Liver Diseases and Treatments Quiz

Paracentesis

• Patients treated with large volume paracentesis (≥ 6 L/day) should take IV albumin (40 g after each tap)
• Major complications of large volume paracentesis include:
  • Hypotension
  • Shock
  • Oliguria
  • Encephalopathy
  • Renal insufficiency
  • Hemorrhage
  • Perforation of the abdominal viscera
  • Infection
  • Protein depletion

Liver Transplantation & TIPS

• Transjugular intrahepatic portosystemic shunt (TIPS) or Liver transplantation should be considered in patients with refractory ascites

Clonidine

• Clonidine may be of benefit in refractory ascites and those with an activated sympathetic nervous system
• Clonidine decreased sympathetic activity and increased glomerular filtration rate (GFR)
• Clonidine dose 0.075 mg BID for 8 days can be used

Portal Hypertension & Esophageal Varices

• Portal hypertension is a result of increased portal venous inflow and increased resistance to portal blood flow through the portal vein due to fibrotic changes within the hepatic sinusoids
• Portal hypertension is further classified as prehepatic, intrahepatic, or posthepatic portal hypertension
• The most important sequel of portal hypertension is variceal development
• Varices develop in the esophagus, stomach, and rectum to compensate for increased blood volume
• Varices are weak superficial vessels, and any additional increase in pressure can cause these vessels to rupture and bleed
• Hemorrhage from varices occurs in 25% - 40% of patients with cirrhosis and is the cause of death for one third of patients

Management of Portal Hypertension and Variceal Bleeding

• Management of varices involves three strategies:
  • Primary prophylaxis to prevent a first variceal bleeding
  • Treatment of active variceal bleeding
  • Secondary prophylaxis to prevent rebleeding in patients who have already bled

Primary Prophylaxis (prevention of a first variceal bleeding)

• Pharmacotherapy is not recommended to prevent the development of varices in patients with cirrhosis who have not yet developed varices
• All cirrhotic patients who develop portal hypertension with varices should receive primary prophylaxis with β-Adrenergic blockers (BB) to reduce portal pressure, thereby reducing the likelihood of variceal rapturing
• BB therapy should be continued for life, because bleeding can occur when therapy is abruptly discontinued
• Therapy should be initiated with Propranolol, 10 mg thrice daily (or 20 mg twice daily) or Nadolol, 20 mg once daily (or 40 mg once daily), and titrated to a reduction in resting heart rate of 20-25% of the baseline, or an absolute heart rate of 55 - 60 beats/min

Treatment of Active Variceal Bleeding (Acute Variceal Hemorrhage)

• Fluid resuscitation is essential; rapid resuscitation with fluids and/or blood products are essential as shock reduces liver blood flow and causes further deterioration of liver function
• Vasoactive drug therapy (somatostatin, octreotide, or terlipessin) are potent vasoconstrictor that decrease splanchnic blood flow and reduce portal and variceal pressures, without significant adverse effects reducing or stopping variceal bleeding
• Combination pharmacologic therapy (vasoactive drugs) plus endoscopic variceal ligation (EVL) or sclerotherapy (when EVL is not technically feasible) is the most rational approach to treatment of acute variceal bleeding
• Prophylactic acid suppression with proton pump inhibitors (PPI) reduces the risk of secondary bleeding which may result from EVL-induced ulcers
• All patients with cirrhosis and gastrointestinal bleeding should receive prophylactic antibiotics because of the risk of severe bacterial infections and sepsis
• If standard therapy fails to control bleeding, an invasive procedure such (TIPS) is done

Prevention of Rebleeding (secondary prophylaxis)

• All patients with a history of variceal bleeding should receive secondary prophylaxis to prevent recurrent bleeding
• A combination of EVL and nonselective β-blockers (Propranolol or Nadolol) is considered the most effective regimen
• The combination therapy of a nonselective β-blocker with isosorbide mononitrate can be used in patients unable to undergo EVL
• Patients who cannot tolerate or who fail pharmacologic and endoscopic interventions can be considered for Transjugular intrahepatic portosystemic shunt (TIPS) to prevent rebleeding

Transjugular intrahepatic portosystemic shunt (TIPS)

• TIPS is a non-surgical procedure to decrease the pressure in the portal vein and involves the placement of one or more stents between the hepatic vein and the portal vein
• The stent is placed so that one end is in the high pressure portal vein and the other end is in the low pressure hepatic vein
• This tube shunts blood around the liver and by so doing lowers the pressure in the portal vein and varices and prevents bleeding from the varices
• Major complications of TIPS include severe encephalopathy and shunt occlusion

Hepatic encephalopathy (HE)

• Serious complication of chronic liver disease and is defined as an alteration in mental status and cognitive function occurring in the presence of liver failure
• The symptoms of HE range from forgetfulness, mental confusion, lethargy, personality changes, somnolence, confusion, and coma
• The symptoms are thought to result from an accumulation of gut-derived nitrogenous substances (neurotoxins) in the systemic circulation
• These substances can enter the CNS and result in alterations of neurotransmitters that affect consciousness and behavior
• Precipitating causes of HE can include:
  • GI bleeding
  • Diuretic-induced hypovolemia and/or electrolyte abnormalities
  • Metabolic alkalosis
  • Drugs
    • Opioids
    • Sedatives
    • Tranquilizers

Types of Hepatic Encephalopathy

• Type A is induced by acute liver failure
• Type B results from portal-systemic bypass without intrinsic liver disease
• Type C occurs with cirrhosis

Spontaneous Bacterial Peritonitis (SBP)

• Most common gram-positive pathogen is Streptococcus pneumoniae
• Patients may be asymptomatic, or may present with unexplained fever, or nonspecific abdominal pain
• The diagnosis of SBP is defined by a polymorphonuclear cell count (PMN) of greater than or equal to 250 cells/μL of the ascitic fluid or a positive bacterial culture of the ascitic fluid
• Patients with cirrhosis have a state of intravascular hypovolemia and organ hypoperfusion; SBP is thought to enhance this effect, resulting in progressive renal hypoperfusion and precipitation of renal failure or hepatorenal syndrome (HRS)

Management of Spontaneous Bacterial Peritonitis (SBP)

• Theraputic antibiotics: patients with diagnosed or suspected SBP should receive broad spectrum antibiotic
  • Third-generation cephalosporin: Cefotaxime, 2 g every 8 hours I.V, or ceftriaxone 2 g/day I.V for 5 days is considered the drug of choice. Also can use Ampicillin /sulbactam (2g /1g I.V.every 6 h)
  • Fluoroquinolones (ciprofloxacin or ofloxacin) may be used. Oral ofloxacin, 400 mg BD every 12 hours for 8 days, is equivalent to IV cefotaxime. Ampicillin and Gentamicin may be used
• Albumin: Plasma volume expansion with albumin in addition to antibiotics decreases the incidence of hepatorenal syndrome (HRS) and improves survival
• Prophylactic antibiotics
  • Primary prevention (prevention of SBP in patients who never develop SBP previously) should be considered in all patients who are at high risk for this complication (e.g. those who experience a variceal hemorrhage). Oral norfloxacin (400 mg BD day), Oral ciprofloxacin 250 – 500 mg once daily or Oral levofloxacin 250 mg once daily (q.d.) or IV ceftriaxone (1 g/day), which may be preferable, for 7 days reduces the risk of bacterial peritonitis in patients hospitalized for acute variceal bleeding
  • Secondary prevention (prevention of SBP in patients who do develop a previous infection): After SBP, there is a high probability of a further episode; therefore, all patients recovering from an initial episode of SBP should be treated with oral prophylactic antibiotics indefinitely. Examples of antibiotic used for secondary prevention are:
    • Norfloxacin (400 mg PO daily)
    • Ttrimethoprim-sulfamethoxazole single dose of 2 tablet (160/800 mg/day) given for 5 days/week
    • Ciprofloxacin 750 mg once weekly
• The patients should be considered for liver transplantation because 2-year survival is 25%– 30% after recovery
• Probiotic therapy in conjunction with antimicrobial treatment does not improve efficacy in the treatment of spontaneous bacterial peritonitis (SBP)

Coagulation

• Most clotting factors are synthesized in the liver, and the levels of these factors can be significantly reduced in chronic liver disease
• Abnormalities in coagulation include
  • Reduction in the synthesis of coagulation factors
  • Excessive fibrinolysis
  • Disseminated intravascular coagulation
  • Thrombocytopenia and platelet dysfunction
• Vitamin K–dependent clotting factor levels are decreased, with factor VII affected first because it has a short half-life
• The net effect of these events is the development of bleeding tendency

Management of Coagulation Disorders

• Treatment is vitamin K (phytomenadione), 10 mg given IV for 3 days
• The patient's INR and prothrombin time are monitored
• Patients with cirrhosis who are actively bleeding receive resuscitation with packed red blood cells targeting a hemoglobin of 7 to 9 g/dL
• Platelet transfusion is used to maintain platelets over 50,000/mm3 during the period of active bleeding
• Cryoprecipitate to maintain fibrinogen levels over 100 mg/dL is also usually recommended
• Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) and anticoagulants should be avoided in all patients with liver disease because of the risk of altering platelet function, causing gastric ulceration and bleeding
• Most hepatologists permit the use of paracetamol in patients with cirrhosis at doses of up to 2000 mg daily

Hepatorenal Syndrome (HRS)

• It is characterized by an intense renal vasoconstriction, which leads to a very low renal perfusion and glomerular filtration rate, as well as a severe reduction in the ability to excrete sodium and free water
• HRS is a form of renal failure, but without renal pathology
• This renal failure occurs in about 10% of patients with advanced cirrhosis or acute liver failure

Types of Hepatorenal Syndrome (HRS)

• Type 1 HRS is acute and progressive kidney failure and characterized by progressive oliguria, a rapid rise of the serum creatinine (>2.5 mg/dL in less than 2 weeks) and a very poor prognosis

Test your knowledge on the management of liver diseases, including large volume paracentesis, liver transplantation, and the use of clonidine in treating refractory ascites. This quiz covers important complications and treatment options for conditions like portal hypertension and esophageal varices.