 months), and persistent (if the patient does not return to his baseline performance between bouts). WEST HEAVEN GRADING OF HE COMMON PRECIPITANTS OF HE *Gastrointestinal bleeding *Post trans-jugular intrahepatic portosystemic shunt (TIPS) *Constipation *Spontaneous bacterial peritonitis and other infections *Narcotics or benzodiazepine use *Hepatocellular carcinoma *Worsening liver function *Diuretic use *Alkalosis *Hypokalemia PATHOGENESIS OF HE * Ammonia accelerates astrocyte swelling and cerebral edema, which lead to the neurologic manifestations. Complications: * Advanced cerebral edema can lead to uncal herniation and death(with > 75% risk in patients with grade IV HE). This is more common in type A, although it can be seen in patients with type C. The diagnosis * usually made on clinical grounds with altered mental status, asterixis, and hypo- or hyperreflexia. *Ammonia levels have very poor specificity and should not be used to diagnose or monitor treatment response. No correlation is found between the degree of HE and ammonia level. * Neurologic imaging (CT , MRI Brain) can be used to identify central causes, such as subdural hematoma. * Laboratory evaluation should focus on ruling out electrolyte abnormalities, SBP, bleeding, volume depletion, and other infections as precipitants. TREATMENT OF HE * Initial treatment is targeted at identifying and treating the precipitating factor * Replacement of animal protein with vegetable and dairy protein can be considered, provided that overall protein intake is not compromised. * Treatment is also aimed at lowering the ammonia level. (A) Disaccharides, such as lactulose, are to mainstay of treatment because of their ability to reduce intraluminal pH, converting ammonia to ammonium and allowing it to be purged from the colon. Lactulose an be administered orally, rectally, or through an NG rube. dose of 60 to 90 g/day, titrated to three to five loose bowel movements daily. (B) Non-absorbable antibiotics, such as rifaximin (1200 mg divided TID), have uncertain efficacy in comatose patients, but appear to be effective in patients treated chronically. (C) Probiotics may play an increasing role in the management of HE. (D) Patients with grade III to IV encephalopathy may require endotracheal intubation for airway protection & prevention of aspiration and should be treated in the ICU. (E) liver transplantation QUESTIONS Hepatopulmonary syndrome is not manifested by : A. Cyanosis B. Widespread intrapulmonary vascular dilatations C. Orthopnea D. Increased alveolar-arterial oxygen gradient Minimal hepatic encephalopathy is classically diagnosed by: A. Psychometric study B. Evoked potential study C. MRI of brain C. Evoked potential study D. Evoked potential study THANK YOU