21 results on '"Alexander, G J"'
Search Results
2. Spontaneous loss of hepatitis C virus RNA from serum is associated with genotype 1 and younger age at exposure.
- Author
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Rolfe KJ, Curran MD, Alexander GJ, Woodall T, Andrews N, and Harris HE
- Subjects
- Adult, Age Factors, Female, Genotype, Hepacivirus classification, Hepacivirus genetics, Humans, Male, RNA, Viral genetics, Serum virology, Hepacivirus isolation & purification, Hepatitis C virology, RNA, Viral blood
- Abstract
A variety of factors have been associated with spontaneous loss of hepatitis C virus (HCV)-RNA from serum, including infecting HCV type, although results are conflicting. This study aimed to investigate further whether infecting HCV type was linked to spontaneous loss of HCV-RNA. Serum samples from 321 untreated HCV antibody positive patients presenting at the Hepatology clinic at Addenbrooke's Hospital, Cambridge between 2004 and 2007 were tested. These individuals were classified either as HCV antibody and HCV-RNA positive (viremic, n = 219) or HCV antibody positive and repeatedly HCV-RNA negative (non-viremic, n = 102). Infecting HCV type was identified by genotyping (viremic) or serotyping (non-viremic). Binomial regression analysis investigated the independent effect of HCV type on spontaneous loss of HCV-RNA from serum by comparing the two groups. Ninety-one percent of patients were found to be either genotype 1 or genotype 3. The prevalence of type 1 infection was greater among non-viremic (64.5%) than viremic individuals (45%). After controlling for the effects of potential confounding factors, multivariable analyses showed that individuals with type 1 infections were more likely to be non-viremic than genotype 3 infections (RR = 2.07; 95% CI: 1.25, 3.43; P = 0.005). Individuals infected at an older age were also less likely to become HCV-RNA negative spontaneously (RR = 0.42 comparing those infected at ≥20 years of age against those infected at <20 years of age, 95% CI: 0.25, 0.72; P = 0.002). In conclusion, the results suggest that HCV genotype 1 infections are more likely than genotype 3 infections to become spontaneously non-viremic, as are infections acquired at younger age., (Copyright © 2011 Wiley-Liss, Inc.) more...
- Published
- 2011
- Full Text
- View/download PDF
Catalog
3. Hepatitis C-associated glomerulonephritis--a novel therapeutic approach.
- Author
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Reed MJ, Alexander GJ, Thiru S, and Smith KG
- Subjects
- Hepacivirus, Humans, Male, Middle Aged, Mycophenolic Acid analogs & derivatives, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Antiviral Agents therapeutic use, Glomerulonephritis drug therapy, Glomerulonephritis etiology, Hepatitis C complications, Interferon-alpha therapeutic use, Mycophenolic Acid therapeutic use
- Published
- 2001
- Full Text
- View/download PDF
4. An association between hepatitis C virus infection and type 2 diabetes mellitus: what is the connection?
- Author
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Alexander GJ
- Subjects
- Humans, Diabetes Mellitus, Type 2 complications, Hepatitis C complications
- Published
- 2000
- Full Text
- View/download PDF
5. Liver transplantation for hepatitis C virus related cirrhosis.
- Author
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Crosbie OM and Alexander GJ
- Subjects
- Diagnosis, Differential, Hepatitis C diagnosis, Hepatitis C virology, Humans, Liver Cirrhosis diagnosis, Recurrence, Treatment Outcome, Hepatitis C surgery, Liver Cirrhosis surgery, Liver Cirrhosis virology, Liver Transplantation
- Abstract
Hepatitis C virus (HCV) related chronic liver disease is now the leading cause for liver transplantation in many centres. Virological recurrence is inevitable following liver transplantation. Excellent patient and graft survival are seen in the short-term, equivalent to that in patients transplanted for other causes of liver disease. However, histological evidence of disease recurrence or hepatitis is present in over half the patients within a year of transplantation, although a small percentage develop progressive cholestatic hepatitis with graft loss within a year. Cirrhosis can develop in the first year after transplantation and 28% of patients have evidence of cirrhosis by 5 years. There is little agreement over the factors that predict the recurrence of disease, development of cirrhosis within the graft and graft or patient survival. Graft loss due to HCV occurs in up to 9% at 5 years and the long-term prognosis may not be comparable to groups transplanted for other diseases. Patients with hepatocellular carcinoma may benefit from liver transplantation if the tumour is small and without vascular invasion. There are, as yet, no clear guidelines regarding the best combination of immunosuppressants in patients with HCV but viral clearance has been achieved with the use of interferon and ribavirin therapy post-operatively. more...
- Published
- 2000
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6. European collaborative study on factors influencing outcome after liver transplantation for hepatitis C. European Concerted Action on Viral Hepatitis (EUROHEP) Group.
- Author
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Féray C, Caccamo L, Alexander GJ, Ducot B, Gugenheim J, Casanovas T, Loinaz C, Gigou M, Burra P, Barkholt L, Esteban R, Bizollon T, Lerut J, Minello-Franza A, Bernard PH, Nachbaur K, Botta-Fridlund D, Bismuth H, Schalm SW, and Samuel D more...
- Subjects
- Female, Follow-Up Studies, Graft Survival, Hepacivirus genetics, Hepatitis C pathology, Hepatitis C physiopathology, Humans, Male, Middle Aged, Prognosis, RNA, Viral analysis, Recurrence, Retrospective Studies, Risk Factors, Survival Analysis, Treatment Outcome, Hepatitis C surgery, Liver Transplantation
- Abstract
Background & Aims: Liver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV. The prognosis and risk factors for morbidity and mortality in this condition were determined., Methods: A retrospective study of 652 consecutive anti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen., Results: Overall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype 1b (RR, 2; 95% CI, 1.3-2.9; P = 0.01), and age > 49 years (RR, 1.4; 95% CI, 1.1-1.8; P = 0.01)., Conclusions: The results of transplantation for HCV-related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 1b, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV. more...
- Published
- 1999
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7. Cryoglobulinaemia in HCV infection: coming in from the cold.
- Author
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Crosbie OM and Alexander GJ
- Subjects
- Antiviral Agents therapeutic use, Hepatitis C therapy, Humans, Interferon alpha-2, Interferon-alpha therapeutic use, Recombinant Proteins, Cryoglobulinemia virology, Hepatitis C complications
- Published
- 1999
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8. Trends in deaths from malignant neoplasia of liver are poor indicator of hepatitis C infection.
- Author
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Harris HE, Ramsay ME, Balogun K, and Alexander GJ
- Subjects
- Humans, Mortality trends, United Kingdom epidemiology, Hepatitis C complications, Liver Neoplasms mortality
- Published
- 1999
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9. Hepatic histology in hepatitis C virus carriers coinfected with hepatitis G virus.
- Author
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Petrik J, Guella L, Wight DG, Pearson GM, Hinton J, Parker H, Allain JP, and Alexander GJ
- Subjects
- Adult, Aged, Female, Fibrosis, Humans, Male, Middle Aged, Polymerase Chain Reaction, RNA, Viral analysis, Carrier State pathology, Flaviviridae genetics, Hepatitis C pathology, Hepatitis, Viral, Human pathology, Liver pathology
- Abstract
Background: A novel flavivirus has been described recently and designated hepatitis G virus (HGV). The virus is transmitted by the parenteral route but it is uncertain whether it is associated with chronic liver disease because liver biopsy is difficult to justify in this group., Aims: To examine histological features of liver biopsy in patients infected with hepatitis C virus (HCV) according to the presence or absence of HCV and HGV RNA., Methods: One hundred and thirty one consecutive HCV carriers undergoing staging liver biopsy were studied retrospectively. In each, HCV RNA and HGV RNA were detected by reverse transcription polymerase chain reaction on serum samples collected at the time of biopsy. The presence of each RNA was correlated with histological features blind to the RNA results; individual histological features of inflammation or fibrosis were scored separately., Results: Nineteen patients were positive for both HGV and HCV RNA in serum, 91 were positive for HCV RNA alone, two were positive for HGV RNA alone, and 19 were negative for both RNA species. Neither age nor sex differed between the groups; a greater proportion of intravenous drug users were HGV RNA positive, but this was not statistically significant. There was no effect of HGV coinfection on the stage of fibrosis or any other histological parameter except steatosis; patients with HCV and HGV RNA had a higher mean score for fat than those patients with HCV RNA alone (p < 0.05)., Conclusions: HGV coinfection has no important effects on histological features in chronic HCV carriers. It is unlikely that HGV infection causes chronic liver disease. more...
- Published
- 1998
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10. Importance of age in chronic hepatitis C virus infection.
- Author
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Wong V, Caronia S, Wight D, Palmer CR, Petrik J, Britton P, and Alexander GJ
- Subjects
- Adolescent, Adult, Age Factors, Aged, Biopsy, Chronic Disease, Disease Progression, Female, Hepatitis Antigens analysis, Hepatitis C blood, Hepatitis C epidemiology, Hepatitis C Antibodies, Humans, Liver diagnostic imaging, Liver enzymology, Liver Cirrhosis diagnostic imaging, Liver Cirrhosis epidemiology, Liver Cirrhosis pathology, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, RNA, Viral blood, Risk Factors, Ultrasonography, Hepatitis C complications, Liver pathology, Liver Cirrhosis etiology
- Abstract
This study was designed to investigate the value of liver biopsy in the management of patients with chronic hepatitis C virus infection and to identify risk factors for fibrosis. It was a prospective audit of clinical, biochemical, virological and radiological features for predicting liver fibrosis in 140 consecutive patients seropositive for antibody against hepatitis C virus. Seventy-five per cent of patients were asymptomatic and 69% had no clinical signs of chronic liver disease. Serum transaminase levels were normal in 44% of patients, less than twice normal in 35% and more than twice normal in 21%. Ultrasound scan was unremarkable in 85%. Sixty-nine per cent of patients were viraemic at the time of liver biopsy. Liver histology revealed that fibrosis was absent in only 10% of patients (stage 0) while cirrhosis was evident in 7% (stage 5). Liver fibrosis was detected in 90% of patients (stage 1, 11%; stage 2, 41%; stage 3, 21%; and stage 4, 10%). Univariate analysis showed that increasing age, clinical signs of chronic liver disease and abnormal ultrasound scan findings were associated with liver fibrosis (P<0.05); however, multiple linear regression analysis of all the clinical features did not reveal a useful model (sensitivity 42% and specificity 23%) for predicting liver fibrosis. Hence, no combination of clinical, biochemical, virological or radiological data was reliable in discriminating the stage of liver fibrosis in patients with chronic hepatitis C virus infection. However, older patients, especially those with clinical signs of chronic liver disease and abnormal ultrasound scan findings, were more likely to have advanced fibrosis. We recommend liver biopsy as the single most important investigation in detecting liver fibrosis. more...
- Published
- 1997
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11. The role for liver biopsy in haemophiliacs infected with the hepatitis C virus.
- Author
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Wong VS, Baglin T, Beacham E, Wight DD, Petrik J, and Alexander GJ
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Chronic Disease, Hepatitis C complications, Humans, Infant, Middle Aged, Biopsy, Hemophilia A complications, Hepatitis C pathology
- Abstract
Assessment of chronic hepatitis C virus infection requires a liver biopsy in most circumstances. There is a reluctance to perform liver biopsy in haemophiliacs because of a perceived risk of haemorrhage, although with adequate factor concentrate replacement in patients without factor concentrate inhibitors it should be safe. We report a 4-year experience of liver biopsy in patients with haemophilia infected with chronic hepatitis C virus. Of 55 patients seropositive for anti-HCV, 35 have undergone liver biopsy; the median age of this group was 33 years (range 13-68). Seven patients had a normal liver. 22 had portal tract inflammation, four with lymphoid aggregates. Mild piece-meal necrosis was observed in only two and no bile duct injury was found. 11 patients had mild mixed micro- and macro-vesicular fat. 19 patients had no evidence of fibrosis despite an estimated median duration of disease of 20 years (range 8-43). In the remaining 16 patients the maximum degree of fibrosis achieved was stage III. Patients with more significant fibrosis could not be identified on the basis of ALT or HCV RNA. There were no complications of liver biopsy in this series. Liver biopsy following a well-defined protocol in chronic hepatitis C virus haemophiliac carriers is safe in the absence of factor concentrate inhibitors. In this young group of patients without HIV infection there was no evidence of significant liver disease despite a considerable duration of disease. Performing liver biopsy allows accurate information to be given to the patient and avoids unnecessary therapy. The relative youth of this group may be important in the light of the benign histology. more...
- Published
- 1997
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12. Hepatitis C virus genomic variability in untreated and immunosuppressed patients.
- Author
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Lawal Z, Petrik J, Wong VS, Alexander GJ, and Allain JP
- Subjects
- Amino Acid Sequence, Base Sequence, DNA, Viral, Hepacivirus immunology, Humans, Liver Cirrhosis immunology, Longitudinal Studies, Molecular Sequence Data, Genetic Variation, Genome, Viral, Hepacivirus genetics, Hepatitis C immunology, Hepatitis C virology, Immune Tolerance, Liver Cirrhosis virology
- Abstract
To investigate whether immune pressure enhances the genetic diversity of the hepatitis C virus (HCV) hypervariable region 1, nucleotide sequences were compared in multiple sera, collected longitudinally, from three untreated patients and four patients undergoing liver transplantation for HCV-related cirrhosis. A minor variant became dominant in three of three patients following transplantation and persisted unchanged for months. Compared with untreated HCV carriers, transplant recipients had fewer quasispecies, fewer nucleotide changes (1.61 and 2.58/month), fewer amino acid sequence changes (0.40 and 1.94/month), as well as higher ratio of transitional to transversional mutations (2.57 and 0.98, P < 0.02) and lower replacement to silent mutations (1.33 and 8.21, P < 0.01). The two patients with the least genomic variation died of HCV graft infection. The data suggest that HCV variants which infect the graft are selected by recipient immune pressure at the time of transplant and that preferential replication in the graft is enhanced by routine immunosuppression. more...
- Published
- 1997
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13. Reactivity of synthetic peptides representing selected sections of hepatitis C virus core and envelope proteins with a panel of hepatitis C virus-seropositive human plasma.
- Author
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Jackson P, Petrik J, Alexander GJ, Pearson G, and Allain JP
- Subjects
- Amino Acid Sequence, Antibody Specificity immunology, Blood Donors, Cross Reactions immunology, Enzyme-Linked Immunosorbent Assay, Genome, Viral, Haptens immunology, Hepacivirus genetics, Hepatitis C blood, Hepatitis C genetics, Hepatitis C Antibodies blood, Humans, Molecular Sequence Data, Polymerase Chain Reaction, Serum Albumin, Bovine immunology, Hepacivirus chemistry, Hepacivirus immunology, Hepatitis C immunology, Hepatitis C Antibodies immunology, Peptides chemical synthesis, Peptides immunology, Viral Core Proteins immunology, Viral Envelope Proteins immunology
- Abstract
A series of 54 synthetic peptides, 15-20 residues long, that represented selected parts of the structural proteins of hepatitis C virus (HCV) were tested for immunoreactivity with a panel of 45 plasma samples from potential blood donors who were known to be seropositive for anti-HCV. Most of the ten peptides that represented the core protein showed reactivity with most of the panel samples. All except one of the 20 peptides that represented non-hypervariable regions of envelope proteins E1 and E2 showed little or no reactivity. In contrast, 18 of the the 24 peptides that represented variants of the hypervariable region 1 of the E2 protein reacted with at least one panel sample. Notably, 40% of the panel samples cross-reacted with two or more different peptides sequences some of which differed by more than 50%. Two panel samples each cross-reacted with seven different peptide sequences. The results suggest a broad anti-hypervariable region antibody specificity in many anti-HCV-seropositive samples and possible limits on the mutability of hypervariable region sequences. The work contributes to understanding the immunogenicity and persistence of HCV. more...
- Published
- 1997
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14. Fibrosis and other histological features in chronic hepatitis C virus infection: a statistical model.
- Author
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Wong VS, Wight DG, Palmer CR, and Alexander GJ
- Subjects
- Adolescent, Adult, Aged, Bile Ducts pathology, Female, Hepatitis C immunology, Hepatitis, Chronic immunology, Humans, Inflammation, Liver immunology, Liver Cirrhosis virology, Male, Middle Aged, Necrosis, Prospective Studies, Hepatitis C pathology, Hepatitis, Chronic pathology, Liver pathology, Liver Cirrhosis pathology
- Abstract
Aims: To study the inter-relation between hepatic fibrosis and other histological features of chronic hepatitis C virus (HCV) infection., Methods: Liver biopsy specimens from 200 consecutive patients with chronic HCV infection were graded and staged separately for necro-inflammatory activity and for fibrosis. The interaction between fibrosis and other histological features was evaluated by univariate and multivariate analysis, followed by hierarchical log linear modelling., Results: The most striking feature was the presence of portal tract inflammation in 177 (89%) of 200 samples. Lymphoid aggregates/follicles were observed either alone or as part of the general inflammatory infiltration of the portal tracts in 120 (60%) of 200 samples. Fatty change (macro- and microvesicular steatosis) was observed in 76 (38%) samples: mild to moderate in 60 (30%) and diffuse in 16 (8%). Bile duct damage was found in 30 (15%) of 200 specimens. Lobular activity was found in 154 (77%) of 200 samples and was significant in 44; piecemeal necrosis was present in 79 (40%). Thirty one (16%) patients had stage 0 liver fibrosis, 27 (14%) had stage 1, 69 (35%) had stage 2, 43 (22%) had stage 3, 16 (8%) had stage 4, and 12 (6%) had stage 5. On log linear analysis, piecemeal necrosis, lobular inflammation and steatosis were linked directly with fibrosis. Portal tract inflammation was linked directly and indirectly via piecemeal necrosis and lobular inflammation with fibrosis. The presence of lymphoid aggregates was associated with bile duct damage., Conclusions: Portal tract inflammation with lymphoid aggregates or follicles, together with fatty change, bile duct damage and/or lobular activity, are characteristic of chronic HCV infection, confirming previous reports. Piecemeal necrosis, lobular inflammation, portal inflammation, and steatosis are linked directly with fibrosis in this statistical model, suggesting a close inter-relation in the development of fibrosis/cirrhosis. more...
- Published
- 1996
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15. Prospective study of hepatitis B vaccination in patients with chronic hepatitis C.
- Author
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Wong V, Wreghitt TG, and Alexander GJ
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- Adult, Chronic Disease, Female, Humans, Male, Prospective Studies, Risk-Taking, Substance Abuse, Intravenous complications, Vaccination, Hepatitis B prevention & control, Hepatitis B Vaccines, Hepatitis C complications
- Published
- 1996
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16. Incidence, character and clinical relevance of mixed cryoglobulinaemia in patients with chronic hepatitis C virus infection.
- Author
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Wong VS, Egner W, Elsey T, Brown D, and Alexander GJ
- Subjects
- Adult, Aged, Base Sequence, Blood Donors, Chronic Disease, Complement C3 analysis, Cryoglobulinemia epidemiology, DNA Primers chemistry, Female, Hepacivirus immunology, Hepatitis Antibodies immunology, Hepatitis B complications, Humans, Kidney physiopathology, Male, Middle Aged, Molecular Sequence Data, RNA, Viral analysis, Rheumatoid Factor analysis, Cryoglobulinemia complications, Hepatitis C complications
- Abstract
Hepatitis C virus (HCV) infection has been implicated in the pathogenesis of mixed cryoglobulinaemia. Several studies have shown the presence of anti-HCV antibodies and HCV-RNA in both sera and cryoglobulins of such patients. However, the prevalence and clinical significance of cryoglobulins remain uncertain in patients with chronic HCV infection. We have studied 113 consecutive patients referred for assessment because of the presence of anti-HCV antibody in serum for the presence of cryoglobulinaemia and ascertained their clinical relevance and immunochemical properties. Twenty-one of 113 (19%) had detectable cryoglobulins with a mean protein concentration of 0.38 g/l (range 0.15-3.34 g/l). Most of these patients were asymptomatic. The cryoglobulins were of type III in 19 (91%) and of type II in two patients (9%). The latter two patients had the highest concentration of cryoglobulins, subnormal C4 and C1q levels suggesting classical pathway activation and vasculitis with renal impairment. The cryoglobulin IgG subclasses were mainly IgG1 and IgG3. HCV-RNA was detected more frequently in the sera of cryoglobulin-positive patients than in cryoglobulin-negative patients. This study showed that mixed cryoglobulinaemia is common in chronic HCV infection, and is predominantly type III. Evidence of systemic or renal disease was rare except in those with type II cryoglobulinaemia, and this may reflect either the concentration of the cryoprecipitate or the presence of a monoclonal complement-activating IgM paraprotein. The detection of HCV-RNA in the majority of the cryoprecipitates further supports the important role of HCV in the etiopathogenesis of essential mixed cryoglobulinaemia, although the mechanism is at present unclear. more...
- Published
- 1996
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17. High prevalence of hepatitis C infection in Afro-Caribbean patients with type 2 diabetes and abnormal liver function tests.
- Author
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Gray H, Wreghitt T, Stratton IM, Alexander GJ, Turner RC, and O'Rahilly S
- Subjects
- Adult, Africa ethnology, Alanine Transaminase blood, Alkaline Phosphatase blood, Black People, Caribbean Region, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 therapy, Diet, Diabetic, Female, Follow-Up Studies, Hepacivirus immunology, Hepatitis Antibodies blood, Hepatitis C complications, Hepatitis C diagnosis, Hepatitis C Antibodies, Humans, Hypoglycemic Agents therapeutic use, Insulin therapeutic use, Liver Function Tests, Male, Middle Aged, Prevalence, Prospective Studies, Time Factors, Treatment Outcome, White People, Diabetes Mellitus, Type 2 complications, Hepatitis C epidemiology
- Abstract
Moderate elevations of serum transaminases are frequently found in patients with diabetes mellitus and are often attributed to fatty infiltration of the liver without further investigation. Recent studies of patients with end-stage liver disease have suggested a possible association between Hepatitis C virus (HCV) antibody positivity and the development of diabetes (mostly Type 2). As a first step in the examination of any potential association between HCV and Type 2 diabetes in subjects without overt liver disease, we examined 200 British patients with Type 2 diabetes (100 White Caucasians, 50 Asians, and 50 Afro-Caribbeans), recruited from the United Kingdom Prospective Study of Diabetes, half of whom had a significant elevation of alanine aminotransferase (ALT) on at least two occasions and half of whom had consistently normal ALT levels. In Afro-Caribbean Type 2 diabetic subjects 7/25 (28%) patients with abnormal ALT and 1/25 (4%) with normal ALT were HCV antibody positive. Among White Caucasian subjects 6/50 (12%) patients with abnormal LFTs and 0/50 with normal LFTs were HCV antibody positive and in Asians the prevalence was 2/25 (8%) and 0/25, respectively. This study suggests that persistent mild to moderate elevation of serum transaminases in a patient with Type 2 diabetes should not automatically be attributed to the metabolic disturbances of diabetes. Particularly in Afro-Caribbean subjects, HCV infection is a major diagnostic consideration. The question of whether HCV infection itself may have a diabetogenic action is worthy of further investigation. more...
- Published
- 1995
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18. Evidence for a link between hepatitis C virus infection and diabetes mellitus in a cirrhotic population.
- Author
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Allison ME, Wreghitt T, Palmer CR, and Alexander GJ
- Subjects
- Adult, Female, Humans, Incidence, Male, Middle Aged, Regression Analysis, Retrospective Studies, Diabetes Complications, Diabetes Mellitus epidemiology, Hepatitis C complications, Liver Cirrhosis complications
- Abstract
Abnormalities of carbohydrate metabolism, including hyperinsulinaemia and insulin resistance, are well recognised complications of cirrhosis. While diabetes mellitus can be explained in many instances on the basis of coincident pancreatic disease, in most the characteristic glucose intolerance of cirrhosis is not readily explicable. A previous clinical observation that hepatitis C virus infection and diabetes mellitus appeared to be associated was formally tested by a retrospective review of 100 consecutive adult patients with cirrhosis undergoing assessment for liver transplantation. Hepatitis C virus was diagnosed by conventional serological and histological criteria. Twenty-three patients had diabetes mellitus, of whom 18 were being treated with insulin. Of the 34 patients with hepatitis C virus-related cirrhosis, 17 (50%) had diabetes mellitus, in contrast to just six (9%) of the 66 patients with cirrhosis unrelated to hepatitis C virus (chi2 = 19.1, p < 0.0001) with an odds ratio for hepatitis C virus by diabetes mellitus status 10.0 (95% confidence interval 3.4 to 29.3). Hierarchical loglinear model analysis of those factors of potential relevance to the development of diabetes mellitus revealed that only hepatitis C virus interacted significantly with diabetes mellitus while the relation between diabetes mellitus and origin, sex, body mass index and severity of cirrhosis was conditional. By multiple logistic regression analysis of diabetes mellitus status in relation to the same variables, only hepatitis C virus status was statistically significant (p < 0.0001). Origin, sex, severity of cirrhosis, body mass index and therapy were not significantly associated.(ABSTRACT TRUNCATED AT 250 WORDS) more...
- Published
- 1994
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19. Association of type III cryoglobulinaemia and hepatitis C virus-related cirrhosis.
- Author
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Goffin E, Oliveira DB, Alexander GJ, Wreghitt T, Lockwood CM, Keogan M, and Allain JP
- Subjects
- Female, Humans, Liver Cirrhosis microbiology, Middle Aged, Cryoglobulinemia complications, Hepatitis C complications, Liver Cirrhosis complications
- Published
- 1992
20. Hepatitis C, D and E virus infection.
- Author
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Sheron N and Alexander GJ
- Subjects
- Adolescent, Adult, Carrier State prevention & control, Child, Hepacivirus genetics, Hepacivirus immunology, Hepatitis Delta Virus genetics, Hepatitis Delta Virus immunology, Humans, Interferons therapeutic use, Hepatitis C prevention & control, Hepatitis C transmission, Hepatitis D prevention & control, Hepatitis D transmission
- Published
- 1990
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21. The interaction of genetic determinants in the outcome of HCV infection: evidence for discrete immunological pathways
- Author
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Hydes, T. J., Moesker, B., Traherne, J. A., Ashraf, S., Alexander, G. J., Dimitrov, B. D., Woelk, C. H., Trowsdale, J., and Khakoo, S. I.
- Subjects
Liver Cirrhosis ,Genotype ,Remission, Spontaneous ,Gene Expression ,Hepacivirus ,Genetic Heterogeneity ,tapasin ,Receptors, KIR ,Humans ,IFN‐λ3/4 ,Retrospective Studies ,Interleukins ,Histocompatibility Antigens Class I ,Histocompatibility Antigens Class II ,Membrane Transport Proteins ,Epistasis, Genetic ,Original Articles ,interferon ,Hepatitis C, Chronic ,Prognosis ,immunogenetics ,Logistic Models ,Host-Pathogen Interactions ,Multivariate Analysis ,killer cell immunoglobulin receptors ,Disease Progression ,Original Article ,Interferons ,hepatitis C - Abstract
Diversity within the innate and adaptive immune response to hepatitis C is important in determining spontaneous resolution (SR) and treatment response. The aim of this study was to analyze how these variables interact in combination; furthering our understanding of the mechanisms that drive successful immunological clearance. Multivariate analysis was performed on retrospectively collected data for 357 patients previously genotyped for interferon (IFN)‐λ3/4, killer cell immunoglobulin (KIR), human leukocyte antigen (HLA) class I and II and tapasin. High resolution KIR genotyping was performed for individuals with chronic infection and haplotypes determined. Outcomes for SR, IFN response and cirrhosis were examined. Statistical analysis included univariate methods, χ2 test for trend, multivariate logistic regression, synergy and principal component analysis (PCA). Although KIR2DL3:HLA‐C1C1 (P = 0.027), IFN‐λ3/4 rs12979860 CC (P = 0.027), tapasin G in individuals with aspartate at residue 114 of HLA‐B (TapG:HLA‐B114D) (P = 0.007) and HLA‐DRB1*04:01 (P = 0.014) were associated with SR with a strong additive influence (χ2 test for trend P < 0.0001); favorable polymorphisms did not interact synergistically, nor did patients cluster by outcome. In the treatment cohort, IFN‐λ3/4 rs12979860 CC was protective in hepatitis C virus (HCV) G1 infection and KIR2DL3:HLA‐C1 in HCV G2/3. In common with SR, variables did not interact synergistically. Polymorphisms predictive of viral clearance did not predict disease progression. In summary, different individuals resolve HCV infection using discrete and non‐interacting immunological pathways. These pathways are influenced by viral genotype. This work provides novel insights into the complexity of the interaction between host and viral factors in determining the outcome of HCV infection. more...
- Published
- 2015
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