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BACKGROUND & AIMS: Bepirovirsen, an antisense oligonucleotide, induces sustained hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA below lower limit of quantification (
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BACKGROUND: There are established risk factors for liver fibrosis (LF), but data on the impact of methotrexate on LF in patients with psoriasis are lacking. OBJECTIVES: This cross-sectional study aimed to determine the prevalence of LF in patients with psoriasis and to evaluate the relationship between LF, cumulative methotrexate dose and other LF risk factors. METHODS: Adults with a history of moderate-to-severe chronic plaque psoriasis were recruited between June 2020 and March 2021. Patients underwent transient elastography to evaluate LF. Three values for liver stiffness measurement (LSM) were assessed, indicating mild or worse LF (≥ 7 kPa), moderate or worse LF (≥ 7.9 kPa) and advanced LF (≥ 9.5kPa). Cumulative methotrexate dose and other potential risk factors for LF were assessed. RESULTS: Overall, 240 patients were recruited and 204 participants with valid LSM values were included in the analysis [median age 48â years [interquartile range (IQR) 37-57]; 51% female sex; 56% body mass index (BMI) ≥ 30 (kg m-2) and a median Alcohol Use Disorders Identification Test (AUDIT) score of 4 (IQR 1-7, 23% score ≥ 8)]. In total, 91% had received methotrexate [median duration 36â months (IQR 14-78)]. Prevalence of LF was 36%, 25% and 17% using LSM ≥ 7 kPa, ≥ 7.9 kPa and ≥ 9.5 kPa, respectively. There was no association between cumulative methotrexate dose [median 2.16 (IQR 0.93-5.2)] and continuous LSM values [unstandardized coefficient 0.16, 95% confidence interval (CI) -0.49 to 0.82, P = 0.626] or using the categorical LSM cutoff values: ≥ 7 kPa [unadjusted odds ratio 1.06 (95% CI 0.97-1.15), P = 0.192], ≥ 7.9 kPa [unadjusted odds ratio 1.03 (95% CI 0.94-1.12), P = 0.577] and ≥ 9.5 kPa (unadjusted odds ratio 1.01, 95% CI 0.91-1.12; P = 0.843). The following risk factors were associated with higher LSM values: BMI (P ≤ 0.001), waist circumference (P ≤ 0.001), metabolic syndrome (P ≤ 0.001), AUDIT score (P = 0.020) and FIB-4 score (P = 0.03). BMI ≥ 28, diabetes and metabolic syndrome were shown to be better predictors of LF compared with FIB-4 score. CONCLUSIONS: This study confirms a high prevalence of significant LF in patients with psoriasis. Cumulative methotrexate dose was not associated with LF. Patients with BMI ≥ 28, metabolic syndrome and diabetes are at higher risk for LF. These risk factors may help to identify when a more detailed liver health assessment is needed.
Psoriasis is a common inflammatory skin disease affecting 3% of the UK population. People with psoriasis appear to have higher rates of liver fibrosis (scarring in the liver from injury or inflammation) compared with people without psoriasis. There are several risk factors for increasing chances of developing liver fibrosis, including obesity, alcohol and diabetes; however, there have been some concerns that methotrexate (a medicine used to treat psoriasis) could also contribute to liver fibrosis. The majority of people needing systemic therapy (such as oral medicines) will try methotrexate first as per National Institute for Health and Care Excellence (NICE) guidance. In this study carried out in the UK, we aimed to look at the relationship between the cumulative dose (total over time) of methotrexate and liver fibrosis and the relationship between other risk factors and liver fibrosis (e.g. body mass index (BMI) (a measure that uses your height and weight to work out whether your weight is healthy), diabetes, alcohol intake and metabolic syndrome (a combination of diabetes, high blood pressure and obesity)). Liver fibrosis was measured using transient elastography, which is a non-invasive technique similar to an ultrasound. We also aimed to find out whether the clinical risk factors for liver fibrosis and a simple test called a 'FIB-4 score' (measured using blood test values and age) can predict a person's chance of developing liver fibrosis, in order to determine which people will benefit most from transient elastography. From our results, we were able to confirm that liver scarring is prevalent in our patients with psoriasis. We did not find an association between cumulative methotrexate and liver scarring. However, BMI, diabetes, metabolic syndrome and FIB-4 score were associated with liver scarring. We found that BMI ≥ 28, metabolic syndrome and diabetes can be used to identify patients who require a liver health assessment. Overall, the study findings suggest that cumulative methotrexate dose is not associated with liver fibrosis in people with a history of moderate-to-severe psoriasis.
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Elasticity Imaging Techniques , Liver Cirrhosis , Methotrexate , Psoriasis , Humans , Methotrexate/adverse effects , Methotrexate/administration & dosage , Psoriasis/drug therapy , Psoriasis/epidemiology , Psoriasis/diagnosis , Female , Male , Middle Aged , Liver Cirrhosis/epidemiology , Liver Cirrhosis/chemically induced , Cross-Sectional Studies , Adult , Risk Factors , Prevalence , Dermatologic Agents/adverse effects , Dermatologic Agents/administration & dosage , Severity of Illness Index , Dose-Response Relationship, DrugABSTRACT
Hepatitis C virus infection (HCV) is prevalent in prisons. Therefore, effective prison HCV services are critical for HCV elimination programmes. We aimed to evaluate the efficacy of a regional HCV prison testing and treatment programme. Between July 2017 and June 2022, data were collected prospectively on HCV test offer and uptake rates, HCV Antibody (HCV-Ab) and HCV-RNA positivity, treatment starts and outcomes for new inmates incarcerated in three prisons. Rates of HCV-Ab and RNA positivity at reception, incidence of new HCV infections and reinfection following treatment were determined. From a total of 39,652 receptions, 33,028 (83.3%) were offered HCV testing and 20,394 (61.7%) completed testing. Including all receptions, 24.5% of tests (n = 4995) were HCV-Ab positive and 8.4% of tests (n = 1713) were HCV-RNA positive. When considering the first test for each individual (median age 34 years; 88.1% male), 14.8% (n = 1869) and 7.2% (n = 905) were HCV-Ab and HCV-RNA positive, respectively. The incidence of new HCV-Ab and RNA positivity was 5.1 and 3.3 per 100 person-years, respectively. Of 1145 HCV viraemic individuals, 18 died within 6 months and 150 were rapidly transferred out of area, leaving 977 individuals with outcomes. Of these, 835 (85.5%) received antivirals and 47 spontaneously cleared the infection, leaving 95 (9.7%) untreated. 607 (72.7%) achieved SVR. 95 patients had reinfection post-treatment (rate 10.1 cases per 100 person-years). Testing for HCV has increased in our prisons and the majority with viraemia are initiated on antiviral treatment. Reassuringly, a significant fall in frequency of HCV-RNA positivity at prison reception was observed suggesting progress towards HCV elimination.
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Hepatitis C , Prisoners , Substance Abuse, Intravenous , Humans , Male , Adult , Female , Prisons , Reinfection , Substance Abuse, Intravenous/epidemiology , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepacivirus/genetics , RNA , England/epidemiology , Hepatitis C Antibodies , Antiviral Agents/therapeutic useABSTRACT
BACKGROUND: Previous studies show the uptake of biannual ultrasound (US) surveillance in patients with cirrhosis is suboptimal. Here, our goal was to understand in broader terms how surveillance is being delivered to cirrhosis patients with cured hepatitis C in the UK. METHODS: Hepatitis C cirrhosis patients achieving a sustained viral response (SVR) to antiviral therapies were identified from the national Hepatitis-C-Research-UK resource. Data on (i) liver/abdominal US examinations, (ii) HCC diagnoses, and (iii) HCC curative treatment were obtained through record-linkage to national health registries. The rate of US uptake was calculated by dividing the number of US episodes by follow-up time. RESULTS: A total of 1908 cirrhosis patients from 31 liver centres were followed for 3.8 (IQR: 3.4-4.9) years. Overall, 10 396 liver/abdominal USs were identified. The proportion with biannual US was 19% in the first 3 years after SVR and 9% for all follow-up years. Higher uptake of biannual US was associated with attending a liver transplant centre; older age and cirrhosis decompensation. Funnel plot analysis indicated significant inter-centre variability in biannual US uptake, with 6/29 centres outside control limits. Incident HCC occurred in 133 patients, of which 49/133 (37%) were treated with curative intent. The number of US episodes in the two years prior to HCC diagnosis was significantly associated with higher odds of curative-intent treatment (aOR: 1.53; 95% CI: 1.12-2,09; p = .007). CONCLUSIONS: This study provides novel data on the cascade of care for HCC in the UK. Our findings suggest biannual US is poorly targeted, inefficient and is not being delivered equitably to all patients.
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Carcinoma, Hepatocellular , Hepatitis C, Chronic , Hepatitis C , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/epidemiology , Liver Neoplasms/therapy , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/epidemiology , Liver Cirrhosis/therapy , Hepatitis C/complications , Hepatitis C/epidemiology , Hepatitis C/drug therapy , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/diagnostic imaging , Hepatitis C, Chronic/drug therapy , Hepacivirus , United Kingdom/epidemiology , Antiviral Agents/therapeutic use , Sustained Virologic ResponseABSTRACT
Hepatitis C virus infection (HCV) is common, and injecting drug use is the major risk factor for acquisition. Understanding HCV reinfection following treatment is an important consideration for HCV elimination programmes. The aim of this work was to assess the frequency and patterns of HCV reinfection in our region to develop avoidance strategies. All individuals who completed anti-HCV treatment with a known outcome in Tyne and Wear, England between January 2016 and May 2021 were included. This was a retrospective analysis of prospectively collected data. HCV reinfection was defined as positive HCV RNA after achieving sustained virological response 12 (SVR12). 788 of 840 patients (76% male; mean age 45.7 ± 11.9 years; 47% Genotype 1; 11% Cirrhosis; 20% started in prison) achieved SVR (94%). 443 patients (56%) had HCV RNA testing post-SVR after a median 0.82 (range 0.1-5.2) years. 56 reinfections (7.1% of all SVRs and 12.6% of SVRs who had post-SVR testing) were diagnosed. The median time to reinfection was 1.37 (range 0.1-4.0) years and the rate of reinfection was 10.5 /100 person years. 45 (80%) reinfections became chronic, 17 of whom were retreated and achieved SVR. 5 individuals developed a second reinfection. Younger age was the only factor independently associated with reinfection (HR 0.91 [0.88-0.94] p < .001). In conclusion, HCV reinfection is common and may slow our HCV elimination efforts. In order to address high reinfection rates, harm minimization approaches need improved, and we have implemented an 'HCV track and trace' pilot to try to reduce onwards HCV transmission.
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Hepatitis C, Chronic , Hepatitis C , Substance Abuse, Intravenous , Adult , Antiviral Agents/therapeutic use , Female , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Incidence , Male , Middle Aged , RNA, Viral/genetics , Recurrence , Reinfection , Retrospective Studies , Substance Abuse, Intravenous/complicationsABSTRACT
BACKGROUND AND AIMS: Patients with cirrhotic refractory ascites ineligible for transjugular intrahepatic shunt (TIPSS) have limited treatment options apart from repeated large volume paracentesis. The alfapump® is an implantable device mobilizing ascites from the peritoneal cavity to the bladder, from where it can be excreted. The aim of this observational cohort study was to prospectively investigate safety and efficacy of the device in a real-world cohort with cirrhotic refractory ascites and contraindications for TIPSS. METHODS: A total of 106 patients received an implant at 12 European centres and were followed up for up to 24 months. Complications, device deficiencies, frequency of paracentesis, clinical status and survival were recorded prospectively. RESULTS: Approximately half of the patients died on-study, about a quarter was withdrawn because of serious adverse events leading to explant, a sixth were withdrawn because of liver transplant or recovery, and nine completed follow-up. The most frequent causes of on-study death and complication-related explant were progression of liver disease and infection. The device reduced the requirement for large-volume paracentesis significantly, with more than half of patients not having required any post-implant. Survival benefits were not observed. Device-related reinterventions were predominantly caused by device deficiencies. A post-hoc comparison of the first 50 versus the last 50 patients enrolled revealed a decreased reintervention rate in the latter, mainly related to peritoneal catheter modifications. CONCLUSIONS: The device reduced paracentesis frequency in a real-world setting. Technical complications were successfully decreased by optimization of management and device modification (NCT01532427).
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Liver Transplantation , Portasystemic Shunt, Transjugular Intrahepatic , Ascites/etiology , Ascites/therapy , Humans , Liver Cirrhosis , Liver Transplantation/adverse effects , Paracentesis/adverse effects , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Portasystemic Shunt, Transjugular Intrahepatic/methods , RegistriesABSTRACT
AIM: Metabolic syndrome (MetS) is a cluster of factors including obesity, hypertension, diabetes, hypercholesterolemia and hyperlipidaemia. It has been associated with an increased risk of colorectal neoplasia. This systematic review and meta-analysis assessed the association between MetS and (i) recurrence of adenomas or occurrence of CRC in patients with prior adenomas, and (ii) survival in patients with CRC. METHOD: MEDLINE, Embase, Scopus and Web of Science were searched up to 22 November 2019. Two authors independently conducted title and abstract screening; full text of eligible studies was evaluated. Where ≥3 studies reported effect measures for a specific outcome, meta-analysis using random effects model was conducted. I2 was used to assess between-study heterogeneity. Quality appraisal was undertaken with the Newcastle-Ottawa Score. RESULTS: The search identified 1,764 articles, 55 underwent full text screening, resulting in a total of 15 eligible studies. Five studies reported on metachronous neoplasia, with differing outcomes precluded a meta-analysis. No consistent relationship between MetS and metachronous neoplasia was found. Ten studies reported on survival outcomes. MetS was associated with poorer CRC-specific survival (HR = 1.8, 95% CI: 1.04-3.12, I2 = 92.7%, n = 3). Progression-free survival was also worse but this did not reach statistical significance (HR = 1.12, 95% CI: 0.89-1.42, I2 = 85.6%, n = 3). There was no association with overall survival (HR = 1.04, 95% CI: 0.94-1.15, I2 = 43.7%, n = 7). Significant heterogeneity was present but subgroup analysis did not account for this. CONCLUSION: MetS is associated with poorer CRC-specific survival, but evidence is inconsistent on metachronous neoplasia. Further research is warranted to better understand the impact of MetS on the adenoma-carcinoma pathway.
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Adenoma , Colorectal Neoplasms , Metabolic Syndrome , Adenoma/complications , Adenoma/epidemiology , Adenoma/pathology , Colorectal Neoplasms/diagnosis , Humans , Metabolic Syndrome/complications , Metabolic Syndrome/epidemiology , ObesityABSTRACT
BACKGROUND & AIMS: Biopsy-confirmed liver fibrosis is a prognostic factor for patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with nonalcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint. METHODS: We searched the MEDLINE, Embase, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH. We collected data on mortality (all cause and liver related) and morbidity (cirrhosis, liver cancer, and all liver-related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, we calculated fibrosis stage-specific relative risk (RR) and 95% confidence interval (CI) values for mortality and morbidities. We performed fixed-effect and random-effect model meta-analyses. Metaregression was used to examine associations among study design (prospective vs retrospective cohort), overall risk of bias (medium or high), and mean duration of follow-up (in years). RESULTS: Our meta-analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared with no fibrosis (stage 0), unadjusted risk increased with increasing stage of fibrosis (stage 0 vs 4): all-cause mortality RR, 3.42 (95% CI, 2.63-4.46); liver-related mortality RR, 11.13 (95% CI, 4.15-29.84); liver transplant RR, 5.42 (95% CI, 1.05-27.89); and liver-related events RR, 12.78 (95% CI, 6.85-23.85). The magnitude of RR did not differ significantly after adjustment for confounders, including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings. CONCLUSIONS: In a systematic review and meta-analysis, we found biopsy-confirmed fibrosis to be associated with risk of mortality and liver-related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in patients with reported NASH. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid endpoint for use in clinical trials.
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Liver Cirrhosis/diagnosis , Liver/pathology , Non-alcoholic Fatty Liver Disease/mortality , Quality of Life , Severity of Illness Index , Biopsy , Confounding Factors, Epidemiologic , Humans , Liver Cirrhosis/mortality , Liver Cirrhosis/pathology , Non-alcoholic Fatty Liver Disease/pathology , Prognosis , Risk AssessmentABSTRACT
Whilst the benefit of direct-acting antiviral agents (DAAs) in achieving sustained virological response (SVR) is now well-accepted, their impact on liver function, particularly in relation to achievement of SVR, has not been well documented. We studied 2394 patients with chronic HCV infection, 1276 receiving DAAs and 1118 interferon-based therapy. Liver function was assessed by the albumin-bilirubin (ALBI) score or grade. Overall survival according to SVR status and baseline ALBI grade was examined. We also studied time to first decompensation according to ALBI grade, as well as longitudinal changes in ALBI score over time according to SVR. Among the patients receiving DAAs, 89% achieved SVR (Japan = 99%, UK = 78%). Amongst the decompensated patients in the UK cohort, three distinct risk groups according to ALBI grade at baseline were observed. The UK patients receiving DAAs, who had predominantly decompensated disease, showed clear evidence of improvement of liver function detectable within 2 years of the start of treatment, especially in those achieving SVR. These early changes in liver function were very similar to those observed in the first 2-3 years after interferon-based therapy. DAAs improve liver function especially in those with decompensated disease who achieve SVR. Experience with interferon-based therapy suggests that failure to achieve SVR is associated with long-term decline in liver function and, in contrast, patients who do achieve SVR can expect long-term disease improvement and subsequent stabilization of liver function. Our initial analysis suggests that those receiving DAAs are likely, in the long term, to follow a similar course.
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Hepatitis C, Chronic , Antiviral Agents/therapeutic use , Bilirubin , Hepacivirus , Hepatitis C, Chronic/drug therapy , Humans , Sustained Virologic ResponseABSTRACT
The first clinical case of persistent HEV infection in England was reported in 2009. We describe the demography, virology and outcomes of patients identified with persistent HEV infection in England and Wales between 2009 and 2017. A series of 94 patients with persistent HEV infection, defined by HEV viraemia of more than 12 weeks, was identified through routine reference laboratory testing. Virology, serology and clinical data were recorded through an approved PHE Enhanced Surveillance System. Sixty-six cases (70.2%) were transplant recipients, 16 (17.0%) had an underlying haematological malignancy without stem cell transplantation, six (6.4%) had advanced HIV infection, five (5.3%) were otherwise immunosuppressed, and one patient (1.1%) had no identified immunosuppression. Retrospective analysis of 46 patients demonstrated a median 38 weeks of viraemia before diagnostic HEV testing. At initial diagnosis, 16 patients (17.0%) had no detectable anti-HEV serological response. Of 65 patients treated with ribavirin monotherapy, 11 (16.9%) suffered virological relapse despite undetectable RNA in plasma or stool at treatment cessation. Persistent HEV infection remains a rare diagnosis, but we demonstrate that a broad range of immunocompromised patients are susceptible. Both lack of awareness and the pauci-symptomatic nature of persistent HEV infection likely contribute to significant delays in diagnosis. Diagnosis should rely on molecular testing since anti-HEV serology is insufficient to exclude persistent HEV infection. Finally, despite treatment with ribavirin, relapses occur even after cessation of detectable faecal shedding of HEV RNA, further emphasising the requirement to demonstrate sustained virological responses to treatment.
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HIV Infections , Hepatitis E virus , Hepatitis E , Demography , Hepatitis E/diagnosis , Hepatitis E/epidemiology , Hepatitis E virus/genetics , Humans , Immunocompromised Host , Neoplasm Recurrence, Local , RNA, Viral , Retrospective Studies , Wales/epidemiologyABSTRACT
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is linked to excessive calorie consumption, physical inactivity, and being overweight. Patients with NAFLD can halt or decelerate progression and potentially reverse their condition by changing their lifestyle behavior. International guidelines recommend the use of lifestyle interventions; however, there remains a discordance between published guidelines and clinical practice. This is primarily due to a lack of NAFLD-specific interventions to support weight loss and improve liver function. OBJECTIVE: This study aims to use intervention mapping to systematically develop a digital intervention to support patients with NAFLD to initiate and maintain changes in their dietary and physical activity behavior to promote weight loss. METHODS: Intervention mapping consisted of 6 steps: step 1 involved a needs assessment with primary and secondary health care professionals (HCPs) and patients with NAFLD; step 2 involved identification of the social cognitive determinants of change and behavioral outcomes of the intervention; step 3 involved linking social cognitive determinants of behavioral outcomes with behavior change techniques to effectively target dietary and physical activity behavior; step 4 involved the development of a prototype digital intervention that integrated the strategies from step 3, and the information content was identified as important for improving knowledge and skills from steps 1 and 2; step 5 involved the development of an implementation plan with a digital provider of lifestyle behavior change programs to patients with NAFLD using their delivery platform and lifestyle coaches; and step 6 involved piloting the digital intervention with patients to obtain data on access, usability, and content. RESULTS: A digital intervention was developed, consisting of 8 modules; self-regulatory tools; and provision of telephone support by trained lifestyle coaches to help facilitate behavioral intention, enactment, and maintenance. A commercial provider of digital lifestyle behavior change programs enrolled 16 patients with NAFLD to the prototype intervention for 12 consecutive weeks. A total of 11 of the 16 participants successfully accessed the intervention and continued to engage with the content following initial log-in (on average 4 times over the piloting period). The most frequently accessed modules were welcome to the program, understanding NAFLD, and food and NAFLD. Goal setting and self-monitoring tools were accessed on 22 occasions (4 times per tool on average). A total of 3 out of 11 participants requested access to a lifestyle coach. CONCLUSIONS: Intervention mapping provided a systematic methodological framework to guide a theory- and evidence-informed co-design intervention development process for patients and HCPs. The digital intervention with remote support by a lifestyle coach was acceptable to patients with NAFLD and feasible to deliver. Issues with initial access, optimization of information content, and promoting the value of remote lifestyle coach support require further development ahead of future research to establish intervention effectiveness.
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Diet Therapy/methods , Life Style , Motor Activity/physiology , Non-alcoholic Fatty Liver Disease/therapy , Weight Loss/physiology , Adult , Aged , Female , Humans , Male , Middle AgedABSTRACT
To achieve elimination of hepatitis C (HCV), a critical group to prioritise for diagnosis and treatment is the prison population, where HCV prevalence is high. A universal offer of blood-borne virus testing (UOBBVT) programme and a new treatment pathway were introduced to seven North East England (NEE) Prisons. Our aim was to assess: (a) the proportion of individuals with active HCV commencing direct-acting antivirals (DAAs); (b) the outcomes following DAA treatment; (3) the reinfection rate following sustained virological response (SVR). Data were collected prospectively on BBVT uptake, HCV positivity, HCV treatment outcomes and reinfection from March 2016 onwards. 8538 individuals had BBV testing. In total, 612 (7.2%) and 374 (4.4%) were HCV antibody positive and HCV RNA positive, respectively. Ultimately, 266 (71%) individuals commenced DAAs. Overall 111 achieved a documented SVR (42%), 17 (6%) failed treatment, 30 (11%) were still on treatment or had not reached 12 weeks post-treatment at time of analysis, and 108 (41%) were lost to follow-up. In those with a known outcome (n = 128), 87% achieved SVR. Worryingly, of those who achieved SVR, 21 (19%) were subsequently identified as having been reinfected (median time from SVR to documented reinfection 13 (range 7-25) months). The reinfection rate was 0.406 cases per person-year follow-up. In conclusion, Implementation of a UOBBVT programme and new treatment pathway resulted in increased diagnosis and treatment of HCV in the NEE prison population. However, the high HCV reinfection rate suggests a need to improve harm reduction approaches.
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Antiviral Agents , Hepatitis C , Reinfection , Substance Abuse, Intravenous , Antiviral Agents/therapeutic use , Cohort Studies , England , Hepatitis C/drug therapy , Humans , Prisons , Recurrence , Substance Abuse, Intravenous/drug therapyABSTRACT
Hepatitis B virus (HBV) infection is estimated to affect 292 million people worldwide, 90% of them are unaware of their HBV status. The Determine HBsAg 2 (Alere Medical Co, Ltd Chiba Japan [Now Abbott]) is a rapid test that meets European Union (EU) regulatory requirements for Hepatitis B surface antigen 2 (HBsAg) analytical sensitivity, detecting the 0.1 IU/mL World Health Organization (WHO) International HBsAg Standard. This prospective, multicentre study was conducted to establish its clinical performance. 351 evaluable subjects were enrolled, 145 HBsAg-positive. The fingerstick whole blood sensitivity and specificity were 97.2% and 98.5% (15' reading, reference assay cut-off 0.05 IU/mL), sensitivity increasing to 97.9% with the prespecified cut-off 0.13 IU/mL (EU regulations). The venous whole blood, serum and plasma sensitivity was 97.2%, 97.9%, and 98.6%, respectively (15' reading); reaching 99%, 99.5% and 100% specificity. A testing algorithm following up an initial positive fingerstick test result with plasma/serum test demonstrates 100% specificity. The Determine HBsAg 2 test gives 15-minute results with high sensitivity and specificity, making it an ideal tool for point-of-care testing, with the potential to enable large-scale population-wide screening to reach the WHO HBV diagnostic targets. The evaluated test improves the existing methods as most of the reviewed rapid tests do not meet the EU regulatory requirements of sensitivity.
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BACKGROUND & AIMS: Cardiovascular disease is the principle cause of death in patients with elevated liver fat unrelated to alcohol consumption, more so than liver-related morbidity and mortality. The aim of this study was to evaluate the relationship between liver fat and cardiac and autonomic function, as well as to assess how impairment in cardiac and autonomic function is influenced by metabolic risk factors. METHODS: Cardiovascular and autonomic function were assessed in 96 sedentary individuals: i) non-alcoholic fatty liver disease (NAFLD) (nâ¯=â¯46, hepatic steatosis >5% by magnetic resonance spectroscopy), ii) Hepatic steatosis and alcohol (dual aetiology fatty liver disease [DAFLD]) (nâ¯=â¯16, hepatic steatosis >5%, consuming >20â¯g/day of alcohol) and iii) CONTROL (nâ¯=â¯34, no cardiac, liver or metabolic disorders, <20â¯g/day of alcohol). RESULTS: Patients with NAFLD and DAFLD had significantly impaired cardiac and autonomic function when compared with controls. Diastolic variability and systolic variability (LF/HF-sBP [n/1]; 2.3 (1.7) and 2.3 (1.5) vs. 3.4 (1.5), p <0.01) were impaired in patients with NAFLD and DAFLD when compared to controls, with DAFLD individuals showing a decrease in diastolic variability relative to NAFLD patients. Hepatic steatosis and fasting glucose were negatively correlated with stroke volume index. Fibrosis stage was significantly negatively associated with mean blood pressure (râ¯=â¯-0.47, pâ¯=â¯0.02), diastolic variability (râ¯=â¯-0.58, pâ¯≤0.01) and systolic variability (râ¯=â¯-0.42, pâ¯=â¯0.04). Hepatic steatosis was independently associated with cardiac function (pâ¯≤0.01); TNF-α (pâ¯≤0.05) and CK-18 (pâ¯≤0.05) were independently associated with autonomic function. CONCLUSION: Cardiac and autonomic impairments appear to be dependent on level of liver fat, metabolic dysfunction, inflammation and fibrosis staging, and to a lesser extent alcohol intake. Interventions should be sought to moderate the excess cardiovascular risk in patients with NAFLD or DAFLD. LAY SUMMARY: Increased levels of fat in the liver impair the ability of the cardiovascular system to work properly. The amount of fat in the liver, metabolic control, inflammation and alcohol are all linked to the degree that the cardiovascular system is affected.
Subject(s)
Autonomic Nervous System/physiopathology , Fatty Liver/physiopathology , Heart/physiopathology , Adult , Aged , Cardiovascular Diseases/etiology , Fatty Liver/complications , Female , Hemodynamics/physiology , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/physiopathologyABSTRACT
BACKGROUND & AIMS: Dietary interventions for weight loss are effective therapies for nonalcoholic fatty liver disease (NAFLD). The Mediterranean diet might benefit these patients, but it is not followed consistently in Northern European countries. We examined factors that determine Mediterranean diet adoption and maintenance in a northern European population. METHODS: We used a mixed-methods approach to investigate the effects of a 12-week Mediterranean diet intervention and perceived barriers and facilitators. Nineteen adults with NAFLD were recruited from a tertiary hepatology center in England. Participants were taught behavioral strategies through the provision of shopping lists, meal planners, and recipes; no advice was given on calorie allowances or physical activities. We used the 14-point Mediterranean diet assessment tool to assess dietary intake, based on a small number of foods in servings per day or servings per week, at baseline and after 12 weeks; participants were assigned scores of low (<5 points), moderate (6-9 points), or high (10-14 points). Semistructured interviews were audiorecorded, transcribed, and analyzed using the framework method. RESULTS: Twelve weeks after the dietary advice, Mediterranean diet adoption significantly increased from moderate to high (mean increase, 2.2 points; from 7.6 ± 2.5 at baseline to 9.8 ± 2.8 at 12 wk) (P = .006). This increase was associated with a mean reduction in body weight of 2.4 kg (from 99.2 ± 17.0 kg at baseline to 96.8 ± 17.5 kg at 12 wk) (P = .001) and increased serum concentrations of high-density lipoprotein cholesterol in 72% of participants (from 1.10 ± 0.8 at baseline to 1.20 ± 1.30 vs 1.00 ± 0.5 at 12 wk) (P = .009). Increased nutrition knowledge and skills, family support, Mediterranean diet promotion in media and clinical settings, and nutritional care facilitated diet changes. Barriers to Mediterranean diet uptake included an obesogenic environment, life stressors, and demand for convenience. Poor understanding of the causes and significance of NAFLD adversely affected readiness to change dietary habits. CONCLUSIONS: In an analysis of patients with NAFLD in the northern United Kingdom, we found a 12-week Mediterranean diet intervention was acceptable and associated with significant reductions in body weight and increased serum levels of high-density lipoprotein. We identified barriers and facilitators that could support appropriate treatment adaptations and guide personalized intervention approaches.
Subject(s)
Diet, Mediterranean , Feeding Behavior , Non-alcoholic Fatty Liver Disease/diet therapy , Patient Compliance , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/epidemiology , United Kingdom/epidemiologyABSTRACT
Following the introduction of direct-acting antivirals (DAA), there have been reports of declining incidence of hepatitis C (HCV)-related liver disease as a liver transplantation indication. In this study, we assessed the impact of DAA on liver transplant indications in the UK and waiting list outcomes for patients with HCV. We assessed UK adult elective liver transplant registrants between 2006 and 2017. The aetiology of liver disease at registration was reclassified using an accepted hierarchical system and changes were assessed over time and compared before and after the introduction of DAA. Registration UKELD scores and 1-year waiting list outcomes were also compared. The proportion of waiting list patients registered with HCV-related cirrhosis reduced after the introduction of DAA from 10.5% in 2013 to 4.7% in 2016 (P < 0.001). Alcohol-related liver disease (ARLD) was the leading indication for liver transplantation followed by liver cancer (26.1% and 18.4% in 2016, respectively). The proportion of registrations with Hepatocellular carcinoma (HCC) associated with HCV reduced from 46.4% in 2013 to 33.7% in 2016 (P = 0.002). For patients with HCV-related cirrhosis at one year the outcomes of death, transplantation, delisting due to improvement or deterioration and awaiting a graft at 1 year were similar. For patients with HCV-related HCC, the proportion dying at 1 year reduced significantly from 2.9% to 0.0% (P = 0.04). These data demonstrate an association between DAA and reduced listing rates for HCV-related cirrhosis and HCC, but no significant changes in waiting list outcomes other than reduced mortality in the HCC group.
Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/virology , Hepatitis C/drug therapy , Liver Cirrhosis/virology , Liver Neoplasms/virology , Liver Transplantation/statistics & numerical data , Waiting Lists , Adult , Hepatitis C/complications , Humans , Liver Transplantation/trends , Retrospective Studies , Severity of Illness Index , Treatment Outcome , United KingdomABSTRACT
With recent advances in antiviral therapy, there is an opportunity to eliminate hepatitis C virus (HCV) from the UK population. HCV is common in incarcerated individuals, with previous estimates suggesting ~7% of the UK prison population is anti-HCV antibody positive. Increasing diagnosis and treatment of HCV in prison is a priority in seeking to eliminate transmission in the general population. Thus the study aimed to assess the impact implementation of: (a) A universal offer of blood borne virus testing (UOBBVT) using dry blood spot testing for prisoners at reception to increase diagnosis; (b) Telemedicine clinics (TC) within North East England (NEE) prisons to increase HCV treatment rates. UOBBVT was initially implemented at Her Majesty's Prison (HMP) Durham, commencing March 2016. From March 2016 to February 2017, 2831 of 4280 (66%) new receptions were offered blood borne virus (BBV) testing. Of these, 1495 (53% of offered) accepted BBV testing, of whom 95 (6.4%) were HCV antibody positive, with 47 of those 95 (49.5%) HCV RNA positive, suggesting a prevalence of active infection in the tested population of 3.1% (95% CI 2.4%-4.2%). Between August 2015 and October 2017, 80 individuals were seen in the TC and 57 (71%) commenced antiviral therapy. Of those with known outcome (n = 29), 100% achieved sustained virological response. In the year prior to implementation, only four patients received HCV treatment. In conclusion, a universal offer of BBV testing to inmates presenting at HMP reception coupled with linkage into specialist care via TC can substantially increase rates of testing, diagnosis and treatment of HCV in this high-prevalence population.
Subject(s)
Dried Blood Spot Testing/statistics & numerical data , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Prisoners/statistics & numerical data , Telemedicine/statistics & numerical data , Antiviral Agents/therapeutic use , England , Hepatitis C/prevention & control , Hepatitis C Antibodies/blood , Humans , Male , Pilot Projects , Prevalence , PrisonsABSTRACT
OBJECTIVE: Liver biopsy is currently the most reliable way of evaluating liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Its inherent risks limit its widespread use. Differential liver DNA methylation of peroxisome proliferator-activated receptor gamma (PPARγ) gene promoter has recently been shown to stratify patients in terms of fibrosis severity but requires access to liver tissue. The aim of this study was to assess whether DNA methylation of circulating DNA could be detected in human plasma and potentially used to stratify liver fibrosis severity in patients with NAFLD. DESIGN: Patients with biopsy-proven NAFLD and age-matched controls were recruited from the liver and gastroenterology clinics at the Newcastle upon Tyne Hospitals NHS Foundation Trust. Plasma cell-free circulating DNA methylation of PPARγ was quantitatively assessed by pyrosequencing. Liver DNA methylation was quantitatively assessed by pyrosequencing NAFLD explant tissue, subjected to laser capture microdissection (LCM). Patients with alcoholic liver disease (ALD) were also subjected to plasma DNA and LCM pyrosequencing. RESULTS: 26 patients with biopsy-proven NAFLD were included. Quantitative plasma DNA methylation of PPARγ stratified patients into mild (Kleiner 1-2) and severe (Kleiner 3-4) fibrosis (CpG1: 63% vs 86%, p<0.05; CpG2: 51% vs 65% p>0.05). Hypermethylation at the PPARγ promoter of plasma DNA correlated with changes in hepatocellular rather than myofibroblast DNA methylation. Similar results were demonstrated in patients with ALD cirrhosis. CONCLUSIONS: Differential DNA methylation at the PPARγ promoter can be detected within the pool of cell-free DNA of human plasma. With further validation, plasma DNA methylation of PPARγ could potentially be used to non-invasively stratify liver fibrosis severity in patients with NAFLD. Plasma DNA methylation signatures reflect the molecular pathology associated with fibrotic liver disease.
Subject(s)
DNA Methylation , Liver Cirrhosis/genetics , Non-alcoholic Fatty Liver Disease/genetics , PPAR gamma/genetics , Severity of Illness Index , Case-Control Studies , Female , Genetic Markers , High-Throughput Nucleotide Sequencing , Humans , Liver Cirrhosis/pathology , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/pathology , PPAR gamma/metabolismABSTRACT
BACKGROUND & AIMS: Pharmacologic treatments for nonalcoholic steatohepatitis (NASH) are limited. Lifestyle interventions are believed to be effective in reducing features of NASH, although the effect of regular exercise, independent of dietary change, is unclear. We performed a randomized controlled trial to study the effect of exercise on hepatic triglyceride content (HTGC) and biomarkers of fibrosis in patients with NASH. METHODS: Twenty-four patients (mean age, 52 ± 14 y; body mass index, 33 ± 6 kg/m2) with sedentary lifestyles (<60 min/wk of moderate-vigorous activity) and biopsy-proven NASH were assigned randomly to groups that exercised (n = 12) or continued standard care (controls, n = 12) for 12 weeks while maintaining their weight. The exercise (cycling and resistance training) was supervised at an accredited sports center and supervised by a certified exercise specialist and recorded 3 times per week on nonconsecutive days. We measured HTGC, body composition, circulating markers of inflammation, fibrosis, and glucose tolerance at baseline and at 12 weeks. RESULTS: Compared with baseline, exercise significantly reduced HTGC (reduction of 16% ± 24% vs an increase of 9% ± 15% for controls; P < .05), visceral fat (reduction of 22 ± 33 cm2 vs an increase of 14 ± 48 cm2 for controls; P < .05), plasma triglycerides (reduction of 0.5 ± 1.0 mmol/L vs an increase of 0.3 ± 0.4 mmol/L for controls; P < .05), and γ-glutamyltransferase (reduction of 10 ± 28 U/L-1 vs a reduction of 17 ± 38 U/L-1 for controls; P < .05). There were no effects of exercise on liver enzyme levels, metabolic parameters, circulatory markers of inflammation (levels of interleukin 6, tumor necrosis factor-α, or C-reactive protein) and fibrosis. CONCLUSIONS: In a randomized controlled trial, 12 weeks of exercise significantly reduced HTGC, visceral fat, and plasma triglyceride levels in patients with NASH, but did not affect circulating markers of inflammation or fibrosis. Exercise without weight loss therefore affects some but not all factors associated with NASH. Clinical care teams should consider exercise as part of a management strategy of NASH, but weight management strategies should be included. Larger and longer-term studies are required to determine the effects of exercise in patients with NASH. ISRCTN registry.com: ISRCTN16070927.