Viraemia,cryoglobulins and autoantibodies in haemodialysis patients infected with hepatitis C virus

OBJECTIVES: The clinical features of hepatitis C virus (HCV) infection depend on the immune and autoimmune reactions induced by the virus. Chronic renal failure might alter the pattern of these reactions. The aim of this study was to determine the prevalence of cryoglobulinaemia, the frequency of autoantibodies and HCV viral load in HCV infected Greek patients on chronic haemodialysis. METHODS: Seventy-three HCV Ab(+) patients on maintenance haemodialysis and 87 otherwise normal patients with chronic HCV infection were evaluated for the presence of cryoglobulins, autoantibodies and viral markers. RESULTS: Cryoglobulins were detected in 22/73 (30.1%) haemodialysis patients and in 23/87 (26.4%) patients with normal renal function (NS). The mean cryocrit value was significantly lower in the haemodialysis group ( = 0.002). Haemodialysis patients had significantly higher levels of C4 component of complement and lower incidence of rheumatoid factor than those of patients with normal renal function. Serum HCV RNA levels were found significantly lower in the haemodialysis group (median, 2.20 Meq/ml; range, 119.9 Meq/ml) than in the group with normal renal function (median, 4.50 Meq/ml; range, 114.9 Meq/ml; = 0.046). The distribution of genotypes was not different between the two groups. CONCLUSIONS: There are subtle differences in autoimmune features of HCV infection if the patients are also haemodialysed for renal failure. HCV viral load is lower in haemodialysis patients, with no difference in the HCV genotype prevalence. The clinical significance of these findings is unknown.     

Cryoglobulinaemia associated with hepatitis C virus: influence of HCV genotypes, HCV-RNA viraemia and HIV coinfection

To determine whether the clinical and immunological expression of patients with cryoglobulinaemia associated with chronic hepatitis C virus (HCV) infection varied according to HCV-RNA load, HCV genotype or human immunodeficiency virus (HIV) coinfection. We studied 340 HCV patients (188 women and 152 men, with a mean age of 49 years) consecutively diagnosed with cryoglobulinaemia between 1993 and 2003 in our hospital. HCV infection was confirmed by serum HCV-RNA determination in all patients. Two hundred and forty-eight (73%) patients had asymptomatic cryoglobulinaemia and 92 (27%) presented cryoglobulinaemic symptoms. Patients with genotype 1 had a higher mean age at diagnosis of cryoglobulinaemia (48.2 vs 40.2 yrs, P < 0.001) and a higher prevalence of cryoglobulinaemic symptoms (25%vs 10%, P = 0.02), especially of vasculitic features (19%vs 5%, P = 0.014). In comparison with monoinfected HCV patients, those with HIV coinfection had a lower mean age at diagnosis of cryoglobulinaemia (40.4 vs 52.8 years, P < 0.001), a lower prevalence of cryoglobulinaemic symptoms (15%vs 34%, P < 0.001), vasculitis (10%vs 28%, P < 0.001), associated systemic autoimmune disease (3%vs 14%, P = 0.001), rheumatoid factor (30%vs 70%, P = 0.001) and hypocomplementaemia (50%vs 78%, P = 0.01). In HCV-HIV patients, a high viral load was associated with a high frequency of symptomatic cryoglobulinaemia, especially in patients with a high viral load of the two viruses (50%vs 7%, P = 0.001) A higher frequency of cryoglobulinaemic symptoms (especially vasculitis) was found in patients with HCV monoinfection and in those carrying HCV genotype 1. In contrast, patients with HIV coinfection presented a threefold lower prevalence of vasculitis. Associated HIV infection significantly attenuated the clinical and immunological expression of cryoglobulinaemia, except in coinfected patients with high viral loads for the two viruses.     

Hepatitis C virus and kidney: a strong association with different clinical aspects

The most frequent kidney disease associated with chronic hepatitis C virus (HCV) infection is membranoproliferative glomerulonephritis in patients with type II mixed cryoglobulinaemia. The principal clinical manifestations of glomerular disease in HCV‐infected patients are the presence of proteinuria and haematuria with or without impaired kidney function. Pharmaceutical regimens vary because the main pathogenesis of renal dysfunction often mediated by cryoglobulins has not been fully elucidated. HCV infection remains common in patients on renal replacement therapy and has an adverse impact on their survival. Safe and effective pharmaceutical regimens have not been yet established and nosocomial spread within dialysis units continues to occur. Monotherapy with interferon for HCV infection is probably more effective in dialysis than in non‐uraemic patients, while experience with ribavirin is limited because of its adverse haemolytic effect. Based on shortage of cadaver kidneys and the fact that HCV renal transplant recipients have better survival than stay on maintenance haemodialysis or at list for transplantation, health organization proposed the use of cadaver kidneys from anti‐HCV‐positive donors, bringing up concerns and conflicting views. This present review describes the main renal manifestations of HCV infection, the epidemiological and clinical characteristics of chronic kidney disease population and comments on the limitations and shortcomings of current therapeutical regiments.     

Viral hepatitis C in patients with renal disease

Hepatitis C in patients with chronic renal failure. Infection with hepatitis C virus (HCV) is a common complication in those patients under chronic dialysis. Prevalence varies from 8% to 65 percent. Immunization against hepatitis A and B for renal patients is always recommended, especially in countries with high prevalence of this type of hepatitis. Interferon as the only antiviral treatment is recommended for patients with chronic renal failure and chronic hepatitis who depend on dialysis. Viral hepatitis is the first cause of morbidity and mortality among renal recipients. Prevalence varies between 4 and 38%, depending on the geographic area. Infection with HCV usually begins before the transplant, although the patient is sometimes infected during the transplant because the donor organs carry the virus. The chronic HCV infection dosen't seem to affect the survival rate of the patient or the organ, compared to the survival rate in patients without the infection. Chronic hepatitis C without cirrhosis is not a contraindication for renal transplant, but cirrhosis is. Liver failure is the cause of death in 8-28% of renal transplant recipients infected with hepatitis C virus.     

Triple antiviral therapy in hepatitis C virus infection with or without mixed cryoglobulinaemia: A prospective,controlled pilot study

BackgroundMixed cryoglobulinaemia is strongly related to hepatitis C virus infection. Treatment with peg-interferon and ribavirin has been indicated as first-line therapy for mild/moderate hepatitis C virus-related mixed cryoglobulinaemia.AimTo evaluate the safety and efficacy of triple boceprevir-based antiviral therapy in patients with or without mixed cryoglobulinaemia previously treated with peg-interferon and ribavirin, and with advanced liver disease.MethodsThirty-five hepatitis C virus-positive patients (17 with asymptomatic mixed cryoglobulinaemia, 5 with symptomatic mixed cryoglobulinaemia, and 11 without mixed cryoglobulinaemia) were treated with triple boceprevir-based antiviral therapy.ResultsIn 19/22 cryoglobulinaemic subjects (86%), the addition of boceprevir induced cryocrit disappearance. Cryocrit behaviour was related to virological response, with improvement of symptoms upon undetectable viraemia and reappearance after virological breakthrough. The rate of sustained virological response was lower in cryoglobulinaemic patients than in patients without mixed cryoglobulinaemia (23.8% vs 70% respectively, p = 0.01).ConclusionBoceprevir-based therapy was safe and effective in cryoglobulinaemic patients. The correlation between direct inhibition of hepatitis C virus replication and clinical improvement in mixed cryoglobulinaemic patients is definitive proof of the key pathogenetic role played by viral replication. Further studies are needed to confirm and clarify the reduced virological response in patients with mixed cryoglobulinaemia.     

Clinical study of cryoglobulinaemia in Chinese patients with chronic hepatitis C

Cryoglobulinaemia is the most common immunological disorders seen in patients with chronic hepatitis C virus (HCV) infection. We evaluated the incidence and clinical significance of cryoglobulinaemia in 122 Chinese patients with chronic hepatitis C. The pathogenic roles of HCV genotypes and viraemia in this phenomenon were also evaluated. Fifty-four (44%) of the 122 patients with chronic hepatitis C had cryoglobulinaemia. Eleven (20%) of the patients with cryoglobulinaemia had symptoms and signs of cutaneous vasculitis, arthralgia, neuropathy and renal involvement. The patients with cryoglobulinaemia were predominantly female and had a significantly higher mean serum level of rheumatoid factor and a lower mean serum C4 level compared with patients without cryoglobulinaemia (50 vs 29%, 23 vs 15 IU/mL, 25 vs 31 mg/dL, respectively, P < 0.05). The mean serum HCV RNA level, HCV genotype, the presence of serum auto-antibodies, and the rate of cirrhosis were not significantly different between the two groups. Univariate logistic regression analysis showed female serum levels of alanine aminotransferase (> 90 U/L), rheumatoid factor (> 15 IU/mL), C3c (< 100 mg/dL) and C4 (< 20 mg/dL) to be significant predictors of cryoglobulinaemia in chronic hepatitis C patients. However, multivariate analysis showed only serum C4 levels (< 20 mg/dL) as a significantly independent predictor. We concluded that 44% of Chinese patients with chronic hepatitis C had cryoglobulinaemia. Serum C4 levels were significantly lower in chronic hepatitis C patients with cryoglobulinaemia and the serum C4 level was the only clinical independent predictor associated with this phenomenon. Hepatitis C virus genotype and serum viral load were not clinical independent predictors.     

Infections with hepatitis B and C viruses in patients on maintenance dialysis in Romania and in former communist countries: yellow spots on a blank map?

We studied prospectively, between 1993 and 1998, the prevalence and incidence of markers against hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV), in 180 patients with chronic renal failure, dialysed in the Nephrological Clinic, Cluj. HBV and HCV markers were common in the patients who were already on haemodialysis in 1993 (antibodies to hepatitis B core antigen [HBcAb]: 57.9-88%; hepatitis B surface antigen [HBsAg]: 8.7-25%; antibodies to HCV [anti-HCV]: 73.7-100%; simultaneous occurrence of HBsAg and anti-HCV antibodies: 4.4-21%). These patients had the longest mean duration of haemodialysis therapy (6.79 +/- 4.82 years). The lowest prevalence was found in 1996, in the groups of patients included in the haemodialysis programme between 1993 and 1996 (HBcAb: 2.2-3.3%; HBsAg: 0-2.2%; anti-HCV antibodies: 0-2.2%; HBsAg and anti-HCV antibodies: 0-2.2%). The patients included since 1996 had, again, a high prevalence of markers (HBsAg: 21.6%; anti-HCV antibodies: 28.6%), despite the short duration of dialysis therapy (1.65 +/- 1.18 years). The incidence of infection was high before 1993, fell markedly between 1993 and 1996 (zero for the HBsAg and 6. 67% year-1 for the anti-HCV antibodies) and rose sharply between 1996 and 1998 (10.2%, respectively 29% year-1). The prevalence of HBV and HCV infections did not correlate with the age of the patients and depended, but only up to 1993, on the quantity of transfused blood. The link between the duration of the haemodialysis and the prevalence of the HBV and/or HCV infection proved nosocomial transmission. The very high prevalence and incidence of HBV and HCV infections, surpassing not only Western countries, but even those of 'developing' countries that are endemic for these infections, is characteristic of some former communist countries. A radical reform of the medical system in these countries is required.     

Hepatitis B and C and renal failure

Hepatitis C is the most common cause of liver disease in the dialysis patient. The prevalence of chronic hepatitis C determined by anti-HCV testing in this population ranges from 6% to 38%. Using second generation EIA assays, the prevalence of anti-HCV among patients participating in the 1997 National Surveillance of Dialysis Associated Diseases in the United States was 9.3%. Polymerase chain reaction testing for HCV RNA has shown that the prevalence of HCV infection can be as high as 20% to 30% of dialysis patients. The causes and source of infection in patients with chronic renal failure on hemodialysis are multiple. Before the introduction of routine screening of blood donors for anti-HCV, blood transfusions were an important risk factor for acquisition of hepatitis C. Other potential sources of infection include exposure to contaminated equipment and nosocomial routes such as patient-to-patient exposure. The risk of infection appears to correlate with the duration of hemodialysis and the number of transfusions. Interestingly, dialysate and buffers have been shown to be virus free even when used in hepatitis C infected patients. The natural history of chronic hepatitis C infection in patients with renal failure is not well characterized. Although persistent elevations in ALT levels occur in 12% to 50% of dialysis patients, the frequency of persistently normal ALT levels in HCV-infected dialysis patients appears to be higher than in HCV-infected patients without renal failure. Overt liver disease and liver failure rarely occur. The degree of inflammation in liver biopsies of renal failure patients is usually mild. Thus, progressive liver disease may be less common in patients with advanced renal disease but further studies are required to assess the true impact of hepatitis C infection in this high risk population. The impact of hepatitis C infection on morbidity and mortality of patients with end-stage renal disease remains poorly defined. Initial studies have failed to show a significant increase in mortality among HCV-infected hemodialysis or renal transplant patients within the first 5 years following transplantation. In contrast, recent studies with extended follow-up of renal transplant recipients suggest that hepatitis C infection may affect patient and graft survival during the second decade. Further studies are required to identify the mechanisms of infection of patients with end-stage renal disease and to define better treatment strategies for these patients before and after kidney transplantation.     

Acute hepatitis C among renal failure patients on chronic haemodialysis

Hepatitis C virus (HCV) infection is common in haemodialysis units, yet little information is available about the clinical feature of acute hepatitis C among renal failure patients. The present study is based on 49 cases of acute hepatitis C seen at a haemodialysis centre where sporadic nosocomial infection was occurring up to June 1993. Liver function tests were done at 4 weekly intervals on all dialysis patients, anti-HCV antibodies were tested by the C-100 and second generation tests and serum HCV-RNA was determined by the branched DNA and Amplicore tests. Diagnosis of acute hepatitis C was made on the basis of an acute rise in alanine aminotransferase (ALT) and seroconversion to positive anti-HCV antibodies. Clinical presentation of acute hepatitis was generally mild with rare overt jaundice and the diagnosis was possible only from increased ALT, which was generally low. Spontaneous resolution of acute hepatitis within 8 months with clearance of viral RNA occurred in only four cases, 91.8% of patients developing chronic hepatitis. Biopsy in 12 cases with high ALT levels showed mild to moderate inflammatory activities. In conclusion, the clinical presentation of acute hepatitis C is generally mild in chronic haemodialysis patients, but spontaneous resolution is infrequent. A longer follow-up period is required for defining the long-term prognosis.     

High frequency of antibodies to Hantaan virus and hepatitis C virus in chronic haemodialysis patients Coincidence or cross-reaction?

Abstract. Objectives. To address the question of whether there is any coincidence or cross-reaction between hepatitis C virus (HCV) and Hantaan virus (both RNA arboviruses), as well as to assess the frequency of antibodies to the above viruses amongst chronic haemodialysis patients in our region. Design. Collection of serum samples from consecutive unselected chronic haemodialysis patients. Setting. A tertiary referral center (University Hospital). Subjects. One hundred and fourteen chronic haemodialysis patients were investigated for the presence of antibodies to HCV (anti-HCV) and Hantaan virus disease (anti-HVD). Eleven unselected non-haemodialysis patients with well-defined haemorrhagic fever with renal syndrome (HFRS) were also investigated for the anti-HCV antibodies comprising the disease control group. Interventions. None. Main outcome measures. The utility of an anti-HVD positive test in chronic haemodialysis patients. Results. Seventeen patients (14.9% 95% confidence interval [CI] 8.4–21.4%) were anti-HCV positive, whereas 15 (13.2%, 95% CI 6.9–19.3%) were anti-HVD positive. An anti-HCV positive test was confirmed by recombinant immunoblot assay (RIBA II) in 88.2%. The presence of anti-HCV antibodies was not associated with transfusions but with the longer duration of haemodialysis (62.8 ± 29.8 vs. 31.2 ± 29.3 months, P < 0.001). Anti-HVD antibodies were not associated with transfusions or with the duration of haemodialysis. Three patients were positive for both anti-HCV and anti-HVD antibodies. None of the 11 patients with well-defined HFRS had anti-HCV antibodies. Conclusions. Chronic haemodialysis patients are a high risk group for HCV infection in association with the duration of haemodialysis and, at least for our geographical area, these patients have to be examined for anti-HVD antibodies especially when a definite causative agent for chronic renal failure is not found. The HVD and HCV infection are not exceptional amongst haemodialysis patients in our region, whereas the possibility of a cross-reaction between these two RNA arboviruses is rather excluded as there was no evidence of HCV infection amongst the patients with well-defined HFRS.     

Chronic hepatitis C and chronic kidney disease: Advances,limitations and unchartered territories

Over the past few years, treatment options for chronic hepatitis C virus (HCV) infection have evolved dramatically. The current approved interferon‐free direct‐acting antiviral (DAA) regimens have been shown to be safe and effective with sustained virologic response (SVR) rates of >90% in most patients. Unique issues yet remain such as the challenges in patients with impaired renal function or decompensated cirrhosis. Patients with stages 4‐5 chronic kidney disease (CKD) have a higher prevalence of HCV infection compared with the general population. Chronic HCV in those on dialysis and in kidney transplant recipients is associated with higher morbidity and mortality than uninfected patients. The HCV‐infected population is also at risk of developing extrahepatic manifestations associated with altered immune system function and chronic inflammation with cryoglobulinaemic vasculitis being the most common of these manifestations. Therefore, patients with CKD stages 4‐5 have to be considered priority patients for HCV therapy. New antiviral therapies have the potential to improve outcomes in this vulnerable patient population, including those on haemodialysis. Recently published studies conducted in kidney transplant recipients have demonstrated successful outcomes. It is thus essential that we carefully select the most appropriate DAA regimen and the best time for treatment in the context of kidney transplantation or cryoglobulinaemic vasculitis. While sofosbuvir, the only approved nucleotide NS5B inhibitor, has been the backbone of most pangenotypic therapeutic regimens, it has a limitation in those with advanced kidney disease. The currently approved regimens for those with stage 4/5 CKD, while effective, have challenges in that they apply to genotype 1/4 and may require RBV for genotype 1a. Globally, genotype 3 is a common infection, and thus, this group with CKD presents a huge unmet need for effective therapies. As therapy of HCV in renal transplant recipients has been highly successful, it provides an opportunity to expand the use of HCV‐infected organs in solid organ transplantation.     

Recovery from hepatitis C virus-positive cryoglobulinaemic glomerulonephritis after interferon therapy

The association between mixed cryoglobulinaemia and chronic hepatitis C virus infection has recently been described. Cryoglobulinaemic glomerulonephritis, a complication of mixed cryoglobulinaemia, is usually treated with immunosuppressive therapy, but, given the presence of viral infection, this therapy is no longer recommended. This report concerns a case of a 30-year-old patient with cryoglobulinaemic glomerulonephritis, refractory to steroid treatment, in whom recovery from hepatitis C virus infection was obtained as well as from cryoglobulinaemic glomerulonephritis after interferon therapy. The clinical symptoms and laboratory tests were normal after prolonged interferon therapy and, 3 years after the end of treatment, the patient is free from disease.     

Complex management issues: management of HCV in the atypical patient.

Some patients with chronic hepatitis C virus (HCV) infection demonstrate atypical features of presentation and clinical course. These features may be due to direct or indirect effects of the underlying HCV infection or may be part of a separate clinical syndrome. Patients that can be categorized as 'atypical' include immunosuppressed individuals (hypogammaglobulinaemic, co-infected with human immunodeficiency virus, recipients of solid organ or haematopoietic cell transplants, those with associated disease requiring chronic immunosuppressive therapy and patients with chronic renal failure on haemodialysis) as well as patients with various extra-hepatic (HCV-associated mixed cryoglobulinaemia, membranoproliferative glomerulonephritis etc) or autoimmune manifestations. Since many of these patients have been excluded from the large trials evaluating the efficacy of interferon-alpha alone or in combination with ribavirin, data regarding management are limited. In this chapter, the available information regarding the treatment of these patients is reviewed and the frequently encountered therapeutic dilemmas discussed. Finally, some reasonable therapeutic approaches are suggested while the need for controlled studies for these groups of patients is emphasized.     

Hepatitis C virus antibodies, viral RNA and genotypes in sera from patients on maintenance haemodialysis

SUMMARY. Patients on maintenance haemodialysis in four dialysis centres were tested for markers of hepatitis C virus (HCV) infection. Antibody to HCV (anti-HCV) was detected by the second-generation enzyme immunoassay in 142 (26%) of the 543 patients and HCV RNA in 117 (22%) of whom four were without detectable anti-HCV in serum. Seventy-seven (66%) were infected with HCV of genotype II/1b, 31 (27%) with genotype III/2a and eight (7%) with genotype IV/2b. in a distribution similar to that in blood donors who carried HCV asymptomatically. Haemodialysis patients had high HCV RNA titres comparable to those of patients with chronic hepatitis C. HCV RNA was detected in 96 (26%) of the 365 patients with a history of transfusion more frequently than in 21 (12%) of the 178 without previous transfusion ( P <0.001). In transfused patients, frequencies of anti-HCV and HCV RNA increased in parallel with the duration of haemodialysis. The frequency of anti-HCV in non-transfused patients, however, did not change appreciably with the duration of haemodialysis up to 22 years. The patients with anti-HCV had a higher frequency of HCV RNA in serum than symptom-free blood donors with anti-HCV (113/142 or 80% vs 109/166 or 66% P <0.01) and the patients with HCV RNA had a lower frequency of elevated aminotransferase levels than blood donors with HCV RNA (5/113 or 4% vs 27/109 or 25%, P <0.00l). These results indicate that transfusion is a significant cause of HCV infection in patients on maintenance haemodialysis, and that these patients are prone to establish the HCV carrier state after infection.     

Hepatitis C virus and kidney disease

Hepatitis C virus (HCV) infection remains frequent in patients on renal replacement therapy and has an adverse impact on survival in infected patients on chronic hemodialysis as well as renal transplant (RT) recipients. Nosocomial spread of HCV within dialysis units continues to occur. HCV is also implicated in the pathogenesis of renal dysfunction often mediated by cryoglobulins leading to chronic kidney disease as well as impairing renal allograft function. The role of antiviral therapy for hepatitis C in patients with renal failure remains unclear. Monotherapy with conventional interferon (IFN) for chronic hepatitis C is probably more effective in dialysis than in non-uraemic patients but tolerance is lower. Limited data only are available about monotherapy with pegylated interferon and combination therapy (pegylated IFN plus ribavirin) for chronic HCV in the dialysis population. Clinical experience with antiviral therapy for acute HCV in dialysis population is encouraging. Interferon remains contraindicated post-RT because of concerns about precipitating graft dysfunction. Sustained viral responses obtained by antiviral therapy in renal transplant candidates are durable after renal transplantation and may reduce HCV-related complications after RT (post-transplant diabetes mellitus, HCV-related glomerulonephritis, and chronic allograft nephropathy).     

Mixed cryoglobulinaemia associated with hepatitis C virus infection: A predictor factor for treatment with interferon?

BACKGROUND AND AIMS: Mixed cryoglobulinaemia (MC) is a frequent finding among patients infected with hepatitis C virus (HCV). The response to treatment with alpha-interferon (alpha-IFN) in these patients is linked to predictive factors. The aim of this study was to ascertain whether the presence of MC was a predictive factor of response in patients treated with alpha-IFN for chronic hepatitis due to HCV. METHODS: Thirty-two patients with MC and HCV infection (24 with chronic hepatitis and eight with cirrhosis) were compared with 30 patients with HCV infection without MC (23 chronic hepatitis, seven cirrhosis) of a similar mean age. All were treated with lymphoblastoid alpha-IFN, at 3 MU, t.i.w., for 6-12 months and then followed up. RESULTS: No statistical difference was observed between the two groups in terms of sustained response (P = 0.83), relapse (P = 0.88) and non-response (P = 0.92). The mean follow up was 24.3 months (range 17-28) for patients with sustained response and for the patients with MC and 22.6 months (range 15-26) for patients without MC. CONCLUSIONS: The presence of cryoglobulinaemia does not influence the response to alpha-IFN in patients with chronic HCV infection.     

Superinfection of TT virus and hepatitis C virus among chronic haemodialysis patients

BACKGROUND: The TT virus (TTV), a new DNA virus found in Japan from a patient with post-transfusion hepatitis non-A-non-G, is frequently positive in the sera of patients with liver disease. It is not established whether this virus causes liver damage. We studied the frequency of superinfection of this virus and hepatitis C virus (HCV) known to be endemic among haemodialysis patients, and the possible deleterious effect of TTV on HCV-induced chronic liver disease. METHODS: We used primers from a conservative region in the TTV genome (Okamoto, 1998) to detect TTV. Sera from 163 dialysis patients positive for anti-HCV and 77 dialysis patients negative for anti-HCV (control) were tested. RESULTS: TT Virus positivity was 35% among HCV antibody (anti-HCV)-positive patients and 45.4% among anti-HCV-negative patients. TT Virus positivity was unrelated to the length of haemodialysis or amounts of blood the patients had received in the past. More anti-HCV-positive patients had a history of transfusion, but TTV positivity was not as closely associated with transfusion as anti-HCV positivity. The severity of chronic liver disease was estimated from peak serum alanine aminotransferase levels in the preceding 6 months. Among anti-HCV positives, TTV-positive patients tended to have less active disease; at least there was no indication that TTV superinfection aggravated chronic hepatitic C in long-term dialysis patients. Four of 35 anti-HCV-negative, TTV-positive patients had chronic active liver disease, while none of the anti-HCV-negative and TTV-negative patients did. CONCLUSIONS: TT Virus infection is prevalent among haemodialysis patients. Its transmission occurs not only by blood transfusion, but also by non-parenteral infection. Superinfection of TTV does not exert deleterious effects on the liver disease induced by HCV. However, it may cause chronic hepatitis in a limited number of patients, but remains dormant most of the time. Triple infection, HCV and TTV plus HBV or HGV (one case each), did not cause severe liver disease.     

Cryoglobulinaemia and rheumatic manifestations in patients with hepatitis C virus infection

OBJECTIVES: To investigate the association of cryoglobulinaemia and rheumatic manifestations in Korean patients with hepatitis C virus (HCV) infection. METHODS: Forty nine Korean patients with HCV infection were recruited. The prevalence, concentration, and type of cryoglobulin (by immunofixation), rheumatoid factor (RF), antinuclear antibody (ANA), and various rheumatological symptoms were investigated and HCV genotype was determined by polymerase chain reaction with genotype specific primer. RESULTS: The prevalence of cryoglobulin was 59% in Korean HCV patients and the concentration of cryoglobulin was 9.8 (7.9) g/l (mean (SD)). The type of cryoglobulinaemia was identified in 23 (80%) of 29 HCV patients with cryoglobulinaemia and they were all type III. There were no differences in age, sex, history of operation and transfusion, proportion of liver cirrhosis between the patients with cryoglobulinaemia and those without cryoglobulinaemia. The frequencies of RF and ANA were 14% and 3.4% respectively in HCV patients with cryoglobulinaemia. There was no difference in HCV genotype between the patients with cryoglobulinaemia and those without cryoglobulinaemia. Clinical features of HCV patients were as follows: arthralgia/arthritis (35%), cutaneous manifestation (37%), Raynaud's phenomenon (8%), paresthesia (44%), dry eyes (22%), dry mouth (10%), oral ulcer (33%), and abdominal pain (14%). However, these rheumatological symptoms did not differ between the two groups. CONCLUSION: Although the rheumatological symptoms were not different between HCV patients with and without cryoglobulinaemia, HCV patients showed various rheumatological manifestations. These result suggests that HCV infection could be included as one of the causes in patients with unexplained rheumatological symptoms.     

Schistosoma mansoni coinfection could have a protective effect against mixed cryoglobulinaemia in hepatitis C patients

Background/Aim: The association between mixed cryogloblinaemia and chronic hepatitis C virus (HCV) infection has been established. However, the factors underlying its great geographical heterogeneity of prevalence have not yet been identified. Concomitant HCV and Schistosoma mansoni infections are common in Egypt. Chronic helminthic infections have been found to decrease the incidence and manifestations of immune‐related diseases. To date, no study has focused on the influence of S. mansoni coinfection on the risk of cryoglobulinaemia in hepatitis C patients. Methods: A cohort of 119 consecutively recruited chronic hepatitis C‐infected patients was studied. Patients' sera were assessed for S. mansoni antibodies and cryoglobulins (CGs) were determined and characterized. Results: Cryoglobulins were detected in 18 of 119 patients (15.1%) included in this study. They were detected in 12 of 45 hepatitis C (26.7%) and six of 74 coinfected patients (8.1%), which was statistically significant, P=0.01. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were also found to be significantly lower in the CG‐positive group compared with the CG‐negative group, P=<0.01. CGs were detected in seven of 21 (33.3%) and in 11 of 98 (11.2%) hepatitis C female and male patients, respectively, indicating a significantly positive association with the female gender, P=0.02. A logistic regression adjusted for gender, AST and ALT showed that hepatitis C patients without schistosomal coinfection are more likely to have cryoglobulinaemia, odds ratio=4.12, 95% confidence interval=1.42–11.95. Conclusion: There is an apparent protective effect of S. mansoni coinfection against mixed cryoglobulinaemia in chronic hepatitis C patients.