Steatohepatitis: Risk factors and impact on disease severity in human immunodeficiency virus/hepatitis C virus coinfection

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an RNA-binding protein expressed in embryonic tissues and multiple cancers. To investigate the role of IMP3 in hepatocellular carcinoma (HCC), its protein expression in the surgically resected unifocal tumors of 377 HCC patients (296 men and 81 women) with ages ranging from 7 to 88 years (mean, 55.49 years) was analyzed by immunohistochemistry. IMP3 was expressed in 255 (67.6%) of 377 resected unifocal primary HCCs. IMP3 protein was predominantly expressed in tumor border and invasive front, and it was more abundant in the satellite nodules and tumor thrombi than in the main tumors. The expression correlated with high alpha-fetoprotein (>200 ng/mL, P < 1 x 10(-7)), larger tumor size (>5 cm, P = 0.006), high tumor grade (P < 1 x 10(-7)), and high tumor stage with vascular invasion and various degrees of intrahepatic metastasis (P < 1 x 10(-7)). IMP3 expression predicted early tumor recurrence (P < 1 x 10(-7)) and was a strong indicator of poor prognosis (P < 0.0001). Depletion of IMP3 with RNA interference in HCC cell line HA22T caused a decrease in cell motility, invasion, and transendothelial migration. Microarray analysis revealed that IMP3 depletion was associated with downregulation of multiple genes involved in tumor invasion. CONCLUSION: Our results indicate that IMP3 plays an important role in tumor invasion and metastasis and is a strong prognostic factor for patients with HCC.     

Risk factors for high-risk human papillomavirus infection in unscreened Malian women

Objective To investigate the epidemiology of human papillomavirus (HPV) infection in Malian women, for whom cervical cancer is the most common cancer and the second most common cause of cancer‐related mortality. Methods Pilot study of 202 women aged 15–65 to determine the prevalence rate of high‐risk HPV infection among unscreened Malian women. Information on risk factors was collected through a standardized, structured interview and clinical examination. High‐risk (HR) HPV DNA was detected using signal amplification methods (hybrid capture II). Results High‐risk HPV DNA was detected in 12% of unscreened women, while visual inspection after application of acetic acid and Lugol’s iodine (VIA/VILI) identified suspicious abnormalities in 2.5% of unscreened women. Histopathological evaluation of VIA/VILI‐positive biopsies revealed no evidence of cervical intraepithelial neoplasia or cervical cancer. The majority of infections occurred among women in the 15–24 year old range. Compared to women who were married or widowed, single women were 3.5 times more likely to be infected with HR HPV. Conclusions The prevalence of infection with cancer causing types of HPV in this study was 12%. These prevalence estimates are consistent with what has been reported previously for other West African countries.     

Direct-acting antivirals for hepatitis C virus infections in patients co-infected with human immunodeficiency virus

Nearly three-quarters of human immunodeficiency virus-hepatitis C virus (HIV-HCV) coinfected patients in France currently need to be cured of their chronic HCV infection. The increase in sustained virological response rates obtained with the recently available HCV protease inhibitors in treatment-na?ve genotype-1 patients has generated considerable hope in these co-infected patients. However, several particularities (such as a higher baseline HCV load, more advanced liver fibrosis, frequent co-morbidities, and the risk of toxicity and drug-drug interactions) have not allowed the direct extrapolation of the results observed in HCV-monoinfected patients to patients with HIV-HCV co-infection. Yet, despite these uncertainties and the little available data from ongoing trials, several proposals can be made not only because the patients and drugs are ready and waiting, but also because the clock is ticking. In general, it can be advocated that HCV triple therapy should be offered to most HIV-infected patients with advanced liver fibrosis, but should be deferred or discussed on a case-by-case basis in those with mild-to-moderate fibrosis. However, such proposals rely on a relatively small amount of evidence and many questions are still pending, as studies in HIV-HCV co-infected patients have been late in coming and are several years behind those in HCV-monoinfected patients. Thus, this situation, in the context of more rapid and more severe infection, and lower response rates with standard care (pegylated interferon and ribavirin), along with the many potential drug-drug interactions (particularly with antiretroviral therapy), underscores the need for earlier evaluation of new strategies, schedules and new direct-acting antivirals in HIV-infected patients.     

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.     

Risk factors associated with hepatitis C among patients co-infected with human immunodeficiency virus: a case-control study

A case-control study was carried out to assess the risk factors associated with hepatitis C in patients infected with human immunodeficiency virus. One hundred eighteen patients tested positive for hepatitis C virus (HCV) and were included as cases, and 117 tested negative for HCV and were included as controls. Information was collected through a questionnaire. The risk factors that showed a significant association with co-infection by multivariate analysis were an age of 30-39 years (odds ratio [OR] = 4.65, 95% confidence interval [CI] = 1.31-16.43), an age of 40-49 years (OR = 6.48, 95% CI = 1.70-24.78), an age > 50 years (OR = 7.50, 95% CI = 1.54-36.68), use of intravenous drugs (OR = 25.46, 95% CI = 4.91-131.88), use of inhaled illicit drugs (OR = 3.56, 95% CI = 1.22-10.44), anal intercourse (OR = 3.93, 95% CI = 1.27-12.13), a sexual partner with a history of liver disease (OR = 5.45, 95% CI = 1.33-22.32), a sexual partner with a history of blood transfusions (OR = 4.79, 95% CI = 0.95-24.19), and sexual partner with a history of intravenous drug use (OR = 3.46, 95% CI = 1.24-9.65).     

Management of the coinfected patient: human immunodeficiency virus/hepatitis B and human immunodeficiency virus/hepatitis C

Deaths from liver disease have increased in persons infected with human immunodeficiency virus (HIV) because of coinfection with chronic hepatitis B and C; consequently, all HIV-infected patients should be screened for hepatitis B and C, and all those susceptible should be vaccinated for hepatitis B. Hepatitis A vaccination is indicated for susceptible coinfected patients. It is also important to stress other means of preventing the transmission of hepatitis, such as safe sex and avoidance of blood exposures. Three oral agents, lamivudine, adefovir, and tenofovir, are active against hepatitis B infection. The need for highly active antiretroviral therapy and hepatitis B therapy should be addressed in a coordinated fashion, since two of these agents are active against both HIV and hepatitis B virus. Oral combination therapy for hepatitis B infection looks promising but needs further study. Combination therapy for chronic hepatitis C with pegylated interferon plus ribavirin is the most effective available therapy and the current standard of care. Prior to therapy, patients should be evaluated for contraindications to therapy. During treatment, they should be closely monitored for adverse events.     

Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections

Alcohol use disorder(AUD) and hepatitis C virus(HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus(HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease. In addition, AUD and HCV infection are also frequent within a proportion of patients with HIV infection, which negatively impacts liver disease. This review summarizes the current knowledge regarding pathological interactions of AUD with hepatitis C infection, HIV infection, and HCV/HIV co-infection, as well as relating to AUD treatment interventions in these individuals.     

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.     

Risk factors for anaemia in human immunodeficiency virus/hepatitis C virus-coinfected patients treated with interferon plus ribavirin

The most frequent and the most troublesome adverse effect of interferon plus ribavirin-based therapy is anaemia. The aim of this analysis was to determine the incidence and risk factors of anaemia (Hb < 10 g/dL) in human immunodeficiency virus/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy. We reviewed all cases of anaemia occurring among 416 patients participating in a randomized, controlled 48-week trial comparing peginterferon (peg-IFN) alpha 2b plus ribavirin with interferon alpha-2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, HCV therapy and clinical and laboratory findings. Sixty-one (15.9%) of the 383 patients who received at least one dose of anti-HCV treatment developed anaemia. In multivariate analysis the risk of anaemia was significantly associated with zidovudine (OR, 3.27 95% CI, 1.64-6.54, P = 0.0008) and peg-IFN (OR, 2.35; 95% CI, 1.16-4.57, P = 0.0179). The risk of anaemia was lower in patients with higher baseline haemoglobin levels (OR, 0.35 95% CI, 0.26-0.49, P < 0.0001) and in patients receiving protease inhibitor-based antiretroviral therapy (OR, 0.51 95% CI, 0.30-0.86, P = 0.0114). Zidovudine discontinuation could help to avoid anaemia associated with anti-HCV therapy.     

Intrafamilial transmission of hepatitis C virus in patients with hepatitis C and human immunodeficiency virus coinfection

OBJECTIVE: The aim of this study was to determine whether hepatitis C virus (HCV)/HIV coinfection of index cases increases intrafamilial transmission (sexual and nonsexual contacts) of HCV. METHODS: We prospectively enrolled 347 subjects, including 87 family members of 53 HCV/HIV-coinfected index cases and 134 family members of 73 HCV-monoinfected index cases, which served as a control group. All index cases and family members were interviewed, and a screening for HCV and HIV using enzyme-linked immunosorbent assays was performed. Positive samples were confirmed by polymerase chain reaction and tested for genotype and HCV RNA viral load. A meta-analysis designed to assess the pooled risk of sexual transmission of HCV among HCV/HIV-coinfected patients was performed. RESULTS: Anti-HCV was detected in 2.2% of family members of HCV-monoinfected index cases and 2.3% of family members of HCV/HIV-coinfected index cases. Viral load was higher in coinfected index cases (7.2 x 10(6) mEq/ml) compared with HCV alone (1.9 x 10(6) mEq/ml), p = 0.01. HCV genotype concordance was observed in three family members of HCV-monoinfected index cases and in two family members of HCV/HIV-coinfected index cases. The pooled OR of the meta-analysis evaluating HIV as a cofactor of sexual transmission of HCV was 1.54 (95% CI = 0.76-3.12). CONCLUSIONS: Our data demonstrate a low prevalence of intrafamilial transmission of HCV, independent of the presence of HCV/HIV coinfection. This finding is supported by meta-analysis, which failed to identify HIV as an important cofactor of sexual transmission in HCV/HIV-coinfected patients.     

Frequency of hepatitis B, C and D and human immunodeficiency virus infections in multi-transfused thalassemics.

Of forty multi-transfused thalassemia patients (26 males, 14 females; mean age 8.1 +/- 5.3 years, range 1-35) with no clinical or biochemical evidence of liver disease, HBsAg, anti-hepatitis C virus and anti-human immunodeficiency virus antibodies were present in 18 (45%), 7 (17.5%) and 1 (2.5%) cases respectively. Three of the 18 (16.7%) HBsAg positive patients were anti-delta antibody positive. Our results indicate that more than 50% of multi-transfused thalassemia patients show serological evidence of one or more of hepatitis B, C and D and human immunodeficiency virus infection.     

Understanding human immunodeficiency virus type 1 and hepatitis C virus coinfection

In recent years, there has been an alarming increase in the number of cases of coinfection with the human immunodeficiency virus type 1 (HIV-1) and the hepatitis C virus (HCV). It is now known that coinfection of HIV-1 patients by HCV can complicate the treatment of these patients with highly active antiretroviral therapy and the interactions between anti-HIV-1 and anti-HCV medications can also affect treatment efficacy and efficiency. Equally concerning, the bidirectional interferences between the two viruses are complex and can modify the natural history of both infections. This review aims to summarize the findings of numerous scientific investigations in the area of HIV/HCV coinfection. These investigations can be broadly classified into 3 groups; (a) immune evasion mechanisms (b) viral evolution and quasispecies diversity and (c) functions of viral proteins and their interactions with host factors. Our cumulative knowledge in this area and future research on the interplay between these two viruses will be important to the development of better antiviral therapeutics.     

Non-initiation of hepatitis C virus antiviral therapy in patients with human immunodeficiency virus/hepatitis C virus co-infection

AIM: To assess whether reasons for hepatitis C virus(HCV) therapy non-initiation differentially affect racial and ethnic minorities with human immunodeficiency virus(HIV)/HCV co-infection.METHODS: Analysis included co-infected HCV treatment-na?ve patients in the University of North Carolina CFAR HIV Clinical Cohort(January 1, 2004 and December31, 2011). Medical records were abstracted to document non-modifiable medical(e.g., hepatic decompensation, advanced immunosuppression), potentially modifiable medical(e.g., substance abuse, severe depression, psychiatric illness), and non-medical(e.g., personal,social, and economic factors) reasons for non-initiation. Statistical differences in the prevalence of reasons for non-treatment between racial/ethnic groups were assessed using the two-tailed Fisher's exact test. Three separate regression models were fit for each reason category. Odds ratios and their 95%CIs(Wald's) were computed.RESULTS: One hundred and seventy-one patients with HIV/HCV co-infection within the cohort met study inclusion. The study sample was racially and ethnically diverse; most patients were African-American(74%), followed by Caucasian(19%), and Hispanic/other(7%). The median age was 46 years(interquartile range = 39-50) and most patients were male(74%). Among the 171 patients, reasons for non-treatment were common among all patients, regardless of race/ethnicity(50% with ≥ 1 non-modifiable medical reason, 66% with ≥1 potentially modifiable medical reason, and 66% with ≥ 1 non-medical reason). There were no significant differences by race/ethnicity. Compared to Caucasians, African-Americans did not have increased odds of nonmodifiable [adjusted odds ratio(a OR) = 1.47, 95%CI: 0.57-3.80], potentially modifiable(a OR = 0.72, 95%CI: 0.25-2.09) or non-medical(a OR = 0.90, 95%CI: 0.32-2.52) reasons for non-initiation.CONCLUSION: Race/ethnicity alone is not predictive of reasons for HCV therapy non-initiation. Targeted interventions are needed to improve access to therapy for all co-infected patients, including minorities.     

Prevalence and virological profiles of hepatitis B infection in human immunodeficiency virus patients

AIM: To determine the prevalence of hepatitis B virus (HBV) in adult human immunodeficiency virus (HIV) patients with CD4+ T-cell count less than 500/mm 3 and without antiretroviral therapy; to describe different HBV-HIV coinfection virological profiles; and to search for factors associated with HBs antigen (HBsAg) presence in these HIV positive patients.METHODS: During four months (June through September 2006), 491 patients were received in four HIV positive monitoring clinical centers in Abidjan. Inclusion criteria: HIV-1 or HIV-1 and 2 positive patients, age ≥ 18 years, CD4+ T-cell count < 500/mL and formal and signed consent of the patient. Realized blood tests included HIV serology, CD4+ T-cell count, quantitative HIV RNA load and HBV serological markers, such as HBsAg and HBc antibody (anti-HBcAb). We performed HBeAg, anti-HBe antibody (anti-HBeAb), anti-HBc IgM and quantitative HBV DNA load in HBsAg positive patients. Anti-HBsAb had been tested in HIV patients with HBsAg negative and anti-HBcAb-positive. HBV DNA was also tested in 188 anti-HBcAb positive patients with HBsAg negative status and without anti-HBsAb. Univariate analysis (Pearsonχ 2 test or Fischer exact test) and multivariate analysis (backward step-wise selection logistic regression) were performed as statistical analysis. RESULTS: Mean age of 491 patients was 36 ± 8.68 years and 73.3% were female. Type-1 HIV was found in 97% and dual-type HIV (type 1 plus type 2) in 3%. World Health Organization (WHO) clinical stage was 1, 2, 3 and 4 respectively in 61 (12.4%), 233 (47.5%), 172 (35%) and 25 patients (5.1%). Median CD4+ T-cell count was 341/mm 3 (interquartile range: 221-470). One hundred and twelve patients had less than 200 CD4+ T-cell/mm 3 . Plasma HIV-1 RNA load was elevated (≥ 5 log 10 copies/mL) in 221 patients (45%). HBsAg and anti-HBcAb prevalence was respectively 13.4% and 72.9%. Of the 66 HBsAg positive patients, 22 were inactive HBV carriers (33.3%), 21 had HBeAg positive hepatitis (31.8%) and 20 had HBeAg negative hepatitis (30.3%). HBeAg and anti-HBeAb were indeterminate in 3 of them. Occult B infection prevalence (HBsAg negative, anti-HBcAb positive, anti-HBsAb negative and detectable HBV DNA) was 21.3%. Three parameters were significantly associated with the presence of HBsAg: male [odds ratio (OR): 2.2;P = 0.005; 95% confidence interval (CI): 1.3-3.8]; WHO stage 4 (OR: 3.2;P = 0.01;95% CI: 1.3-7.9); and aspartate aminotransferase (AST) level higher than the standard (OR: 1.9;P = 0.04; 95% CI: 1.02-3.8). CONCLUSION: HBV infection prevalence is high in HIV-positive patients. HBeAg positive chronic hepatitis and occult HBV infection are more frequent in HIVpositive patients than in HIV negative ones. Parameters associated with HBsAg positivity were male gender, AIDS status and increased AST level.     

Prevalence of coinfection with human immunodeficiency virus and hepatitis C virus in Japan

People with human immunodeficiency virus (HIV) infection are frequently infected with hepatitis C virus (HCV), because of the common transmission routes. Since the dissemination of hyperactive antiretrovirus therapy (HAART), the morbidity and mortality associated with HIV infection have declined. However, the reduction in mortality due to opportunistic infection has made HCV-associated liver diseases the leading cause of mortality in Western countries. A similar situation is assumed in Japan, but the status of coinfection with HIV and HCV is unclear. We conducted a nationwide survey to determine the prevalence of coinfection with HIV and HCV by distributing a questionnaire to the hospitals in the HIV/AIDS Network of Japan. Among 4877 patients reported to be HIV-positive, 935 (19.2%) were also positive for the anti-HCV antibody. Most (84.1%) of the patients coinfected with HIV and HCV were recipients of blood products. These data, for the first time, show the current status of coinfection with HIV and HCV in Japan. A detailed analysis of the progression and severity of liver diseases in the coinfected patients is expected.     

Risk factors connected with hepatitis C infections in Finland.

Risk factors of 160 hepatitis C virus antibody (anti-HCV) positive patients, found in our serological routine, were analyzed. 89% of the patients had been exposed to blood (64% had a history of i.v. drug abuse, 24% had used whole blood or blood products, 0.6% had a profession connected with blood exposure). 8.1% of the patients had lived or travelled in Southern countries, notably in Africa and in the Eastern Mediterranean, 0.6% had an anti-HCV positive sex partner. 2.5% of the patients had no known risk factors.