SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neurons.

An increasing number of patients experiences prolonged symptoms, whose profile and timeline remain uncertain, a condition that has been defined as post COVID. The majority of recovered hospitalized patients manifests at least one persistent symptom even sixty days after the first clinical manifestation's onset. Particularly, in light of the COVID-19-related symptomatology, it has been hypothesized that SARS-CoV-2 might affect the dopamine pathway. However, no scientific evidence has been produced so far. To this end, human iPSC-derived dopaminergic neurons were infected with EU, Delta and Omicron SARS-CoV-2 variants. The infection with EU and Delta variants, but not with Omicron, results in a reduced intracellular content and extracellular release of dopamine. Indeed, the tyrosine hydroxylase was found to be significantly upregulated at the mRNA level, while being greatly reduced at the protein level. The major downstream synthetic enzyme DOPA-decarboxylase and the dopamine transporter were significantly downregulated both at the mRNA and protein level. Notably, in vitro SARS-CoV-2 infection was also associated with an altered MAP2 and TAU expression and with an increased presence of neuronal stress markers. These preliminary observations suggest that the dopamine metabolism and production are affected by SARS-CoV-2, partially explaining some of the neurological symptoms manifested.

Characteristics of 1573 healthcare workers who underwent nasopharyngeal swab testing for SARS-CoV-2 in Milan, Lombardy, Italy.

OBJECTIVES: The management of healthcare workers (HCWs) exposed to confirmed cases of coronavirus disease 2019 (COVID-19) is still a matter of debate. We aimed to assess in this group the attack rate of asymptomatic carriers and the symptoms most frequently associated with infection. METHODS: Occupational and clinical characteristics of HCWs who underwent nasopharyngeal swab testing for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a university hospital from 24 February 2020 to 31 March 2020 were collected. For those who tested positive and for those who tested positive but who were asymptomatic, we checked the laboratory and clinical data as of 22 May to calculate the time necessary for HCWs to then test negative and to verify whether symptoms developed thereafter. Frequencies of positive tests were compared according to selected variables using multivariable logistic regression models. RESULTS: There were 139 positive tests (8.8%) among 1573 HCWs (95% confidence interval, 7.5-10.3), with a marked difference between symptomatic (122/503, 24.2%) and asymptomatic (17/1070, 1.6%) workers (p < 0.001). Physicians were the group with the highest frequency of positive tests (61/582, 10.5%), whereas clerical workers and technicians had the lowest frequency (5/137, 3.6%). The likelihood of testing positive for COVID-19 increased with the number of reported symptoms; the strongest predictors of test positivity were taste and smell alterations (odds ratio = 76.9) and fever (odds ratio = 9.12). The median time from first positive test to a negative test was 27 days (95% confidence interval, 24-30). CONCLUSIONS: HCWs can be infected with SARS-CoV-2 without displaying any symptoms. Among symptomatic HCWs, the key symptoms to guide diagnosis are taste and smell alterations and fever. A median of almost 4 weeks is necessary before nasopharyngeal swab test results are negative.

Clinical features and outcomes of hepatocellular carcinoma in Caucasian cirrhotic patients on long-term analogue therapy for hepatitis B.

BACKGROUND: Long-term oral nucleos(t)ide analogue (NUC) therapy in hepatitis B virus (HBV)-related compensated cirrhotics prevents clinical decompensation but not hepatocellular carcinoma (HCC) development. AIMS: To define the clinical features and outcomes of HCC in long-term NUC-treated HBV patients. METHODS: All HCCs developing between 2005 and 2016 in NUC-treated HBV patients under surveillance were studied, excluding those that occurred within the first 6 months of therapy. Clinical features of HCC, alpha faetoprotein (AFP) patterns and patients' outcome were studied. RESULTS: Seventy-six HCC patients were included. Median age was 67 (40-83) years, 84% males, 96% Caucasian, 95% HBeAg-negative, 96% with undetectable HBV DNA, 83% with normal ALT levels, and 92% with compensated cirrhosis. Median serum AFP levels were 4 (1-3615) ng/mL (>7 ng/mL in 36%). HCC was monofocal in 78%, had a median diameter of 20 (6-57) mm and was in its early stage in 92% which allowed potentially curative treatments in 78% (39% ablation, 28% surgical resection, 11% liver transplantation). Overall, a complete response was obtained in 61 (80%) patients: in 40 after a first-line treatment, in 3 after the second-line treatment, in 2 after the third-line treatment, while 16 underwent liver transplantation (8 as second line). During 45 (7-144) months after HCC diagnosis, 19 patients died, 84% from HCC progression. The median time to recurrence was 20.2 (3-53) months, and the cumulative 5-year liver-related survival was 74%. CONCLUSIONS: HCCs developing in patients under long-term NUC treatment were single, small tumours, amenable to curative therapies able to confer excellent 5-year survival rates.

Acute respiratory distress syndrome in adenovirus type 4 pneumonia: A case report.

Human adenoviruses (HAdVs) cause a wide spectrum of clinical syndromes, depending on species and types, from mild respiratory infections to deadly pneumonia: in particular, severe infections occur in immunocompromised patients. In this report, we describe the case of a 36 years-old woman admitted to our intensive care unit (ICU) with severe respiratory distress syndrome caused by adenovirus pneumonia, that required invasive respiratory support (mechanical ventilation and extracorporeal membrane oxygenation). Molecular assays detected the virus in respiratory and plasma specimen and sequencing procedure identified HAdV type 4. Patient improved after cidofovir administration. Leukopenia and subsequent bacterial infection occurred, but the patient recovered completely and was discharged from the hospital after 54days.

Comparative evaluation of the new xTAG GPP multiplex assay in the laboratory diagnosis of acute gastroenteritis. Clinical assessment and potential application from a multicentre Italian study.

OBJECTIVE: Gastroenteritis caused by a single pathogen or multiple pathogens remains a major diagnostic challenge for the laboratory. The treatment of diarrhoea is based on microbiological results. Diagnosis is achieved using different laboratory techniques that have variable sensitivity and specificity. xTAG GPP is a new multiplex PCR assay that simultaneously detects 15 different pathogens responsible for diarrhoea. The results of the first multicentre study in Italy to evaluate the potential clinical application of the GPP assay in the laboratory diagnosis of diarrhoea are reported here. METHODS: Faeces specimens (N=664) from hospitalized patients were tested with the GPP assay using a Luminex 200 instrument. All specimens were run using comparator methods following a routine algorithm: culture for bacteria, enzyme immunoassay and PCR for viruses, and microscopy for parasites. RESULTS: Of the samples tested with the GPP, 53.61% (356/664) gave positive results, as compared to 45.33% by routine testing. Of the positive specimens, 34.55% showed the presence of genomic DNA from multiple pathogens. The Luminex method showed an increase in the percentage of positivity of 8.28%. CONCLUSIONS: The GPP assay can be considered a helpful tool for the detection of gastrointestinal pathogens, with a hands-on time of 5h; it provides accurate data for the clinical management of hospitalized patients and for epidemiological surveillance.

Optic neuritis associated with influenza B virus meningoencephalitis.

Various postinfectious neurological manifestations have been described associated to influenza viruses. Optic neuritis is a serious, often reversible disease reported among several infectious diseases and vaccines complications. We report a case of optic neuritis following an influenza B virus infection in a 10-year-old male.

Fulminant multiorgan failure due to varicella zoster virus and HHV6 in an immunocompetent adult patient, and anhepatia.

Varicella is a well-known contagious disease of childhood that can also affect both immunodepressed and immunocompetent adults. The present observations concern a previously healthy adult patient who presented with a fulminant hepatitis evolving in multiorgan failure (MOF), associated with an atypical papulo-ethemateous cutaneous rash without fever. An hepatic biopsy showed massive necrosis. Because of the persistent MOF and severe hemodynamic instability, total hepatectomy was performed as a bridge to urgent liver transplantation (OLT). Despite temporary improvement, the patients condition progressively deteriorated and he died 11 hours after the hepatectomy, i.e. 7 days after admission to the intensive care unit. High viral loads of varicella zoster virus (VZV) and human herpes virus 6 (HHV6) were demonstrated in the blood and in DNA at post mortem examination of the liver, kidneys, lung, and heart. We hypothesize that VZV infection may occasionally occur in immunocompetent patients due to extremely virulent strains that can be rapidly fatal. The clinical influence of simultaneous infection with HHV6 is not clear. Moreover, the role of a previous steroid treatment as a trigger for a temporary immunodepressed state must be considered. The diagnosis of liver disease from VZV should always be clinically suspected in the presence of concurrent atypical skin lesions and a temporarily immunocompromised state. Therapy with acyclovir was ineffective in our patient. Based on the wide spectrum of VZV infections, fulminant MOF in immunocompetent adults must raise the possibility of VZV with simultaneous HHV6 infection with early listing of the patient for a urgent OLT, possibly with a total hepatectomy as a bridge, due to the therapeutic uncertainty of medical treatments.

Failure of adefovir 20 mg to improve suboptimal response in lamivudine-resistant hepatitis B patients treated with adefovir 10 mg and lamivudine.

Nine patients with lamivudine-resistant chronic hepatitis B infection who had been treated with adefovir 10 mg/day and had had a suboptimal response but did not have genotypic resistance to adefovir were treated with high-dose adefovir (20 mg/day). The response to the increased dose of adefovir was compared with the response in 15 patients with a suboptimal response who did not receive an increase in the dose of adefovir. The increase in the dose of adefovir did not lead to a significant reduction in hepatitis B DNA when compared with patients maintained on the standard dose. These data suggest that increasing the dose of adefovir in patients with a suboptimal response does not lead to an improved response.

Kinetics of hepatitis B virus load and haemodialysis: a prospective study.

The control of the spread of hepatitis B virus (HBV) infection within dialysis units has been an important goal in the management of patients on regular dialysis but infected patients continue to enter the dialysis system. It is evident that HBV viraemia in hepatitis B surface antigen (HBsAg)-positive patients on dialysis is low but it remains unclear whether haemodialysis per se can contribute to viral load reduction in such patients. HBV DNA was determined in 40 HBsAg-positive patients on maintenance haemodialysis immediately before and at the end of a 4-h haemodialysis session. The same measurements were repeated 48 and 72 h later. Twenty (50%) of 40 HBsAg-positive patients had detectable HBV DNA in serum. Detectable HBV DNA in serum was not predicted by demographic, clinical or biochemical parameters. HBV load decreased in the majority of patients after haemodialysis, although the difference was not significant (29 390 +/- 48 820 vs 23 862.8 +/- 4 350 copies/mL, NS). There was a strong relationship between mean HBV DNA levels before dialysis and absolute reduction of HBV DNA during haemodialysis sessions (r = 0.75, P = 0.0001). No difference occurred in the magnitude of change in HBV DNA titre when comparing cellulosic to synthetic membranes. Haemodialysis per se leads to a reduction in HBV load in HBsAg-chronic carriers on maintenance dialysis. This phenomenon could explain the low viral loads in these patients. Prospective studies are in progress to identify the mechanisms responsible for reduction in HBV load during haemodialysis.

Antiviral therapy of hepatitis C in chronic kidney diseases: meta-analysis of controlled clinical trials.

Hepatitis C virus (HCV) infection remains frequent in patients with chronic kidney disease and the detrimental role of HCV on survival is well-established in this population. Several authors have reported on efficacy and safety of antiviral therapy for hepatitis C in this polulation but there is no clear consensus on management. To evaluate efficacy and safety of antiviral therapy for hepatitis C in patients with chronic kidney disease, we performed a systematic review of the published medical literature and completed a meta-analysis of controlled clinical trials. The primary outcome was sustained virological response (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses. We identified 13 studies including 539 unique patients; 10 (76.9%) concerned patients on maintenance dialysis. Only prospective, controlled clinical trials were included. Pooling of study results showed a significant increase of viral response in study (patients treated with antiviral therapy) than control patients (patients who did not receive therapy), the pooled odds ratio (OR) of failure to obtain a sustained viral response was 0.081 [95% confidence intervals (CI), 0.029-0.230], P = 0.0001. The pooled OR of drop-out rate was significantly increased in study vs control patients, OR = 0.389 (95% CI, 0.155-0.957), P = 0.04. The studies were heterogeneous with regard to viral response and drop-out rate. In the subset of clinical trials (n = 6) involving only dialysis patients receiving interferon (IFN) monotherapy for chronic HCV, there was a significant difference in the risk of failure to obtain a sustained viral response (study vs control patients), OR = 0.054 (95% CI, 0.019; 0.150), P = 0.0001 (random-effects model). No significant (NS) heterogeneity was found (Q = 14.604, P = 1.0). No difference in the drop-out rate between study and control patients was shown, OR = 0.920 (95% CI, 0.367; 2.311), NS. This result being homogeneous (Q = 3.639, P = 0.388). Our meta-analysis showed that the viral response was greater in patients with chronic kidney disease who received antiviral therapy than controls. No difference in the drop-out rate between study and control patients occurred in the subgroup of dialysis patients on IFN monotherapy. These results support IFN-based therapy for hepatitis C in patients on maintenance dialysis.

The impact of hepatitis C virus infection on survival in dialysis patients: meta-analysis of observational studies.

The impact of hepatitis C virus (HCV) infection on mortality of patients receiving regular dialysis remains unclear. The assessment of the natural history of HCV in dialysis population is difficult because of the low progression of HCV-related liver disease over time and the reduced life expectancy in patients with end-stage renal disease. The aim of the study was to conduct a systematic review of the published medical literature concerning the impact of HCV infection on the survival of patients undergoing maintenance dialysis. The relative risk of mortality was regarded as the most reliable outcome end-point. Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effects pooled estimates for mortality with HCV across the published studies. We identified seven studies involving 11 589 unique patients on maintenance dialysis; two (29%) were case-control studies. Pooling of study results demonstrated that presence of anti-HCV antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted relative risk (aRR) (all-cause mortality) was 1.34 with a 95% confidence interval (CI) of 1.13-1.59. Heterogeneity statistics, R(i) = 0.48 (P-value by Q-test = 0.13). In a sensitivity analysis including only (n = 5) cohort studies, the pooled aRR was 1.38 (95% CI, 1.20-1.59); heterogeneity statistics R(i) = 0.46. As a cause of death, hepatocellular carcinoma and liver cirrhosis were significantly more frequent among anti-HCV-positive than -negative dialysis patients. Our meta-analysis indicates that anti-HCV-positive patients on dialysis have an increased risk of mortality compared with HCV-negative patients. The excess risk of death in HCV-positive patients may be at least partially attributed to chronic liver disease with its attendant complications.

Gamma glutamyltranspeptidase activity and viral hepatitis in dialysis population.

BACKGROUND: Numerous investigations have reported that viral hepatitis is associated with significant hepatocellular damage, as expressed by raised aminotransferases in serum, in dialysis population. However, scarce information exists on the activity of gamma glutamyltranspeptidase (GGTP) in dialysis patients with infection by hepatotropic viruses. OBJECTIVES: We measured serum GGTP values in a large cohort (n=757) of patients receiving long-term dialysis; healthy controls were also included. The relationship between GGTP values and a series of demographic, clinical, and biochemical parameters was analyzed. METHODS: Serum GGTP levels were tested by spectrophotometry. A subset (n=333) of dialysis patients was tested by molecular technology (branched-chain DNA (bDNA) assay) to evaluate the relationship between serum GGTP and HCV viremia. A subgroup (n=78) of dialysis patients was analyzed by an ultrasound scan of gallbladder and biliary tract to assess the presence of gallstone disease. Multivariate analyses were made using regression models; serum GGTP values were included as a dependent variable. The usefulness of serum GGTP levels in detecting HBsAg and anti-HCV positivity was evaluated using receiver operating characteristics (ROC) curve analysis. RESULTS: Univariate analysis showed that serum GGTP levels were significantly higher in HBsAg positive and/or anti-HCV positive patients than in HBsAg negative/anti-HCV negative patients on dialysis; 85.1+/-184.1 versus 25.86+/-23.9 IU/l (P=0.0001). The frequency of raised GGTP levels was 22.2% (41/184) among dialysis patients with chronic viral hepatitis. Multivariate analysis showed a significant and independent association between serum GGTP values and positive HBsAg (P=0.005) and anti-HCV antibody (P=0.0001) status. Mean GGTP values were significantly higher in study patients than controls, 32.32+/-60.02 versus 23.5+/-16.92 IU/L (P=0.01); however, no significant difference with regard to GGTP between study and healthy cohorts persisted after correction for age, gender, race, and viral markers. No relationship between gallstone disease and serum GGTP was found (NS). An independent and significant association (P=0.0291) between raised GGTP levels and detectable HCV RNA in serum was noted among patients tested by biology molecular techniques. ROC technology demonstrated that GGTP was equally useful for detecting HBV (P=0.0004) and HCV (P=0.0005) among dialysis patients. CONCLUSIONS: We found an independent and significant association between serum GGTP values and HBsAg and/or anti-HCV antibody in dialysis population. Twenty-two percent of dialysis patients with chronic viral hepatitis had elevated GGTP. No difference in GGTP between HBsAg- negative/anti-HCV- negative dialysis patients and healthy individuals was found. Routine testing for serum GGTP levels to assess liver disease induced by hepatotropic viruses or other agents in dialysis population is suggested.

Meta-analysis: anti-viral therapy of hepatitis C virus-related liver disease in renal transplant patients.

BACKGROUND: The efficacy and safety of interferon-based therapy in renal transplant recipients with hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue. AIM: To evaluate efficacy and safety of antiviral therapy with interferon (interferon alone or interferon plus ribavirin) in renal transplant patients with hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical trials. METHODS: The primary outcomes were sustained virological response (as a measure of efficacy) and/or drop-out rate (as a measure of tolerability). We used the random-effects model of DerSimonian and Laird, with heterogeneity and sensitivity analysis. RESULTS: We identified 12 clinical trials (102 unique patients); there was one controlled study. The summary estimate for sustained virological response and drop-out rate was 18.0% (95% CI 7.0-29.0%) and 35.0% (95% CI 20-50%), respectively. The most frequent side-effect requiring interruption of treatment was graft dysfunction (n = 28; 71.7%). Meta-regression analysis showed an inverse and significant association between reference year and drop-out logit rate (P = 0.012); an inverse link between sustained virological response logit rate and frequency of hepatitis C virus genotype 1 (P = 0.067) and cirrhosis (P = 0.08) was found, even if no statistical significance was reached. No publication bias was observed. CONCLUSIONS: Interferon-based therapy of hepatitis C has poor tolerance and safety after renal transplant. The optimal treatment of hepatitis C after renal transplant requires additional agents or alternative therapeutic approaches.

Occult hepatitis B virus infection in dialysis patients: a multicentre survey.

BACKGROUND: The epidemiology and clinical significance of occult hepatitis B virus infection (serum hepatitis B surface antigen-negative patients with detectable hepatitis B virus viraemia in serum) remains controversial with only limited information about its prevalence in patients on long-term dialysis. AIM: To address the epidemiology of occult HBV infection in a large cohort of dialysis patients. METHODS: We screened a large cohort (n = 585) of Italian chronic dialysis patients; from this population, a group of hepatitis B virus surface antigen seronegative patients (n = 213) was tested by Amplicor hepatitis B virus Monitor Test to detect hepatitis B virus viraemia (hepatitis B virus-DNA) in serum. RESULTS: Occult hepatitis B virus infection was absent (zero of 213 = 0%). Persistent hepatitis B virus surface antigen carriage was less frequent than anti-hepatitis B virus core antibody (anti-hepatitis B core antigen) seropositive status in this study group [1.88% (11 of 585) vs. 36% (216 of 585), P = 0.0001]. No dialysis patients seropositive for anti-hepatitis B core antibody in serum (zero of 123 = 0%) had detectable hepatitis B virus-DNA by polymerase chain reaction technology. No significant association between abnormal biochemical liver tests and serum anti-hepatitis B core antibody was noted in our population. Nominal logistic regression analysis demonstrated an independent and significant relationship between anti-HCV antibody and anti-hepatitis B virus core antibody in serum (Wald chi-square 16.06, P = 0.0001). The rate of seropositive patients for anti-hepatitis B virus core antibody was higher among study patients than controls with normal renal function [36.9% (216 of 585) vs. 21.4% (59 of 275), P = 0.0001]; this difference partially persisted after correction for demographic parameters, and viral markers. CONCLUSION: In conclusion, occult hepatitis B virus was absent in our study group. Anti-hepatitis B core antibody was significantly related to presence of anti-HCV antibody supporting shared modes of transmission. Clinical studies based on molecular biology techniques provided with higher sensitivity are planned.

De novo HCV infection among dialysis patients: a prospective study by HCV core antigen ELISA assay.

BACKGROUND: Dialysis patients remain a high-risk group for hepatitis C virus infection. The current diagnosis of hepatitis C virus in dialysis patients includes serological measurement of anti-hepatitis C virus antibody; however, nucleic acid amplification technology for assessing hepatitis C virus viraemia is commonly used in other populations. An enzyme-linked immunosorbent assay test for detecting antibody to hepatitis C nucleocapsid core antigen (hepatitis C virus core antigen) in human serum has been recently developed (hepatitis C virus Core Antigen enzyme-linked immunosorbent assay test). It is conceived for screening of donor blood products to significantly reduce the 'serologic window' occurring before seroconversion during acute hepatitis C virus. AIM AND METHODS: A cohort (n = 72) of patients on maintenance haemodialysis in a single unit in the years 2000-2003 was included. Study patients were tested monthly by hepatitis C virus Core Antigen enzyme-linked immunosorbent assay in a prospective, clinical trial. Routine results obtained by hepatitis C virus Core Antigen enzyme-linked immunosorbent assay test were confirmed by assessing hepatitis C virus viraemia by branched-chain DNA (bDNA) signal amplification assay. RESULTS: De novo hepatitis C virus infection was identified in three patients during the study period; the hepatitis C virus incidence was 1.38% (95% confidence intervals, 1.31-4.09) per year. In each patient, hepatitis C virus core antigen testing allowed the serological identification of acute hepatitis C virus before anti-hepatitis C virus seroconversion. Hepatitis C virus RNA testing confirmed the results obtained by hepatitis C virus Core Antigen enzyme-linked immunosorbent assay in all cases. The time from initial hepatitis C virus detection by hepatitis C virus Core Antigen Assay and anti-hepatitis C virus seroconversion was not greater than four weeks. Two (67%) of three patients with de novo hepatitis C virus acquisition were HBsAg negative; both these patients underwent an initial phase of hepatitis C virus viraemia that was associated with an increase in alanine aminotransferase activity and preceded the seroconversion to anti-hepatitis C virus antibody. Nosocomial transmission of hepatitis C virus between haemodialysis patients was implicated in at least two (67%) of these three patients. CONCLUSIONS: Serological testing for hepatitis C virus core antigen can identify acute hepatitis C virus infection before anti-hepatitis C virus seroconversion. The time from initial hepatitis C virus detection by hepatitis C virus core antigen assay and anti-hepatitis C virus seroconversion was not >4 weeks. De novo acquisition of hepatitis C virus in haemodialysis was associated with a rise in alanine aminotransferase levels. Hepatitis C virus core antigen enzyme-linked immunosorbent assay test results can be obtained in routine laboratories without the need of special equipment or training. Hepatitis C virus core antigen testing among anti-hepatitis C virus negative patients on maintenance dialysis is suggested in order to early assess de novo hepatitis C virus within dialysis units.

Natural history of hepatitis C virus infection in adult renal graft recipients.

AIM: To study the natural history of hepatitis C virus infection in renal transplantation, 464 HbsAg negative patients were prospectively studied from 1989. METHODS: AntiHCV was tested by ELISA II and HCVRNA by Amplicor HCV RNA tests. RESULTS: Two hundred nine patients were antiHCV positive (C+). HCVRNA was confirmed in 89% of C+ patients. Compared with the 255 anti-HCV negative (C-), C+ had undergone longer periods of dialysis (P = .0001), were more transfused (P = .01), and included more retransplants (P = .002). Immunosuppression was azathioprine (AZA) plus steroids in 133 and cyclosporine (CsA) in 331 patients. Liver biopsy showed chronic active hepatitis in 50, cirrhosis in 8, and fibrosing cholestatic hepatitis in 2 patients. Histologic progression of liver disease was confirmed in 18 of 26 patients. The causes of death in 84 patients (51 C+ vs 33 C-) were cardiovascular disease in 49%, sepsis in 13%, liver failure in 14%, neoplasia in 21%, and hepatocarcinoma in 2%. The 14-year patient survival was 75% in C+ and 86% in C- (P = .002). By multivariate analysis, age (>40) (P = .001) and C+ (P = .019) correlated with a worse patient survival. If patients were stratified according to age (<40 vs > or =40), younger C+ patients had a lower survival probability (P = .03). The 14-year graft survival was 44% in C+ vs 60% in C- patients (P = .001) but pure graft survival was similar (68% in C+ vs 72% in C-) (P = .13). CONCLUSION: The presence of C+ significantly reduced both patient and graft survival in the long-term with liver failure being the second most frequent cause of death.

Review article: hepatitis C virus infection and type-2 diabetes mellitus in renal diseases and transplantation.

A link between hepatitis C virus infection and development of diabetes mellitus has been suggested by many investigators; however, this remains controversial. The mechanisms underlying the association between hepatitis C virus and diabetes mellitus are unclear but a great majority of clinical surveys have found a significant and independent relationship between hepatitis C virus and diabetes mellitus after renal transplantation and orthotopic liver transplantation. We have systematically reviewed the scientific literature to explore the association between hepatitis C virus and diabetes mellitus in end-stage renal disease; in addition, data on patients undergoing orthotopic liver transplantation were also analysed. The unadjusted odds ratio for developing post-transplant diabetes mellitus in hepatitis C virus-infected renal transplant recipients ranged between 1.58 and 16.5 across the published studies. The rate of anti-hepatitis C virus antibody in serum was higher among dialysis patients having diabetes mellitus (odds ratio 9.9; 95% confidence interval 2.663-32.924). Patients with type-2 diabetes-related glomerulonephritis had the highest anti-hepatitis C virus prevalence [19.5% (24/123) vs. 3.2% (73/2247); P < 0.001] in a large cohort of Japanese patients who underwent renal biopsy. The link between hepatitis C virus and diabetes mellitus may explain, in part, the detrimental role of hepatitis C virus on patient and graft survival after orthotopic liver transplantation and/or renal transplantation. Preliminary evidence suggests that anti-viral therapies prior to renal transplantation and novel immunosuppressive regimens may lower the occurrence of diabetes mellitus in hepatitis C virus-infected patients after renal transplantation. Clinical trials are under way to assess if the hepatitis C virus-linked predisposition to new onset diabetes mellitus after renal transplantation may be reduced by newer immunosuppressive medications.

[Hepatitis C virus and renal transplantation]. / Infezione da virus dell'epatite C (HCV) e trapianto renale.

Liver disease has emerged as an important cause of morbidity and mortality after renal transplantation (RT). Hepatitis C virus (HCV) is the leading cause of liver disease after RT. The impact of HCV infection on patient and graft survival is currently a major concern. Retrospective studies with appropriate follow-up have mainly demonstrated that HCV positive patients have greater mortality compared to HCV negative recipients after RT. Novel investigations by large databases (United States Renal Data Systems (USRDS)) have shown that recipients of donor HCV-positive kidneys are at an independently increased risk of mortality, adjusted hazard ratio 2.12 (95% confidence interval (95% CI), 1.72-2.87, p<0.001); there was no evidence that any subgroup was less affected. With appropriate informed consent, the use of a renal graft from an HCV positive donor could be offered to an HCV infected recipient. Many renal transplant candidates have satisfactory virological responses to antiviral therapy; the persistence of HCV clearance over a prolonged follow-up after RT has been recently noted. Further prospective studies are needed to define better the course of HCV infection among renal allograft recipients.

[HCV-related liver disease in hemodialysis population: clinical and biochemical characteristic]. / Epatopatia HCV-correlata in emodialisi: manifestazioni biochimiche e cliniche.

Hepatitis C virus (HCV) infection remains frequent among patients on maintenance dialysis. It has been claimed that infrequent and slight abnormalities in serum aminotransferase activity could occur in dialysis patients with HCV. We describe a 61-year-old male patient on maintenance dialysis who acquired HCV by a nosocomial route. The natural history of HCV in this patient over 8 yrs featured frequent and high increases in serum aminotransferase and gamma-glutamyl transpeptidase (gamma-GT) levels. In December 2001, serum GOT and GPT were, respectively, 965 and 1294 UI/L; gamma-GT activity was 241 UI/L. HCV genotype was 2a/2c; median HCV RNA values in serum were 2.3 x 105 UI/mL (range, 1.14 x 104 to 4.6 x 105 UI/mL). Total bilirubin, serum albumin, and colinesterase levels remained normal over the entire follow-up. Liver biopsy was not performed and interferon (IFN) therapy was not given. Currently, biochemical liver tests (GOT/GPT/gamma-GT) are in the upper range of normal values and the patient remains viremic. Efficacy and tolerability of initial monotherapy with IFN for chronic hepatitis C among dialysis patients are briefly discussed. Further studies are warranted to define the optimal anti-viral regimen for chronic hepatitis C in the dialysis population.

Epidemiology and clinical significance of hepatotropic infections in dialysis patients. Recent evidence.

Hepatitis C virus (HCV) infection is frequent among patients receiving long-term dialysis in developed and developing countries. It is difficult to assess the natural history of HCV in the dialysis population; however, recent studies have demonstrated that positive anti-HCV status is a significant and independent risk factor for mortality among dialysis patients. Recent meta-analyses have shown that interferon (IFN) initial monotherapy is effective in the treatment of chronic hepatitis C among dialysis patients, but tolerance to IFN mono-therapy was rather poor. Large, multicenter and prospective trials based on pegylated IFN for the treatment of chronic hepatitis C are planned. The frequency of HBV infection in patients undergoing maintenance dialysis in the industrialized world is low but not negligible; persistent HBsAg seropositivity is much higher in less-developed countries. Recent surveys have shown that detectable HBsAg/ HBV DNA status in serum is an independent and significant predictive factor for hepatocellular dysfunction in dialysis patients. No significant difference in morbidity and mortality between dialysis patients according to hepatitis B surface antigen status has been consistently shown. Preliminary reports suggest that lamivudine appears to be safe and effective in patients receiving long-term dialysis.