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Many Americans are infected with HCV. Most were born between 1945 and 1964 and can be identified with current screening criteria. History of injection drug use is the strongest risk factor for infection.

An RNA virus, designated hepatitis G virus (HGV), was identified from the plasma of a patient with chronic hepatitis. Extension from an immunoreactive complementary DNA clone yielded the entire genome (9392 nucleotides) encoding a polyprotein of 2873 amino acids. The virus is closely related to GB virus C (GBV-C) and distantly related to hepatitis C virus, GBV-A, and GBV-B. HGV was associated with acute and chronic hepatitis. Persistent viremia was detected for up to 9 years in patients with hepatitis. The virus is transfusion-transmissible. It has a global distribution and is present within the volunteer blood donor population in the United States.

One concern is to what extent the subset of NHANES participants evaluated for HCV infection and diabetes was representative of the entire NHANES population sample. This is a significant question because the overall NHANES sample is considered the best representation of the general population of the United States, a collection of subjects free of the bias usually present in clinic-based investigations. Thus, it was reassuring that the subset of NHANES that could be evaluated for HCV infection and diabetes was both large (9,841 persons) and similar to other NHANES members with respect to many factors, including all recognized correlates of both HCV infection and diabetes. 1 This representation essentially eliminates the potential for selection bias. Another strength of the NHANES analysis is the careful testing for HCV infection performed by the Hepatitis Branch at the Centers for Disease Control and Prevention. Because HCV infection was assessed by second-generation enzyme immunoassay and confirmed by supplemental antibody testing, there is no doubt that most positive results reflect true HCV exposure. Indeed, in the subset tested for both HCV antibody and RNA, HCV RNA was detected in all but 26%, the percent one would expect to have cleared infection if all antibody-positive subjects had been previously infected. 3 Dr. Everhart raised the question of whether the antibody testing should be the main determinant of HCV or if the analysis should be restricted to persons with both HCV antibody and RNA. 2 If one were convinced that the association exists exclusively because ongoing HCV infection caused diabetes, it would have been appropriate to restrict the analysis to persons whose blood contained both HCV antibodies and RNA. Because too little is known about the pathogenesis and temporal sequence of HCV infection and diabetes to make these assumptions, the analysis initially was presented using antibody testing as the marker of HCV exposure. Nonetheless, Dr. Nainan and coworkers at the Centers for Disease Control and Prevention generously provided the HCV RNA data. For the subset for whom there is HCV RNA testing, the age-adjusted odds of type 2 diabetes in persons with HCV RNA and antibody was 2.48 (95% CI 1.23-5.01) compared with 0.98 for persons with HCV antibody but not RNA. If confirmed , these data are not consistent with the conjecture that diabetes leads to HCV infection, but instead favor hypotheses suggesting that persistent HCV infection is associated with the subsequent development of diabetes. Another important discovery in the analysis of HCV infection and type 2 diabetes in NHANES was the difference in the magnitude and direction of the association in persons of relatively young ages. Type 2 diabetes is a clinically heterogeneous syndrome that, according to the Cecil Textbook of Medicine, "typically appears after the age of 40 years." 4 In NHANES III, type 2 diabetes was not associated with HCV infection in persons less than 40 years of age. 1 Type 2 diabetes may be a different condition when it mani...

Globally, hepatitis C virus (HCV) has infected an estimated 130 million people, most of whom are chronically infected. HCV-infected people serve as a reservoir for transmission to others and are at risk for developing chronic liver disease, cirrhosis, and primary hepatocellular carcinoma (HCC). It has been estimated that HCV accounts for 27% of cirrhosis and 25% of HCC worldwide. HCV infection has likely been endemic in many populations for centuries. However, the wave of increased HCV-related morbidity and mortality that we are now facing is the result of an unprecedented increase in the spread of HCV during the 20 th century. Two 20 th century events appear to be responsible for this increase; the widespread availability of injectable therapies and the illicit use of injectable drugs.

Hepatitis C Virus (HCV) infection appears to be endemic in most parts of the world, with an estimated overall prevalence of 3%. However, there is considerable geographic and temporal variation in the incidence and prevalence of HCV infection. Using age-specific prevalence data, at least three distinct transmission patterns can be identified. In countries with the first pattern (e.g., United States, Australia), most infections are found among persons 30-49 years old, indicating that the risk for HCV infection was greatest in the relatively recent past (10-30 years ago) and primarily affected young adults. In countries with the second pattern (e.g., Japan, Italy), most infections are found among older persons, consistent with the risk for HCV infection having been greatest in the distant past. In countries with the third pattern (e.g., Egypt), high rates of infection are observed in all age groups, indicating an ongoing high risk for acquiring HCV infection. In countries with the first pattern, injection drug use has been the predominant risk factor for HCV infection, whereas in those with the second or third patterns, unsafe injections and contaminated equipment used in healthcare-related procedures appear to have played a predominant role in transmission. Much of the variability between regions can be explained by the frequency and extent to which different risk factors have contributed to the transmission of HCV. Because different strategies are required to interrupt different patterns of HCV transmission, determining the epidemiology of HCV infection in areas where that information has not yet been assessed is critical for developing appropriate prevention programs.

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