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BACKGROUND. The use of hepatitis C virus–positive (HCV+) donors has expanded the donor pool for orthotopic heart transplantation (OHT). This study evaluated center-level trends and utilization of HCV+ donors for OHT. METHODS. Data were extracted from the Scientific Registry of Transplant Recipients on adults (≥18 y) undergoing OHT between January 1, 2016 and December 31, 2019. Centers performing

The methanol, chloroform and aqueous leaf extracts of Newbouldia laevis Were obtained using cold extraction method. Phytochemical screening {qualitative} of the extracts was investigated and the inhibitory activity of extracts against the isolates were assayed by agar well diffusion technique. The concentrations were varied from 100 mg/ml to 400 mg/ml and zones of inhibition at every concentration were recorded. The bacterial isolates including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Streptococcus pnuemoniae and Salmonella sp. The extracts revealed the presence of flavonoids, tannins, terpenes, alkanoids, phenolics, saponins and cardiac glycosides with exception of chloroform extract that revealed the presence of alkanoids, saponins and tannins only. Antibacterial activity revealed that methanol extract had the highest potency with 23.03±0.33e mm, followed by aqueous extract with 21.75±0.22d mm zones of inhibition against S. aureus, and the chloroform extract had the highest activity of 16.0±0.59d mm zone of inhibition against Salmonella sp. while aqueous extract had the least zone of inhibition against P. mirabilis with 10.07±0.67a mm on isolates. All the extracts, irrespective of the extracting solvents had a minimum inhibitory concentrations {MIC} range of 6.25 – 50 mg/ml and minimum bactericidal concentrations {MBC} range of 12.5 – 100 mg/ml. Findings from this research shows that N. laevis has high antibacterial potency against pathogens in blood even in comparison with some conventional antibiotics used.

Background: The impact of hepatitis virus infection on arterial calcification (AC) was not studied. Objective: To study the prevalence, severity and distribution of AC in incident hemodialysis patients with hepatitis B and C viral infection. Cases and methods: 172 stage 5 CKD adults (98 male and 74 female) were included; 58 of them were seronegative for both hepatitis B and C (SN group), 48 were positive for hepatitis B virus infection (HBV group) and 66 were hepatitis C virus positive (HCV group). Beside histopathology of the obtained arterial samples, all these cases were examined for body mass index (BMI), serum calcium (Ca), phosphorus (P), alkaline phosphatase (AP), serum albumin, uric acid (UA), alanine transaminase (ALT), parathormone (PTH), fibroblast growth factor 23(FGF23), interleukin 6 (IL6), and 25 hydroxy vitamin D (25 (OH) vit D), hemoglobin concentration, and serum ferritin. Results: 86 (50%) of the cases had AC; 11 of them were in SN group (19%), 9 in HBV group (18.8%) and all the 66 HCV group (100%). In SN group, 4 had intimal calcification, 5 had medial calcification, and 2 had both intimal and medial calcification. In HBV group, 9 had intimal calcification, while no cases were encountered with either medial or both site calcifications. In HCV group, 16 had intimal calcification, 31 had medial calcification, and 19 had both intimal and medial calcification. Calcification was in the form of spots in one case in SN group, and 6 cases in HBV group, a single plaque of calcification in 5 cases of SN group, 3 cases of HBV group, and 16 cases of HCV group, multiple plaques were detected in 4 cases in SN group, and 31 cases in HCV group, and diffuse calcification in one case in SN group, and 19 cases in HCV group.In HBV group, calcification was only detected in patients with high viremia, while all patients with low or moderate viremia were devoid of calcification. In HCV group, all patients with low viremia had intimal solitary plaque of calcification, all patients with moderate viremia had multiple plaques of medial calcification, while all patients with high viremia had diffuse intimal and medial calcification. Both groups of viral hepatitis were significantly different in comparison to SN group in either distribution or calcification score (P

Background and objectives: Carotid atherosclerosis is the second leading cause of mortality and a leading cause of major disability. Conventional risk factors like diabetes, hypertension, smoking and hyperlipidemia have been established to play pivotal role in the etiology of atherosclerosis. Besides these risk factors, inflammation due to infections is being considered as a possible cause of the disease. Among infectious agents Hepatitis C has been proposed to play a major role in the etiology of Carotid atherosclerosis. The Current study was conducted to see the frequency of carotid atherosclerosis in patients having hepatitis C virus (HCV) infection in our population. Objectives: To determine the frequency of carotid atherosclerosis in already diagnosed HCV positive patients. Study Design: Cross Sectional.Study Settings: The study was carried out in medical inpatient and outpatient departments of Sir Ganga Ram Hospital, Lahore. Study duration: Six months i.e from 28 April to 27 October 2016.Patients & Methods: Three eighty three (383) patients were included in the study according to inclusion criteria and carefully applying exclusion criteria after inquiring detailed history and doing clinical examination. Data Collection Procedure: Demographics like name, age, gender & address were noted. Patient’s detailed history about HCV was asked and Carotid Doppler was performed by researcher {using ultrasound machine APLIU TOSHIBA}, and findings were confirmed by the senior consultant Radiologist of the hospital who had vast experience in dealing such kind of patients and then presence of carotid atherosclerosis in HCV positive patients was noted. All this information was taken on Performa. Results: Carotid atherosclerosis was present in 131(34.2%), absent in 252(65.8%) patients and diabetes present in 246 (64.2%) patients and absent in 137(35.8%). Of 131 patients, 70(54%) were males and 61(46%) females. 54(41%) patients had hepatitis C for < 3 years and 77(59%) for ≥ 3 years. 93(71%) patients had positive family history of atherosclerosis while 38(29%) patients had none. Mean BMI of total patients was 29.64± 6.64; 119(31.1%) patients of BMI

Background: Direct-acting antivirals have changed the landscape of hepatitis C virus (HCV) care. While transplantation with HCV-positive donor organs is increasing, little is known about providers’ attitudes toward this topic. The aim of this study is to determine providers’ attitudes toward HCV-positive kidney transplantation. Methods: Willing transplant and nontransplant nephrologists, transplant surgeons, and mid-level providers completed an online survey from April through May 2018. The survey asked about HCV knowledge and willingness to transplant HCV-positive antibody, nucleic acid testing-positive kidneys into HCV-negative recipients. Descriptive analyses including mean and median for continuous variables and frequencies for categorical variables were calculated. Results: Seven-hundred surveys were emailed and 99 providers (62 transplant nephrologists, 28 nontransplant nephrologists, 7 transplant surgeons, and 2 advanced practice providers) completed the survey (participation rate 14.1%). All providers knew that HCV was curable, with 60% believing that it had no effect on transplant success and 32% thinking it reduced transplant success. Providers were significantly more likely to offer a HCV-positive organ to HCV-positive recipients compared to HCV-negative recipients in all queried circumstances (p < 0.005 in all cases), especially with increasing impact on patient’s quality of life. While only 39% of providers would offer a HCV-positive organ for transplant to a patient without HCV if it reduced the waitlist time by 1 year, 92% would offer a HCV-positive organ if it reduced the waitlist time by 4 years. However, only 47% thought that the use of HCV-positive kidneys should be for routine care, while 38% believed it should be reserved for research purposes only. There were no significant differences between transplant and nontransplant nephrologists in attitudes toward HCV-positive kidney transplantation. Providers believed that donor organs from those who were obese, >50 years old, or had died from a cardiac arrest were significantly more likely to reduce the likelihood of a successful transplant 1-year posttransplant when compared with a HCV-positive organ (p < 0.005 in all cases). Eighty-six percent of providers had concerns about HCV curability posttransplant. Conclusion: Although 92% of providers were willing to offer a HCV-positive kidney for transplant as patient waitlist time increases, less than half supported offering HCV-positive transplantation for routine care rather than for research. The results underscore the need for further education and data about the efficacy and safety of HCV-positive kidney transplantation.

Although statin therapy is a primary treatment to prevent cardiac allograft vasculopathy (CAV), its use may be delayed due to pharmacologic interactions in the early post-transplant period among heart transplant (HT) recipients with hepatitis C virus positive (HCV+) donors. Further examination of the possible benefits of early, nonstatin lipid-lowering therapies (LLT), such as PCSK9 inhibitors (PCSK9i), among this specific subset of transplant recipients is therefore becoming increasingly important. We report a 60-year-old man who received a HT from a HCV+ donor for end-stage ischemic cardiomyopathy. In the early post-transplant period, there was concern for drug-drug interactions between statin, immunosuppressant, and direct acting antiviral (DAA) therapy. In addition, prior to transplant, he reported statin-associated muscle symptoms in response to multiple statins, which persisted despite attempts to re-challenge and use an every-other-day dosing strategy. Therefore, the patient was started on PCSK9i therapy after transplantation and while receiving curative DAA therapy for HCV. As the number of HT recipients of HCV+ donors continue to rise, investigation into the safety and benefits of early use of PCSK9i for the reduction of CAV and improved cardiovascular and mortality outcomes should be pursued.

Background Transplant practices related to use of organs from hepatitis C virus–infected donors (DHCV+) is evolving rapidly. Methods We surveyed US kidney transplant programs by email and professional society LISTSERV postings between July 2019 and January 2020 to assess attitudes, management strategies, and barriers related to use of viremic (nucleic acid testing positive [NAT+]) donor organs in recipients who are not infected with HCV. Results Staff at 112 unique programs responded, representing 54% of US adult kidney transplant programs and 69% of adult deceased donor kidney transplant volume in 2019. Most survey respondents were transplant nephrologists (46%) or surgeons (43%). Among the responding programs, 67% currently transplant DHCV antibody+/NAT− organs under a clinical protocol or as standard of care. By comparison, only 58% offer DHCV NAT+ kidney transplant to recipients who are HCV−, including 35% under clinical protocols, 14% as standard of care, and 9% under research protocols. After transplant of DHCV NAT+ organs to recipients who are uninfected, 53% start direct-acting antiviral agent (DAA) therapy after discharge and documented viremia. Viral monitoring protocols after DHCV NAT+ to HCV uninfected recipient kidney transplantation varied substantially. 56% of programs performing these transplants report having an institutional plan to provide DAA treatment if declined by the recipient’s insurance. Respondents felt a mean decrease in waiting time of ≥18 months (range, 0–60) justifies the practice. Program concerns related to use of DHCV NAT+ kidneys include insurance coverage concerns (72%), cost (60%), and perceived risk of transmitting resistant infection (44%). Conclusions Addressing knowledge about safety and logistic/financial barriers related to use of DHCV NAT+ kidney transplantation for recipients who are not infected with HCV may help reduce discards and expand the organ supply. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020_11_25_KID0004592020.mp3

Background and Aims With more transplant centers in the United States are accepting hepatitis C virus infected (HCV+) deceased donor kidneys (dHCV+), the trend of non-utilization and decline of these organs have not been re-examined. Method We used data from the national Organ Procurement and Transplantation Network on deceased donor kidneys between Jan 2000 and Dec 2018 in the United States. Kidney non-utilization for HCV+ was defined as a positive donor HCV status and positive hepatitis as the reason for non-utilization. dHCV+ kidney decline was defined as a donor HCV+ status among kidneys recovered for transplantation but not transplanted. We assessed associations of a dHCV+ status with kidney non-utilization or decline, adjusted for donor characteristics (age, race, sex, body mass index, diabetes, hypertension, kidney donor profile index), using multivariable logistic regression. Results A total of 274,570 deceased donor kidneys procured for transplantation between 2000 and 2018 were identified. Among these kidneys, 4.1% were from dHCV+. Proportion of dHCV+ non-utilization among all non-utilized kidneys increased from 2000-2005 (3.9%) and then subsequently declined. This proportion increased slightly to 1.1% in 2014 and decreased to 0.5, 0.8, 0.4, 0.6% in 2015-2018, respectively. Multivariable-adjusted odds ratios for dHCV+ non-utilization and decline by year demonstrate consistently an increasing trend from 2000-2006 followed by a decreasing trend from 2006-2011 (Fig A-B). Multivariable-adjusted odds ratios for dHCV+ (compared to dHCV-) non-utilization and decline increased to 6.56 (95% CI 5.30-8.12) and 6.66 (95% CI 5.39-8.24), respectively, in 2012, and decreased to 2.32 (95% CI 2.01-2.69) and 2.28 (95% CI 1.98-2.64), respectively, in 2018. Conclusion dHCV+ non-utilization and decline have decreased in the last few years, particularly after 2014. 2018 had a historic lowest odds ratio for non-utilization and decline of dHCV+ organs, which reflects the increased acceptability of transplant centers to these kidneys. Overall, since 2014, the odds ratios for dHCV+ non-utilization and decline decreased by half. Yet, there is more room for decreasing the non-utilization and decline for these potentially life-saving organs.

The causal link between chronic hepatitis C and glycometabolic alterations has been confirmed by much biochemical, clinical, and epidemiological research work, but what is still controversial is the long-term clinical impact of sustained virologic response (SVR) achieved by direct-acting antiviral agents (DAAs) on patients with type 2 diabetes mellitus (DM). The aim of this paper is to summarize the biochemical and clinical consequences to DM of DAA-based therapy for hepatitis C virus (HCV) infection. An electronic search of Embase, PubMed, MEDLINE, Ovid, and the Cochrane Database of Systematic Reviews was conducted for publications assessing whether clearance of HCV achieved by interferon (IFN)-free antiviral therapy determines significant changes in glycometabolic control and clinical outcomes of diabetic patients. A beneficial effect of SVR obtained by DAA therapy on DM prevention and the short-term outcome of glycometabolic alterations are acknowledged by most of the studies. Whether this effect is maintained over the long term with a significant clinical impact on diabetic and liver disease is still a matter of debate.

Under current guidelines, hepatitis C virus (HCV)-positive livers are not transplanted into HCV-negative recipients because of adverse posttransplant outcomes associated with allograft HCV infection. However, HCV can now be cured post-LT (liver transplant) using direct-acting antivirals (DAAs) with >90% success; therefore, HCV-negative patients on the LT waiting list may benefit from accepting HCV-positive organs with preemptive treatment. Our objective was to evaluate whether and in which HCV-negative patients the potential benefit of accepting an HCV-positive (i.e., viremic) organ outweighed the risks associated with HCV allograft infection. We developed a Markov-based mathematical model that simulated a virtual trial of HCV-negative patients on the LT waiting list to compare long-term outcomes in patients: (1) willing to accept any (HCV-negative or HCV-positive) liver versus (2) those willing to accept only HCV-negative livers. Patients receiving HCV-positive livers were treated preemptively with 12 weeks of DAA therapy and had a higher risk of graft failure than those receiving HCV-negative livers. The model incorporated data from published studies and the United Network for Organ Sharing (UNOS). We found that accepting any liver regardless of HCV status versus accepting only HCV-negative livers resulted in an increase in life expectancy when Model for End-Stage Liver Disease (MELD) was ≥20, and the benefit was highest at MELD 28 (0.172 additional life-years). The magnitude of clinical benefit was greater in UNOS regions with higher HCV-positive donor organ rates, that is, Regions 1, 2, 3, 10, and 11. Sensitivity analysis demonstrated that model outcomes were robust. CONCLUSION Transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm. (Hepatology 2018;67:2085-2095).

Aim Iron overload is frequently reported in haemodialysis (HD) patients particularly those with chronic hepatitis C virus (HCV) infection. Soluble haemojuvelin (sHJV) has recently emerged as one of the significant regulators of iron homeostasis and hepcidin expression. The aim of the present study was to evaluate the potential associations of sHJV and hepcidin with inflammation, iron parameters and erythropoietin requirement in prevalent HD patients with HCV. Methods Serum sHJV and hepcidin were measured in 60 prevalent HD patients with [group I (n = 30)] and without [group II (n = 30)] HCV, and controls (n = 30) by enzyme-linked immunosorbent assay. Parameters related to anaemia, iron metabolism, inflammation, sHJV and hepcidin were measured. Results Serum hepcidin in HCV positive versus negative groups was 89.40 ± 46.08 ng/mL and 224.1 ± 72.36 ng/mL, P = 0.000, respectively, while sHJV was 245 ± 1.338 ng/mL and 254 ± 0.762 ng/mL, P = 0.147, respectively in positive versus negative patients. In group I, hepcidin correlated with serum ferritin (r = -0.512 P = 0.005) and transferrin saturation (TSAT%) (r = 0.572, P = 0.000) and sHJV correlated with ferritin (r = 0.40, P 0.000), TSAT% (r = 0.450, P = 0.002) and a significant correlation also existed between sHJV and hepcidin (r = -0.259, P = 0.045). In the regression analysis, ferritin and TSAT% were able to predict sHJV; (standardized β = 0.52, P 0.001) and (standardized β = 0.48, P 0.010). Ferritin and sHJV were also able to predict hepcidin (standardized β = 0.627, P = 0.006) and (standardized β = 0.300, P = 0.007) in group I. Conclusion Soluble haemojuvelin levels seem to be associated with iron overload parameters and hepcidin levels in HCV positive HD patients.

Hepatitis C virus (HCV) infection in renal allograft recipient is associated with increased morbidity and mortality. At present, only few studies related to treatment and outcomes of HCV-infected renal allograft recipients with DAAs have been published. We aimed the study to assess the efficacy and safety of sofosbuvir-based regimens in HCV-infected renal allograft recipients. We analyzed data of 22 eligible HCV-infected renal allograft recipients (14 genotype-3, 6 genotype-1, one each genotype-2 and 4) who were treated with DAAs at our institute. DAA regimen included sofosbuvir and ribavirin with or without ledipasvir or daclatasvir for 12-24 weeks. Patients were followed up for 24 weeks after completion of treatment. A rapid viral response of 91%, end of therapy response of 100%, and sustained viral response at 12 and 24 weeks of 100% with rapid normalization of liver enzymes were observed. Therapy was well tolerated except for ribavirin-related anemia. A significant decrease in tacrolimus trough levels was observed and most patients required increase in tacrolimus dose during the study. Treatment with newer DAAs is effective and safe for the treatment of HCV-infected renal allograft recipients.

Peripheral blood mononuclear cells (PBMCs) play a critical role in clearing hepatitis C virus (HCV). PBMC defects have been linked with HCV infection; however, the underlying mechanisms remain obscure. We hypothesized that PBMCs of HCV-infected patients are more susceptible to programmed cell death (PCD), and are therefore unable to clear HCV. We compared spontaneous PBMC PCD and cytokine [interleukin (IL)-1, -6, -8, -10, and -12] secretion between untreated (naive) HCV+ and treated [sustained responder (SR)] patients with HCV, and HCV− healthy controls. Spontaneous PBMC PCD was assessed by annexin-V fluorescein isothiocyanate/propidium iodide staining, and cytokine levels were measured by cytometric bead array. Differences between groups were analyzed through paired and nonpaired t tests and Mann–Whitney U test. The rate of spontaneous PCD was higher in PBMCs of naive HCV+ patients (p

Background & objective Atypical chemokine receptor 1(ACKR1) represents an atypical chemokine receptor that can bind promiscuously to various chemokines. Chemokines play a crucial role to recruit leukocyte subsets migration through the endothelium and into liver against the virus during the progression of hepatitis C virus (HCV) infection. Most HCV positive patients can lead to liver fibrosis. Hyaluronic acid (HA), laminin (LN), collagen IV(C-IV) and amino-terminal pro-peptide of Type-III pro-collagen (PIII NP) are indices of the extent of liver fibrosis. The aim of this study was to investigate the association between ACKR1 polymorphism and liver fibrosis with these four serum liver markers in HCV positive patients. Methods From April 2015 to December 2015, a total of 210 patients (109 males and 101 females) with chronic HCV infection at Dalian Infectious Hospital were recruited to participate in this study. ACKR1 genotyping was using TaqMan probes method. HA, LN, C-IV and PIII NP were detected by using diagnostic kits. Results We compared serum levels of HA, LN, C-IV and PIII NP between FY*A/FY*A and FY*A/FY*B patients and the differences were not significant (P=0.905, P=0.298, P=0.880 and P=0.470, respectively). Conclusions This study has attempted to elucidate the role of ACKR1 polymorphism in liver fibrosis progression of HCV infection, our results demonstrated that ACKR1 polymorphism is not directly associated with the fibrogenesis in HCV positive patients.

Diffuse large B cell lymphoma (DLBCL) patients carrying hepatitis C virus (HCV) have higher risk of treatment toxicity and complications. The aim of this study was to assess the impact of HCV in a series of DLBCL patients treated with immunochemotherapy. 321 patients (161 M/160F; median age, 66 years) diagnosed with de novo DLBCL in a single center between 2002 and 2013 were included. Immunodeficiency-related lymphomas were excluded. HCV+ cases were defined by the presence of IgG anti-HCV. Main clinico-biological characteristics and outcome were analyzed according to the viral status. Two hundred ninety patients were HCV− and 31 HCV+. HCV+ patients were older (median age 71 vs. 64 years, P = 0.03), had more often B symptoms (P = 0.013), spleen (P = 0.003), and liver (P = 0.011) involvement, higher rate of early death (

Background/objective: HCV viremia has been known to provoke a plethora of autoimmune syndromes as well as nonspecific rheumatologic manifestations. HCV is the most frequent cause of mixed cryoglobulinemia, which is characterized by endothelial deposition of rheumatoid factor containing immune complexes and endorgan vasculitis. Rheumatoid factor positivity is found to be more prevalent among patients with HCV infection compared to the general population. The aim of the study was to ascertain the relationship of rheumatoid factor titer with cryoglobuliemia in hepatitis C virus positive patients and to assess its relation with different disease characteristics. Methods: A cross sectional study was carried out through one year. Fifty patients known to suffer from HCV were subjects of the study. Patients were interviewed and demographic, clinical and serologic data were recorded. All patients were tested for cryoglobulins by crude method and rheumatoid factor titer was determined in all patients. Child-Pugh classification was used for assessment of liver cell failure. Data were analyzed by the Statistical Package for the Social Sciences (SPSS, version 17). Data analysis is done by using Chi-Squared test (χ2) test and Fisher’s exact test as appropriate. Associations between interval, ordinal and dichotomous variables were tested by Pearson`s Product Moment Correlation Coefficients (r). Results: Cryoglobulinemia was detected in 36 (72%) patients out of the 50 HCV patients. Rheumatoid Factor (RF) was positive in 38% patients (76%). All HCV patients who were positive for cryoglobulin had a positive RF. Presence of RF found to be positively significantly correlated with the presence of cryogloulins in HCV patients. Conclusions: HCV infection is a major contributing factor of mixed cryoglobulinemia with elevation in RF titre. Positive anti-HCV antibodies together with highly positive RF titre in the presence of musculoskeletal, neurological and cutaneous manifestations strongly suggest the diagnosis of mixed cryoglobulinemia.

There are several different liver disorders which may occur concurrently post-HSCT. This chapter covers the history of hepatitis C virus (HCV) before the development of direct-acting antiviral therapy. The case discusses an HCV-negative patient who received a transplant from his HCV-positive donor. The patient had well-established hepatic GVHD but later developed a rapid rise in his aminotransferases coupled with a rapid rise in his HCV viral copy number. The pathology of fibrosing cholestatic hepatitis (FCH) is described and compared with the pathologic features typical of hepatic GVHD. The differential diagnoses of rapidly rising posttransplant liver tests are discussed.

Hepatitis C virus infection is associated with several glomerular diseases, most commonly cryoglobulinemic glomerulonephritis, which is typically secondary to type II mixed cryoglobulinemia. We present a patient with hepatitis C virus infection and cryoglobulinemic glomerulonephritis secondary to type I (monoclonal) cryoglobulinemia that is likely related to a concurrent hepatitis C virus infection-associated lymphoproliferative disorder. We list the differential diagnosis of cryoglobulinemic glomerulonephritis. Additionally, the case draws attention to the possibility that, rarely, even clinically undetectable "occult" B-cell lymphoproliferative disorders may result in significant kidney disease.

This study investigated whether the expression of CD44 variant 9 (CD44v9) might be a functional marker of tumor-initiating stem-like cells in primary hepatocellular carcinomas (HCCs) of hepatitis C virus (HCV)(+) patients and provide an indicator of patient survival, as well as associated mechanisms. A total of 90 HCV(+) HCC patients who underwent surgery from 2006 to 2011 were enrolled and monitored for 2-8 years. Expression of CD44v9 was validated immunohistochemically in all HCCs, followed by comparative proteome, survival, and clinicopathological analyses. CD44 variant 8--10 was further evaluated in diethylnitrosamine-induced HCCs of C57Bl/6J mice. Focally localized CD44v(+) cells with a membranous staining pattern were detected in human HCV(+) and mouse HCCs. CD44v9(+) cells of HCCs were predominantly negative for Ki67 and P-p38, indicating decrease of cell proliferation in the CD44v9(+) tumor cell population, likely to be related to suppression of intracellular oxidative stress due to activation of Nrf2-mediated signaling, DNA repair, and inhibition of xenobiotic metabolism. CD44v9 IHC evaluation in 90 HCV(+) HCC cases revealed that positive expression was significantly associated with poor overall and recurrence-free survival, a younger age, poor histological differentiation of HCCs, and high alkaline phosphatase levels compared with patients with negative expression. CD44v9 is concluded to be a potential biomarker of tumor-initiating stem-like cells and a prognostic marker in HCV(+) HCC patients associated with Nrf2-mediated resistance to oxidative stress.

Background: Viral hepatitis is the most common liver disease in pregnancy and is also the most common cause of jaundice in pregnancy in tropical countries. Risk factors for transmission are intravenous drug abuse, surgical and dental procedures done without adequate sterilization of instruments, sexual route etc. Early diagnosis and management can prevent maternal and fetal complications. This study was done to evaluate the frequency, risk factors and pregnancy outcome in hepatitis B virus (HBV) and hepatitis C virus (HCV) positive antenatal women.Methods: This case control study was conducted in Teerthankar Mahaveer Medical College and Research Centre, Moradabad, Uttar Pradesh, India from January 2017 to June 2018 on total 2511 pregnant women. The serum samples were checked for presence of hepatitis B surface antigen (HBsAg) and presence of IgG antibodies to HCV. Analysis of sociodemographic profile, risk factors and pregnancy outcome were done in all HBV and HCV positive women.Results: Out of 2511 pregnant women, 292 were tested positive for hepatitis. Maximum number of women were in the age group of 21-30 years. Most of the seropositive women were multipara. Frequency of positivity was maximum for HCV (67.1%). The risk factors for transmission in study population were intravenous drug abuse, blood transfusion, history of surgery and tattooing.Conclusions: Hepatitis infection rate is increasing. Universal screening for HBV and HCV can be recommended in pregnant women in developing countries. Education and awareness of public and health care workers can reduce the risk of transmission.

Objective High-risk donors for patients with end-stage cardiac or pulmonary disease awaiting transplantation represent an opportunity for access to more organs and therefore can significantly decrease the waiting list mortality. The objective of this study is to investigate the use of hepatitis B virus core antibody positive or hepatitis C virus seropositive donors for pediatric heart transplantation. Methods Data were reviewed from the United Network of Organ Sharing database (June 2008 to June 2015). A total of 3 hepatitis C seropositive and 9 hepatitis B core antibody positive donor hearts were identified for transplantation. Factors of age, underlying diagnosis, transplant year, extracorporeal membrane oxygenation, inotrope support, hepatitis C virus serostatus, and hepatitis B virus surface antigen status were used for 2 separate propensity score models. Standardized difference was evaluated for these variables before and after match. Survival was compared between the matched cohorts. Results Post-transplant graft survivals for recipients of hepatitis C virus positive donors and hepatitis B virus core antibody positive donors were similar to matched recipients of hepatitis C virus negative and hepatitis B virus core antibody negative donors, respectively. Conclusions The study has a small cohort to derive any significant conclusions, but the results are encouraging and consistent with the current trends among adult thoracic and pediatric kidney transplantation and demonstrates that hepatitis C virus positive and hepatitis B virus core antibody positive donors are not often used for pediatric heart transplantation.

Objective To assess the Histological alteration of liver in asymptomatic HCV PCR positive family blood donors. Methods This is a prospective cross sectional study carried out at Blood Transfusion Services, Clinical & Molecular Laboratory and Pakistan Health Research Council, Jinnah Postgraduate Medical Centre, Karachi from January 2011 to December 2016. One hundred thirteen (113) Anti HCV and HCV RNA positive family blood donors with normal or slightly raised ALT during three consecutive bimonthly visits were included. After taking consent liver biopsy was done to see the histopathological changes in these study participants. The software program SPSS for windows (Ver.19) was utilized for all statistical analysis. Results One hundred thirteen blood donors who were Anti HCV and HCV RNA positive were included. Ninety eight were male and 15 Female with a mean age of 32.3±6.94 years. Nineteen (16.8%) had significant inflammation of grade 2-3. Nine (8.0%) had significant fibrosis and steatosis was seen in 65 (57.5%) cases. Cirrhosis or advanced liver disease was not found in this series. Conclusion HCV infected individual with normal ALT level having good physical health, without any sign of advanced liver disease on ultrasonography and routine laboratory investigation like AST, Gamma GT, Alkaline Phosphatase, serum albumin, A/G ratio, platelet count and PT, INR might be highly helpful to predict mild or progressive liver disease. Ultimately it reduces the need of liver biopsy, an invasive procedure having significant complications.

Introduction: Hepatitis C Virus (HCV) infection is the significant cause of morbidity and mortality in Haemodialysis (HD) patients and kidney transplant recipients. HD technique may contribute to in maintaining the inflammatory state in many HD patients. Oxidative stress, inflammation and endothelial dysfunction are common in patients with End-Stage Renal Disease (ESRD). Aim: To assess the possible relationships between oxidative stress, inflammatory and endothelial dysfunction markers with HCV positive status on maintenance HD. Materials and Methods: The study enrolled 22 patients with ESRD, seropositive for HCV; 22 patients with ESRD, seronegative for HCV on maintenance HD and 19 healthy subjects as controls. In the present study, high sensitivity C-reactive protein (hs-CRP) was estimated by immunoturbidimetry method, Homocysteine (Hcy) was estimated by enzymatic recycling method, Malondialdehyde (MDA), Ferric Reducing Ability of Plasma (FRAP) and Nitric oxide (NO) were estimated by spectrophotometric method and Carotid Intima Media Thickness (CIMT) was estimated by Carotid Ultrasonography. Results: There is statistically significant increase in serum MDA, Hcy, hs-CRP, CIMT levels and statistically significant decrease in serum NO and FRAP levels in HCV positive and HCV negative groups when compared to controls. Correlation analysis of CIMT with other markers in the study showed statistically significant negative correlations among CIMT with FRAP and NO and statistically significant positive correlations among CIMT with hsCRP and Hcy but no association with MDA. Conclusion: Oxidative stress, inflammation, and endothelial dysfunction might be associated with HCV infection in ESRD patients on maintenance HD.

AIM To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C (CHC) treated with new Direct-Acting Antiviral agents (DAAs) compared to pegylated interferon-2α plus ribavirin (P/R) therapy. METHODS This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus (HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017. The patients were divided into two groups: patients that underwent therapy with DAAs and patients that underwent HCV treatment with P/R. Patients were assessed by a dermatologist for psoriasis symptoms, collecting Psoriasis Area Severity Index (PASI) scores and the Dermatology Quality of Life Index (DLQI). PASI and DLQI scores were evaluated 24 wk after the end of HCV treatment and were assumed as an outcome of the progression of psoriasis. Switching to a different bDMARD was considered as an inadequate response to biological therapy. The dropout of HCV therapy and sustained virological response (SVR) were considered as outcomes of HCV therapy. RESULTS Fifty-nine psoriatic patients in biological therapy underwent antiviral therapy for CHC. Of this, 27 patients were treated with DAAs and 32 with P/R. After 24 wk post treatment, the DLQI and the PASI scores were significantly lower (P < 0.001 and P < 0.005, respectively) in the DAAs group compared with P/R group. None of the patients in the DAAs group (0/27) compared to 8 patients of the P/R group (8/32) needed a shift in biological treatment. CONCLUSION DAAs seem to be more effective and safe than P/R in HCV-positive psoriatic patients on biological treatment. Fewer dermatological adverse events may be due to interferon-free therapy.

Purpose The goal of this study was to utilize data from the United Network of Organ Sharing (UNOS) database to assess disparities in utilization of hepatitis C virus (HCV)+ hearts for transplant. Methods We obtained de-identified data from UNOS from 2/1/16-1/31/18. We divided these donors into three categories: HCV -, HCV antibody+/ nucleic acid test negative (HCV+/ NAT-) and HCV NAT+. Utilization rate was calculated as a percentage of number of hearts successfully transplanted / number of donors recovered. Organ quality was indirectly assessed using donor age and ejection fraction (EF). Differences in means were assessed via ANOVA and categorical variables via chi2 analysis. Results Among 20,442 donors, 18,948 were HCV-, 511 were HCV+ NAT- and 983 were HCV NAT+. The overall mean utilization rate of HCV- hearts was 33.7% (standard deviation, SD 1.74) whereas the HCV+/NAT- was 11.6% (SD 7.15) and NAT+ was 7.1% (SD 4.94, p organ procurement organizations (OPOs) out of 5 in the Region that facilitated 73% of donors. Proportion of transplanted hearts with EF>55% was similar (HCV- 93.1% vs. HCV+/NAT- 89.8% vs. NAT+ 97.3%, p=0.73). Proportion of transplanted hearts with donor age Conclusion We note disparities at a national, regional, and OPO level in the utilization of hearts for transplantation based on HCV status. Given early outcomes of HCV+ heart transplant , we believe there is opportunity to increase heart transplantation rates in the US.

BACKGROUND: The clinical presentation of patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphoma (DLBCL) is different from their HCV-negative counterparts, but the underlying molecular and pathological characteristics are largely under investigated. The virus has a role in lymphomagenesis, as witnessed by the curative potential of antiviral therapy in HCV-related low-grade B-cell lymphomas.METHODS: We performed a case-control study including 44 HCV-positive cases of de novo DLBCL, comparing them with 132 HCV-negative patients as controls (ratio 3 to 1). Cases and controls were matched for age, lactate dehydrogenase level and international prognostic index at presentation. Patients were studied by gene expression profiling for cell-of-origin determination and to perform differential expression analysis between groups, fluorescence in-situ hybridisation and immunohistochemistry for MYC, BCL2 and BCL6, TP53 mutations, and diagnostic specimens reviewed to exclude transformation from low-grade lymphoma.RESULTS: Compared to the HCV-negative controls, patients with HCV-positive de novo DLBCL had differential expression of genes that regulate innate immune response and modulate apoptotic pathways, have higher proliferative index, and lack BCL2 translocations.CONCLUSIONS: HCV-positive DLBCL have distinct molecular and pathological features compared to the HCV-negative counterparts.British Journal of Cancer advance online publication, 26 September 2017; doi:10.1038/bjc.2017.345 www.bjcancer.com.

BackgroundTreatment of hepatitis C virus infection in post-transplantation patients is a challenge due to poor tolerance and low success rates.ObjectiveTo determine the response rate to pegylated interferon and ribavirin in post-liver transplant patients with hepatitis C recurrence.MethodsBetween 18 May 2002 and 18 December 2011, 601 patients underwent liver transplantation at our service (Hospital Universitário Walter Cantídio, University of Ceará), 176 (29.2%) of whom were hepatitis C virus positive. Forty received antiviral therapy and were included in this cohort study. Twenty-eight (70%) completed the treatment protocol, which consisted of pegylated interferon and ribavirin for 48 weeks.ResultsThe sustained virological response rate was 55% according to intention-to-treat analysis. Recipient age and exposure to antiviral drugs prior to liver transplantation were associated with sustained virological response in the multivariate analysis. Patients were followed for 57 months on the average. Survival at 1 and 5 years was 100% in responders, versus 100% and 78%, respectively, in non-responders.ConclusionSustained virological response rates were satisfactory in our series of liver transplantation patients, and decreased with increasing recipient age. Non-exposure to antiviral drugs prior to liver transplantation was positively associated with sustained virological response. The overall survival of responders and non-responders was similar. ContextoO tratamento da infecção do vírus da hepatite C pós-transplante é um desafio devido à baixa tolerância dos pacientes e às baixas taxas de resposta.ObjetivoDeterminar a taxa de resposta ao interferon peguilado e ribavirina no tratamento da recorrência da hepatite C após transplante de fígado.MétodosEntre 18 de maio de 2002 e 18 de dezembro de 2011, 601 pacientes realizaram transplante hepático no Hospital Universitário Walter Cantídio, 176 (29,2%) desses eram infectados pelo vírus da hepatite C. Quarenta pacientes receberam terapia antiviral e foram incluídos nesse estudo. Vinte e sete (70%) completaram o protocolo de tratamento, que consistia de interferon peguilado e ribavirina por 48 semanas.ResultadosA taxa de resposta virológica sustentada foi de 55% de acordo com a análise por intenção de tratar. A idade dos receptores e a exposição prévia ao transplante de antivirais foram fatores associados com a resposta virológica sustentada na análise multivariada. Pacientes foram acompanhados por 57 meses em média. A sobrevida em 1 e 5 anos foi de 100% em respondedores, enquanto que em não respondedores foi de 100% e 78% respectivamente.ConclusãoA resposta virológica sustentada foi satisfatória na série de pacientes transplantados e diminuiu com o aumento da idade. A não exposição prévia ao transplante a drogas antivirais teve impacto positivo na chance de resposta virológica sustentada. A sobrevida global foi similar em respondedores e não respondedores.

There is a paucity of data regarding long-term renal graft survival in hepatitis C virus positive (HCV+) patients. We analyzed our institution's experience with HCV+ renal transplantation and factors contributing to subsequent renal graft failure.We analyzed 1,679 adult, deceased donor, single-organ renal transplants occurring between 2000 and 2012. Recipient and donor demographics, HCV serostatus, and graft outcome and function were evaluated.Of 1,679 patients, 195 HCV+ recipients (R+) received renal transplants from HCV+ donors (D+), in contrast to 1,418 HCV negative (HCV-) recipients (R-) who received grafts from HCV- donors (D-), and 66 R+ patients who received D- kidneys. Death-censored graft survival in the R+/D+ population was better than graft survival for R+/D- patients, despite R+/D+ patients having higher rates of hypertension and African Americans. Waitlist times for patients accepting HCV+ grafts was 318 days (for R+/D+ patients) versus 613 days (R-/D-) or 570 days (R+/D-). On multivariate analysis, waitlist times were independently predictive of graft failure.R+/D+ patients spent less time on the transplant waitlist, which contributed to improved death censored graft survival when compared with R+/D- patients.

Background. Only a few biomarkers based on metabolic parameters for evaluating liver fibrosis have been reported. The aim of this study was to investigate the relevance of an index obtained from three metabolic variables (glycated albumin: GA, glycated hemoglobin: HbA1c, and branched-chain amino acids to tyrosine ratio: BTR) to the degree of liver fibrosis in hepatitis C virus virus- (HCV-) positive patients.Methods. A total of 394 HCV-positive patients were assessed based on the values of a new index (GA/HbA1c/BTR). The index findings were used to investigate the relationship with the degree of liver fibrosis.Results. The new index showed an association with the stage of fibrosis (METAVIR scores: F0-1: 0.42 ± 0.10, F2: 0.48 ± 0.15, F3: 0.56 ± 0.22, and F4: 0.71 ± 0.30). The index was negatively correlated with three variables of liver function: the prothrombin time percentage (P<0.0001), albumin level (P<0.0001), and cholinesterase level (P<0.0001). The new index showed a higher correlation related to liver function than FIB-4 and the APRI did. In addition, the index showed a higher AUROC value than that of FIB-4 and the APRI for prediction of liver cirrhosis.Conclusion. The new metabolism-related index, GA/HbA1c/BTR value, is shown to relate to the degree of liver fibrosis in HCV-positive patients.

Background: Hepatocellular Carcinoma is the 5 th most common neoplasm in the world and 4 th most common cancer death. Most patients with HCC have an underlying chronic liver disease (often cirrhosis), resulting mainly from chronic infection by Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), excessive alcohol consumption, and often an association of these causes. HCC has recently gained more interest due to its increasing incidence in industrialized countries. Objective: To determine the frequency of hepatocellular carcinoma in hepatitis C reactive cirrhotic patients. Methods: Place and duration of study: Department of medicine, civil hospital Karachi. Duration: Six months from 16-12-2012 to 15-6-2013. Subjects and methods: Patients admitted in medical wards of civil hospital Karachi with liver cirrhosis due to hepatitis C virus were included in the study. Investigation relevant to hepatocellular carcinoma like alpha fetoprotein and ultrasound was performed. If the Alpha fetoprotein is greater, then 200 ng/ml in the setting of a mass in a cirrhotic liver the likelihood of hepatocellular carcinoma is greater then 90% and biopsy is not required. Results: Overall mean age was 41.1 ± 7.1 years with Male:Female = 4.2:1. Out of 141 cases; hepatocellular carcinoma was diagnosed in 8 (5.7%) of patients with HCV related cirrhosis with mean age 48.6 ± 6.4 years. Proportion of hepatocellular carcinoma was high 7 (6.1%) in male. 7 (6.4%) cases had child pugh-C, 1 (5%) case had child pugh-B and while no HCC was seen in child pugh-A. Conclusion: In this study hepatocellular carcinoma was 5.7% in cases with hepatitis-C induced cirrhosis. Older age (>54 years), male sex and child pugh-C were predominant factors leading to hepatocellular carcinoma.