Untreated Hepatitis C Virus Patients Research Articles

Long-Term Survival and Cancer Risk in the Hepatitis C Virus-Infected Patients After Antiviral Treatment: A Nationwide Cohort Study.

Background: Exposure to the Hepatitis C virus (HCV) has been identified as one of the most critical risk factors for Hepatocellular carcinoma (HCC). Interferons and direct-acting antivirals (DAAs) have been used to treat HCV infection with high rates (95%) of prolonged virological response, a suitable safety profile, and good compliance rates. Methods: We obtained information from Taiwan's Health and Welfare Data Science Center. (HWDSC). In this observational cohort research, patients with HCV who received a diagnosis in Taiwan between 2011 and 2018 were included. Results: 78,300 untreated HCV patients were paired for age, sex, and index date with 39,150 HCV patients who received interferon or DAAs treatment. Compared to the control group, the Interferon or DAAs treatment sample has fewer low-income individuals and more hospitalization requirements. The percentage of kidney illness was reduced in the therapy group compared to the control group, but the treatment group had a greater comorbidity rate of gastric ulcers. Interferon or DAA therapy for HCV-infected patients can substantially lower mortality. All cancer diagnoses after HCV infection with interferon treatment aHR 95% CI = 0.809 (0.774-0.846), Sofosbuvir-based DAA aHR 95% CI = 1.009 (0.737-1.381) and Sofosbuvir free DAA aHR 95% CI = 0.944 (0.584-1.526) showing cancer-protective effects in the INF-treated cohort but not DAA. Conclusion: Following antiviral therapy, women appear to have a more substantial preventive impact than men against pancreatic, colorectal, and lung cancer. Interferon or DAAs treatment effect was more significant in the cirrhotic group.

Curtailing infection risks in hepatitis C patients: the effect of antiviral treatment in revision shoulder arthroplasty

BackgroundRevision shoulder arthroplasty (RevSA) is a complex procedure that can result in various postoperative complications. However, the impact of hepatitis C virus (HCV) on postoperative complications after RevSA remains unclear due to limited and inconsistent evidence. This study aims (1) to investigate the incidence of postoperative complications in patients with HCV undergoing RevSA, and (2) to evaluate the impact of HCV treatment on complication rates at different time points after the revision procedure, specifically at 90 days, 1 year, and 2 years MethodsWe queried a national, all-payer database to investigate recent trends in the utilization of RevSA among HCV patients to assess postoperative complication rates, including venous thromboembolism, wound complication, transfusion, and prosthetic joint infection. Statistical analyses involved propensity score matching to create balanced cohorts and logistic regression to determine the relative risk of postoperative complications. "Data was analyzed with the SPSS Statistics software (version 24.0 for Windows; IBM, Armonk, NY, USA). The study included patients who underwent partial or total RevSA procedures between January 1, 2010, and December 31, 2020. Patients were identified based on medical claims that included procedural codes for RevSA and associated diagnosis codes for PJI or insertion/removal of an antibiotic spacer. A Bonferroni correction was utilized because many tests were performed and statistical significance was set at p=0.0125. ResultsThe HCV cohort demonstrated higher prosthetic joint infection (PJI) rates at one-year (5.5 vs 3.9%, p=0.006) and two-year follow-ups (6.7 vs 4.6%, p=0.006). However, no significant differences emerged in venous thromboembolism (VTE) and wound complications rates between the HCV and non-HCV cohorts. Comparing untreated and treated HCV patients, the former showed significantly higher PJI rates at two-year p=0.010, while the treated group had significantly lower odds ratios for PJI. When comparing treated HCV patients with the no HCV cohort, minimal differences were found in postoperative outcomes, indicating no significant difference in the risk of complications between the groups ConclusionOur study observed an association between HCV patients who received antiviral treatment prior to RevSA and a reduced incidence of PJI compared to untreated HCV patients. When comparing this group to the non-HCV controls, there was no significant difference in the incidence of PJI, suggesting a potential association between antiviral treatment and the observed risk patterns in HCV patients. Proper management of HCV-positive patients during RevSA is crucial for improving outcomes and reducing complications.

Does pre-arthroplasty antiviral treatment for hepatitis C reduce complication rates after total shoulder arthroplasty? A matched cohort study.

Hepatitis C virus (HCV) is associated with increased complications of risk after arthroplasty. The purpose of this study was to examine the impact of HCV and a pre-arthroplasty antiviral treatment on complications following total shoulder arthroplasty (TSA). A retrospective matched cohort study was conducted using an administrative claims database. Patients who underwent TSA were identified with Current Procedural Terminology -23472 and International Classification of Diseases procedural codes. A total of 1244 HCV patients were matched 1:3 with 3732 noninfected controls across age, sex, diabetes mellitus, tobacco use, and obesity. The HCV patients with treatment before TSA were identified by claims containing antiviral drug codes. Multivariable logistic regression was used to compare rates of 90-day medical complications and prosthesis-related complications within 2 years postoperatively for (1) HCV patients vs. controls, (2) antiviral-treated HCV patients vs. controls, and (3) antiviral-treated HCV patients vs. untreated HCV patients. Patients with HCV exhibited significantly higher rates of blood transfusion (OR 2.12), acute kidney injuries (OR 1.86), inpatient readmission (OR 2.06), revision TSA (OR 1.48), dislocation (OR 1.92), mechanical complications (OR 1.39), and prosthetic joint infection (OR 1.53) compared to controls. Antiviral-treated HCV patients exhibited a significantly lower rate of myocardial infarction (OR 0.27) and comparable rates of all other complications relative to controls (all P>.05). Compared to untreated HCV patients, antiviral-treated HCV patients exhibited significantly lower rates of 90-day medical complications (OR 0.57) and prosthetic joint infection (OR 0.36). HCV is associated with significantly increased complication rates after TSA. Antiviral treatment before TSA may reduce the risk of postoperative complications.

Effect of Interleukin 28B SNP rs12979860 Genotype on Viral Load in Hepatitis C Virus in Kolar Population, Karnataka, India

Introduction: The natural course of Hepatitis C Virus (HCV) infection is influenced by a number of host and viral variables. Interleukin 28B (IL28B) is a kind of interleukin. A Single Nucleotide Polymorphism (SNP) designated as rs12979860 was reported to predict viral clearance with and without treatment. Subjects with the GG (favourable) IL28B rs12979860 genotype were more likely to clear the infection spontaneously and respond well to therapy. These findings imply that people who have the “favourable” GG genotype have a lower viral burden than those who have the “unfavourable” AA genotype. Aim: To determine the effect of IL28B SNP rs12979860 genotype on HCV viral load in Kolar population, Karnataka, India. Materials and Methods: The present study was a case-control study which was carried out in Department of Microbiology, Sri Devaraj Urs Medical College, Kolar, Karnataka, India. Subjects were enrolled from Department of Medicine of R. L. Jalapa Hospital and Research centre, teaching hospital of Sri Devaraj Urs Medical College between November 2020 to March 2021. A total of 248 were taken of which 124 were HCV antibody-positive and 124 were controls. The effect of IL28B rs12979860 SNP on HCV viral load and clearance among HCV-infected patients were examined. Detection and quantification of HCV-RNA was determined by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). IL28B rs12979860 genotyping was performed using PCR and Restriction Fragment Length Polymorphism (RFLP) technique and specific primers. Statistical analysis was done by using open epi tool. The frequency, percentage and Chi-square test were used to analyse categorical variable. A p-value <0.05 was considered as significant. Results: In this study the frequency of G/G genotype was considerably high 83 (67%) compared to G/A 17 (13.7%) and A/A 24 (19.3%) and in group 2 the frequency of G/G genotype 84 (67.7%), G/A genotype 34 (27.4%) and A/A genotype 6 (4.9%). There was a statistically significant difference in both the HCV infected and healthy controls groups (p=0.002). The average (±SEM) HCV viral load was 4.6±3.6×107 , 9.4±7.7×107 and 5.5±5.2×107 IU/mL in patients with the IL28B rs12979860 GG, GA and AA respectively. Also there was a significance between the viral load and IL28B rs 12979860 (p-value <0.05). Conclusion: Thus, present study results indicate that the IL28B rs12979860 genotype has an effect on viral load in untreated HCV patients. These findings highlight the importance of viralhost interactions in influencing the outcome of HCV infection.

The oral microbiome of treated and untreated chronic HCV infection: A preliminary study.

Chronic hepatitis C virus (HCV) infection is a debilitating disease that is lately treated using direct-acting antivirals (DAAs). Changes in the oral microbiome were detected in other liver diseases; however, oral microbiome was never investigated in patients having chronic HCV infection, whether pre- or post-treatment. This case-control preliminary study enrolled three equal groups: Group (I): untreated HCV patients; group (II): HCV patients who achieved viral clearance after DAA administration; and group (III): healthy controls. For each participant, a buccal swab was harvested and its 16S rRNA was sequenced. The oral microbiome of chronic HCV patients had a significantly distinct bacterial community compared to healthy controls, characterized by high diversity and abundance of certain pathogenic species. These changes resemble that of oral lichen planus patients. After treatment by DAAs, the oral microbiome shifted to a community with partial similarity to both the diseased and the healthy ones. Chronic HCV is associated with dysbiotic oral microbiome having abundant pathogenic bacteria. With HCV clearance by DAAs, the oral microbiome shifts to approach the healthy composition.

The preoperative management of Hepatitis C may improve the outcome after total knee arthroplasty

With an ageing population of patients who are infected with hepatitis C virus (HCV), the demand for total knee arthroplasty (TKA) in this high-risk group continues to grow. It has previously been shown that HCV infection predisposes to poor outcomes following TKA. However, there is little information about the outcome of TKA in patients with HCV who have been treated successfully. The purpose of this study was to compare the outcomes of TKA in untreated HCV patients and those with HCV who have been successfully treated and have a serologically confirmed remission. A retrospective review of all patients diagnosed with HCV who underwent primary TKA between November 2011 and April 2018 was conducted. HCV patients were divided into two groups: 1) those whose HCV was cured (HCV-C); and 2) those in whom it was untreated (HCV-UT). All variables including demographics, HCV infection characteristics, surgical details, and postoperative medical and surgical outcomes were evaluated. There were 64 patients (70 TKAs) in the HCV-C group and 63 patients (71 TKAs) in the HCV-UT cohort. The mean age at the time of surgery was 63.0 years (sd 7.5; 44 to 79) in the HCV-C group and 61.7 years (sd 6.9; 47 to 88) in the HCV-UT group. HCV-UT patients had a significantly longer mean hospital stay (3.4 days vs 2.9 days; p = 0.04), were more likely to be transferred to the intensive care unit (14.1% vs 4.3%; p = 0.04), and were significantly more often discharged to a post-acute care facility (39.4% vs 14.3%; p < 0.01). HCV-UT patients had significantly more postoperative infections (15.5% vs 4.3%; p = 0.03), surgical complications (21.1% vs 7.1%; p = 0.02), and revision TKA (12.7% vs 1.4%; p < 0.01) than HCV-C patients. The preoperative treatment of HCV can reduce the risk of complications, including prosthetic joint infection and revision TKA. We recommend that HCV treatment regimens should be integrated into the preoperative optimization protocol for this high-risk group of patients. Cite this article: Bone Joint J 2019;101-B:667-674.

Expression of SOCS1 and SOCS3 Genes in Interferon-Treated and Direct-Acting Antiviral Drugs-Treated Hepatitis C Patients.

Genetics of host plays a significant role in susceptibility and pathogenesis of disease. During hepatitis C virus (HCV) infection, HCV proteins interfere with interferon (IFN) signaling pathways and upregulate transcription of suppressor of cytokine signaling 1 and 3 genes (SOCS1 and SOCS3), which results in impaired immune response. In this study, we evaluated relative expression of SOCS1 and SOCS3 in untreated HCV patients and patients treated with 2 different treatment strategies that are, (IFN therapy and direct-acting antiviral (DAA) drug regimen. To study gene expression, peripheral blood mononuclear cells (PBMCs) were isolated by using Histopaque. Total RNA was extracted from PBMCs by using BIOzol. Nine microgram of total RNA from each sample was used and reverse transcribed into single-stranded complementary DNA (cDNA) by using M-MLV reverse transcriptase (Invitrogen). The synthesized cDNA was diluted to a final concentration of 500 ng/μL. This diluted cDNA was further used for expression analysis of SOCS1and SOCS3 genes using Rotor Gene Q Real-Time PCR Detection System (QIAGEN). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was amplified as a housekeeping gene. We found that the SOCS1 expression in IFN and DAA-treated patient groups was 5.4 fold and 1.2 fold, respectively, high compared with the healthy controls (IFN versus healthy, P = 0.019 and DAA versus healthy, P = 0.91), whereas the SOCS3 expression in IFN and DAA-treated patient groups was 3.7 fold and 2 fold, respectively, high in comparison with the expression in healthy controls (IFN versus healthy, P = 0.025 and DAA versus healthy, P = 0.03). We also found a significant difference in the relative expression of SOCS1 and SOCS3 in DAAs-treated and IFN/ribavirin (RBV)-treated and untreated individual. We concluded that by targeting HCV proteins with DAAs, SOCS1, and SOCS3 transcription can be more effectively normalized compared to the treatment with IFN/RBV therapy.

Direct medical costs associated with the extrahepatic manifestations of hepatitis C infection in Europe.

Hepatitis C virus (HCV) infection is a systemic disease associated with both hepatic and extrahepatic manifestations. The burden associated with the hepatic manifestation of HCV infection has been well documented in Europe, although that of HCV extrahepatic manifestations remains unknown. In this study, we estimated the annual direct medical costs associated with HCV extrahepatic manifestations in five European countries. A previously validated economic model was used to estimate the annual direct medical cost associated with HCV extrahepatic manifestations. Global excess prevalence of extrahepatic manifestations in HCV patients relative to that in non-HCV patients was obtained from a recent meta-analysis. Per-patient per-year inpatient, outpatient and medication costs to treat each extrahepatic manifestation were from the literature, national databases or expert opinion if unavailable otherwise. All costs were adjusted to 2016 euros (€). The overall direct medical costs associated with HCV extrahepatic manifestations were calculated by multiplying the total per-patient per-year costs of each by the respective excess prevalence rates and then by the size of the HCV-infected population in each country. Treatment impact with direct-acting antivirals (DAAs) was explored using HCV extrahepatic manifestations excess prevalence rates among cured patients compared to untreated HCV patients, as sourced from a meta-analysis. The total annual direct medical cost associated with HCV extrahepatic manifestations was estimated to be 2.17 billion euro (€), with a per-HCV-patient cost ranging from €899 to €1647 annually. DAA treatment was projected to result in cost savings of €316 million per year. We find that the annual economic burden of extrahepatic manifestations is significant and may be partly mitigated by treatment with DAAs.

Direct-acting antiviral treatment for hepatitis C virus infection and risk of incident liver cancer: a retrospective cohort study.

Eradication of hepatitis C virus (HCV) infection via interferon-based treatment lowers hepatocellular carcinoma risk; some research suggests this effect extends to interferon-free treatment. The objective of this retrospective cohort study was to examine the association of direct-acting antiviral (DAA) exposure with risk of incident liver cancer in real-world data. From United States administrative claims data through March 31, 2017, we identified 30 183 adult HCV patients exposed to DAAs. For comparison, we identified contemporary adult HCV patients without evidence of HCV treatment (N = 137 502), and historical HCV patients treated with interferon prior to the introduction of DAAs (N = 12 948). Included patients had at least 12 months of prior enrolment and no evidence of prior liver cancer at baseline. Hazard ratios (HRs) estimating risk of incident liver cancer associated with DAA treatment were calculated using Cox proportional hazards methods. Relative to untreated HCV patients, DAA-treated patients were older, more likely to be male, and more likely to have cirrhosis at baseline. After adjustment, DAA treatment was associated with a significantly reduced risk of liver cancer relative to no treatment (adjusted HR = 0.84, 95% CI: 0.73-0.96), and relative to interferon-based treatment in the pre-DAA era (HR = 0.69, 95% CI: 0.59-0.81). In this large, population-based study, DAA-based treatment was associated with a reduced risk of incident liver cancer relative to both no HCV treatment and to interferon-based treatment in the pre-DAA era. As additional follow-up time of DAA-treated patients accrues, we anticipate that the long-term benefits of DAA treatment will become more apparent.

IL28B SNPs rs12979860 and rs8099917 Are Associated with Inflammatory Response in Argentine Chronic HCV Patients

Background: Hepatitis C virus (HCV) is a major cause of chronic liver disease, including cirrhosis and liver cancer. The aim of our study was to determine whether IL28B single nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 can be considered a prognostic host factor in untreated chronic HCV patients. Methods: We set up a real-time Allele Specific PCR amplification to determine the allele present in each polymorphic site, and statistically grouped and compared this result with clinical data. Results: We determined rs12979860 and rs8099917 genotype and allele frequencies in a single cohort of untreated chronically HCV-infected patients. We found significant associations between higher inflammatory activity, measured as ALT levels or METAVIR scores and rs12979860 CC (P = 0.0013 and P = 0.0033, respectively) and rs8099917 TT (P = 0.0005 and P = 0.0264, respectively) genotypes. Interestingly, considering both genotypes together, we also found association with ALT levels (P = 0.0003; OR = 5.125) or METAVIR scores (P = 0.0038; OR = 5.179), suggesting and additive effect on liver inflammation in these patients. Conclusion: we show association between hepatic inflammatory activity in a single Argentinean untreated chronically HCV cohort and SNPs located in the interferon lambda gene region. The studied polymorphisms, together with further innate and adaptive immune responses, clearly play a role in modulating the HCV infected patients outcome, contributing to hepatic inflammation and possible fibrosis/cirrhosis.

Chronic hepatitis C virus (HCV) increases the risk of chronic kidney disease (CKD) while effective HCV treatment decreases the incidence of CKD.

We assessed the risk of chronic kidney disease (CKD) in chronic hepatitis C virus (HCV)‐infected patients and the incidence reduction of CKD after receipt of HCV treatment. We also evaluated the risk of membranoproliferative glomerulonephritis (MPGN) and cryoglobulinemia in chronic HCV patients. A retrospective cohort analysis of the Truven Health MarketScan Database (2008‐2015) in the United States was conducted. In a cohort of 56,448 HCV‐infected patients and 169,344 propensity score (1:3)–matched non‐HCV patients, we examined the association of HCV infection with the incidence of CKD. Of 55,818 HCV patients, 6.6 % (n = 3666), 6.3% (n = 3534), and 8.3% (n = 4628) patients received either interferon‐based dual, triple, or all‐oral direct acting antiviral agent therapy, respectively, whereas 79% of patients did not receive any HCV treatment. Cox proportional hazards models were used to compare the risk of developing CKD in HCV patients compared with non‐HCV patients and treated patients compared with untreated HCV patients. In a multivariate time‐varying Cox regression model, HCV‐infected patients had a 27% increased risk of CKD compared with non‐HCV patients (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.18‐1.37). Among HCV patients, individuals who received the minimally effective HCV treatment for dual, triple, or all‐oral therapy had a 30% decreased risk of developing CKD (HR, 0.70; 95% CI, 0.55‐0.88). In addition, HCV‐infected patients experienced a twofold and a nearly 17‐fold higher risk of MPGN (HR, 2.23; 95% CI, 1.84‐2.71) and cryoglobulinemia (HR, 16.91; 95% CI, 12.00‐23.81) respectively, compared with non‐HCV patients. Conclusion: HCV‐infected individuals in the United States are at greater risk of developing CKD, MPGN, and cryoglobulinemia. Minimally effective treatment of HCV infection can prevent the development of CKD, although the association was not significant for all‐oral therapy. (Hepatology 2018;67:492‐504).

Safety and Efficacy of Treatment of Hepatitis C in Kidney Transplant Recipients With Directly Acting Antiviral Agents.

With the development of all oral, interferon-free directly acting antiviral (DAA) medications, treatment of hepatitis C virus (HCV) infection in renal transplant recipients is possible, but limited data exists on its safety and efficacy. We performed a retrospective cohort analysis of patients transplanted at our center with HCV who have been started on DAAs. Primary endpoints included sustained virologic response as defined as negative viral load at 12 weeks postcompletion of therapy and allograft function. A total of 31 patients met inclusion criteria. The most commonly used regimen was sofosbuvir and ledipasvir (n = 21). Of the treated patients, 100% had undetectable viral load at the completion of therapy. Of the 31 patients treated, 30 (97%) achieved sustained virologic response. Both graft and patient survivals at most recent follow-up was 100%. There was no significant change in glomerular filtration rate (GFR) before or after therapy (64.2 ± 16.5 mL/min per body surface area before vs. 58.9 ± 17.5 mL/min per body surface area after therapy; P = 0.22); however, 3 patients now have GFR less than 20. A total of 6 (19.3%) of 31 patients had worsening proteinuria during or shortly after therapy. Patients with more than 500 mg/g of proteinuria at the start of treatment were significantly more likely to develop worsening proteinuria than those with less than 500 mg/g of proteinuria at the start of therapy (P < 0.001). Retrospective review of 20 untreated HCV patients did not demonstrate worsening allograft function and proteinuria during a median follow-up time of 1386 days (range, 332-6254). Our preliminary data demonstrate that DAAs can be used safely and effectively in patients after kidney transplantation. Patients with proteinuria or lower GFR should be monitored more closely.

Serum Levels of Endothelial Monocyte-Activating Polypeptide-II in Hepatitis C Patients

Objectives: Endothelial monocyte-activating polypeptide-II (EMAP-II) is a cytokine with pro-inflammatory and immune-suppressive properties. The goal of this study was to assess serum EMAP-II in treated and untreated Hepatitis C virus (HCV) patients. Furthermore, we determined the relationship between serum EMAP-II levels with the clinic pathological and laboratory parameters in patients with HCV. Methods: 25 control patients (Group I), 25 treated HCV patients (Group II) and 25 newly diagnosed, untreated patients with HCV (Group III) were included in this study. Serum EMAP-II levels were detected by Enzyme linked immunosorbent assay (ELISA), and HCV RNA was assessed by real time-PCR (RT-PCR). The results were evaluated against clinical and laboratory data. Results: Serum EMAP-II levels were significantly elevated in newly diagnosed, untreated HCV patients compared to treated HCV and control patients (p<0.001). We found that serum EMAP-II levels correlated positively with HCV RNA in untreated HCV patients (p<0.001). While serum albumin and platelet count correlated negatively with serum EMAP-II levels (p<0.001), a positive correlation was observed between EMAP-II and serum bilirubin (p<0.001). Conclusions: Increased serum EMAP-II levels are present in newly diagnosed HCV patients compared to treated HCV and control patients, suggesting EMAP-II as a novel biomarker for HCV diagnosis.

Peripheral lymphocyte subsets in chronic hepatitis C: Effects of 12 weeks of antiviral treatment with interferon-alpha plus ribavirin

Chronic infection with hepatitis C virus (HCV) causes a quantitative and functional alteration in innate and adaptative immunity. In the present work, we determined by flow-cytometry the profile of blood lymphocyte of untreated HCV patients and in subjects of this group that achieved or not an early virologic response at 12-weeks of treatment with interferon-α plus ribavirin. Twenty-six untreated HCV patients and 20 control healthy individuals were enrolled in the study. Untreated HCV patients had a higher proportion of B cell and a lower proportion of CD8+ T cell and NK cells than healthy individuals did, but the proportions of CD4+ T cells and Treg cells (CD4+CD25+Foxp3+) were similar in these patients and controls. Untreated HCV patients presenting cryoglobulinemia had a lower proportion of Treg cells and a lower Treg/NK cell ratio when compared with those without cryoglobulins. Nineteen out of 26 untreated HCV patients remained in the study and were treated with Interferon-α plus ribavirin. At 12-weeks of treatment, 10 of them achieved early virologic response (EVR), whereas 9 were non-responders (NR). EVR patients differed from NR patients in the increase of their proportion of NK cells at 12 weeks of treatment. In conclusion, untreated HCV patients exhibit an altered profile of blood lymphocyte subsets, including a reduction in the proportion of CD4+CD25+FoxP3+T regulatory cells in patients that present cryoglobulinemia. An early virological response at 12-weeks of treatment with IFN-α plus ribavirin seems to be associated a significant improvement in the proportion of NK cells of HCV treated patients.

ASSOCIATION BETWEEN CRYOGLOBULINEMIA AND THYROID DYSFUNCTION IN HEPATITIS C CARRIERS

Introduction: Cryoglobulinemia is a biomarker of autoimmunity correlated with hepatitis C virus (HCV) infection. Objective: Report the association between the presence of mixed-cryoglobulinemia and thyroid dysfunction (TD) in hepatitis C virus carriers before and during treatment with pegylatedinterferon-alpha (Peg-IFN-α). Methods: Prospective cohort study. Results: Sixty-five untreated HCV patients, 38 women and 27 men were included in this study. Mean age of patients was 49.61 ± 11.83 years. Cryoglobulinemia was demonstrated in 24 (36.92%) patients. The TD was demonstrated in 2 patients (3.10%) before treatment with IFN-α, in 4 patients (6.20%) at 12th week, and 8 patients (12.30%) at 24th week; whereas autoimmune thyroid (TPO-Ab) positive was demonstrated in 3 patients (4.60%) before treatment, in 7 patients (10.80%) at 12th week, and 12 patients (18.50%) at 24th week. In the sample analyzed, the risk of a patient with cryoglobulinemia develop TD was 2.74 (95% CI: 1.95–12.95) times that of a patient without cryoglobulinemia in the 12th week of treatment and 1.83 (95% CI: 1.03–7.08) times in the 24th week of antiviral treatment, and risk of a patient with cryoglobulinemia for develop TPO Ab positive was 2.44 (95% CI: 1.46–5.98) times that of a patient without cryoglobulinemia in the 12th week of treatment, and 1.31 (95% CI: 1.05–2.89) times in the 24th weeks of antiviral treatment. Conclusion: We concluded that thyroid function evaluation should be recommended for HCV carriers that are seropositive for cryoglobulinemia.

High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation

The presence of autoantibodies against C-reactive protein (anti-CRP) has been reported in association with autoimmunity and histopathology in chronic hepatitis C virus (HCV) infection. Resistin could play a role in the pathogenesis of hepatitis, although results on HCV infection are ambiguous. Here we retrospectively analyzed anti-CRP and resistin levels in the sera of 38 untreated and well-characterized HCV patients at the time of their first liver biopsy. HCV activity and general health were assessed by a physician at least yearly until follow-up ended. Anti-CRP and resistin were also measured in patients with autoimmune hepatitis (AIH) and nonalcoholic fatty liver disease (NAFLD). Anti-CRP antibodies were registered in all HCV patients, whereas only a few AIH (11%) and NAFLD (12%) sera were positive. Anti-CRP levels were related to histopathological severity and were highest in patients with cirrhosis at baseline. Resistin levels were similar in HCV, AIH, and NAFLD patients, but high levels of resistin were associated with early mortality in HCV patients. Neither anti-CRP nor resistin predicted a response to interferon-based therapy or cirrhosis development or was associated with liver-related mortality. We conclude that anti-CRP antibodies are frequently observed in chronic HCV infection and could be a useful marker of advanced fibrosis and portal inflammation.

Direct Medical Care Costs Among Pegylated Interferon Plus Ribavirin-Treated and Untreated Chronic Hepatitis C Patients

Hepatitis C virus (HCV) is a common and expensive infectious disease. The current standard of care for HCV infection, pegylated interferon with ribavirin (PEG-RBV), is costly and has a significant adverse event profile. To quantify the direct economic burden of HCV infection and PEG-RBV treatment for HCV. Using a large administrative claims database, we evaluated the medical and prescription drug costs of patients with HCV from 2002 to 2007. A cohort of patients with PEG-RBV was 1:1 propensity score-matched to a cohort of untreated HCV patients. Multivariate models adjusted for demographic and clinical characteristics in evaluating the effect of PEG-RBV treatment on direct medical expenditure. The matched analysis included 20,002 patients. PEG-RBV-treated patients had higher total direct medical costs ($28,547 vs. $21,752; P<0.001), outpatient pharmacy costs ($17,419 vs. $2,900; P<0.001), and outpatient physician visit costs ($894 vs. $787; P<0.001), but lower inpatient costs ($3,942 vs. $9,543; P<0.001) and emergency room costs ($366 vs. $505; P<0.001). After multivariate adjustment, PEG-RBV use was associated with an additional $9,423 in total direct medical costs and an additional $12,244 in HCV-related total medical costs. Total HCV-related medical costs are higher for treated than untreated patients, driven mostly by higher outpatient pharmacy costs, which outweigh higher HCV-related inpatient costs incurred by untreated patients.

Interleukin-32: A new proinflammatory cytokine involved in hepatitis C virus-related liver inflammation and fibrosis

Interleukin 32 (IL-32) is a recently described proinflammatory cytokine that activates p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), thereby inducing proinflammatory cytokines such as IL-1β and tumor necrosis factor alpha (TNF-α). We investigated the role of IL-32 in patients with chronic hepatitis C virus (HCV) infection. Steady-state hepatic messenger RNA (mRNA) levels of IL-32 were determined in a cohort of 90 subjects; anti-IL-32 staining was used in a second cohort of 132 consecutive untreated chronic HCV patients. Correlations with histological features of steatosis, inflammation, and fibrosis were made. In vitro, endogenous IL-32 in monocytes and in the human hepatoma cell line Huh-7.5 were examined. The effects of IL-32-overexpression and IL-32-silencing on HCV replication were studied using HCV luciferase reporter viruses. There were highly significant positive associations between hepatic IL-32 mRNA expression and liver steatosis, inflammation, fibrosis, smooth muscle actin (SMA) area, and serum alanine aminotransferase (ALT) levels. IL-32 protein expression was positively associated with portal inflammation, SMA area, and ALT. In vitro, IL-1β and TNF-α significantly induced IL-32 expression in human Huh-7.5 cells. Alone, stimulation with interferon alpha (IFN-α) did not induce IL-32 expression in Huh-7.5. However, IFN-α exerted a significant additive effect on TNF-α-induced but not IL-1β-induced IL-32 expression, particularly in CD14+ monocytes. This effect was dependent both on NF-κB and Jak/STAT signaling. Viral infection of Huh-7.5 cells resulted in a significant (11-fold) induction of IL-32 mRNA expression. However, modulation of IL-32 in Huh-7.5 cells by overexpression or silencing did not influence HCV virus replication as determined by luciferase assays. IL-32 is a novel proinflammatory cytokine involved in HCV-associated liver inflammation/fibrosis. IL-32 is expressed by human hepatocytes and hepatoma cells and its expression is regulated by proinflammatory stimuli.

Smooth muscle antibodies and cryoglobulinemia are associated with advanced liver fibrosis in Brazilian hepatitis C virus carriers

Cryoglobulinemia and non-organ-specific-autoantibody are biomarkers of autoimmunity of the chronic infection caused by hepatitis C virus (HCV). In this work, we report the association between the presence of smooth muscle antibodies (SMA) and cryoglobulinemia and chronic liver disease in HCV carriers. Sixty-five untreated HCV patients, 38 women and 27 men were included in this study. Cryoglobulinemia was tested by cryoprecipitation, SMA by indirect fluorescent antibody test, and liver fibrosis and hepatocellular inflammation activity was investigated by histology of liver biopsy using the METAVIR score. The prevalence of SMA in the patients was 33.8% and cryoglobulinemia was demonstrated in 36.9% patients. Cryoglobulinemia and SMA seropositivity was associated with advanced fibrosis (p < 0.05). The presence of SMA and cryoglobulinemia was not associated with hepatocellular inflammation activity, age, carrier gender or HCV genotype. We concluded that liver biopsy should be recommended for HCV carriers that are seropositive for SMA or cryoglobulinemia.

Smooth muscle antibodies and cryoglobulinemia are associated with advanced liver fibrosis in Brazilian hepatitis C virus carriers

Cryoglobulinemia and non-organ-specific-autoantibody are biomarkers of autoimmunity of the chronic infection caused by hepatitis C virus (HCV). In this work, we report the association between the presence of smooth muscle antibodies (SMA) and cryoglobulinemia and chronic liver disease in HCV carriers. Sixty-five untreated HCV patients, 38 women and 27 men were included in this study. Cryoglobulinemia was tested by cryoprecipitation, SMA by indirect fluorescent antibody test, and liver fibrosis and hepatocellular inflammation activity was investigated by histology of liver biopsy using the METAVIR score. The prevalence of SMA in the patients was 33.8% and cryoglobulinemia was demonstrated in 36.9% patients. Cryoglobulinemia and SMA seropositivity was associated with advanced fibrosis (p < 0.05). The presence of SMA and cryoglobulinemia was not associated with hepatocellular inflammation activity, age, carrier gender or HCV genotype. We concluded that liver biopsy should be recommended for HCV carriers that are seropositive for SMA or cryoglobulinemia.