Comparison of LI-RADS with other non-invasive liver MRI criteria and radiological opinion for diagnosing hepatocellular carcinoma in cirrhotic livers using gadoxetic acid with histopathological explant correlation.

AIM: To establish the diagnostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) for hepatocellular carcinoma (HCC) and compare its performance to that of international criteria from European Assofor the Study of the Liver (EASL), Japan Society of Hepatology (JSH), Asian Pacific Association for the Study of the Liver (APASL), and Organ Procurement and Transplantation Network (OPTN), and to the reporting radiologist's overall opinion regarding the probability of a nodule being a HCC by correlating with a histological diagnosis from whole liver explants. MATERIALS AND METHODS: The present single-centre, retrospective review selected participants based on the following criteria: adults (≥18 years) listed for liver transplantation in 2014/2015, with liver cirrhosis at the time of magnetic resonance imaging (MRI) with hepatocyte specific contrast agent, and at least one liver lesion ≥10 mm on MRI with histology from subsequent liver explant for comparison. Each lesion was assessed against international criteria and given a "radiologist opinion" score of 1-5 (1 = definitely benign, 5 = definitely HCC). RESULTS: Total 268 patient records were reviewed, with 105 eligible lesions identified from 47 patients. Median lesion size was 15.5 mm (range 10-68 mm). Sensitivity (%), specificity (%), and positive predictive value (PPV; %) for LI-RADS LR5 was 45, 89, and 89, for LI-RADS LR4+5 + TIV was 61, 80, and 86, for EASL was 44, 86 and 86, for JSH/APASL was 64, 81, and 87, for OPTN was 36, 90, and 88, and for "radiologist impression" of probably or definitely HCC was 79, 79, and 88 respectively. CONCLUSIONS: MRI has moderate sensitivity and good specificity for the diagnosis of HCC with considerable variation depending on criteria used. OPTN criteria have the best specificity, but low sensitivity. "Radiologist opinion" gives highest overall accuracy with increases in sensitivity and reduction in specificity when compared to the imaging criteria.

The effects of phytoestrogens on postmenopausal health.

Phytoestrogens are a group of non-steroidal polyphenolic plant-based substances, commonly used for the treatment of menopause-related conditions. They have both genomic and non-genomic effects, displaying weak affinity for estrogen receptors (ER) and preferentially binding to ER-B over ER-A. However, evidence for the benefits of phytoestrogen consumption has been limited. We conducted a review of recent literature, focusing on systematic reviews and meta-analyses reporting on postreproductive health effects of phytoestrogens. While many trials concerning dietary and supplementary phytoestrogens have been conducted, evidence of clinical efficacy is heterogeneous and inconclusive. There appears to be reduction in the vasomotor symptoms of menopause with phytoestrogen intake; however, it is likely small and slow in onset. Phytoestrogens also appear to improve bone mineral density and markers of cardiovascular risk; however, there is inadequate research regarding long-term outcomes. There appear to be no harmful effects of phytoestrogens on breast, endometrial cancer or colorectal cancer and phytoestrogens intake may in fact be protective. Research regarding the effect of phytoestrogens on cognition is mixed, with most studies reporting no significant association. Overall, individual variations in the metabolism of phytoestrogens and age-related genomic effects may account for the considerable variability in the measured effects of phytoestrogens.

Food waste management during the COVID-19 outbreak: a holistic climate, economic and nutritional approach.

Improving the food supply chain efficiency has been identified as an essential means to enhance food security, while reducing pressure on natural resources. Adequate food loss and waste (FLW) management has been proposed as an approach to meet these objectives. The main hypothesis of this study is to consider that the "strong fluctuations and short-term changes" on eating habits may have major consequences on potential FLW generation and management, as well as on GHG emissions, all taking into account the nutritional and the economic cost. Due to the exceptional lockdown measures imposed by the Spanish government, as a consequence of the emerging coronavirus disease, COVID-19, food production and consumption systems have undergone significant changes, which must be properly studied in order to propose strategies from the lessons learned. Taking Spain as a case study, the methodological approach included a deep analysis of the inputs and outputs of the Spanish food basket, the supply chain by means of a Material Flow Analysis, as well as an economic and comprehensive nutritional assessment, all under a life cycle thinking approach. The results reveal that during the first weeks of the COVID-19 lockdown, there was no significant adjustment in overall FLW generation, but a partial reallocation from extra-domestic consumption to households occurred (12% increase in household FLW). Moreover, the economic impact (+11%), GHG emissions (+10%), and the nutritional content (-8%) complete the multivariable impact profile that the COVID-19 outbreak had on FLW generation and management. Accordingly, this study once again highlights that measures aimed at reducing FLW, particularly in the household sector, are critical to make better use of food surpluses and FLW prevention and control, allowing us to confront future unforeseen scenarios.

Short- and long-term mortality after liver transplantation in patients with and without hepatocellular carcinoma in the UK.

BACKGROUND: The increasing demand for liver transplantation has led to considerable changes in characteristics of donors and recipients. This study evaluated the short- and long-term mortality of recipients with and without hepatocellular carcinoma (HCC) in the UK between 1997 and 2016. METHODS: First-time elective adult liver transplant recipients in the UK were identified and four successive eras of transplantation were compared. Hazard ratios (HRs) comparing the impact of era on short-term (first 90 days) and longer-term (from 90 days to 5 years) mortality were estimated, with adjustment for recipient and donor characteristics. RESULTS: Some 1879 recipients with and 7661 without HCC were included. There was an increase in use of organs donated after circulatory death (DCD), from 0 per cent in era 1 to 35·2 per cent in era 4 for recipients with HCC, and from 0·2 to 24·1 per cent for non-HCC recipients. The 3-year mortality rate decreased from 28·3 per cent in era 1 to 16·9 per cent in era 4 (adjusted HR 0·47, 95 per cent c.i. 0·35 to 0·63) for recipients with HCC, and from 20·4 to 9·3 per cent (adjusted HR 0·44, 0·36 to 0·53) for those without HCC. Comparing era 4 with era 1, improvements were more marked in short-term than in long-term mortality, both for recipients with HCC (0-90 days: adjusted HR 0·20, 0·10 to 0·39; 90 days to 5 years: adjusted HR 0·52, 0·35 to 0·75; P = 0·043) and for non-HCC recipients (0-90 days: adjusted HR 0·32, 0·24 to 0·42; 90 days to 5 years: adjusted HR 0·52, 0·40 to 0·67; P = 0·024). CONCLUSION: In the past 20 years, the mortality rate after liver transplantation has more than halved, despite increasing use of DCD donors. Improvements in overall survival can be explained by decreases in short-term and longer-term mortality.

ANTECEDENTES: La creciente demanda de trasplante hepático ha determinado cambios considerables en las características de los donantes y receptores. En este estudio, se evaluó la mortalidad a corto y a largo plazo de los receptores de trasplante hepático por carcinoma hepatocelular (hepatocelular carcinoma, HCC) y no-HCC en el Reino Unido entre 1997 y 2016. MÉTODOS: Se identificaron los receptores adultos de un primer trasplante hepático electivo en el Reino Unido y se compararon cuatro eras sucesivas de trasplante. Se estimaron los cocientes de riesgos instantáneos ajustados (adjusted hazard ratio, aHR) que comparaban el impacto de la era en la mortalidad a corto plazo (primeros 90 días) y a largo plazo (de 90 días a 5 años) ajustando por las características del receptor y del donante. RESULTADOS: Se incluyeron 1.879 receptores HCC y 7.661 receptores no-HCC. Hubo un aumento en el uso de donantes después de parada cardíaca (donors following circulatory death, DCD) del 0% en la era 1 al 35,2% en la era 4 para los receptores HCC y del 0,2% al 24,1% para los receptores no-HCC. La mortalidad a los 3 años disminuyó de 28,3% en la era 1 a 16,9% en la era 4 (aHR 0,47, i.c. del 95% 0,35-0,63) para receptores HCC y de 20,4% a 9,3% (aHR 0,44, 0,36-0,53) para receptores no-HCC. Comparando la era 1 y la era 4, las mejoras en la mortalidad a corto plazo fueron más marcadas que en la mortalidad a largo plazo, tanto para receptores HCC (aHR 0-90 días 0,20, 0,10-0,39; 90 días-5 años 0,52, 0,35-0,75; P =舁0,04) como para receptores no-HCC (aHR 0-90 días 0,32, 0,24-0,42; 90 días-5 años 0,52, 0,40-0,67; P =舁0,02). CONCLUSIÓN: En los últimos 20 años, la mortalidad después del trasplante de hígado se ha reducido a más de la mitad, a pesar del uso cada vez mayor de donantes DCD. Las mejoras en la supervivencia global pueden explicarse por la disminución de la mortalidad a corto y largo plazo.

Liver transplantation outcomes after transarterial chemotherapy for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) awaiting liver transplantation is widespread, although evidence that it improves outcomes is lacking and there exist concerns about morbidity. The impact of TACE on outcomes after transplantation was evaluated in this study. METHODS: Patients with HCC who had liver transplantation in the UK were identified, and stratified according to whether they received TACE between 2006 and 2016. Cox regression methods were used to estimate hazard ratios (HRs) for death and graft failure after transplantation adjusted for donor and recipient characteristics. RESULTS: In total, 385 of 968 patients (39·8 per cent) received TACE. Five-year patient survival after transplantation was similar in those who had or had not received TACE: 75·2 (95 per cent c.i. 68·8 to 80·5) and 75·0 (70·5 to 78·8) per cent respectively. After adjustment for donor and recipient characteristics, there were no differences in mortality (HR 0·96, 95 per cent c.i. 0·67 to 1·38; P = 0·821) or graft failure (HR 1·01, 0·73 to 1·40; P = 0·964). The number of TACE treatments (2 or more versus 1: HR 0·97, 0·61 to 1·55; P = 0·903) or the time of death after transplantation (within or after 90 days; P = 0·291) did not alter the outcome. The incidence of hepatic artery thrombosis was low in those who had or had not received TACE (1·3 and 2·4 per cent respectively; P = 0·235). CONCLUSION: TACE delivered to patients with HCC before liver transplant did not affect complications, patient death or graft failure after transplantation.

ANTECEDENTES: La quimioembolización transarterial (transarterial chemoembolization, TACE) en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC) se utiliza como puente al trasplante hepático, aunque falta evidencia de que mejore los resultados y la morbilidad relacionada es motivo de preocupación. En este estudio se evaluó el impacto de la TACE en los resultados tras el trasplante para analizar las complicaciones. MÉTODOS: Se identificaron los receptores de trasplante hepático por HCC en el Reino Unido y se estratificaron según si habían recibido TACE entre 2006 y 2016. Se utilizó el método de regresión de Cox para estimar los cocientes de riesgos instantáneos (hazard ratio, HR) para la mortalidad post-trasplante y el fallo del injerto ajustados por las características del donante y del receptor. RESULTADOS: En total, 385 (39,8%) de 968 pacientes recibieron TACE, observándose similar supervivencia del paciente a los 5 años después del trasplante: 75,2% (i.c. del 95%: 68,8% a 80,5%) con TACE y 75,0% (70,5% a 78,8 %) sin TACE. Después de ajustar según las características del donante y del receptor, no hubo diferencias en la mortalidad (HR: 0,96, 0,67 a 1,38; P = 0,82) o en el fallo del injerto (HR: 1,01, 0,73 a 1,40; P = 0,96). El número de tratamientos con TACE (≥ 2 tratamientos TACE HR: 0,97, 0,61 a 1,55; P = 0,90) o el período de tiempo después del trasplante (mortalidad del paciente antes o después de 90 días; P = 0,29) no alteró el resultado. La incidencia de trombosis de la arteria hepática fue baja en aquellos que recibieron TACE o no (1,3% y 2,5%, respectivamente; P = 0,23). El fallo del injerto debido a eventos oclusivos fue similar en el grupo de pacientes que recibieron TACE (8,0% o 11/137) o que no la recibieron (6,7% o 5/75) TACE (P = 0,74). CONCLUSIÓN: La administración de TACE en pacientes con HCC antes del trasplante hepático no influyó en las complicaciones post-trasplante, la mortalidad del paciente o el fallo del injerto.

Potential formation of PCDD/Fs in triclosan wastewater treatment: An overall toxicity assessment under a life cycle approach.

Wastewater may contain a diverse group of unregulated pollutants known as emerging pollutants, such as pharmaceuticals and personal care products (PPCPs). Triclosan (TCS) is a personal care product widely used as an antiseptic or preservative in cosmetics, hand wash, toothpaste and deodorant soaps. Advanced oxidation processes (AOPs) have been used as effective and alternative treatments for complex wastewater. However, an important criterion for the assessment of AOPs and their operation conditions could be the potential formation of new toxic secondary products, such as polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), especially when emerging pollutants are present in the media. If these are omitted from environmental management studies, the real environmental impacts of a WWTPs (wastewater treatment plants) may be underestimated. Consequently, the current study aims to evaluate the environmental impacts derived from electrooxidation (EOX), one of the most effective oxidation technologies, of emerging pollutants using Life Cycle Assessment. The analyses were performed for the treatment of effluents containing TCS, firstly without considering the formation of PCDD/Fs and, thereafter, considering the effects of these compounds. Total toxicity, calculated through different methods and corresponding impact factors, were evaluated for each stage of the process when different electrolytes are used, including PCDD/Fs formation. Finally, a sensitivity analysis was carried out to study i) the effect of the TCS initial concentration on the environmental impacts associated to ecotoxicity for the different life cycle methods and ii) the influence of changing the organic pollutant on PCDD/Fs formation employing 2-chlorophenol (2-CP). As a result, LCIA methods demonstrate that they are not fully adapted to the computation of PCDD/Fs in the water compartment, since only 2,3,7,8-tetraclorodibenzo-p-dioxina (2,3,7,8-TCDD) is present as a substance in the impact categories assessed, ignoring the remaining list of PCDD/Fs.

Regionalizing eco-toxicity characterization factors for copper soil emissions considering edaphic information for Northern Spain and Portuguese vineyards.

The management of vineyards depends on the use of plant protection agents. Regardless of the numerous environmental impacts that these pesticides generate during their production, their dosage as pest control agents in vineyards causes an important toxic effect that must be monitored. Copper-based inorganic pesticides are the most widely used agents to control fungal diseases in humid wine-growing regions. It is, however, significant that the environmental analysis of their use through the Life Cycle Assessment (LCA) methodology does not provide detailed information on the potential toxicity of this type of pesticides. Hence, most studies report average values for copper characterization factors (CFs), excluding local soil characteristics. The objective of the study was the spatial characterization of the ecotoxicity factors of copper soil emissions as a function of the chemical characteristics of vineyard soils located in Portugal and Galicia (NW Spain). A multiple linear regression model was applied to calculate the comparative toxic potential. Subsequently, CFs for copper were calculated based on spatial differentiation considering the variable properties of the soil within each wine appellation. The CFs obtained for the area evaluated ranged from 141 to 5937 PAF·m3·day/kgCu emitted, for fibric histosols (HSf) and dystic cambisols (CMd), respectively. Moreover, the average values obtained for Galician and Portuguese soils were 1145 and 2274 PAF·m3·day/kgCu emitted, respectively. The results obtained illustrate the high variability of CF values as a function of the chemical characteristics of each type of soil. For example, Cu soil mobility was linked to organic carbon content and pH. Finally, to validate the representativeness of the calculated CFs, these were applied to the results of 12 literature life cycle inventories of grape production in the area evaluated, revealing that impact scores associated with Cu emissions can considerably vary when spatially-differentiated CFs are implemented.

Combined application of Life Cycle Assessment and linear programming to evaluate food waste-to-food strategies: Seeking for answers in the nexus approach.

The great concern regarding food loss (FL) has been studied previously, but in an isolated way, disregarding interdependencies with other areas. This paper aims to go a step further by proposing a new procedure to assess different waste management alternatives based on the nexus approach by means of an integrated Water-Energy-Food-Climate Nexus Index (WEFCNI). The environmental profile of the waste management techniques is determined using Life Cycle Assessment (LCA) which, in combination with Linear Programming (LP), explores the optimal aggregation of weighting factors that lead to an aggregated nexus index. The management of residues from the anchovy canning industry in Cantabria (Spain) has been used as a case study, considering the three current applied alternatives: (i) valorisation of FL as animal feed in aquaculture (food waste-to-food approach), (ii) incineration of FL with energy recovery, and (iii) landfilling with biogas recovery. The last two considered the use of energy recovered to produce a new aquaculture product (food waste-to-energy-to-food scenarios). The results indicate that incineration is the best performing scenario when the nutritional energy provided by the valorisation alternative is not high enough and the valorisation technology presents the highest water consumption. Therefore, a minimisation in the consumption of natural resources is suggested in order to improve the application of circular economy within the sector. The use of the nexus index as an environmental management tool is extendable to any food system with the aim of facilitating the decision-making process in the development of more sustainable products.

BDA hospital dentists survey 2017.

In 2016 the BDA undertook to investigate the demographics and distribution of its hospital members alongside their morale and motivation. This is the first time the BDA had undertaken such a survey and it is the first time any workforce research into the Hospital Dental Services (HDS) has been published by any party. Subsequent freedom of information requests have suggested that BDA HDS member data is representative of the overall HDS workforce. Of particular note is the distribution of some of the 'smaller' specialties with some seemingly only existing at dental school level alongside morale and motivation levels in relation to other dental roles.

The first national clinical audit for rheumatoid arthritis.

The first national audit for rheumatoid and early inflammatory arthritis has benchmarked care for the first 3 months of follow-up activity from first presentation to a rheumatology service. Access to care, management of early rheumatoid arthritis and support for self care were measured against National Institute for Health and Care Excellence quality standards; impact of early arthritis and experience of care were measured using patient-reported outcome and experience measures. The results demonstrate delays in referral and accessing specialist care and the need for service improvement in treating to target, suppression of high levels of disease activity and support for self-care. Improvements in patient-reported outcomes within 3 months and high levels of overall satisfaction were reported but these results were affected by low response rates. This article presents a summary of the national data from the audit and discusses the implications for nursing practice.

Assessing the treatment costs and the fertilizing value of the output products in digestate treatment systems.

The objective of this paper was to advance towards finding sustainable solutions to deal with biogas digestate and contribute to faster development of the market for digestate treatment products. The study compares digestate treatment costs through four different treatment plants, estimates the potential fertilizing and humus value (PFHV) of the derived products and allocates the cash flows to show the possible regional benefits. The treatment costs for the pre-dried solid fraction of digestate ranged from €19 to €23/tonne output. These costs may be covered by vending treatment products at a price reaching at least 34-41% of their PFHV (ca €55/tonne). Treatment of raw digestate generates high operating costs (€216-247/tonne output), much higher than the PFHV of the products (ca €35-51/tonne). For such systems either the treatment has to be financially subsidized by the authorities or €13-32/tonne input should be covered by the substrate deliverers as a disposal fee. Nevertheless, a well-prepared investment concept in this field may allow the local binding of up to 80% of total cash flows. Finally, the current difficult market situation of the treatment products can be primarily improved by clearing their legal status at European level.

Operator training requirements and diagnostic accuracy of Fibroscan in routine clinical practice.

BACKGROUND: Fibroscan is a quick, non-invasive technique used to measure liver stiffness (kPa), which correlates with fibrosis. To achieve a valid liver stiffness evaluation (LSE) the operator must obtain all the following three criteria: (1) ≥10 successful liver stiffness measurements; (2) IQR/median ratio <0.30 and (3) ≥60% measurement success rate. OBJECTIVES: To assess the operator training requirements and the importance of adhering to the LSE validity criteria in routine clinical practice. METHODS: We retrospectively analysed the LSE validity rates of 2311 Fibroscans performed (1 August 2008 to 31 July 2011) in our tertiary liver outpatients department at the University Hospital Birmingham, UK. The diagnostic accuracy of Fibroscan was assessed in 153 patients, by comparing LSE (valid and invalid) with the modified Ishak fibrosis stage on liver biopsy. RESULTS: Learning curve analysis highlighted that the greatest improvement in validity of LSE rates occurs in the operator's first 10 Fibroscans, reaching 64.7% validity by the 50th Fibroscan. The correlation between LSE and the fibrosis stage on liver biopsy was superior in patients with a valid LSE (n=97) compared with those with an invalid LSE (n=56) (rs 0.577 vs 0.259; p=0.022). Area under receiving operating characteristics for significant fibrosis was greater when LSE was valid (0.83 vs 0.66; p=0.048). Using an LSE cut-off of 8 kPa, the negative predictive value of valid LSE was superior to invalid LSE for the detection of significant (84% vs 71%) and advanced fibrosis (100% vs 93%). CONCLUSIONS: Fibroscan requires minimal operator training (≥10 observed on patients), and when a valid LSE is obtained, it is an accurate tool for excluding advanced liver fibrosis. To ensure the diagnostic accuracy of Fibroscan it is essential that the recommended LSE validity criteria are adhered to in routine clinical practice.

Systematic review: pentoxifylline for the treatment of severe alcoholic hepatitis.

BACKGROUND: Acute alcoholic hepatitis (AH) is a severe manifestation of alcoholic liver disease with a grave prognosis. Pentoxifylline, an oral antitumour necrosis factor agent, has been reported to reduce mortality and incidence of hepatorenal syndrome (HRS) in severe alcoholic hepatitis (SAH). AIM: To summarise evidence for the use of pentoxifylline in SAH. METHODS: A literature search was undertaken using MeSH terms 'hepatitis, alcoholic' and 'pentoxifylline' using the set operator AND. We included randomised controlled trials examining pentoxifylline in SAH, published as abstracts or full manuscripts. Risk ratios (RRs) were calculated for pooled data using random effects modelling. Risk of bias was assessed using Cochrane group criteria and quality of trials assessed using 'Consolidated Standards of Reporting Trials' CONSORT guidelines. RESULTS: Ten trials including 884 participants were included, from six papers and four abstracts. There was significant heterogeneity between trials regarding control groups and trial end-points. Treatment was given for 28 days in all trials except one. Pooling of data showed a reduced incidence of fatal HRS with pentoxifylline compared with placebo (RR: 0.47, 0.26-0.86, P = 0.01), but no survival benefit at 1 month (RR: 0.58, 0.31-1.07, P = 0.06). There were no significant differences between treatment groups in trials of pentoxifylline vs. corticosteroid, or vs. combination therapy. CONCLUSIONS: Pentoxifylline appears superior to placebo in prevention of fatal HRS and thus may be effective treatment of SAH when corticosteroids are contraindicated. However, multiple trials have failed to show conclusive superiority of either pentoxifylline or corticosteroids.

Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program.

BACKGROUND: Non-alcoholic fatty liver disease has reached epidemic proportions in type 2 diabetes (T2D). Glucagon-like peptide-1 analogues are licensed in T2D, yet little data exist on efficacy and safety in liver injury. AIM: To assess the safety and efficacy of 26-week liraglutide on liver parameters in comparison with active-placebo. METHODS: Individual patient data meta-analysis was performed using patient-level data combined from six 26-week, phase-III, randomised controlled T2D trials, which comprise the 'Liraglutide Effect and Action in Diabetes' (LEAD) program. The LEAD-2 sub-study was analysed to assess the effect on CT-measured hepatic steatosis. RESULTS: Of 4442 patients analysed, 2241 (50.8%) patients had an abnormal ALT at baseline [mean ALT 33.8(14.9) IU/L in females; 47.3(18.3) IU/L in males]. Liraglutide 1.8 mg reduced ALT in these patients vs. placebo (-8.20 vs. -5.01 IU/L; P = 0.003), and was dose-dependent (no significant differences vs. placebo with liraglutide 0.6 or 1.2 mg). This effect was lost after adjusting for liraglutide's reduction in weight (mean ALT difference vs. placebo -1.41 IU/L, P = 0.21) and HbA1c (+0.57 IU/L, P = 0.63). Adverse effects with 1.8 mg liraglutide were similar between patients with and without baseline abnormal ALT. In LEAD-2 sub-study, liraglutide 1.8 mg showed a trend towards improving hepatic steatosis vs. placebo (liver-to-spleen attenuation ratio +0.10 vs. 0.00; P = 0.07). This difference was reduced when correcting for changes in weight (+0.06, P = 0.25) and HbA(1c) (0.00, P = 0.93). CONCLUSIONS: Twenty-six weeks' liraglutide 1.8 mg is safe, well tolerated and improves liver enzymes in patients with type 2 diabetes. This effect appears to be mediated by its action on weight loss and glycaemic control.

Despite poor interferon response in advanced hepatitis C virus infection, models of protease inhibitor treatment predict maximum treatment benefit.

BACKGROUND: Protease inhibitors have improved sustained virological response (SVR) rates for subjects with genotype 1 hepatitis C virus infection (HCV). There is however uncertainty regarding how, and in whom, these agents should be used. In previously treated subjects, prior response to interferon has a major effect on SVR rates with protease inhibitor therapy. AIM: To assess the benefits of treatment and to understand the utility of a stopping rule for subjects with a poor interferon response following a 4-week lead-in with pegylated interferon and ribavirin. METHODS: Treatment responses and long-term outcomes were modelled using hypothetical 1000 subject cohorts with 5 years of follow-up. Treatment strategies were compared with number needed to treat (NNT) and comparative effectiveness approaches. RESULTS: Over 5 years of follow-up the NNT to prevent liver-related mortality for subjects with advanced fibrosis was substantially lower than that for subjects with all fibrosis stages (18 vs. 60) indicating particular benefit in this high-risk population. The use of a stopping rule for subjects with advanced fibrosis and a poor interferon response after a 4-week lead-in reduces the number of subjects exposed to a protease inhibitor by 55%. However, 33% fewer liver-related deaths are prevented using this strategy, indicating that there is unacceptable harm associated with this approach over a 5-year follow-up period. CONCLUSIONS: Subjects with advanced fibrosis should be prioritised for triple therapy on the basis of need. Treatment should be continued regardless of initial interferon response to maximise the early prevention of hepatitis C virus-related mortality.