Hepatitis C Virus Monoinfection Research Articles

OCCULT HEPATITIS B VIRUS INFECTION IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION AND HEPATOCELLULAR CARCINOMA

Hepatocellular carcinoma is one of the most common cancers worldwide. Primary known risk factors for HCC are Hepatitis C virus (HCV), Hepatitis B virus (HBV) and alcoholic liver disease. There is little information about occult HBV and its relation to HCC in chronic . We aimed to evaluate the prevalence and the possible clinical impact of occult HBV infection in chronic HCV patients with hepatocellular carcinoma. Patient and methods: A total number of 140 patients with hepatocellular carcinoma were examined, 118 patients were included in this study. They had positive HCV-RNA, negative HBsAg and radiological evidence of Hepatocellular carcinoma, previous antiviral therapy or serological evidence of autoimmune hepatitis and were divided into two groups according to their HBc-Ab status: Group (I) 93 patients positive for HBc-Ab (Occult HBV/HCV dual infection), Group (II) 25 patients negative for HBc-Ab (HCV mono infection). The rest of HCC patients were coinfected with HCV and HBV, 8 patients had HBV infection (+ve HBV sAg and –ve HCV Ab) and 4 patients had negative tests for both HCV and HBV were excluded. Results: A statistically significant increase in serum levels of AST, ALT, bilirubin, Alpha-fetoprotein with more cirrhosis, ascites, liver decompensation (according to Child-Turcott-Pugh score) and more hepatic focal lesions and malignant portal vein thrombosis (through radiological diagnosis) in Group (I) as compared to Group (II), while there was no statistically significant difference among Group (I) and Group (II) as regarding PT% or spleen size. Conclusion: Occult HBV infection is extensively common among HCC chronic hepatitis C infected patients and presence of occult HBV infection is associated with more deterioration of liver status. Key words: Occult HBV, chronic HCV, HCC.

The influence of hepatitis B and C virus coinfection on liver histopathology in children.

The influence of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection on liver histology in children remains unknown. We analyzed histopathological features in 70 treatment-naïve children: 10 with HBV/HCV coinfection (case group A), 30 with HBV (control group B), and 30 with HCV (control group C). Liver biopsies were scored for grading and staging according to Knodell’s modified system and were tested for an association with demographic and laboratory data. The mean grade was higher in coinfected children compared to control group C (6.2 ± 3.0 vs. 4.2 ± 2.5, p = 0.04), but not control group B (p = 0.47). A higher proportion of patients with moderate to severe necroinflammation were observed in case group A compared to isolated HCV (p = 0.05). Mean staging did not differ between the case and control groups. Multivariate analysis revealed that HBV/HCV coinfection and aminotransferase activity were independently associated with moderate to severe necroinflammatory activity Conclusion: HBV/HCV coinfection was associated with moderate to severe necroinflammation irrespective of age at biopsy or duration of infection and led to significantly higher necroinflammatory activity than HCV monoinfection. HBV/HCV coinfection did not enhance fibrosis. High aminotransferase levels were positively associated with moderate to severe necroinflammation.

Do the epidemiology, physiological mechanisms and characteristics of hepatocellular carcinoma in HIV-infected patients justify specific screening policies?

Reducing the incidence of hepatocellular carcinoma (HCC) in HIV-infected patients has become a serious problem when managing these patients. There are many explanations for this disease evolution, which notably include their longer survival under effective antiviral therapy and also the more rapid evolution of chronic liver disease. Despite recent advances in the management of hepatitis B (HBV) and hepatitis C (HCV) viral diseases, which will probably increase the number of patients achieving a virological response, HIV-infected patients with cirrhosis are still at risk of the onset of HCC. This evolution to HCC is also correlated to other comorbidities such as excessive alcohol consumption and nonalcoholic steatohepatitis (NASH). HCC thus remains a public health issue in this population. The poor prognosis and aggressiveness of HCC have been fully demonstrated, but the mechanisms underlying this aggressiveness are not yet well defined. As well as underlying mechanisms that contribute to accelerating hepatocarcinogenesis in HIV-infected patients, there are other reasons why HIV-infected patients should be considered a higher risk population. This review discusses the principal epidemiological determinants; the mechanisms of pathogenesis; and the treatment of HCC in HIV/HBV and HIV/HCV coinfected patients. It also discusses the probable need to develop a specific screening policy for HCC in this population in order to prevent the rapid development and to make them more amenable to a curative treatment.

The impact of antihyperlipidemic drugs on the viral load of patients with chronic hepatitis C infection: a meta-analysis.

Several studies investigating the role of statins and fibrates in chronic hepatitis C virus (HCV) infection offered so far conflicting evidence regarding the antiviral potency of these medications, whereas combination of these drugs with pegylated interferon and ribavirin improved in some trials therapeutic outcome. We conducted a literature search to identify trials that included monoinfected HCV patients, treated with statins or fibrates as monotherapy with the primary end point of our meta-analysis being the quantitative change of HCV-RNA induced by these medications. Logarithmic changes of the viral load (ΔlogVL) and confidence intervals (CIs) were calculated according to the DerSimonian-Laird estimate. Statistical heterogeneity was assessed with the I² statistic. We identified eight observational studies that evaluated the potency of bezafibrate and different statins as monotherapy to induce a significant reduction of HCV-RNA in HCV-monoinfected patients (n = 281). Overall, a significant reduction of viral load with mean 0.19 [log10 IU/mL] (95%-confidence interval, (CI) 0.11-0.28) could be observed when antihyperlipidemic medications were administered. Bezafibrate featured the highest antiviral efficacy (0.45 log10 reduction, 95%-CI, 0.17-0.72) among all medications and fluvastatin (0.20 log10 reduction, 95%-CI, 0.09-0.31) among all statins tested. Based on meta-analysis, fibrates and statins induce a reduction of HCV viral load. We suggest that the addition of statins and fibrates to antiviral regimes, especially in HCV patients with concomitant dyslipidemia, could beside the established reduction of cardiovascular risk increase the potency of antiviral therapy.

Hepatitis C in HIV-infected patients: impact of direct-acting antivirals.

Approximately 30% of HIV-infected patients are co-infected with hepatitis C virus (HCV). After the release of highly active antiretroviral therapy, liver disease has become the leading cause of morbidity and mortality in HIV patients. Prior to 2011, HCV treatment with pegylated-interferon and ribavirin in HCV/HIV co-infected patients only allowed 14-38% of patients with HCV genotype 1 to achieve a sustained virologic response (SVR). Additionally, treatment was commonly discontinued as a result of adverse events. Recently, simeprevir and sofosbuvir have been approved by the US Food and Drug Administration (FDA) for HCV mono-infection. Sofosbuvir has been given FDA approval in co-infected patients offering unprecedented SVR rates and the potential for interferon-free therapy. HCV therapies that are in the pipeline offer improved treatment times, safety profiles, and rates of SVR. Despite these improvements, several new issues including adherence, drug-drug interactions with antiretroviral therapies, adverse events, resistance, and patient selection may complicate therapy. This article reviews the current status of direct-acting antivirals (DAA)-containing regimens for HIV/HCV co-infected patients in the USA. New results investigating telaprevir and boceprevir are also discussed as they are relevant for locations where new DAAs are not available. The impact future interferon-free therapies may have on co-infected patients is also discussed.

Activation of extrinsic apoptosis pathway in HCV monoinfected and HIV-HCV coinfected patients, irrespective of liver disease severity.

Chronic hepatitis C virus (HCV) infection is associated with increased levels of peripheral T cell apoptosis. We aimed to study whether T cell apoptosis markers indicate pathways that may contribute to clinical progression in HCV monoinfected and HIV-HCV coinfected patients. Activation of the extrinsic apoptosis pathways was measured by levels of death receptor Fas, initiator caspase 8 and effector caspases 3 and 7 activity and Annexin V binding on peripheral CD4 and CD8 T cells of HCV monoinfected and HIV/HCV coinfected patients, as well as healthy controls and HIV-infected, hepatitis B virus-infected and primary biliary cirrhosis disease controls. Association with liver fibrosis was assessed by biopsy or by transient elastography. HCV monoinfected and HIV-HCV coinfected patients displayed enhanced peripheral CD4 and CD8 T cell apoptosis. Caspase 8 activity was highest in HIV-HCV coinfection, without enhanced downstream activity of caspases 3 and 7. Level of peripheral T cell apoptosis was independent of liver fibrosis or other disease parameters in all disease groups. The extrinsic apoptosis pathway is upregulated in HCV monoinfection and HIV-HCV coinfection, but this is independent of liver disease severity.

A preliminary assessment of the clinical utility of measuring hepatitis C virus antibody to evaluate infection status

To investigate the potential of hepatitis C virus (HCV) antibody measurement as a clinical approach to determine the infection status and potential for spontaneous-resolution among patients with HCV mono-infection and HCV/human immunodeficiency virus (HIV) co-infection. A total of 340 individuals who tested positive for serum anti-HCV antibodies and/or serum anti-HW antibodies were enrolled for study in 2009 from a single village in central China. Markers of liver function (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and infection (anti-HCV antibodies, CD4⁺ T cell counts, HCV genotype, and HCV viral load) were measured at baseline and follow-up (in July 2012). At follow-up,the subjects were grouped according to ongoing HCV mono-infection (n=129), ongoing HCV/HIV co-infection (n=98), spontaneously resolved (SR)-HCV in mono-infection (n=65), and SR-HCV in HCV/HIV co-infection (n=48) for statistical analysis. Almost all of the subjects in the ongoing HCV mono-infection group showed high levels of HCV antibodies (S/CO more than or equal to 10), but the majority of the subjects in the SR-HCV in mono-infection group and in the ongoing HCV/HIV co-infection group. The SR-HCV mono-infection group showed a remarkable decrease in HCV antibodies from 2009 (HIV:7.75 ± 3.8; HIV+:7.61 ± 3.47) to 2012 (HIV:5.51 ± 3.67; HIW:4.93 ± 3.35) (HIV:t =10.67, P less than 0.01; HIV+:t =9.52, P less than 0.01). The ongoing HCV/HIV co-infection group showed a positive correlation between HCV antibodies S/CO ratio and CD4⁺ T cell count (r=028, P=0.008). In the ongoing HCV mono-infection group,the levels of HCV antibodies were significantly higher in individuals infected with HCV-1b than in those with HCV-2a (14.74 ± 1.68 vs.14.08 ± 1.44, t=2.20, P=0.03). In the ongoing HCV/HIV co-infection group, the numbers of subjects with elevated (more than 40 U/L) liver function markers were significantly different according to the HCV genotype infection:HCV-1b:ALT, 25/42 vs.16/56 (x²=9.45, P=0.002); HCV2a:AST, 28/42 vs.18/56 (x²=11.49, P=0.001). The HCV RNA positive rate was significantly higher in subjects with high HCV antibody cutoff values (S/CO more than or equal to 10) than in those with low HCV antibody (S/CO less than 10) (HIV:128/151 vs.1/43, x²=102.11, P less than 0.01; HIV+:88/98 vs.10/48, x²=69.44, P less than 0.01), regardless of HIV co-infection. Significantly more subjects in the ongoing HCV mono-infection group had elevated (more than 40 U/L) ALT or AST than the subjects in the SR-HCV mono-infection group with high levels of HCV antibody (S/CO more than or equal to 10) (ALT:57/128 vs.2/23, x²=10.52, P=0.001; AST:57/128 vs.0/23, x²=16.45, P less than 0.01). Serum HCV antibody levels, in combination with other clinical information such as liver function and HIV infection status, may aid in the preliminarily evaluation of an individual's HCV infection status and likelihood for spontaneous resolution. Low levels of HCV antibody (S/CO less than 10) may indicate a better chance of SR-HCV, after ruling out the possibility of suffering from immunosuppressive diseases such as HIV infection.

GB Virus C infection in Patients With HIV/Hepatitis C Virus Coinfection: Improvement of the Liver Function in Chronic Hepatitis C

Background:Previous studies in patients with hepatitis C virus (HCV)/HIV coinfection have shown that the presence of GBV-C is associated with significantly less compensated and decompensated cirrhosis, and an improvement in cirrhosis-free survival.Objectives:This study aimed to describe the effect of GBV-C in patients with chronic hepatitis C and HIV coinfection.Patients and Methods:We retrospectively studied 105 injecting drug users with chronic hepatitis C and HIV coinfection and 72 patients with chronic HCV mono-infections. Plasma samples were tested for GBV-C RNA with primers to the 5’untranslated region gene. HIV and HCV viral load, CD4+ and CD8+ cell count, and the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested in all patients.Results:GBV-C RNA was identified in 34 (32.38%) of the patients with HIV/HCV coinfection, and in 24 (33.33%) of the patients with HCV mono-infection. GBV-C infection was associated with significantly lower ALT and AST levels in patients with chronic hepatitis C and HIV coinfection, but not in those HCV mono-infections. The presence of GBV-C infection was not correlated with CD4+ and CD8+ cell count, gender, age, HIV load, HCV load, and HCV genotype.Conclusions:This study found that GBV-C infection has a high frequency among injecting drug users with HIV/HCV coinfection and HCV mono-infection in Yunnan, China. In patients with chronic hepatitis C and HIV coinfection, GBV-C RNA was associated with significantly lower ALT and AST levels, suggesting a beneficial effect of GBV-C infection on chronic hepatitis C.

Towards hepatitis C eradication from the HIV-infected population

Around 10–15% of the 35 million people living with HIV worldwide have chronic hepatitis C virus (HCV) infection and are prone to develop liver-related complications. Exposure to HCV is almost universal among injecting drug users and is on the rise among homosexual men. Response to peginterferon-ribavirin therapy is generally lower in coinfection compared to HCV monoinfection. For this reason, the advent of direct-acting antivirals (DAA) is eagerly awaited for this population. The results of trials using DAA in coinfection show that treatment response rates are similar to those obtained in HCV monoinfection. Thus, HIV should no longer be considered as a “special” population, as long as antiretroviral therapy is given and drug interactions are taken into account. Envisioning HCV eradication from the HIV population faces major challenges ahead, including identification of the large number of undiagnosed individuals, and ensuring wide access to the best but often expensive HCV medications. This article forms part of a symposium in Antiviral Research on “Hepatitis C: next steps toward global eradication”.

Deaths Among People With Hepatitis C in New York City, 2000-2011

Infection with hepatitis C virus (HCV) increases the risk of death from liver and nonliver-related diseases. Coinfection with human immunodeficiency virus (HIV) further increases this risk. Surveillance data (2000-2010) and mortality data (2000-2011) maintained by the New York City Department of Health and Mental Hygiene (DOHMH) were deterministically cross-matched. Factors associated with and causes of death among HCV-infected adult decedents were analyzed. Between 2000 and 2011, 13 307 HCV-monoinfected adults died, and 5475 adults coinfected with HCV/HIV died. Decedents with HCV monoinfection were more likely to have died of liver cancer (odds ratio [OR] = 9.2), drug-related causes (OR = 4.3), and cirrhosis (OR = 3.7), compared with persons with neither infection. HCV/HIV-coinfected decedents were more likely to have died of liver cancer (OR = 2.2) and drug-related causes (OR = 3.1), compared with persons with neither infection. Among coinfected decedents, 53.6% of deaths were attributed to HIV/AIDS, and 94% of deaths occurred prematurely (before age 65). Among persons with HCV who died, more than half died within 3 years of an HCV report to DOHMH. HCV-infected adults were at increased risk of dying and of dying prematurely, particularly from conditions associated with HCV, such as HIV/AIDS or drug use. The short interval between HCV report and death suggests a need for earlier testing and improved treatment.

Hepatitis C Direct-acting Antiviral Agents

Hepatitis C virus (HCV)-related liver disease is a major source of mortality in HIV-infected patients. Approximately one third of all patients with HIV are co-infected with HCV. Patients co-infected with HIV/HCV have shown lower rates of sustained virologic response with pegylated-interferon and weight-based ribavirin as well as more rapid progression of fibrosis than those with HCV mono-infection. Several direct-acting antiviral agents (DAAs), developed originally for HCV mono-infection, are being reevaluated for HIV/HCV co-infection. In addition, entirely new DAAs are being developed, including, interferon-free regimens with fewer side effects, allowing novel treatment opportunities for difficult-to-treat patients. In order for HCV DAAs to be successfully used in the HIV/HCV co-infected population several hurdles must be overcome, including adverse event management and drug-drug interactions. The aim of this review is to discuss the results of trials for new HCV therapies being developed for HIV/HCV co-infected patients and the impact of interferon-free regimens on treatment in the future.

Predictors of liver-related death among people who inject drugs in Vancouver, Canada: a 15-year prospective cohort study.

IntroductionWhile HIV/AIDS remains an important cause of death among people who inject drugs (PWID), the potential mortality burden attributable to hepatitis C virus (HCV) infection among this population is of increasing concern. Therefore, we sought to identify trends in and predictors of liver-related mortality among PWID.MethodsData were derived from prospective cohorts of PWID in Vancouver, Canada, between 1996 and 2011. Cohort data were linked to the provincial vital statistics database to ascertain mortality rates and causes of death. Multivariate Cox proportional hazards regression was used to examine the relationship between HCV infection and time to liver-related death. A sub-analysis examined the effect of HIV/HCV co-infection.Results and discussionIn total, 2,279 PWID participated in this study, with 1,921 (84.3%) having seroconverted to anti-HCV prior to baseline assessments and 124 (5.4%) during follow-up. The liver-related mortality rate was 2.1 (95% confidence interval [CI]: 1.5–3.0) deaths per 1,000 person-years and was stable over time. In multivariate analyses, HCV seropositivity was not significantly associated with liver-related mortality (adjusted relative hazard [ARH]: 0.45; 95% CI: 0.15–1.37), but HIV seropositivity was (ARH: 2.67; 95% CI: 1.27–5.63). In sub-analysis, HIV/HCV co-infection had a 2.53 (95% CI: 1.18–5.46) times hazard of liver-related death compared with HCV mono-infection.ConclusionsIn this study, HCV seropositivity did not predict liver-related mortality while HIV seropositivity did. The findings highlight the critical role of HIV mono- and co-infection rather than HCV infection in contributing to liver-related mortality among PWID in this setting.

Efficacy of Treatments for Patients with Chronic Liver Disease due to Coinfection with Hepatitis B and C Viruses

The hepatitis B virus (HBV) and the hepatitis C virus (HCV) are the leading causes of chronic liver disease. Patients with chronic liver disease who are co infected with both HBV and HCV develop cirrhosis and hepatocellular carcinoma (HCC) more rapidly than patients with monoinfection with HBV alone or HCV alone. However, standard-of-care recommendations have not been well established for patients with HBV/HCV co infection. In this study, a literature review was conducted on the efficacy of therapies for patients with HBV/HCV coinfection. Many papers reported that following combination therapy with interferon (IFN) plus ribavirin (RBV), there were no significant differences in the rate of achievement of a sustained virological response (SVR) to HCV between patients with HBV/HCV coinfection and patients with HCV monoinfection. However, the efficacy of these therapies for HBV infection in coinfected patients is complex. In patients with HBV/HCV coinfection characterized by a predominance of HCV, it is highly probable for serum hepatitis B surface antigen (HBsAg) titers to decrease or disappear during or after IFN/RBV combination therapy. On the other hand, reactivation of HBV due to the suspected inhibition of HCV replication is sometimes detected in coinfected patients during or after IFN/RBV combination therapy.

CIHR Canadian HIV Trials Network Co-Infection and Concurrent Diseases Core: Updated Canadian guidelines for the treatment of hepatitis C infection in HIV-hepatitis C coinfected adults.

Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Management of HIV-HCV coinfection is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens. To update national standards for the management of HCV-HIV coinfected adults in the Canadian context. A standing working group with specific clinical expertise in HIV-HCV coinfection was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published data regarding HCV antiviral treatments and to update the Canadian HIV-HCV coinfection guidelines. Recent data suggest that the gap in sustained virological response rates between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All HIV-HCV coinfected individuals should be assessed for HCV therapy. First-line treatment for genotypes 1 through 6 includes pegylated interferon and weight-based ribavirin dosing plus the nucleotide sofosbuvir for 12 weeks. Sofosbuvir in combination with the protease inhibitor simeprevir is another first-line consideration for genotype 1 infection. Sofosbuvir with ribavirin for 12 weeks (genotype 2) and 24 weeks (genotype 3) is also recommended as first-line treatment. Recommendations may not supersede individual clinical judgement.

Updates on the treatment and outcomes of dual chronic hepatitis C and B virus infection

Dual hepatitis C virus (HCV)/hepatitis B virus (HBV) infection is found in HBV or HCV endemic areas, and in specific populations exhibiting a high risk of parenteral viral transmission. Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients. The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations. Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections. Strikingly, approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV. The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined. Furthermore, approximately 30% of dually infected patients lost hepatitis B surface antigen (HBsAg) within 5 years after the start of peginterferon-based therapy, and 40% of them harbored occult HBV infection. The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations. Moreover, the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored. Finally, the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future, which warrants further clinical trials.

Treatment of patients with dual hepatitis C virus and hepatitis B virus infection: Resolved and unresolved issues

Dual hepatitis C virus (HCV)/hepatitis B virus (HBV) infection is not uncommon in HCV or HBV endemic areas and among subjects at risk of parenteral transmission. In patients dually infected with hepatitis C and B, the disease manifestations are usually more severe than those with either virus infection. In the past decade, the following issues have been resolved. In dually infected patients with active hepatitis C, combined pegylated interferon alfa plus ribavirin was effective, the treatment outcomes being similar to patients with HCV monoinfection. During long-term follow-up, the HCV response was sustained in around 97% of patients; and the long-term outcomes including the development of hepatocellular carcinoma and liver-related mortality were improved. However, several clinical issues remain to be resolved. First, host and viral factors influencing the long-term outcomes and treatment options in patients with dual HCV/HBV infection await further studies. Second, about 60% of dually infected patients with baseline undetectable serum HBV DNA levels develop HBV reactivation after the start of treatment. How to prevent and treat HBV reactivation should be clarified. Third, about 30% of dually infected patients lose hepatitis B surface antigen at 5 years after the end of combination therapy; the mechanisms need further investigations. Fourth, the optimal treatment strategies for dually infected patients with active hepatitis B or established cirrhosis should be explored in future clinical trials. Finally, the role of new direct-acting antiviral-based therapy for the treatment of patients with dual HCV/HBV infection also remains to be evaluated.

Correlates of Elevated Interleukin-6 and C-Reactive Protein in Persons With or at High Risk for HCV and HIV Infections

HIV and hepatitis C virus (HCV) infections may increase interleukin-6 (IL-6) and C-reactive protein (CRP). However, relationships between inflammatory biomarkers, chronic viral infections, clinical factors, and behavioral factors remain poorly understood. Using linear regression, we modeled cross-sectional associations between loge IL-6 or loge CRP levels and HCV, HIV, injection drug use, and comorbidity among 1191 injection drug users. Mean age was 47 years, 46.0% reported currently injecting drugs, 59.0% were HCV monoinfected, and 27% were HCV/HIV coinfected. In multivariable models, higher loge IL-6 was associated with HCV monoinfection [β = 0.191, 95% confidence interval (CI): 0.043 to 0.339] and HCV/HIV coinfection (β = 0.394, 95% CI: 0.214 to 0.574). In contrast, HCV monoinfection (β = -0.523, 95% CI: -0.275 to -0.789) and HCV/HIV coinfection (β = -0.554 95% CI: -0.260 to -0.847) were associated with lower CRP. Lower CRP with HCV infection was independent of liver fibrosis severity, synthetic function, or liver injury markers; CRP decreased with higher HCV RNA. Increased injection intensity was associated with higher IL-6 (P = 0.003) and CRP (P < 0.001); increasing comorbidity (P < 0.001) and older age (P = 0.028) were associated with higher IL-6; older age was associated with higher CRP among HCV-uninfected participants (P = 0.021). HIV and HCV infections contribute to chronic inflammation; however, reduced CRP possibly occurs through HCV-mediated mechanisms. Findings highlight potentially modifiable contributors to inflammation.

Treatment of Genotype 2 and Genotype 3 Hepatitis C Virus (HCV) Infection in Human Immunodeficiency Virus Positive Patients

Approximately 25% of persons living with the human immunodeficiency virus (HIV) are coinfected with the hepatitis C virus (HCV). In cohort studies of HIV-HCV coinfection, HCV genotypes 2 and 3 account for 15%-64% of disease. Compared with HCV monoinfection, liver disease is accelerated in coinfected patients, and anti-HCV treatment is less successful. This article reviews the current knowledge and recommendations for management of HCV genotype 2 and 3 infection in patients living with HIV. While pegylated interferon (PEG-IFN)/ ribavirin (RBV) remains the standard treatment for HCV genotype 2/3 infection, ongoing clinical trials with more effective therapies will soon be available. In particular, an IFN sparing regimen of sofosbuvir/RBV may become available in 2014. It is also evident that HCV genotypes 2 and 3 respond differently to therapy and should be approached differently both in practice and in clinical trials. Issues including drug-drug interactions between anti-HCV and anti-HIV therapies are addressed.

Expression of inhibitory markers is increased on effector memory T cells during hepatitis C virus/HIV coinfection as compared to hepatitis C virus or HIV monoinfection

Hepatitis C virus (HCV)/HIV coinfection is associated with rapid progression of hepatic fibrosis and liver disease. T-cell response has been implicated in the pathophysiological outcome of the disease. This study sought to evaluate the role of memory T-cell exhaustion in enhancing immune dysfunction during coinfection. Sixty-four patients were included in the study; HCV monoinfected (n = 21), HIV monoinfected (n = 23), HCV/HIV coinfected (n = 20), and healthy controls (n = 20). Peripheral blood mononuclear cells (PBMCs) were isolated; immunophenotyped and functional assays were performed. A significant increase in the naive T cells and central memory T cells and a marked reduction in effector memory T cells (TEM) were observed with coinfection as compared to monoinfection. Inhibitory markers programmed death 1 (PD-1) and T-cell immunoglobulin and mucin domain containing molecule 3 (TIM3) were highly upregulated on TEM in coinfection and functionally, these TEM cells displayed lowered proliferation. Increased expression of PD-1 and TIM3 correlated with decreased levels of CD8+CD107a+ TEM cells in coinfection. Pro-inflammatory cytokines interferon-γ and interleukin-2 (IL-2) secretion by TEM cells were also reduced during chronic viral infection. Secretion of IL-10, a human cytokine synthesis inhibitory factor, was significantly upregulated in CD4 TEM with HCV/HIV coinfection in comparison to HCV monoinfection. TEM cells play an important role during viral infection and enhanced expression of inhibitory markers is associated with decreased proliferation and cytotoxicity and increased IL-10 production, which was pronounced in HCV/HIV coinfection. Thus, decreased TEM functionality contributes to diminished host immune responses during HCV/HIV coinfection as compared to HCV or HIV monoinfection.

Non-invasive assessment of liver steatosis and fibrosis in HIV/HCV- and HCV- infected patients

Background. Conflicting data have been reported on the prevalence of liver steatosis, its risk factors and its relationship with fibrosis in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection or with HCV mono-infection.Aim. The study aims were to assess steatosis prevalence and its risk factors in both HCV groups. We also evaluated whether steatosis was linked with advanced fibrosis. Sixty-eight HIV/HCV co-infected and 69 HCV mono-infected patients were consecutively enrolled. They underwent liver ultrasonography and transient elastography. Bright liver echo-pattern was used to diagnose steatosis; advanced fibrosis was defined as liver stiffness > 9.5 kPa and FIB–4 values > 3.25. The optimal stiffness cut-off according to FIB–4 > 3.25 was evaluated by ROC analysis.Results. No significant difference was found in steatosis-prevalence between mono- and co-infected patients (46.3 vs. 51.4%). Steatosis was associated with triglycerides and impaired fasting glucose/diabetes in HCV mono-infected, with lipodystrophy, metabolic syndrome, total-cholesterol and triglycerides in co-infected patients. Stiffness > 9.5 was significantly more frequent in co-infection (P < 0.003). Advanced fibrosis wasn't significantly associated with steatosis. The area under the ROC curve was 0.85 (95% CI 0.79–0.9). On multivariate analysis steatosis was associated with triglycerides in both HCV mono- and co-infected groups (P < 0.02; P < 0.03).Conclusion. Although steatosis was common in both HCV mono- and co-infected patients, it was not linked with advanced fibrosis. Triglycerides were independent predictors of steatosis in either of the HCV-groups. Dietary interventions and lifestyle changes should be proposed to prevent metabolic risk factors.