Hepatitis C genotype 1.

PURPOSE OF REVIEW: To assess advances in the treatment of genotype 1 (G1 hepatitis C virus), in particular, the development of new interferon (and ribavirin)-free treatment regimes. RECENT FINDINGS: The treatment of hepatitis C has advanced rapidly over the last 24 months. Newer interferon-containing regimes have been developed with improved tolerability, and interferon-free regimes with outstanding efficacy and improved tolerability have been developed. SUMMARY: New treatment regimes for hepatitis C virus have significantly altered the outlook for patients with hepatitis C. New interferon-containing treatment regimes with simeprevir and sofosbuvir, which have improved response rates, have shorter treatment durations and fewer side-effects are becoming available, and interferon-free regimes have been developed. The interferon-free regimes involve multidrug combinations or two-drug combinations and offer the possibility of shorter treatment duration with 8 or 12 weeks. The efficacy of the interferon-free regimes is striking with response rates of well over 90% reported in a wide range of different patient populations. The rapid progress in the treatment of hepatitis C will hopefully result in a cure for most patients, thereby significantly decreasing the morbidity and mortality associated with hepatitis C virus infection.

Non-invasive markers of liver fibrosis in fatty liver disease are unreliable in people of South Asian descent.

OBJECTIVE: Liver biopsy is the most accurate method for determining stage and grade of injury in non-alcoholic fatty liver disease (NAFLD). Given risks and limitations of biopsy, non-invasive tests such as NAFLD fibrosis score, aspartate transaminase (AST) to platelet ratio index, Fib-4, AST/alanine transaminase ratio and BARD are used. Prevalence and severity of NAFLD and metabolic syndrome vary by ethnicity, yet tests have been developed in largely white populations. We tested our hypothesis that non-invasive tests that include metabolic parameters are less accurate in South Asian compared with white patients. DESIGN: Retrospective cross-sectional. SETTING: Specialist liver centre. PATIENTS: Patients with histologically confirmed NAFLD. INTERVENTIONS: Scores calculated using clinical data taken within 1 week and compared with histology (Kleiner). MAIN OUTCOME MEASURES: Diagnostic test characteristics. RESULTS: 175 patients were identified. South Asians (n=90) were younger, had lower body mass index and lower proportion of obesity compared with white patients (n=79), with comparable rates of diabetes and liver injury. Tests are less sensitive at detecting advanced fibrosis in South Asian compared with white patients. Relative risk of correct diagnosis in white patients compared with South Asians is 1.86 (95% CI 1.4 to 2.6). In binary logistic regression models, ethnicity and platelet count predicted accuracy. Transient elastography was equally and highly accurate in both ethnicities. CONCLUSIONS: Blood test-based non-invasive scores are less accurate in South Asian patients, irrespective of metabolic parameters. Ethnicity should be considered when devising risk-stratification algorithms for NAFLD.

The molecular mechanisms of vascular restenosis: Which genes are crucial?

Many patients with coronary heart disease undergo percutaneous transluminal coronary angioplasty (PTCA) to improve myocardial tissue perfusion. However, a major complication after revascularisation procedures is restenosis of the injured artery. The molecular mechanism involved is not fully elucidated and no successful treatment is currently available. Animal models are preliminary tools that can help improve our understanding of the pathogenesis and treatment of restenosis in humans. Attracted by well-defined genetic systems, a number of investigators began to use the mouse as an experimental system for restenosis research. They demonstrated that several stages involved in this process include thrombus formation, inflammatory cell infiltration and smooth muscle cell (SMC) accumulation to form neointimal lesions. By using transgenic and knockout mice a number of genes related to these processes have been found to play a major role in mediating lesion formation, e.g. the plasminogen system, matrix metalloproteinases (MMP), adhesion molecules, cytokines and signal transducers. This review will not attempt to cover all aspects of related genes or molecules, but will rather focus on several groups of genes, by which the major progress in understanding the mechanisms of the disease has been made. The information obtained by using animal models could be essential for a better understanding of the pathogenesis of restenosis in humans and to provide a basis for therapeutic intervention.

Hepatitis E infection is an under recognized cause of acute decompensation in patients with chronic liver disease.

BACKGROUND/AIMS: We aimed to assess characteristics of patients with a positive hepatitis E virus serology with emphasis on acute on chronic liver disease. METHODS: This was a retrospective audit performed at a large teaching hospital. RESULTS: Of the 164 patients tested, 15(9.1%) had a positive serology (hepatitis E virus IgG and or IgM) of whom two also had a positive hepatitis E virus RNA. Six (42.8%) had underlying chronic liver disease and presented with deteriorating liver tests±decompensation. In one patient (16%) acute hepatitis E virus infection was the aetiology for the decompensation and in three the positive hepatitis E virus IgG was a reflection of prior subclinical infection. However, in two of the six patients with unexplained decompensation there was delay (150-270 days) in obtaining a hepatitis E virus serology, which may have resulted in a negative hepatitis E virus IgM at time of testing. CONCLUSIONS: 9.1% of patients presenting with abnormal liver tests at a large teaching hospital in south east England have a positive hepatitis E virus serology of whom 42.8% have acute on chronic liver disease. In 16% hepatitis E virus infection is the aetiology for the acute decompensation. This may be an under representation as in >30% of patients with unexplained decompensation there is considerable delay in requesting a hepatitis E virus serology.