Hepatitis C among predialysis patients: prevalence and characteristics in a large cohort of patients.

BACKGROUND: The factors associated with hepatitis C virus (HCV) infection in predialysis patients need to be better investigated. The aims of this study were to evaluate the prevalence, risk factors, clinical, biochemical and virological characteristics of chronic HCV infection in predialysis patients. METHODS: Anti-HCV antibodies were determined in a large cohort of predialysis patients. Epidemiological and laboratorial characteristics of HCV infection were evaluated in predialysis patients and this group was matched to a control group consisting of predialysis patients without viral infection (1:3) and compared in terms of risk factors and alanine aminotransferase (ALT) levels. Logistic regression analysis was applied to identify variables independently associated with chronic HCV infection. RESULTS: A total of 1,041 patients (61% males) with a mean age of 61 +/- 15 years and mean creatinine clearance of 36 +/- 18 ml/min were included. Forty-one (3.9%) patients were anti-HCV positive and, of these, 39 (95%) presented viremia. Predialysis patients with HCV more frequently showed a history of blood transfusion before 1992 (66.7 vs. 10.3%; p < 0.001) and major surgeries (53.8 vs. 17.1%; p < 0.001), a higher proportion of undetermined etiology of kidney disease (43.6 vs. 17.1%; p = 0.001), and higher ALT levels (1.3 vs. 0.4 xULN; p < 0.001). History of blood transfusion before 1992 (p < 0.001; OR: 19), intravenous drug abuse (p = 0.002; OR: 69) and ALT levels (p < 0.001; OR: 50) were the variables that were independently associated with chronic HCV infection. The accuracy of ALT in detecting HCV infection was 92%. The most prevalent HCV genotype was 1b (48.7%) and 56.5% of patients presented high HCV viral load. CONCLUSION: Chronic HCV infection among predialysis patients is related to increased parenteral exposure. Elevated ALT levels suggest the need for HCV screening as part of the predialysis care since ALT seems to be a good marker of this infection.

Hepatitis C in chronic kidney disease: predialysis patients present more severe histological liver injury than hemodialysis patients?

BACKGROUND: The characteristics of hepatitis C virus (HCV) infection in predialysis patients are poorly understood and they could be different from hemodialysis patients. AIMS: To evaluate the demographics, laboratory and histological characteristics of chronic HCV infection in predialysis patients and to compare them with those observed in hemodialysis patients. METHODS: Thirty-nine predialysis patients with chronic HCV infection were compared to HCV-infected hemodialysis patients (ratio of 1:3) in terms of demographics, laboratory and histological characteristics. The fibrosis progression rate (FPR) was calculated as the ratio between fibrosis stage and duration of infection. RESULTS: Predialysis patients were older (57 +/- 10 vs. 45 +/- 12 years; p < 0.001), presented a higher proportion of elevated alanine aminotransferase (71.8 vs. 41.0%; p = 0.001) and aspartate aminotransferase (64.1 vs. 26.5%; p < 0.001), a higher proportion of interface hepatitis (66.7 vs. 47%; p = 0.033) and more advanced fibrosis (71.8 vs. 16.2%; p = 0.001). Among patients with estimated duration of infection, predialysis patients presented a longer duration of infection (22 vs. 6 years; p < 0.001) and no difference in FPR was observed between groups (p = 0.692). CONCLUSION: Although predialysis patients with HCV infection present more severe histological injury than hemodialysis patients, this finding probably reflects a longer duration of infection with no evidence supporting that hepatitis C presents a more aggressive course in this group.

Cutaneous amyloidosis associated with primary biliary cirrhosis.

Primary cutaneous amyloidosis is defined as the deposition of amyloid in the skin in the absence of systemic involvement. The association between primary cutaneous amyloidosis and other diseases, although rare, has been documented for connective tissue disorders such as systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis. We report the case of a 41-year-old woman who developed primary biliary cirrhosis in association with primary cutaneous amyloidosis. This association has not been reported before in the literature.

Interferon-alpha therapy within the first year after acute hepatitis C infection in hemodialysis patients: efficacy and tolerance.

BACKGROUND: Interferon monotherapy significantly reduces the chronicity rate of acute hepatitis C in nonuremic patients. In this clinical study, we evaluated the efficacy and tolerance of interferon-alpha therapy for acute hepatitis C in hemodialysis patients. METHODS: Patients with acute hepatitis C, established on the basis of seroconversion to anti-hepatitis C virus and the presence of hepatitis C virus RNA, received a low dose of interferon-alpha (3 MU three times per week) for 12 months or a high dose (5 MU three times per week, preceded by a daily induction dose) for 6 months. Response to treatment was defined as undetectable hepatitis C virus RNA at the end of treatment and sustained virological response was defined as persistent negative hepatitis C virus RNA 6 months after the end of treatment. RESULTS: Twenty-three patients were treated, 16 with a low dose of interferon-alpha and seven with a high dose. At the end of treatment, hepatitis C virus RNA was undetectable in 16/23 patients (70%). Of these, 6/23 patients (26%) relapsed and 10/23 (43%) maintained a sustained virological response (38% in lower doses vs. 57% in higher doses). Treatment was well tolerated and only three patients discontinued therapy (13%). CONCLUSION: Interferon-alpha within the first year after acute hepatitis C in hemodialysis patients was found to be safe and effective, inducing a sustained virological response in 43% of cases. This study supports the routine indication of acute hepatitis C treatment with interferon-alpha for hemodialysis patients, and higher doses administered for a shorter period of time should be tried according to the tolerance of the patients.

Factors associated with the intensity of liver fibrosis in renal transplant patients with hepatitis B virus infection.

BACKGROUND: Hepatitis B may show a more aggressive course after kidney transplantation, but the factors associated with the progression of fibrosis in this group have not been identified. OBJECTIVES: To determine the influence of hepatitis B virus (HBV) viral load and host-related factors on the progression of hepatic fibrosis in hepatitis B virus-infected renal transplant recipients. PATIENTS AND METHODS: Renal transplant patients positive for HBV surface antigen (HBsAg) and submitted to a liver biopsy because of evidence of viral replication were included. Patients with advanced fibrosis (METAVIR F3-F4) were compared with patients with mild fibrosis (F0-F2) regarding sex, age, estimated time since infection, post-transplant time, donor type, history of renal transplantation, alanine aminotransferase, anti-hepatitis C virus, HBeAg and quantitative hepatitis B virus-DNA. Logistic regression analysis was applied to identify variables independently associated with more advanced fibrosis. RESULTS: Fifty-five patients (75% men, 41+/-11 years) with a mean post-transplant time of 5+/-4 years were included. HBeAg was detected in 67% of the patients and anti-hepatitis C virus in 35%. The median hepatitis B virus-DNA level was 2.8 x 10(8) copies/ml. Seventeen (31%) patients had advanced fibrosis. Using logistic regression analysis, the only variable that showed an independent association with more advanced stages of fibrosis was post-transplant time (P=0.03, odds ratio: 1.2, 95% confidence interval: 1.02-1.45). CONCLUSION: Hepatitis B virus viral load, although very high, and hepatitis B virus/hepatitis C virus coinfection are not related to the intensity of liver fibrosis in renal transplant patients infected with hepatitis B virus. Post-transplant time was the only factor independently associated with more advanced liver fibrosis, suggesting the influence of immunosuppression on the progression of liver disease in these patients.

Is autoimmune hepatitis a frequent finding among HCV patients with intense interface hepatitis?

AIM: To evaluate the overlap of autoimmune hepatitis in hepatitis C virus (HCV)-infected patients with intense interface hepatitis. METHODS: Among 1759 patients with hepatitis C submitted to liver biopsy, 92 (5.2%) presented intense interface hepatitis. These patients were evaluated regarding the presence of antinuclear antibody (ANA), anti-smooth muscle antibody (SMA) and anti-liver/kidney microsomal antibody (LKM-1), levels of gamma-globulin and histological findings related to autoimmune hepatitis (plasma cell infiltrate and presence of rosettes). RESULTS: Among patients with hepatitis C and intense interface hepatitis there was a low prevalence of autoantibodies (ANA = 12%, SMA = 5%, LKM-1 = 0%) and the median gamma-globulin level was within the normal range. Typical histological findings of autoimmune disease were observed in only two cases (2%). After applying the score for diagnosis of autoimmune hepatitis, only one patient was classified with a definitive diagnosis of autoimmune hepatitis. Since overlap with autoimmune hepatitis was not the explanation for the intense necroinflammatory activity in patients with chronic hepatitis C we sought to identify the variables associated with this finding. The presence of intense interface hepatitis was associated with more advanced age, both at the time of infection and at the time of the biopsy, and higher prevalence of blood transfusion and alcohol abuse. CONCLUSION: Although possible, overlap with autoimmune hepatitis is a very rare association in HCV-infected patients with intense interface hepatitis, an unusual presentation which seems to be related to other host variables.

Factors associated with the progression of hepatic fibrosis in end-stage kidney disease patients with hepatitis C virus infection.

BACKGROUND: Few studies have evaluated the histological aspects of hepatitis C virus (HCV) infection in hemodialysis patients and the factors related to the progression of hepatic fibrosis in this population have not been defined. AIM: To evaluate the influence of host-related factors on the fibrosis progression in end-stage renal disease (ESRD) patients with HCV infection. METHODS: HCV-infected ESRD patients who submitted to liver biopsy were included. The fibrosis stages were classified according to METAVIR scoring system. For the identification of factors associated with more advanced liver fibrosis, the patients were classified into two groups: group 1, absence of septal fibrosis (F0-1) and group 2, presence of septal fibrosis (F2-4). Groups 1 and 2 were compared regarding demographic, epidemiological, and laboratory variables and logistic regression analysis was used to identify the variables that were independently associated with the presence of septal fibrosis. RESULTS: A total of 216 ESRD patients (63% men, 44+/-11 years) were included. In the histological analysis, the fibrosis stages were as follows: F0=36%, F1=41%, F2=12%, F3=7, and 4% had cirrhosis (F4). In the logistic regression model, the variables that were independently associated with the presence of septal fibrosis were duration of infection, estimated age at infection, coinfection with HBV and aspartate aminotransferase levels. CONCLUSION: These findings support the importance of obtaining an adequate immune response to HBV vaccination and careful monitoring of liver disease in patients who become infected at an advanced age and/or those presenting elevated aspartate aminotransferase levels, as these are the main factors associated with the presence of septal fibrosis in ESRD patients.

Clinical and laboratory characteristics of acute hepatitis C in patients with end-stage renal disease on hemodialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) undergoing hemodialysis are a risk group for hepatitis C virus (HCV) infection. The characteristics of acute hepatitis C infection in this population are not well known. GOALS: To evaluate the clinical and laboratory characteristics of acute hepatitis C in ESRD patients treated with hemodialysis. STUDY: ESRD patients on hemodialysis with acute hepatitis C, characterized by elevated alanine aminotransferase (ALT) followed by anti-HCV seroconversion were studied. RESULTS: Thirty-six patients (58% females, 44+/-12 y), with a mean time on hemodialysis of 2 years, were included. Only 2 (6%) patients had jaundice. ALT elevation was observed in all patients. Median peak ALT was 4.7 x upper limit of normal. The median interval between ALT elevation and anti-HCV seroconversion was 1 month (0 to 8). None of the patients with detectable HCV-RNA showed spontaneous clearance of viremia within 12 weeks of follow-up. Three (8%) patients presented ALT elevation followed by anti-HCV seroconversion with undetectable HCV-RNA. CONCLUSIONS: Acute hepatitis C is frequently asymptomatic in ESRD patients on hemodialysis and should be suspected in all patients presenting elevated ALT. Determination of HCV-RNA is important for the confirmation of infection. Anti-HCV seroconversion seems to occur early and spontaneous clearance of HCV-RNA is uncommon.