The clinical course of patients with advanced cirrhosis is often complicated by a number of important sequelae that can occur regardless of the underlying cause of the liver disease. These include portal hypertension and its consequences of gastroesophageal variceal hemorrhage, splenomegaly, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, and hepatocellular carcinoma (Table 308-2).
Portal hypertension is defined as the elevation of the hepatic venous pressure gradient (HVPG) to >5 mmHg. Portal hypertension is caused by a combination of two simultaneously occurring hemodynamic processes: (1) increased intrahepatic resistance to the passage of blood flow through the liver due to cirrhosis and regenerative nodules, and (2) increased splanchnic blood flow secondary to vasodilation within the splanchnic vascular bed. Portal hypertension is directly responsible for the two major complications of cirrhosis: variceal hemorrhage and ascites. Variceal hemorrhage is an immediate life-threatening problem with a 20–30% mortality rate associated with each episode of bleeding. The portal venous system normally drains blood from the stomach, intestines, spleen, pancreas, and gallbladder, and the portal vein is formed by the confluence of the superior mesenteric and splenic veins. Deoxygenated blood from the small bowel drains into the superior mesenteric vein along with blood from the head of the pancreas, the ascending colon, and part of the transverse colon. Conversely, the splenic vein drains the spleen and the pancreas and is joined by the inferior mesenteric vein, which brings blood from the transverse and descending colon as well as from the superior two-thirds of the rectum. Thus, the portal vein normally receives blood from almost the entire GI tract.
The causes of portal hypertension are usually subcategorized as prehepatic, intrahepatic, and posthepatic (Table 308-3). Prehepatic causes of portal hypertension are those affecting the portal venous system before it enters the liver; they include portal vein thrombosis and splenic vein thrombosis. Posthepatic causes encompass those affecting the hepatic veins and venous drainage to the heart; they include BCS, venoocclusive disease, and chronic right-sided cardiac congestion. Intrahepatic causes account for over 95% of cases of portal hypertension and are represented by the major forms of cirrhosis. Intrahepatic causes of portal hypertension can be further subdivided into presinusoidal, sinusoidal, and postsinusoidal causes. Postsinusoidal causes include venoocclusive disease, while presinusoidal causes include congenital hepatic fibrosis and schistosomiasis. Sinusoidal causes are related to cirrhosis from various causes.
Table 308-3 Classification of Portal Hypertension |Favorite Table|Download (.pdf)
Table 308-3 Classification of Portal Hypertension
Portal vein thrombosis
Splenic vein thrombosis
Massive splenomegaly (Banti's syndrome)
Congenital hepatic fibrosis
Hepatic sinusoidal obstruction (venoocclusive syndrome)
Inferior vena caval webs
Severe congestive heart failure
Cirrhosis is the most common cause of portal hypertension in the United States, and clinically significant portal hypertension is present in >60% of patients with cirrhosis. Portal vein obstruction may be idiopathic or can occur in association with cirrhosis or with infection, pancreatitis, or abdominal trauma.
Coagulation disorders that can lead to the development of portal vein thrombosis include polycythemia vera; essential thrombocytosis; deficiencies in protein C, protein S, antithrombin 3, and factor V Leiden; and abnormalities in the gene-regulating prothrombin production. Some patients may have a subclinical myeloproliferative disorder.
The three primary complications of portal hypertension are gastroesophageal varices with hemorrhage, ascites, and hypersplenism. Thus, patients may present with upper GI bleeding, which, on endoscopy, is found to be due to esophageal or gastric varices, with the development of ascites along with peripheral edema, or with an enlarged spleen with associated reduction in platelets and white blood cells on routine laboratory testing.
Over the last decade, it has become common practice to screen known cirrhotics with endoscopy to look for esophageal varices. Such screening studies have shown that approximately one-third of patients with histologically confirmed cirrhosis have varices. Approximately 5–15% of cirrhotics per year develop varices, and it is estimated that the majority of patients with cirrhosis will develop varices over their lifetimes. Furthermore, it is anticipated that roughly one-third of patients with varices will develop bleeding. Several factors predict the risk of bleeding, including the severity of cirrhosis (Child's class, MELD score); the height of wedged-hepatic vein pressure; the size of the varix; the location of the varix; and certain endoscopic stigmata, including red wale signs, hematocystic spots, diffuse erythema, bluish color, cherry red spots, or white-nipple spots. Patients with tense ascites are also at increased risk for bleeding from varices.
In patients with cirrhosis who are being followed chronically, the development of portal hypertension is usually revealed by the presence of thrombocytopenia; the appearance of an enlarged spleen; or the development of ascites, encephalopathy, and/or esophageal varices with or without bleeding. In previously undiagnosed patients, any of these features should prompt further evaluation to determine the presence of portal hypertension and liver disease. Varices should be identified by endoscopy. Abdominal imaging, either by CT or MRI, can be helpful in demonstrating a nodular liver and in finding changes of portal hypertension with intraabdominal collateral circulation. If necessary, interventional radiologic procedures can be performed to determine wedged and free hepatic vein pressures that will allow for the calculation of a wedged-to-free gradient, which is equivalent to the portal pressure. The average normal wedged-to-free gradient is 5 mmHg, and patients with a gradient >12 mmHg are at risk for variceal hemorrhage.
Treatment: Variceal Hemorrhage
Treatment for variceal hemorrhage as a complication of portal hypertension is divided into two main categories: (1) primary prophylaxis and (2) prevention of re-bleeding once there has been an initial variceal hemorrhage. Primary prophylaxis requires routine screening by endoscopy of all patients with cirrhosis. Once varices that are at increased risk for bleeding are identified, primary prophylaxis can be achieved either through nonselective beta blockade or by variceal band ligation. Numerous placebo-controlled clinical trials of either propranolol or nadolol have been reported in the literature. The most rigorous studies were those that only included patients with significantly enlarged varices or with hepatic vein pressure gradients >12 mmHg. Patients treated with beta blockers have a lower risk of variceal hemorrhage than those treated with placebo over 1 and 2 years of follow-up. There is also a decrease in mortality related to variceal hemorrhage. Unfortunately, overall survival was improved in only one study. Further studies have demonstrated that the degree of reduction of portal pressure is a significant feature to determine success of therapy. Therefore, it has been suggested that repeat measurements of hepatic vein pressure gradients may be used to guide pharmacologic therapy; however, this may be cost-prohibitive. Several studies have evaluated variceal band ligation and variceal sclerotherapy as methods for providing primary prophylaxis.
Endoscopic variceal ligation (EVL) has achieved a level of success and comfort with most gastroenterologists who see patients with these complications of portal hypertension. Thus, in patients with cirrhosis who are screened for portal hypertension and are found to have large varices, it is recommended that they receive either beta blockade or primary prophylaxis with EVL.
The approach to patients once they have had a variceal bleed is first to treat the acute bleed, which can be life-threatening, and then to prevent further bleeding. Prevention of further bleeding is usually accomplished with repeated variceal band ligation until varices are obliterated. Treatment of acute bleeding requires both fluid and blood-product replacement as well as prevention of subsequent bleeding with EVL.
The medical management of acute variceal hemorrhage includes the use of vasoconstricting agents, usually somatostatin or Octreotide. Vasopressin was used in the past but is no longer commonly used. Balloon tamponade (Sengstaken-Blakemore tube or Minnesota tube) can be used in patients who cannot get endoscopic therapy immediately or who need stabilization prior to endoscopic therapy. Control of bleeding can be achieved in the vast majority of cases; however, bleeding recurs in the majority of patients if definitive endoscopic therapy has not been instituted. Octreotide, a direct splanchnic vasoconstrictor, is given at dosages of 50–100 μg/h by continuous infusion. Endoscopic intervention is employed as first-line treatment to control bleeding acutely. Some endoscopists will use variceal injection therapy (sclerotherapy) as initial therapy, particularly when bleeding is vigorous. Variceal band ligation is used to control acute bleeding in over 90% of cases and should be repeated until obliteration of all varices is accomplished. When esophageal varices extend into the proximal stomach, band ligation is less successful. In these situations, when bleeding continues from gastric varices, consideration for transjugular intrahepatic portosystemic shunt (TIPS) should be made. This technique creates a portosystemic shunt by a percutaneous approach using an expandable metal stent, which is advanced under angiographic guidance to the hepatic veins and then through the substance of the liver to create a direct portocaval shunt. This offers an alternative to surgery for acute decompression of portal hypertension. Encephalopathy can occur in as many as 20% of patients after TIPS and is particularly problematic in elderly patients and in those patients with preexisting encephalopathy. TIPS should be reserved for those individuals who fail endoscopic or medical management or who are poor surgical risks. TIPS can sometimes be used as a bridge to transplantation. Surgical esophageal transsection is a procedure that is rarely used and generally is associated with a poor outcome.
Prevention of Recurrent Bleeding (Fig. 308-3)
Once patients have had an acute bleed and have been managed successfully, attention should be paid to preventing recurrent bleeding. This usually requires repeated variceal band ligation until varices are obliterated. Beta blockade may be of adjunctive benefit in patients who are having recurrent variceal band ligation; however, once varices have been obliterated, the need for beta blockade is lessened. Despite successful variceal obliteration, many patients will still have portal hypertensive gastropathy from which bleeding can occur. Nonselective beta blockade may be helpful to prevent further bleeding from portal hypertensive gastropathy once varices have been obliterated.
Management of recurrent variceal hemorrhage. This algorithm describes an approach to management of patients who have recurrent bleeding from esophageal varices. Initial therapy is generally with endoscopic therapy often supplemented by pharmacologic therapy. With control of bleeding, a decision needs to be made as to whether patients should go on to a surgical shunt or TIPS (if they are Child's class A) and be considered for transplant, or if they should have TIPS and be considered for transplant (if they are Child's class B or C). TIPS, transjugular intrahepatic portosystemic shunt.
Portosystemic shunt surgery is less commonly performed with the advent of TIPS; nonetheless, this procedure should be considered for patients with good hepatic synthetic function who could benefit by having portal decompressive surgery.
Splenomegaly and Hypersplenism
Congestive splenomegaly is common in patients with portal hypertension. Clinical features include the presence of an enlarged spleen on physical examination and the development of thrombocytopenia and leukopenia in patients who have cirrhosis. Some patients will have fairly significant left-sided and left upper quadrant abdominal pain related to an enlarged and engorged spleen. Splenomegaly itself usually requires no specific treatment, although splenectomy can be successfully performed under very special circumstances.
Hypersplenism with the development of thrombocytopenia is a common feature of patients with cirrhosis and is usually the first indication of portal hypertension.
Ascites is the accumulation of fluid within the peritoneal cavity. Overwhelmingly, the most common cause of ascites is portal hypertension related to cirrhosis; however, clinicians should remember that malignant or infectious causes of ascites can be present as well, and careful differentiation of these other causes are obviously important for patient care.
The presence of portal hypertension contributes to the development of ascites in patients who have cirrhosis (Fig. 308-4). There is an increase in intrahepatic resistance, causing increased portal pressure, but there is also vasodilation of the splanchnic arterial system, which, in turn, results in an increase in portal venous inflow. Both of these abnormalities result in increased production of splanchnic lymph. Vasodilating factors such as nitric oxide are responsible for the vasodilatory effect. These hemodynamic changes result in sodium retention by causing activation of the renin-angiotensin-aldosterone system with the development of hyperaldosteronism. The renal effects of increased aldosterone leading to sodium retention also contribute to the development of ascites. Sodium retention causes fluid accumulation and expansion of the extracellular fluid volume, which results in the formation of peripheral edema and ascites. Sodium retention is the consequence of a homeostatic response caused by underfilling of the arterial circulation secondary to arterial vasodilation in the splanchnic vascular bed. Because the retained fluid is constantly leaking out of the intravascular compartment into the peritoneal cavity, the sensation of vascular filling is not achieved, and the process continues. Hypoalbuminemia and reduced plasma oncotic pressure also contribute to the loss of fluid from the vascular compartment into the peritoneal cavity. Hypoalbuminemia is due to decreased synthetic function in a cirrhotic liver.
Development of ascites in cirrhosis. This flow diagram illustrates the importance of portal hypertension with splanchnic vasodilation in the development of ascites. *Antinatriuretic factors include the renin-angiotensin-aldosterone system and the sympathetic nervous system.
Patients typically note an increase in abdominal girth that is often accompanied by the development of peripheral edema. The development of ascites is often insidious, and it is surprising that some patients wait so long and become so distended before seeking medical attention. Patients usually have at least 1–2 L of fluid in the abdomen before they are aware that there is an increase. If ascitic fluid is massive, respiratory function can be compromised, and patients will complain of shortness of breath. Hepatic hydrothorax may also occur in this setting, contributing to respiratory symptoms. Patients with massive ascites are often malnourished and have muscle wasting and excessive fatigue and weakness.
Diagnosis of ascites is by physical examination and is often aided by abdominal imaging. Patients will have bulging flanks, may have a fluid wave, or may have the presence of shifting dullness. This is determined by taking patients from a supine position to lying on either their left or right side and noting the movement of the dullness to percussion. Subtle amounts of ascites can be detected by ultrasound or CT scanning. Hepatic hydrothorax is more common on the right side and implicates a rent in the diaphragm with free flow of ascitic fluid into the thoracic cavity.
When patients present with ascites for the first time, it is recommended that a diagnostic paracentesis be performed to characterize the fluid. This should include the determination of total protein and albumin content, blood cell counts with differential, and cultures. In the appropriate setting, amylase may be measured and cytology performed. In patients with cirrhosis, the protein concentration of the ascitic fluid is quite low, with the majority of patients having an ascitic fluid protein concentration <1 g/dL. The development of the serum ascites-to-albumin gradient (SAAG) has replaced the description of exudative or transudative fluid. When the gradient between the serum albumin level and the ascitic fluid albumin level is >1.1 g/dL, the cause of the ascites is most likely due to portal hypertension; this is usually in the setting of cirrhosis. When the gradient is <1.1 g/dL, infectious or malignant causes of ascites should be considered. When levels of ascitic fluid proteins are very low, patients are at increased risk for developing SBP. A high level of red blood cells in the ascitic fluid signifies a traumatic tap or perhaps a hepatocellular cancer or a ruptured omental varix. When the absolute level of polymorphonuclear leukocytes is >250/μL, the question of ascitic fluid infection should be strongly considered. Ascitic fluid cultures should be obtained using bedside inoculation of culture media.
Patients with small amounts of ascites can usually be managed with dietary sodium restriction alone. Most average diets in the United States contain 6 to 8 g of sodium per day, and if patients eat at restaurants or fast-food outlets, the amount of sodium in their diet can exceed this amount. Thus, it is often extremely difficult to get patients to change their dietary habits to ingest <2 g of sodium per day, which is the recommended amount. Patients are frequently surprised to realize how much sodium is in the standard U.S. diet; thus, it is important to make educational pamphlets available to the patient. Often, a simple recommendation is to eat fresh or frozen foods, avoiding canned or processed foods, which are usually preserved with sodium. When a moderate amount of ascites is present, diuretic therapy is usually necessary. Traditionally, spironolactone at 100–200 mg/d as a single dose is started, and furosemide may be added at 40–80 mg/d, particularly in patients who have peripheral edema. In patients who have never received diuretics before, the failure of the above-mentioned dosages suggests that they are not being compliant with a low-sodium diet. If compliance is confirmed and ascitic fluid is not being mobilized, spironolactone can be increased to 400–600 mg/d and furosemide increased to 120–160 mg/d. If ascites is still present with these dosages of diuretics in patients who are compliant with a low-sodium diet, then they are defined as having refractory ascites, and alternative treatment modalities including repeated large-volume paracentesis, or a TIPS procedure should be considered (Fig. 308-5). Recent studies have shown that TIPS, while managing the ascites, does not improve survival in these patients. Unfortunately, TIPS is often associated with an increased frequency of hepatic encephalopathy and must be considered carefully on a case-by-case basis. The prognosis for patients with cirrhosis with ascites is poor, and some studies have shown that <50% of patients survive 2 years after the onset of ascites. Thus, there should be consideration for liver transplantation in patients with the onset of ascites.
Treatment of refractory ascites. In patients who develop azotemia in the course of receiving diuretics in the management of their ascites, some will require repeated large-volume paracentesis (LVP), some may be considered for transjugular intrahepatic portosystemic shunt (TIPS), and some would be good candidates for liver transplantation. These decisions are all individualized.
Spontaneous Bacterial Peritonitis
SBP is a common and severe complication of ascites characterized by spontaneous infection of the ascitic fluid without an intraabdominal source. In patients with cirrhosis and ascites severe enough for hospitalization, SBP can occur in up to 30% of individuals and can have a 25% in-hospital mortality rate. Bacterial translocation is the presumed mechanism for development of SBP, with gut flora traversing the intestine into mesenteric lymph nodes, leading to bacteremia and seeding of the ascitic fluid. The most common organisms are Escherichia coli and other gut bacteria; however, gram-positive bacteria, including Streptococcus viridans, Staphylococcus aureus, and Enterococcus sp., can also be found. If more than two organisms are identified, secondary bacterial peritonitis due to a perforated viscus should be considered. The diagnosis of SBP is made when the fluid sample has an absolute neutrophil count >250/μL. Bedside cultures should be obtained when ascitic fluid is tapped. Patients with ascites may present with fever, altered mental status, elevated white blood cell count, and abdominal pain or discomfort, or they may present without any of these features. Therefore, it is necessary to have a high degree of clinical suspicion, and peritoneal taps are important for making the diagnosis. Treatment is with a second-generation cephalosporin, with cefotaxime being the most commonly used antibiotic. In patients with variceal hemorrhage, the frequency of SBP is significantly increased, and prophylaxis against SBP is recommended when a patient presents with upper GI bleeding. Furthermore, in patients who have had an episode(s) of SBP and recovered, once-weekly administration of antibiotics is used as prophylaxis for recurrent SBP.
The hepatorenal syndrome (HRS) is a form of functional renal failure without renal pathology that occurs in about 10% of patients with advanced cirrhosis or acute liver failure. There are marked disturbances in the arterial renal circulation in patients with HRS; these include an increase in vascular resistance accompanied by a reduction in systemic vascular resistance. The reason for renal vasoconstriction is most likely multifactorial and is poorly understood. The diagnosis is made usually in the presence of a large amount of ascites in patients who have a stepwise progressive increase in creatinine. Type 1 HRS is characterized by a progressive impairment in renal function and a significant reduction in creatinine clearance within 1–2 weeks of presentation. Type 2 HRS is characterized by a reduction in glomerular filtration rate with an elevation of serum creatinine level, but it is fairly stable and is associated with a better outcome than that of Type 1 HRS.
HRS is often seen in patients with refractory ascites and requires exclusion of other causes of acute renal failure. Treatment has, unfortunately, been difficult, and in the past, dopamine or prostaglandin analogues were used as renal vasodilating medications. Carefully performed studies have failed to show clear-cut benefit from these therapeutic approaches. Currently, patients are treated with midodrine, an α-agonist, along with octreotide and intravenous albumin. The best therapy for HRS is liver transplantation; recovery of renal function is typical in this setting. In patients with either type 1 or type 2 HRS, the prognosis is poor unless transplant can be achieved within a short period of time.
Portosystemic encephalopathy is a serious complication of chronic liver disease and is broadly defined as an alteration in mental status and cognitive function occurring in the presence of liver failure. In acute liver injury with fulminant hepatic failure, the development of encephalopathy is a requirement for a diagnosis of fulminant failure. Encephalopathy is much more commonly seen in patients with chronic liver disease. Gut-derived neurotoxins that are not removed by the liver because of vascular shunting and decreased hepatic mass get to the brain and cause the symptoms that we know of as hepatic encephalopathy. Ammonia levels are typically elevated in patients with hepatic encephalopathy, but the correlation between severity of liver disease and height of ammonia levels is often poor, and most hepatologists do not rely on ammonia levels to make a diagnosis. Other compounds and metabolites that may contribute to the development of encephalopathy include certain false neurotransmitters and mercaptans.
In acute liver failure, changes in mental status can occur within weeks to months. Brain edema can be seen in these patients, with severe encephalopathy associated with swelling of the gray matter. Cerebral herniation is a feared complication of brain edema in acute liver failure, and treatment is meant to decrease edema with mannitol and judicious use of intravenous fluids.
In patients with cirrhosis, encephalopathy is often found as a result of certain precipitating events such as hypokalemia, infection, an increased dietary protein load, or electrolyte disturbances. Patients may be confused or exhibit a change in personality. They may actually be quite violent and difficult to manage; alternatively, patients may be very sleepy and difficult to rouse. Because precipitating events are so commonly found, they should be sought carefully. If patients have ascites, this should be tapped to rule out infection. Evidence of GI bleeding should be sought, and patients should be appropriately hydrated. Electrolytes should be measured and abnormalities corrected. In patients presenting with encephalopathy, asterixis is often present. Asterixis can be elicited by having patients extend their arms and bend their wrists back. In this maneuver, patients who are encephalopathic have a “liver flap”—i.e., a sudden forward movement of the wrist. This requires patients to be able to cooperate with the examiner and obviously cannot be elicited in patients who are severely encephalopathic or in hepatic coma.
The diagnosis of hepatic encephalopathy is clinical and requires an experienced clinician to recognize and put together all of the various features. Often when patients have encephalopathy for the first time, they are unaware of what is transpiring, but once they have been through the experience for the first time, they can identify when this is developing in subsequent situations and can often self-medicate to impair the development or worsening of encephalopathy.
Treatment: Hepatic Encephalopathy
Treatment is multifactorial and includes management of the above-mentioned precipitating factors. Sometimes hydration and correction of electrolyte imbalance is all that is necessary. In the past, restriction of dietary protein was considered for patients with encephalopathy; however, the negative impact of that maneuver on overall nutrition is thought to outweigh the benefit when treating encephalopathy, and it is thus discouraged. There may be some benefit to replacing animal-based protein with vegetable-based protein in some patients with encephalopathy that is difficult to manage. The mainstay of treatment for encephalopathy, in addition to correcting precipitating factors, is to use lactulose, a nonabsorbable disaccharide, which results in colonic acidification. Catharsis ensues, contributing to the elimination of nitrogenous products in the gut that are responsible for the development of encephalopathy. The goal of lactulose therapy is to promote 2–3 soft stools per day. Patients are asked to titrate their amount of ingested lactulose to achieve the desired effect. Poorly absorbed antibiotics are often used as adjunctive therapies for patients who have had a difficult time with lactulose. The alternating administration of neomycin and metronidazole has commonly been employed to reduce the individual side effects of each: neomycin for renal insufficiency and ototoxicity and metronidazole for peripheral neuropathy. More recently, rifaximin at 550 mg twice daily has been very effective in treating encephalopathy without the known side effects of neomycin or metronidazole. Zinc supplementation is sometimes helpful in patients with encephalopathy and is relatively harmless. The development of encephalopathy in patients with chronic liver disease is a poor prognostic sign, but this complication can be managed in the vast majority of patients.
Malnutrition in Cirrhosis
Because the liver is principally involved in the regulation of protein and energy metabolism in the body, it is not surprising that patients with advanced liver disease are commonly malnourished. Once patients become cirrhotic, they are more catabolic, and muscle protein is metabolized. There are multiple factors that contribute to the malnutrition of cirrhosis, including poor dietary intake, alterations in gut nutrient absorption, and alterations in protein metabolism. Dietary supplementation for patients with cirrhosis is helpful in preventing patients from becoming catabolic.
Abnormalities in Coagulation
Coagulopathy is almost universal in patients with cirrhosis. There is decreased synthesis of clotting factors and impaired clearance of anticoagulants. In addition, patients may have thrombocytopenia from hypersplenism due to portal hypertension. Vitamin K–dependent clotting factors are Factors II, VII, IX, and X. Vitamin K requires biliary excretion for its subsequent absorption; thus, in patients with chronic cholestatic syndromes, vitamin K absorption is frequently diminished. Intravenous or intramuscular vitamin K can quickly correct this abnormality. More commonly, the synthesis of vitamin K–dependent clotting factors is diminished because of a decrease in hepatic mass, and, under these circumstances, administration of parenteral vitamin K does not improve the clotting factors or the prothrombin time. Platelet function is often abnormal in patients with chronic liver disease, in addition to decreases in platelet levels due to hypersplenism.
Bone Disease in Cirrhosis
Osteoporosis is common in patients with chronic cholestatic liver disease because of malabsorption of vitamin D and decreased calcium ingestion. The rate of bone resorption exceeds that of new bone formation in patients with cirrhosis resulting in bone loss. Dual x-ray absorptiometry (DEXA) is a useful method for determining osteoporosis or osteopenia in patients with chronic liver disease. When a DEXA scan shows decreased bone mass, treatment should be administered with bisphosphonates that are effective at inhibiting resorption of bone and efficacious in the treatment of osteoporosis.
Hematologic Abnormalities in Cirrhosis
Numerous hematologic manifestations of cirrhosis are present, including anemia from a variety of causes including hypersplenism, hemolysis, iron deficiency, and perhaps folate deficiency from malnutrition. Macrocytosis is a common abnormality in red blood cell morphology seen in patients with chronic liver disease, and neutropenia may be seen as a result of hypersplenism.