A census of baryons in the Universe from localized fast radio bursts.

More than three-quarters of the baryonic content of the Universe resides in a highly diffuse state that is difficult to detect, with only a small fraction directly observed in galaxies and galaxy clusters1,2. Censuses of the nearby Universe have used absorption line spectroscopy3,4 to observe the 'invisible' baryons, but these measurements rely on large and uncertain corrections and are insensitive to most of the Universe's volume and probably most of its mass. In particular, quasar spectroscopy is sensitive either to the very small amounts of hydrogen that exist in the atomic state, or to highly ionized and enriched gas4-6 in denser regions near galaxies7. Other techniques to observe these invisible baryons also have limitations; Sunyaev-Zel'dovich analyses8,9 can provide evidence from gas within filamentary structures, and studies of X-ray emission are most sensitive to gas near galaxy clusters9,10. Here we report a measurement of the baryon content of the Universe using the dispersion of a sample of localized fast radio bursts; this technique determines the electron column density along each line of sight and accounts for every ionized baryon11-13. We augment the sample of reported arcsecond-localized14-18 fast radio bursts with four new localizations in host galaxies that have measured redshifts of 0.291, 0.118, 0.378 and 0.522. This completes a sample sufficiently large to account for dispersion variations along the lines of sight and in the host-galaxy environments11, and we derive a cosmic baryon density of [Formula: see text] (95 per cent confidence; h70 = H0/(70 km s-1 Mpc-1) and H0 is Hubble's constant). This independent measurement is consistent with values derived from the cosmic microwave background and from Big Bang nucleosynthesis19,20.

Short-term changes observed in multiparametric liver MRI following therapy with direct-acting antivirals in chronic hepatitis C virus patients.

METHODS: We applied multiparametric MRI to assess changes in liver composition, perfusion and blood flow in 17 patients before direct-acting antiviral (DAA) therapy and after treatment completion (within 12 weeks of last DAA tablet swallowed). RESULTS: We observed changes in hepatic composition indicated by a reduction in both liver longitudinal relaxation time (T1, 35 ± 4 ms), transverse relaxation time (T2, 2.5 ± 0.8 ms; T2* 3.0 ± 0.7 ms), and liver perfusion (28.1 ± 19.7 ml/100 g/min) which we suggest are linked to reduced pro-inflammatory milieu, including interstitial oedema, within the liver. No changes were observed in liver or spleen blood flow, splenic perfusion, or superior mesenteric artery blood flow. CONCLUSION: For the first time, our study has shown that treatment of HCV with DAAs in patients with cirrhosis leads to an acute reduction in liver T1, T2 and T2* and an increase in liver perfusion measured using MR parameters. The ability of MRI to characterise changes in the angio-architecture of patients with cirrhosis after intervention in the short term will enhance our understanding of the natural history of regression of liver disease and potentially influence clinical decision algorithms. KEY POINTS: • DAAs have revolutionised the treatment of hepatitis C and achieve sustained virological response in over 95% of patients, even with liver cirrhosis. • Currently available non-invasive measures of liver fibrosis are not accurate after HCV treatment with DAAs, this prospective single-centre study has shown that MRI can sensitively measure changes within the liver, which could reflect the reduction in inflammation with viral clearance. • The ability of MRI to characterise changes in structural and haemodynamic MRI measures in the liver after intervention will enhance our understanding of the progression/regression of liver disease and could potentially influence clinical decision algorithms.

Historical epidemiology of hepatitis C virus (HCV) in selected countries.

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

A luminous fast radio burst that probes the Universe at redshift 1.

Fast radio bursts (FRBs) are millisecond-duration pulses of radio emission originating from extragalactic distances. Radio dispersion is imparted on each burst by intervening plasma, mostly located in the intergalactic medium. In this work, we observe the burst FRB 20220610A and localize it to a morphologically complex host galaxy system at redshift 1.016 ± 0.002. The burst redshift and dispersion measure are consistent with passage through a substantial column of plasma in the intergalactic medium and extend the relationship between those quantities measured at lower redshift. The burst shows evidence for passage through additional turbulent magnetized plasma, potentially associated with the host galaxy. We use the burst energy of 2 × 1042 erg to revise the empirical maximum energy of an FRB.

Effectiveness of a nurse-led alcohol liaison service in a secondary care medical unit.

Alcohol misuse is a common reason for hospital admission. While there is considerable evidence from other areas that provision of specialised alcohol services can reduce alcohol intake, there is currently less evidence for medical departments in an acute hospital setting. Nottingham hospitals initiated such a service in 2002-3 based around two nurse specialists who provided input to inpatients with alcohol-related physical disease and provided links to community-based services for alcohol misuse. This service assessed 3632 patients over five years and has seen a reduction in hospital admissions, violent incidents against staff and primary care attendances. It is believed that this model of care is an effective means of intervening in people with alcohol-related problems.

Autoantibodies in chronic hepatitis C virus infection and their association with disease profile.

Autoantibodies are commonly detected in chronic hepatitis C (HCV) but their significance remains uncertain. We assessed the prevalence of anti-nuclear (ANA) and anti-smooth muscle (ASM) antibodies within a cohort of 963 treatment-naïve HCV patients. We also assessed for differences between autoantibody-positive and autoantibody-negative patients in demographics, markers of disease activity and response to anti-viral treatment. One hundred and seventy-two patients (17.9%) had at least one autoantibody, of which were 104 (10.8%) ASM, 54 (5.6%) ANA and 14 (1.5%) positive for both. Autoantibody-positive patients were older (43 vs 39 years, P = 0.001) caused by an age-related increase in ANA (but not ASM). There were no differences in gender, alcohol intake, ethnicity or viral genotype. The presence of autoantibodies, and specifically ASM, was associated with an increase in interface hepatitis score amongst men (1.1 vs 0.8, P = 0.005) but no difference in other necroinflammatory measures, liver function tests or immunoglobulins (Ig). There was no difference in initial fibrosis stage or rate of fibrosis progression. Autoantibodies did not affect response to anti-viral treatment. We conclude that autoantibodies are frequent in HCV infection. Anti-nuclear antibodies increase with age, whereas ASM antibodies are associated with interface hepatitis in men. Neither autoantibody carries increased risk of fibrosis progression or failure of therapy.

A single fast radio burst localized to a massive galaxy at cosmological distance.

Fast radio bursts (FRBs) are brief radio emissions from distant astronomical sources. Some are known to repeat, but most are single bursts. Nonrepeating FRB observations have had insufficient positional accuracy to localize them to an individual host galaxy. We report the interferometric localization of the single-pulse FRB 180924 to a position 4 kiloparsecs from the center of a luminous galaxy at redshift 0.3214. The burst has not been observed to repeat. The properties of the burst and its host are markedly different from those of the only other accurately localized FRB source. The integrated electron column density along the line of sight closely matches models of the intergalactic medium, indicating that some FRBs are clean probes of the baryonic component of the cosmic web.

Response rates to combination therapy for chronic HCV infection in a clinical setting and derivation of probability tables for individual patient management.

Evidence for efficacy of established treatment guidelines for chronic hepatitis C virus (HCV) disease is based on multinational randomized controlled trials (RCTs). Strategies for managing HCV, however, require an assessment of the effectiveness of intervention in routine clinical practice. We report the outcomes of combination therapy in a large cohort of HCV-infected individuals in the UK. A total of 347 (113 genotype 1, 234 genotype non-1) patients were treated with pegylated interferon and ribavirin according to current guidelines. Forty-two (37.2%) of those with genotype 1 infection and 164 (70.1%) with genotype non-1 infection achieved sustained viral response (SVR). Thirty-nine (11%) patients withdrew from treatment. In addition to viral genotype, factors predictive of a response to therapy were age at start of treatment and disease stage on pretreatment liver biopsy. Multivariate regression analysis demonstrated that the effects of age [odds ratio 0.5; 95% confidence interval (0.31-0.82) per 10-year increment (P = 0.006)] were confined to genotype 1 disease. In order to further inform the management of the individual patient, a multivariate logistic model was used to predict the probability of SVR for subgroups defined by disease stage, genotype and age at commencement of therapy. This model revealed striking differences in predicted response rates between subgroups and provided a strong rationale for early treatment, particularly for those with genotype 1 disease. Our study demonstrates that results comparable with those of RCTs can be achieved in clinical practice, and suggests that prediction of response rates based on probability modelling will provide a valuable adjunct to individual patient management.

Obesity and type 2 diabetes are important risk factors underlying previously undiagnosed cirrhosis in general practice: a cross-sectional study using transient elastography.

BACKGROUND: Rising cirrhosis incidence and mortality in the United Kingdom has been attributed predominantly to excess alcohol consumption. However, metabolic risk factors such as Type 2 diabetes and obesity may also be important. AIM: To screen at-risk individuals in general practice for undetected cirrhosis using transient elastography and study the risk factors underlying these cases. METHODS: The study was undertaken in 4 general practices (adult patient population 20 868) between February 2012 and September 2014. Patients with defined risk factors for chronic liver disease (hazardous alcohol use and/or Type 2 diabetes) were identified from the General Practice electronic records and invited for transient elastography. Elevated liver stiffness was defined as ≥8 kPa. Cirrhosis was confirmed by established histological, radiological and biochemical methods. RESULTS: Two thousand three hundred and sixty eight patients were invited for transient elastography and 899/919 who attended (97.8%) had valid measurements. Of these 230 patients had elevated liver stiffness (25.6%) and 27 had cirrhosis (2.9%). Risk factors for new cirrhosis diagnoses were obesity and/or Type 2 diabetes in 16 patients (59.3%), alcohol alone in 3 (11.1%) and both alcohol and obesity and/or diabetes in eight (29.6%). Presence of cirrhosis was significantly increased in obese patients with Type 2 diabetes or hazardous alcohol use compared to non-obese (odds ratio 9.4 [95% CI 2.2-40.9] and 5.6 [95% CI 1.6-19.7] respectively). CONCLUSIONS: The number of new cases of cirrhosis diagnosed clearly demonstrates that existing estimates of prevalence are likely to be gross underestimates. Obesity was an important risk factor for cirrhosis within both alcohol users and diabetics.

Peanut lectin: a mitogen for normal human colonic epithelium and human HT29 colorectal cancer cells.

BACKGROUND: The protein peanut agglutinin (PNA) is a galactose-binding lectin whose receptor, the Thomsen-Friedenreich (TF) blood-group antigen, shows increased expression in hyperplastic and neoplastic colonic epithelium. PURPOSE: Our hypothesis was that, under these conditions, increased lectin receptors could interact with dietary lectins, which would act as tumor promoters by stimulating cell proliferation. This study was designed to confirm whether active PNA is recoverable from feces after ingestion of peanuts and to assess the mitogenic effect of PNA on proliferation of epithelial cells in the colon. METHODS: Peanut lectin was extracted from feces by lactose-agarose affinity chromatography and was assayed for hemagglutinating activity. Cultured explants of histologically normal biopsy specimens of colonic mucosa from 31 patients were examined. Crypt cell production rate and incorporation of [3H]N-acetylglucosamine into mucin were assessed as indicators of proliferative and metabolic responses to PNA. In addition, we evaluated the separate and combined effects of PNA and epidermal growth factor (EGF) on cell proliferation in human HT29 colorectal cancer cells, by using tritiated thymidine incorporation and cell counts. RESULTS: Peanut lectin extracted from feces showed hemagglutinating activity toward desialylated red blood cells similar to that of a lectin preparation extracted from raw peanuts. Evaluation of biopsy specimens of normal colonic mucosa demonstrated that PNA at a concentration of 25 micrograms/mL caused statistically significant increases in crypt cell production (31% [mean] +/- 5% [SD]; P = .00005) and mucus synthesis (77% +/- 12%; P less than .000001). At 7.5-100 micrograms/mL, PNA was mitogenic for the HT29 colorectal cancer cell line. At 25 micrograms/mL, PNA alone produced a statistically significant increase in thymidine incorporation (44% [mean] +/- 3.7% [SD]; P = .002). For PNA in combination with EGF at 100 pg/mL, the increase was significantly greater (222% +/- 11.2%) than that for EGF alone (57% +/- 5%; P = .003). CONCLUSIONS: These results suggest that expression of the PNA receptor, TF antigen, by hyperplastic or neoplastic colonic epithelium may affect cell proliferation. IMPLICATIONS: It is possible that dietary lectins such as PNA, which bind to the TF antigen, promote cell proliferation and thus cancerous growth, while galactose-containing vegetable fiber would inhibit this effect by competing for binding by these lectins.

Prevention of progression to cirrhosis in hepatitis C with fibrosis: effectiveness and cost effectiveness of sequential therapy with new direct-acting anti-virals.

BACKGROUND: The new direct-acting anti-virals (DAAs) for hepatitis C virus (HCV) infection offer higher cure rates, but at a much higher cost than the standard interferon-based treatments. AIM: To identify the cost-effective treatment for patients with HCV infection with F3 liver fibrosis who are at high risk of progression to cirrhosis. METHODS: A decision-analytic Markov model compared the health benefits and costs of all currently licensed treatments as single treatments and in sequential therapy of up to three lines. Costs were expressed in pound sterling from the perspective of the UK National Health Service. Health benefits were expressed in quality-adjusted life years. RESULTS: Treatment before progression to cirrhosis always offers the most health benefits for the least costs. Sequential therapy with multiple treatment lines cures over 89% of patients across all HCV genotypes while ensuring a cost-effective use of resources. Cost-effective regimes for HCV genotype 1 patients include first-line oral therapy with sofosbuvir-ledipasvir while peginterferon continues to have a role in other genotypes. CONCLUSIONS: The cost-effective treatment for HCV can be established using decision analytic modelling comparing single and sequential therapies. Sequential therapy with DAAs is effective and cost-effective in HCV patients with F3 fibrosis. This information is of significant benefit to health care providers with budget limitations and provides a sound scientific basis for drug treatment choices.

The long-term management of patients with bleeding duodenal ulcers.

BACKGROUND: Gastrointestinal haemorrhage is a common complication of duodenal ulcers. Patients who bleed are at substantial risk of recurrent bleeding. AIM: To determine whether appropriate therapeutic steps were taken to reduce the risk of recurrent haemorrhage in patients with a bleeding duodenal ulcer. METHODS: The management of patients surviving a duodenal ulcer bleed in the University Hospital. Nottingham, was assessed by case-note review before (1993) and after (1995-1996) institution of clinical guidelines. The following measures aimed at reducing the risk of recurrent haemorrhage were considered appropriate: stopping non-steroidal anti-inflammatory drugs (NSAIDs) when these were implicated in bleeding; successful eradication of Helicobacter pylori if present; and long-term maintenance acid-suppression therapy. RESULTS: In 1993, appropriate steps were taken to reduce the risk of recurrent haemorrhage in only 48% of cases. Following the institution of guidelines, management improved significantly in 1995-1996 (appropriate in 83% of cases, P < 0.001), was associated with increased referral to gastroenterologists (P < 0.001), improved patient compliance with follow-up (P < 0.05), and more rigorous attempts to identify (P < 0.001) and ensure clearance (P < 0.001) of H. pylori. CONCLUSION: In this study, inadequate long-term management of patients with a bleeding duodenal ulcer was common. This was to a failure to adopt strategies aimed at reducing the risk of ulcer relapse and rebleeding. The quality of care improved significantly following the institution of guidelines and encouragement to refer to gastroenterologists.

Rectal bismuth subsalicylate as therapy for ulcerative colitis.

In a prospective open study, 15 patients with ulcerative colitis which was unresponsive to conventional therapy were treated with enemas containing bismuth subsalicylate (700 or 800 mg b.d.). Nine out of the 15 patients showed a significant clinical response, and 6 had gone into complete clinical remission after 8 weeks treatment. Sigmoidoscopoic appearances of the rectal mucosa showed improvement in 9 out of 15 patients at 2 weeks, and 11 out of 15 at 8 weeks. The mucosa appeared sigmoidoscopically normal in 6 out of 15 at 8 weeks. It proved possible to reduce the oral prednisolone dosage from a median of 15 mg/day (range 10 to 35 mg/day) to 6 mg/day (range 0 to 18 mg/day) after 8 weeks of treatment; 5 patients were no longer taking oral steroids at this time. Rectal bismuth subsalicylate appears likely to be an effective therapy in ulcerative colitis and controlled trials are now required.

A pilot study to investigate the use of oxpentifylline (pentoxifylline) and thalidomide in portal hypertension secondary to alcoholic cirrhosis.

BACKGROUND: Tumour necrosis factor-alpha is thought to be important in the pathogenesis of portal hypertension. Oxpentifylline (pentoxifylline) and thalidomide inhibit endotoxin-induced tumour necrosis factor-alpha production in vitro. AIMS: To assess the toxicity of oxpentifylline (pentoxifylline) and thalidomide in cirrhosis and their effect on the hepatic venous pressure gradient and tumour necrosis factor-alpha production. METHODS: In an open-label pilot study, 20 abstinent patients with stable alcoholic cirrhosis and oesophageal varices were recruited; 12 patients completed haemodynamic measurements before and after treatment with oxpentifylline (pentoxifylline) 1800 mg (n=6) or thalidomide 200 mg (n=6) daily for 2 weeks. Tumour necrosis factor-alpha production was assessed in ex vivo monocyte cultures stimulated with endotoxin. RESULTS: Thalidomide reduced the hepatic venous pressure gradient from 19.7 mmHg (9.3-23.5 mmHg) to 12.2 mmHg (4.7-19.5 mmHg) (P=0.03) without reducing the hepatic blood flow or altering systemic haemodynamic parameters. Thalidomide reduced ex vivo tumour necrosis factor-alpha production by approximately 50%. Oxpentifylline (pentoxifylline) had no significant effect on any of the parameters measured. Side-effects led to dose reduction or treatment withdrawal in 40% of patients. CONCLUSION: Thalidomide, but not oxpentifylline (pentoxifylline), reduces the hepatic venous pressure gradient in stable alcoholic cirrhotics, an effect that may be mediated by the inhibition of tumour necrosis factor-alpha production. The role of tumour necrosis factor-alpha inhibitory drugs in the therapy of portal hypertension should be investigated in a randomized controlled trial.

Fracture risk of women with primary biliary cirrhosis: no increase compared with general population controls.

AIM: Patients with primary biliary cirrhosis may be at increased risk of osteoporosis but to what extent this is reflected in an increased fracture risk is unknown. We have enquired about the fracture experience of female primary biliary cirrhosis patients compared with sex- and age-matched controls. METHODS: Patients aged 30-75 with primary biliary cirrhosis and age-matched controls were sent a postal questionnaire asking about their fracture history and details of risk factors for osteoporosis. RESULTS: 85 eligible patients with primary biliary cirrhosis and 116 controls responded. Forty-one per cent of patients with primary biliary cirrhosis and 30% of controls reported ever having had a fracture odds ratio 1.5 (95% confidence interval: 0.80-2.89). Twenty-eight per cent of primary biliary cirrhosis patients and 23.3% of controls reported a fracture after the age of 30, odds ratio 1.2 (95% confidence interval: 0.57-2.56), and 14.1% of primary biliary cirrhosis patients and 12.1% of controls reported a low impact fracture of the long bones or of the vertebrae odds ratio 1.0 (95% confidence interval: 0.31-2.68). CONCLUSIONS: No overall increased fracture risk in patients with primary biliary cirrhosis was observed. As a group, unselected patients with primary biliary cirrhosis do not represent a population at particularly high risk of osteoporotic fracture and thus targeting them for osteoporosis screening and treatment is not justified. Further work investigating subgroups of patients with primary biliary cirrhosis at potentially high risk of osteoporosis, such as those with advanced disease or severe cholestasis is required.

Use of specific ELISA for the detection of antibodies directed against p53 protein in patients with hepatocellular carcinoma.

AIMS: To analyse the significance of antibodies to p53 protein as a serological marker for changes in p53 gene expression in patients with hepatocellular carcinoma. METHODS: Thirty eight patients with hepatocellular carcinoma, 19 showing accumulation of p53 protein by immunohistochemistry and 19 having no accumulation, were studied. The presence of anti-p53 was tested using a novel ELISA utilising a recombinant p53 protein as a capture system and verified by western blotting. p53 gene mutations were sought by single strand conformational polymorphism and DNA sequencing analyses. RESULTS: Of 19 patients with p53 protein accumulation in tumour tissue, 10 (52%) had antibodies to p53 in serum by ELISA. Four patients with p53 negative immunohistochemistry also had detectable anti-p53. Western blot analysis confirmed the specificity of the ELISA positive serum samples. The presence of anti-p53 was independent of serum alpha-fetoprotein and was detected in 50% of small tumours while only 8% were alpha-fetoprotein positive. Mutations affecting exons 5 and 6 seem to be more frequently associated with development of anti-p53, than mutations in exons 7 or 8. CONCLUSIONS: The ELISA for anti-p53 is a convenient and specific tet for the detection of humoral response to alterations in p53 gene expression and could be of value in the diagnosis and characterisation of patients with hepatocellular carcinoma.

The effect of lectins on crypt cell proliferation in organ culture.

Lectins are highly active biological molecules that are present in large quantities in the human diet. Changes in colonic epithelial glycoconjugates, such as the enhanced expression of the Thomsen-Friedenreich (TF) antigen, are commonly seen in hyperplastic, premalignant, and malignant colorectal epithelium (1,2). As lectins, such as peanut agglutinin would be expected to bind to TF expressed on the epithelial cell (3), it is possible to hypothesize that this interaction could have profound biological effects. This hypothesis has been confirmed by the finding that PNA stimulates proliferation in colonic cancer cell lines (4) and in colonic explants from both normal (4) and diseased colonic epithelium (5). These findings suggest that many lectins may have effects on growth and oncogenesis in the colon; there is therefore a need for laboratory techniques to quantitate changes in proliferation in the human colonic epithelium.

Long term acid suppressing treatment in general practice.

OBJECTIVE: To determine the current practice in selected general practices for prescribing long term (> 6 months) treatment to suppress gastric acid secretion. SETTING: Seven general practices in the Harrow area that always or usually refer to Northwick Park Hospital. SUBJECTS: 60,148 patients on lists of the general practices. DESIGN: Identification of patients receiving long term treatment through repeat prescribing data, followed by a manual and computer survey of patients' notes for indications and investigations. Patient compliance and views on treatment were sought by a postal questionnaire. MAIN OUTCOME MEASURES: Indications for treatment, treatment given, investigations undertaken before and during treatment. RESULTS: 492 patients (0.82% of the population) were taking long term acid suppressing treatment. The most common diagnosis was duodenal ulcer disease (183 (37%) of all patients); oesophageal disease (118 (24%)) was also common. 93 patients (19%) were treated for abdominal pain where no diagnosis had been reached or who had only a diagnosis of gastritis on endoscopy. Ranitidine was prescribed in 394 (80%) patients. 298 (74%) patients found treatment helpful, but 108 (27%) had a poor understanding of their diagnosis. 317 patients (78%) took their drug as prescribed. 37 patients were also taking prescribed non-steroidal anti-inflammatory drugs and an additional 43 patients took regular aspirin or ibuprofen without prescription. CONCLUSIONS: Long term acid suppressing treatment is common, and a substantial number of patients are taking these drugs long term without a diagnosis having been reached. It is hoped that protocols for investigation and treatment will improve these figures. Patients need to be better informed about their disease and the possible adverse effects of taking non-steroidal anti-inflammatory drugs in acid related upper gastrointestinal disease.

Review article: 2014 UK consensus guidelines - hepatitis C management and direct-acting anti-viral therapy.

BACKGROUND: Therapeutic options for the management of hepatitis C virus (HCV) infection have evolved rapidly over the past two decades, with a consequent improvement in cure rates. Novel therapeutic agents are an area of great interest in the research community, with a number of these agents showing promise in the clinical setting. AIMS: To assess and present the available evidence for the use of novel therapeutic agents for the treatment of HCV, updating previous guidelines. METHODS: All Phase 2 and 3 studies, as well as abstract presentations from international Hepatology meetings were identified and reviewed for suitable inclusion, based on studies of new therapies in HCV. Treatment-naïve and experienced individuals, as well as cirrhotic and co-infected individuals were included. RESULTS: Sofosbuvir, simeprevir and faldaprevir, along with pegylated interferon and ribavirin, have a role in the treatment of chronic HCV infection. The precise regimens are largely dependent on the patient characteristics, patient and physician preferences, and cost implication. CONCLUSIONS: Therapies for chronic HCV have evolved dramatically in recent years. Interferon-free regimens are now possible without compromise in the rate of sustained viral response. The decision as to which regimen is most appropriate is multifactorial, and based on efficacy, safety and cost.