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Cirrhosis, the final sequela of chronic hepatic insult, is characterized by the presence of fibrous septa throughout the liver subdividing the parenchyma into hepatocellular nodules (Fig. 31-13).35 Cirrhosis is the consequence of sustained wound healing in response to chronic liver injury. Approximately 40% of cirrhotic patients are asymptomatic, but progressive deterioration leading to the need for liver transplantation or death is typical after the development of end-stage liver disease (ESLD). The complications of ESLD include progressive hyperbilirubinemia, malnutrition, decreased synthetic function of the liver, coagulopathy, portal hypertension (i.e., ascites and variceal bleeding), hepatic encephalopathy, and life-limiting fatigue. ESLD carries a 5-year mortality of 50%, with 70% of deaths due to liver failure.36 In the United States, cirrhosis accounts for 30,000 deaths per year and is the most common nonneoplastic cause of death among patients with hepatobiliary and digestive diseases. An additional 10,000 to 12,000 deaths occur annually due to HCC, the most rapidly increasing neoplasm in the United States.36.
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Morphologic Classification of Cirrhosis
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Morphologically, cirrhosis can be described as micronodular, macronodular, or mixed. Micronodular cirrhosis is characterized by thick regular septa, small uniform regenerative nodules, and involvement of virtually every hepatic lobule. Macronodular cirrhosis frequently has septa and regenerative nodules of varying sizes. The regenerative nodules consist of irregularly sized hepatocytes with large nuclei and cell plates of varying thickness. Mixed cirrhosis is present when regeneration is occurring in a micronodular liver and over time converts to a macronodular pattern. This morphologic categorization is limited, and cirrhosis is a dynamic process in which nodule size varies over time. The three patterns correlate poorly with etiology, and the same pattern can result from a variety of disease processes. Conversely, a single disease process can demonstrate several morphologic patterns. Irrespective of etiology and morphologic pattern, the cirrhotic liver frequently demonstrates right hepatic lobe atrophy, caudate lobe and left lateral segment hypertrophy, recanalization of the umbilical vein, a nodular surface contour, dilatation of the portal vein, gastroesophageal varices, and splenomegaly on radiographic evaluation.
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Etiology of Cirrhosis
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Cirrhosis can result from a wide range of disease processes, including viral, autoimmune, drug-induced, cholestatic, and metabolic diseases (Table 31-3). In the diagnosis of alcoholic liver disease, documentation of chronic alcohol abuse is imperative. Liver biopsy will reveal the typical findings of alcoholic hepatitis, including hepatocyte necrosis, Mallory bodies, neutrophil infiltration, and perivenular inflammation. Patients with nonalcoholic steatohepatitis (NASH) often endorse a history of diabetes mellitus or metabolic syndrome. The diagnosis of NASH requires the demonstration of steatohepatitis on biopsy, the lack of a history of significant alcohol consumption, and exclusion of other causes of hepatic steatosis. Although cryptogenic cirrhosis, or cirrhosis without an apparent cause, accounted for a third of all cases in the past, this proportion has declined over time as it becomes increasingly apparent that many of such patients may actually have unrecognized NASH.
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Chronic hepatitis C infection is the most common cause of chronic liver disease and the most frequent indication for liver transplantation in the United States. The identification of chronic hepatitis C infection is facilitated by serologic assays that detect antibody to hepatitis C and molecular assays that quantify hepatitis C viral RNA. Chronic hepatitis B, on the other hand, can be diagnosed based on the detection of hepatitis B surface antigen (HBsAg) more than 4 to 6 months after initial infection. Additional tests of hepatitis B viral replication, such as the hepatitis B e antigen (HBeAg) and hepatitis B viral DNA, can be used to confirm ongoing infection and to guide appropriate antiviral therapy.
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Autoimmune causes of cirrhosis include primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. Patients with primary biliary cirrhosis may be asymptomatic or may present with a history of fatigue, pruritus, and skin hyperpigmentation that is not related to jaundice. Antimitochondrial antibodies will test positive in the vast majority of cases. Affected patients also may have marked elevations in serum cholesterol, while hyperbilirubinemia is seen late in the course of the disease. Primary sclerosing cholangitis is a chronic cholestatic disease of the liver associated with ulcerative colitis and Crohn’s disease. The clinical presentation can include pruritus, steatorrhea, fat-soluble vitamin deficiencies, and metabolic bone disease. The diagnosis is often established by imaging of the biliary tree, which reveals a characteristic picture of diffuse, multifocal strictures with focal dilation of the bile ducts resulting in a beaded appearance. Complications are common and can include biliary strictures, cholangitis, cholelithiasis, and cholangiocarcinoma. Autoimmune hepatitis is often accompanied by an elevation in serum globulins, particularly gamma globulins. Liver biopsy will show nonspecific changes such as a portal mononuclear cell infiltrate with the characteristic presence of plasma cells. Many patients with autoimmune hepatitis will respond to treatment with prednisone with or without azathioprine.
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Hereditary hemochromatosis is the most common metabolic disorder causing cirrhosis. This entity should be suspected if the patient’s clinical presentation includes skin hyperpigmentation, diabetes mellitus, pseudogout, cardiomyopathy, or a family history of cirrhosis. Elevated plasma ferritin and increased iron saturation levels suggest the presence of iron overload, but these findings also can be seen in other diseases of the liver. Confirmatory testing can be achieved by means of genetic testing, liver biopsy, or by assessing the response to phlebotomy. Other uncommon metabolic disorders leading to cirrhosis include Wilson’s disease and α1-antitrypsin deficiency.
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Clinical Manifestations of Cirrhosis
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The clinical history associated with cirrhosis can include fatigue, anorexia, weight loss, jaundice, abdominal pain, peripheral edema, ascites, GI bleeding, and hepatic encephalopathy. On physical examination, a number of findings have been described in patients with cirrhosis. Spider angiomata and palmar erythema are believed to be caused by alterations in sex hormone metabolism. Finger clubbing may be a consequence of hypoalbuminemia, while the pathogenesis of white nail beds and Dupuytren’s contractures are less well understood. Males may develop features of feminization such as gynecomastia, loss of chest and axillary hair, and testicular atrophy. Splenomegaly is common, whereas the cirrhotic liver itself may be enlarged, normal sized, or small. Ascites and pleural effusion can be seen with fluid accumulation. Portal hypertension can manifest as caput medusae and/or the presence of the Cruveilhier-Baumgarten murmur, a venous hum that can be auscultated in the epigastrium resulting from collaterals between the portal system and the remnant of the umbilical vein. Jaundice usually does not appear until the bilirubin rises above 2 to 3 mg/dL. Asterixis can be detected in patients with hepatic encephalopathy. Other manifestations include fetor hepaticus, as well as features suggestive of malnutrition such as weakness, weight loss, and temporal muscle wasting.
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Although fat stores and muscle mass are reduced, resting energy expenditure is increased. Muscle cramps occur frequently in the cirrhotic patient and are felt to correlate with ascites, low mean arterial pressure, and plasma renin activity. Abdominal hernias are common with ascites and should be electively repaired only in patients with well-compensated cirrhosis; otherwise, the hernia should be repaired at the time of or after hepatic transplantation. HCC can occur in all forms of cirrhosis, and every cirrhotic patient should undergo screening for the development of HCC every 6 months via imaging and measurement of a serum α-fetoprotein (AFP) level. Cirrhosis is associated with increased cardiac output and heart rate as well as decreased systemic vascular resistance and blood pressure. Patients with cirrhosis are more prone to infections due to impaired phagocytic activity of the reticuloendothelial system. Bacterial infections, often of intestinal origin, are common and must be suspected in a patient with unexplained pyrexia or clinical deterioration. Spontaneous bacterial peritonitis also is seen in cases of cirrhosis with ascites. Intrinsic drug metabolism is reduced in the cirrhotic liver, and this fact needs to be recognized when prescribing medications.
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Laboratory Findings Associated with Cirrhosis
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Laboratory findings vary in the cirrhotic patient depending on the degree of compensation; however, in general, a number of trends are seen. The cirrhotic patient usually has a mild normocytic normochromic anemia. The white blood cell and platelet counts are reduced, and the bone marrow is macronormoblastic. The PT is prolonged and does not respond to vitamin K therapy, and the serum albumin level is depressed. Urobilinogen is present and urinary sodium excretion is diminished in the presence of ascites. The serum levels of bilirubin, transaminases, and alkaline phosphatase may all be elevated. However, normal liver function test results do not eliminate the possibility of cirrhosis.
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The diagnosis of cirrhosis can be made in many cases from a constellation of clinical features, laboratory values, and radiographic findings. Histopathologic examination of liver tissue is occasionally needed to confirm the diagnosis of cirrhosis and in determining disease etiology, activity, and progression. Liver biopsy can be performed via a percutaneous, transjugular, or laparoscopic approach. If needed, ultrasound or CT guidance can be helpful in obtaining an adequate sample and avoiding other viscera.
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Various serologic markers of hepatic fibrosis are currently being investigated to help predict the presence of cirrhosis without the need for liver biopsy. However, no currently available marker is sufficiently accurate for clinical use. Ultrasound elastography, which measures the stiffness of the liver by inducing an elastic shear wave that propagates through the tissue, shows promise as a noninvasive test in identifying patients with advanced fibrosis and cirrhosis. (See earlier section, “Radiologic Evaluation of the Liver.”)
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Hepatic Reserve and Assessment of Surgical Risk in the Cirrhotic Patient
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Assessing the hepatic reserve of the cirrhotic patient is important, because cirrhosis and portal hypertension can have a negative impact on the outcome of nontransplant surgical procedures. Patients with liver disease undergoing surgery are at increased risk for surgical and anesthesia-related complications. The actual risk depends on the type of anesthetic used, the specific surgical procedure performed, and the severity of liver disease. Previous studies have demonstrated that emergency operations, cardiac surgery, hepatic resections, and abdominal surgery, particularly cholecystectomy, gastric resection, and colectomy, generate the highest operative risk among cirrhotic patients. Additionally, preoperative patient characteristics such as anemia, ascites, encephalopathy, malnutrition, hypoalbuminemia, hypoxemia, infection, jaundice, portal hypertension, and prolonged PT have also been associated with inferior outcomes after surgery. Nontransplant surgical procedures are contraindicated in patients with acute fulminant hepatitis and those with severe decompensated chronic hepatitis.
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A number of laboratory tests have been used to assess hepatic reserve in patients with cirrhosis. Tests of indocyanine green, sorbitol, and galactose elimination capacity as well as the carbon-13 galactose breath test and carbon-13 aminopyrine breath test have all been disappointing clinically due to their dependence on flow to the liver as well as the unavailability and complexity of the tests. The monoethylglycinexylidide (MEGX) test, which measures MEGX formation after the administration of lidocaine, has been shown to be approximately 80% sensitive and specific in diagnosing cirrhosis. However, this test loses both sensitivity and specificity as the serum bilirubin level rises and interferes with the fluorescent readout system.
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Child-Turcotte-Pugh Score
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The Child-Turcotte-Pugh (CTP) score was originally developed to evaluate the risk of portocaval shunt procedures performed for portal hypertension and subsequently has been shown to be useful in predicting surgical risks of other intra-abdominal operations on cirrhotic patients (Table 31-4). Numerous studies have demonstrated overall surgical mortality rates of 10% for patients with class A cirrhosis, 30% for those with class B cirrhosis, and 75% to 80% for those with class C cirrhosis.37 The CTP score is derived from five variables as shown in Table 31-4. The problems with the CTP score are the presence of subjective variables (encephalopathy and ascites), its narrow range (5 to 15 points), and the equal weighting given to each variable. Multiple retrospective studies have demonstrated that perioperative mortality and morbidity rates correlate well with the CTP score, and for over 30 years, this measure had been used as the principal predictor of operative risk.
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Model for End-Stage Liver Disease Scoring System
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The Model for End-Stage Liver Disease (MELD) is a linear regression model based on objective laboratory values (INR, bilirubin level, and creatinine level). It was originally developed as a tool to predict mortality after transjugular intrahepatic portosystemic shunt (TIPS) but has been validated and used as the sole method of liver transplant allocation in the United States since 2002. The MELD formula is as follows:
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MELD Score = 9.57 Ln(SCr) + 3.78 Ln(Tbil) + 11.2 Ln(INR) + 6.43
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where Ln represents natural logarithm, SCr is serum creatinine level (in milligrams per deciliter), and Tbil is serum bilirubin level (in milligrams per deciliter).
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A number of studies have examined the relative values of MELD and CTP scores in predicting postoperative mortality in cirrhotic patients undergoing nontransplant surgical procedures. Northup and colleagues demonstrated that MELD score was the only statistically significant predictor of 30-day mortality.38 In this study, mortality increased by approximately 1% for each MELD point up to a score of 20 and by 2% for each MELD point above 20. A comparison of the MELD model with the CTP classification showed good correlation between the two measures in predicting mortality, especially in the setting of emergency surgery.39 In these studies, the relative risk of mortality increased by 14% for each 1-point increase in MELD score. As a result, it has been proposed that patients with a MELD score below 10 can safely undergo elective surgery, those with MELD between 10 and 15 may undergo surgery with caution, while those with MELD scores in excess of 15 should not be subjected to elective surgical procedures.40
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The portal venous system contributes approximately 75% of the blood and 72% of the oxygen supplied to the liver. In the average adult, 1000 to 1500 mL/min of portal venous blood is supplied to the liver. However, this amount can be significantly increased in the cirrhotic patient. The portal venous system is without valves and drains blood from the spleen, pancreas, gallbladder, and abdominal portion of the alimentary tract into the liver. Tributaries of the portal vein communicate with veins draining directly into the systemic circulation. These collateral communications occur at the gastroesophageal junction, anal canal, falciform ligament, splenic venous bed and left renal vein, and retroperitoneum (Fig. 31-14). The normal portal venous pressure is 5 to 10 mmHg, and at this pressure, very little blood is shunted from the portal venous system into the systemic circulation. As portal venous pressure increases, however, the collateral communications with the systemic circulation dilate, and a large amount of blood may be shunted around the liver and into the systemic circulation.
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Imaging of the Portal Venous System and Measurement of Portal Venous Pressure
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The patency of the portal vein and the nature of the collateral circulation should be established. An understanding of portal vein patency and anatomy is crucial before undertaking portosystemic shunts, hepatic resection, or hepatic transplantation. The simplest initial investigation is abdominal ultrasonography. A large portal vein suggests portal hypertension but is not diagnostic. Doppler ultrasound is capable of outlining the anatomy of the portal vein, excluding the presence of thrombosis, and identifying the direction of portal venous blood flow. Doppler ultrasound also is useful in evaluating blood flow through surgical shunts and TIPS. Abdominal CT and magnetic resonance angiography both are capable of revealing portal vein anatomy as well as patency. Visceral angiography and portal venography are reserved for cases that cannot be evaluated satisfactorily by noninvasive methods and require further clarification of portal patency or anatomy.
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The most accurate method of determining portal hypertension is hepatic venography. The most commonly used procedure involves placing a balloon catheter directly into the hepatic vein and measuring the free hepatic venous pressure (FHVP) with the balloon deflated and the wedged hepatic venous pressure (WHVP) with the balloon inflated to occlude the hepatic vein. The hepatic venous pressure gradient (HVPG) is then calculated by subtracting the free from the wedged venous pressure (HVPG = WHVP – FHVP). The HVPG represents the pressure in the hepatic sinusoids and portal vein and is a measure of portal venous pressure. Clinically significant portal hypertension is evident when HVPG exceeds 10 mmHg.
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Etiology and Clinical Features of Portal Hypertension
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The causes of portal hypertension can be divided into three major groups: presinusoidal, sinusoidal, and postsinusoidal.41 Although multiple disease processes can result in portal hypertension (Table 31-5), in the United States, the most common cause of portal hypertension is usually an intrahepatic one, namely, cirrhosis. The most significant clinical finding associated with portal hypertension is the development of gastroesophageal varices, which are mainly supplied by the anterior branch of the left gastric (coronary) vein.
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Portal hypertension also results in splenomegaly with enlarged, tortuous, and even aneurysmal splenic vessels. Splenomegaly is frequently associated with functional hypersplenism, causing leukopenia, thrombocytopenia, and anemia. Ascites occurs in the setting of severe portal hypertension in combination with hepatocyte dysfunction. The umbilical vein may recannulate and dilate, leading to visible collaterals on the abdominal wall. Anorectal varices are present in approximately 45% of cirrhotic patients and must be distinguished from hemorrhoids, which do not communicate with the portal system and are not present at increased incidence in patients with portal hypertension. Large spontaneous venous shunts may form between the portal venous system and the left renal vein or the IVC, but these shunts are ineffective in reducing portal venous pressures and preventing bleeding from gastroesophageal varices.
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Management of Gastroesophageal Varices
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The most significant manifestation and the leading cause of morbidity and mortality related to portal hypertension is variceal bleeding. Approximately 30% of patients with compensated cirrhosis and 60% of patients with decompensated cirrhosis have esophageal varices. One third of all patients with varices will experience variceal bleeding. Each episode of bleeding is associated with a 20% to 30% risk of mortality. If left untreated, 70% of patients who survive the initial bleed will experience recurrent variceal hemorrhage within 2 years of the index hemorrhage.
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Prevention of Variceal Bleeding
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Current measures aimed at preventing variceal bleeding include the administration of nonselective β-blockers and prophylactic endoscopic surveillance with variceal band ligation. Meta-analyses have demonstrated that nonselective β-blockers such as propranolol and nadolol reduce the index variceal bleed by approximately 45% and decrease bleeding mortality by 50%.42 However, approximately 20% of patients do not respond to β-blockade, and another 20% cannot tolerate β-blockade due to medication side effects. Endoscopic surveillance with prophylactic variceal band ligation has been associated with a lower incidence of a first variceal bleed.43 Variceal band ligation is recommended for patients with medium to large varices, performed every 1 to 2 weeks until obliteration, followed by esophagogastroduodenoscopy (EGD) 1 to 3 months later and surveillance EGD every 6 months to monitor for recurrence of varices.
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Management of Acute Variceal Hemorrhage
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Patients with acute variceal hemorrhage should be admitted to an ICU for resuscitation and management. Blood resuscitation should be performed carefully to reach a hemoglobin level of approximately 8 g/dL. Overzealous replacement of blood products and administration of saline can lead to both rebleeding and increased mortality. Administration of fresh frozen plasma and platelets can be considered in patients with severe coagulopathy. Use of recombinant factor VIIa has not been shown to be more beneficial than standard therapy and therefore is not recommended at this time. Cirrhotic patients with variceal bleeding have a high risk of developing bacterial infections, which are associated with increased risks of rebleeding and mortality. Spontaneous bacterial peritonitis accounts for approximately half of these infections, with urinary tract infections and pneumonias comprising the remainder. The use of short-term prophylactic antibiotics (e.g., ceftriaxone 1 g/d intravenously) has been shown both to decrease the rate of bacterial infections and to increase survival.
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Vasoactive medications decrease blood flow to the gastroesophageal varices and can be initiated as soon as the diagnosis of variceal bleeding is made. Although vasopressin is the most potent available vasoconstrictor, its use is limited by its systemic vasoconstrictive effects that can produce hypertension, myocardial ischemia, arrhythmias, ischemic abdominal pain, and limb gangrene. Octreotide, a somatostatin analog, has the advantage that it can be administered for 5 days or longer, and it is currently the preferred pharmacologic agent for initial management of acute variceal bleeding. In addition to pharmacologic therapy, endoscopy with variceal band ligation should be carried out as soon as possible. This combination of pharmacologic and endoscopic therapy has been shown both to improve the initial control of bleeding and to increase the 5-day hemostasis rate.43
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When medical and endoscopic measures fail to control variceal hemorrhage, balloon tamponade using a Sengstaken-Blakemore tube will control refractory bleeding in up to 90% of patients. However, its application is limited due to the potential for complications, which include aspiration, airway obstruction, and esophageal perforation due to overinflation or pressure necrosis. Therefore, the use of a Sengstaken-Blakemore tube should not exceed 36 hours to avoid tissue necrosis, and this treatment modality should only be considered a temporary bridge to more definitive measures of variceal hemorrhage control.
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Transjugular Intrahepatic Portosystemic Shunt
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The TIPS procedure involves implantation of a metallic stent between an intrahepatic branch of the portal vein and a hepatic vein radicle. The needle track is dilated until a portal pressure gradient of ≤12 mmHg is achieved. TIPS can be performed in 95% of patients by an experienced interventional radiologist, controls variceal bleeding in >90% of cases refractory to medical treatment, and should not affect subsequent hepatic transplantation. Possible complications include bleeding either intra-abdominally or via the biliary tree, infections, renal failure, decreased hepatic function, and hepatic encephalopathy, which occur in 25% to 30% of patients after the TIPS procedure. A high rate of thrombosis is seen and can be attributed to intimal hyperplasia of the metallic stent. Frequent follow-up with repeated interventions such as dilation or restenting often are needed to maintain TIPS patency.
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Balloon-Occluded Retrograde Transvenous Obliteration
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The balloon-occluded retrograde transvenous obliteration (BRTO) procedure has been used for the specific management of bleeding gastric varices in patients with spontaneous gastrorenal or splenorenal shunts shown on contrast-enhanced cross-sectional imaging. Using a transjugular or transfemoral approach, a balloon-occlusion catheter is directed through the left renal vein into the spontaneous shunt, which is then obliterated with the use of a sclerosing agent. BRTO effectively controls hemorrhage from gastric varices and preserves portal flow to the liver, thereby reducing the risk of hepatic encephalopathy relative to TIPS. The occlusion of spontaneous shunts, however, can theoretically exacerbate portal hypertension, precipitate hemorrhage from esophageal varices, and exacerbate the accumulation of ascites.
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The need for surgical shunts has been reduced since the introduction of the TIPS procedure and hepatic transplantation. At this time, the recommendation is that surgical shunts be considered only in patients who have MELD scores of <15, who are not candidates for hepatic transplantation, or who have limited access to TIPS therapy and the necessary follow-up. The aim of the surgical shunt is to reduce portal venous pressure, maintain total hepatic and portal blood flow, and avoid the high incidence of complicating hepatic encephalopathy. Patient survival is determined by hepatic reserve.
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The portacaval shunt, as first described by Eck in 1877, either joins the portal vein to the IVC in an end-to-side fashion and completely disrupts portal vein flow to the liver, or joins it in a side-to-side fashion and thereby maintains partial portal venous flow to the liver. Currently this shunt is rarely performed due to the high incidence of hepatic encephalopathy and decreased liver function resulting from the reduction of portal perfusion. The Eck fistula also makes subsequent hepatic transplantation much more technically difficult.
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The mesocaval shunt uses an 8- or 10-mm polytetrafluoroethylene (PTFE) graft to connect the superior mesenteric vein to the IVC. The mesocaval shunt is technically easier to perform and can be easily ligated during subsequent hepatic transplantation. The smaller caliber of the shunt avoids the deleterious effects of portal blood flow deprivation on hepatic function. Small-diameter portosystemic shunts have been reported to reduce the incidence of encephalopathy but at the expense of increased risks of shunt thrombosis and rebleeding.
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The surgical shunt currently used most often is the distal splenorenal or Warren shunt (Fig. 31-15). This shunt is technically the most difficult to perform. It requires division of the gastroesophageal collaterals and allows venous drainage of the stomach and lower esophagus through the short gastrosplenic veins into the spleen, and ultimately decompresses the left upper quadrant by allowing the splenic vein to drain directly into the left renal vein via an end-to-side splenic to left renal vein anastomosis. This shunt has the advantages of being associated with a lower rate of hepatic encephalopathy and decompensation and not interfering with subsequent liver transplantation.
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Nonshunt Surgical Management of Refractory Variceal Bleeding
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In the patient with extrahepatic portal vein thrombosis and refractory variceal bleeding, the Sugiura procedure may be considered. The Sugiura procedure consists of extensive devascularization of the stomach and distal esophagus along with transection of the esophagus, splenectomy, truncal vagotomy, and pyloroplasty. As with performance of surgical shunts, patient survival is dependent on hepatic reserve at the time of the surgical procedure. Experience in Western countries is somewhat limited, and a number of modifications have been made to the original Sugiura procedure over time.
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Hepatic Transplantation
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Patients with cirrhosis, portal hypertension, and variceal bleeding usually die as a result of hepatic failure and not acute blood loss. Therefore, hepatic transplantation must be considered in the patient with ESLD, because it represents the patient’s only chance for definitive therapy and long-term survival. Hepatic transplantation also can be considered for the patient with variceal bleeding refractory to all other forms of management. Survival after hepatic transplantation is not affected adversely by the previous performance of endoscopic variceal band ligation, TIPS, or splenorenal or mesocaval shunts. Previous creation of an Eck fistula, however, does make hepatic transplantation much more technically difficult, and therefore this procedure should be avoided in the transplant candidate. In addition to saving the patient’s life, hepatic transplantation reverses most of the hemodynamic and humoral changes associated with cirrhosis.
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Budd-Chiari syndrome (BCS) is an uncommon congestive hepatopathy characterized by the obstruction of hepatic venous outflow. The incidence of BCS is 1 in 100,000 of the general population worldwide.44 Patients may present with acute signs and symptoms of abdominal pain, ascites, and hepatomegaly or more chronic symptoms related to long-standing portal hypertension. BCS is defined as primary when the obstructive process involves an endoluminal venous thrombosis. BCS is considered as a secondary process when the veins are compressed or invaded by a neighboring lesion originating outside the vein.
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A thorough evaluation demonstrates one or more thrombotic risk factors in approximately 75% to 90% of patients with primary BCS.44 Primary myeloproliferative disorders, such as essential thrombocythemia or polycythemia rubra, account for approximately 35% to 50% of the primary cases of BCS. All known inherited thrombophilias also have been implicated in the development of BCS. Activated protein C resistance, generally related to factor V Leiden mutation, is present in approximately 25% of patients. Anticardiolipin antibodies, hyperhomocysteinemia, and oral contraceptive use all have been shown to be risk factors for BCS.44
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Clinically significant BCS is usually the result of obstruction of two or more of the major hepatic veins. The obstruction results in hepatomegaly, liver congestion, and right upper quadrant pain. In addition, liver perfusion via the portal vein may be decreased, and 70% of affected patients have noninflammatory centrilobular necrosis on biopsy. Although ALF is rare, most patients will go on to develop chronic portal hypertension and ascites. Caudate lobe hypertrophy occurs in approximately 50% of cases and is due to the fact that the caudate lobe has direct venous drainage into the IVC. This caudate lobe hypertrophy, in turn, can result in further obstruction of the IVC.
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Abdominal ultrasonography is the initial investigation of choice and can demonstrate the absence of hepatic vein flow, spider web hepatic veins, and collateral hepatic veins.45 CT or MRI of the abdomen also is capable of demonstrating hepatic vein thrombosis and evaluating the IVC but is limited in that it cannot show direction of blood flow. The definitive radiographic study to evaluate BCS is hepatic venography to determine the presence and extent of hepatic vein thrombus as well as measure IVC pressures.
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Initial treatment consists of diagnosing and medically managing the underlying disease process and preventing extension of the hepatic vein thrombosis through systemic anticoagulation. The BCS-associated portal hypertension and ascites can be medically managed in a manner similar to that in most cirrhotic patients. Radiologic and surgical intervention should be reserved for patients whose condition is nonresponsive to medical therapy. Percutaneous angioplasty and TIPS, in combination with thrombolytic therapy, are the preferred strategies to restore the outflow of blood from the liver. Thrombolytic therapy alone may be attempted for acute thrombosis. Surgical shunting, namely with the side-to-side portacaval shunt, essentially turns the portal vein into a hepatic outflow tract. Most patients with a portacaval shunt show improvement in hepatic function and fibrosis at 1 year without significant hepatic encephalopathy.45 However, the enthusiasm for this procedure has been curbed due to the relatively high rate of operative mortality and shunt dysfunction. Patients with progressive BCS and manifestations of ESLD will ultimately require hepatic transplantation.