The majority of patients with cirrhosis will have ascites at presentation. Ascites can be detected on physical examination using various techniques. In patients with known cirrhosis and a largely distended or tense abdomen, the presence of ascites may be obvious, but in other patients percussion of the abdomen for flank dullness or shifting dullness and the presence of a fluid wave can confirm the diagnosis. However, physical exam is not a sensitive way to determine the presence or absence of a mild or moderate amount of ascites. Ultrasound provides a readily available, quick, and inexpensive way to determine the amount and location of ascites and to facilitate paracentesis. Computed tomography also shows the presence and extent of ascites, but is more cumbersome than ultrasound.
Examination of ascitic fluid is crucially important in the cirrhotic with new-onset ascites, clinical deterioration, change in mental status, or fever. This procedure can be performed using a commercial kit or by using a 14- to 18-gauge IV catheter. The peritoneal cavity can be entered in the midline (infraumbilical) or in the lower quadrants, taking care to avoid the inferior epigastric vessels and any grossly dilated abdominal wall veins. Ascitic fluid obtained from a diagnostic paracentesis should be sent for cell count, culture, and total protein concentration. Inoculating blood culture bottles at the bedside prior to sending them to the laboratory increases clinical yield.9 Other tests that may be helpful in selected situations are highlighted in Table 84-2. Large-volume ascites and the presence of a tense abdomen are indications for large-volume paracentesis, especially when the patient's respiratory status is compromised due to the restrictive effect on the diaphragm.
Table 84–2. Diagnostic Paracentesis ||Download (.pdf)
Table 84–2. Diagnostic Paracentesis
|Always Send||Sometimes Send||Rarely Send||Unhelpful|
|Cell count||Lactate dehydrogenase||Cytology||pH|
|Total protein||Gram stain||Tuberculosis smear/culture||Tumor markers|
|Albumin (on first paracentesis)||Glucose||Adenosine deaminase||Cholesterol|
Spontaneous Bacterial Peritonitis
One of the primary reasons to perform diagnostic paracentesis in the ICU is to detect the presence of infection, most importantly spontaneous bacterial peritonitis (SBP). SBP should be suspected in a cirrhotic with fever, abdominal pain, encephalopathy, or acute hemodynamic decompensation. Previous studies have shown that regardless of the reason a patient with cirrhosis requires admission to the hospital, a diagnostic paracentesis will reveal evidence of SBP in 7% to 17%, so any patient with ascites who is transferred to the ICU should be monitored carefully for SBP.10 Definitive diagnosis of SBP is made by finding >250 polymorphonuclear leukocytes (PMNs)/mm3 on diagnostic paracentesis, as well as a culture positive for a single organism. If only one of the above criteria is met the condition is termed culture-negative neutrocytic ascites or bacterascites, respectively (Table 84-3), but this is generally treated the same as confirmed SBP. Culture of more than one bacterial species should prompt suspicion for secondary peritonitis or perforated viscus. The bacterial pathogens that cause SBP are typically Escherichia coli (43%), Streptococcus species (23%), or Klebsiella pneumoniae (11%). Anaerobic organisms, Enterococcus spp., and Pseudomonas spp. are rarely involved. Treatment of SBP requires parenteral antibiotics that cover these common pathogens. Those with evidence of SBP should be treated with an intravenous third-generation cephalosporin such as cefotaxime at a dose of 2 g IV every 8 hours.11 Treatment for 5 days appears equivalent to a longer regimen of 10 days.12 Evidence also suggests that patients at risk for SBP (i.e., ascitic protein <1 g/dL, gastrointestinal hemorrhage, and previous episode of SBP) should be given prophylaxis with an oral fluoroquinolone.13 Unfortunately, increasing frequency of quinolone-resistant SBP and gram-positive infection, especially in the ICU setting, may be related to such long-term prophylaxis.14 Once a particular organism is identified, antibiotic coverage can be narrowed. In patients who do not adequately respond or continue to worsen on empiric antibiotic coverage, the antibiotic regimen should be revised and alternative bases for treatment failure considered.
Table 84–3. Diagnosis of Peritonitis ||Download (.pdf)
Table 84–3. Diagnosis of Peritonitis
|Spontaneous Bacterial Peritonitis||Culture-Negative Neutrocytic Ascites||Bacterascites||Secondary Peritonitis|
|PMN count (cells/mm3)||>250||>250||<250||>250|
|Culture||Single organism||Negative||Single organism||Multiple organisms|
|Protein||Usually low||Usually low||Usually low||Usually >1g/dL|
|Treatment||Third-generation cephalosporin||Third-generation cephalosporin||Directed antibiotics||Empiric broad-spectrum antibiotics, surgical intervention|
Sodium restriction and diuretics are first-line treatments in the management of ascites. Patients should not receive more than 2 g sodium (88 mEq) per day. Optimal treatment usually involves the combination of spironolactone with a loop diuretic. It is our practice to maintain a ratio of 40 mg of oral furosemide to 100 mg of oral spironolactone. In patients with severe liver compromise, spironolactone should only be administered once daily, as the half-life is increased by hepatic insufficiency. These doses can be increased to 160 mg of furosemide and 400 mg of spironolactone daily if the patient has stable renal function. The dose of diuretics should be reduced if the patient develops increasing hyponatremia or worsening renal function.15
Diuretic-Resistant and Recurrent Ascites
Repeated large-volume paracentesis of up to 4 to 6 L/day can be performed safely in patients who are diuretic resistant or difficult to control. Postparacentesis circulatory dysfunction, characterized by decreased peripheral vascular resistance, increased plasma renin activity, hyponatremia, and azotemia has been described in patients receiving large-volume paracentesis without volume expansion.16,17 Paracentesis of 6 L or more should be supplemented by intravenous albumin at 6 to 8 g per liter removed. In patients undergoing paracentesis of less than 6 L, no fluid replacement may be needed or normal saline can be given.18 Transjugular intrahepatic portosystemic shunting (TIPSS) should be considered for patients who are unable to tolerate diuretics or are diuretic resistant.19
Complications of Paracentesis
Paracentesis is considered a relatively safe procedure, with the most common complication being persistent drainage from the abdominal wall. Significant bleeding complications even in patients with thrombocytopenia and coagulopathy are rare, so it is not necessary to routinely administer blood products to all patients.20 Abdominal wall hematoma and hemoperitoneum occur rarely and may require investigation in patients who develop severe hemodynamic instability after paracentesis.
Up to 30% of cirrhotic patients with ascites have hyponatremia. Elevated levels and increased half-life of vasopressin contribute to the inability to excrete free water. Even modest decreases in serum sodium may have an adverse effect on hepatic encephalopathy. In general, severe hyponatremia indicates a poor prognosis. The presence of this electrolyte abnormality becomes more important in the ICU when diuretics, fluids for nutrition, or vasopressin analogues are given for sepsis or variceal bleeding. Patients with moderate to severe hyponatremia should be placed on free water restriction with strict monitoring of input and output.21 Diuretics should be given judiciously and use of vasopressin analogues should be limited. Recent studies of an orally active vasopressin V2 receptor antagonist suggest that this therapy has promise in correcting hyponatremia and fluid overload in this patient population.22
Widespread use of potassium-sparing diuretics and predisposition to development of renal failure in severe liver disease can cause hyperkalemia. As in any other setting, severe hyperkalemia is a relative emergency and should be managed accordingly. Potassium-sparing diuretics should be discontinued with the knowledge that the half-life of drugs such as spironolactone is increased in the setting of liver disease. Sodium polystyrene compounds may be used cautiously with attention given to further sodium and water retention.23
Cirrhosis is frequently complicated by the presence of hepatic encephalopathy (HE) or portosystemic encephalopathy (PSE). HE can be characterized as a range of neurologic and psychiatric disorders caused by underlying severe liver disease in the absence of other known neurologic disease. In cirrhosis, HE is generally reversible if a precipitant can be determined.
Though HE is commonly recognized clinically, the lack of standardization to describe the syndrome has led to difficulty in determining the pathophysiology and performing valid clinical trials. HE in chronic liver disease likely results from the actions of circulating substances on the brain that are normally cleared by the working liver. Ammonia has long been implicated in the pathogenesis of encephalopathy, though serum levels tend to correlate poorly with grade of encephalopathy. Evidence currently suggests that the astrocyte is a key to the development of hepatic encephalopathy. Astrocytes treated in vitro with ammonia show morphologic changes similar to those seen in vivo in both humans and animals with chronic liver disease and HE. These changes also include alterations seen in Alzheimer's type II astrocytosis. Changes in astrocytes, which normally regulate the extracellular environment and excitability of neurons, result in changes in neurotransmission. Elevated serum ammonia levels decrease glutamate uptake by astrocytes and increase extracellular glutamate concentrations. These changes in glutamate metabolism may be responsible for the disordered neurotransmission seen in HE. Other studies have implicated increased tone at γ-aminobutyric acid (GABA) receptors due to endogenously-derived benzodiazepines in HE. The peripheral-type benzodiazepine (PBR) receptor, located on the outer mitochondrial membrane of astrocytes, has been shown to be upregulated both in postmortem human brains from encephalopathic patients, and in vitro by astrocytes exposed to ammonia. The PBR is intimately involved in regulating synthesis of neurosteroids, which are potent ligands of the GABA-A receptor. Finally, in vitro, astrocytes exposed to elevated manganese levels show similar changes in glutamate uptake to those exposed to ammonia. Interestingly, the increased signal seen on T1 magnetic resonance imaging of the basal ganglia in the majority of cirrhotic patients has been attributed to manganese, and suggests that it has a role in the pathogenesis of HE.24–27
Due to the lack of standardization in defining and clinically diagnosing HE, a working party was assembled in 1998 and recently published a consensus statement. Type A encephalopathy is defined as that associated with acute liver failure. Type B encephalopathy is that associated with portosystemic bypass in the absence of underlying hepatocellular disease. Type C encephalopathy is that associated with cirrhosis and portal hypertension or portosystemic shunts. Type C hepatic encephalopathy, the focus of this chapter, is further subdivided into minimal, episodic, and persistent. Episodic encephalopathy can further be divided into spontaneous (without a known precipitant), precipitated, and recurrent. Precipitants include drugs that alter mental status, GI bleeding, overdiuresis, azotemia, electrolyte abnormalities, or infection. Recurrent encephalopathy is defined as two or more episodes occurring within 1 year. Minimal encephalopathy is brain dysfunction in the absence of clinical symptoms. Stages of hepatic encephalopathy can range from derangements only detectable by psychometric testing to overt coma. Early findings may include depression, reversal of the sleep-wake cycle, or difficulty concentrating. As encephalopathy worsens, physical signs such as asterixis and “milk-maid's grip” become apparent. Still later, the patient may progress to increasing confusion, obtundation, and overt coma.28 In the intensive care unit, protection of the airway is most critical in patients entering the later stages of encephalopathy (stages 3 and 4). Patients who have lesser degrees of encephalopathy in the setting of cirrhosis should be treated and offending factors removed to prevent escalation of the problem (Table 84-4).
Table 84–4. Stages of Encephalopathy ||Download (.pdf)
Table 84–4. Stages of Encephalopathy
|Stage 0||No detectable changes in personality or behavior||Absent||None|
|Stage I||Depression, changes in sleep-wake cycle, behavioral changes, inattention, poor concentration||Usually absent||Usually none|
|Stage II||Mild somnolence or lethargy, inappropriate behavior||Grossly present||Diffuse slowing|
|Stage III||Increased somnolence, gross disorientation||Present or Absent||Abnormal|
The presence of worsening encephalopathy warrants a search for underlying precipitants (Table 84-5). If possible, psychoactive drugs such as narcotics and benzodiazepines should be discontinued immediately. Underlying occult and overt gastrointestinal bleeding and infection should also be ruled out and treated if present. Electrolyte abnormalities should be corrected. Once underlying precipitants have been sought and adequately managed, treatment of hepatic encephalopathy is aimed at reducing further absorption of toxins from the gut. Lactulose, a nonabsorbable disaccharide, can be administered orally every 1 to 2 hours until a bowel movement is produced. At this point, lactulose can be given at regular intervals to produce two to three soft bowel movements per day. Lactulose likely exerts its effects by reducing absorption of toxins from the gut, both by decreasing transit time through the gut, as well as by altering the luminal pH. The change in pH effectively converts intraluminal ammonia to a quaternary ion and hinders its absorption. Despite the widespread use of lactulose and other nonabsorbable disaccharides for HE, a recent review of 22 trials showed the benefit of these therapies to be mild or nil, and inferior to antibiotics.29 Therefore if lactulose fails to improve encephalopathy, antibiotics such as neomycin and metronidazole, which presumably alter the gut flora, should be given.30 More recently, a novel nonabsorbed antibiotic (rifaximin) has been studied in hepatic encephalopathy with encouraging results.31 Although available in the U.S., this product is not yet FDA-approved for treatment of HE. Based on the “endogenous benzodiazepine” hypothesis of hepatic encephalopathy, the use of flumazenil, a benzodiazepine antagonist, has been studied and may have some beneficial effects in severe HE. A randomized, placebo-controlled study of 527 cirrhotic patients with stage 3 and 4 encephalopathy revealed improvement of both neurologic and electroencephalographic scores after administration of flumazenil with lactulose. Use of flumazenil in unselected patients with hepatic encephalopathy has not been validated.32
Table 84–5. Precipitants of Encephalopathy ||Download (.pdf)
Table 84–5. Precipitants of Encephalopathy
|Infection (spontaneous bacterial peritonitis, pneumonia, bacteremia)|
|Increased protein intake|
Renal dysfunction occurs at a high rate in patients with advanced cirrhosis. In the setting of advanced liver disease, hepatorenal syndrome (HRS) is defined as the development of renal failure with normal renal histology in the absence of nephrotoxic drugs, sepsis, intrinsic renal disease, and hypovolemia. Hepatorenal syndrome usually occurs in the setting of advanced liver disease with ascites and is often a lethal complication. It occurs in up to 39% of patients with underlying cirrhosis and ascites within 5 years.33 Hepatorenal syndrome is divided into two types, based on severity of kidney dysfunction. Type I hepatorenal syndrome is rapidly progressive, defined as doubling of the serum creatinine level to >2.5 mg/ dL or a 50% reduction in 24-hour creatinine clearance to a level <20 mL/min in less than 2 weeks. Type II HRS progresses slowly and renal function may remain stable for extended periods of time. Precipitants of hepatorenal syndrome may include excessive diuresis, use of prostaglandin inhibitors such as nonsteroidal anti-inflammatory drugs, and large-volume paracentesis or underlying critical illness such as sepsis, hypovolemia, or gastrointestinal bleeding. Severe electrolyte abnormalities (e.g., hyponatremia) and fluid overload are common once renal dysfunction is established, and these must be frequently sought and treated. Medications affected by renal dysfunction may require dose reduction.
The pathogenesis of hepatorenal syndrome appears to be due to severe renal vasoconstriction and decreased renal perfusion. In the peripheral vasodilation model of advanced liver disease, the kidneys perceive a persistent prerenal state and adapt accordingly through vasoconstriction. Activation of the renin-angiotensin system results in increased levels of angiotensin and aldosterone. Levels of antidiuretic hormone and norepinephrine also increase, causing severe renal vasoconstriction. As a consequence, sodium and water retention is exaggerated, exacerbating both ascites and peripheral edema. Early in cirrhosis, the kidneys adapt by overproducing renal prostaglandins, resulting in renal vasodilation and preservation of renal perfusion and function. The importance of prostaglandins in preserving renal function explains the cirrhotic patient's increased sensitivity to the effects of prostaglandin inhibitors such as nonsteroidal anti-inflammatory drugs. As liver disease progresses and splanchnic vasodilation predominates, the heightened effects of potent vasoconstrictors dominate the kidney and override the prostaglandin effect, leading to the hepatorenal syndrome.34
Hepatorenal syndrome is diagnosed in the setting of advanced liver disease by excluding other causes of renal failure. In the ICU, patients may have multiple reasons for renal failure. Other causes need to be systematically excluded prior to delivering a diagnosis of HRS. In diagnosing HRS, underlying intrinsic renal disease should be ruled out by examining urine sediment and imaging the kidneys with ultrasound. Nephrotoxicity due to drugs such as aminoglycosides, cyclosporine, and tacrolimus should also be considered. Hypovolemia can closely mimic HRS and deserves special mention here. Patients should be given a fluid challenge of 1.5 L normal saline with repeat measurement of serum creatinine. No change in the value supports the diagnosis of HRS. Acute tubular necrosis, commonly seen in the critical care setting, can be differentiated from HRS through measurement of the urine sodium. Urine sodium is usually <10 mEq/L in HRS and >20 mEq/L in acute tubular necrosis. In 1998, the International Ascites Club proposed consensus criteria for diagnosis of HRS. In addition to the presence of chronic or acute liver disease with advanced hepatic failure and portal hypertension, major criteria include: (1) serum creatinine >1.5 or creatinine clearance <40 mL/min, (2) absence of shock, bacterial infection, nephrotoxic drugs and fluid losses, (3) no improvement in serum creatinine following withdrawal of diuretics and 1.5 L fluid challenge with normal saline, and (4) proteinuria <500 mg/dL and normal renal ultrasound.35
While prevention of HRS largely depends on the natural history of the underlying liver disease, the setting of spontaneous bacterial peritonitis warrants special consideration. One third of patients with SBP will develop some degree of renal impairment.36 Recent evidence suggests that intravenous albumin administration during treatment of SBP can prevent development of renal impairment. In a study of 126 patients with cirrhosis and SBP, administration of intravenous albumin along with an antibiotic resulted in a decreased development of renal impairment and decreased mortality. Patients were randomized to receive cefotaxime or cefotaxime plus intravenous albumin (1.5 g/kg on day 1, followed by 1 g/kg on day 3). Rates for development of nonreversible renal impairment during hospitalization were 33% vs. 10% in the antibiotic and antibiotic plus albumin groups, respectively. At 3 months, the mortality rate for the combined treatment group was nearly half that of the antibiotic-alone group.37
Of the complications of cirrhosis, HRS has the worst prognosis. Expected median survival time is 2 weeks and 6 months for type I and II HRS, respectively. Liver transplantation is the only definitive means for reversal and cure of HRS. Unfortunately, in the critically ill, concomitant factors such as sepsis may render the patient unsuitable for transplant. Generally, patients in the ICU with HRS should have aggressive monitoring of fluid balance and weight, as well as evaluation and treatment of electrolyte abnormalities. Fluid overload and refractory ascites are common in patients with HRS. Patients with type I HRS should be managed with fluid restriction to avoid a positive fluid balance. Fluid overload in type II HRS can be managed with diuretics as long as a significant natriuresis is obtained. Potassium-sparing diuretics should be discontinued or used very cautiously in both groups to avoid hyperkalemia. Renal replacement therapy may be needed for patients with severe electrolyte disturbance, fluid overload, or acidosis. Vasoconstrictor therapy has been relatively well studied in the treatment of HRS. The theory behind treatment with vasoconstrictors suggests that administration results in constriction of the dilated splanchnic circulation, alleviating the intense vasoconstriction caused by endogenous vasoconstrictors released by the renal axis. Both vasopressin analogues and α-adrenergic agonists in combination with intravenous albumin have been studied in this setting. Terlipressin, a vasopressin analogue that acts at V1 receptors, when administered with albumin, resulted in improved renal function in 60% of patients, suppression of the renin-angiotensin and sympathetic systems, and a survival advantage in those who responded. Complete responders to terlipressin treatment have a low recurrence rate of HRS. While median survival time is only increased moderately, this may allow enough time for definitive treatment by liver transplantation.38,39 The use of midodrine, an orally administered α-adrenergic agonist, along with octreotide also improved renal function for a large majority of patients, while octreotide alone seems to have no effect.40,41 The use of TIPSS appears to improve renal function in patients with both type I and II HRS.42,43 In type I HRS, TIPSS should be considered in patients who fail to respond to vasoconstrictors. In type II HRS, TIPSS results in decreased progression to type I HRS, improved hemodynamics, and benefit for refractory ascites, but overall survival is unchanged compared to patients managed with repeated paracentesis and intravenous albumin.43,44
The relationship between severe liver disease and pulmonary abnormalities has long been recognized. Pulmonary disease secondary to hepatic injury can be divided into hepatopulmonary syndrome (HPS) and portopulmonary hypertension. Hepatopulmonary syndrome, characterized by an increased alveolar-arterial oxygen gradient (a-a)O2, varying degrees of hypoxemia, and pulmonary vasodilation in the setting of liver disease is more common than previously thought. Recent studies suggest that up to 47% of patients with cirrhosis have some degree of pulmonary vasodilation detectable by diagnostic studies.45 The pathogenesis of the HPS lies in vasodilation of the capillary and precapillary beds of the lung due to increased circulating vasodilators such as nitric oxide (NO) in severe liver disease. In some patients, hypoxemia is seen due to dilation of the pulmonary vasculature that results in right-to-left shunting. In others, ventilation-perfusion mismatch causes hypoxemia, and other theories have been proposed. Clinical manifestations of HPS include platypnea, orthodeoxia, and reduced diffusing capacity for carbon monoxide. Platypnea, defined as dyspnea in the upright position that is relieved by lying supine, and orthodeoxia, which is defined as arterial deoxygenation in the upright position that is relieved by recumbancy, are seen in a majority of patients with severe hypoxemia. In the ICU setting, the importance of HPS lies in the increased mortality of these patients. A recent prospective study of 111 patients with cirrhosis showed that the presence and severity of HPS were independent risk factors for death.46 HPS is diagnosed by demonstrating an increased age-adjusted (a-a)O2 along with intrapulmonary vascular dilation. Perfusion scanning using technetium 99m-labeled macroaggregated albumin and subsequent demonstration of uptake in the kidneys or brain suggests intracardiac or intrapulmonary shunt. More commonly and easily, the shunt may be demonstrated by contrast echocardiography using microbubbles. The presence of the microbubbles in the left side of the heart after four to six cardiac cycles demonstrates the intrapulmonary shunt.47 Despite significant ventilation-perfusion mismatch, some cirrhotic patients may not manifest hypoxemia due to increased cardiac output and hyperventilation. This may bear on the cirrhotic patient who becomes critically ill, because as oxygen consumption rises or cardiac output becomes limited, the gas-exchange defect may become manifest.
Medical therapies in general have proved ineffective for the treatment of HPS. Supplemental oxygen may only temporarily correct the underlying hypoxemia. For many years, hypoxemia has been a contraindication to liver transplantation. Recently, studies showing reversal of the findings of HPS in transplanted patients have resulted in rethinking of this doctrine.48 As a result, HPS is an indication for orthotopic liver transplantation. However, perioperative complications are frequent in these patients, and at times the resolution of hypoxemia is very protracted, even following successful transplantation. Since the institution of the model for end-stage liver disease (MELD) score in 2002, the United Network for Organ Sharing now reviews cases of hepatopulmonary syndrome for possible assigning of additional points.
Portopulmonary hypertension is the presence of mean pulmonary pressure >25 mm Hg in the presence of portal hypertension and the absence of left heart failure. The condition is present in 5% to 10% of patients undergoing evaluation for liver transplant. Overall, mortality is greatly increased, with a median survival time of 6 months.49 Many medical therapies have been tried in the setting of portopulmonary hypertension, yet long-term studies and adequate guidelines are lacking. Intravenous prostacyclin, β-blockers, nitrates, and inhaled NO all show promise in treatment of this condition. Multiple reports show improvement of pulmonary artery pressure (PAP) after liver transplantation, but intraoperative and perioperative mortality is high for patients with a mean PAP >40.50–52
Judging expected survival and allocating available donor livers for liver transplantation has historically raised questions rooted in both medicine and ethics. The Child-Turcotte-Pugh (CTP) classification, based on degree of encephalopathy, amount of ascites, serum bilirubin, albumin, and prothrombin time, predicts both survival and surgical risk in cirrhotic patients. Until 2002, the CTP classification was intricately tied to allocation of donor livers. Unfortunately, the classification inherently had values that lacked objectivity in predicting survival. The MELD score was developed prospectively, using methodologically accurate methods and continuous variables, in contrast to the CTP score, and is currently used to stratify potential liver recipients.53
Model for End-Stage Liver Disease
The model for end-stage liver disease (MELD), a purely objective measurement adopted by the Organ Procurement and Transplantation Network (OPTN) in 2002, has been validated in many studies to predict survival.54 (Table 84-6). The MELD score is now used as one measure in allocation of donor livers and has been validated in patients on the transplantation waiting list. The MELD score predicts severity of liver disease based on serum creatinine, serum bilirubin, and International Normalized Ratio. The variable for etiology of liver disease has been omitted in the currently used classification. Three-month mortality with a MELD score <9 is 1.9%. Three-month mortality with a MELD score of ≥40 is 71%.55,56
Table 84–6. Calculating the Model for End-Stage Liver Disease (MELD) Score ||Download (.pdf)
Table 84–6. Calculating the Model for End-Stage Liver Disease (MELD) Score
|MELD score = ||[0.957 × Loge(creatinine mg/dL) |
|+ 0.378 × Loge(bilirubin mg/dL) |
|+ 1.120 × Loge(International Normalized Ratio) |
|+ 0.643] × 10|