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
