Impact of sustained virologic response on glucose parameters among patients with chronic hepatitis C treated with direct-acting antivirals.

Objective: The aim of this study was to evaluate the glycated hemoglobin (HbA1c) levels before and after sustained virologic response (SVR) and investigate the baseline characteristics associated with improved glycemic control in patients with chronic hepatitis C (CHC) achieving SVR after directacting antivirals (DAA) therapy. Materials and methods: Consecutive adult patients with CHC who achieved SVR after DAA treatment between January 2016 and December 2017 at Hospital de Clínicas de Porto Alegre (RS, Brazil) were prospectively included. Levels of HbA1c were measured up to 24 weeks before DAA therapy and 12 weeks after SVR. Exclusion criteria were decompensated cirrhosis, HIV and/or hepatitis B virus, liver disease of other etiologies, and/or modification of prediabetes/ type 2 diabetes mellitus (PDM/T2DM) management. The primary outcome was a comparison of HbA1c levels before and after SVR. Secondary outcomes were the baseline variables associated with improved glycemic control. Results: The study included 207 patients with a mean age of 60.6±10.7 years, of whom 51.7% were women, 56% had cirrhosis, 37.7% had HCV genotype 3, and 54.5% had baseline T2DM or PDM. The median HbA1c level reduced significantly after SVR (5.5%, interquartile range [IQR] 4.9%-6.3%) compared with baseline (5.7%, IQR 5.3%-6.7%; p = 0.01). The baseline characteristics associated with improved HbA1c after SVR were cirrhosis, genotype 3, and age ≤ 60 years. Conclusion: Among patients with CHC, SVR after DAA was associated with HbA1c reduction, particularly in those with cirrhosis, genotype 3, and age ≤ 60 years.

LDL particle size and antioxidant HDL function improve after sustained virological response in patients with chronic HCV.

HCV infection is associated with an increased incidence of cardiovascular (CV) events. Mechanisms underlying this association remain unknown. In our study, twenty HCV patients (median age 60.5 years, 65% male and 80% with cirrhosis) were evaluated prior, during and after direct-acting antiviral treatment. Ninety percent of patients achieved sustained virological response (SVR). Significant changes were observed in LDL particle size index, measured by LDL-C/apoB ratio, which increased after treatment (p = 0.023). In addition, HDL antioxidant capacity improved gradually from 34.4% at baseline to 42.4% at 4 weeks (p = 0.011), 65.9% at end of treatment EOT (p = 0.002) and remained elevated at 12-week (p = 0.001) after EOT compared to baseline values. Our findings suggest that a shift to a less atherogenic lipid profile may be a possible mechanism associated with CV risk reduction in patients with HCV infection achieving SVR.

Adherence to a Fish-Rich Dietary Pattern Is Associated with Chronic Hepatitis C Patients Showing Low Viral Load: Implications for Nutritional Management.

Hepatitis C virus (HCV) infection is influenced by genetic (e.g., APOE polymorphisms) and environmental factors between the virus and the host. HCV modulates the host's lipid metabolism but dietary components influence lipids and in vitro HCV RNA replication. Few data exist on the role of dietary features or patterns (DPs) in HCV infection. Herein, we aimed to evaluate the nutritional profiles of chronic HCV (CHC) and spontaneous clearance (SC) Mexican patients in the context of APOE alleles and their correlation with HCV-related variables. The fibrosis-related APOEε3 allele prevailed in CHC and SC patients, who had four DPs ("meat and soft drinks", DP1; "processed animal and fried foods", DP2; "Mexican-healthy", DP3; and "fish-rich", DP4). In CHC subjects, polyunsaturated fatty acid intake (PUFA ≥ 4.9%) was negatively associated, and fiber intake (≥21.5 g/day) was positively associated with a high viral load (p < 0.036). High adherence to fish-rich DP4 was associated with a higher frequency of CHC individuals consuming PUFA ≥ 4.9% (p = 0.004) and low viral load (p = 0.036), but a lower frequency of CHC individuals consuming fiber ≥21.5 g/day (p = 0.038). In SC and CHC individuals, modifying unhealthy DPs and targeting HCV-interacting nutrients, respectively, could be part of a nutritional management strategy to prevent further liver damage.

Changes in Liver Stiffness and Noninvasive Fibrosis Scores in Egyptian Adolescents Successfully Treated with Ledipasvir-Sofosbuvir for Chronic Hepatitis C Virus Infection.

OBJECTIVE: To assess changes in noninvasive liver fibrosis measurements after chronic hepatitis C eradication by direct-acting antivirals in Egyptian adolescents. STUDY DESIGN: Liver stiffness measurement (LSM), by vibration-controlled transient elastography and noninvasive fibrosis scores (Firbosis-4, aspartate aminotransferase-platelet ratio index), was obtained before and 12 months after eradication with ledipasvir-sofosbuvir. The primary outcome was a more than 30% decrease in LSM with resulting fibrosis stage regression for initial fibrosis of F2 or higher and nonprogression of F0-F1, using the Ishak score (F0-F6). The secondary outcome was change in noninvasive fibrosis scores after treatment. RESULTS: Analyzing 85 patients, the median baseline LSM was 5.8 (IQR, 4.2-6.5) and at follow-up 5.1 kPa (IQR, 4-6 kPa) (P = .045); 62 (73%) met the primary outcome, 16 patients (19%) experienced regression, and 46 (54%) nonprogression of LSM. Of 18 with initial fibrosis of F2 0r higher, 13 regressed to F0-F1 and 2 from F6 to F5, 1 unchanged at F3, and 1 increased to F3 and 1 to F4. Among 67 patients with a baseline fibrosis of F0-F1, 62 were unchanged and 5 increased-4 to F2 and 1 to F3. Although 23 (27%) had a more than 30% LSM increase, only 7 (8%), with associated comorbidities (4 ß-thalassemia, 3 hepatic steatosis), had increased fibrosis stage. The median baseline FIB-4 and aspartate aminotransferase-platelet ratio index scores were 0.34 (IQR, 0.22-0.47) and 0.35 (0.24-0.57), and at follow-up 0.3 (IQR, 0.22-0.34) and 0.2 (0.18-2.8) (P < .001, <.001), respectively. CONCLUSIONS: Chronic hepatitis C eradication by direct-acting antiviral agents in Egyptian adolescents was associated with nonprogression or regression of liver fibrosis, by noninvasive fibrosis measurements, at 12 months after treatment in the majority of cases.

Circulating vascular adhesion protein-1(VAP-1): a possible biomarker for liver fibrosis associated with chronic hepatitis B and C.

Vascular adhesion protein-1 (VAP-1) is a multifunctional protein that plays a role in chronic liver diseases and fibrogenesis. The present study aimed to investigate the possible association of VAP-1 levels with the severity of disease progression in chronic hepatitis (CH) B and C patients with differing stages of fibrosis (F0-4), CHB/CHC-related cirrhosis, and hepatocellular carcinoma (HCC). The VAP-1 concentration in patient sera was determined by ELISA. The VAP-1 levels were compared between the F0 group and the F1, F2, F3, F4, cirrhosis, and HCC groups of CHB patients and between the F1 group and the F2, F3, F4, cirrhosis, and HCC groups of CHC patients. The levels of VAP-1 were significantly increased in CHB patients with progressive stages of fibrosis, with the highest concentration being found in those with stage F4 (severe fibrosis). A statistically significant difference was found between F0 and F4 in patients with CHB, but no statistically significant difference was observed between F1 and F4 in patients with CHC. Interestingly, there was no statistically significant difference in VAP-1 levels between patients with cirrhosis and HCC (either CHB or CHC, independently). Moreover, no relationship was found between VAP-1 and ALT levels in either CHC or CHB patients. In general, the VAP-1 levels were significantly higher in CHB than in CHC patients (P < 0.01). In conclusion, we suggest that the VAP-1 level may be a noninvasive biomarker for monitoring the severity of fibrogenesis in patients with hepatitis B infection.

Successful DAA therapy for chronic hepatitis C reduces HLA-DR on monocytes and circulating immune mediators: A long-term follow-up study.

INTRODUCTION: After DAA treatment for chronic hepatitis C infection, peripheral monocyte subsets from patients who achieved sustained virological response (SVR) reduced compared to healthy control. Improvement in inflammatory parameters and liver stiffness has been observed. However, little is known about the long-term impact of DAA treatment on peripheral monocyte subsets and immune mediators levels. OBJECTIVES: We aimed to examine peripheral monocyte subsets and immune mediators levels in Brazilian chronic HCV patients after long-term successful IFN-free SOF-based treatment. MATERIAL AND METHODS: We analyzed CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocytes and 27 immune mediators by flow cytometry and analysis of multiple secreted proteins assay, respectively, in monoinfected chronic HCV patients receiving IFN-free sofosbuvir-based regimens followed before treatment, at SVR and one year after the end of treatment (1y). RESULTS: Twenty-one biomarkers decreased significantly at 1y and 55-80 % of patients this reduction at 1y. Experimented patients presented a greater modulation of immune mediators at 1y. HLA-DR expression significantly decreased on CD14++CD16- and CD14++CD16+ monocytes at 1y when compared to SVR. CONCLUSIONS: Successful DAA therapy did not modify monocyte subsets frequency but reduced monocyte activation at 1y and sustained the downregulation and restoration of circulating immune mediators, indicating that long-term reversal of inflammation status could occur after HCV eradication.

The TGFB1 -509C/T polymorphism and elevated TGF-ß1 levels are associated with chronic hepatitis C and cirrhosis.

The IFN-γ and TGF-ß1 cytokines perform antagonistic activities in the immune response, and polymorphisms in these genes may induce changes in their plasma levels and influence the course of chronic Hepacivirus C (HCV) infection. The present study evaluated the IFNG +874A/T and TGFB1 -509 C/T polymorphisms in 99 samples from patients with chronic hepatitis C and in 300 samples from healthy donors, and the present study also investigated the association of cytokine plasma level with disease stage. Polymorphisms were identified by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay. The frequency of the IFNG +874A/T polymorphic allele was not associated with susceptibility to HCV infection, but it was associated with lower inflammatory activity (p = 0.0432). The frequency of the TGFB1 -509C/T polymorphic (TT) genotype was associated with HCV infection (p = 0.0062) and a higher risk of infection (OR = 2.0465; p = 0.0091). Plasma levels of IFN-γ were higher in TT genotype carriers among the control (p = 0.0012) and HCV groups (p = 0.0064) as well as in patients with fibrosis (p = 0.0346) and patients with a high degree of inflammatory activity (p = 0.0381). The highest TGF-ß1 levels were found in HCV-infected (p = 0.0329) individuals and in TT genotype carriers. Patients with cirrhosis had higher TGF-ß1 (p = 0.0400). IFN-γ and TGF-ß1 levels showed a negative correlation (p = 0.0001). In conclusion, the TGFB1 -509C > T polymorphism is associated with a risk of developing chronic hepatitis C, leading to increased TGF-ß1, which inhibits IFN-γ production, contributing to the progression to cirrhosis.

Anti-rod and ring antibodies in patients with chronic hepatitis C using direct-acting antivirals.

Anti-rods and rings (anti-RR) antibody induction is related to the combination of interferon and ribavirin in the treatment of hepatitis C virus (HCV) infection. If the main factor leading to this autoimmune reaction is the combination of these drugs, is not well known, but in vitro studies shows that ribavirin alone can induce rods and rings structures. New direct-acting antivirals (DAAs) permit HCV treatment without needing interferon but may be associated with ribavirin in the most difficult-to-treat patients. The aim of this study is to evaluate the occurrence of anti-RR in patients with chronic HCV infection, before and after 12 weeks of treatment with DAAs, with and without ribavirin. From Jun 2016 to Oct 2017, 52 HCV-infected patients were screened for anti-RR before and after DAA therapy, including sofosbuvir, daclatasvir, simeprevir, and ribavirin. Serum samples were analyzed using indirect immunofluorescence. The anti-RR was present in 11 (21%) of the 52 patients (51.9% male and mean age of 59.1 years) before using DAAs. All of them had been previously treated and previous exposed to interferon/ribavirin, with exposure time to ribavirin associated with the presence of anti-RR. After 12 weeks of DAA treatment, 3 patients (5.7%) developed the antibody in low titers, and two of them (66%) were interferon/ribavirin experienced. Only one of the 29 naïve patients (3.44%) developed anti-RR during the current treatment. Anti-RR was present in patients previously treated with interferon/ribavirin and can emerge after DAA treatment probably at a lower frequency than after interferon/ribavirin treatment.

Viral eradication restores normal iron status in chronic hepatitis C patients with abnormal iron studies.

INTRODUCTION AND OBJECTIVES: Abnormal serum iron studies are seen in a third or more of patients with chronic hepatitis C infection (HCV), where they have been linked to accelerated fibrosis progression and increased risk of hepatocellular carcinoma and sometimes lead to concern for coexisting hereditary hemochromatosis. The aim of this study was to assess the effect of HCV eradication in patients with abnormal serum iron studies prior to treatment with direct-acting antiviral agents (DAAs). PATIENTS: HCV-infected subjects with iron studies obtained before and after successful treatment with DAAs were identified (n=27). All had one or more abnormal iron test before treatment. RESULTS: Following HCV eradication, serum iron, transferrin-iron saturation and ferritin levels decreased significantly (pre- versus post-treatment, p<0.01 for each). Serum iron and/or transferrin-iron saturations normalized in 16/19 subjects and raised ferritin levels returned to the normal range in 14/18 subjects, including several with pretreatment transferrin-iron saturation >90% and/or serum ferritin >1000ng/mL. Elimination of HCV infection was associated with a significant reduction in post-treatment ferritin levels even among subjects whose ferritin levels were within normal limits at baseline. Risk factors for other conditions associated with abnormal iron status were present in the few cases in which iron studies failed to normalize following DAA treatment. CONCLUSIONS: Eradication of HCV infection restores normal iron status in most patients with abnormal iron tests, including those whose baseline parameters are suggestive of hemochromatosis.

Differential production of insulin-like growth factor-binding proteins in liver fibrosis progression.

Noninvasive methods for liver disease diagnoses offer great advantages over biopsy, but they cannot be utilized in all cases. Therefore, specific indicators for chronic liver disease management are necessary. The aim was to assess the production of insulin-like growth factor-binding proteins (IGFBPs) 1-7 and their correlation with the different stages of fibrosis in chronic hepatitis C (CHC). A prospective, cross-sectional, multicenter study was conducted. CHC patients were categorized by FibroTest® and/or FibroScan®. Serum concentrations of IGFBPs 1-7 were determined through multiple suspension arrangement array technology. Significant differences were validated by the Kruskal-Wallis and Mann-Whitney U tests. Logistic regression models were performed to assess the association between the IGFBPs and fibrosis stages. The association was determined utilizing odds ratios (ORs), and receiver operating characteristic (ROC) curves were constructed to distinguish the IGFBPs in relation to the diagnosis of fibrosis. IGFBP-1 and IGFBP-7 concentrations were higher in CHC than in the healthy individuals, whereas IGFBP-3, IGFBP-5, and IGFBP-6 were downregulated in the patients. An apparent increase of all the IGFBPs was found at fibrosis stage F4, but with different regulations. IGFBP-2, -4, -6, and -7 had the best OR, showing the relation to fibrosis progression. The ROC curves showed that IGFBP-7 was the only protein that distinguished F1 from F3 and F2 from F3. IGFBPs participate in liver fibrosis progression and could be employed as circulating novel protein panels for diagnosis and as possible therapeutic targets in liver fibrosis progression.

Association of seasonality and serum albumin concentration with vitamin D deficiency in subjects with chronic hepatitis C infection living in a sunny country.

OBJECTIVE: This study aimed to analyse the relationship between vitamin D deficiency and the season when the blood sample was obtained from subjects with chronic hepatitis C (CHC) infection. DESIGN: A cross-sectional study was conducted on a representative sample. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D [25(OH)D] concentration <50 nmol/l, based on the values set forth by the Endocrine Society guideline for higher-risk populations. Seasonality was defined according to solstices and equinoxes. The association of seasonality and clinical/laboratory characteristics with vitamin D deficiency was assessed using a multivariate logistic regression analysis. SETTING: NUPAIG Viral Hepatitis Outpatient Clinic of the Universidade Federal de São Paulo - Brazil. PARTICIPANTS: Adult subjects with CHC infection (n 306). RESULTS: The prevalence of vitamin D deficiency was 16 %, whereas the median serum 25(OH)D concentration was 87 (interquartile range, 59; third quartile = 118) nmol/l. Serum concentration was consistently lower in samples collected in spring and winter than in other seasons. In multivariate analysis, vitamin D deficiency was found to be independently associated with male gender, serum albumin concentration and with samples drawn in winter and spring. CONCLUSIONS: The findings show not only the relevance to consider season as a factor influencing 25(OH)D concentration but also the need to actively screen for hypovitaminosis D in all patients with CHC infection, especially in females and those with low albumin concentration.

Human platelet antigen-3 polymorphism as a risk factor for rheumatological manifestations in hepatitis C.

INTRODUCTION: Hepatitis C virus (HCV) infection is involved in the pathogenesis of autoimmune and rheumatic disorders. Although the human platelet antigens (HPA) polymorphism are associated with HCV persistence, they have not been investigated in rheumatological manifestations (RM). This study focused on verifying associations between allele and genotype HPA and RM in patients with chronic hepatitis C. METHODS: Patients (159) with chronic hepatitis C of both genders were analyzed. RESULTS: Women showed association between HPA-3 polymorphisms and RM. CONCLUSIONS: An unprecedented strong association between rheumatological manifestations and HPA-3 polymorphism, possibly predisposing women to complications during the disease course, was observed.

Baseline resistance associated substitutions in HCV genotype 1 infected cohort treated with Simeprevir, Daclatasvir and Sofosbuvir in Brazil.

BACKGROUND: The World Health Organization estimates that 1% of the world population (71 million) is infected with hepatitis C virus (HCV). In 2015, three direct-acting antivirals (DAAs), simeprevir (SMV), sofosbuvir (SOF) and daclatasvir (DCV) were included in the Brazilian protocol for the treatment of chronic hepatitis C. Despite the fact that the use of these drugs is associated with higher treatment response rates and with lower incidence of side effects, studies have shown the association between the presence of viral resistance mutations and the failure of pharmacological treatment. AIM: This way, this study aimed to evaluate the safety and effectiveness of treatment for HCV genotypes 1a and 1b infected patients with these DAAs, also analyzing the occurrence and prevalence of baseline resistance associated substitutions (RAS), observing the impact of these mutations into the treatment success. METHODS: Clinical data were collected from all the 262 HCV infected patients included for comparative analysis, while serum samples collected from 144 of these individuals, before treatment, were submitted to molecular biology approaches for mutation analysis into NS3, NS5A and NS5B regions. RESULTS: Regarding the treatment regimens, 49.6% of the patients received SOF+DCV±ribavirin and 50.4% used SOF+SMV±ribavirin. The sustained virological response at 12 weeks post-treatment (SVR12) rate was 92.7% (93.9% for SOF plus DCV and 91.7% for SOF plus SMV). No clinical or laboratorial factor was statistically associated with SVR. The most common adverse reactions were haematological events, nausea/vomiting, headache and asthenia. Out of 144 blood samples, 70 (48.6%) had detected RAS, 34.8% treated with SOF+DCV±ribavirin and 61.3% SOF+SMV±ribavirin. The resistance mutations against SMV were detected into NS3: substitutions G122S (28%), I170V (22.7%), Y56F (17.3%) and V132I (14.7%). The mutations against DCV R30Q (9.1%), P58H (6.1%) and Q62E (6.1%) were observed into NS5A, and for SOF the mutations A421V (10.6%), L159F (6.4%) and C316N (6.4%) were present inside NS5B viral protein. Four patients did not reach SVR, three of them presented viruses carrying RAS (1 treated with SOF+DCV and 2 with SOF+SMV). Some of these mutations, like R30Q (present in relapsing samples) and L159F, are well known by their influence on antiviral resistance, while others, like C316N, have a compensatory effect on viral fitness, maintaining these baseline RAS. CONCLUSION: The use of treatment regimens composed of SOF and DCV or SOF and SMV showed a high SVR rate, despite of a high rate of RAS, and a good tolerability profile in patients with HCV genotype 1. However, the high occurrence of baseline RAS observed in this casuistic is still a concern and studies like this show the necessity to understand how they are maintained in the population and to direct more efficiently the use of DAAs.

A combination of α-fetoprotein, midkine, thioredoxin and a metabolite for predicting hepatocellular carcinoma.

INTRODUCTION AND OBJECTIVES: The heterogenous nature of hepatocellular carcinoma (HCC) motivated this attempt at developing and validating a model based on combined biomarkers for improving early HCC detection. PATIENTS/MATERIALS AND METHODS: This study examined 196 patients for an estimation study (104 patients with HCC, 52 with liver cirrhosis and 40 with liver fibrosis) and 122 patients for the validation study (80 patients with HCC, 42 with liver cirrhosis). All patients were positive for hepatitis C virus. Four markers were measured: Midkine and thioredoxin using ELISA, 1-methyladenosine and 1-methylguanosine using a gas chromatography-mass spectrometry (GC-MS). The results were compared with alpha-fetoprotein (AFP). The performance of the model was estimated in BCLC, CLIP and Okuda staging systems of HCC. RESULTS: The model yielded high performance with an area under ROC (AUC) of 0.94 for predicting HCC in patients with liver cirrhosis, compared with AUC of 0.69 for AFP. This model had AUCs of 0.93, 0.94 and 0.94 in patients who had only one single nodule, absent macrovascular invasion and tumor size <2cm, respectively, compared with AUCs of 0.71, 0.6 and 0.59 for AFP. The model produced AUCs of 0.91 for BCLC (0-A), 0.92 for CLIP (0-1) and 0.94 for Okuda (stage I) compared with AUCs of 0.56, 0.58 and 0.64 for AFP. No significant difference was found between AUC in the estimation and the validation groups. CONCLUSION: This model may enhance early-stage HCC detection and help to overcome insufficient sensitivity of AFP.

The relative expression of hepatocellular and cholestatic liver enzymes in adult patients with liver disease.

INTRODUCTION AND OBJECTIVES: Hepatocellular liver injury is characterized by elevations in serum alanine (ALT) and aspartate (AST) aminotransferases while cholestasis is associated with elevated serum alkaline phosphatase (ALP) levels. When both sets of enzymes are elevated, distinguishing between the two patterns of liver disease can be difficult. The aim of this study was to document the predicted ranges of serum ALP values in patients with hepatocellular liver injury and ALT or AST values in patients with cholestasis. MATERIALS AND METHODS: Liver enzyme levels were documented in adult patients with various types and degrees of hepatocellular (non-alcoholic fatty liver disease, hepatitis B and C, alcohol and autoimmune hepatitis) and cholestatic (primary biliary cholangitis and primary sclerosing cholangitis) disease. RESULTS: In 5167 hepatocellular disease patients with ALT (or AST) values that were normal, 1-5×, 5-10× or >10× elevated, median (95% CI) serum ALP levels were 0.64 (0.62-0.66), 0.72 (0.71-0.73), 0.80 (0.77-0.82) and 1.15 (1.0-1.22) fold elevated respectively. In 252 cholestatic patients with ALP values that were normal, 1-5× or >5× elevated, serum ALT (or AST) values were 1.13 (0.93-1.63), 2.47 (2.13-2.70) and 4.57 (3.27-5.63) fold elevated respectively. In 56 patients with concurrent diseases, ALP levels were beyond predicted values for their hepatitis in 38 (68%) and ALT (or AST) values beyond predicted values for their cholestatic disorder in 24 (43%). CONCLUSIONS: These data provide health care providers with predicted ranges of liver enzymes in patients with hepatocellular or cholestatic liver disease and may thereby help to identify patients with concurrent forms of liver disease.

HEPLA: A multicenter study on demographic and disease characteristics of patients with hepatitis C in Latin America.

INTRODUCTION AND OBJECTIVES: Currently, there are limited data on the epidemiology and disease characteristics of patients with chronic hepatitis C (CHC) in Latin America. The primary objective of this study was to evaluate demographic and disease characteristics of patients with CHC in Latin America. PATIENTS AND METHODS: HEPLA was a non-interventional, multicenter study of the epidemiology and disease characteristics of patients with CHC in Argentina, Brazil, Chile, Colombia, and Mexico. RESULTS: Of the 817 included patients, the median age was 58 years, 53.9% were female, and 39.3% had cirrhosis. Overall, 41.2% were treatment naive, 49.8% were treatment experienced, and 8.9% were currently undergoing treatment. In patients with available data, genotype 1b accounted for 41.6% of infections, followed by genotype 1a (29.9%) and genotype 3 (11.3%). Probable mode of infection was transfusion in 46.8% of patients. Liver-related comorbidities were present in 26.4% of patients and non-liver-related comorbidities were present in 72.3%. Most patients (71.8%) received concomitant medications, with proton-pump inhibitors (20.8%) being the most commonly reported. CONCLUSIONS: At the time the HEPLA study was carried out, the data from this cross-section of patients in Latin America showed that the CHC population has variation in disease and viral characteristics, with a minority of patients receiving treatment and many patients having advanced disease. Increased awareness and access to treatment are necessary in Latin America in order to meet the goal of hepatitis C virus elimination by 2030.

Insulin resistance in nondiabetic Egyptian patients with chronic hepatitis C virus. / Resistencia a la insulina en pacientes egipcios no diabéticos infectados con el virus de hepatitis C crónica.

INTRODUCTION AND OBJECTIVE: Insulin resistance and diabetes mellitus are frequently associated with chronic hepatitis C virus (HCV) infection, and it is thought that the presence of insulin resistance aggravates liver disease. We aimed to evaluate insulin resistance in nondiabetic Egyptian patients with chronic HCV infection. MATERIALS AND METHODS: Sixty nondiabetic patients with chronic HCV infection and 30 healthy nondiabetic non-HCV-infected volunteers were enrolled in our study. They were divided into 3 groups: group 1 included 30 patients with chronic HCV infection with no cirrhosis, group 2 included 30 patients with chronic HCV infection and cirrhosis of the liver, and group 3 included 30 healthy volunteers as controls. The entire study population underwent a detailed clinical history and physical examination, weight and height measurement, routine laboratory tests, and viral marker determination that included hepatitis B surface antigen and HCV antibodies. PCR analysis was carried out on the patients with positive HCV antibodies. Fasting blood sugar and fasting insulin levels were measured in all the patients, and insulin resistance was calculated according to the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Patients with cirrhosis of the liver (2 patients with Child class A, 12 patients with Child class B, and 16 patients with Child class C) showed higher insulin resistance levels (2.76±0.97) than the patients with chronic HCV infection and no cirrhosis (2.03±0.743) and the control group (1.22±0.38). The p value was significantly different between the 3 groups. There were direct and significant correlations between insulin resistance, fasting blood sugar, and fasting insulin levels. Patients with chronic HCV infection showed significantly higher fasting insulin and glucose levels than the control group. CONCLUSION: Chronic HCV-infected patients showed significantly higher insulin resistance levels than the normal population, even in the absence of hepatic dysfunction and cirrhosis.

Human platelet antigen-3 polymorphism as a risk factor for rheumatological manifestations in hepatitis C

Abstract INTRODUCTION: Hepatitis C virus (HCV) infection is involved in the pathogenesis of autoimmune and rheumatic disorders. Although the human platelet antigens (HPA) polymorphism are associated with HCV persistence, they have not been investigated in rheumatological manifestations (RM). This study focused on verifying associations between allele and genotype HPA and RM in patients with chronic hepatitis C. METHODS: Patients (159) with chronic hepatitis C of both genders were analyzed. RESULTS: Women showed association between HPA-3 polymorphisms and RM. CONCLUSIONS: An unprecedented strong association between rheumatological manifestations and HPA-3 polymorphism, possibly predisposing women to complications during the disease course, was observed.

Immunological Dynamics Associated with Direct-Acting Antiviral Therapies in Naive and Experimented HCV Chronic-Infected Patients.

The therapeutic strategies used in the treatment of hepatitis C are essentially based on the combination of direct-acting antiviral agents (DAAs). This therapy has been shown to be very effective in relation to patient adherence to treatment and has shown high rates of sustained virological response (SVR). However, the immunological dynamics of patients infected with HCV is poorly understood. This fact led us to investigate the immune system of naive and experienced patients, who we followed before the therapy and three months after the end of treatment. In this study, 35 naive and experienced Brazilian patients with chronic hepatitis C and 50 healthy donors (HD group) were studied. The analysis of the soluble immunological biomarkers was performed using the flow cytometry methodology. The SVR rate was >90% among the 35 patients. Before treatment, correlations in the naive HCV group demonstrated a mix of inflammatory response occurring with moderate correlations between chemokines, inflammatory cytokines, and Th2 profile, with a strong regulation between IL-10 and IL-17A. On the other hand, experienced patients demonstrated a poor interaction between cytokines, chemokines, and cells with a strong correlation between IL-10, IL-6, CXCL-10, and CD8+ besides the interactions between IFN-γ and IL-4. Furthermore, naive and experienced patients seem to have a distinct soluble biomarker profile; therefore, a long-term follow-up is needed to evaluate patients treated with DAAs.

Prevalence and characteristics of anti-HCV positivity and chronic hepatitis C virus infection in HFE p.C282Y homozygotes.

INTRODUCTION AND AIM: Observations of hepatitis C virus (HCV) infection in adults with hemochromatosis are limited. MATERIALS AND METHODS: We determined associations of serum ferritin (SF) with anti-HCV in non-Hispanic white North American adults in a post-screening examination. Cases included p.C282Y homozygotes (regardless of screening transferrin saturation (TS) and SF) and participants (regardless of HFE genotype) with high screening TS/SF. Controls included participants without p.C282Y or p.H63D who had normal screening TS/SF. Participants with elevated alanine aminotransferase underwent anti-HCV testing. We determined prevalence of chronic HCV infection in consecutive Alabama and Ontario referred adults with HFE p.C282Y homozygosity. RESULTS: In post-screening participants, anti-HCV prevalence was 0.3% [95% CI: 0.02, 2.2] in 294 p.C282Y homozygotes, 9.5% [7.2, 12.3] in 560 Cases without p.C282Y homozygosity, and 0.7% [0.2, 2.3] in 403 Controls. Anti-HCV was detected in 7.2% of 745 participants with and 0.8% of 512 participants without elevated SF (odds ratio 9.9 [3.6, 27.6]; p<0.0001). Chronic HCV infection prevalence in 961 referred patients was 1.0% (10/961) [95% confidence interval (CI): 0.5, 2.0]. Ten patients with chronic HCV infection had median age 45y (range 29-67) and median SF 1163µg/L (range 303-2001). Five of eight (62.5%) patients had biopsy-proven cirrhosis. CONCLUSIONS: Odds ratio of anti-HCV was increased in post-screening participants with elevated SF. Prevalence of anti-HCV in post-screening participants with HFE p.C282Y homozygosity and chronic HCV infection in referred adults with HFE p.C282Y homozygosity in North America is similar to that of Control participants with HFE wt/wt and normal screening TS/SF.