Autoimmunity against pancreatic islets and other tissues before and after interferon-alpha therapy in patients with hepatitis
C virus chronic infection.
C Betterle ,
P Fabris ,
R Zanchetta ,
B Pedini ...,
G Tositti ,
E Bosi and
F de Lalla
Department of Medical and Surgical Sciences, University of Padua, Italy. betterle@ux1.unipd.it
Abstract
OBJECTIVE: The aim of the study was to investigate the prevalence of clinical and latent autoimmune diseases in Italian patients
with hepatitis C virus (HCV) chronic infection before and after treatment with interferon-alpha (IFN-alpha). RESEARCH DESIGN
AND METHODS: The evidence of clinical autoimmune disease and the presence of autoantibodies were assessed in 70 patients with
HCV chronic infection. Autoantibodies to islet cell (ICA), glucagon-producing cells (GCA), parietal cell (PCA), adrenal cortex
(ACA), adrenal medulla (AdMA), nuclei (ANA), liver-kidney microsomal (LKM-Ab), mitochondrial, and smooth muscle (SMA) were
tested using the classic indirect immunofluorescence technique. Autoantibodies to GAD (GADAb), second islet cell autoantigen
(IA2-Ab), and insulin (IAA) were tested by radioimmunoassay and thyroid microsomal autoantibodies (TMHA) and thyroglobulin
autoantibodies (TGHA) were assessed by hemoagglutination test. RESULTS: None of the 70 patients studied showed evidence of
clinical disease before treatment with IFN-alpha. However, 1 (1.4%) patient was positive for ICA, 2 (2.8%) were positive for
GCA, 2 (2.8%) for GADAb, 5 (7.1%) for PCA, 2 (2.8%) for ANA, 3 (3.7%) for SMA, 4 (5.7%) for TMHA, and 2 (2.8%) for TGHA. These
frequencies were not significantly different when compared with healthy control subjects. There were 29 (41%) patients who
were positive for IAA at low titers compared with 2% of the control subjects (significantly different P < 0.0001). ICA titers
of one patient positive for ICA/GADAb increased during the IFN-alpha therapy, and the patient developed type 1 diabetes 5
months after the beginning of treatment. IAA levels did not change during the course of treatment, and none of the IAA+ patients
developed diabetes. Thyroid autoantibody titers increased in 3 of the 4 initially positive patients, with 1 patient becoming
positive and 2 thyroid antibody-positive patients developing overt hypothyroidism during IFN-alpha treatment. PCA titers increased
in 1 of 5 positive patients. Antibodies to other autoantigens did not change during the course of treatment. CONCLUSIONS:
We have not found an increased frequency of clinical or latent autoimmune diseases in patients with chronic HCV infection.
However, this study suggests that screening patients for autoantibodies (in particular, thyroid and pancreas) before and during
IFN-alpha therapy may be useful in assessing the risk of patients developing autoimmune disease.
The introduction of highly active anti-retroviral therapy (HAART) for Human Immunodeficiency Virus (HIV) infection has significantly improved the life expectancy of HIV positive patients. Hepatitis C ...virus (HCV) co-infection is common in HIV infected patients and is now a significant cause of morbidity and mortality. Optimal management and treatment of HCV in HIV infected patients is therefore essential. Interferon-alpha (IFN-alpha) and ribavirin is the mainstay of treatment for HCV infection in HIV infected people. The sustained virological response rate (SVR) with combination therapy is lower than that commonly observed in HCV mono-infected patients. This is, at least in part, due to the very high treatment drop out rates. Ribavirin in combination with HAART is associated with particular side effects such as mitochondrial toxicity. Therefore, vigilant monitoring of patients during therapy, in specialist centers is essential. Pegylated interferon (PEG-IFN) plus ribavirin is particularly promising as it is easier to administer and will probably become the treatment of choice for co-infected patients. A SVR is associated with genotype 2 and 3, in addition to a high CD4+ cell count and a low HCV load prior to therapy. The progression of HCV related liver disease in HIV positive patients is faster than in subjects with HCV infection alone. As a result, there is an increasing incidence of cirrhosis and end-stage liver disease in co-infected patients. Liver transplantation is being evaluated in many centers. To date the experiences are very limited but encouraging in term of survival rate.
Summary
Aims To assess how much patients with hepatitis C virus infection know about their condition and what impact it has on their lifestyle.
Materials and methods A multiple‐choice questionnaire ...was administered anonymously to 364 hepatitis C virus‐infected subjects just before their first specialist visit.
Results Even before hepatitis C virus infection was diagnosed, 257 subjects (70.6%) already knew something about this infection. Overall, 36% of patients had changed the way they behaved within the family, 25.5% had changed their sexual habits, 46.9% had changed their diet, and 69% reported having stopped or limited their alcohol intake after being told they were hepatitis C virus positive. Hepatitis C virus infection had a negative impact on the psychological status in 44.2% of patients. This effect was significantly greater among women and was independent of either the duration of their infection or any counselling received from the general practitioner. The need for specific treatment was reported by 59.8%. A demand for more detailed information about hepatitis C virus was expressed by 89.9% of patients.
Conclusions Hepatitis C virus changes all aspects of lifestyle and psychological status. The patients’ strong demand for more information suggests that counselling and educational programmes must be an integral part of the activities of both the general practitioner and the specialist.
Many case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively.
To evaluate the incidence and the ...clinical significance of hyperamylasemia in 507 consecutive adult patients with acute gastroenteritis.
The clinical significance of hyperamylasemia, related predisposing factors and severity of gastroenteritis were assessed.
Hyperamylasemia was detected in 10.2 % of patients studied. Although amylasemia was found over four times the normal values in three cases, the clinical features of acute pancreatitis were recorded in only one case (0.1%). Hyperamylasemia was more likely (17%) where a microorganism could be identified in the stools (p < 0.01). Among patients with positive stool samples, Salmonella spp. and in particular S. enteritidis, was the microorganism most frequently associated with hyperamylasemia 17/84 (20.2 %) and 10/45 (22.2%), respectively, followed by Rotavirus, Clostridium difficile and Campylobacter spp. Patients with hyperamylasemia had more severe gastroenteritis with an increased incidence of fever (80 % vs 50.6 %, O.R. 3.0; P < 0.01), dehydration (18% vs 8.5%; O.R. 2.5; P < 0.05), and a higher mean number of evacuations per day (9.2 vs 7.5; P < 0.05) than those with amylasemia in the normal range. Hyperamylasemia was significantly associated with cholelithiasis, (30.0 % vs 10.7%, O.R. 3.5; P < 0.01) and chronic gastritis or duodenal ulceration (22.0 % vs 10.2%, O.R. 2.4, P < 0.05).
Hyperamylasemia is relatively frequent, and is associated with severe gastroenteritis. However, acute pancreatitis in the setting of acute gastroenteritis, is a rare event.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Type 1 diabetes mellitus is the result of an autoimmune process characterized by pancreatic beta cell destruction. It has been reported that chronic hepatitis C infection is associated with ...type 2 diabetes mellitus, but not with type 1. Although the prevalence of markers of pancreatic autoimmunity in hepatitis C virus‐positive patients is not significantly different to that reported in the general population, it increases during alpha‐interferon therapy from 3 to 7%, probably due to the immunostimulatory effects of this cytokine. To date, 31 case reports of type 1 diabetes mellitus related to interferon treatment have been published. Type 1 diabetes mellitus occurs more frequently in patients treated for chronic hepatitis C than for other conditions and is irreversible in most cases. In 50% of these patients, markers of pancreatic autoimmunity predated treatment, the majority of cases having a genetic predisposition. Thus, in predisposed individuals, alpha‐interferon can either induce or accelerate a diabetogenic process already underway. We suggest that islet cell autoantibodies and glutamic acid decarboxylase autoantibodies should be investigated before and during interferon treatment in order to identify subjects at high risk of developing type 1 diabetes mellitus.
Retreatment of chronic hepatitis C patients nonresponders to interferon (IFN) alone with the standard dose of IFN 3 million units (MU) thrice weekly (TIW) plus ribavirin for 24 weeks has yielded low ...sustained virological response (SVR), averaging 8%. The aim of the present, open‐labelled, randomized study was to evaluate the efficacy of IFN induction therapy followed by prolonged high dose of IFN plus ribavirin in nonresponders. One hundred and fifty‐one patients were randomized to receive 5 MU daily of IFN alfa‐2b (group 1, n = 73) or 5 MU TIW of IFN alfa 2b (group 2, n = 78) for 4 weeks followed by IFN (5 MU TIW) plus ribavirin (1000/1200 mg/daily) for 48 weeks in both groups. In an intention‐to‐treat analysis, the sustained virological response (SVR) at 24‐week follow‐up was 33 and 23% for group 1 and 2, respectively (P = 0.17). The overall SVR was 52 and 18% in patients with genotype 2/3 and 1/4, respectively. Among genotype 1/4 patients the SVR was 29 and 11% for age younger or older than 40 years. Compared with genotype 2/3 patients, the risk (95% confidence interval) of nonresponse to retreatment was 3.0‐fold (1.17–8.0) in younger genotype 1/4 patients and 8.4‐fold (3.0–23.29) in older genotype 1/4 patients. In conclusion these results suggest that retreatment with a reinforced regimen should be focused in nonresponder genotype 2/3 patients and younger genotype 1/4 patients, who are most likely to benefit. Induction therapy does not improve SVR.
Patients hospitalized in the authors' institution for erysipelas or cellulitis between January 1995 and December 2002 were included in this retrospective review. Two hundred cases of soft tissue ...infections were hospitalized during the study period. The mean age of the patients was 58 years. The most commonly involved site was the leg (66%), followed by the arm (24%) and face (6%). Most patients (71%) had a recognized risk factor for soft tissue infection. Fever was present in 71% of cases, with a mean duration of 3 days. Blood cultures were positive in 3 out of 141 (2%) cases, whereas cutaneous swabs were positive in 73 out of 92 (79%) cases. On admission, white blood cells counts (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were elevated above normal levels in 100 out of 191 (50%) cases, 151 out of 176 (85%) cases, and 150 out of 154 (97%) cases, respectively. Patients with a hospital stay of more than 10 days had significantly higher CRP and ESR values than patients hospitalized for 10 days or less (
P<0.01). A single antibiotic was used as treatment in 115 cases, whereas in the remaining 85 cases a combination of two antibiotics was administered. The most commonly used antibiotics were amoxicillin-clavulanic acid as single agent and penicillin with clindamycin as combination therapy. The mean duration of hospitalization was 7 days for patients treated with a single antibiotic and 11 days for patients treated with an antibiotic combination. A recurrence of infection occurred in 34 (17%) patients. Soft tissue infections are common and have a high degree of morbidity and require prolonged hospitalization and antibiotic treatment. Microbiological diagnosis is difficult and treatment is based on empiric evidence. ESR and CPR levels on admission may predict the severity of the disease and duration of hospitalization.
Background:
The relationship between serum parameters of gastric function and Helicobacter pylori infection in human immunodeficiency virus (HIV)‐positive patients is almost unknown.
Aims:
To ...investigate in HIV‐infected patients: (i) the relationship between serum gastrin and serum pepsinogens over the progressive phases of HIV‐related disease; (ii) the impact of H. pylori infection on gastrin and pepsinogen serum levels and its relation to antral histology; (iii) the prevalence of parietal cell autoantibodies.
Methods:
Fifty‐nine HIV‐positive patients were studied by upper endoscopy plus gastric antral biopsy. Serum samples were tested for gastrin, pepsinogen A, pepsinogen C and parietal cell autoantibodies.
Results:
In patients without overt acquired immunodeficiency syndrome (AIDS), or with a CD4+ count of > 100 × 106 cells/L, mean serum levels of gastrin and pepsinogen C were higher than in subjects with AIDS or with a CD4+ count of < 100 × 106 cells/L (P < 0.01). Only one patient was found to be positive for parietal cell autoantibodies. H. pylori infection was associated with increased values of gastrin and pepsinogen C only in HIV‐positive patients without AIDS or with a CD4+ count of > 100 × 106 cells/L. Atrophy was more frequent in patients with overt AIDS than in those without overt AIDS (57% vs. 33%, P=N.S.), and/or in patients with a CD4+ count of < 100 × 106 cells/L than in those with a CD4+ count of > 100 × 106 cells/L (62% vs. 26%, P < 0.05).
Conclusions:
HIV‐positive patients without overt AIDS have increased serum levels of gastrin and pepsinogen C compared with HIV‐positive patients with overt AIDS.
Objectives
The aims of this study were to evaluate the prevalence and impact of Chlamydia pneumoniae infection in HIV‐positive patients and to establish the relationship between C. pneumoniae ...infection and lipid profile.
Methods
Detection of C. pneumoniae was by polymerase chain reaction (PCR) on Peripheral Blood Mononuclear Cells (PBMCs) collected from 97 HIV‐positive patients. Samples were collected after overnight fast in EDTA‐treated tubes. On the same day, patients were also tested for routine chemistry, HIV viral load, CD3, CD8 and CD4 cell counts and lipid profile cholesterol, high‐density lipoproteins (HDLs), low‐density lipoproteins (LDLs) and triglycerides.
Results
The overall prevalence of C. pneumoniae was 39%. The prevalence of C. pneumoniae was inversely related to the CD4 lymphocyte count (P=0.03). In the naive group, C. pneumoniae‐positive patients had both significantly higher HIV load (71 021±15 327 vs. 14 753±14 924 HIV‐1 RNA copies/mL; P=0.03) and lower CD4 cell count (348.0±165.4 vs. 541.7±294.8; P=0.04) than C. pneumoniae‐negative patients. Moreover, treatment‐naive patients with C. pneumoniae infection had significantly higher mean levels of cholesterol (185.3±56.2 vs. 124.8±45.9 mg/dL; P=0.01), triglycerides (117.2±74.7 vs. 68±27.6 mg/dL; P=0.04) and LDL (122.4±60.1 vs. 55.6±58 mg/dL; P=0.05) than C. pneumoniae‐negative patients.
Conclusions
These data indicate that, in HIV‐positive subjects, C. pneumoniae infection is relatively frequent and is associated with both low CD4 cell count and high HIV load. Furthermore, C. pneumoniae appears to be associated with hyperlipidaemia and might therefore represent a further risk factor for cardiovascolar disease in HIV‐positive patients.
Background
: Ursodeoxycholic acid (UDCA) is able to improve biochemical markers of cholestasis, with a parallel decrease in transaminases, in various cholestatic liver diseases.
Aim
: To evaluate the ...effects of UDCA administration on acute viral hepatitis‐related cholestasis and the course of acute viral hepatitis.
Methods
: Seventy‐nine consecutive patients with acute viral hepatitis (HBV: 43, HCV: 11, HAV: 15, HEV: 3, Non A‐E: 7) were randomized to receive either UDCA for 3 weeks or no treatment. Liver biochemistry and serum bile acid determinations were run at weekly intervals.
Results
: No significant differences were observed in mean percentage decreases in transaminases between treated and untreated patients. By contrast, cholestatic indexes decreased significantly more quickly in patients treated with UDCA than in controls, and this effect was more evident in patients with increasing alanine transaminase levels at admission. After a peak at the end of the first week of therapy, serum levels of conjugated ursodeoxycholic acid (CUDCA) showed a gradual decrease. Conjugated cholic acid (CCA) and chenodeoxycholic acid (CCDCA) showed a progressive decrease with the resolution of viral hepatitis, but no influence of UDCA administration was observed.
Conclusions
: Our study demonstrates that UDCA significantly improves cholestatic indices in patients with acute viral hepatitis, but this effect does not seem to affect the course of the illness.
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