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Chronic acral hyperkeratotic dermatosis includes several conditions such as lichen simplex chronicus (LSC), hypertrophic lichen planus (HLP), psoriasis vulgaris (Ps), acral acanthosis nigricans, acquired zinc deficiency, and necrolytic acral erythema (NAE). LSC, Ps, and HLP respond to conventional treatments such as topical corticosteroids, immuno-modulators such as tacrolimus, and oral methotrexate. Zinc-responsive acral hyperkeratosis is a novel entity that resembles the above mentioned diagnoses clinically but fails to respond to the above treatment options. NAE is a rare condition, commonly associated with hepatitis C virus infection and manifest similar clinical features of zinc-responsive acral hyperkeratosis, but differs histopathologically. Both conditions show a good response to oral zinc supplementation. As there is a paucity of literature on zinc-responsive acral hyperkeratosis, we are highlighting the case.

Background: Hepatitis C virus [HCV] infection is a global health problem. Children with certain risk factors are at high risk of infection.Objective: The present study aimed to evaluate the prevalence of HCV among high-risk Egyptian children.Methods: The study included 1357 children aged 3-15 years with risk factors of HCV including receiving blood products, hemodialysis, previous surgical intervention, insulin therapy and positive family history. They were subjected to careful history taking, thorough clinical examination and routine laboratory investigations. All children were tested for HCV antibodies using commercial 4th generation enzyme-linked immunosorbent assay [ELISA] kits. Those with positive results were further assessed using polymerase chain reaction [PCR].Results: Among the studied patients, there were 89 children [6.6 %] with positive HCV Ab and 73 children [5.4 %] with positive PCR test for HCV. Using multivariate logistic regression, significant predictors of HCV infection in the studied children were blood transfusion [OR: 1.23, CI: 0.019-13.4], Intravenous [IV] injection [OR: 10.962, CI: 1.937-62.026] and previous operation [OR: 3.12, CI: 1.046-31.6].Conclusion: HCV infection is highly prevalent among high-risk children. Blood transfusion, IV injection and exposure to surgery are independent risk factors for infection in this population.

Background Shanghai, as a pilot city of China to achieve the goal of eliminating hepatitis C, its strategy of allocating medical resources is a pressing problem to be solved. This study aims to infer the time-spatial clustering patterns of HCV-infected cases, and grasp the dynamic genotype distribution of HCV, thereby inform elimination strategies of HCV with efficacy and efficiency. Methods Reported HCV cases including their demographic information in Shanghai city from 2005 to 2018 were released from the National Infectious Disease Reporting Information System, population data at community scale, geographical layers of hospitals, communities and districts were gathered from former research. Blood samples of HCV-infected individuals were collected during 2014–2018 from 24 sentinel hospitals, HCV-antibody test, qualitative nucleic acid test and NS5B/5’UTR gene amplification were performed accordingly to determine the genotypes of the specimen. Furthermore, global and local spatial self-correlation analysis of both acute and chronic HCV infections were conducted at community scale year by year, then time-spatial clusters of acute and chronic HCV infections and HCV genotype distribution of specimen collected from sentinel hospitals by districts were mapped by using Arcmap10.1. Results A total of 2631 acute HCV cases and 15,063 chronic HCV cases were reported in Shanghai from 2005 to 2018, with a peak in 2010 and 2017, respectively. The mean age of chronic HCV patients was 49.70 ± 14.55 years, 3.34 ± 0.32 years older than the acute (t = 10.55, P-value Conclusions Despite the low prevalence of HCV infection, it is still needed to push forward the elimination process in Shanghai, as there is a certain amount of HCV infected people waiting to be treated. The time-spatial clustering patterns and the dynamic of HCV genotype distribution together indicated a changing constitution of different transmission routes of HCV infection, thus, a focused strategy may be needed for high-risk population related to genotype 3 infection like drug users, in addition to an enforcement of the existing measures of preventing the iatrogenic and hematogenic transmission of HCV.

Aims: Glucose-regulated protein 78 (GRP-78) is one of the basic markers of endoplasmic reticulum (ER) stress in tissues. It is known that ER stress develops in the livers of patients infected with hepatitis C. In this study, the aim was to assess serum GRP78 levels which have not previously been investigated as a stress marker in chronic hepatitis C patients (CHC).Methods: This case control study includes patients with chronic hepatitis C (CHC) infection in our Infectious Diseases clinic (n=60) and a healthy control group without any additional chronic disease (n=60). Serum GRP78 levels were measured with enzyme-linked immunosorbent assay (ELISA), then correlation analysis was performed for serum GRP78 levels with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and HCV-RNA levels.Results: A significant positive correlation was observed between HCV-RNA, ALT and AST levels in CHC patients (P, Amaç: Glikozla düzenlenen protein 78 (GRP-78) dokudaki endoplazmik retikulum (ER) stresinin temel göstergelerinden birisidir. Hepatit C ile enfekte hastalarda karaciğerde ER stresinin geliştiği bilinmektedir. Bu çalışmada kronik hepatit C (KHC) hastalarında bir stres belirteci olarak daha önce incelenmemiş olan serum GRP78 düzeylerinin değerlendirilmesi amaçlanmıştır.Yöntemler: Çalışmamız, Enfeksiyon Hastalıkları polikliniğimize başvuran Kronik Hepatit C (KHC) enfeksiyonu tanısı almış hasta grubu (n=60) ve ek kronik hastalığı olmayan sağlıklı kontrol (n=60) grubundan oluşan bir vaka kontrol çalışmasıdır. Serum GRP78 seviyesi Enzyme-Linked Immuno Sorbent Assay (ELISA) ile ölçülmüş, ardından GRP78 ile alanin aminotransferaz (ALT), aspartat aminotransferaz (AST), HCV-RNA düzeyleri arasında korelasyon analizi yapılmıştır.Bulgular: KHC hastalarında HCV-RNA düzeyleri ile ALT ve AST düzeyleri arasında anlamlı bir ilişki izlenmiştir (sırasıyla P

Cytokines play an important role in modulating inflammation during viral infection, including hepatitis C virus (HCV) infection. Genetic polymorphisms of cytokines can alter the immune response against this infection. The objective of this study was to investigate the possible association between chronic hepatitis C virus infection susceptibility and cytokine gene polymorphism for interleukin-10 (IL-10) rs1800896 and rs1800871, interleukin 6 (IL-6) rs1800795, TNF-α rs1800629, and TGF-β1 rs1800471 in Malay male drug abusers. The study was conducted on 76 HCV-positive (HP) male drug abusers and 40 controls (HCV-negative male drug abusers). We found that there were significant differences in the frequencies of genotype for IL-10 rs1800871 (p = 0.0386) and at the allelic level for IL-10 rs1800896 A versus G allele (p = 0.0142) between the HP group and the control group. However, there were no significant differences in gene polymorphism in interleukin 6 rs1800795, TNF-α rs1800629 and TGF-β1 rs1800471. These findings suggest significant associations between gene polymorphism for IL-10 rs1800871, IL-10 rs1800896 (at the allelic level) and susceptibility to HCV infection among Malay male drug abusers.

Objective Hepatitis C virus (HCV) infection is a major cause of liver disease. Since symptoms of chronic liver disease usually appear only late in the course of the disease, infected individuals may remain undiagnosed until advanced disease has developed. We aimed to investigate which screening strategies would be most effective to detect individuals unaware of their infection. Methods We developed a mathematical model for HCV disease progression and compared the current practice of HCV testing in Switzerland with the following screening strategies: intensive screening of active injection drug users (IDU), screening of former IDU, screening of individuals originating from countries with high HCV prevalence, screening of individuals born 1951–1985 (birth-cohort) and universal screening. All screening interventions were considered in addition to a baseline scenario that reflected the current practice of HCV testing. Results Within the first 4 years (2018–2021), every year, on average 650 cases were diagnosed in the baseline scenario, 660 with intensified IDU screening, 760 with former IDU screening, 830 with origin-based screening, 1420 with birth-cohort screening and 1940 with universal screening. No difference in liver-related mortality and incidence of end-stage liver disease between the screening scenarios was observed. Conclusion Our results suggest that only large-scale screening of the general population could substantially accelerate the rate of HCV diagnosis and treatment in Switzerland and other countries with similar epidemics. However, this implies screening of a large population with low prevalence, and may trigger considerable numbers of false-positive and borderline test results.

Context: Hepatitis C virus (HCV) is a potential cause of morbidity and mortality worldwide. It is most commonly transmitted through injecting drug use; the reuse or inadequate sterilization of medical equipment and the transfusion of unscreened blood products. Management of thalassemia requires long-term blood transfusion. Though it improves the overall survival, it carries a definite risk of infection which is expected to be higher in resource limited settings. Aims: To find the percentage of transfusion-transmitted infections (TTIs) in multitransfused patients of thalassemia in Eastern India. Settings and Design: The study was conducted to assess blood safety in rural population in India by measuring the percentage of TTIs including HCV in multitransfused thalassemia patients. Methods and Materials: One hundred and twenty three patients with major beta-thalassemia were enrolled in this study. The blood samples were tested using ELISA technique for all TTIs. HIV fourth generation kits, HbsAg, HCV third generation kits, malaria and syphilis, parbovirus IgM and parbovirus IgG kits, HEV Antigen and IgM antibody were used. Statistical Analysis Used: Proportions and means were calculated for categorical and continuous variables, respectively. Chi-square test was applied and P value of

Background The universal treatment of diagnosed patients with chronic HCV infection has been widely conducted in Italy since 2017. However, the pool of individuals diagnosed but yet to be treated in Italy has been estimated to end around 2025, leaving a significant proportion of infected individuals undiagnosed/without care. Estimates of this population are currently unknown. Methods A probabilistic modelling approach was applied to estimate annual historical HCV incident cases by their age-group (0–100 years) distribution from available literature and Italian National database (1952 to October 2019). Viraemic infection rates were modelled on the main infection routes in Italy: people who inject drugs (PWID), tattoos, sexual transmission, glass syringe use, blood transfusion and vertical transmission. Annual liver fibrosis stage transition probabilities were modelled using a Markov model. The number of HCV viraemic asymptomatic (fibrosis stage F0-F3:potentially undiagnosed/unlinked to care) and symptomatic (fibrosis stage F4: potentially linked to care) individuals was estimated. Results By October 2019, total viraemic HCV individuals in Italy (excluding treated patients since 1992) were estimated to be 410,775 (0.68 % of current population of Italy; 95 % CI: 0.64−0.71%, based on the current Italian population), of which 281,809 (0.47 %; 95 % CI:0.35−0.60%) were fibrosis stage F0-F3. Among different high risk groups in stage F0-F3, the following distribution was estimated: PWID; 52.0 % (95 % CI:37.9–66.6 %), tattoo; 28.8 % (95 % CI:23–32.3 %), sexual transmission; 12.0 % (95 % CI:9.6–13.7 %), glass syringe and transfusion; 6.4 % (95 % CI:2.4–17.8 %), and vertical transmission; 0.7 % (95 % CI:0.4–1.2 %). Conclusion Under the assumption that most untreated HCV-infected individuals with stage F0-F3 are undiagnosed, more than 280,000 individuals are undiagnosed and/or unlinked to care in Italy. Marked heterogeneity across the major routes of HCV transmission was estimated. This modelling approach may be a useful tool to characterise the HCV epidemic profile also in other countries, based on country specific epidemiology and HCV main transmission routes.

Background and objectives Chronic liver disease (CLD) encompasses a variety of etiologies, and the infectious causes are mainly hepatitis B and hepatitis C virus. Chronic alcohol abuse and non-alcoholic fatty liver disease also have a major contribution to CLD. The Child-Pugh scoring system indicates the probable prognosis and mortality risk of a patient with cirrhosis. The primary objective of this research is to observe the mortality risks of CLD caused by a variety of etiologies mentioned above. The secondary objective is to determine the biochemical markers that are correlating with the severity of the study groups. Another aim was to determine the Model for End-Stage Liver Disease (MELD) scoring of each study group predicting the severity of disease among the Child-Pugh classification. Materials and methods We broadly classified the etiologies into two study groups: (1) hepatitis B, C associated CLD (hepatitis B, C--CLD) and (2) non-hepatitis B, C associated CLD (non-hepatitis B, C-CLD). This study was conducted as a descriptive, retrospective study involving patients admitted to the Gastroenterology Department at Dow University Hospital between July 2019 and December 2019. All patients who met the inclusion criteria were included in the study in order to document their levels of severity markers of CLD. A total of 167 individuals met the inclusion criteria, and the sampling was done through non-probability consecutive methods. All continuous variables were described as mean and standard deviations, which were then compared using an independent sample t-test. The comparison of categorical data was done either using the chi-square test or Fisher's exact test accordingly. A p-value of

Background & Aims Patients hospitalised because of mental illness often have risk factors for contracting HCV. Scaling-up HCV screening for all psychiatric inpatients as a case-detection strategy for viral elimination is underexplored. This study aimed to evaluate the cost-effectiveness of scaling-up HCV screening and treatment for psychiatry hospital admissions in Switzerland vs. the current standard-of-care risk-based approach, where only those with a history of substance misuse disorder are offered testing. Methods HCV prevalence by history of substance misuse disorder was analysed in medical records from inpatient admissions to a Swiss psychiatry department. Cost-effectiveness was analysed from a healthcare provider perspective through a decision-tree screening model, using these HCV prevalence data. Model and parameter uncertainty were assessed using deterministic and probabilistic sensitivity analyses. Results Prevalence of HCV in psychiatry inpatients with a history of substance misuse disorder (n = 1,013) was 25.7%, compared with 3.5% among the remaining inpatients (n = 3,535). Scaling up HCV screening and treatment for all psychiatry admissions was cost-effective vs. the risk-based approach, with an incremental cost-effectiveness ratio of US$9,188 per quality-adjusted life-year gained. The incremental cost-effectiveness ratio remained cost-effective considering a HCV prevalence as low as 0.07%. The population-level net monetary benefit of the generalised screening approach was US$435,156,348, with 917 additional patients per year detected and treated at a cost of US$3,294 per person (vs. US$2,122 under risk-based screening). Conclusions Scaling up HCV screening and treatment at diagnosis with all-oral, interferon-free regimens as a generalised approach for psychiatric admissions was cost-effective and could support reaching World Health Organization targets for HCV elimination by 2030. Lay summary Patients hospitalised because of mental illness often have risk factors for HCV. We found that testing all psychiatry patients in hospital for HCV was cost-effective compared with testing only patients who have a history of substance misuse. Scaling up HCV testing and treatment could help to wipe out HCV., Graphical abstract, Highlights • Screening all psychiatry admissions for HCV was cost-effective vs. standard-of-care. • Generalised HCV screening enabled 917 extra patients to be treated per year. • Scaling-up HCV testing to all psychiatry admissions would support HCV elimination.

Introduction:the aim of the present study was to determine the frequency of HBsAg and anti-HCV antibodies in health care providers (HCPs) at three referral hospitals in Libya, and to correlate the HBsAg status with history of hepatitis B vaccination among HCPs. Methods:one hundred eighty-two HCPs, with a mean age (±SD) of 32.9±8 years and age range from 20 to 59 years, were enrolled in this study. They were 50 doctors, 68 nurses, 42 laboratory technicians, 12 hospital cleaners, five anesthesia technicians and five midwives. They were tested, after obtained a written consent, for the presence of HBsAg and anti-HCV antibodies by enzyme linked immuno-sorbent assay (ELISA) techniques. A pre-test questionnaire was filled by each HCP to verify place of work, working period, type of work, status of HBV vaccination, and history of needle stick injury. Results:four HCPs have anti-HCV antibodies positive (2.2%) and nine were HBsAg positive (4.9%). Only 52% (95/182) of the HCPs received full dose of hepatitis B vaccine, while the others either not completed the vaccination schedule or have not receive it. One hundred (54.9%) of the participants had exposed to blood via needle stick injury during their work, 6 (6%) of them were HBsAg positive and three (3%) were anti-HCV positive. Needle stick injury was considered as primary risk factor in 66.7% (6/9 HCPs) of HBsAg-positives and 75% (3/4 subjects) of anti-HCV-positives. Conclusion:the present study showed a higher frequency of HBsAg than anti-HCV among HCPs in three major hospitals in Libya. This difference may be explained by the low hepatitis B vaccination rate and the high rate of needle stick injury among this high risk group for these infections.

Patients undergoing hemodialysis are at an increased risk of hepatitis C virus (HCV) infection. The implementation of standard infection control measures can substantially decrease the risk of infections and other nosocomial infections. To study the HCV infection rates and genotypes in maintenance hemodialysis subjects in a dialysis unit. A total of 196 maintenance hemodialysis subjects were tested for HCV RNA for one year at a tertiary care teaching hospital in northeast India continuously. Genotyping was performed using direct sequencing (Sanger sequencing) of the 5′UTR‐core region. The HCV infection rate was 26.0%. On phylogenetic analysis, 29 sequences clustered around genotype 3 and subtype 3f were observed. High sequence similarities (75–100% homology) were observed among the isolated sequences. High molecular similarities in the isolates from the same dialysis unit with a high infection rate (26.0%) over a relatively short period of study (10 months) indicated an ongoing nosocomial transmission. Nosocomial transmission by subtype 3f is rare, and it has not been reported in dialysis cases previously. The strain is most likely evolving from common strains such as 3b or 3i and may spread due to migration or movement of people. Urgent implementation of adequate infection control measures is required., A high infection rate of HCV (26%) was detected in the dialysis unit of a tertiary care hospital. All the strains of HCV were of the same genotype and subtype 3 f. This is the first time an outbreak of HCV 3f subtype is reported.

Hepatitis C virus (HCV) infection in kidney transplant recipients (KTRs) can be successfully treated with direct antiviral agents (DAA). The aim of our study was to analyze different measures of vascular function during and after the DAA treatment. As we have observed the improvement of blood pressure (BP) control in some individuals, we have conducted an analysis of potential explanatory mechanisms behind this finding. Twenty-eight adult KTRs were prospectively evaluated before and 15 months after start of DAA therapy. Attended office BP (OBP), augmentation index (AIx), pulse wave velocity (PWV), flow-mediated dilation (FMD), liver stiffness measurement (LSM), and liver steatosis assessment (controlled attenuation parameter (CAP)) were measured. In half of the patients, improvement of OBP control (decline of systolic BP by at least 20 mmHg or reduction of the number of antihypertensive drugs used) and parallel central aortic pressure parameters, including AIx, was observed. There was a significant decrease in CAP mean values (241 &plusmn, 54 vs. 209 &plusmn, 30 dB/m, p &lt, 0.05) only in patients with OBP control improvement. Half of our KTRs cohort after successful HCV eradication noted clinically important improvement of both OBP control and central aortic pressure parameters, including AIx. The concomitant decrease of liver steatosis was observed only in the subgroup of patients with improvement of blood pressure control.

Hepatic parenchymal disease, including chronic viral hepatitis, has traditionally been considered a relative contraindication to islet transplantation as the islets are infused into the recipient’s liver. We present a case study of a patient with treated chronic hepatitis C infection (HCV) who safely received an autologous islet transplant following total pancreatectomy with excellent clinical outcomes. The patient was a 60-year-old woman diagnosed with debilitating abdominal pain secondary to chronic pancreatitis and with preserved islet function. She had previously been treated >10 years prior to surgical evaluation with interferon monotherapy for 1 year that led to sustained virologic response, including at the time of surgical evaluation for total pancreatectomy and islet autotransplantation (TPIAT). She underwent comprehensive preoperative evaluation of the liver, including liver biopsy, which showed no significant portal inflammation or fibrosis. Following a multidisciplinary meeting and discussion of the potential risks for the patient, the decision was made to proceed with TPIAT. The patient underwent a standard total pancreatectomy, and an autologous islet dose of 6638 islet equivalents/kg body weight was infused into the liver via the portal vein. Portal vein pressure was monitored throughout the infusion with a transient peak pressure of 27 cm H2O (basal pressure of 14 cm H2O) and final pressure of 23 cm H20 at 10 min post-infusion. Aside from a transient transaminitis, liver enzymes were normal at the time of hospital discharge. At greater than 1 year of follow-up, the patient has improved quality of life, with reduction in narcotic analgesia, remains insulin independent (with normal islet function), and has normal liver function. This case illustrates that islet autotransplant into the liver can be safely performed and suggests that carefully selected patients with liver disease may be eligible for TPIAT.

In December 2017, our academic medical center implemented universal hepatitis C virus screening among adult hospitalized patients. We reviewed charts of patients screening positive outside the birth cohort (1945–1965) in the first 6 months after implementation. Documented risk factors were common in younger patients but rare in patients born before 1945.

Background This study aimed to investigate the occurrence and risk factors of thyroid dysfunction (TD) in patients with chronic hepatitis C (CHC) infection in Taiwan. Methods The data in this study were obtained from the Taiwan National Health Insurance Research (Taiwan NHIR) database between 2001 and 2013. CHC patients treated with pegylated interferon/ribavirin (PEG-IFN/RBV) were enrolled as case patients, and nontreated CHC patients were enrolled as controls and were matched at a control:case ratio of 3:1 by index date, age (± 3 years), and sex. We compared the cumulative incidence of TD between the cohorts at follow-up until 2013. Results During the study period, 3810 cases and 9393 controls were included in the study. Among the study subjects, 173 (4.5%) case patients and 244 (2.6%) controls were diagnosed with TD during the follow-up period. The types of TD were hypothyroidism (42.9%), hyperthyroidism (31.2%), and thyroiditis (25.9%). Compared to controls during the 13-year follow-up, patients treated with PEG-IFN/RBV had a higher incidence rate of TD (P

Liver disease due to hepatitis C infection in renal transplant recipients is difficult to treat and often associated with reduced patient survival. A 43-year-old male, a renal allograft recipient, presented at 6 years follow-up with significant weight loss over 3 months. He was detected to have new onset diabetes mellitus together with hepatitis C virus (HCV) infection (genotype 1). His HCV load remained high despite the change of immuno-suppression from tacrolimus to cyclosporine. A decision to treat with a new anti-viral combination of ledipasvir and sofosbuvir for 12 weeks was taken. Within 3 weeks, his raised serum transaminases levels normalized and viral load became undetectable. At the end of 16 weeks, he continues to do well with normal renal function, has sustained remission from hepatitis C infection and resolution of diabetes.

A 65-year-old man presented with a 2-year history of severe bilateral proptosis, palpable lymphadenopathy and moderate hepatosplenomegaly. A blood test was positive for hepatitis C infection. CT showed palpebral infiltrative lesions with regional progression through the temporal and masticatory spaces to the pharynx and hypopharynx causing almost complete airway obstruction. A palpebral biopsy was consistent with low-grade Bcl-2+ extra-nodal MALT non-Hodgkin B-cell lymphoma. The patient received six cycles of rituximab-based chemotherapy with clinical remission at 9-month follow-up. Bilateral proptosis is a rare presentation of several diseases. When brain CT excludes cavernous sinus pathology, thyroid ophthalmopathy or haematological malignancy should be considered. LEARNING POINTS: Bilateral proptosis is a rare presentation with a broad differential diagnosis, and is most frequently is caused by cavernous sinus disease, thyroid ophthalmopathy or haematological malignancy.Hepatitis C may be associated with MALT lymphoma and presents mainly at non-gastric locations even with few hepatic manifestations of the infection.Long-term low-grade lymphoma may present with severe disseminated disease at diagnosis, but treatment response is generally good. info:eu-repo/semantics/publishedVersion

Background Hepatitis B and C viruses are known to be carcinogenic and have been associated with the development of non-Hodgkin’s lymphoma as well as hepatocellular carcinoma. The incidence of head and neck cancer is increasing worldwide, and early diagnosis is vital in order to achieve good oncological outcomes. Objectives To investigate the association between chronic hepatitis B and C infection, and head and neck squamous cell carcinoma (HNSCC). Study design We performed a retrospective case control study with 774 head and neck squamous cell carcinoma (HNSCC) patients undergoing treatment, and 1518 cancer-free controls undergoing hernia surgery. Hepatitis B and C serologies were tested prior to treatment, and cases and controls were age- and sex-matched before analysing rates of infection. Results HNSCC patients were more likely than controls to have evidence of chronic hepatitis B (OR = 2.76; CI 95 %, 1.64–4.64) and hepatitis C (OR = 2.59; 95 % CI, 1.46–4.60) infection. No substantial association was found between hepatitis B and C infection and other known risk factors for head and neck cancer. Conclusions These findings suggest a positive association between both hepatitis B and hepatitis C chronic infection, and HNSCC. More work is needed to establish a causal role, however an awareness of the possibility of increased risk of HNSCC may lead to earlier diagnosis and better outcomes in patients with hepatitis B and C.

Hepatitis C virus (HCV) has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential detail in the pathogenesis of virus-related autoimmune and lymphoproliferative disorders, ranging from clonal expansion of B-cells with organ and non-organ-specific autoantibody production up to overt non-Hodgkin’s lymphoma along a continuous step-by-step model of B-cell lymphomagenesis, where the intermediated mixed cryoglobulinemia could be considered as a stage of suppressible antigen-driven lymphoproliferation. The HCV long-lasting extrahepatic replicative state generates an abnormal systemic immunological response, including rheumatoid factor (RF) and cryo- and non-cryoprecipitable immune complexes, as well as clinical manifestations, comprising dermatitis, polyarthralgias and arthritis, pulmonary disease, aplastic anemia, glomerulonephritis and vasculitis. The mechanism of these extra-hepatic disorders is thought of as linked to immune complex disease, but their pathogenesis is poorly clarified. Immune-suppressive treatment could induce high-level hepatitis C viremia and impair hepatic disease. We report a female patient, whose chronic HCV-related liver cirrhosis with associated explosive, but oligosymptomatic lymphoproliferative immune response, i.e., RF beyond three thousand times the upper of normal range (unr), type II cryoglobulinemia with cryocrit 40% and monoclonal gammopathy IgM-k, has been successfully and safely treated by long-lasting (sixty-six months) combined antiviral therapy (pegylated interferon alfa and ribavirin), at moderate and tapering dose regimen, prolonged for nearly 24 months after the first viral suppression. At the last follow-up (fifty-one months), the patient was showing very-long term antiviral response, progressive decline of secondary immune activation and absence of significant side-effects. Further research is required to fully verify the real impact on therapeutic choice/regimen.

To estimate the effect of hepatitis C virus (HCV) coinfection on the development of complications and progression of human immunodeficiency virus (HIV) disease among HIV-infected elite controllers. Single-center retrospective cohort. Kaplan–Meier methods, prevalence ratios, and Cox proportional-hazards models were used. In all, 55 HIV-infected elite controllers were included in this study. Among them, 45% were HIV/HCV coinfected and 55% were HIV mono-infected. Median follow-up time for the cohort was 11 years. Twenty-five patients experienced a complication and 16 lost elite controller status during the study period. HCV coinfected patients were 4.78 times (95% confidence interval 1.50–15.28) more likely to develop complications compared with HIV mono-infected patients. There was no association between HCV coinfection status and loss of elite control (hazard ratio 0.75, 95% confidence interval 0.27–2.06). Hepatitis C virus coinfection was significantly associated with the risk of complications even after controlling for sex, injecting drug use, and older age. HCV coinfected patients had higher levels of cellular activation while also having similar levels of lipopolysaccharide and soluble CD14. HCV coinfection was not associated with loss of elite controller status. Taken together, this suggests that HCV coinfection does not directly affect HIV replication dynamics or natural history, but that it may act synergistically with HIV to produce a greater number of associated complications. Continued follow-up will be needed to determine whether HCV cure through the use of direct-acting antivirals among HIV/HCV coinfected elite controllers will make the risk for complications among these patients similar to their HIV mono-infected counterparts.

In the European Union, it is estimated that there are 5.5 million individuals with chronic infection of hepatitis C. Intravenous drug abuse is undoubtedly the key source of the hepatitis C epidemic in Europe and the most efficient mode of transmission of HCV infections (primarily due to short incubation time, but also because the virus is introduced directly into the blood stream with the infected needle). Potentially high-risk and vulnerable populations in Europe (and the world) include immigrants, prisoners, sex workers, men having sex with men, individuals infected with HIV, psychoactive substance users etc. Since there is a lack of direct evidence of clinical benefits of HCV testing, decisions related to testing are made based on indirect evidence. Clinical practice has shown that HCV antibody tests are mostly adequate for identification of HCV infection, but the problem is that this testing strategy does not hit the target. As a result of this health care system strategy, a large number of infected patients remain undetected or they are diagnosed late. There is only a vague link between screening and treatment outcomes since there is a lack of evidence on transmission risks, multiple causes, risk behavior, ways of reaching screening decisions, treatment efficiency, etc. According to results of limited number of studies it can be concluded that there is a need to develop targeted programmes for detection of HCV and other infections, but there also a need to decrease potential harms.

Introduction Asunaprevir (ASV) is a potent, pangenotypic, twice-daily hepatitis C virus (HCV) NS3 inhibitor indicated for the treatment of chronic HCV infection. Methods A population pharmacokinetic (PPK) model was developed using pooled ASV concentration data from 1239 HCV-infected subjects who received ASV either as part of the DUAL regimen with daclatasvir or as part of the QUAD regimen with daclatasvir and peg-interferon/ribavirin. Results A two-compartment model with first-order elimination from the central compartment, an induction effect on clearance, and an absorption model consisted of zero-order release followed by first-order absorption adequately described ASV PK after oral administration. A typical value for ASV clearance (CL/F) was 50.8 L/h, increasing by 43% after 2 days to a CL/F of 72.5 L/h at steady-state, likely due to auto-induction of cytochrome P450 3A4 (CYP3A4). Factors indicative of hepatic function were identified as key influential covariates on ASV exposures. Subjects with cirrhosis had an 84% increase in ASV area under the concentration time curve (AUC) and subjects with baseline aspartate aminotransferase (AST) above 78 IU/L had a 58% increase in area under the concentration time curve (AUC). Asians subjects had a 46% higher steady-state AUC relative to White/Caucasian subjects. Other significant covariates were formulation, age, and gender. Conclusion The current PPK model provided a parsimonious description of ASV concentration data in HCV-infected subjects. Key covariates identified in the model help explain the observed variability in ASV exposures and may guide clinical use of the drug. Funding Bristol-Myers Squibb. Electronic supplementary material The online version of this article (10.1007/s40121-018-0197-y) contains supplementary material, which is available to authorized users.

The hepatitis C virus (HCV) is a global health threat. The available data suggests that HCV prevalence is at about 2-3% of the world’s population (130-170 million people), and in 2013 alone almost 700,000 deaths were directly attributed to HCV. In spite of this tremendous burden, globally less than 1% of people with a chronic hepatitis infection were receiving treatment, and HCV is one of the few communicable disorders that continue to grow, with a 47% increase in mortality over the last two decades.[2] The majority of HCV-infected individuals are unaware of their infection, and screening for HCV was not recommended until recently. This may facilitate the spread of HCV not only in high-risk groups, but also in populations with low HCV prevalence affected by the recent humanitarian crisis with mass migration from regions with higher HCV rates. In May 2016 the World Health Organization adopted the first-ever global strategy to reduce the incidence of all viral hepatitis by 90%, and mortality by 65% by 2030, which requires both the prevention of HCV transmission in high-risk groups and effective treatment for individuals already infected.

Background and aims In Europe a wide variation in HCV prevalence between countries was described, ranging from 0.1 to 6.0%, higher in Eastern Europe than in Western Europe, which may threaten the biological safety of donated blood. The HCV frequency among blood donors in Romania has has made the object of only very few published studies. The aim of this study was to analyze the frequency of anti-HCV antibodies in blood donors from Cluj County (Romania) and its trend, in the period 2006-2011. Patients and methods Between 2006-2011 all donors, new and repeat donors were screened for hepatitis C virus infections using enzyme-linked immunosorbent assay (ELISA). Reactive results were confirmed using radioimmunoblotting assay (RIBA). The frequency and trends were analyzed using the T-test and X 2 -test. Results There were 95,181 donors tested in the blood transfusion centre (BTC) laboratories between 2006-2011. The overall prevalence was 0.254 % (95% CI 0.222-0.286). The prevalence rates of anti-HCV antibodies increased with age between both genders, being higher among women, starting to decrease after the age of 51. Conclusions The results of this study demonstrate a high HCV prevalence in donations from 2006 to 2011, as compared to other countries in Europe, especially among first time blood donors, an infection that might be a potential threat to blood safety.

Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major health problem in the world. Hairdressers (barbers) are in continuous contact with scissors and blades, and are considered a high-risk group for these infections. Objectives: The aim of this study was to analyze the prevalence of hepatitis B and C infections in barbers in Tehran and to evaluate their attitudes and knowledge about the occupational risk of these infections. Methods: Six hundred eleven barbers were included in this study. A group of 556 bakers were also selected from the same regions, as a low-risk control group. Serum levels of hepatitis B surface antigen (HBsAg), HBsAg-specific antibody (HBsAb), hepatitis B core antigen-specific antibody (HBcAb), and hepatitis C virus-specific (anti-HCV) antibody markers were measured with the enzyme-linked immunosorbent assay (ELISA). Participants were interviewed using a questionnaire consisting of four sections: demographic information, awareness, behavior, and personal attitudes. Results: There were no significant differences in the frequency of HBsAg between the two groups. However, the frequency of HCV Ab in barbers was significantly higher than that in bakers (P < 0.005). In addition, the frequency of HBsAb marker in barbers was significantly correlated with increased awareness (P < 0.05) and number of tattoos (P < 0.001). HBcAb marker was significantly correlated with age (P < 0.001) and duration of professional career (P < 0.005). With age, barbers’ attitudes improved significantly (P < 0.05). Conclusions: Being a barber alone is not a potential risk factor for HBV infection, while HCV infection is still an occupational health hazards for barbers. We suggest more extensive case-control studies with regard to rates of hepatitis B and C markers among barbers in other Iranian cities to assess the incidence of hepatitis B and C infections among this population.

Background: Diabetes is a fast-growing health problem in Egypt with a significant impact on morbidity, mortality, and health care resources. Currently, the prevalence of type 2 diabetes (T2D) in Egypt is around 15.6% of all adults aged 20 to 79. Objective: To describe the epidemiology, principal causes, associated risk factors, cultural aspects, and challenges that may contribute to the rapid rise in T2D in Egypt. Methods: Review of papers in PubMed and relevant gray literature. Findings: The International Diabetes Federation (IDF) has identified Egypt as the ninth leading country in the world for the number of patients with T2D. The prevalence of T2D in Egypt was almost tripled over the last 2 decades. This sharp rise could be attributed to either an increased pattern of the traditional risk factors for T2D such as obesity and physical inactivity and change in eating pattern or other risk factors unique to Egypt. These include increased exposure to environmental risk factors like pesticides and increased prevalence of chronic hepatitis C.. Conclusions: Prevention, early identification, and effective intervention are integral components of effective T2D care in Egypt. These strategies may reduce the expanding economic burden associated with T2D care.

Few studies have evaluated the prevalence of replicating hepatitis C virus (HCV) infection in sub-Saharan Africa. Among 1812 individuals infected with human immunodeficiency virus, no patient in rural Mozambique and 4 patients in urban Zambia were positive for anti-HCV antibodies. Of these, none had confirmed HCV replication.

Introduction : Although hepatitis C virus (HCV) screening is recommended for all HIV-infected patients initiating antiretroviral therapy, data on epidemiologic characteristics of HCV infection in resource-limited settings are scarce. Methods : We searched PubMed and EMBASE for studies assessing the prevalence of HCV infection among HIV-infected individuals in Africa and extracted data on laboratory methods used. Prevalence estimates from individual studies were combined for each country using random-effects meta-analysis. The importance of study design, population and setting as well as type of test (anti-HCV antibody tests and polymerase chain reactions) was examined with meta-regression. Results : Three randomized controlled trials, 28 cohort studies and 121 cross-sectional analyses with 108,180 HIV-infected individuals from 35 countries were included. The majority of data came from outpatient populations (55%), followed by blood donors (15%) and pregnant women (14%). Based on estimates from 159 study populations, anti-HCV positivity prevalence ranged between 3.3% (95% confidence interval (CI) 1.8–4.7) in Southern Africa and 42.3% (95% CI 4.1–80.5) in North Africa. Study design, type of setting and age distribution did not influence this prevalence significantly. The prevalence of replicating HCV infection, estimated from data of 29 cohorts, was 2.0% (95% CI 1.5–2.6). Ten studies from nine countries reported the HCV genotype of 74 samples, 53% were genotype 1, 24% genotype 2, 14% genotype 4 and 9% genotypes 3, 5 or 6. Conclusions : The prevalence of anti-HCV antibodies is high in HIV-infected patients in Africa, but replicating HCV infection is rare and varies widely across countries. Keywords: HIV infection; hepatitis C infection; Africa; meta-analysis; antibody test; polymerase chain reaction; genotype. To access the supplementary material to this article please see Supplementary Files in the column to the right (under Article Tools). (Published: 9 June 2016) Citation: Azevedo TCL et al. Journal of the International AIDS Society 2016, 19 :20711 http://www.jiasociety.org/index.php/jias/article/view/20711 | http://dx.doi.org/10.7448/IAS.19.1.20711

Background: Hepatitis C virus (HCV) infection is a global public health problem and is a leading cause of morbidity and death, with regional variations in genotype prevalence. Objectives: This study aimed to explore the prevalence of anti-HCV seropositivity among patients with hereditary anemias, the association of anti-HCV seropositivity with selected risk factors and the common HCV genotypes. Patients and Methods: This prospective descriptive study was carried out on patients with hereditary anemias from January 2010 through December 2014 registered at the Center for Hereditary Blood Diseases. A total of 2778 patients (1282 males and 1496 females) were recruited, their mean age was 13.19 ± 9.40 years. Patients were screened for HCV antibodies using an enzyme-linked immunosorbent assay test. Quantitation of the HCV viral load and genotype were assessed using polymerase chain reaction (PCR). Results: The frequency of anti-HCV seropositivity was higher in 2010 (33.7%) and declined progressively over the following 4 years (31.7%, 20.2%, 10.8%, and 9.2%), respectively. Out of 424 patients with two positive anti-HCV tests at least 6 months apart, 215 (50.7%) had positive results with PCR. The most frequent genotype was 4 in 43 (56.5%), followed by 1 in 31 (40.7%) patients; 1a: 21.1% and 1b: 19.6%. A significant association was found between anti-HCV seropositivity and type of disease, and deferoxamine pump use, P < 0.05. Conclusions: Anti-HCV seropositivity is declining among multitransfused patients with hereditary anemias in Basra, Iraq, and genotype 4 is the most common in these patients.

Kidney transplantation from a hepatitis C virus (HCV)-positive donor to an HCV-negative recipient till recently has been a contraindication. In view of the excellent sustained virological response (SVR) rates with directly acting antiviral agents, HCV-positive donors are being considered for the HCV-negative recipients in a few centers. We report the successful transplantation of an HCV-negative recipient transplanted with an HCV-positive donor kidney. Donor was treated with sofosbuvir and ribavirin for 12 weeks. At 10th and 16th weeks of starting treatment, her HCV-RNA PCR was negative. Three weeks later, transplantation was performed with basiliximab induction and triple immunosuppression with tacrolimus, mycophenolate, and prednisolone. The recipient was administered sofosbuvir and ribavirin for 12 weeks. He attained good graft function with a stable creatinine. His serial alanine transaminases were normal on 3rd, 6th, and 12th months, respectively. Six months posttransplant his anti-HCV antibody, and HCV-RNA PCR were negative.

Introduction. Thrombocytopenia is a common finding in chronic liver diseases and it is caused by different pathophysiological mechanisms. Immunologic thrombocytopenic purpura (ITP) in hepatitis C infection is a distinct clinical entity. Possible reasons for ITP in this case could be capabillity of HCV to induce autoimmune phenomena but also immunomodulatory effects of interferon that is used for HCV infection treatment. The specific laboratory parameters for ITP diagnosis during HCV infection have not been defined yet. Case Outline. A 37-year-old patient diagnosed with HCV infection was treated with PEG-interferon and Ribavirin during 24 weeks. The partial response was achieved after the therapy with reduction of viral replications. One month after therapy completion, the patient was hospitalized due to skin haemorrhagic syndrome and a serious degree of thrombocytopenia (2?109/l). The number and megakaryocyte morphology in bone marrow aspirate were normal. An assay of thrombocyte kinetics by radioactive marker (Indium 111) showed rapid thrombocyte destruction and their early seljuestration in the spleen. Conclusion. Results of assays about thrombocyte kinetics during HCV infection show enchanced thrombocyte destruction in the liver. Accordingly, the most important parameter for ITP diagnosis in HCV infection, in this case, was rapid thrombocyte destruction and their early sequestration in the spleen approved by Indium kinetics. Also, in support of ITP is the increment of thrombocyte number during therapy with intravenous immunoglobulins. Thrombocytopenia was developing during antiviral therapy and on indirect conclusion is that viral replication is not the reason for it.

Hepatitis C infection is a worldwide problem. The global prevalence of the hepatitis C virus (HCV) averages 3%. Moreover, its prevalence among patients undergoing haemodialysis (HD) varies worldwide, ranging from as low as 1% to up to 70%. There are few data on its prevalence in developing countries, and even less information is available on HD patients. A literature review revealed that the prevalence of HCV infection among patients undergoing HD in Latin America ranges from 4.2 to 83.9%, with most data stemming from Argentina, Brazil, Mexico, Peru, Chile, Venezuela and Cuba. The most common genotype was genotype 1, and subtype 1b was the most frequent. The risk factors associated with this condition were the duration of the HD treatment and blood transfusion before hepatitis C screening. In addition, HCV RNA detection by polymerase chain reaction is crucial for the diagnosis of HCV infection in HD patients. Trials using combinations of new oral antiviral drugs, such as sofosbuvir and combo (ombitasvir, paritaprevir, ritonavir and dasabuvir), should be the next step in the improvement of care among HD patients with HCV, because these therapeutic agents apparently do not require dose adjustment according to renal function. Finally, information on this subgroup of patients remains unavailable in some countries; therefore, additional studies are needed to determine the prevalence trend of HCV infection in these populations.

Background: Hepatitis C Virus (HCV) infection is diagnosed by antibody and RNA based methods. Patients with anti-HCV sample rate/ cutoff rate (S/CO) ratios > 1 are reported as anti-HCV positive. RNA based methods are introduced to confirm positivity in seropositive samples. Objectives: The current study aimed to assess relationship between S/CO rates and HCV-RNA levels in the laboratory to identify HCV viremia in patients with a positive anti-HCV. Patients and Methods: All serum samples were assayed for anti-HCV by ELISA method. A total of 265 anti-HCV positive patients were tested for HCV-RNA testing by quantitative method using Artus HCV RG Real-time Polymerase Chain Reaction (RT- PCR) kit. Statistical analysis was done by SPSS version 16. Results: Of the 265 patients with HCV infection, 204 (77%) were male and the mean age was 43.53 ± 13.17 years, ranging 1 - 81 years. No correlation was found between S/CO ratios and HCV-RNA levels. There was significant difference in S/CO ratio between viremic and non- viremic subjects. The sensitivity, specificity, negative predictive value, and positive predictive value were 100%, 81.4%, 100%, and 77.2%, respectively in the S/CO ratio of 2.7. Conclusions: The present study indicated that anti-HCV S/Co ratio is useful to predict non-viremic patients. A cut-off value of 2.7 can determine the usefulness of HCV-RNA testing. Patients with S/CO < 2.7 are not viremic; therefore, HCV-RNA testing is not recommended. It is suggested that laboratories report S/CO ratio along with anti-HCV results to manage HCV infection better, especially in countries that quantitative HCV testing is expensive or not available.

Background Seventeen of 172 included studies in a recent systematic review of blood tests for hepatic fibrosis or cirrhosis reported diagnostic accuracy results discordant from 2 × 2 tables, and 60 studies reported inadequate data to construct 2 × 2 tables. This study explores the yield of contacting authors of diagnostic accuracy studies and impact on the systematic review findings. Methods Sixty-six corresponding authors were sent letters requesting additional information or clarification of data from 77 studies. Data received from the authors were synthesized with data included in the previous review, and diagnostic accuracy sensitivities, specificities, and positive and likelihood ratios were recalculated. Results Of the 66 authors, 68% were successfully contacted and 42% provided additional data for 29 out of 77 studies (38%). All authors who provided data at all did so by the third emailed request (ten authors provided data after one request). Authors of more recent studies were more likely to be located and provide data compared to authors of older studies. The effects of requests for additional data on the conclusions regarding the utility of blood tests to identify patients with clinically significant fibrosis or cirrhosis were generally small for ten out of 12 tests. Additional data resulted in reclassification (using median likelihood ratio estimates) from less useful to moderately useful or vice versa for the remaining two blood tests and enabled the calculation of an estimate for a third blood test for which previously the data had been insufficient to do so. We did not identify a clear pattern for the directional impact of additional data on estimates of diagnostic accuracy. Conclusions We successfully contacted and received results from 42% of authors who provided data for 38% of included studies. Contacting authors of studies evaluating the diagnostic accuracy of serum biomarkers for hepatic fibrosis and cirrhosis in hepatitis C patients impacted conclusions regarding diagnostic utility for two blood tests and enabled the calculation of an estimate for a third blood test. Despite relatively extensive efforts, we were unable to obtain data to resolve discrepancies or complete 2 × 2 tables for 62% of studies.

Background and Objectives: Pakistan is among the countries having high prevalence of HCV infection in the population but there is dearth of proper epidemiological data regarding acquisition of HCV infection in the pregnant population. Our objective was to determine the seroprevalence of HCV antibodies in healthy pregnant women and to assess the potential risk factors for HCV infection in HCV positive subjects and in the control group. Methodology: This cross sectional and comparative study was conducted from 1st January to 31st December 2010 in the Department of Obstetrics/Gynaecology Unit–I, Liaquat University Hospital Hyderabad. Sera were collected from all admitted pregnant women and tested for HCV anti bodies using Elisa kits (Abbott, USA). Data were analyzed using SPSS version 16.0 statistical package. Results: The seroprevalence of HCV among pregnant population was found to be 4.7%. HCV positive women were more likely to have a history of blood transfusion (OR 1.99, 95% CI 1.26- 3.12), History of therapeutic injection use (OR 2.46, 95% CI 1.43-4.26), history of surgery (OR 1.72, 95% CI 1.12-2.66) and history of sharing household products (OR 1.81, 95% CI 1.14-2.87). Conclusion: HCV seropositive pregnant women were more likely to have a history of blood transfusion, therapeutic injection use, surgery and sharing household items.

Mixed cryoglobulinemia (MC) is a small-vessel systemic vasculitis characterized by the presence of cryoglobulins, immunoglobulin complexes that precipitate at low temperatures ( < 37 oC) inducing the inflammatory process. The most frequent etiology is hepatitis C infection (HCV) (1). Rituximab (RTX), an anti-CD20 monoclonal antibody, has recently emerged as the treatment of choice for severe MC (2). We present a case of severe hepatitis C virus-induced MC that was controlled and maintained in remission with RTX for 26 months, a remarkable prolonged period of time.

Background: The regression of hepatitis C virus (HCV)-associated lymphoma with antiviral treatment (AT) is the strongest argument in favour of an etiological link between lymphoma, especially marginal zone lymphoma (MZL), and HCV infection. In addition, the favourable impact of AT on overall survival of these patients has been reported (Arcaini 2014, Michot 2015). Although there is a clear association across the studies between the lymphoma regression and the clearance of HCV, the direct anti-lymphoma activity of interferon (IFN) cannot be ruled out. AT is undergoing a revolution: new antiviral drugs, including direct-acting antiviral (DAA) like sofosbuvir (SOF) cure more than 90% of infections. However, data on new IFN-free regimens in HCV-associated lymphoproliferative disorders are scanty and based on clinical reports (Rossotti 2015; Sultanik 2015; Carrier 2015). Patients and Methods: We analyzed virological and hematological response of 26 patients (pts) with indolent B-cell non-Hodgkin lymphomas (NHL) or chronic lymphocytic leukemia (CLL) and HCV infection treated with an IFN-free AT. We included the 5 cases reported in literature (Rossotti 2015; Sultanik 2015; Carrier 2015) with updated follow up. Results: Histological, virological and hematological features are summarized in Table 1. Histology distribution was as follows: 12 splenic MZL, 6 extranodal MZL of MALT, 2 leukemic MZL, 2 nodal MZL, 2 CLL/SLL, 1 lymphoplasmacytic lymphoma (LPL) and 1 low grade NHL NOS. Cryoglobulins were present in 13 (symptomatic cryoglobulinemia in 5). HCV genotype was 1 in 15 pts, 2 in 4 pts, 3 in 3 pts and 4 in 2 pts, NA in 2 pts. Three pts previously received chemotherapy and 4 underwent IFN-based therapy before. Twenty-four pts received a SOF-based regimens (SOF + simeprevir in 10, SOF + ribavirin in 5, SOF + daclatasvir in 8, SOF + ledipasvir in 1) and 2 pts other regimens (ombitasvir + paritaprevir + ritonavir + ribavirin and faldaprevir + deleobuvir + ribavirin). In one pt with renal MZL 4 rituximab (R) doses have been added to SOF + simeprevir. Median AT duration was 12 weeks (range: 6-24). At time of present analysis, virological response is available in 21 pts while hematological response has been assessed in 20 pts. A sustained virological response has been obtained in 20 pts; hematological response has been observed only in pts with HCV clearance: in particular 8 pts (all MZL) achieved a complete response and 4 (all MZL) a partial response (comprising one treated also with R) while 5 had stable disease (response by histology is summarized in Table 1). In 7 pts response duration is +1 mo (in 2 pts), +2 mo (in 1 pt), +6 mo (in 3 pts), and +22 mo (in 1 pt); 6 pts (60%) cleared cryoglobulins after AT. After a median follow-up of 6 mo (range: 1-28), 2 pts progressed: one pt shifted to DLBCL and one pt without virological response progressed and died of lymphoma; another pt with hematological CR died of metastatic hepatocellular carcinoma 8 mo after AT. Complete data for all pts will be presented at the meeting. Conclusions: Our study shows that a significant rate of hematological response can be achieved in HCV-associated MZL also with IFN-free AT. These data are a strong rationale for planning prospective trials with DAA in this setting. Table 1. Features of 26 pts with NHL associated with HCV infection treated with IFN-free regimen and lymphoma response by histology N % Age, median (range) 26 57 (40-78) M/F 11/15 42/58 - Marginal-zone lymphoma SplenicNodalExtranodal of MALTLeukemic MZL- CLL - Lymphoplasmacytic lymphoma - Low-grade B-cell NHL NOS 22 12 2 6 2 2 1 1 84.7 46.2 7.7 23.1 7.7 7.7 3.8 3.8 Ann Arbor stage III-IV 19 73 B symptoms 4 15 ECOG 0 1 2 3 11 10 0 1 50 45 0 5 BM involvement 14 54 Extranodal disease 17 65 Splenic involvement 13 50 Liver involvement 5 19 Nodal disease 15 58 Bulky disease 7 27 Leukemic disease 9 35 Elevated LDH 8/22 36 Elevated b2-microglobulin 8/10 80 Albumin Disclosures No relevant conflicts of interest to declare.

HCV Infection is a global burden disease and it is related to the development of progressive liver fibrosis, cirrhosis and hepatocellular carcinoma. At least 80% of the persons that have an acute infection evolve to chronicity. This event affects the patient and their contacts for the risk of acquiring the infection. Once chronic HCV is present some factors accelerate progression: older age, obesity, alcohol consumption, etc. Severity of fibrosis is one of the most important factors to be analyzed before deciding to treat a patient. Pegylated interferon and ribavirin is the .standard of care. for this disease, however, it has many side effects, some of them life threatening. That is the reason why this treatment must be indicated in the right moment in the right patient. A complete medical evaluation must be done previously to initiate treatment. Other concurrent problems must be ruled out or treated. Decompensated cirrhosis, autoimmune diseases or other uncontrolled disease are contraindication to HCV treatment. Previous failure to treatment for HCV must be analyzed to identify the reasons for that event and consider retreatment. Cryoglobulinemia and membranoproliferative glomerulonephritis are indications for treatment independent from the severity of liver disease.br /

金沢大学医薬保健研究域医学系, Polyethylene glycol-interferon ﾎｱ (PEG-IFNﾎｱ) has been used as the standard treatment for hepatitis C virus (HCV) infection. There have been no previous reports of polyradiculoneuropathy with anti-ganglioside antibodies induced by PEG-IFNﾎｱ-2b. We report a 59-year-old man who developed polyradiculoneuropathy during treatment with PEG-IFN ﾎｱ-2b for chronic HCV infection. Serum levels of anti-asialo-GM1 (GA1) and anti-GM1 antibodies were elevated. Cessation of therapy with double filtration plasmapheresis resulted in marked improvement in his symptoms accompanied by a reduction in the antibody level. PEG-IFN ﾎｱ-2b may induce peripheral neuropathy mediated by anti-GA1 and anti-GM1 antibodies. © 2009 The Japanese Society of Internal Medicine.

No study has evaluated circulating CXCL10 in patients with mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) chronic infection. The aim of this study is to measure inteferon-inducible protein 10 (CXCL10/IP-10), interferon-gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) (Th1 cytokines) in a series of cryoglobulinemic patients and to correlate this parameter to the clinical phenotype.Serum CXCL10, IFN-gamma, and TNF-alpha were assayed in 102 patients with hepatitis C-associated cryoglobulinemia (MC + HCV), in 102 sex- and age-matched patients with type C chronic hepatitis without cryoglobulinemia (HCV+), and in 102 sex- and age-matched controls.Cryoglobulinemic patients showed significantly higher mean CXCL10 serum levels than controls (P0.0001) or HCV+ patients (P0.0001) (397 +/- 132 pg/mL, 92 +/- 53 pg/mL, 280 +/- 149 pg/mL, respectively). Moreover, CXCL10 was significantly increased in 30 cryoglobulinemic patients with active vasculitis compared to those without it (460 +/- 104 pg/mL vs 369 +/- 139 pg/mL, respectively; P0.001). Both groups of MC + HCV patients with or without active vasculitis had serum CXCL10 significantly higher than HCV+ patients (P0.001, P= 0.02, respectively). IFN-gamma levels were not significantly different in MC + HCV than in HCV+ patients or controls. Serum TNF-alpha levels were significantly higher in MC + HCV than in HCV+ patients or controls (median [interquartile range]: 12.0 [9.8], 5.7 [5.4], 1.3 [2.1] pg/mL, respectively; P0.0001).The study demonstrates high CXCL10 and TNF-alpha serum levels in patients with hepatitis C-associated cryoglobulinemia. Moreover, in MC + HCV patients, increased CXCL10 levels were significantly associated with the presence of active vasculitis.

The objective of the present study was to determine the presence of hepatic iron overload in patients with chronic HCV infection and to correlate it with histologic alterations, HCV genotype and response to therapy. Liver tissue samples from 95 patients with chronic hepatitis C were divided into two groups: group I, presence of iron overload in hepatic tissue (Perls' staining) and group II, no iron overload. Hepatic iron overload was detected in 30 (31.6%) of 95 patients. Of the 69 patients tested by genotyping, 49 (71.01%) were genotype 1 and 20 (28.99%) genotype non-1. Iron overload was detected in 14 (28.6%) patients with genotype 1 and in 6 (30%) with genotype non-1 (P = 0.906). There was a significant difference in fibrosis stage between groups (P = 0.005). In group I (N = 30), one patient had stage F0/F1 of fibrosis, while in group II (N = 65), 22 (33.8%) patients had minimal or no fibrosis. Fibrosis stage F2/F3 was observed in 70% of group I patients compared to 46.2% of group II. Eighty-five patients were treated with a combination of interferon and ribavirin; 29 of them (34.1%) had a sustained virologic response and 8 (27.6%) of them had hepatic iron overload. Iron overload was detected in 18 (32.1%) of the 56 non-responders (P = 0.73). Hepatic iron overload was frequent among patients with chronic hepatitis C and was associated with a more severe stage of liver fibrosis. There was no association between iron overload and HCV genotype and response to interferon and ribavirin therapy.

Hepatitis C is a major public health problem in the United States. Although the incidence of new infections declined substantially in the past decade, approximately 25,000 persons are infected each year. In total, an estimated 2.7 million Americans have chronic hepatitis C virus (HCV) infection and are at risk for HCV-related chronic liver disease and hepatocellular carcinoma (HCC). The most common exposure associated with HCV infection is use of injection drugs. Other less commonly identified risk factors include sexual contact; transfusions before blood screening was implemented; and occupational, nosocomial, and perinatal exposures. Although sources of HCV infection are the same for men and women, the overall prevalence of HCV infection is lower among women than men, which is likely related to the lower prevalence of injection-drug use among women. The risk for HCV transmission from mother to infant is about 5%–6%; transmission occurs only from women who are HCV RNA positive and is higher among those coinfected with HIV (≈18.7%) than among women not infected with HIV (≈5.4%). The influence of factors such as maternal viral titer and interventions at the time of delivery is unclear. Studies indicate that breastfeeding is not a risk factor for perinatal transmission. Most hepatitis C prevention strategies are gender neutral and include screening and testing donors of blood, plasma, organ, tissue, and semen; virus inactivation of plasma-derived products; effective infection control practices; identification, counseling, and testing of at-risk persons; and medical management of infected persons. Pregnant women with risk factors for infection should be identified, screened, and counseled regarding the risk for perinatal transmission.