Cirrhosis part 2 Flashcards
How is portal hypertension defined?
Clinical syndrome characterized by a pathological increase in the portal pressure gradient (hepatic venous pressure gradient).
What does an HVPG > 5 mmHg indicate?
Increased portal pressure
What does an HVPG > 10 mmHg indicate?
Clinically significant portal hypertension (varices, bleeding, ascites, SBP - spontaneous bacterial peritonitis).
How is portal hypertension defined in terms of hepatic venous pressure gradient (HVPG)?
The elevation of the hepatic venous pressure gradient (HVPG) to >5mmHg
What are the two main factors contributing to portal hypertension?
Increased intrahepatic resistance of blood flow through the cirrhotic liver.
Increased splanchnic blood flow secondary to vasodilation.
What are the two major complications of portal hypertension?
Variceal hemorrhage (20–30% mortality rate associated with each episode of bleeding).
Ascites.
How are the causes of portal hypertension typically categorized?
Prehepatic, intrahepatic, and posthepatic.
What are the major clinical features of portal hypertension?
Gastroesophageal varices with hemorrhage
Ascites (± edema)
Enlarged spleen with associated reduction in platelets and white blood cells (Hypersplenism)
What proportion of patients with cirrhosis have varices?
One-third of patients with cirrhosis have varices.
What proportion of patients with varices will develop bleeding?
One-third of patients with varices will develop bleeding
What factors increase the risk of variceal bleeding?
Child’s class
MELD score
HVPG > 12 mmHg (N=5mmHg)
Endoscopic stigmata: hematocystic spots, diffuse erythema, cherry red spots
The size of the varix
The location of the varix
Patients with tense ascites
How are varices identified?
endoscopy
What can abdominal imaging (CT or MRI) demonstrate in the context of varices?
Abdominal imaging (CT or MRI) can demonstrate a nodular liver and changes of portal hypertension with intraabdominal collateral circulation.
How might patients with acute variceal bleeding present?
Hematemesis
Melena
Hematochezia
What are the goals of resuscitation in acute variceal hemorrhage?
To replace blood volume lost to a goal of a hematocrit of 25%
Transfusing platelets (to increase levels >50.000)
Transfusing fresh frozen plasma (to reverse coagulopathy)
Intubation in active bleeding to protect the airways from aspiration
What antibiotic prophylaxis is used to reduce the risk of developing infection, including SBP?
Ceftriaxone 1g/day, 5-7 days i.v.
Norfloxacin 400mg twice daily /7 days
What vasoactive agents are used to control bleeding in acute variceal hemorrhage?
Vasopressin plus nitroglycerin (serious side effects)
Terlipressin (vasopressin analog): 0.5-2mg i.v., every 4-6h
Somatostatin or its analogs (Octreotide) - it is safe with very few side effects), bolus 50 μg followed by 50 μg/hour, for up to 5 days
What is the use of balloon tamponade in acute variceal hemorrhage?
Immediate control of hemorrhage
What endoscopic therapies are used in acute variceal hemorrhage?
Esophageal variceal ligation: placement of the rubber bands on variceal columns
Sclerotherapy: injection a sclerosing agent (ethanolamine oleat, sodium morrhuate) into or adjacent to a varix
What is balloon tamponade used as a bridge to?
A bridge to TIPS or liver transplantation
What are the complications of balloon tamponade?
Aspiration
Esophageal necrosis
not more than 24h inflated
What is a Transjugular intrahepatic portosystemic shunt (TIPS)?
A technique that creates a portosystemic shunt using an expandable metal stent, which is advanced to the hepatic veins and then through the substance of the liver to create a direct portocaval shunt.
What is a potential complication of TIPS?
20% of patients may present encephalopathy
When is TIPS typically used?
TIPS should be reserved for those individuals who failed endoscopic or medical management as a bridge to transplantation
What does primary prophylaxis of esophageal varices require?
Screening by endoscopy of all patients with cirrhosis.
To identify varices at increased risk for bleeding.
What medications are used for primary prophylaxis of esophageal varices?
Nonselective β blockade (Propranolol 20mgx2/day heart rate 50-55/min, Nadolol, Carvedilol 12.5 mg/day) - reduce risk of variceal hemorrhage.
What endoscopic procedure is used for primary prophylaxis of esophageal varices?
Endoscopic variceal ligation (EVL).
What is required for secondary prophylaxis of esophageal varices?
The patients who had a variceal bleed require the prevention of further bleeding.
What treatments are used for secondary prophylaxis of esophageal varices?
Nonselective β blockers + repeated variceal band ligation until varices are obliterated.
What are the clinical features of ascites?
Increase in abdominal girth (+edema)
Shortness of breath (hepatic hydrothorax)
Malnutrition with muscle wasting
What are the physical examination findings in ascites?
Bulging flanks
The presence of shifting dullness
A fluid wave sign
What imaging modalities can detect subtle amounts of ascites?
Ultrasound or CT scanning
What is hepatic hydrothorax?
Free flow of ascitic fluid into the thoracic cavity through the diaphragm
Which side is hepatic hydrothorax more common on?
More common on the right side
What tests are performed on ascitic fluid obtained through diagnostic paracentesis?
Determination of total protein and albumin content
Cytology (blood cell counts)
Cultures
Amylase
What is the typical protein concentration in ascites due to cirrhosis?
low
What does a SAAG <1.1 g/dL suggest?
Ascites due to inflammation, infection (tuberculosis peritonitis), malignancy
How is ascitic fluid infection confirmed?
(inoculation of culture media)
What dietary restriction is important in the treatment of ascites?
Sodium restriction from diet (to eat fresh or frozen foods, avoiding preserved foods) 90 mmol/day
hat is the first-line diuretic therapy for ascites?
Spironolactone at 100–200…..400mg add
Furosemide at 40–80 mg/d (a loop d) ……. 160mg/day
If ascitic fluid is not being mobilized, what adjustments can be made to medication?
Spironolactone can be increased to 400 mg/d and furosemide increased to 160 mg/d + Albumin 40mg/day
What defines refractory ascites?
If ascites is still present with these dosages of diuretics in patients who are compliant with a low-sodium diet, then they are defined as having refractory ascites.
What treatment options are available for refractory ascites?
Repeated large-volume paracentesis (+albumin 8g/l)
TIPS, peritoneovenous shunt, automated flow pumps to move ascitic fluid to the bladder
Liver transplantation
What monitoring is essential during ascites treatment?
The fluid intake, output and urine sodium should be monitored
Complications of diuretic treatment
● Hypotension, Renal failure (massive diuresis)
● Hyponatremia
● Hypokaliemia
● Metabolic acidosis
● Muscle cramps
● Precipitation of portal systemic encephalopathy
What is the definition of spontaneous bacterial peritonitis (SBP)?
Spontaneous infection of the ascitic fluid without an intraabdominal source.
What is the pathogenesis of SBP?
Bacterial translocation: gut flora cross the intestine into mesenteric lymph nodes leading to bacteremia and seeding of the ascitic fluid.
What are the common causative organisms of SBP (etiology)?
Gram-negative bacteria: Escherichia coli
Gram-positive bacteria: Streptococcus viridans, Staphylococcus aureus, Enterococcus
What are the clinical features of SBP?
No symptoms or fever
Altered mental status
Abdominal pain or discomfort
What does the laboratory profile show in SBP?
Elevated white blood cell count
What are the diagnostic criteria for SBP on paracentesis?
Neutrophil count in ascitic fluid sample: >250 cells/μL
Bedside cultures should be obtained
What is the treatment for SBP?
Third-generation cephalosporin, Cefotaxime 1gx2 or Ceftazidime: 2g at 8h i.v. - 5 days At 72h, PMN↓ >25%
Albumin i.v., 1.5g/Kg at the time of diagnosis and then 1.0g/Kg at day 3, reduces renal impairment
How are multidrug-resistant organisms in SBP treated?
Broader spectrum antibiotics (e.g., vancomycin-tazobactam, imipenem, ertapenem)
What medications are used for long-term prophylaxis of SBP?
Norfloxacin (400mg/day) or Trimethoprim-Sulfamethoxazole
To prevent the recurrence
What should be considered if more than two organisms are identified in SBP?
Secondary bacterial peritonitis due to a perforated viscus.
What are the common precipitating factors for hepatorenal syndrome?
Gastrointestinal bleeding
Sepsis
Spontaneous peritonitis
Rapid diuresis, especially with marked ascites, no peripheral edema
What conditions should be considered in the differential diagnosis of hepatorenal syndrome?
Hypovolemia-induced renal failure: gastrointestinal bleeding, fluid losses from diarrhea, renal losses from excessive diuretic therapy
Parenchymal renal disease: glomerulonephritis, vasculitis
Drug-induced renal failure: NSAIDs, aminoglycosides, acetylsalicylic acid, intravenous contrast agents
What preventive measures can be taken to reduce the risk of hepatorenal syndrome?
Prophylactic treatment of precipitated factors: i.v. albumin (1.5g/kg on the first day and another dose (1g/kg) after 48 hours) in SBP and sepsis, antibiotic treatment
What vasoconstrictors are used in the treatment of hepatorenal syndrome?
Midodrine (α-agonist) + octreotide + i.v. albumin
Terlipressin + i.v. albumin (HRS type 1)
What is the definitive treatment for hepatorenal syndrome?
Liver transplantation
What is the prognosis for patients with type 1 or type 2 hepatorenal syndrome (HRS)?
In patients with type 1 or type 2 HRS, the prognosis is poor unless a transplant can be achieved within a short period of time.
What is the definition of hepatic encephalopathy (HE)?
An alteration in mental status and cognitive function occurring in the presence of liver failure often associated with portal systemic shunt.
In what conditions does HE or portal systemic encephalopathy (PSE) occur?
HE or portal systemic encephalopathy (PSE) occurs in acute liver injury with fulminant hepatic failure or more commonly in severe chronic liver diseases.
What are the two main patterns of hepatic encephalopathy?
HE can be episodic or chronic persistent.
What are the episodic forms of hepatic encephalopathy?
Spontaneous
Precipitated
Recurrent
What is minimal or subclinical encephalopathy?
No obvious abnormalities in cognition or behavior but with abnormal psychometric tests.
What is the underlying mechanism of hepatic encephalopathy (HE)?
Accumulation of nitrogen products derived from the gut have adverse effects on brain function.
How do gut-derived neurotoxins reach the brain in HE?
Gut-derived neurotoxins, not removed by the liver (because of vascular shunting and decreased hepatic mass), get to the brain and cause the neuropsychiatric symptoms.
What role does ammonia play in HE?
Ammonia is absorbed from the gut, converted to urea via the urea cycle in the liver; in HE, NH3 bypasses liver via porto-systemic shunting.
What are the effects of ammonia on the brain?
Blocks chloride channels
Modulates γ-aminobutyric acid (GABA)
Increases brain glutamine (astrocytes)
↓ ATP production, cerebral edema
What is the goal of treatment strategies for HE in relation to ammonia?
Treatment strategies have the purpose to decrease gut production of ammonia.
What other substances are implicated in the pathogenesis of HE?
False neurotransmitters
Mercaptans
Manganese
Deposits in basal ganglia and induces extrapyramidal symptoms
Short-chain fatty acids
Aromatic-amino acids
Naturally occurring benzodiazepines
What are the additional contributors to the pathogenesis of hepatic encephalopathy (HE)?
Altered levels of other neurotransmitters
Increased permeability of the blood-brain barrier
Increased inflammatory cytokines
Alterations in the gut microbiome
What are the main domains affected by hepatic encephalopathy?
Level of consciousness
Level of alertness
Intellectual function
Neuromuscular abnormalities
Personality and behavior
What are common behavioral changes in patients with hepatic encephalopathy due to cirrhosis?
Patients may be confused or exhibit a change in personality.
May be very sleepy and difficult to awaken.
May be quite violent and difficult to manage.
What is asterixis, and how is it elicited?
Asterixis (patients extend their arms and bend their wrists back).
What is a “liver flap”?
Patients who are encephalopathic have a “liver flap”-i.e., a sudden forward movement of the wrist.
What are the key components of a diagnosis approach for hepatic encephalopathy (HE)?
Documented chronic parenchymal liver disease
Evidence of portal-systemic shunts
Mental status changes
Clinical diagnosis (there is no confirmatory diagnostic test)
What is the first step in treating HE?
To identify and to treat any precipitating factors (hydration and correction of electrolyte imbalance).
What is impaired in subclinical or minimal encephalopathy?
Ability to drive a car is impaired.
What dietary modifications are recommended for HE?
Diet: protein restriction (40-60g) no under <0.75g/kg.
Replace animal-based protein with vegetable-based protein: increases elimination of nitrogen products in stool.
What is the goal of lactulose therapy?
The goal of lactulose therapy is to promote 2–3 soft stools per day.
How does lactulose work in the treatment of HE?
Lactulose, a nonabsorbable disaccharide, is broken down by fecal flora in the colon to short fatty acids; results in decreased fecal pH that traps ammonia by acidifying it to ammonium chloride.
pH acid inhibits ammonia production by urea-splitting microorganisms.
How do evacuation enemas contribute to HE treatment?
Evacuation enemas contribute to the elimination of nitrogen products in the gut.
How is lactulose typically administered?
Oral liquid, 30 - 45ml, 2-4xday, titrated to 2-4 stools (can be given by NG tube if the patient is unable to safely swallow or via enema if intolerant to the oral route)
What are the other contributions of lactulose in HE treatment?
Decreased GI transit time and decreased time for ammonia absorption
Increased uptake of ammonia by gut flora
Displacement of urease-producing ammonia species (which break down urea into ammonia) by non-urease producing species
What poorly absorbed antibiotics can be used in HE treatment, and how do they work?
Effect on gut flora and ammonia production:
Rifaximin at 550 mg twice daily (1200mg/day)
Neomycin (use with caution due to renal insufficiency and ototoxicity)
Metronidazole (use with caution due to peripheral neuropathy)
Is zinc supplementation beneficial in HE?
Zinc supplementation is sometimes helpful and it is relatively harmless.
Is L-ornithine L-aspartate (LOLA) helpful in HE?
sometimes
What is the effectiveness of combined lactulose-rifaximin therapy?
Combined lactulose-rifaximin therapy is effective in treating and preventing episodes of HE.
What is the prognostic significance of developing HE in chronic liver disease?
The development of HE in patients with chronic liver disease is a poor prognostic sign, but this complication can be managed in the vast majority of patients.
What is the triad that defines hepatopulmonary syndrome?
Liver disease
↑ alveolar-arterial gradient (O2)
Intrapulmonary vascular dilatations and shunts
What are the clinical findings in hepatopulmonary syndrome?
Dyspnea
Platypnea (dyspnea relieved by lying
down)
Finger clubbing
Cyanosis (intrapulmonary right-to-left shunting)
Orthodeoxia (the arterial oxygenation falls on changing from the supine position to standing up)
What investigations are used to diagnose hepatopulmonary syndrome?
99Tc MAA (albumin aggregate) scanning and contrast-enhanced echocardiography - the presence of intrapulmonary microvascular shunting
What is the treatment for hepatopulmonary syndrome?
Liver transplantation
What is the strongest risk factor for hepatocellular carcinoma (HCC)?
Cirrhosis
75-85% association of HCC with cirrhosis
What conditions increase the risk for cirrhosis-associated HCC?
Several conditions are associated with an increased risk for cirrhosis-associated HCC (viral hepatitis, alcohol, autoimmune chronic active hepatitis, cryptogenic cirrhosis, and NASH).
How does chronic hepatitis B carrier status affect the incidence of HCC?
Chronic hepatitis B carrier status ↑ incidence of HCC.
What is unique about HBV-associated HCC?
HBV-associated HCC, only half of the patients have cirrhosis; the remainder having chronic active hepatitis.
What is a characteristic of HCV-associated HCC patients?
HCV-associated HCC patients tend to have more frequent and advanced cirrhosis.
What chemical carcinogen is a risk factor for HCC?
A product of the Aspergillus fungus, aflatoxin B1.
It contaminates stored grains in hot, humid places, peanuts, and rice (stored in unrefrigerated conditions).
Aflatoxin inhibits the p53 suppressor tumoral gene.
Higher incidence rates are observed in Africa and China.
What other chemical carcinogens are possible risk factors for HCC?
Possible carcinogenic drugs (contraceptive hormones).
What are the common clinical features of HCC?
Abdominal pain
Weight loss
Weakness
Jaundice
Nausea
Abdominal swelling, a consequence of ascites (due to the chronic liver disease or be due to an expanding tumor)
What serious complications can lead to death in HCC?
Central necrosis or acute hemorrhage into the peritoneal cavity leads to death.
What causes jaundice in HCC?
(due to obstruction of the intrahepatic ducts).
What are the physical signs of HCC related to the liver itself?
Hepatomegaly, hepatic nodularity, liver bruits in 6–25%, ascites
What is a common systemic symptom in HCC?
fever
What are the physical signs of chronic liver disease that may be present in HCC?
Jaundice, dilated abdominal veins, palmar erythema, gynecomastia, testicular atrophy, and peripheral edema
What is Budd-Chiari syndrome, and how is it related to HCC?
Budd-Chiari syndrome (due to HCC invasion of the hepatic veins); tense ascites and a large tender liver
What are some examples of paraneoplastic syndromes associated with HCC?
Hypoglycemia
Erythrocytosis
Hypercalcemia
Hypercholesterolemia
Dysfibrinogenemia
Carcinoid syndrome
Increased thyroxine-binding globulin
Gynecomastia, testicular atrophy
Porphyria cutanea tarda
What is α-fetoprotein (AFP), and what is its role as a serum tumor marker for HCC?
α-fetoprotein (AFP) is a serum tumor marker for HCC.
It is only increased in approximately one-half of patients.
What is des-carboxy prothrombin (DCP), and how is it related to HCC?
Des-carboxy prothrombin (DCP) is a protein induced by vitamin K absence.
It is increased in 80% of HCC patients.
What newer types of biomarkers are being used in HCC diagnosis?
Newer biomarkers: tissue- and serum-based genomics profiling.
What standard laboratory tests should be performed in the workup for HCC?
Standard liver function tests should be performed.
What serology should be measured in the workup for HCC?
Hepatitis A, B, and C serology should be measured.
What two vascular abnormalities are characteristic of HCC and can be detected by imaging?
hypervascularity of the tumor mass (neovascularization) and thrombosis by tumor invasion of portal veins.
What is the role of a helical/triphasic CT scan of the abdomen in HCC diagnosis?
To detect the vascular lesions typical of HCC, tumor size and extent.
What information does MRI provide in HCC diagnosis?
MRI provides detailed information, especially with the newer contrast agents.
What is Ethiodol (Lipiodol) used for in HCC diagnosis?
Ethiodol (Lipiodol), delivered by hepatic artery injection (5–15 ml) is retained by liver tumors and can be detected by CT imaging, 1 week later.
When is surgical resection an option for HCC?
Without cirrhosis or cirrhosis Child A
Solitary nodule <5cm, no vascular invasion, no lymph nodes involved
What is percutaneous ablation, and when is it used?
Using ethanol or radiofrequency
A bridge to transplant or for poor surgical candidates
What are the criteria for liver transplantation in HCC?
Solitary nodule >5 cm in size or three nodules each < 3cm, no evidence of metastasis
Need a priority system, not only MELD score
What is transarterial embolization, and what are the criteria for its use?
Non-curative option
Without evidence of vascular or metastatic disease
No portosystemic shunt
Chemotherapeutic agents (doxorubicin and cisplatin) are administered directly into the arterial branches supplying the tumor (chemoembolization)
What medications are used in chemotherapy for HCC?
Sorafenib, bevacizumab - effective palliative option
Who is at risk for HCC and should be screened?
For patients at risk for HCC (hepatitis B carriers and hepatitis B cirrhosis and cirrhosis of any etiology)
How is screening and surveillance for HCC performed?
Use ultrasound and α-fetoprotein every 6-12 months
