Hepatobiliary Disease
7.1 Cirrhosis
Natasha Schneider
Michael A. Pilla
Patients with chronic liver disease are having surgery in greater numbers in part related to the improved long-term survival of patients with cirrhosis. There are particular perioperative concerns unique to this population that are taken into account when considering if a candidate is appropriate for surgery. Elective surgery may be contraindicated in some patients with significant impairments to hepatic function. Cirrhosis is defined as chronic hepatocyte damage leading to progressive fibrosis with distortion of the hepatic architecture and the formation of fibrotic nodules. Pathologic and genetic conditions that lead to the development of cirrhosis are numerous and include hepatitis, toxins, and inherited genetic disorders. A list of some of these major etiologies can be found in Table 7.1.
Despite the cause of cirrhosis, the basic metabolic and synthetic functions of the liver are progressively disrupted and worsen with time and severity of disease. This can lead to a multitude of derangements in homeostasis and organ function, affecting the gastrointestinal, pulmonary, cardiac, circulatory, renal, hematologic, neurologic, and immunologic systems to varying degrees. The liver’s role in bile production and excretion are affected, resulting in an increase of total bilirubin and jaundice. A decrease in the production of procoagulant factors and fibrinogen and an increase in platelet sequestration with hypersplenism lead to a decrease in coagulation, increasing the severity of bleeding during a surgical procedure. Significant ascites may reduce pulmonary compliance and impair ventilation and oxygenation during surgery.
It is important to clarify preoperatively the degree of liver dysfunction, which along with the type of surgery significantly impacts the overall risk. Careful assessment preoperatively may uncover undiscovered significant liver disease. A reported history of illicit drug use, previous blood transfusions, heavy alcohol use, jaundice, or a family history of hereditary liver disease prompts further investigation. In patients with a known history of cirrhosis, it is critical to determine by history and physical examination the presence of compensated or decompensated disease. Patients with a history of complications of liver disease such as variceal bleeding, ascites, spontaneous bacterial peritonitis, hepatocellular carcinoma, hepatorenal syndrome (HRS), or hepatopulmonary syndrome have decompensated cirrhosis and are at higher risk during surgical interventions than patients with compensated disease. Findings which may herald undiagnosed liver disease include temporal or peripheral muscle wasting, spider
angiomata, palmar erythema, a distended abdomen with ascites, a firm nodular liver, splenomegaly, scleral icterus, or jaundice.
angiomata, palmar erythema, a distended abdomen with ascites, a firm nodular liver, splenomegaly, scleral icterus, or jaundice.
TABLE 7.1 Etiologies of Cirrhosis | ||||||||||||
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Laboratory assessment of hepatic function and coagulation parameters are recommended if there is concern for unrecognized or known significant liver disease. A basic assessment for patients with cirrhosis includes a complete blood count, comprehensive metabolic panel, and INR which allows for model for end-stage liver disease (MELD) calculation. Abdominal imaging will evaluate for an enlarged portal vein, development of collaterals, intra-abdominal varices, splenomegaly, or ascites, all indicative of portal hypertension which increases risk, especially in abdominal surgeries.
There are various scores and calculators available for risk stratification of patients with advanced liver disease undergoing surgery. One of the oldest tools for risk assessment is the Child-Turcotte-Pugh (CTP) score which has been used since the 1960s for determining morbidity and mortality risk in cirrhotic patients. This scoring system was originally developed by Child and Turcotte to assess risk of patients undergoing portocaval shunt surgery (1). However, the nutritional assessment proposed in the original scoring system was substituted by the PT by Pugh for risk assessing treatment strategies for patients with esophageal variceal bleeding (2). The currently used CTP score is calculated using the variables in Table 7.5. Two similar studies have looked at the risk of abdominal surgeries in patients with CTP classes A, B, and C and found that risk correlated with severity of disease. Mortality was 10%, 30%, and 76% to 82% for CTP classes A, B, and C, respectively (3,4). However, CTP class alone does not tell the entire story, as patients with CTP class A and the presence of portal hypertension have a higher surgical morbidity than those with CTP class A without portal hypertension. Moreover, the type of surgery has a significant impact on risk aside from the CTP score.
UNOS, the United Network for Organ Sharing (www.unos.org), is the administrative body that allocates all donated organs in the United States utilizing MELD
scores and in the pediatric population, pediatric end-stage liver disease (PELD) scores as a way to rank liver transplant recipient candidates in descending order of severity of disease. Higher scores indicate more severe disease burden and an increased likelihood of death from untreated disease. Though the MELD score is used primarily to rank candidates for transplantation by expected mortality based on the severity of their liver disease, MELD score may be useful in the preoperative evaluation of the patient with cirrhosis to quickly grade the severity of their disease.
scores and in the pediatric population, pediatric end-stage liver disease (PELD) scores as a way to rank liver transplant recipient candidates in descending order of severity of disease. Higher scores indicate more severe disease burden and an increased likelihood of death from untreated disease. Though the MELD score is used primarily to rank candidates for transplantation by expected mortality based on the severity of their liver disease, MELD score may be useful in the preoperative evaluation of the patient with cirrhosis to quickly grade the severity of their disease.
The MELD scoring system uses a multivariate regression model to calculate a risk of death from the patient’s liver disease based on the prognostic factors consisting of serum creatinine, total bilirubin, INR values, and serum sodium, reflecting both hepatic synthetic and excretory function. Patients are assigned a MELD score based on a calculation (5), with scores rounded to the nearest whole number.
A study out of Mayo compared cirrhotic patients having digestive, orthopedic, and cardiovascular surgeries to a control group of cirrhotic patients undergoing minor surgical procedures and ambulatory patients and found that MELD score, American Society of Anesthesiologists (ASA) class, and age predicted mortality (6). Mayo published an online risk assessment tool to determine postoperative mortality that incorporates age, ASA class, and MELD score (7). This model has been validated in a cohort of Korean cirrhotic patients and was found to accurately reflect short-term mortality (30-day and 90-day), but it overestimated long-term mortality (>1 year) (8).
The decision to pursue aggressive diagnosis, quantification, and optimization of patients before surgery with suspected cirrhotic liver disease is based primarily on the type of planned surgery. Procedures involving outpatient diagnostic (i.e., endoscopy, colonoscopy) or sedation/MAC cases (i.e., cataract extraction) require minimal laboratory investigation and optimization. One should take into consideration whether or not patients with suspected liver disease, including those presenting with significant varices, are appropriate candidates for procedures in free-standing ambulatory surgery centers that often are not equipped to deal with potential complications that may arise, such as bleeding requiring transfusion. A recently published study found that an INR <2.5 or a platelet count >40,000/µL or more in cirrhotic patients having dental extractions was associated with minimal risk for bleeding, while an INR of >2.5 increased the bleeding rate by 40% (9). Decompensation of patients with significant hepatic dysfunction may not occur until 7 to 10 days following routine outpatient procedures.
The cirrhotic patient requiring more invasive or substantial interventions (i.e., endoscopic retrograde cholangiopancreatography [ERCP], cholecystectomy or hepatic resection) is at risk of adverse events if elevated PT, thrombocytopenia, or hypofibrinogenemia is detected. There remains significant controversy as to whether preoperative interventions such as vitamin K or factor VII administration or fresh-frozen plasma (FFP), platelet, and cryoprecipitate transfusions are either unnecessary due to adequate hemostatic function (despite aberrations on standard laboratory tests) or the beneficial effects so short lived that the treatment may carry more risk (i.e., transfusion complications) than benefit. Despite elevation in PT and reduced levels of both fibrinogen and platelets, the compensated cirrhotic patient often possesses adequate hemostatic function. A review of cirrhotic patients presenting for cardiac catheterization found no support for prophylactic administration of FFP and the risks of portal vein thrombosis with factor VII administration (10). One of the most
sensitive tests to evaluate coagulation function is the thromboelastograph (TEG), which measures real-time whole blood coagulation including speed, strength, and stability of coagulation. Many institutions other than major transplantation centers may not have this technology available.
sensitive tests to evaluate coagulation function is the thromboelastograph (TEG), which measures real-time whole blood coagulation including speed, strength, and stability of coagulation. Many institutions other than major transplantation centers may not have this technology available.
Decompensated cirrhotic patients may have significant anemia. The decision to transfuse is based on other factors, including cardiac comorbidity or symptomatology, rather than on a specific hemoglobin value. When in doubt, the healthcare professional evaluating a patient with cirrhosis for preoperative assessment is advised to speak to the referring surgeon or anesthesia provider to elucidate risks, concerns, or questions specific to the procedure and the planned anesthetic.
REFERENCES
1. Child CG III, Turcotte JG. Surgery and portal hypertension. In: Child CG III, ed. The Liver and Portal Hypertension. Philadelphia, PA: Saunders, 1964;50.
2. Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646-649.
3. Garrison RN, Cryer HM, Howard DA, et al. Clarification of risk factors for abdominal operations in patients with hepatic cirrhosis. Ann Surg. 1984;199:648-655.
4. Mansour A, Watson W, Shayani V, et al. Abdominal operations in patients with cirrhosis: still a major surgical challenge. Surgery. 1997;122,730-735. Discussion 735-736.
5. https://optn.transplant.hrsa.gov/resources/allocation-calculators/meld-calculator/. Accessed October 25, 2016.
6. Teh SH, Nagorney DM, Stevens SR, et al. Risk factors for mortality after surgery in patients with cirrhosis. Gastroenterology. 2007;132: 1261-1269.
7. http://www.mayoclinic.org/medical-professionals/model-end-stage-liver-disease/post-operative-mortality-risk-patients-cirrhosis. Accessed October 25, 2016.
8. Kim SY, Yim HY, Park SM, et al. Validation of a Mayo post-operative mortality risk prediction model in Korean cirrhotic patients. Liver Int. 2011;31:222-228.
9. Cocero N, Bezzi M, Martini S, Carossa S. Oral surgical treatment of patients with chronic liver disease: Assessments of bleeding and its relationship with thrombocytopenia and blood coagulation parameters. J Oral Maxillofac Surg. 2017;75(1):28-34.
10. Mahmoud AM, Elgendy IY, Choi CY, et al. Risk of bleeding in end-stage liver disease patients undergoing cardiac catheterization. Tex Heart Inst J. 2015;42:414-418.
7.2 Alcoholic Hepatitis
Natasha Schneider
Michael A. Pilla
Alcoholic liver disease encompasses a spectrum of liver injury from mere hepatic steatosis without dysfunction to hepatitis with or without cirrhosis. These stages are not necessarily linear and may present simultaneously.
Alcoholic hepatitis is defined by the presence of jaundice and liver dysfunction in the setting of relatively recent heavy alcohol use. It is not uncommon for alcohol use to have ceased several weeks before presentation of clinical decompensation. In addition to jaundice, other common presenting symptoms include fever, ascites, right upper quadrant abdominal pain, anorexia, and muscle wasting. Physical examination may reveal tender hepatomegaly, ascites, spider angiomata, palmar erythema, muscle wasting, and jaundice.
The characteristic laboratory abnormalities seen in alcoholic hepatitis include moderate elevations in the hepatic transaminases, typically in a 2:1 pattern of serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT). It is rare to have aminotransferases greater than 500 IU/L, and if seen prompts evaluation for other causes of hepatitis. Elevated white blood cell count with predominance of neutrophils is common and may not reflect active infection. However, infection should be ruled out in these patients including a diagnostic paracentesis, as risk for infectious complications is quite high. Other abnormalities include elevated bilirubin and INR. An increased serum creatinine may be a result of intravascular volume depletion. If the creatinine does not correct with colloid repletion, HRS must be considered, which portends an extremely poor prognosis. Liver biopsy is not required for the diagnosis of alcoholic hepatitis. A biopsy will demonstrate macrovesicular steatosis with hepatocellular damage characterized by ballooned hepatocytes.
Patients with alcoholic hepatitis can present with fever, leukocytosis, and right upper quadrant pain which may be misdiagnosed as acute cholecystitis. This presentation, in addition to significant hyperbilirubinemia and heavy reported alcohol use, raises concern for alcoholic hepatitis. Cholecystectomy in these patients carries a high risk of morbidity and mortality and should be avoided.
Prognostic scoring systems are used to evaluate the severity of alcoholic hepatitis. Maddrey’s discriminant function (DF) (1) is defined as DF = 4.6 × (PT in seconds – control PT) + serum bilirubin in mg/dL. A value greater than 32 is consistent with severe alcoholic hepatitis and portends the highest short-term mortality risk. The MELD (2) score (and more recently the MELD-Na score) is a complicated logarithmic scoring system. It incorporates the patient’s serum creatinine, bilirubin, sodium and INR, and renal replacement therapy (2). The MELD score ranges from 6 to 40, with higher scores indicating higher risk of short-term mortality. A MELD score greater than 21 in patients with alcoholic hepatitis is associated with a 90-day mortality of 20% (3). This risk would be higher in the setting of surgery. The MELD score is comparable to the DF in predicting mortality.
Alcoholic hepatitis is thought to be a relative contraindication to surgery. Elective surgeries should be delayed in these patients. Some have suggested at least a 12-week delay in elective surgery from the onset of acute alcoholic hepatitis. Supportive care should be provided in the interim, and elective surgery is only to be pursued when the patient is demonstrating clinical improvement in laboratory assessment as well as symptoms of portal hypertension. It is imperative that patients be counseled on alcohol cessation.
If emergency surgery is needed, alcoholic hepatitis, especially more severe forms, will greatly increase morbidity and mortality. In a landmark study from 1972 assessing open versus percutaneous liver biopsies in patients with alcoholic hepatitis, the mortality rate for those having a surgical approach was 58% compared with 10% for those done percutaneously (4). Other studies cite a high mortality from portosystemic shunts and exploratory laparotomy in the setting of alcoholic hepatitis (5).
If presented with a patient with alcoholic hepatitis, determination of surgical necessity versus delay in care must be carefully evaluated due to the extreme risk in anesthetizing these patients. Coordination of care among surgeons, anesthesiologists, and hepatologists is mandated for emergency procedures.
REFERENCES
1. Maddrey WC, Boitnott JK, Bedine MS, et al. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology. 1978;75:193-199.
2. https://optn.transplant.hrsa.gov/resources/allocation-calculators/meld-calculator/. Accessed October 25, 2016.
3. Dunn W, Jamil LH, Brown LS, et al. MELD accurately predicts mortality in patients with alcoholic hepatitis. Hepatology. 2005;41:353-358.
4. Greenwood SM, Leffler CT, Minkowitz S. The increased mortality rate of open liver biopsy in alcoholic hepatitis. Surg Gynecol Obstet. 1972;134:600-604.
5. Powell-Jackson P, Greenway B, Williams R. Adverse effects of exploratory laparotomy in patients with unsuspected liver disease. Br J Surg. 1982;69:449-451.
7.3 Viral Hepatitis
Natasha Schneider
Michael A. Pilla
Viral hepatitis can be categorized as either acute or chronic. There does not appear to be an increased risk of surgery in patients with chronic disease, such as chronic hepatitis B or C, in the absence of cirrhosis. Surgery is avoided until further workup if patients with known chronic viral hepatitis are found to have abnormalities in liver synthetic function. Abnormalities in bilirubin, INR, fibrinogen, platelets, or albumin may herald undiagnosed advanced liver disease and require further investigation. Historically, surgery is contraindicated in patients presenting with acute viral hepatitis. Acute viral hepatitis is defined as inflammation in the liver secondary to acute acquisition of one of the hepatitis viruses, A, B, or rarely C, D, or E. These are acquired in a variety of ways that are specific to each virus, including fecal-oral transmission, sexual exposure, and blood-borne exposure (see Table 7.2).
Acute infection is often associated with markedly elevated hepatic transaminases, AST, and ALT. Symptoms are highly variable and range from very mild to fulminant hepatic failure. Physical examination may reveal icteric sclera, jaundice, and hepatomegaly. Laboratory tests demonstrate a hepatocellular pattern, which is characterized by a marked elevation in AST and ALT, not uncommonly exceeding 1,000 IU/L. Bilirubin or alkaline phosphatase may be elevated. Further evaluation
includes serologies as noted in Table 7.2. Of note, active hepatitis B is required for hepatitis D infection.
includes serologies as noted in Table 7.2. Of note, active hepatitis B is required for hepatitis D infection.
TABLE 7.2 Viral Hepatitis, Modes of Transmission, Serologic, and Other Testing Modalities | ||||||||||||||||||||||||
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Elective surgeries are avoided in the setting of acute viral hepatitis due to increased morbidity and mortality. Acute viral hepatitis may be a causative factor in acute liver failure requiring hepatic transplantation and is the number one cause of acute failure in developing countries (1). Surgery may be considered once there is evidence of sustained improvement in markers of liver inflammation and normal function. Surgical intervention with acute viral hepatitis is strongly discouraged, as additional stressors during active infection may precipitate liver failure and mortality.
REFERENCE
1. Bernal W, Auzinger G, Dhawan A, et al. Acute liver failure. The Lancet. 2010;376:190-201.
7.4 The Patient for Liver Transplantation
Cinnamon L. Sullivan
Patients for liver transplantation are a diverse group secondary to the range of causes of liver failure from fulminant hepatic failure (FHF), acute-on-chronic disease, chronic disease, and low MELD score disease with exception points for hepatocellular carcinoma or portopulmonary hypertension (PoPH) (1). Even though some patients come for evaluation with little to no sequelae of end-stage liver disease (ESLD), transplant centers tend to standardize the preoperative assessment. There is a need to identify those patients who might not tolerate the dramatic intraoperative physiologic stress. Transplant centers are evaluated and regulated based on 1-year graft and patient survival, and therefore, selection of appropriate patients is critical. It is important to have baseline cardiopulmonary tests for comparison that can be performed yearly to reassess the patient’s candidacy and risk stratification. ESLD has negative effects on essentially all organ systems, yet there is limited ability for optimization, as the disease is constantly progressing. Therefore, repeat testing is mandatory. This unique preoperative approach maintains stewardship of a valuable but scarce resource.
The likelihood of a patient receiving an organ for transplantation depends on placement on the waiting list. MELD score is used to stratify patients on the liver transplant waiting list, as it has good positive predictive value for 1-year mortality. Unlike CTP score, which has the subjective elements of hepatic encephalopathy and severity of ascites, MELD is calculated using the more objective criteria of INR, bilirubin, and creatinine. MELD-Na has been shown to be an even better predictor of patient waitlist mortality if their baseline MELD is >11 and has been used since January 2016 for stratifying patients on the waiting list (2,3).
HEPATIC ENCEPHALOPATHY
Cerebral edema is the primary cause of death in FHF. Measures to decrease intracranial pressure (ICP) are required with hepatic encephalopathy (HE) grade 3 or 4. The current recommendations are to maintain serum sodium levels at 150 to 154 mmol/L and perform maneuvers to increase cerebral perfusion pressure, such as moderate
elevation of the head of the bed, increasing mean arterial pressure, and continuous renal replacement therapy (CRRT) in patients with concurrent renal failure to avoid hypervolemia and hyponatremia. Hyperventilation is effective to treat surges in ICP and prevent herniation, but prolonged use has deleterious effects on cerebral oxygenation and may cause rebound intracranial hypertension. A PaCO2 goal of 25 to 35 mm Hg is recommended while other therapies are initiated. The use of an extradural screw or “bolt” is highly effective in monitoring ICP, but the incidence of intracranial hemorrhage has led many centers to eschew its use. Transcranial Doppler (TCD), optic nerve sheath diameter (ONSD), tympanic membrane displacement (TMD), and pupillometry are noninvasive techniques with varying sensitivity and specificity. TCD is the most reliable when tested compared to intraventricular pressure monitoring. One limitation of TCD is the inability to get one of the four recommended views during an examination because the patient is typically turned lateral for the suboccipital window. The transtemporal, transorbital, and submandibular views provide information on perfusion in the circle of Willis with the exception of the basilar arteries (4). If monitoring is not available, empiric measures to increase cerebral perfusion pressure should be employed in FHF patients with HE grade 3 and 4. Patients with chronic or acute-on-chronic liver disease do not have the same neurologic sequelae, so standard evaluation of neurologic status will suffice. Hyponatremia is present in 50% of ESLD patients, and 20% have serum sodium <130 mmol/L. Acute shifts in serum sodium are avoided to prevent central pontine myelinolysis.
elevation of the head of the bed, increasing mean arterial pressure, and continuous renal replacement therapy (CRRT) in patients with concurrent renal failure to avoid hypervolemia and hyponatremia. Hyperventilation is effective to treat surges in ICP and prevent herniation, but prolonged use has deleterious effects on cerebral oxygenation and may cause rebound intracranial hypertension. A PaCO2 goal of 25 to 35 mm Hg is recommended while other therapies are initiated. The use of an extradural screw or “bolt” is highly effective in monitoring ICP, but the incidence of intracranial hemorrhage has led many centers to eschew its use. Transcranial Doppler (TCD), optic nerve sheath diameter (ONSD), tympanic membrane displacement (TMD), and pupillometry are noninvasive techniques with varying sensitivity and specificity. TCD is the most reliable when tested compared to intraventricular pressure monitoring. One limitation of TCD is the inability to get one of the four recommended views during an examination because the patient is typically turned lateral for the suboccipital window. The transtemporal, transorbital, and submandibular views provide information on perfusion in the circle of Willis with the exception of the basilar arteries (4). If monitoring is not available, empiric measures to increase cerebral perfusion pressure should be employed in FHF patients with HE grade 3 and 4. Patients with chronic or acute-on-chronic liver disease do not have the same neurologic sequelae, so standard evaluation of neurologic status will suffice. Hyponatremia is present in 50% of ESLD patients, and 20% have serum sodium <130 mmol/L. Acute shifts in serum sodium are avoided to prevent central pontine myelinolysis.
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