Quick Facts
In full:
Harvey James Alter
Born:
September 12, 1935, New York, New York (age 89)
Awards And Honors:
Nobel Prize (2020)
Subjects Of Study:
hepatitis C virus

Harvey J. Alter (born September 12, 1935, New York, New York) is an American physician and virologist known for his discoveries pertaining to viruses that cause hepatitis, particularly his contributions to the discovery and isolation of hepatitis C virus (HCV). His research laid the basis for the development of blood donor screening programs to prevent the transmission of hepatitis via blood transfusion. For his discovery of HCV, he was awarded the 2020 Nobel Prize in Physiology or Medicine, shared with British-born virologist Michael Houghton and American virologist Charles M. Rice.

Alter was born to Jewish parents and was raised in New York City. He earned a bachelor’s degree (1956) and a medical degree (1960) from the University of Rochester. He remained there at Strong Memorial Hospital as a resident before transferring to Bethesda, Maryland, to work in the Clinical Center at the National Institutes of Health (NIH). Following a yearlong residency (1964–65) at the University of Washington in Seattle, Alter worked as a fellow in hematology (1965–66) at Georgetown University Hospital in Washington, D.C. He subsequently served as director of hematology research (1966–69) at Georgetown. In 1969 Alter returned to the NIH, joining the Department of Transfusion Medicine as a senior investigator, a position he held for the remainder of his career. In 1972 he became chief of the infectious diseases section and in 1987 associate director for research at the NIH Clinical Center, posts that he also maintained for the duration of his career.

Alter’s first major breakthrough came in the early 1960s while working at NIH, when he and American research physician Baruch S. Blumberg discovered the so-called Australia antigen. The researchers observed the antigen in the blood from an Australian aborigine and detected it in about 11 percent of American leukemia patients and in only a very small percentage of healthy Americans. The protein was subsequently identified as a surface antigen of hepatitis B virus (HBV). Alter helped develop an assay to detect the antigen, named HBsAg, in donor blood. The later development of a highly sensitive method of HBsAg detection in donor blood led to a dramatic decrease in transfusion-associated hepatitis (TAH).

In 1970s Alter and colleagues, during investigations of patients who developed TAH found that some patients were not positive for antigens to HBV, hepatitis A virus (HAV), or other viruses associated with the condition. Further studies, in which chimpanzees inoculated with non-A, non-B human plasma or serum developed hepatitis, led the researchers to conclude that a third transmissible agent was capable of causing TAH. In the mid-1980s Alter urged blood banks to test donor blood for hepatitis B core antibody (anti-HBc), which served as a surrogate marker for non-A, non-B hepatitis virus. Subsequent introduction of anti-HBc testing was associated with a further decline in TAH incidence to about 4 percent.

In 1989 Houghton and colleagues reported the isolation of a complementary DNA clone derived from the RNA genome of the non-A, non-B hepatitis agent. Later that year Alter and Houghton jointly reported the detection of HCV in transfusion patients who developed non-A, non-B hepatitis. In 1990 an assay for anti-HCV testing of donor blood was introduced, further reducing TAH incidence to just 1 percent. The later development of more sensitive assays led to the near elimination of TAH.

In addition to receiving the Nobel Prize, Alter received the Albert Lasker Award for Clinical Medical Research (2000; shared with Houghton) and the Canada Gairdner International Award (2013; shared with American virologist Daniel W. Bradley). Alter was an elected member of the U.S. National Academy of Sciences (2002) and the National Academy of Medicine (2002).

Kara Rogers

hepatitis C, infectious disease of the liver, the causative agent of which is known as hepatitis C virus (HCV). About 71 million people worldwide have chronic HCV infection, making hepatitis C a major source of chronic liver disease. The burden of HCV infection varies depending on country and population. In Egypt, for example, roughly 10–15 percent of people between ages 15 and 59 are chronically infected with HCV. In Sweden, by contrast, the prevalence is about 0.5 percent. HCV prevalence is especially high among intravenous drug users.

The discovery and isolation of HCV in the late 1980s and the subsequent development of blood screening assays and therapies for chronic HCV infection were the basis of the 2020 Nobel Prize in Physiology or Medicine. The prize was shared by American virologists Harvey J. Alter and Charles M. Rice and British-born scientist Michael Houghton.

Transmission of HCV

Transmission of HCV is largely through direct contact with human blood. Routes of transmission include the reuse of unsterilized needles (e.g., needle sharing among intravenous drug users), syringes, or other medical equipment; transfusion with blood that was not screened for HCV; or transplantation of solid organs infected with HCV. HCV can be transmitted through sexual contact or perinatally (during childbirth). Infrequent modes of transmission include ear or body piercing, acupuncture, and tattooing, which can occur when inadequately sterilized equipment is used. HCV is not spread via casual contact (e.g., kissing), breast-feeding, or contaminated foods or water.

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Symptoms of HCV infection

About 70 to 80 percent of individuals who contract HCV show no symptoms of acute hepatitis. When present, symptoms of acute illness may include fever, malaise, nausea, jaundice, arthralgia (joint pain), dark urine, pale stools, and abdominal pain. Acute symptoms typically subside within several weeks. In very rare instances, primarily when another chronic liver disease (e.g., hepatitis B) is present, acute illness culminates in fulminant (sudden) hepatic failure.

In roughly 70 to 90 percent of persons infected with HCV, the virus persists in the liver following the acute phase of infection. In the majority of cases, chronic infection is asymptomatic for decades. The infection may be noticed only after routine blood tests reveal elevated levels of liver enzymes, by which time liver function has begun to decline. Symptomatic patients may experience fatigue, nausea, anorexia, myalgia (muscle pain), arthralgia, weakness, and weight loss. Complications arising from chronic HCV infection include cirrhosis (scarring or fibrosis of the liver), liver failure, and liver cancer.

Chronic HCV infection is also associated with cryoglobulinemia, the accumulation of abnormal antibodies that are made in response to certain diseases or infections. The antibodies can aggregate and deposit in small blood vessels and cause vasculitis (blood vessel inflammation). Symptoms of cryoglobulinemia include joint pain and swelling, a purple skin rash, swelling of the legs, and nerve pain. Abnormal blood flow resulting from cryoglobulinemia may lead to Raynaud phenomenon, in which small blood vessels in the fingers and toes spasm in response to cold temperatures.

Diagnosis and treatment of HCV infection

Hepatitis C is rarely diagnosed at the time of infection, since few individuals are symptomatic. Asymptomatic cases may be detected, however, through recommended screening in high-risk populations, such as intravenous drug users and recipients of blood transfusions or organ transplants in which the tissues were not initially tested for HCV. Diagnostic testing and screening for hepatitis C centres on the detection of circulating antibodies and RNA specific to HCV. HCV RNA is detectable within 1 to 3 weeks of infection, and the antibodies are usually detectable within 8 to 12 weeks.

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Treatment of hepatitis C is focused on the elimination of viral infection, improvement of liver function, and the prevention of cirrhosis and liver cancer. Liver function may be improved with the use of interferon, which reduces HCV replication and stimulates the immune system to fight HCV infection. Interferon is often given in combination with ribavirin, an antiviral drug that mimics nucleosides (the building blocks of DNA and RNA) and thereby interferes with viral reproduction. Ribavirin may also be used in combination with agents known as sofosbuvir and velpatasvir, which inhibit key molecules involved in HCV RNA replication. Treatment of end-stage or advanced liver disease and cirrhosis caused by HCV infection is also possible with liver transplantation, though recurrence of detectable HCV infection is almost universal after transplantation.

Because of the high global incidence of HCV, many transplanted organs carry the virus, placing at risk of the disease even previously uninfected individuals in need of an organ transplant. In many instances, however, antiviral drugs can effectively block or cure HCV infection that originates from a transplanted infected organ, enabling recipients to lead healthy, productive lives following transplantation.

Preventive measures for HCV infection

Treatment options for hepatitis C are expensive, noncurative, and out of reach for the majority of people living in less-developed countries. Hence, prevention of infection remains an important public health goal.

HCV has a high mutation rate and multiple genotypes, which have challenged the development of an HCV vaccine. As a result, the primary means of prevention include infection-control practices in health care settings (e.g., sterilization of equipment), the screening and testing of blood and organ donors, and viral inactivation in plasma-derived products. The development in the 1990s of highly effective assays to screen for HCV in donor blood greatly reduced the transmission of the virus in health care settings.

Risk-reduction counseling may help prevent the transmission of HCV among individuals who inject drugs.

Christine Curry The Editors of Encyclopaedia Britannica