A study of the natural history of hepatitis C infection within a geographically determined population (Trent HCV study)

Lawson, Adam (2012) A study of the natural history of hepatitis C infection within a geographically determined population (Trent HCV study). DM thesis, University of Nottingham.

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Abstract

The epidemiology and natural history of Hepatitis C has been studied in a large geographically determined population (Trent HCV study).

It has previously been suggested that patients with Hepatitis C and a persistently normal Alanine aminotransferase (PNALT) represent a group of patients with mild disease and at low risk of disease progression. Patients with PNALT were, therefore, compared to those with an elevated ALT. The majority of patients initially fulfilling the definition of a PNALT had an abnormal ALT within 3 years of follow-up. They also demonstrated similar rates of fibrosis progression as a sub-group of HCV infected patients with an elevated ALT who were re-biopsied prior to any institution of therapy. They, therefore, warrant the same consideration with regard to treatment.

The morbidity and mortality associated with Hepatitis C with severe fibrosis was assessed in a group of patients with a liver biopsy demonstrating Ishak fibrosis stage  4. A worse prognosis than previously reported was observed for this patient population. Once decompensation develops, HCV infection is associated with a high mortality rate. Indicators of poor synthetic liver function and hypergammaglobulinaemia were important prognostic factors for mortality, while combination antiviral therapy was associated with improved survival.

The majority of HCV infected patients (75%) diagnosed with hepatocellular carcinoma (HCC) were known to have cirrhosis at least 6 months prior to diagnosis of HCC and were, therefore, amenable to surveillance. There was a variable application of surveillance, however, and no significant improvement in survival was demonstrated. Age, duration of infection and immunoglobulin G levels were associated with an increased risk of HCC in cirrhotic patients in the univariate analysis. Achieving an SVR was associated with a reduced risk. No variable in cirrhotic patients was shown to be independently associated with HCC in the multivariate analysis.

A comparison of disease progression and treatment outcome in White and Asian (Indian subcontinent) patients was made. Asian patients generally presented at an older age and with more severe disease on biopsy. The patient’s ethnic group was not associated with the likelihood of either an SVR or completion of therapy. Instead cirrhosis and a raised GGT were associated with a failure to achieve SVR in the multivariate analysis.

The platelet count is a surrogate marker for the severity of liver fibrosis and correlates with the Ishak fibrosis stage. An analysis of factors associated with an SVR was performed. In the multivariate model, age at start of treatment was the only independent predictor of SVR in Genotype 1, while estimated duration of infection and Ishak stage were predictors in genotype 2/3 patients. The platelet count was not an independent predictor of SVR or completion of therapy.

Item Type:Thesis (DM)
Supervisors:Irving, W.L.
Faculties/Schools:UK Campuses > Faculty of Medicine and Health Sciences > School of Molecular Medical Sciences
ID Code:2477
Deposited By:Dr Adam Lawson
Deposited On:11 Oct 2012 15:26
Last Modified:11 Oct 2012 15:26

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