Prevalence of human immunodeficiency virus/hepatitis C virus co-infection in Brazil and associated factors: a review

The hepatitis C virus and human immunodeficiency virus share the same transmission routes, which makes co-infection an unfavorable condition for the natural history of both viral diseases. In this context, it should be highlighted that the knowledge of the extent of co-infection and associated risk factors is a vital tool for prevention and control over infectious diseases. The aim of this study was to review the literature, seeking to examine the prevalence of human immunodeficiency virus/hepatitis C virus co-infection reported in studies conducted in Brazil, and identify the main risk factors associated with co-infection.The electronic search was conducted in the Medline, Lilacs and SciELO databases. The following keywords were used: human immunodeficiency virus and Hepatitis C or hepatitis C virus and Brazil. The search led to 376 articles, of which 69 were selected for data extraction. We excluded animal studies, reports or case series, review articles, letters to the editor, other types of hepatitis and those studies in which co-infected patients were intentionally selected for comparison to single infected individuals. As a result, 40 articles were reviewed. The majority of the population in these studies was male (71%) and young adults, with a mean age of 26.7 years. The prevalence of hepatitis C virus co-infection among individuals living with human immunodeficiency virus in the studies conducted in Brazil ranged from 3.3% (serum samples) to 82.4% (drug users), with an average of 20.3%. The findings reveal that the prevalence of human immunodeficiency virus/hepatitis C virus co-infection is highly variable, depending on the characteristics of the study population. Risk factors associated with human immunodeficiency virus/hepatitis C virus co-infection were injection drug use and blood transfusion.     

Coinfection of hepatitis B and hepatitis C virus in HIV-infected patients in south India

AIM To screen for the co-infection of hepatitis B (HBV)and hepatitis C virus (HCV) in human immunodeficiency virus (HIV) infected patients insouthern India.METHODS Five hundred consecutive HIV infected patients were screened for Hepatitis B Virus (HBsAg and HBV-DNA) and Hepatitis C virus (anti-HCV and HCV-RNA)using commercially available ELISA kits; HBsAg, HBeAg/anti-HBe (Biorad laboratories, USA) and anti-HCV (Murex Diagnostics, UK). The HBV-DNA PCR was performed to detect the surface antigen region (pre S-S). HCV-RNA was detected by RT-PCR for the detection of the constant 5' putative non-coding region of HCV.RESULTS HBV co-infection was detected in 45/500 (9%)patients and HCV co-infection in 11/500 (2.2%) subjects.Among the 45 co-infected patients only 40 patients could be studied, where the detection rates of HBe was 55%(22/40), antiHBe was 45% (18/40) and HBV-DNA was 56% (23/40). Among 11 HCV co-infected subjects, 6(54.5%) were anti-HCV and HCV RNA positive, while 3(27.2%) were positive for anti-HCV alone and 2 (18%)were positive for HCV RNA alone.CONCLUSION Since the principal routes for HIV transmission are similar to that followed by the hepatotropic viruses, as a consequence, infections with HBV and HCV are expected in HIV infected patients.Therefore, it would be advisable to screen for these viruses in all the HIV infected individuals and their sexual partners at the earliest.     

Multicenter study of intrafamilial transmission of hepatitis C virus in human immunodeficiency virus infection

OBJECTIVE: Intrafamilial transmission of hepatitis C virus in human immunodeficiency virus and hepatitis C virus co-infections is not well documented. This cross-sectional study evaluated the transmission of hepatitis C virus in the sexual partners of hepatitis C virus and human immunodeficiency virus co-infected patients. METHODS: Hemophiliacs and transfused hepatitis C virus and human immunodeficiency virus co-infected patients who were being seen in three French university hospitals, and their sexual partners were studied by a face-to-face interview using an epidemiological questionnaire and by biological tests: antibodies against hepatitis C virus, hepatitis C virus RNA, and ALT activity. RESULT: Fifty-two subjects were included: 26 cases and their 26 sexual partners. Three sexual partners (11.5 %) had anti-hepatitis C virus antibodies, two of whom had an undetermined RIBA test. All three had a risk factor for hepatitis C virus infection (transfusion, intra-muscular injections with re-usable needles). Two of these three partners were also human immunodeficiency virus antibody positive. Hepatitis C virus RNA was negative in all sexual partners. CONCLUSION: This study provides evidence of a low prevalence of anti-hepatitis C virus antibodies in sexual partners of hepatitis C virus and human immunodeficiency virus co-infected patients. It does not support intra-familial transmission of hepatitis C virus.     

Management of hepatitis C in human immunodeficiency virus-infected patients

Hepatitis C virus-related liver disease and its associated complications are steadily emerging health concerns in persons co-infected with human immunodeficiency virus. The increasing number of liver-related deaths in human immunodeficiency virus-hepatitis C virus co-infected individuals supports the compelling argument for more aggressive treatment in these patients. The safety and efficacy of interferon/ribavirin in human immunodeficiency virus/hepatitis C virus co-infected patients is currently under evaluation. Despite well-documented concern over highly active antiretroviral therapy-associated hepatotoxicity human immunodeficiency virus/hepatitis C virus co-infected patients should be offered antiretroviral therapy. Since management of co-infected patients is complex a multidisciplinary approach is needed in order to facilitate care and help patients to achieve a positive outcome.     

Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation

Liver transplantation for human immunodeficiency virus(HIV)positive patients with viral hepatitis co-infection is increasingly offered in many North American and European liver transplant centers.Prior studies have demonstrated acceptable post-transplant outcomes and no increased risk of HIV complications in patients coinfected with hepatitis B virus(HBV).However,liver transplantation in HIV positive patients with hepatitis C virus(HCV)has poorer outcomes overall,requiring careful selection of candidates.This review aims to summarize the published literature on outcomes after transplant in HIV patients with HBV or HCV related end-stage liver disease and recommendations for management.In particular the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates and importance of multidisciplinary management will be discussed.     

慢性丙型肝炎患者混合或重叠感染其他病原体状况分析

目的了解丙型肝炎病毒（HCV）感染者混合或重叠感染乙型肝炎病毒（HBV）、人免疫缺陷病毒（HIV）和梅毒螺旋体（TP）的状况,为HCV感染的防治提供依据。方法采用ELISA法检测乙型肝炎病毒标志物、抗TP和抗HIV;采用化学发光法检测抗HCV;采用蛋白印迹法确认HIV感染。结果在169例HCV感染者中,重叠感染HBV 25例（14.8%）、HIV 4例（2.4%）、TP 9例（5.3%）,重叠感染HBV和TP 2例（1.2%）,重叠感染HBV和HIV 2例（1.2%）;静脉吸毒者重叠感染HIV（6.7%）和TP（11.1%）的比例均明显高于非静脉吸毒者（P〈0.05）;男性患者重叠感染HBV的比例（19.7%）明显高于女性患者（3.8%,P〈0.01）,女性患者重叠感染TP的比例（11.5%）明显高于男性患者（2.6%,P〈0.05）。结论随着感染方式的多元化,慢性丙型肝炎患者重叠感染其他病原体的情况更加常见。     

High prevalence, low pathogenicity in hepatitis G virus in kidney transplant recipients

BACKGROUND: Prevalence and pathogenicity of hepatitis G virus infection in long-term renal transplant recipients, are not fully known. AIM: To evaluate long-term impact of HGV infection on liver disease of renal transplanted patients. PATIENTS AND METHODS: A total of 155 hepatitis B surface antigen negative kidney transplant recipients, followed for a mean of 11 years after renal transplantation, were studied. Of these 48 (31%) patients had persistently elevated serum aminotransferase values. Frozen serum samples were tested for HGV-RNA and HCV-RNA by nested reverse transcribed polymerase chain reaction, and for anti-hepatitis G virus and anti-hepatitis C virus by enzyme-linked immunosorbent assay Hepatitis C virus-RNA was typed by a line probe assay and quantified by a branched DNA signal amplification assay RESULTS: Hepatitis G virus-RNA was detected in 37 (24%) patients and anti-hepatitis G virus in another 26 (17%). Seventy (45%) patients had serum anti-hepatitis C virus and 63 of these (90%) had serum hepatitis C virus-RNA. Hepatitis G virus-RNA positive and negative patients were similar in terms of age, sex, duration of dialysis, rate of transfusion, chronic liver disease, rate of hepatitis C virus infection and immunosuppressive therapy. Fifteen (41%) hepatitis G virus-RNA seropositive patients were hepatitis C virus co-infected. Hepatitis C virus-RNA levels were significantly lower in the 15 hepatitis C virus/hepatitis G virus co-infected patients than in the 48 patients with hepatitis C virus infection only (2.2 vs 10.8 MEq/ml, p = 0.02). Only 3 hepatitis G virus carriers had persistently elevated alanine aminotransferase compared to 29 hepatitis C virus carriers (14% vs 60%, p < 0.001), 10 patients co-infected with both hepatitis G virus and hepatitis C virus, and in 6 patients with neither infection (67% vs 8%, p < 0.001). CONCLUSIONS: Hepatitis G virus infection is common among kidney transplant patients, it carries a low risk of chronic liver disease even in long-term follow-up. Low levels of hepatitis C virus-RNA found in hepatitis G virus carriers suggest an interaction between these two viruses in immunosuppressed patients.     

Effect of duration of hepatitis B virus infection on the association between human immunodeficiency virus type-1 and hepatitis B viral replication.

This study examined the effect of duration of hepatitis B virus infection on the association between human immunodeficiency virus type-1 infection and hepatitis B viral replication. Twenty-five chronic HBsAg carriers were studied. Presence of hepatitis B virus DNA and expression of HBeAg were more frequent among 20 chronic HBsAg carriers positive for human immunodeficiency virus type-1 antibody compared with five chronic HBsAg carriers negative for human immunodeficiency virus type-1 antibody, but the associations were not statistically significant. Hepatitis B virus DNA and HBeAg were inversely related to duration of hepatitis B virus infection (p less than 0.001). Stratifying for duration of hepatitis B virus infection, the presence of viral replication was similar among patients negative and positive for antibody to human immunodeficiency virus type-1. Hepatitis B virus DNA levels did not increase with the decline of cellular immunity over time. In conclusion, hepatitis B virus replication among chronic carriers may be a function of duration of hepatitis B virus infection rather than of an effect of human immunodeficiency virus type-1.     

Hepatitis B virus infection: co-infection with hepatitis C virus, hepatitis D virus, and human immunodeficiency virus

Hepatitis B virus (HBV) shares routes of transmission, namely exchange of infected body fluids, sharing of contaminated needles, and blood transfusion, with other hepatotropic viruses, such as hepatitis C virus (HCV) and hepatitis D virus (HDV) and with systemic retroviral infections, such as the human immunodeficiency virus (HIV). Thus, many HBV infected patients are co-infected with other viral pathogens. Co-infection appears to increase the risk of progression of liver disease and may have important ramifications on choice of antiviral medication and treatment regimen. This article reviews the current knowledge of co-infection of HBV with HCV, HDV, and HIV.     

重叠乙型和丙型肝炎病毒感染的临床与病理分析

目的 观察HBV和HCV重叠感染的临床与病理,探讨HBV和HCV相互作用的特点.方法 收集226例慢性肝病患者的血清学指标,实时荧光定量PCR法测定HBV DNA和HCVRNA,ELISA检测HBV血清标志物、抗-HCV抗体.行肝穿刺活组织病理检查、免疫组织化学HBsAg、HBcAg和原位杂交HBV DNA、HCV RNA检测.计数资料比较采用X2检验或Fisher确切率检验.结果 HBV和HCV重叠感染的重度慢性肝炎患者比例为62.50%,高于HBV或HCV单独感染者的27.05%和30.56%(X2=14.70,P＜0.01).HBV感染组的血ALT、AST、TBil、DBil和Alb高于HBV和HCV重叠感染组和HCV感染组,差异均有统计学意义(X2=8.52,P＜0.05).重叠感染组和HBV感染组的血HBsAg与肝内HBsAg一致率比较,差异均有统计学意义(X2=15.60,P＜0.01).HBV和HCV重叠感染组血清HBV DNA阳性率为12.5%,低于HBV单独感染组的87.7%(X2=17.66,P＜0.01);而HBV和HCV重叠感染组HCV RNA阳性率为75.0%,低于HCV单独感染组的80.6%,差异无统计学意义(P＞0.05).结论 HBV和HCV重叠感染导致的肝损伤更明显.     

Association between chronic hepatitis B virus infection and diabetes among Asian Americans and Pacific Islanders

BACKGROUND: Asians have a higher prevalence of both diabetes (diabetes mellitus) and chronic hepatitis B virus infection compared to Caucasians. The aim of this study was to investigate whether hepatitis B virus infection was associated with diabetes mellitus among Asian Americans and Pacific Islanders. METHODS: We reviewed the electronic medical records of 411 Asian and 424 Pacific Islanders seen at our medical centre over a 5-year period. Diabetes mellitus was defined by the presence of two or more random blood glucose levels > or =200mg/dL, an ICD-9 diagnostic code of diabetes mellitus, or use of medications for diabetes mellitus. Hepatitis B virus infection was defined by a positive HBsAg test. RESULTS: Diabetes mellitus was diagnosed in 223 of the 835 subjects (26.7%), whereas hepatitis B virus infection was diagnosed in 56 (13.8%) of the 407 subjects tested for HBsAg. Overall, the prevalence of diabetes mellitus was significantly higher in patients with hepatitis B virus than in those without hepatitis B virus (58.9% vs. 33.3%, P<0.001), and this remained significant after adjustment for potential confounding variables (OR=3.17; 95% CI, 1.58-6.35). When Asians and Pacific Islanders were analysed separately, the prevalence of diabetes mellitus in patients with hepatitis B virus was significantly higher than in those without hepatitis B virus among Asians (65.0% vs. 27.5%, P<0.001) but not in Pacific Islanders (43.8% vs. 37.1%, P=0.60). Among the 390 subjects who were tested for both hepatitis B virus and hepatitis C virus, the prevalence of diabetes mellitus was 29.4% in uninfected subjects, 44.4% in patients with hepatitis B virus monoinfection, 47.2% in patients with hepatitis C virus monoinfection and 85.0% in patients with hepatitis B virus and hepatitis C virus coinfection (P<0.001). CONCLUSIONS: Hepatitis B virus infection is strongly associated with diabetes mellitus among Asian Americans, but not in Pacific Islanders, whereas hepatitis C virus infection was associated with diabetes mellitus in both ethnic groups.     

合并乙型肝炎病毒感染对丙型肝炎病毒核心抗原检测的影响

目的 探讨合并HBV感染对慢性HCV感染者血清丙型肝炎病毒核心抗原(HCVcAg)检出情况的影响. 方法 收集2005年12月-2009年10月慢性丙型肝炎患者和HBV/HCV合并感染者资料,检测血清HCVcAg和HCV RNA,对后者血清进行HBV DNA、HBeAg检测,分析HCVcAg检出率与HBeAg、HBV DNA定量检测的关系.用独立两组多分类的X2检验方法进行统计学分析. 结果 共收集88例慢性丙型肝炎患者和62例HBV/HCV合并感染者资料,血清HCVcAg的检出率分别为72.7％(64/88)和38.7％ (24/62),两者比较,x2= 17.358,P＜0.01,差异有统计学意义.HCV RNA检出率分别为81.8％ (72/88)和53.2％ (33/62),两者比较,x2=20.110,P＜0.01,差异有统计学意义.62例HBV/HCV合并感染者血清中,HBeAg阳性和HBeAg阴性感染者HCVcAg检出率分别为28.6％ (12/42)和60.0％ (12/20),两者比较,x2=5.641,P=0.011,差异有统计学意义.HCV RNA阳性率分别为42.9％ (18/42)和80.0％ (16/20),两者比较,X2=7.547,P＜ 0.01,差异有统计学意义.HBV DNA阳性和阴性时HCVcAg检出率分别为39.1％ (18/46)和37.5％ (6/16),两者比较,P＞0.05,差异无统计学意义.与单纯HCV感染者血清HCVcAg检出率72.7％ (64/88)比较,HBeAg阴性合并感染者为60.0％ (12/20),x2=1.266,P=0.261,差异无统计学意义;HBV DNA阴性合并感染者为37.5％ (6/16),x2=7.635,P＜0.01,差异有统计学意义.结论 HBV/HCV合并感染时HCVcAg检出率较低,可能是由于HBeAg抑制HCV的复制,从而减少HCVcAg的表达所致.     

The significance of antibody to hepatitis C virus in patients with chronic hepatitis B.

We assessed the prevalence and clinical significance of antibodies to hepatitis C virus among a cohort of 148 patients with chronic hepatitis B virus infection. Sixteen patients (11%) had anti-hepatitis C virus detectable by enzyme-linked immunoassay. The results from eight of these patients were positive by recombinant immunoblot assay. The results of recombinant immunoblot assay testing were not consistent; therefore the analysis of the patients' data was based on anti-hepatitis C virus enzyme-linked immunoassay results. Patients with chronic hepatitis B with anti-hepatitis C virus were more likely to be cirrhotic (44% vs. 21%) and to have decompensated liver disease (24% vs. 6%). Hepatitis B virus replication appeared to be suppressed in patients with both infections as measured by hepatitis B virus-associated DNA polymerase activity (mean = 2,055 vs. 2,555 cpm). Human immunodeficiency virus infection was more common in the anti-hepatitis C virus positive group (36% vs. 11%). Thus hepatitis C virus appears to suppress hepatitis B virus replication and to cause more severe liver disease in patients with chronic hepatitis B infection.     

Hepatitis B and C virus co-infections in human immunodeficiency virus positive North Indian patients

INTRODUCTION Diseases of the hepatobiliary system are a major problem in patients with human immunodeficiency virus (HIV) infection. An estimated one-third of deaths in HIV patients are directly or indirectly related to liver disease. Liver diseases in HI…     

Pruritus in patients with chronic human immunodeficiency virus, hepatitis B and C virus infections

AIM: The prevalence of pruritus was prospectively determined in 310 patients of whom 119 had hepatitis C virus infection, 91 hepatitis C virus and human immunodeficiency virus, 51 human immunodeficiency virus infection alone, 31 hepatitis B virus and human immunodeficiency virus coinfection and 18 were HBsAg carriers. RESULTS: Patients in the first three groups were more likely to complain of itching (22%, 28% and 25%, respectively) than HBsAg carriers (8.2%, p=0.01. Laboratory data were not different between groups, except for the human immunodeficiency virus group, whose alkaline phosphatase levels were highest, and CD4 counts were lowest (median 30 cells/mm3). Patients with hepatitis C, including those with human immunodeficiency virus, had similar hepatitis C virus RNA levels in patients with or without pruritus. There was no difference in hepatic inflammation or fibrosis between those with and those without pruritus. CONCLUSION: 20% of patients with chronic hepatitis C and 8% of hepatitis B patients complain of pruritus. Patients with pruritus have laboratory and histologic parameters comparable to those without.     

Significance of blood analysis in hemophiliacs co-infected with human immunodeficiency virus and hepatitis viruses

AIM： To study the effect of hepatitis virus infection on cirrhosis and liver function markers in HIV-infected hemophiliacs.
METHODS： We have analyzed the immunological, liver function and cirrhosis markers in a cohort of hemophiliacs co-infected with human immunodeficiency virus （HIV） and hepatitis viruses.
RESULTS： There was no difference in immunological markers among co-infected patients and patients infected with HIV only and those co-infected with one or more hepatitis virus. Although liver function and cirrhosis markers remained within a normal range, there was a worsening trend in all patients co-infected with hepatitis virus C （HCV）, which was further exacerbated in the presence of additional infection with hepatitis virus B （HBV）.
CONCLUSION： Co-infection with HIV, HBV and HCV leads to worsening of hyaluronic acid and liver function markers. Increases in serum hyaluronic acid may be suggestive of a predisposition to liver diseases.     

Emergence of resistant hepatitis B virus strains during long-term lamivudine therapy in human immunodeficiency virus co-infected patients

Seven patients co-infected with hepatitis B virus (HBsAg and HBeAg carriers, quantifiable HBV DNA with the bDNA technic) and human immunodeficiency virus received a triple antiretroviral combination therapy, including lamivudine (150 mg twice a day). Hepatitis B viral load rapidly became undetectable in 6/7 patients. It remained below the level of detection in 2 subjects, after 20 and 22 months of treatment, with one of them achieving HBeAg/anti-HBe seroconversion. However, in the other 4 individuals, hepatitis B viremia increased again after 8 to 16 months of lamivudine-containing regimen. The last patient was a non-responder. The 4 relapsers developed a double mutation Leu(528) for Met(528) and Met(552) for Val(552), on hepatitis B virus polymerase, either concomitant (M8 and M16) with a hepatitis B virus DNA increase, or 2 months earlier (M10 and M12). The high frequency of hepatitis B virus resistance to lamivudine emphasizes the necessity of identifying more effective strategies, such as double combination therapies.     

Co-infection of hepatitis B and hepatitis C virus in human immunodeficiency virus-infected patients in New York City,United States

AIM： To study the prevalence and risk factors associated with triple infection with human immunodeficiency virus （HIV）/hepatitis B virus （HBV）/hepatitis C virus （HCV） in an urban clinic population. METHODS： Retrospective chart review of 5639 patients followed at St. Luke＇s-Roosevelt Hospital HIV Clinic （Center for Comprehensive Care） in New York City, USA from January 1999 to May 2007. The following demographic characteristics were analyzed： age, sex, race and HIV risk factors. A multiple logistic regression analysis was performed to evaluate the influence of demographic factors on acquisition of these viruses. RESULTS： HIV/HBV, HIV/HCV and HIV/HBV/HCV infections were detected in 252/5639 （4.47%）, 1411/5639 （25.02%） and 89/5639 （1.58%） patients, respectively. HIV/HBV co-infections were associated with male gender （OR 1.711; P = 0.005）, black race （OR 2.091, P 〈 0.001）, men having sex with men （MSM） （OR 1.747, P = 0.001）, intravenous drug use （IDU） （OR 0.114, P 〈 0.001）, IDU and heterosexual activity （OR 0.247; P = 0.018）, or unknown （OR 1.984, P = 0.004）.HIV/HCV co-infections were associated with male gender （OR 1.241; P = 0.011）, black race （OR 0.788; P = 0.036）, MSM （OR 0.565; P 〈 0.001）, IDU （OR 8.956; P 〈 0.001）, IDU and heterosexual activity （OR 9.106; P 〈 0.001）, IDU and MSM （OR 9.179; P 〈 0.001）, or transfusion （OR 3.224; P 〈 0.001）. HIV/HBV/HCV coinfections were associated with male gender （OR 2.156; P = 0.015）, IDU （OR 6.345; P 〈 0.001）, IDU and heterosexual activity （OR 9.731; P 〈 0.001）, IDU and MSM （OR 9.228; P 〈 0.001）, or unknown （OR 4.219; P = 0.007）. CONCLUSION： Our study demonstrates that coinfection with HBV/HCV/HIV is significantly associated with IDU. These results highlight the need to intensify education and optimal models of integrated care, particularly for populations with IDU, to reduce the risk of viral transmission.     

Prevalence of hepatitis B virus infection in Japanese patients with HIV.

Patients with HIV infection are frequently infected with hepatitis viruses, which are presently the major cause of mortality in HIV-infected patients after the widespread use of highly active antiretrovirus therapy. We previously reported that approximately 20% of HIV-positive Japanese patients were also infected with hepatitis C virus (HCV). Hepatitis B virus (HBV) infection may also be an impediment to a good course of treatment for HIV-infected patients, because of recurrent liver injuries and a common effectiveness of some anti-HIV drugs on HBV replication. However, the status of co-infection with HIV and HBV in Japan is unclear. We conducted a nationwide survey to determine the prevalence of HIV-HBV co-infection by distributing a questionnaire to the hospitals belonging to the HIV/AIDS Network of Japan. Among the 5998patients reported to be HIV positive, 377 (6.4%) were positive for the hepatitis B surface antigen. Homosexual men accounted for two-thirds (70.8%) of the HIV-HBV co-infected patients, distinct from HIV-HCV co-infection in Japan in which most of the HIV-HCV co-infected patients were recipients of blood products. One-third of HIV-HBV co-infected patients had elevated serum alanine aminotransferase levels at least once during the 1-year observation period. In conclusion, some HIV-infected Japanese patients also have HBV infection and liver disease. A detailed analysis of the progression and activity of liver disease in co-infected patients is needed.     

Hepatitis C viremia in patients with hepatitis C virus infection.

Sera from 103 patients were tested for hepatitis C virus RNA by nested polymerase chain reaction assay. Using primers from the highly conserved 5'-untranslated region, we detected hepatitis C virus RNA in 67 (88.2%) of 76 patients positive for antibody to hepatitis C virus by both second-generation and neutralization enzyme immunoassays. Hepatitis C virus RNA was detected in 93% of patients who had been infected for 10 yr or less and in 89% of those who had been infected for longer than 10 yr. Hepatitis C virus RNA was detected in all patients with chronic hepatitis, active cirrhosis or hepatocellular carcinoma and in 50% of those with nonspecific reactive hepatitis or inactive cirrhosis. Hepatitis C virus RNA was not detected in sera from 22 patients negative for antibody to hepatitis C virus or in 5 patients positive for antibody to hepatitis C virus by second-generation but not by neutralization enzyme immunoassay. Using primers from the less conserved nonstructural region 4, we detected hepatitis C virus RNA at a lower frequency, in 66% of patients who were positive for antibody to hepatitis C virus by both second-generation and neutralization enzyme immunoassays. The detection rate was higher in patients with frequent parenteral exposure. Our study showed that hepatitis C viremia can be detected in most patients with hepatitis C virus infection, including those with long-standing infection or advanced liver disease.