HCV-negative Group Research Articles

Hepatitis C virus attributable liver cancer in the country of Georgia, 2015–2019: a case–control study

BackgroundHepatitis C virus (HCV) infection can lead to a type of primary liver cancer called hepatocellular carcinoma (HCC). Georgia, a high HCV prevalence country, started an HCV elimination program in 2015. In addition to tracking incidence and mortality, surveillance for the HCV-attributable fraction of HCC is an important indicator of the program’s impact. This study assesses HCV infection-attributable HCC in the Georgian population.MethodsThis case–control study utilized HCV programmatic and Georgian Cancer Registry data from 2015–2019. Bivariate logistic regression and age- and sex-stratified analyses assessed HCV and liver cancer association. HCV-attributable liver cancer proportions for the HCV-exposed and total population were calculated. A sub-analysis was performed for HCC cases specifically.ResultsThe total study population was 3874 with 496 liver cancer cases and 3378 controls. The odds for HCV-infected individuals developing liver cancer was 20.1 (95% confidence interval [CI] 15.97–25.37), and the odds of developing HCC was 16.84 (95% CI 12.01–23.83) compared to the HCV-negative group. Odds ratios varied across strata, with HCV-infected older individuals and women having higher odds of developing both liver cancer and HCC. A large proportion of liver cancer and HCC can be attributed to HCV in HCV-infected individuals; however, in the general population, the burden of liver cancer and HCC cannot be explained by HCV alone.ConclusionHCV was significantly associated with a higher risk of developing liver cancer and HCC in the Georgian population. In addition, given Georgia’s high HCV burden, increased HCC monitoring in HCV-infected patients is needed.

The Association of Glycemic Index, Glycemic Load, and Daily Carbohydrates Intake with the Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Background: Glycemic index (GI), glycemic load (GL) and daily carbohydrates intake have been associated with a variety of cancers, but their implications in hepatocellular carcinoma (HCC) remain controversial. The purpose of our study is to investigate the association of GI, GL and daily carbohydrates intake with the risk of HCC. Methods: Systematic searches were conducted in PubMed, Embase and Web of Science until November 2020. According to the degree of heterogeneity, random effect model or fixed effect model was chosen to obtain the pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Results: Four cohort studies and three case-control studies were eventually included. The pooled results showed no significant association of GI (RR = 1.11, 95% CI = 0.80-1.53), GL (RR = 1.09, 95% CI = 0.76-1.55), and daily carbohydrates intake (RR = 1.09, 95% CI = 0.84-1.32) with the risk of HCC in the general population. Subgroup analysis revealed that in hepatitis B virus (HBV) or/and hepatitis C virus (HCV)-positive group, GI was irrelevant to the risk of HCC (RR = 0.65, 95% CI = 0.32-1.32), while a high GL diet was associated with a higher risk of HCC (RR = 1.52, 95% CI = 1.04-2.23). In contrast, in HBV and HCV-negative group, both GI (RR = 1.23, 95% CI = 0.88-1.70) and GL (RR = 1.17, 95% CI = 0.83-1.64) were not associated with the risk of HCC. Conclusion: A high GL diet increases the risk of HCC in those with viral hepatitis. A low GL diet is recommended for them to reduce the risk of HCC.

Transplantation of liver from hepatitis C-infected donors to hepatitis C RNA-negative recipients: Histological and virologic outcome.

The virologic and histologic outcomes of a hepatitis C virus (HCV)-infected liver graft into an HCV-negative recipient are not well understood. We aimed to evaluate thesustained virologic response(SVR)rate and the liver histology at 1year post-Orthotopic liver transplantation (OLT) with an HCV-infected graft. A total of 33 patients received the HCV antibody (Ab)+/nucleic acid amplification test (NAT)+ graft. Of these patients, 23 were HCV-negative recipients and 10 were HCV-positive recipients. The 1-year biopsy data were available for 24 patients: 15 patients in HCV-negative group who received an HCV Ab+/NAT+graft and 9 patients in HCV-positive group who received an HCV Ab+/NAT+ graft. Patients with (+) HCV ribonucleic acid (RNA) were started ondirect-acting antiviral (DAA) treatment approximately 107days after OLT using either a Glecaprevir-Pibrentasvir or Sofosbuvir-Velpatasvir or Sofosbuvir-Ledipasvir. All patients (n=33) were treated withDAA and achieved SVR. The 1-year post-OLT liver biopsies were available in 24 patients: 9 patients had F1 and F2 fibrosis and 17 patients had minimal to moderate inflammation.There was no statistical difference in fibrosis and inflammation between the HCV-negative vs. HCV-positive recipients. All patients who received the NAT+ graft developed viremia and subsequently achieved SVR with treatment. At 1year protocol liver biopsy, patients had inflammation consistent with viral hepatitis despite the successful eradication of HCV.

Hepatitis C Virus Infection and Chemotherapy in Breast Cancer: A Retrospective Chart Analysis.

Breast cancer and hepatitis C virus (HCV) infection are major health problems in the U.S. Despite these highly prevalent diseases, there is limited information on the effect of HCV infection among patients with breast cancer receiving chemotherapy and the potential challenges they face during treatment. Currently, there are no guidelines for chemotherapy administration in HCV-positive patients with breast cancer. We performed a retrospective case-control analysis on six patients with breast cancer with active HCV infection and 12 HCV-negative matched controls who received chemotherapy between January 2000 and April 2015. We investigated dose delays, dose changes, hospitalization, hematologic reasons for dose delays, and variation in blood counts during chemotherapy from the patients' medical records. Fisher's exact test was used for statistical comparison of the outcome variables between the two groups. When compared with the HCV-negative patients, the HCV-positive group was at a significantly higher risk of dose delays (100% vs. 33%, p value .013), dose changes (67% vs. 8%, p value .022), hospitalization during chemotherapy (83% vs. 25%, p value .043), and hematotoxicity related dose delays (83% vs. 8%, p value .003). HCV-positive patients took a longer time to complete treatment than the HCV-negative group. Patients with HCV receiving chemotherapy for breast cancer are more likely to experience complications such as dose delays, dose modifications, and hospitalization. Future studies to confirm our findings and investigate on the effect of concurrent HCV and breast cancer treatment are warranted. This study found that hepatitis C infection is associated with a greater risk of treatment delays and dose modifications in patients with breast cancer receiving cytotoxic chemotherapy. Hepatitis C-positive patients have a higher treatment burden with dose changes, hospitalizations, and longer treatment periods than noninfected patients. Further prospective investigations to confirm these findings are warranted in a larger patient population. Given that hepatitis C infection can be curable with direct-acting antivirals, treatment of hepatitis C may alleviate treatment challenges during chemotherapy and improve survival for patients with breast cancer.

Malnutrition inflammation index in chronic haemodialysis patients with or without hepatitis C virus infection

BackgroundHepatitis C virus infection is one of the main causes of chronic liver disease worldwide. Both chronic hepatitis C and chronic kidney disease are common and serious diseases; this work aimed to determine the clinical impact of HCV infection on malnutrition inflammation index score in chronic kidney disease patients.This study was conducted on 96 patients on haemodialysis. They were divided into two groups. The first group was composed of 46 patients who were on maintenance haemodialysis and had chronic hepatitis C. The second group was composed of 50 patients on haemodialysis who were negative for hepatitis C.ResultsHCV-infected patients were associated with higher malnutrition inflammation score values (10% had MIS 16–20) compared to non-infected patients (2% only had MIS 16–20).ConclusionThe prevalence of malnutrition was higher in the HCV-positive than the HCV-negative group.

SUN-324 Kidney derangements during chronic Hepatitis-C infection – interim results from the HCVKID study

Hepatitis C infection is known to cause kidney derangements. HCV-related nephropathy may show different histopathologic patterns and both glomerular and tubulointerstitial damage have been described. Kidney injury may result from immune-mediated tissue damage or from direct effects of HCV and other, yet unknown mechanisms may be involved. HCV-related nephropathy may appear at any time during the natural history of HCV infection. Objective of the prospective, observational HCVKID-study is to assess the prevalence of renal manifestations among patients suffering from chronic HCV in Finland cross-sectionally, complemented by long-term analysis to identify changes from baseline. Assessments of renal variables are made at baseline and one year after the eradication treatment. HCV-negative control group is enrolled by an occupational healthcare provider and will be used for comparisons between HCV-positive and HCV-negative groups. This analysis compares baseline characteristics between HCV-positive patients with renal manifestations and HCV-positive patients without renal manifestations. The outcome of interest, renal deterioration, is evaluated using urine and blood testing. Baseline data includes clinical and treatment characteristics. For this analysis, 145 HCV-PCR-positive male and female patients (≥ 18 years old) were eligible for the study. Exclusion criteria were HIV or Hepatitis B positivity and other underlying diseases that may influence kidney function and had emerged before the transmission of HCV. Renal manifestation was stated if s-creatinine was > 100 µmol/l in male or > 90 µmol/l in female or eGFR < 60 ml/min/1.73m2 or spot urine analysis revealed hematuria (u-erythrocytes ≥ 20 x10(E6)/l), tubular proteinuria (u -A1Miglo ≥ 12 mg/l) or glomerular proteinuria (u-AlbCrea in men ≥ 2.5 mg/mmol, in women ≥ 3.5 mg/mmol). Prevalence of any renal finding was 15.2 %. Baseline characteristics between HCV-positive patients with and without renal manifestations did not differ significantly (Table 1). HCV-genotype profile was significantly different in patients with renal manifestations, genotype 3 being the most usual genotype. Route of infection, stage of fibrosis, estimated time since HCV-transmission or viral load did not differ significantly (Table 2). Basic laboratory tests showed no significant differences (Table 3). Dipstick proteinuria and hematuria were more common in renal manifestation group as could be expected. The most common renal manifestation was tubular proteinuria (p<0.0001 vs. without renal manifestations). The amount of glomerular proteinuria was not statistically different between those with renal manifestations and those without. The level of proteinuria did not generally exceed the level necessitating kidney biopsy. Serum creatinine was not different between the groups, but eGFR was significantly less in those with renal manifestations. Serum cystatin-C was statistically higher in males with renal manifestation (Table 4). Tubular proteinuria marker was deranged reflecting renal lesions due to tubulointerstitial damage. It may be postulated that HCV could infect several renal cell types including also renal tubular cells. Tubular cell damage may even be the earliest sign of renal dysfunction caused by HCV and warrants testing when HCV patients are being evaluated.

Acceptance of HCV-Positive Donor Hearts Improves Organ Acceptance Selectivity: Single Center Experience

Purpose Due to the shortage of donor hearts in the United States, it is essential we continuously evaluate strategies aimed at increasing donor organ availability. Our institution sought to expand the cardiac donor pool by utilizing hepatitis C virus (HCV) positive donor hearts. In a single center retrospective study, we examined the quality of HCV-positive donor hearts as compared to HCV-negative donor hearts. Methods Between October 2015 and October 2018, 111 cardiac transplants occurred at our center. 23 of these organs came from HCV-positive donors. Baseline donor characteristics were examined for all cardiac transplants and donor quality between HCV-positive and HCV-negative donors compared. Results Twenty-three (20%) of patients received HCV-positive hearts. On average the HCV-positive donors were accepted by our program at lower match sequence numbers than HCV-negative donors (sequence 12±17 versus 64±103, p 0.05 for all comparisons) was seen between HCV-positive and HCV-negative donor hearts. Acceptance of HCV-positive donor hearts facilitated dual-organ transplantation with 3 (13%) patients receiving dual organs as compared to only 4 (4%) in the HCV-negative recipient group. All patients who received HCV-positive donor hearts were alive at the time of this analysis compared to 89% in the HCV-negative group. Conclusion In this single-center study, patients who underwent HCV-positive donor heart transplantation received hearts at lower sequence numbers with a trend toward lower donor age. Short-term outcomes with HCV-positive donor hearts are favorable. Acceptance of HCV-positive donor hearts represents a potential approach to safely expand the available donor pool.

Diagnostic and Prognostic Value of Nuclear Factor Kappa-B in Diffuse Large B Cell Lymphoma in Egyptian Patients with Hepatitis C Virus Genotype 4

Background: Members of the NFκB [p65] family have potential diagnostic and prognostic role in various inflammatory diseases and Lymphomas. Aim: We studied NFκB [p65] in paraffin blocks of hepatitis-C-virus [HCV] positive genotype-4 and HCV negative diffuse large B-cell lymphoma [DLBCL] patients, aiming at identification of its differential expression and prognosis in DLBCL and its subtypes; GCB and ABC. This is to establish its relation to HCV infection and its role in lymphogenesis. Besides assessing the role of new directly acting antiviral drugs [Sofusbuvir/Ledipasvir] concomitantly administered to [CHOP] combination in HCV positive DLBCL. Subjects and Methods: NFκB [p65] expression was assessed using Anti-NFκB [p65] antibody semi-quantitative technique in 30 newly diagnosed DLBCL patients [HCV positive [n = 15], HCV negative [n = 15]. Results: NFκB [p65] expression was higher in the HCV positive DLBCL patients than their HCV negative counterpart, with a positive correlation with the viral load [r = 0.536, p = 0.088]. NFκB [p65] expression was significantly more frequently detected in the ABC subtype than GCB subtype [p = 0.04]. Patients who expressed NFκB [p65] had higher incidence of extranodal involvement, advanced stages, higher LDH levels and IPI score. Besides, the expression of NFκB [P65] revealed an inferior overall response [OR] [p = 0.044]. Higher complete response rates to CHOP concomitantly with antiviral [ledipasvir/sofosbuvir] were encountered in the HCV positive group. In HCV positive group, NFκB [P65] displayed a positive relationship with the viral load and liver enzymes [p = 0.04], besides an inverse relation with serum albumin. This raises the possibility that NFκB [p65] expression is suggestive of the hepatic necro-inflammation in HCV patients. The ABC group presented more in advanced stages than GCB. Higher frequency of the ABC subgroup exhibited intermediate to high viral load, while it was less in the GCB. A statistically significant difference was found in the NFκB [p65] positive patients as regards MUM1 expression among the two groups [p ≤ 0.001]. Double positive [CD10+, MUM1+] and triple negative [CD10-, BCL6-, MUM1-] cases were encountered in the HCV positive group, and were characterized with a high NFκB [p65] expression. Conclusion: NFκB [p65] is expressed in patients with DLBCL, more frequently in ABC than in GCB subtypes. Expression of NFκB [p65] is associated with poor response to therapy in DLBCL. The NFκB [p65] disclosed an increased expression in HCV positive DLBCL compared to HCV negative group. The viral load displayed a positive correlation with the NFκB [p65] expression. Simultaneous administration of DAAs in combination with CHOP disclosed a better response and high tolerability.

The relationship between anemia, serum hepcidin levels, and chronic hepatitis C in chronic hemodialysis patients

BackgroundHepcidin is a small peptide that is produced by hepatocytes and circulates in the plasma. It plays a central role in regulating the iron status in the body.AimThe aim of this study was to measure serum hepcidin levels in maintenance hemodialysis (MHD) patients and identify a possible impact of chronic hepatitis C virus (HCV) infection on the severity of anemia.Patients and methodsThis cross-sectional study was conducted on a cohort of 80 MHD patients (40 HCV positive and 40 HCV negative) and 20 healthy age-matched and sex-matched participants who participated as normal controls. Serum hepcidin and highly-sensitive C-reactive protein were measured in patients to study their possible effect on hematological and inflammatory parameters when compared with the control group.ResultsMHD patients had significantly higher serum hepcidin levels than did controls. The HCV-positive group had significantly lower serum hepcidin and ferritin levels when compared with the HCV-negative group. All MHD patients had significantly higher levels of serum highly-sensitive C-reactive protein than did controls. Hepcidin was also found to correlate with age and serum ferritin levels among MHD patients.ConclusionChanges in serum hepcidin levels are associated with iron status and microinflammation in MHD patients. If used as a diagnostic tool, it may improve targeting and timing of iron therapy by identifying patients during periods of reticuloendothelial blockage of iron transport. This is important to avoid iron overload, especially in HCV-positive patients, which may otherwise cause liver injury resulting in fibrosis, cirrhosis, and finally HCC. We also revealed the value of ferritin levels, which seemed to play an important role in determining the severity of liver disease related to liver fibrosis and microinflammatory activity.

Cardiovascular mortality among liver transplant recipients with nonalcoholic steatohepatitis in the United States-a retrospective study.

Nonalcoholic steatohepatitis (NASH) has become an increasingly important indication for liver transplantation (LT), and there has been a particular concern of excessive cardiovascular-related mortality in this group. Using the United Network for Organ Sharing-Standard Transplant Analysis and Research (UNOS STAR) dataset, we reviewed data on 56,995 adult transplants (January 2002 through June 2013). A total of 3,170 NASH liver-only recipients were identified and were matched with 3,012 non-NASH HCV+ and 3,159 non-NASH HCV- controls [matched 1:1 based on gender, age at LT (±3 years), and MELD score (±3)]. Cox regression analysis revealed significantly lower hazard of all-cause (HR 0.669; P < 0.0001) and cardiovascular-related mortality (HR 0.648; P < 0.0001) in the NASH compared to the non-NASH group after adjusting for diabetes, BMI, and race. Relative to the non-NASH HCV-positive group, NASH group has lower hazard of all-cause (HR 0.539; P < 0.0001) and cardiovascular-related mortality (HR 0.491; P < 0001). A lower hazard of all-cause mortality (HR 0.844; P = 0.0094) was also observed in NASH patients compared to non-NASH HCV-negative group, but cardiovascular mortality was similar (HR 0.892; P = 0.3276). LT recipients with NASH have either lower or similar risk of all-cause and cardiovascular-related mortality compared to its non-NASH counterparts after adjusting for diabetes, BMI, and race.

Malignancies in hepatitis C virus-positive and -negative kidney transplant recipients: A case-controlled study.

Malignancies and lymphoma are common complications after kidney transplantation. However, no link has been made between the incidence of malignancies and hepatitis C virus (HCV) infection in this setting. This case-controlled study compared the incidence of malignancies, including lymphoma, between kidney transplant (KT) patients with or without HCV replication. A total of 99 HCV-positive RNA-positive KT patients were matched with 198 (1:2) anti-HCV-negative patients according to age, gender, and date of transplantation, and were followed for 145.8±78.4months. During the follow-up period, 28 HCV-positive (28%) cases developed at least one cancer, and 64 (32%) patients developed cancer in the HCV-negative group (P=not significant [ns]). Survival without a cancer was similar between both groups. Thirteen HCV-positive patients (13%) developed at least one solid cancer vs 29 (15%) HCV-negative patients (P=ns). Survival without a solid cancer was similar between both groups. Three patients from the HCV-positive and 4 from the HCV-negative group developed a lymphoma. Only 2 patients from the HCV group died from hepatocellular carcinoma. Survival without a skin cancer was similar between both groups. Patient and death-censored graft survival rates were significantly lower in the HCV group. The incidences and types of malignancies were similar in the HCV-positive and HCV-negative KT patients.

Long-term outcomes of hepatitis C virus infected renal allograft recipients

Background and Aim: This study aims to study the long-term outcomes of hepatitis C virus (HCV)-infected renal allograft recipients, which is still debatable. Materials and Methods: In this study (study period - January 2003 to December 2013), we studied long-term outcomes of 106 living donor renal allograft recipients - 53 HCV-infected (33 genotype 3 and 20 genotype 1) and 53 age- and gender-matched HCV-noninfected patients. Results: Thirty-nine (73.6%) patients detected HCV positive during dialysis, while 14 (26.4%) before the start of dialysis. Forty (75.5%) patients were positive for both anti-HCV and HCV RNA, while 13 (24.5%) were HCV RNA positive and anti-HCV negative. Twelve and nine patients died among HCV positive and negative groups, respectively. Major cause of death was sepsis in both groups. Hepatic failure contributed to mortality in four HCV-positive patients, two of them also had graft failure. Patient and death noncensored graft survival rates at 1, 5, and 10 years of follow-up in HCV-positive group were 100% and 100%; 79.8% and 70.8%; 58.9% and 37.8%; respectively; and in HCV-negative group were 100% and 100%; 95.9% and 91.8%; 58.9% and 27.4%; respectively. Conclusions: The long-term survival of HCV-positive renal transplant recipients was not inferior to that of HCV-negative recipients.

Outcomes of Renal Allograft Recipients With Hepatitis C

BackgroundStudies on the effect of hepatitis C virus (HCV) infection showed decreased graft survival compared to HCV-negative matched patients. It was also identified as an independent risk factor for graft loss and mortality in kidney transplantation patients. ObjectiveThis study was designed to evaluate the 10-year graft and patient outcomes of renal allograft recipients with HCV infection at the National Kidney and Transplant Institute. MethodsThis is a retrospective study of patients who underwent renal transplantation with HCV infection and a group who were HCV-negative in the same post-transplantation period. Data were gathered from the in-patient and out-patient clinic records. ResultsPatient survival was significantly lower in the HCV-positive than in the HCV-negative group. The mean duration of patient survival was 154.95 (+4.95) months (12 years and 10 months) in HCV-negative patients compared to 141 (+6.52) months (11 years and 9 months) in the HCV-positive group (P = .05). Graft survival did not differ significantly between HCV-positive and HCV-negative recipients (P = .734). The mean duration of graft survival was 137 (+7.68) months (11 years and 5 months) in HCV-negative patients compared to 130 (+6.84) months (10 years and 10 months) in HCV-positive patients. Short- and long-term outcomes including biopsy-proven acute rejection, transplant glomerulopathy, chronic allograft nephropathy, renal function, and proteinuria were similar in both groups. ConclusionRejection, glomerulopathy, and renal function were similar in both groups. HCV progression was also observed in patients with detectable HCV-RNA 6 months before transplantation.

Lack of Impact of Hepatitis C Virus Infection on Graft Survival After Kidney Transplantation—A Portuguese Single-Center Experience

BackgroundHepatitis C virus infection (HCV) is a common problem among kidney transplant (KT) recipients. The long-term burden of HCV infection on graft survival after kidney transplantation is controversial. MethodsWe performed a retrospective study including all renal transplant recipients with HCV infection (n = 34) compared with a control group (n = 80). The prevalence of HCV infection was 2.7%. The median follow-up period was 134 months (11 years). Graft survival and associated risk factors were assessed by means of Cox proportional hazard analysis. ResultsWe found that HCV-positive patients remained on dialysis for longer periods (P = .001) and received transplants at a younger age (P = .03). Actuarial graft survival rates at 1, 5, and 10 years after KT were, respectively, 94.1%, 78.1%, and 66.9%, in the HCV-positive group and 94.9%, 89.1%, and 80.4% in the HCV-negative group. Graft survival did not differ significantly between groups (P = .154). A higher incidence of major cardiovascular disease among HCV-positive patients (P = .004) was noted. Multivariate analysis showed that HCV infection was not an important risk factor for graft loss (adjusted hazard ratio, 2.810; 95% confidence interval, 0.925–8.541; P = .069). Among the HCV-positive population, immunosuppression with cyclosporine or azathioprine conveyed better graft survival. ConclusionsOur findings suggest that the long-term impact of HCV infection on graft survival after KT is not significant. KT remains a safe and effective modality of renal replacement in HCV-infected patients with end-stage renal disease.

Study of the impact of viral load of hepatitis C on patients with concomitant psoriasis vulgaris

Background and study aimConcomitant hepatitis C virus (HCV) infection and psoriasis vulgaris (PV) are not uncommon coexisting diseases, especially in areas with high viral hepatitis endemicity. To date, data about the interaction between both diseases are scarce. Therefore, we aimed to describe the possible interplay between the HCV viral load and psoriatic activity in concomitant Egyptian diseased patients. Patients and methodsBetween December 2011 and August 2013, all psoriatic patients attending Assiut University Hospital outpatient clinics were tested for HCV serologic assay. Patients with positively coexisting diseases were further reevaluated for psoriasis area severity index (PASI) score assessment, liver function tests, HCV-RNA-polymerase chain reaction (PCR) assays, and sonographic examination of the liver. For comparative purposes, another matched group (n=26) with psoriasis only (HCV-negative group) was enrolled as a control. ResultsDuring the period of the study, 20 patients with concomitant PV and HCV infection (HCV-positive group; 50% males, mean age of 44.15±10.66years) were recruited. The mean PASI score was 44.75±10.38 and clinical signs of liver dysfunction were observed in 40% (n=8), 100% had abnormal liver function tests (n=20), and 75% had sonographic findings of cirrhosis (n=15). The PASI score was significantly higher in the HCV-positive psoriatic group compared to the HCV-negative control (p<0.001). Significant correlations were detected between the PASI score and the viral loads, and also with alanine aminotransferase (ALT). ConclusionWhen HCV was found concomitantly with PV, a high possibility of severe disease pattern will be expected that entails special precautions in the treatment process.

Relevance of lipopolysaccharide levels in HIV-associated neurocognitive impairment: the Neuradapt study

Contributory factors to HIV-associated neurocognitive disorders (HAND) have been shown to include age, co-morbid infections, medication toxicity, virological, genetic and vascular mechanisms, as well as microbial translocation of lipopolysaccharide (LPS), which is suspected to trigger monocyte activation and increase trafficking of infected cells into the brain. In this study, our aim was to assess the degree of neurocognitive impairment in a group of randomly selected HIV-infected patients and investigate potential risk factors, including LPS plasma levels. Furthermore, we evaluated the relevance of LPS as a potential marker for screening patients with mild neurocognitive impairment. LPS plasma levels were compared among patients with HAND and those with no HAND. As LPS has also been shown to be elevated in hepatitis C co-infection, the analysis was stratified according to the presence or not of hepatitis C virus (HCV) co-infection. Differences between groups were evaluated using chi-square tests and Kruskal-Wallis non-parametric tests. Stepwise logistic regression was performed to identify independent risk factors for HAND in the subgroups of HCV-positive and negative patients. A p value <0.05 was considered significant. Analyses were conducted using SPSS® software. From December 2007 to July 2009, 179 patients were tested (mean age 44, 73 % male, 87 % on treatment, 30 % HCV co-infected, median CD4 504/ml and 67 % with viral load below 40 copies/ml). HAND was identified in 40/179 patients (22 %), the majority displaying asymptomatic neurocognitive impairment or mild neurocognitive disorder. Univariate analysis showed that age, illicit drug use, hepatitis C co-infection, prior AIDS-defining events, CD4/CD8 ratio and LPS plasma levels were significantly associated with HAND. The median LPS level was 98.2 pg/ml in the non-HAND group versus 116.1 pg/ml in the HAND group (p < 0.014). No differences were found in LPS values between subgroups of impairment. There was a clear association between LPS levels and HAND in the HCV-positive group (p = 0.036), while there was none in the HCV-negative group (p = 0.502). No difference in degree of hepatic fibrosis was found between the HAND and non-HAND groups. In conclusion, LPS levels were associated with HAND in the HCV-positive group, while, in the HCV-negative group, age and pro-viral DNA were the only variables independently associated with HAND. There was no difference in degree of liver disease as predicted by score of fibrosis between HAND and non-HAND groups. The role of HCV co-infection and higher LPS levels in the pathogenesis of HAND in patients with viral suppression on treatment requires further investigation.

Effect of hepatitis C virus infection on erythropoiesis in patients on hemodialysis

BackgroundErythropoietin is a hormone that regulates erythropoiesis and is mainly produced by the kidneys. Several animal studies as well as a few case reports and case series have demonstrated that regenerating hepatic tissue can produce more erythropoietin than normal hepatic tissue. The purpose of the study was to examine the difference in hemoglobin and hematocrit levels as well as epoetin dosage in patients on hemodialysis with and without hepatitis C (HCV).MethodsA retrospective chart review was performed. Seventy-six patients were included in the study (19 with HCV and 57 without HCV) at a ratio of 1:3. Exclusion criteria were a history of gastrointestinal bleeding or blood transfusion over the previous six months, polycystic kidney disease, and pregnancy. Variables examined included gender, age, duration of hemodialysis, hemoglobin, hematocrit, epoetin dose, aspartate transaminase, and ferritin levels over a three-month period.ResultsThe patients were divided into two groups. The first consisted of patients with HCV on hemodialysis and the second of patients on hemodialysis without HCV. Mean hemoglobin was 12.6 ± 1.2 g/dL for the HCV-positive group and 11.9 ± 1.1 g/dL for the HCV-negative group. The difference was statistically significant (P = 0.03). Mean hematocrit was higher in the HCV-positive group, but was not significantly different at 39.08% ± 4.06% versus 37.43% ± 3.4% in the HCV-negative group (t-test, P = 0.11). Further, the HCV-positive group required less epoetin, but this was not significantly different from that required in the HCV-negative group at 6258 ± 5208 IU versus 7596 ± 7056 IU, respectively (t-test, P = 0.38).ConclusionIn our study, patients with HCV infection were found to have higher hemoglobin and hematocrit levels and lower epoetin requirements than those without HCV. Although the findings were not statistically significant, the computed values between these two groups of patients did follow a general trend. Further investigation with more patients, a longer duration of follow-up, and incorporation of additional medical variables is needed to clarify the role of HCV on erythropoiesis in hemodialysis patients.

Monoclonal Gammopathy Among Patients With Chronic Hepatitis C Virus Infection

BackgroundAn association between monoclonal gammopathies and chronic liver diseases has been previously reported. Hence, the objective of this study was to determine the prevalence of monoclonal gammopathies in patients with chronic hepatitis C virus (HCV) infection in Egypt. MethodsThis is a prospective study of 200 HCV-positive and 100 HCV-negative patients with chronic liver diseases recruited consecutively at the Kasr El Aini Hospital Departments of Internal Medicine and Hematology, Cairo University. Clinical data were gathered, serum protein electrophoresis was performed and immunoelectrophoresis was carried out for the detection of monoclonal component. Histological examination of bone marrow was performed in patients with monoclonal gammopathy. ResultsA monoclonal band was detected in 2% of the HCV-positive patients and in 0% of the HCV-negative patients (P > 0.05). ConclusionsIn this study, 4 cases of monoclonal gammopathy of undetermined significance were observed in the HCV-positive group, whereas none was observed in the HCV-negative group, which supports prior observations that HCV infection is associated with an excess risk for monoclonal gammopathy of undetermined significance.

Effect of chronic hepatitis C virus infection on bone mineral density in pediatric renal transplant recipients

Previous studies have suggested that loss of bone mineral density (BMD) frequently occurs in patients with chronic viral liver disease, presenting with histologically proven liver cirrhosis. However, little is known about the occurrence of bone disease in non-cirrhotic patients with chronic hepatitis C virus (HCV) infection. Furthermore, to the best of our knowledge, such an effect has never been studied in pediatric renal transplant recipients. The aim of this study was to assess the impact of HCV infection on BMD in pediatric renal transplant patients. We performed a cross-sectional study to assess BMD and HCV in 83 patients who received living renal allotransplants in the Mansoura Urology and Nephrology Center between 1983 and 2005. The mean age of the study patients at transplantation was 13.4 ± 2.9 years; there were 53 males (63.9%) and 30 females (36.1%). BMD was studied using dual energy X-ray absorptiometry at various time intervals up to 16 years after transplantation (mean duration after transplantation was 48 ± 34 months, range 12- 192 months). Thirty-three patients tested positive for HCV-RNA (positive group) and 50 patients were negative (negative group), and we compared the BMD between the two groups. Before transplantation, 58 patients (69.9%) were on maintenance hemodialysis, four (4.8%) were on peritoneal dialysis and 21 (25.3%) were pre-emptive. Among the HCV-positive group, six patients (18.2%) had osteoporosis, 17 (51.5%) had osteopenia and ten (30.3%) had normal BMD. In the HCV-negative group, ten patients (20.0%) had osteoporosis, 24 (48.0%) had osteopenia and 16 (32.0%) had normal BMD. The difference was not significant between the two groups (P = 0.9). Also, there was no significant difference in the serum creatinine, calcium, phosphorus and parathormone levels between the two groups. Our results suggest that chronic HCV infection does not pose a risk for low BMD in pediatric renal transplant recipients.

Effects of concomitant hepatitis C virus infection in patients with underlying lupus nephritis on long-term renal outcome

Despite recent advances in the management of lupus nephritis (LN), these unfortunate patients are at a higher risk of developing chronic kidney disease (CKD). Concomitant chronic hepatitis C virus (HCV) infection is associated with adverse outcome in patients with LN and further compounds the risk as some of these patients choose to undergo kidney transplantation in the near future. Objectives. The aim of the present study is to evaluate the long-term impact of chronic HCV infection in patients with underlying Class IV LN on renal function, progression to end-stage renal disease (ESRD) and patient survival. Retrospective analysis of the medical records of 134 nondialysis-dependent patients with biopsy-proven World Health Organization Class IV LN with chronic HCV infection was done from January 1995 to January 2008 at King Khalid University Hospital, Riyadh, Saudi Arabia. Primary and the secondary end points were death or the development of ESRD. The patients were followed over a period of 6.7 ± 3.3 (1-14.4) years. From a total of 134 biopsy-proven Class IV LN patients, 15 (11.2%) patients were HCV positive of which 2 (13.3%) patients were male and 13 (86.7%) patients were female. One hundred and nineteen (88.8%) patients were HCV negative of which 17 (14.3%) were male and 102 (85.7%) were female. The mean age was 32.47 ± 11.8 years. Eight (53.3%) patients in the HCV-positive group versus 19 (22.6%) patients in the HCV-negative group progressed to severe renal impairment with serum creatinine >350 μmol/L (P = 0.024). A total of 8 (53.3%) patients in the HCV-positive group versus 18 (17.3%) in HCV-negative group progressed to ESRD (P = 0.005). The mean creatinine clearance was higher (43.3 ± 33 mL/min) in the HCV-negative LN group at last follow-up than in the HCV-positive patients (25 ± 34.9 mL/min) with a statistically significant P-value of 0.0463. Five patients (33.3%) with HCV-positive LN died in comparison to eight (7.6%) patients who were HCV negative P = 0.03; however, the cause of hospital mortality was mainly cardiovascular disease (CVD) and infection and none of the patients died of chronic liver disease, although there was significant deterioration of the liver function at the end of the study. Kaplan-Meier survival estimates showed a significantly inferior renal function and rapid deterioration to ESRD in LN patients with concomitant HCV infection, with a dialysis free survival of 95 and 80% for the HCV-negative group and 90 and 65% for the HCV-positive groups at the end of 5 and 10 years respectively, with a highly significant P-value of <0.05 at the end of 10 years. The present study highlights that concomitant HCV infection in patients with LN is associated with worse renal outcome, higher rate of progression to ESRD and reduced patient survival.