Linda A. Moyer

The Prevalence of Hepatitis C Virus Infection in the United States, 1988 through 1994

BACKGROUND Because many persons with chronic hepatitis C virus (HCV) infection are asymptomatic, population-based serologic studies are needed to estimate the prevalence of the infection and to develop and evaluate prevention efforts. METHODS We performed tests for antibody to HCV (anti-HCV) on serum samples from 21,241 persons six years old or older who participated in the third National Health and Nutrition Examination Survey, conducted during 1988 through 1994. We determined the prevalence of HCV RNA by means of nucleic acid amplification and the genotype by means of sequencing. RESULTS The overall prevalence of anti-HCV was 1.8 percent, corresponding to an estimated 3.9 million persons nationwide (95 percent confidence interval, 3.1 million to 4.8 million) with HCV infection. Sixty-five percent of the persons with HCV infection were 30 to 49 years old. Seventy-four percent were positive for HCV RNA, indicating that an estimated 2.7 million persons in the United States (95 percent confidence interval, 2.4 million to 3.0 million) were chronically infected, of whom 73.7 percent were infected with genotype 1 (56.7 percent with genotype 1a, and 17.0 percent with genotype 1b). Among subjects 17 to 59 years of age, the strongest factors independently associated with HCV infection were illegal drug use and high-risk sexual behavior. Other factors independently associated with infection included poverty, having had 12 or fewer years of education, and having been divorced or separated. Neither sex nor racial-ethnic group was independently associated with HCV infection. CONCLUSIONS In the United States, about 2.7 million persons are chronically infected with HCV. People who use illegal drugs or engage in high-risk sexual behavior account for most persons with HCV infection.

Acute non-A-E hepatitis in the United States and the role of hepatitis G virus infection

BACKGROUND Little is known about the relation of the newly discovered hepatitis G virus (HGV) to the cause and clinical course of acute and chronic viral hepatitis. METHODS We selected patients from a surveillance study of acute viral hepatitis in four U.S. counties who had acute disease during 1985 to 1986 or 1991 to 1995. Serum samples were tested for HGV RNA by the polymerase chain reaction. RESULTS HGV RNA was detected in 4 of 45 patients with a diagnosis of non-A-E hepatitis (9 percent), 23 of 116 patients with hepatitis C (20 percent), 25 of 100 patients with hepatitis A (25 percent), and 32 of 100 patients with hepatitis B (32 percent) (P<0.05 for the comparison of hepatitis B with hepatitis non-A-E or C). The clinical characteristics of the acute illness were similar for patients with HGV alone and those with hepatitis A, B, or C with or without HGV infection. During a follow-up period of one to nine years, chronic hepatitis did not develop in any of the patients with HGV alone, but 75 percent were persistently positive for HGV RNA, as were 87 percent of those with both hepatitis C and HGV infection. The rates of chronic hepatitis were similar in patients with hepatitis C alone (60 percent) and those with both hepatitis C and HGV infection (61 percent). CONCLUSIONS The evidence from this surveillance study does not implicate HGV as an etiologic agent of non-A-E hepatitis. Persistent infection with HGV was common, but it did not lead to chronic disease and did not affect the clinical course in patients with hepatitis A, B, or C.

Incidence and Risk Factors for Acute Hepatitis B in the United States, 1982–1998: Implications for Vaccination Programs

From 1982-1998, enhanced sentinel surveillance for acute hepatitis B was conducted in 4 counties in the United States to determine trends in disease incidence and risk factors for infection. During this period, the reported incidence of acute hepatitis B declined by 76.1% from 13.8 cases per 100,000 in 1987 to 3.3 cases per 100,000 in 1998. Cases associated with injection drug use (IDU) decreased by 90.6%, men who have sex with men (MSM) by 63.5%, and heterosexual activity by 50.7%. During 1994-1998, the most commonly reported risk factor for infection was high-risk heterosexual activity (39.8%) followed by MSM activity (14.6%) and IDU (13.8%). Over half of all patients (55.5%) reported treatment for a sexually transmitted disease (STD) or incarceration in a prison or jail prior to their illness, suggesting that more than half of the acute hepatitis B cases might have been prevented through routine hepatitis B immunization in STD clinics and correctional health care programs.

The Diverse Patterns of Hepatitis A Epidemiology in the United States—Implications for Vaccination Strategies

Hepatitis A is the most frequently reported vaccine-preventable disease in the United States. Hepatitis A incidence and risk factors during 1983-1995 were examined among cases reported to the studys Sentinel Counties: Denver County, Colorado; Pierce County, Washington; Jefferson County, Alabama; and Pinellas County, Florida. Of 4897 serologically confirmed cases, 611 patients (13%) were hospitalized and 9 (0.2%) died. The average incidence was 14.7/100, 000 (range, 0.6-100.7/100,000, depending on county and year). The frequency of reported sources of infection varied by county, but the largest single group overall (52%) did not report a source. During 3-year communitywide outbreaks in Denver (1991-1993) and Pierce (1987-1989) Counties, rates increased 4- and 13-fold, respectively, and increased in all age, racial/ethnic, and risk groups. During communitywide outbreaks, hepatitis A is not limited to specific risk groups; sustained nationwide reductions in incidence are more likely to result from routine childhood vaccination than from targeted vaccination of high-risk groups.

The importance of preventing hepatitis C virus infection among injection drug users in the United States

Injection drug use is the single most important risk factor for acquiring hepatitis C virus (HCV) infection. Injection drug users acquire this infection rapidly after initiating injection practices, and up to 90% of them are chronically infected with HCV. HCV infection is a major cause of chronic liver disease, and persons infected with HCV are at risk for chronic hepatitis, cirrhosis, and primary hepatocellular carcinoma, and they risk transmitting HCV infection to others. Preventive measures for HCV infection are limited. The heterogeneous nature of HCV and its ability to undergo rapid mutation appear to prevent the development of an effective neutralizing immune response, obstructing development of a vaccine. Prevention of HCV infection must rely on educational and programmatic efforts aimed at preventing drug use, providing substance abuse treatment for persons who inject illicit drugs, and encouraging safer injection practices. These efforts should include messages about the risk and prevention of all blood-borne pathogens, including HCV, hepatitis B virus, and human immunodeficiency virus.

Incidence of Hepatitis B Virus Infection in the United States, 1976–1994: Estimates from the National Health and Nutrition Examination Surveys

Precise estimates of the incidence of hepatitis B virus (HBV) infection are required to assess the impact of immunization and other prevention strategies in the United States. Race- and age-specific prevalence data obtained from the second and third National Health and Nutrition Examination Surveys (NHANES II, 1976-1980, and NHANES III, 1988-1994) were used to estimate the annual incidence of HBV infection by catalytic modeling. During the period covered by NHANES II, an estimated 323,462 persons were infected annually, and 334,863 were infected annually during the period covered by NHANES III. No statistically significant declines in prevalence of HBV infection occurred between the two surveys, a period during which hepatitis B vaccination targeted only limited numbers of high-risk adults.

National surveillance of hemodialysis associated diseases in the United States, 1990

To determine trends in several hemodialysis associated diseases and practices, the Centers for Disease Control (CDC), in collaboration with the Health Care Financing Administration (HCFA), performed a mail survey of chronic hemodialysis centers in the United States in 1990. Of 1,995 centers surveyed, 1,882 (94%) representing 140,608 patients and 36,907 staff members responded. As in recent years, the 1990 survey found that certain hemodialysis practices are increasing in frequency, including treatment of water with reverse osmosis and deionizer units; use of bicarbonate dialysate and high-flux dialysis; and reuse of disposable dialyzers (in 1990, 70% of centers reused dialyzers). Hepatitis B surface antigen (HBsAg) was present at low frequency in patients (incidence, 0.2%; prevalence, 1.2%) and staff (incidence, 0.04%; prevalence, 0.3%). Antibody to hepatitis B surface antigen was present in 20% of patients and 58% of staff, and was significantly related to levels of hepatitis B vaccine coverage. Pyrogenic reactions in the absence of septicemia were reported by 20% of centers and were associated with use of high-flux dialyzer membranes and reuse of dialyzers (particularly in centers where the maximum number of reuses was 40 or more). Septicemia among hemodialysis patients was reported by 49% of centers. Twenty-six percent of centers reported providing hemodialysis for patients infected with human immunodeficiency virus (HIV), and 1.1% of dialyzed patients had known HIV infection.

National surveillance of dialysis associated diseases in the United States, 1992

To determine trends in a number of hemodialysis associated diseases and practices, the Centers for Disease Control and Prevention, in collaboration with the Health Care Financing Administration, completed a mail survey of chronic hemodialysis centers in the United States in 1992. Of 2,321 centers surveyed, 2,170 (93%) representing 170,028 patients and 43,535 staff members responded. In 1992, 2,049 (94%) centers used bicarbonate dialysate as the primary method of dialysis, 765 (35)% used high flux dialysis, and 1,569 (72%) reused dialyzers, continuing the trends toward increased use of these methods. Central (subclavian or jugular) venous catheters were used in > or = 1 patient as permanent vascular access for hemodialysis at 69% of dialysis centers. Hepatitis B surface antigen was present at low frequency in patients (incidence = 0.1%, prevalence = 1.2%) and staff members (incidence - 0.03%, prevalence = 0.3%). Among centers that had > or = 1 hepatitis B surface antigen positive patient, the incidence of hepatitis B virus infection was lower in those centers that used a separate room for dialysis of patients positive for hepatitis B surface antigen. From 1991 to 1992, reported hepatitis B vaccine coverage increased from 17% to 24% among patients and from 56% to 69% among staff members; in absolute terms, these were the largest single year increases since introduction of hepatitis B vaccine. The prevalence of antibody to hepatitis C virus was 8.1% among patients and 1.6% among staff members. Pyrogenic reactions in the absence of septicemia were reported by 19% of centers and associated with use of high flux dialysis. New dialyzer syndrome was reported by 24% of centers, most frequently by centers using regenerated cellulose or cuprophan membranes. Human immunodeficiency virus was known to be present in 1.5% of patients; 34% of centers reported providing hemodialysis to one or more patients infected with HIV.

National surveillance of dialysis associated diseases in the United states-1994

Dialysis centers in the United States were surveyed in 1994 regarding a number of hemodialysis associated diseases and practices. A total of 2,449 centers, representing 206,884 patients and 50,314 staff members, responded. In 1994, 99% of centers used bicarbonate dialysate as the primary method of dialysis, 45% used high flux dialysis, and 75% reused dialyzers. Hepatitis B vaccine had been administered to 31% of patients and to 80% of staff members. Acute infection with hepatitis B virus occurred in 0.1% of patients and was more likely to be reported by centers with lower proportions of patients vaccinated against hepatitis B virus and those not using a separate room and dialysis machine to treat hepatitis B surface antigen positive patients. The prevalence of antibody to hepatitis C virus was 10.5% among patients and 1.9% among staff members and varied according to geographic region. Pyrogenic reactions in the absence of septicemia were reported by 22% of centers and were most highly associated with dialyzer reuse. Human immunodeficiency virus infection was reported to be present in 1.5% of patients; 37% of centers provided hemodialysis to one or more patients infected with human immunodeficiency virus.

Hepatitis C Virus in the Hemodialysis Setting: A Review with Recommendations for Control

Hepatitis C virus (HCV) is the causative agent of most cases of bloodborne non-A, non-B (NANB) hepatitis in the United States and throughout the wodd (1-3). Nationally, the Centers for Disease Control and Prevention (CDC) estimates that 150,000 new infections with HCV occur each year and account for an estimated 21% of all acute viral hepatitis in the United States (CDC, unpublished data). Of particular concern are the chronic consequences that frequently occur as a result of HCV infection, potentially leading to chronic active hepatitis, cirrhosis, and liver cancer (4). Second-generation serologic assays for the detection of antibody to HCV (anti-HCV) contain recombinant proteins derived from both structural (core) and nonstructural regions of the HCV genome. These assays have detected anti-HCV in 70%-mo of patients with NANB hepatitis ( 5 , 6). Among patients with HCV infection, second generation assays detect anti-HCV in approximately W o (5). One of the major advantages of second generation assays is detection of antibody earlier in the course of infection (7): five to six weeks after onset of hepatitis in WO ofpatients compared with W64090 with earlier assays (5 ; HJ Alter, personal communication). For some patients with hepatitis C, however, semconversion may not occur for six to nine months after exposure or onset of symptoms, and a negative test early in the course of the infection does not exclude the diagnosis of hepatitis C (5). Some patients with NANB hepatitis remain persistently negative for anti-HCV but have hepatitis C; in these patients, HCV infection can only be detected with the use of research-based assays such as polymerase chain reaction (PCR) or immunofluorescence techniques ( 5 ) . Other patients with NANB hepatitis who remain persistently negative for anti-HCV may be infected with another viral hepatitis agent (non-ABCDE) or their liver idammation may be due to another cause (5 , 8, 9). For these reasons, the diagnosis of hepatitis C should