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Pediatric Liver Disease

Key Points 1 The liver is physiologically immature during the perinatal period, and significant maturational changes in hepatic metabolic processes occur in early life. These metabolic processes affect the presentation of and reaction to viral and toxin exposures. 2 Inherited and metabolic liver diseases commonly present in infants and young children; the etiologies of liver disease in adolescents are more similar to those in adults (…

The Liver in Systemic Disease

Key Points 1 Abnormal liver biochemical test levels are associated with many different systemic diseases. These abnormalities are generally incidental, but in some systemic diseases the liver may be severely compromised ( Table 24.1 ). TABLE 24.1 The Liver in Systemic Disease Disorder(s) Hepatic Manifestations Liver Biochemical Test Levels (Most Common Abnormalities) Cardiovascular Heart failure Vascular congestion; hepatomegaly ↑Bili; ↑ALT; ↑PT Ischemic (hypoxic) hepatitis Hepatocellular necrosis…

The Liver in Pregnancy

Key Points 1 Liver diseases in pregnancy include those that occur exclusively in pregnancy and those that occur coincidentally in pregnancy or are present at the time of pregnancy. 2 Normal physiologic changes in pregnancy may alter the normal range for liver biochemical tests ( Table 23.1 ). TABLE 23.1 Changes in Liver Biochemical Test Levels in Normal Pregnancy From Olans LB, Wolf JL. Liver disease…

The Liver in Heart Failure

Key Points 1 Liver involvement (cardiac hepatopathy) in either forward or backward heart failure is frequent, the extent of which depends on the severity of the heart failure. 2 Backward heart failure causes congestion of the liver with hepatomegaly with or without ascites and nonspecific liver biochemical test abnormalities. 3 Forward heart failure causes hypoxic damage to the liver if the circulatory failure is acute, severe,…

Budd-Chiari Syndrome and Other Vascular Disorders

Key Points 1 Hepatic vein occlusion, or Budd-Chiari syndrome (BCS), is an uncommon disorder characterized by hepatomegaly, ascites, and abdominal pain. The disorder most often occurs in patients with an underlying thrombotic diathesis including polycythemia vera, factor V Leiden mutation, protein C deficiency, antithrombin deficiency, paroxysmal nocturnal hemoglobinuria, tumors, and chronic inflammatory diseases. 2 The diagnosis is confirmed by visualization of thrombus or absent flow in…

Alpha-1 Antitrypsin Deficiency and Other Metabolic Liver Diseases

Key Points 1 Alpha-1 antitrypsin deficiency (α-1 ATD) is the most common metabolic liver disease in childhood. The diagnosis should be considered in all adults and children with chronic hepatitis or cirrhosis of unknown origin. α-1 ATD is associated with chronic liver disease in 10% of affected adults and in 10% to 15% of affected children. 2 Hereditary tyrosinemia is characterized by progressive liver failure, renal…

Wilson Disease and Related Disorders

Key Points 1 Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by disease-specific defects in the ATP7B gene that encodes a copper-transporting P-type adenosine triphosphatase (ATPase) expressed primarily in the trans-Golgi network of hepatocytes. 2 Loss of ATP7B function is responsible for defective biliary excretion of copper by liver cells that leads to pathologic accumulation of hepatic copper and secondary organ injury…

Hemochromatosis

Key Points 1 Hereditary hemochromatosis (HH) is an inherited disorder characterized by iron-mediated tissue injury reflecting impaired regulation of intestinal iron absorption. 2 Classic HH is most commonly associated with autosomal recessive inheritance of mutations in the HFE gene that create unregulated intestinal iron absorption. 3 Mutations in other genes such as hemojuvelin, hepcidin, transferrin receptor 2, and ferroportin are rare causes of HH. 4 Although…

Primary Sclerosing Cholangitis

Key Points 1 Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that frequently occurs in association with inflammatory bowel disease (IBD), usually ulcerative colitis. 2 The diagnosis of PSC is based on clinical, biochemical, and, most importantly, cholangiographic findings in the absence of secondary causes of sclerosing cholangitis. 3 The etiology of PSC remains unknown, but both genetic and environmental factors are involved and evidence…

Primary Biliary Cholangitis

Key Points 1 Primary biliary cholangitis (PBC, formerly known as primary biliary cirrhosis) is a chronic cholestatic liver disease that typically affects middle-aged women. Its pathogenesis includes a combination of environmental and genetic factors. 2 Genetic studies suggest that the human leukocyte antigen (HLA) and type 1 helper T-cell (Th1)/interleukin-12 signaling axis are particularly relevant biologically in the origin of this autoimmune small-duct lymphocytic cholangitis. 3…

Hepatic Encephalopathy

Key Points 1 Hepatic encephalopathy (HE) occurs only in the setting of significant liver disease. Any neuropsychiatric symptom or sign in a patient with severe liver dysfunction should be considered HE until proven otherwise. 2 HE may be covert or overt. 3 HE associated with acute liver failure is uncommon; its clinical course and treatment are distinct from those of encephalopathy complicating chronic liver disease. 4…

Hepatorenal Syndrome

Key Points 1 The term hepatorenal syndrome (HRS) refers to kidney failure in patients with decompensated cirrhosis. 2 HRS is characterized by a rapid decline of kidney function and is associated with a poor prognosis and high resource utilization. 3 In 1996, the International Ascites Club proposed the first diagnostic criteria to define HRS, and with time these criteria have evolved to incorporate an updated definition…

Ascites and Spontaneous Bacterial Peritonitis

Key Points 1 Cirrhosis accounts for 85% of the cases of ascites in the United States; the development of ascites is associated with a 50% 2-year survival rate. 2 Abdominal paracentesis with ascitic fluid analysis is a safe and cost-effective strategy in the differential diagnosis of ascites. Routine ascitic fluid tests include cell count, inoculation of fluid into blood culture bottles, albumin, and total protein, with…

Portal Hypertension and Gastrointestinal Bleeding

Key Points 1 Patients with cirrhosis with clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] >10 mm Hg) develop esophageal varices at a rate of 8% per year. This threshold is also required for development of other complications of portal hypertension, such as ascites. 2 Patients with cirrhosis in whom esophageal varices develop have a risk of a variceal hemorrhage of 5% to 15% per…

Cirrhosis and Portal Hypertension

Key Points 1 The major causes of cirrhosis include chronic hepatitis B, chronic hepatitis C, alcoholic liver disease, nonalcoholic steatohepatitis (NASH), and hemochromatosis. 2 Etiologic classification of cirrhosis is more clinically relevant than morphologic classification (micronodular, macronodular, mixed), because morphologic appearance is relatively nonspecific with regard to etiology, and important management and treatment decisions are best addressed once the cause of cirrhosis has been determined. 3…

Drug-Induced and Toxic Liver Disease

Key Points 1 The 10 most frequent causes of acute drug-induced liver injury (DILI) in the prospective Drug-Induced Liver Injury Network (DILIN) are amoxicillin-clavulanic acid (amox-clav), isoniazid (INH), nitrofurantoin, sulfamethoxazole-trimethoprim (SMX-TMP), minocycline, cefazolin, azithromycin, ciprofloxacin, levofloxacin, and diclofenac. These 10 drugs represent more than one third of the 190 agents reported to DILIN. 2 Although a rare event, acute DILI remains the most frequent overall cause…

Fatty Liver and Nonalcoholic Steatohepatitis

Key Points 1 Hepatic steatosis, the accumulation of triglyceride droplets in hepatocytes, is found in one third to one half of all adults in the United States and is an important cause of elevated serum aminotransferase levels (typically <250 U/L). 2 Steatosis without significant inflammation or fibrosis on biopsy is a benign hepatic condition, although it is associated with insulin resistance and indicates an increased risk…

Alcoholic Liver Disease

Key Points 1 Alcoholic liver disease (ALD) remains one of the most prevalent forms of liver disease in the United States. Worldwide, numerous epidemiologic studies have confirmed a correlation between per capita alcohol consumption and liver-related deaths. 2 The risk of hepatotoxicity increases if a threshold level of alcohol consumption is exceeded; however, even consistently high consumption infrequently causes cirrhosis. Variables influencing the progression of chronic…

Autoimmune Hepatitis

Key Points 1 Criteria for the diagnosis of autoimmune hepatitis have been codified with development of two diagnostic scoring systems that can support clinical judgment in the diagnosis of difficult cases. 2 Presentations range from acute severe (fulminant) to asymptomatic and mild. 3 Genetic factors within ( DRB1∗0301 , DRB1∗0401 , DRB1∗1301 , DQB1∗0201 , DRB1∗07 ) and outside (diverse polymorphisms) the major histocompatibility complex (MHC)…

Hepatitis Caused by Other Viruses

Key Points 1 Systemic viral infections can cause liver injury that ranges from mild asymptomatic and transient elevation of serum aminotransferase levels to acute icteric hepatitis or rarely severe hepatitis with acute liver failure (ALF). 2 The clinical presentation may be indistinguishable from liver injury caused by the principal hepatotropic viruses. 3 Mild liver enzyme elevations are a common feature of many systemic viral infections and…