Porth's Essentials of Pathophysiology, 4e

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Disorders of Hepatobiliary and Exocrine Pancreas Function

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or sofosbuvir plus ribavirin. 19 Treatment for HCV is 70% to 80% effective, but is costly and has side effects. These side effects range from flulike symptoms, which are almost universal, to more serious and less common side effects, such as psychiatric symptoms (depression, anxiety), thyroid dysfunction, and bone marrow sup- pression. Although most persons with HCV infection are candidates for treatment, many have other health problems that are contraindications to therapy. Liver transplantation is a treatment option for those with advanced decompensated cirrhosis from viral hepa- titis. Liver transplantation, however, is not a cure for viral hepatitis, as it often reoccurs in the transplanted liver. Autoimmune Hepatitis Autoimmune hepatitis is a chronic and progressive form of hepatitis of unknown origin that is associated with high levels of serum immunoglobulins, including auto- antibodies. 3,4,20 Although the disorder is usually seen in young women, it can occur in either sex at any age. Clinical and laboratory observations have led to the hypothesis that autoimmune hepatitis is a multifactorial disorder, with genetic and environmental factors playing important roles. Most knowledge about the genetics of the disease has focused on the human leukocyte antigen (HLA) genes that reside in the major histocompatibil- ity complex (MHC), located on the short arm of chro- mosome 6 (see Chapter 15). The environmental agents assumed to induce autoimmune hepatitis are viruses, immunizations, herbal products such as black cohash, and medications such as minocycline, methyldopa, ator- vastatin, simvastatin, interferons, and nitrofurantoin. 3,20 Autoantibodies, in particular antinuclear antibody and anti–smooth muscle antibody, have been found in serum of those with autoimmune hepatitis, although the exact function of these antibodies in this condition is unknown. Two distinct types of autoimmune hepatitis have been broadly identified based on the presence of circu- lating antibodies. 2,4,20 Type I autoimmune hepatitis, the most common form of the disease, is characterized by increased levels of anti–smooth muscle and antinuclear autoantibodies. Approximately 30% of cases occur in women younger than 40 years of age, a third of whom have other autoimmune diseases. 4 Type II autoimmune hepatitis, a rare disorder, occurs mainly in children 2 to 14 years of age and is characterized by the presence of antibody to liver and kidney microsomes and liver cytosol. 4 The disorder is often accompanied by other autoimmune disorders, especially type 1 diabetes mel- litus and thyroiditis. The genetic component for this type of autoimmune hepatitis is less well defined than for type 1. Clinical manifestations of the disorder cover a spec- trum that extends from no apparent symptoms to the signs of liver failure. Physical examination may reveal no abnormalities, but may also reveal hepatomegaly, sple- nomegaly, jaundice, and signs and symptoms of chronic liver disease. In asymptomatic cases, the disorder may be discovered when abnormal serum enzyme levels are identified during performance of routine screening tests.

Acute hepatitis D occurs in two forms: coinfection that occurs simultaneously with acute hepatitis B, and a superinfection in which hepatitis D is imposed on chronic hepatitis B. 3,16 The delta agent often increases the severity of HBV infection. The routes of transmission of hepatitis D are similar to those for hepatitis B. In the United States, infection is restricted largely to persons at high risk for HBV infec- tion, particularly injecting drug users. The greatest risk is in HBV carriers; these persons should be informed about the dangers of HDV superinfection. Hepatitis D is diagnosed by detection of antibody to HDV (anti- HDV) in the serum or HDV RNA in the serum. There is no specific treatment for hepatitis D. Because the infec- tion is linked to hepatitis B, prevention of hepatitis D should begin with prevention of hepatitis B through vaccination. The hepatitis E virus is an enveloped, single-stranded RNA virus. It is transmitted by the fecal–oral route and causes manifestations of acute hepatitis that are similar to hepatitis A. It does not cause chronic hepatitis or the carrier state. 3 A distinguishing feature of HEV infection is the high mortality rate (approximately 20%) among pregnant women, owing to the development of fulmi- nant hepatitis. The infection occurs primarily in devel- oping coutries of the world. The only reported cases in the United States have been in persons who have recently been in an endemic area. Chronic Viral Hepatitis. Chronic hepatitis is defined as a chronic inflammatory reaction of the liver, or posi- tive viral serologies of more than 6 months’ duration. Chronic viral hepatitis is the principal cause of chronic liver disease, cirrhosis, and hepatocellular cancer in the world and now ranks as the chief reason for liver trans- plantation in adults. 17 Of the hepatotropic viruses, only three are known to cause chronic hepatitis—HBV/ HDV and HCV. In both HBV and HCV, fibrosis and clini- cal manifestations of chronic disease result from host immune responses directed against viral antigens. In response to these viral antigens, the host immune system directs cytoxic T lymphocytes and cytokines to inhibit viral replication (Chapter 15), the effects of which induce inflammation and liver injury. There are several treatment options for chronic viral hepatitis. Drugs used in the treatment of chronic hepati- tis B include the recombinant human interferon-2 α and peginterferon or nucleotide analog antiretroviral agent. Persons with active viral replication may be treated with recombinant human interferon-2 α and peginterferon. Peginterferons were developed by adding a polyeth- ylene glycol (PEG) moiety to an interferon molecule (PEG-IFN), resulting in a prolonged serum half-life and the ability to administer the compound once weekly. Nucleoside and nucleotide analogs (e.g., entecavir, tenofovir) have shown good efficacy and better toler- ance and may be used instead of interferon for treat- ment of chronic HBV infection. 18 The current treatment for persons with chronic hepatitis C is a combination of peginterferon (alfa-2b or alfa-2a) plus ribavirin (a nucle- oside analog), plus sofosbuvir (a polymerase inhibitor)