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🌱 來自: Huppert’s Notes
Cirrhosis and its Complications🚧 施工中
Cirrhosis and its Complications
Decompensated cirrhosis
• Decompensated cirrhosis: Defined by any one of: ascites, hepatic encephalopathy, and/or variceal bleed
• Etiologies of new decompensated cirrhosis: Infection, insults to the liver (drugs, toxins, herbs, shellfish), GI bleeding, ischemia/clotting (e.g., Budd-Chiari)
• Clinical features: Cirrhosis can cause clinical manifestations that affect almost any organ system (see Figure 4.7)
FIGURE 4.7: Systemic clinical manifestations of liver cirrhosis. Cirrhosis can cause clinical manifestations that affect almost every organ system.
Portal hypertension
• Definition: Pressure gradient of >6 mmHg between the portal and hepatic veins
• Pathophysiology: 1) Increased resistance to portal flow at the level of the sinusoids due to disruption of blood flow by scarring/formation of parenchymal nodules; 2) Increased portal venous blood flow resulting from splanchnic circulation in response to nitric oxide release
• Etiologies: Intrahepatic (i.e., cirrhosis; much less commonly schistosomiasis, massive fatty change, diffuse fibrosing granulomatous disease such as sarcoidosis, amyloidosis, or infiltrative malignancy, and diseases of the microcirculation such as nodular regenerative hyperplasia); can also occur due to prehepatic (e.g., portal vein thrombosis) and posthepatic (e.g., Budd-Chiari, severe right-sided heart failure, constrictive pericarditis) causes
Ascites
• Description: Accumulation of excessive fluid in the peritoneal cavity. See differential diagnosis for ascites in Table 4.10. Cirrhosis is the most common cause of ascites (85%).
• Pathophysiology: 1) Portal hypertension (high hydrostatic pressure); 2) Hypoalbuminemia (low oncotic pressure); in addition, splanchnic dilatation results in lower systemic blood pressure, activating the RAAS system and resulting in additional fluid and sodium retention
• Diagnosis: Perform a paracentesis; the ascites fluid characteristics can inform the differential diagnosis for the cause of ascites fluid accumulation (See Table 4.10)
TABLE 4.10 • Differential Diagnosis for the Cause of Ascites Based on Ascites Fluid Characteristics
• Treatment: 1) Salt restrict <2 g/day, 2) Furosemide + spironolactone, 3) Paracentesis
Spontaneous bacterial peritonitis (SBP)
• Spontaneous vs. secondary bacterial peritonitis:
- Spontaneous bacterial peritonitis (SBP): Infection of ascites, without an evident surgically treatable intraabdominal source, which almost always occurs in patients with cirrhosis and ascites
- Secondary bacterial peritonitis: Infection of ascites in the presence of a surgically treatable intraabdominal source, due to peritonitis with or without perforation. It is crucial to distinguish these conditions, because secondary bacterial peritonitis requires intraabdominal surgery, whereas surgery can be harmful for patients with SBP.
• Pathogenesis: Translocation of bacteria from the gut lumen across the intestinal wall
• Microbiology: E. coli, Klebsiella, S. pneumoniae
• Clinical features: Ascites due to cirrhosis with fever, abdominal pain/tenderness, and/or altered mental status; however, >10% of patients have no symptoms, and thus clinical suspicion should be high and ascitic fluid should be sampled for essentially all admitted patients with cirrhotic ascites
• Diagnosis: 1) Ascitic fluid with PMNs >250 cells/mm3, 2) Positive ascitic fluid bacterial culture, 3) Absence of a cause of secondary bacterial peritonitis (Gram stain with a large number of bacteria can be suggestive of secondary bacterial peritonitis; if suspicion is high for secondary bacterial peritonitis but imaging does not reveal a source, then perform repeat paracentesis at 48 hours)
• Treatment: Ceftriaxone or cefotaxime
• Prophylaxis: Antibiotic prophylaxis with ciprofloxacin or trimethoprim-sulfamethoxazole is indicated for patients with a prior episode of SBP, prior variceal hemorrhage, or ascitic fluid protein concentration <1 g/dL
Hepatohydrothorax
• Description: Presence of pleural effusion on CXR in the presence of ascites and in the absence of another reason to have a pleural effusion (e.g., cardiac, pulmonary, or pleural disease)
• Pathophysiology: Due to leakage of ascitic fluid through diaphragmatic defects; R-sided defects are more common since the L-sided diaphragm is thicker and more muscular
• Clinical features: Dyspnea, cough, pleurisy, hypoxemia. Hepatohydrothorax are 80% R-sided, 15% L-sided, 5% bilateral
• Diagnosis: CXR; thoracentesis with pleural fluid sampling demonstrates transudative fluid similar to ascitic fluid with a low protein concentration (<2.5 g/dL), SAAG >1.1 g/dL
• Treatment: 1) Medical management identical to ascites (i.e., sodium restriction, diuresis), 2) If refractory to medical management, consider other therapies such as recurrent thoracenteses or TIPS
Portosystemic shunts (collaterals and varices)
• Pathophysiology: Portal hypertension results in reversal of blood flow from the portal to systemic circulation, causing dilation of collateral vessels and development of new vessels
• Locations: Esophagus/stomach (esophageal varices, gastric varices, portal hypertensive gastropathy), rectum (hemorrhoids), periumbilical/abdominal wall collaterals (caput medusae: dilated subcutaneous veins extending from the umbilicus laterally)
• Management of esophageal varices:
- Prescribe beta blockers for the prevention of variceal bleeding
- Perform surveillance EGD for varices at an appropriate interval (See Table 4.11)
TABLE 4.11 • EGD Surveillance for Patients with Cirrhosis
- Modify routine management of GIB if concerned for variceal bleeding: Two large-bore IVs, PPI, type and screen plus ceftriaxone 1 g IV daily and octreotide 50 mcg IV bolus plus 50 mcg/hr infusion
- Consider TIPS for uncontrolled bleeding if low MELDNa score and no pulmonary hypertension
Splenomegaly
• Description: Enlargement of the spleen to as large as 1000 gm
• Pathophysiology: Long-standing congestion of the spleen due to portal hypertension
• Complications: Thrombocytopenia (due to sequestration; low TPO production also contributes); less commonly can cause pancytopenia
Hepatic encephalopathy (HE)
• Description: Not a single clinical entity; spectrum of disturbances in consciousness/mental status, ranging from subtle sleep-wake and behavioral changes to deep coma/death, likely due to combination of reversible metabolic encephalopathy, brain atrophy, and brain edema.
• Pathophysiology: Ammonia is the most well-documented contributing neurotoxin. It is thought to alter neuronal electrical activity and increase intracellular osmolarity, which contributes to increased cerebral edema
• Clinical features: Confusion, asterixis (flap), hyperreflexia, fetor hepaticus (musty breath)
• Grading (West-Haven): 1) Sleep-wake disturbance, 2) Dissociation, asterixis, 3) Marked confusion, 4) Coma
• Triggers for worsening HE: Infection, GIB, portal vein thrombosis, medications (e.g., benzodiazepines, opioids), inappropriate lactulose dosing
• Treatment: 1) Lactulose prevents ammonia absorption; 2) Rifaximin kills ammonia-producing gut flora; 3) Zinc deficiency is common so zinc supplementation is sometimes administered, but benefit for HE is understudied.
Hepatopulmonary syndrome
• Etiology: Hypoxemia and intrapulmonary vascular dilatation in the presence of liver disease; occurs in up to 30% of patients with decompensated cirrhosis
• Pathophysiology: Intrapulmonary vascular dilatations allow rapid blood flow through the capillary bed and do not provide enough time for oxygen diffusion, resulting in shunt physiology (Q>>V). Since blood flow is dependent (i.e., shifts with gravity) in the lungs, flow in the lung bases increases when sitting upright (Q). Therefore, for patients with hepatopulmonary syndrome, shunting and symptoms worsen when sitting in the upright position
• Clinical features: Dyspnea; easier to breathe while lying flat (platypnea) and worsening arterial oxygen saturation if upright (orthodeoxia)
• Diagnosis: PaO2 <80 mmHg on room air, echo with intrapulmonary shunting
• Treatment: Supplemental oxygen, liver transplantation
Portopulmonary hypertension
• Description: Pulmonary hypertension in the presence of portal hypertension; present in 5–9% of liver transplant candidates
• Pathophysiology: Poorly understood; seems to relate to pulmonary vasoconstriction/remodeling in presence of portal hypertension
• Clinical features: Symptoms are variable, most commonly dyspnea, clubbing, fatigue, chest pain, syncope
• Diagnosis: TTE may be suggestive; confirm with right heart catheterization
• Treatment: Patients may be candidates for pulmonary artery hypertension therapy based on functional class (e.g., prostacyclin analogues, endothelin antagonists, phosphodiesterase inhibitors); avoid TIPS due to the risk of worsening right heart failure
Hepatorenal syndrome (HRS)
• Description: Renal failure occurring in patients with liver failure who have no other morphologic or functional reasons for renal impairment
• Pathophysiology: Decreased renal perfusion pressure due to systemic (including splanchnic) vasodilatation and resultant hypoperfusion/RAAS activation
• Subtypes:
- Type 1: More severe; doubling of baseline Cr to >2.5 mg/dL in a period of <2 weeks
- Type 2: Less severe; usually associated with diuretic-refractory ascites
• Diagnosis:
- Hepatic disease with portal hypertension
- AKI (prior definitions required Cr >1.5 mg/dL; however, this is evolving)
- Absence of any other apparent cause of AKI (e.g., shock, nephrotoxic drugs, obstruction; obtain renal ultrasound to evaluate for obstruction, urinalysis to evaluate for proteinuria or RBC)
- No improvement in function after albumin challenge (i.e., cessation of diuretics plus IV albumin 1 g/kg/day for 2 days)
• Treatment: MOA (Midodrine, Octreotide, Albumin); if critically ill, use norepinephrine and albumin; consider TIPS or dialysis for bridge to transplant in patients who fail medical therapy
Other clinical features of cirrhosis
• Hypoestrogenism: 1) Spider angiomas, 2) Palmar erythema, 3) Gynecomastia, 4) Testicular atrophy, 5) Amenorrhea, 6) Low libido
• Decreased hepatic synthetic/biochemical function: Hypoalbuminemia, decreased clotting factors (leading to INR prolongation)
• Thrombocytopenia: Results from splenic sequestration, decreased TPO production; suggestive lab abnormality for the presence of portal hypertension
Healthcare maintenance in cirrhosis
• Hepatocellular carcinoma (HCC) screening: Patients with cirrhosis have an increased risk of HCC; screen with q6mo abdominal imaging (e.g., abdominal ultrasound or quad phase CT) and serum AFP
• Hepatic osteodystrophy: Osteoporosis, osteopenia. Check DEXA, calcium, and vitamin D.
• Immunizations: Hepatitis A, hepatitis B, influenza, 23-valent pneumococcal polysaccharide vaccine (PSSV23)
• Avoidances: Alcohol, oysters/raw shellfish (due to risk of Vibrio infection in setting of relative immunocompromise), opioids; minimize use of acetaminophen (up to 2 grams/day is classic limit, although evidence for this limit is lacking), NSAIDs, sedating medications (e.g., benzodiazepines)
• Nutrition: Muscle wasting is common; high-protein diet is critical
Scoring systems used for the assessment of prognosis in liver cirrhosis
• Model for End-Stage Liver Disease (MELD)-Sodium (Na) Score:
- Definition: A scoring system for assessing the severity of chronic liver disease that uses lab values including: serum bilirubin, creatinine, INR, and sodium to predict 3-month survival
- Clinical uses:
• Scores range from 6–40, with higher scores correlating with increased severity of liver dysfunction and higher 3-month mortality.
• In 2002, MELD-Na was accepted by the United Network of Organ Sharing (UNOS) for prioritization of patients awaiting liver transplantation in the United States.
• Child-Pugh:
- Definition: A scoring system to assess the prognosis of chronic liver disease, mainly cirrhosis. The score employs five clinical measures of liver disease: Total bilirubin, serum albumin, prothrombin time, ascites, and hepatic encephalopathy.
- Clinical uses:
• MELD-Na is more widely used, given its better prognostic value, but Child-Pugh is still referenced and utilized in some settings (e.g., HCC treatment guidelines in oncology).