Extrahepatic manifestations of hepatitis C among United States male veterans

Hepatitis C virus (HCV) has been associated with several extrahepatic conditions. To date, most studies assessing these associations involved small numbers of patients and lacked a control group. Using the computerized databases of the Department of Veterans Affairs, we carried out a hospital-based case-control study that examined all cases of HCV-infected patients hospitalized during 1992 to 1999 (n = 34,204) and randomly chosen control subjects without HCV (n = 136,816) matched with cases on the year of admission. The inpatient and outpatient files were searched for several disorders involving the skin (porphyria cutanea tarda [PCT], vitiligo, and lichen planus); renal (membranous glomerulonephritis [GN] and membranoproliferative glomerulonephritis); hematologic (cryoglobulin, Hodgkin's and non-Hodgkin's lymphoma [NHL]); endocrine (diabetes, thyroiditis); and rheumatologic (Sj?gren's syndrome). The association between HCV and these disorders was examined in multivariate analyses that controlled for age, gender, ethnicity, and period of military service. Patients in the case group were younger in age (45 vs. 57 years), were more frequently nonwhite (39.6% vs. 26.3%), and were more frequently male (98.1% vs. 97.0%). A significantly greater proportion of HCV-infected patients had PCT, vitiligo, lichen planus, and cryoglobulinemia. There was a greater prevalence of membranoproliferative GN among patients with HCV but not membranous GN. There was no significant difference in the prevalence of thyroiditis, Sj?gren's syndrome, or Hodgkin's or NHL. However, NHL became significant after age adjustment. Diabetes was more prevalent in controls than cases, but no statistically significant association was found after adjustment for age. In conclusion, we found a significant association between HCV infection and PCT, lichen planus, vitiligo, cryoglobulinemia, membranoproliferative GN, and NHL. Patients presenting with these disorders should be tested for HCV infection.     

HIV and hepatitis C coinfection

Coinfection with HIV and the hepatitis C virus (HCV) or hepatitis B virus (HBV) is a growing public health concern. Because the diseases are spread in similar ways--notably through shared use of needles to inject drugs and sexual activity--many people are coinfected with HIV and HCV, HIV and HBV, or even all three viruses. Hepatitis C and hepatitis B are viral infections of the liver; over time they can lead to serious consequences including liver cirrhosis and liver cancer. Most studies show that HIV infection leads to more aggressive hepatitis C or hepatitis B and a higher risk of liver damage. Studies of how HCV and HBV affect HIV disease are less clear. Most research shows that HCV does not accelerate HIV disease progression, but HIV/HCV coinfection may impair immune system recovery after starting antiretroviral therapy. Coinfection can complicate treatment. People with liver damage due to chronic hepatitis are more likely to experience hepatotoxicity (liver toxicity) related to anti-HIV drugs. In addition, drugs used to treat HIV and hepatitis can interact and side effects may be exacerbated. Most experts recommend that HIV should be controlled first before a person begins HCV treatment. With careful management, most people with HIV/HCV or HIV/HBV coinfection can be successfully treated for both diseases. In fact, several recent studies suggest that HIV/HCV-coinfected people with well-controlled HIV disease and relatively high CD4 cell counts may do as well as those with HCV alone.     

HIV and hepatitis C coinfection

The significant burden of HIV/hepatitis C virus (HCV) coinfection is increasingly recognized worldwide, and in particular within the Asia–Pacific region. Individuals who are coinfected with both viruses are at risk from accelerated liver disease and consequently cirrhosis, liver failure, and hepatocellular carcinoma. In addition, coinfected individuals may have altered immunological responses to HAART and are at increased risk of highly active antiretroviral therapy (HAART)–related hepatotoxicity. Treatment for HCV infection in HIV-infected individuals is with standard pegylated interferon and ribavirin therapy, and all HIV/HCV coinfected subjects should undergo suitability for HCV treatment assessment. Response rates to HCV therapy are generally 10–15% lower than in HCV monoinfection, and therapy may be complicated by issues of drug interactions and significant toxicity. However, greater understanding of baseline factors can contribute to better prediction of treatment outcome, and monitoring of on-treatment virological responses increasingly allows individualization of therapy. Where possible, treatment of HCV is often advisable before HAART is required to avoid the issues of drug interactions on HCV therapy and the risk of HAART-related hepatotoxicity. Early diagnosis of both HIV and HCV infection is essential to most effectively manage HIV-HCV-coinfected individuals. New therapies, including HCV protease and polymerase inhibitors, are in development and may widen therapeutic options for HIV-HCV-coinfected individuals into the future.     

Prevalence of gallbladder disease among persons with hepatitis C virus infection in the United States

Although cirrhosis is a known risk factor for gallstones, little is known about gallbladder disease (GBD) in individuals with hepatitis C virus (HCV) infection. We determined the association between chronic HCV infection and GBD in a representative sample of adults in the United States. Data on HCV infection and GBD were available for 13,465 persons 20 to 74 years of age who participated in the Third National Health and Nutrition Examination Survey. The presence of GBD (gallstones or cholecystectomy) was determined using abdominal ultrasonography, and HCV infection was assessed via a positive HCV antibody test and a positive HCV RNA test. Overall, 1.6% of adults (95% CI, 1.1-2.1) had chronic HCV infection and 12.5% (95% CI, 11.3-13.7) had GBD. After adjusting for potential confounding variables, the odds of gallstones (OR = 3.20; 95% CI, 1.08-9.45) and cholecystectomy (OR = 4.57; 95% CI, 1.57-13.27) among HCV-positive men was significantly higher compared with HCV-negative men. In contrast, the adjusted odds of gallstones (OR = 2.55; 95% CI, 0.58-11.25) and cholecystectomy (OR = 0.70; 95% CI, 0.21-2.37) among HCV-positive women was not significantly higher. The odds of GBD increased significantly with the severity of liver disease as assessed via elevated serum bilirubin levels and low levels of serum albumin and platelets. In conclusion, chronic HCV infection was strongly associated with GBD among men but not women in the United States, and GBD was more common in adults with severe liver disease.     

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 type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States

BACKGROUND: Hepatitis C virus (HCV) infection may contribute to the development of diabetes mellitus. This relationship has not been investigated at the population level, and its biological mechanism remains unknown. OBJECTIVE: To examine the prevalence of type 2 diabetes among persons with HCV infection in a representative sample of the general adult population of the United States. DESIGN: Cross-sectional national survey. SETTING: The Third National Health and Nutrition Examination Survey, 1988-1994. PARTICIPANTS: 9841 persons older than 20 years of age for whom data on HCV infection and diabetes were complete. MEASUREMENTS: The presence of diabetes was ascertained by using American Diabetes Association guidelines based on fasting plasma glucose measurement and medication history. Presence of HCV infection was assessed by testing for serum HCV-specific antibodies (anti-HCV). RESULTS: Of the 9841 persons evaluated, 8.4% had type 2 diabetes and 2.1% were anti-HCV positive. Type 2 diabetes occurred more often in persons who were older, were nonwhite, had a high body mass index, and had low socioeconomic status. Type 2 diabetes was less common in persons who acknowledged previous illicit drug use. After adjustment for these factors, persons 40 years of age or older with HCV infection were more than three times more likely than those without HCV infection to have type 2 diabetes (adjusted odds ratio, 3.77 [95% CI, 1.80 to 7.87]). None of the 19 persons with type 1 diabetes were anti-HCV positive. CONCLUSION: In the United States, type 2 diabetes occurs more often in persons with HCV infection who are older than 40 years of age.     

Prevalence and determinants of hepatitis delta virus infection among HIV/hepatitis B-coinfected adults in care in the United States

Hepatitis delta virus (HDV) infection increases the risk of liver complications compared to hepatitis B virus (HBV) alone, particularly among persons with human immunodeficiency virus (HIV). However, no studies have evaluated the prevalence or determinants of HDV infection among people with HIV/HBV in the US. We performed a cross-sectional study among adults with HIV/HBV coinfection receiving care at eight sites within the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) between 1996 and 2019. Among patients with available serum/plasma specimens, we selected the first specimen on or after their initial HBV qualifying test. All samples were tested for HDV IgG antibody and HDV RNA. Multivariable log-binomial generalized linear models were used to estimate prevalence ratios (PRs) with 95% CIs of HDV IgG antibody-positivity associated with determinants of interest (age, injection drug use [IDU], high-risk sexual behaviour). Among 597 adults with HIV/HBV coinfection in CNICS and available serum/plasma samples (median age, 43 years; 89.9% male; 52.8% Black; 42.4% White), 24/597 (4.0%; 95% CI, 2.4%–5.6%) were HDV IgG antibody-positive, and 10/596 (1.7%; 95% CI, 0.6%–2.7%) had detectable HDV RNA. In multivariable analysis, IDU was associated with exposure to HDV infection (adjusted PR = 2.50; 95% CI, 1.09–5.74). In conclusion, among a sample of adults with HIV/HBV coinfection in care in the US, 4.0% were HDV IgG antibody-positive, among whom 41.7% had detectable HDV RNA. History of IDU was associated with exposure to HDV infection. These findings emphasize the importance of HDV testing among persons with HIV/HBV coinfection, especially those with a history of IDU.     

Prevalence of hepatitis C virus seropositivity among hospitalized US veterans

BACKGROUND: Hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis in the United States and abroad. HCV antibody prevalences ranging from 10 to 90% have been reported in intravenous drug abusers, hemodialysis patients, and persons suffering from other liver diseases, whereas HCV seropositivity rates for volunteer-blood donor populations are generally under 1%. However no information has been available concerning the prevalence of HCV in general hospital populations in the United States. METHODS: We examined the rate of HCV seropositivity in 530 patients admitted to the Atlanta VA Medical Center between November 1993 and November 1994. The test population consisted of 400 random hospital admissions, 100 successive admissions to the surgical service, and 30 random admissions to the gastrointestinal service. Serum samples were assayed for HCV antibodies by a second generation EIA, and all repeat reactives were re-examined using a supplemental research assay to confirm the presence of HCV antibodies. Complete chart reviews were carried out on all HCV seropositive patients and on 100 HCV seronegative patients. RESULTS: Sixty-two of the 530 patients tested (11.7%) were repeatedly positive for HCV antibodies. Of these 62 repeat reactives, 56 (90.3%) were positive and 3 others (4.8%) indeterminate by the supplemental assay. The HCV seropositivity rate after supplemental testing was 11.8% for random admissions, 5.0% for surgical admissions, and 13.3% for patients admitted to the gastroenterology service. HCV-associated risk factors in HCV seropositive patients included a history of intravenous drug abuse, current or previous alcohol abuse, previous or concurrent liver disease, previous blood transfusions, hemodialysis, and multiple sex partners or unsafe sex. CONCLUSIONS: HCV infection may be more prevalent among hospitalized VA patients (and among other US hospital populations) than previously expected.     

HIV and hepatitis C virus coinfection update

Sharing routes of transmission, hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) are often harbored in the same host, establishing chronic infections characterized by high serum viral loads. HIV-1 impacts the course of HCV infection by increasing the rate of HCV viral persistence, quantitative viral loads, and liver fibrosis progression rate. HCV in turn affects HIV management, particularly by increasing the risk of hepatotoxicity. Future studies will focus on understanding the pathogenesis of accelerated liver fibrosis in HIV-infected individuals, the natural history of HCV in the era of antiretroviral therapy, and the principles of managing these two infections within the same individual.     

HIV, hepatitis B and hepatitis C coinfection in Kenya

There are few data regarding hepatitis and HIV coinfection in Africa. In 378 HIV seropositive individuals in Nairobi, 23 (6%) were hepatitis B virus (HBV) and HIV coinfected, four (1%) were hepatitis C virus (HCV) and HIV coinfected and one patient was infected with all three viruses. Coinfected individuals were more likely to be men and older; a lack of HBV vaccination was a risk factor for HIV/HBV coinfection (P = 0.001) and tenofovir containing regimens appeared most effective at reducing HBV viral load.     

Management of hepatitis C/HIV coinfection

PURPOSE OF REVIEW: One third of HIV-infected individuals in Europe and the USA have a hepatitis C coinfection. With the introduction of highly active antiretroviral therapy for treatment of HIV, liver disease caused by chronic hepatitis C virus infection has now become an increasingly important cause of morbidity and mortality among HIV-infected patients. Therefore, treatment strategies for management of hepatitis C coinfection in HIV-infected individuals are urgently needed. RECENT FINDINGS: With the introduction of pegylated interferon/ribavirin combination therapy significantly improved treatment options for HIV/hepatitis C virus-coinfected patients have become available, leading to sustained virological response rates of over 40%. Increasing knowledge on the management of adverse events under hepatitis C therapy and optimized selection of antiretrovirals in HIV/hepatitis C virus-coinfected patients has helped to reduce complications and improve overall treatment outcome. SUMMARY: Treatment with pegylated interferon plus ribavirin is safe and effective in HIV/hepatitis C virus-coinfected patients. Longer treatment durations of 48 weeks are recommended for genotype 2 or 3. Positive predictive factors for sustained response are hepatitis C virus genotype 2 or 3 and early treatment response.     

High prevalence of hepatitis C virus infection among immigrants from the former Soviet Union in the New York City metropolitan area: results of a community-based screening program

BACKGROUND:  Inadequate sterilization and reuse of medical equipment likely contributed to hepatitis C virus (HCV) transmission in the former Soviet Union (FSU). Although New York leads the nation in the number of immigrants from the FSU, the epidemiology of HCV infection has not been evaluated in this population. The aims of this study were to determine the prevalence of and risk factors for HCV infection among immigrants from the FSU in the New York metropolitan area.
METHODS:  We conducted a 3-day community-based HCV screening program in the two boroughs of the New York metropolitan area with the highest density of FSU immigrants (Brooklyn and Queens). Russian cable television was used to invite subjects to come in for free HCV testing. In the last 2 days of screening, each person also completed an HCV risk factor questionnaire.
RESULTS:  The overall prevalence of HCV seropositivity among the 283 subjects was 28.3% (95% confidence interval [CI] 23.0–33.5%). The prevalence of HCV infection was similar in men and women (30.3% vs 26.5%, P = 0.48) and was highest in subjects ≥70 yr old (35.0%). HCV seropositivity was 11.1% in immigrants from Russia, 29.0% from Uzbekistan, 31.0% from the Ukraine, and 36.8% from other regions. Intramuscular injections (odds ratio 9.1, 95% CI 2.0–42.4) and blood transfusions (odds ratio 3.2, 95% CI 1.2–9.0) were the only variables that were significantly associated with HCV infection in the multivariable analysis.
CONCLUSIONS:  In this community-based screening program we found a high prevalence of HCV infection among immigrants from the FSU, and these infections likely resulted from inadequately sterilized medical equipment and blood transfusions. Universal HCV testing should be strongly considered for all FSU immigrants.     

HIV and hepatitis C coinfection within the CAESAR study

The declining incidence of AIDS-related opportunistic diseases among people with HIV infection has shifted the focus of clinical management to prevention and treatment of comorbidities such as chronic liver disease. The increased risk of hepatitis C virus (HCV)-related advanced liver disease in people with HIV infection makes early HCV diagnosis a priority. To assess HCV prevalence and predictors of HIV/HCV coinfection, we have conducted a retrospective analysis of people enrolled in the CAESAR (Canada, Australia, Europe, South Africa) study, a multinational randomized placebo-controlled study of the addition of lamivudine to background antiretroviral therapy. The impact of HCV on HIV disease progression was also examined. Anti-HCV antibody testing on 1649 CAESAR study participants demonstrated a HIV/HCV coinfection prevalence of 16.1%, which varied from 1.9% in South Africa to 48.6% in Italy. The strongest predictor of HIV/HCV coinfection was HIV exposure category (P<0.0001), with odds ratios (ORs) compared to homosexual as follows: injecting drug use (IDU), 365 [95% confidence interval (CI): 179-742]; transfusion or blood products, 32.2 (95% CI: 15.2-67.6); homosexual and IDU, 22.9 (95% CI: 8.5-62.1). The prevalence of HIV/HCV was low (3.7%) among homosexual men without reported IDU. Other predictors of HIV/HCV coinfection were alanine aminotransferase (ALT), country of residence, ethnicity and stage of HIV disease. A history of IDU or ALT > or =40 U/L at baseline had a positive predictive value (PPV) of 35%, negative predictive value (NPV) of 96%, sensitivity of 82% and specificity of 71% for HIV/HCV coinfection. HIV disease progression was similar in HIV monoinfected and HIV/HCV coinfected patients. People with HIV and a history of IDU or elevated liver function tests should be targeted for HCV testing. The low prevalence of HIV/HCV coinfection among homosexual men without a history of IDU suggests low efficiency of sexual HCV transmission.     

Vertically acquired paediatric coinfection with HIV and hepatitis C virus

Both HIV and hepatitis C virus (HCV) can be transmitted from mother to child during pregnancy and delivery. Vertical transmission of HIV and HCV separately is most likely from HIV/HCV-coinfected mothers; however, transmission of both infections is less frequent. The effect of HCV coinfection on HIV-related disease remains unclear; whereas most studies indicate no effect, recent results suggest HCV in adults accelerates HIV progression. Little is known about how HIV coinfection affects HCV progression in children and the information available is based on small numbers of patients. Paediatric HIV treatment is extremely successful and it is vital to determine if HCV coinfection alters the effectiveness of this treatment. The hepatotoxicity of many HIV therapies and the possible negative impact of HCV on this treatment, alongside the interactions and contraindications of many HIV and HCV therapies, further limits the choice of paediatric treatments for coinfected children. Future research must therefore focus on vertically acquired HIV/HCV coinfection to inform treatment trials addressing coinfection management.