Hepatitis

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Chapter 171 Hepatitis

image General Considerations

Hepatitis refers to inflammation (-itis) of the liver (hepar-). Inflammation lasting less than 6 months is known as acute hepatitis, whereas that lasting longer than 6 months is called chronic hepatitis. In people with acute hepatitis who do not progress to chronic disease, all of the symptoms, signs, and blood test abnormalities return to normal without permanent or long-term sequelae. People who progress from acute to chronic hepatitis are at risk of progressing to cirrhosis and its complications, such as portal hypertension and hepatocellular carcinoma (HCC). Hepatitis is a term that encompasses many inflammatory causes, such as autoimmune liver disease, obesity, alcoholic liver disease, and some medications and herbs. Only hepatitis caused by a virus (viral hepatitis) is potentially infectious to others. This chapter focuses on viral hepatitis A, B, and C.

Hepatitis A is caused by a virus of the Picornaviridae family and is transmitted via the fecal–oral (enteric) route by person-to-person contact. Prior to its identification in 1973, hepatitis A was known as infectious hepatitis. It is the most common cause of acute viral hepatitis in the United States, with approximately one third of adults having evidence of prior exposure, as do almost all people living in areas of poor sanitation. Although infection with the hepatitis A virus (HAV) does not lead to chronic disease, it accounts for an estimated 100 deaths each year in the United States.

Hepatitis B is caused by a virus of the Hepadnaviridae family and is transmitted via the parenteral route through blood or blood products, through sexual contact, or from mother–child transmission during pregnancy and childbirth. Prior to its identification in 1963, it was known as serum hepatitis. Approximately 350 to 400 million people worldwide, including 1.25 million people in the United States, are chronically infected with the hepatitis B virus (HBV), defined through blood work as a positive hepatitis B surface antigen (HBsAg) and a positive hepatitis B core antibody (HBcAb). Chronic HBV infection is the most common cause of cirrhosis and liver cancer worldwide.1

Hepatitis C is caused by a virus of the Flaviviridae family and is transmitted via the percutaneous route through blood-to-blood contact. Intravenous drug users, anyone who received a blood or a blood-product transfusion prior to 1992, individuals born to a mother infected with the hepatitis C virus (HCV), and those who may be at increased risk for exposure to infected blood, such as health care or public safety workers, are at increased risk of infection. Unlike the case with HBV, sexual contact is an inefficient means of HCV transmission. Prior to its identification in 1989, it was known as non-A non-B hepatitis. An estimated 130 million people worldwide, 5 million of whom are in the United States, have been exposed to HCV, and approximately 350,000 to 500,000 people per year die of HCV-related liver disease.2,3

image Diagnostic Considerations

A diagnosis of hepatitis is made via a combination of a thorough history and physical examination, laboratory tests including serial liver function tests (aspartate aminotransferase [AST] and alanine aminotransferase [ALT], which are known together as transaminases), and hepatitis-specific serologies in addition to imaging studies. Because these evaluations typically do not accurately correlate with the extent of damage done to the liver, a liver biopsy is often necessary to determine the grade (degree of inflammation) and stage (degree of fibrosis) of the disease as well as the need for therapy.

Prevention

All people with chronic liver disease or chronic hepatitis of any etiology should receive immunizations for hepatitis A and B if they have not already been exposed to these viruses. The hepatitis A vaccination was first approved by the FDA in 1995. The development of the hepatitis B vaccine represents one of the most important advances in medicine. This is the first and only vaccine in history that can simultaneously prevent liver cancer, cirrhosis, and a sexually transmitted disease, hepatitis B. The FDA approved the hepatitis B vaccine in 1981, and the improved version has been available since 1986.

It is considered safe to administer the hepatitis B vaccine to pregnant women if needed. Infants born to HBsAg-positive mothers should receive both the hepatitis B vaccination and the hepatitis B immune globulin (HBIG) within 12 hours of birth. See Box 171-1 for a list of those at increased risk for hepatitis B and who therefore should receive the hepatitis B vaccination.

There is currently no vaccine available to prevent HCV. One of the major barriers to the development of this vaccine involves the complex HCV population of mutant strains, known as quasispecies, that can exist in a person infected with hepatitis C.

The hepatitis A virus can be killed by boiling infected foods for at least three minutes and by disinfecting surfaces with bleach. It is best to avoid eating raw or partially cooked mollusks (clams, oysters, mussels, and scallops), as these fish often live in HAV-contaminated rivers and seas. When traveling to areas of the world known to have a high incidence of hepatitis A, it is especially important to eat well-cooked foods and to drink only bottled water. Sanitizing diaper-changing tables is also important, as hepatitis A–infected infants are typically a silent source for the spread of hepatitis A infection. Meticulous handwashing is of great importance after using the bathroom, before eating a meal, and before preparing food for others.

The avoidance of unprotected sex will greatly reduce the likelihood of infection with HBV. Employing a barrier such as a condom, dental dam, female condom, and finger cot will decrease the risk of transmission and acquisition of HBV. Although the risk of sexual transmission of HCV is rare, protected sex is recommended if a person engages in anal sex, has multiple sex partners, has frequent prostate infections, has open cuts or sores on the genitalia, or is menstruating. People with hepatitis B or C should avoid sharing anything that may contain even the tiniest amount of their blood, including toothbrushes, razors, and nail clippers.

In order to further reduce the likelihood of spreading hepatitis B and C, people who are using injection drugs should never share needles with others or inject themselves with a used needle. A drop of blood so minuscule that it cannot be seen by the human eye may contain hundreds or even thousands of HBV and/or HCV particles. Even meticulous cleaning may not totally eradicate the virus from a needle. If a person needs unused needles but cannot obtain them, he or she should seek out a needle-exchange program. Alternatively, needle use can be limited to autodestruct syringes. These needles are not reusable. They are designed to self-destruct after one use so that they cannot be reused or shared with others. Of course the best advice for a person who continues to use illicit drugs is to discontinue this activity immediately and seek help at a drug rehabilitation center. Also, anyone who intends to get a tattoo or have a body part pierced should deal only with establishments that are clean and that adhere to meticulous sterilization practices.

image Therapeutic Considerations

Conventional Therapies

The goals of treatment of chronic hepatitis are to achieve sustained viral suppression or total elimination of the virus from the body; to slow or prevent progression to cirrhosis, hepatic decompensation, and HCC; and to prevent transmission to others. Chronic hepatitis B is not curable. Conventional treatment options for hepatitis B include either nucleoside/nucleotide analogues (NAs) or pegylated interferon. Interferons (IFNs) are a family of proteins made naturally by the body that have antiviral, antiproliferative, and immunomodulatory properties. IFN and pegylated IFN have been shown to be effective in reducing HBV replication and inducing disease remission. However, the efficacy of IFN is limited to a narrow population of HBV patients. In addition, its numerous side effects, difficult subcutaneous route of administration, cost, and associated high relapse rate after medication is discontinued have hampered its use for patients with chronic HBV. There are currently five FDA-approved NAs for the treatment of chronic HBV. NAs are quite effective for suppressing HBV replication, induction of disease remission, and the improvement of long-term outcomes. However, the length of time during which patients are treated is not predefined; and is determined by specific parameters that may differ from one patient to another, and treatment may be indefinite for some. Furthermore, long-term use of NAs can be complicated by the selection of antiviral-resistant mutations.

In contrast to hepatitis B, hepatitis C is a curable disease in many patients. This is referred to as a sustained virologic response rate (SVR) and ranges between approximately 20% to 90% (i.e., it is a measure of virus suppression). Length and success of HCV treatment are dependent upon a variety of factors (see Box 171-2). Pegylated interferon (PI) administered subcutaneously once a week, along with oral ribavirin (RBV) pills daily for 24 to 48 weeks, is the current standard of care (SOC) treatment for patients with chronic hepatitis C genotypes 2 and 3, and was the SOC for patients with genotype 1 (G1), the most common and most difficult to cure genotype worldwide. In May 2011, a major advance in the field of hepatology occurred. With the addition of a protease inhibitor, either telaprevir (Incivek, manufactured by Vertex) or boceprevir, (Victrelis, manufactured by Merck), to SOC treatment, SVRs jumped from approximately 42% to as high as 86% for many G1 patients. And, between 44% and 60% of treatment naïve G1 patients are now capable of being cured in just 24 to 28 weeks as opposed to 48 weeks. However, numerous adverse events (AEs), complex treatment regimens, exorbitant costs, and the potential for the development of drug-resistance, may decrease their therapeutic usefulness. This underscores the need for clinicians to be aware of the effects of natural and integrative therapies on the progression of HCV, and of the potential benefits of these therapies either with or without SOC treatment for chronic hepatitis C.

Several nutrients and herbs, discussed later, have been shown to inhibit viral reproduction, improve immune system function, and stimulate regeneration of the damaged liver cells.

Lifestyle Recommendations

Sleep

Experimental studies have demonstrated that sleep deprivation results in poorer immune function, such as reduced natural killer cell activity, suppressed interleukin-2 production, and increased levels of circulating proinflammatory cytokines.6,7 A recent study showed that survival was inversely associated with sleep disturbance among 156 patients with cirrhosis. The study’s authors suggested that tailored behavioral interventions might help to improve overall health-related quality of life and could potentially improve patient outcomes.8 Sleep problems have been reported in patients with chronic hepatitis C, with about 60% to 65% of individuals reporting such complaints. Subjects administered IFN-α demonstrated increased waking after sleep onset, decreased sleep efficiency, and reduced stage 3 and/or 4 sleep.9 Evidence also suggests that impairments in sleep quality exist independent of antiviral therapy with IFN-α and prior to the advanced stages of liver disease.10 Sleep deprivation has also been found to attenuate antibody response to hepatitis A immunization.11 In terms of sleep duration, individuals with less than 7 hours of regular sleep are approximately three times more likely to develop a cold when exposed to nasally introduced rhinovirus than those with 8 hours or more of sleep.12 It may therefore be prudent to encourage proper sleep habits and a duration of 8 hours or more in order to optimize immune and antiviral benefits in the hepatitis patient as well.

Exercise

The benefits of exercise for people with liver disease are numerous. Studies of patients with hepatitis C incorporating exercise as part of their therapy with SOC show that they can safely participate in an exercise program, create clear changes in the way they perceive their bodies and its capacities, as well as improve their self-confidence, all of which can lead to far-reaching changes in the way this disease and the constraints of treatment are perceived.13 Because fatigue is probably the most common as well as one of the most bothersome symptoms affecting people with chronic hepatitis, exercise can provide a boost of energy and also improve cardiovascular function. Exercise leads to a reduction in total body fat, which is important to all people with liver disease. When total body fat is reduced, the fat content of the liver is also reduced, often resulting in a significant reduction in elevated liver enzymes.13 Thus, it is recommended that all patients with chronic hepatitis incorporate an exercise program combining weight training and aerobics into their daily routine as tolerated once they have been medically cleared by their physicians.

Fruit and Hepatitis C

Blueberries have been found to inhibit the replication of HCV,14 and rats fed diets high in blueberries were protected from developing acute hepatitis.15 This effect may be due to the antioxidant properties of the flavonoid proanthocyanidin that is a component of blueberry leaves.

Naringenin, a flavanoid contained in grapefruit and other citrus fruits, has been found to have antiinflammatory, antioxidant, and lipid-lowering properties and may act as a promoter of carbohydrate metabolism. Naringenin has been found to lower very low density lipoprotein cholesterol. It is suspected that the hepatitis C virus may “hitch a ride” on cholesterol—a theory that has held up in test tube experiments. Studies have demonstrated that naringenin can inhibit or reduce steatosis, (the deposition of fat in the liver),16 in addition to inhibiting HCV viral replication.17 It is important to remember that grapefruit contains furanocoumarins and flavonoids, which can inhibit components of the cytochrome P450 drug metabolism pathway leading to toxic levels of many medications.18,19

Nutrient Therapeutics

Vitamins C and E

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