Objectives: To compare the rate of hepatic fibrosis progression in hepatitis C virus (HCV) infected and human immunodeficiency virus (HIV)-HCV coinfected patients, and to identify factors that may influence fibrosis progression. Patients and methods: A total of 153 HCV infected and 55 HCV-HIV coinfected patients were identified from two London hospitals. Eligible patients had known dates of HCV acquisition, were HCV-RNA positive, and had undergone a liver biopsy, which was graded using the Ishak score. Univariate and multivariate logistic regression analyses were used to identify factors associated with fibrosis progression rate and the development of advanced fibrosis (stages 3 and 4). Results: The estimated median fibrosis progression rate was 0.17 units/year (interquartile range (IQR) 0.10-0.25) in HIV-HCV coinfected and 0.13 (IQR 0.07-0.17) in HCV monoinfected patients (p=0.01), equating to an estimated time from HCV infection to cirrhosis of 23 and 32 years, respectively. Older age at infection (p<0.001), HIV positivity (p=0.019), higher alanine aminotransferase (ALT) level (p=0.039), and higher inflammatory activity (p<0.001) on first biopsy were all independently associated with more rapid fibrosis progression. ALT was correlated with histological index (r=0.35, p<0.001). A CD4 cell count <250×10 6 /l was independently associated with advanced liver fibrosis (odds ratio 5.36 (95% confidence interval 1.26-22.79)) and was also correlated with a higher histological index (r=−0.42, p=0.002). Conclusion: HIV infection modifies the natural history of HCV by accelerating the rate of fibrosis progression by 1.4 fold, and the development of advanced fibrosis threefold. A low CD4 cell count was independently associated with advanced disease and correlated with higher histological index, which suggests that early antiretroviral therapy may be of benefit in slowing HCV progression in coinfected patients. N umerous seroprevalence studies have shown a high rate of coinfection with hepatitis C virus (HCV) among human immunodeficiency virus 1 (HIV-1) infected patients, ranging from 3-15% in homosexual/bisexual men to approximately 80% among injecting drug users and 98% among haemophiliacs.

Varicella is a common contagious infection in childhood with increasing incidence in adults. Pneumonia, although rare, is the most serious complication that commonly affects adults. Over the last two decades there have been major advances in the understanding of Varicella infections, management and prevention. This review discusses the epidemiology, pathogenesis, pulmonary manifestation, morbidity, longterm clinical consequences and current state of management of Varicella pneumonia in adults. Prevention and other disease-modifying therapy are also discussed.

Background-The epidemiology and natural history of hepatitis C virus (HCV) infection in the UK are uncertain. Previous reports are from small or selected populations such as blood donors or tertiary referral centres. Aims-To study the epidemiology and natural history of HCV infection. Methods-Prospective study incorporating five centres within the Trent region. Patients were managed and followed up according to a commonly agreed protocol. Subjects-A total of 1128 HCV positive patients. Patients with haemophilia, human immunodeficiency virus, and chronic renal failure were excluded. Results-Between September 1991 and December 1998, 2546 anti-HCV positive patients were identified of whom 1128 (44%) were enrolled in the cohort. A risk factor(s) for infection was identified in 93.4% of patients who completed the questionnaire; 81% of patients were HCV RNA positive. A total of 397 initial liver biopsies were scored by a single pathologist. These showed a correlation between high alcohol intake and fibrosis score. Multivariate analysis showed fibrosis to be associated with age over 40, past evidence of hepatitis B virus infection, and higher necroinflammatory grade but not with sex, viral genotype, maximum known alcohol intake, estimated duration of infection, or mode of transmission. Twelve (7.8%) of 153 patients who received interferon therapy had sustained serum virus clearance. Sixty six patients have died during the follow up period, 31 with a liver related cause of death. This represents a considerable excess over the expected death rate for a cohort of this age and sex distribution. Conclusions-HCV infection is an emerging health problem in the Trent region. Identifying risk factors for infection and disease severity will enhance understanding and facilitate improved intervention. An excess mortality in infected individuals is already evident in this unselected cohort. (Gut 2001;48:707-713)

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