Retrospective cohort study of liver transplantation in the United Kingdom between 1994 and 2010: the impact of hepatitis C infection.

BACKGROUND: Liver transplantation is an important and established treatment option for chronic hepatitis C virus (HCV) related end-stage liver disease (HCV-related ESLD). This study describes trends in elective liver transplantation among persons with HCV-related ESLD. STUDY DESIGN: Retrospective cohort. METHODS: Analyses of United Kingdom (UK) Transplant Registry data for the period 1994 to 2010, with follow-up information extending to 2011. RESULTS: Annual registrations for liver transplantation increased linearly and alcoholic liver cirrhosis (2075, 24%) and HCV-related ESLD (1213, 14%) were the most common indications. HCV-related ESLD patients were mainly aged 40-49 years (32%) and 50-59 years (43%); males (76%); and of white ethnicity (74%). Overall, 75% (956/1213) received a liver transplant with a linear increase over the period (OR 1.11, 95% CI 1.08, 1.13). Pre transplant mortality was unchanged (adjusted OR 1.0, 95% CI 0.96, 1.05) and post-transplant mortality decreased in both HCV-related (adjusted OR 0.77, 95% CI 0.68, 0.88) and non-HCV-related ESLD (adjusted OR 0.82, 95% CI 0.75, 0.89) patients. CONCLUSION: The increase in demand for and receipt of liver transplants among persons with HCV-related ESLD requires coordinated efforts to increase not only organ donation, but investment in HCV prevention programmes and improved access to hepatitis C treatment services.

Hydroxychloroquine, hydroxyurea and didanosine as initial therapy for HIV-infected patients with low viral load: safety, efficacy and resistance profile after 144 weeks.

OBJECTIVES: To evaluate the long-term safety and efficacy of the combination of hydroxychloroquine, hydroxyurea and didanosine. METHODS: We recruited antiretroviral-naive patients with viral loads less than 100 000 HIV-1 RNA copies/mL and CD4 counts greater than 150 cells/microL. All patients received hydroxychloroquine (200 mg), hydroxyurea (500 mg) and didanosine (125-200 mg) twice daily. Clinical and laboratory safety assessments and measurements of viral load and CD4 count were made at regular intervals, and genotypic resistance testing was performed on samples with detectable viral load at 48, 96 and 144 weeks. RESULTS: Fourteen of the 17 patients who commenced therapy remained on treatment at 144 weeks. Treatment was well tolerated but caused neutropenia, usually mild and transient, in 12 patients (71%). Mean viral load was reduced by 1.6 log(10) copies/mL below baseline (P<0.001), eight patients (47%) had undetectable viral load (<400 copies/mL), and two patients (12%) had detectable viral load but no detectable resistance mutations at week 144. Four patients (24%) had detectable viral load together with major resistance mutations (three with both 74 V and 184 V, and one with both 62 V and 65R) at week 144, but still had viral load suppression below baseline. Mean CD4 count was increased by 106 cells/microL above baseline (P=0.07) at week 144. CONCLUSIONS: This novel and well-tolerated combination controls viral replication during long-term follow up, with development of few resistance mutations. With careful monitoring it may be a useful strategy for delaying highly active antiretroviral therapy (HAART) and associated toxicity in selected patients with low initial viral loads.

Correlation of baseline quantitative plasma human immunodeficiency (HIV) type 1 RNA viral load with clinical status and CD4+ T-cell counts in treatment-naïve HIV-positive patients in Singapore.

INTRODUCTION: Quantitative measurement of plasma HIV-1 RNA viral load has been available in Singapore since 30 November 1996. This study investigates the relationship, in antiretroviral-naïve, HIV-positive Singapore residents, between the baseline HIV-1 RNA viral load and clinical status at the time of quantification. The association of HIV-1 RNA viral load with CD4+ T-cell counts was also studied. MATERIALS AND METHODS: HIV-1 RNA viral load was determined using Amplicor HIV-1 Monitor Test. One hundred and eighty subjects had baseline plasma HIV-1 RNA levels quantified during the period 30 November 1996 to 27 July 1998. They were classified into three clinical groups: A for asymptomatic infection (n = 110), B for symptomatic infection (n = 29) and C for AIDS (n = 41). RESULTS: The differences between mean HIV-1 RNA levels were statistically significant (P < 0.001) for groups A and B (mean difference = -0.61 log10), and for groups A and C (mean difference = -0.75 log10). However, there was no statistically significant difference (P = 0.68) between groups B and C (mean difference = -0.13 log10). Of those subjects with CD4+ T-cell counts measured within 30 days of viral load quantification, there were statistically significant negative correlations between HIV-1 viral load and CD4+ T-cell counts for groups A (n = 91, r = -0.536, P < 0.01) and C (n = 34, r = -0.446, P < 0.01) but not group B (n = 26, r = -0.297, P > 0.05). CONCLUSION: This suggest that the more advanced the phase of HIV infection, the higher the baseline plasma viral load and the lower the CD4+ T-lymphocyte counts.