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Title: The natural history and treatment of hepatitis C in the South-East of Scotland
Author: Delahooke, Toby Edward Stuart
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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Background: Since the discovery of Hepatitis C there have been studies of the natural history of the infection. The outcome is dependent on whether the research is performed in the community or in hospital and where the patients are drawn from. Scotland is a country with a low prevalence of Hepatitis C infection but Edinburgh has a large intravenous drug using population in whom the prevalence is high. The Royal Infirmary of Edinburgh is the main tertiary centre for the assessment and treatment of these patients. Aim: Describe the characteristics of those patients that have ongoing Hepatitis C infection that have been referred and assessed. Describe the progression of the disease to cirrhosis and its complications. Identify the independent factors that influence this progression. Describe the outcome of treatment with interferon monotherapy, combination standard interferon and ribavirin and combination pegylated interferon and ribavirin, and identify the predictors of response. Methods: All patients that have been referred to the Royal Infirmary of Edinburgh and assessed between 1990 and 2004 with Hepatitis C infection. Retrospective analysis of the patient's case notes, laboratory, pathology and endoscopy records was performed. There was entry of data into a specially constructed Microsoft Access relational database. Kaplan-Meier analysis was used to describe progression. Cox regression analysis was used to identify independent predictors of progression. A sustained viral response was the primary end-point of the treatment studies, with binary logistical regression to identify predictors of this outcome. Documentation of adverse events for each treatment was made. Results: Six hundred and ninety-four patients were identified that have ongoing infection. This cohort was made up of a significant proportion of middle-aged men who have acquired the infection less than 20 years ago, principally through intravenous drug use, who have a significant history of alcohol abuse. At least 22% of patients have had cirrhosis diagnosed clinically, although only about half of these have had it confirmed by biopsy or laparoscopy. In 12% of patients at least one complication of cirrhosis has been recorded. Grade 2 oesophageal varices have been found in about 7% of patients overall, but only half of these have bled. A major complication of cirrhosis has occurred in 10.5% and Hepatocellular carcinoma (HCC) in 3.3%. So far only 13 patients have been transplanted. Eleven percent of the cohort has died and in those in whom the cause is known, liver-related death is twice as common as non-liver-related death. It has not been possible to establish a median time from infection to cirrhosis or its complications but it appears to be in excess of 35 years. The age of the patient and previous alcohol intake of greater than 50 units per week for more than five years independently influences progression. A steady improvement in the efficacy of treatment with the introduction of each new treatment regime has been confirmed. In interferon nai've patients, treated with pegylated interferon and ribavirin, the sustained viral response rate was 29.0% and 59.3% for genotype 1 and genotype 2 or 3 infections respectively. Significant side effects occurred with treatment that necessitated both dose reduction and sometimes its termination. About 45% of all patients referred and assessed each year were deemed suitable for treatment and listed. Conclusion: Chronic Hepatitis C infection is a significant health problem in Edinburgh with large numbers being referred for assessment, treatment and management of the complications of cirrhosis. The natural history of the infection and how it is influenced by therapy is becoming clearer, in particular the influence of alcohol and the age of the patient. Treatments are effective, although do have significant side effects that affect compliance.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available