Impact of previous hepatitis B infection on the clinical outcomes from chronic hepatitis C? A population-level analysis.

Chronic coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is associated with adverse liver outcomes. The clinical impact of previous HBV infection on liver disease in HCV infection is unknown. We aimed at determining any association of previous HBV infection with liver outcomes using antibodies to the hepatitis B core antigen (HBcAb) positivity as a marker of exposure. The Scottish Hepatitis C Clinical Database containing data for all patients attending HCV clinics in participating health boards was linked to the HBV diagnostic registry and mortality data from Information Services Division, Scotland. Survival analyses with competing risks were constructed for time from the first appointment to decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver-related mortality. Records of 8513 chronic HCV patients were included in the analyses (87 HBcAb positive and HBV surface antigen [HBsAg] positive, 1577 HBcAb positive and HBsAg negative, and 6849 HBcAb negative). Multivariate cause-specific proportional hazards models showed previous HBV infection (HBcAb positive and HBsAg negative) significantly increased the risks of decompensated cirrhosis (hazard ratio [HR]: 1.29, 95% CI: 1.01-1.65) and HCC (HR: 1.64, 95% CI: 1.09-2.49), but not liver-related death (HR: 1.02, 95% CI: 0.80-1.30). This is the largest study to date showing an association between previous HBV infection and certain adverse liver outcomes in HCV infection. Our analyses add significantly to evidence which suggests that HBV infection adversely affects liver health despite apparent clearance. This has important implications for HBV vaccination policy and indications for prioritization of HCV therapy.

The use of selective serotonin receptor inhibitors (SSRIs) is not associated with increased risk of endoscopy-refractory bleeding, rebleeding or mortality in peptic ulcer bleeding.

BACKGROUND: Observational studies have consistently shown an increased risk of upper gastrointestinal bleeding in users of selective serotonin receptor inhibitors (SSRIs), probably explained by their inhibition of platelet aggregation. Therefore, treatment with SSRIs is often temporarily withheld in patients with peptic ulcer bleeding. However, abrupt discontinuation of SSRIs is associated with development of withdrawal symptoms in one-third of patients. Further data are needed to clarify whether treatment with SSRIs is associated with poor outcomes, which would support temporary discontinuation of treatment. AIM: To identify if treatment with SSRIs is associated with increased risk of: (1) endoscopy-refractory bleeding, (2) rebleeding or (3) 30-day mortality due to peptic ulcer bleeding. METHODS: A nationwide cohort study. Analyses were performed on prospectively collected data on consecutive patients admitted to hospital with peptic ulcer bleeding in Denmark in the period 2006-2014. Logistic regression analyses were used to investigate the association between treatment with SSRIs and outcome following adjustment for pre-defined confounders. Sensitivity and subgroup analyses were performed to evaluate the validity of the findings. RESULTS: A total of 14 343 patients were included. Following adjustment, treatment with SSRIs was not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] [95% Confidence Interval (CI)]: 1.03 [0.79-1.33]), rebleeding (OR [95% CI]: 0.96 [0.83-1.11]) or 30-day mortality (OR [95% CI]: 1.01 [0.85-1.19]. These findings were supported by sensitivity and subgroup analyses. CONCLUSIONS: According to our data, treatment with SSRIs does not influence the risk of endoscopy-refractory bleeding, rebleeding or 30-day mortality in peptic ulcer bleeding.

Costs and quality of life associated with acute upper gastrointestinal bleeding in the UK: cohort analysis of patients in a cluster randomised trial.

OBJECTIVES: Data on costs associated with acute upper gastrointestinal bleeding (AUGIB) are scarce. We provide estimates of UK healthcare costs, indirect costs and health-related quality of life (HRQoL) for patients presenting to hospital with AUGIB. SETTING: Six UK university hospitals with >20 AUGIB admissions per month, >400 adult beds, 24 h endoscopy, and on-site access to intensive care and surgery. PARTICIPANTS: 936 patients aged ≥18 years, admitted with AUGIB, and enrolled between August 2012 and March 2013 in the TRIGGER trial of AUGIB comparing restrictive versus liberal red blood cell (RBC) transfusion thresholds. PRIMARY AND SECONDARY OUTCOME MEASURES: Healthcare resource use during hospitalisation and postdischarge up to 28  days, unpaid informal care, time away from paid employment and HRQoL using the EuroQol EQ-5D at 28  days were measured prospectively. National unit costs were used to value resource use. Initial in-hospital treatment costs were upscaled to a UK level. RESULTS: Mean initial in-hospital costs were £2458 (SE=£216) per patient. Inpatient bed days, endoscopy and RBC transfusions were key cost drivers. Postdischarge healthcare costs were £391 (£44) per patient. One-third of patients received unpaid informal care and the quarter in paid employment required time away from work. Mean HRQoL for survivors was 0.74. Annual initial inhospital treatment cost for all AUGIB cases in the UK was estimated to be £155.5 million, with exploratory analyses of the incremental costs of treating hospitalised patients developing AUGIB generating figures of between £143 million and £168 million. CONCLUSIONS: AUGIB is a large burden for UK hospitals with inpatient stay, endoscopy and RBC transfusions as the main cost drivers. It is anticipated that this work will enable quantification of the impact of cost reduction strategies in AUGIB and will inform economic analyses of novel or existing interventions for AUGIB. TRIAL REGISTRATION NUMBER: ISRCTN85757829 and NCT02105532.

Attendance at specialist hepatitis clinics and initiation of antiviral treatment among persons chronically infected with hepatitis C: examining the early impact of Scotland's Hepatitis C Action Plan.

Primary goals of the Hepatitis C Action Plan for Scotland Phase II (May 2008-March 2011) were to increase, among persons chronically infected with the hepatitis C (HCV) virus, attendance at specialist outpatient clinics and initiation on antiviral therapy. We evaluated progress towards these goals by comparing the odds, across time, of (a) first clinic attendance within 12 months of HCV diagnosis (n = 9747) and (b) initiation on antiviral treatment within 12 months of first attendance (n = 5736). Record linkage between the national HCV diagnosis (1996-2009) and HCV clinical (1996-2010) databases and logistic regression analyses were conducted for both outcomes. For outcome (a), 32% and 45% in the respective pre-Phase II (before 1 May 2008) and Phase II periods attended a specialist clinic within 12 months of diagnosis; the odds of attendance within 12 months increased over time (OR = 1.05 per year, 95% CI: 1.04-1.07), but was not significantly greater for persons diagnosed with HCV in the Phase II era, compared with the pre-Phase II era (OR = 1.1, 95% CI: 0.9-1.3), after adjustment for temporal trend. For outcome (b), 13% and 28% were initiated on treatment within 12 months of their first clinic attendance in the pre-Phase II and Phase II periods, respectively. Higher odds of treatment initiation were associated with first clinic attendance in the Phase II (OR = 1.9, 95% CI: 1.5-2.4), compared with the pre-Phase II era. Results were consistent with a positive impact of the Hepatitis C Action Plan on the treatment of chronically infected individuals, but further monitoring is required to confirm a sustained effect.

The efficacy and safety of treating hepatitis C in patients with a diagnosis of schizophrenia.

Treating chronic hepatitis C with pegylated interferon alpha may induce or exacerbate psychiatric illness including depression, mania and aggressive behaviour. There is limited data regarding treatment in the context of chronic schizophrenia. We sought to establish the safety and efficacy of treating patients with schizophrenia. Patient and treatment data, prospectively collected on the Scottish hepatitis C database, were analysed according to the presence or absence of a diagnosis of schizophrenia. Time from referral to treatment, and the proportion of patients commencing treatment in each group, was calculated. Outcomes including sustained viral response rates, reasons for treatment termination and adverse events were compared. Of 5497 patients, 64 (1.2%) had a diagnosis of schizophrenia. Patients with schizophrenia (PWS) were as likely to receive treatment as those without [28/61(46%) vs 1639/4415 (37%) P = 0.19]. Sustained viral response (SVR) rates were higher in PWS [21/25 (84%) vs 788/1453 (54%) P < 0.01]. SVR rates by genotype were similar [4/8 (50%) vs 239/684 (35%) Genotype 1 (P = 0.56), 17/17 (100%) vs 599/742 (81%) non-Genotype 1 (P = 0.09)]. Adverse events leading to cessation of treatment were comparable [2/25(8%) vs 189/1453 (13%) P: 0.66]. Patients with schizophrenia are good candidates for hepatitis C treatment, with equivalent SVR and treatment discontinuation rates to patients without schizophrenia.

The use of hemospray in portal hypertensive bleeding; a case series.

Hemospray is a haemostatic agent licensed for endoscopic haemostasis of non-variceal upper gastrointestinal bleeding (NVUGIB) in Europe and Canada. Hemospray has been shown to be safe and effective in achieving haemostasis in bleeding peptic ulcers in a prospective clinical study and several further case series have described the use of hemospray in other non-variceal causes of gastrointestinal bleeding. Portal hypertensive gastropathy and colopathy are common in patients with portal hypertension. As hemospray is an easy to apply, non-contact method, which can cover large areas of mucosa, it may be of benefit in acute non-variceal portal hypertensive bleeding. We present data from the first four consecutive patients presenting to our institution with acute haemorrhage secondary to non-variceal diffuse portal hypertensive bleeding treated with hemospray.

The management of alcoholic hepatitis: a prospective comparison of scoring systems.

BACKGROUND: The assessment of alcoholic hepatitis remains controversial. Several scores have been developed or used for this purpose. AIM: To study the use of the Glasgow Alcoholic Hepatitis Score (GAHS), the Discriminant Function (DF), Model for End-Stage Liver Disease (MELD) and the ABIC (age, bilirubin, INR and creatinine) scores as well as scores to assess corticosteroid response in the management of alcoholic hepatitis. METHODS: A total of 182 patients were studied prospectively. The GAHS, MELD, ABIC and DF scores were recorded on admission and serially over the first week of hospital management. Treatment with corticosteroids or pentoxifylline was considered if the GAHS was ≥9. RESULTS: There were no differences in outcome between favourable scores as per recommended cut-off points. Patients with a GAHS<9 had similar outcome whether their MELD, DF or ABIC scores were favourable or unfavourable. Treated patients with a GAHS≥9 had a significantly better 90-day outcome than those who did not: 58% and 30% respectively, P = 0.01; HR 0.33 (0.14, 0.78). Patients treated with corticosteroids who had a fall in bilirubin of 25% after a week of treatment had an improved survival: 82% compared with 44% [P = 0.0005: HR 3.70 (1.77, 7.73)]. The Lille Score or a 25% fall in bilirubin had greater sensitivities than an early change in bilirubin level (95% and 90% compared with 58%) to assess treatment response. CONCLUSIONS: In this single-centre study, a GAHS ≥9 identified patients who may benefit from treatment of alcoholic hepatitis. Intention-to-treat randomised-controlled trials using a GAHS ≥9 as the threshold for treatment are needed to validate these findings. Response to corticosteroids can be assessed using the Lille Score or by a 25% fall in bilirubin.

Upper gastrointestinal bleeding: what's the score?

Upper gastrointestinal haemorrhage (UGIH) is a common medical emergency. Recent publications have emphasised the need for early risk assessment of patients with this condition to help direct management. Several risk scores have been developed for UGIH and are variably used in clinical practice. In this article, we discuss the various risk scoring systems for this condition and summarise the available evidence for their use.

Multicentre comparison of the Glasgow Blatchford and Rockall Scores in the prediction of clinical end-points after upper gastrointestinal haemorrhage.

BACKGROUND: The Glasgow Blatchford Score (GBS) is increasingly being used to predict intervention and outcome following upper gastrointestinal haemorrhage (UGIH). AIM: To compare the GBS with both the admission and full Rockall scores in predicting specific clinical end-points following UGIH. PATIENTS AND METHODS: Data on consecutive patients presenting to four UK hospitals were collected. Admission history, clinical and laboratory data, endoscopic findings, treatment and clinical follow-up were recorded. Using ROC curves, we compared the three scores in the prediction of death, endoscopic or surgical intervention and transfusion. Results A total of 1555 patients (mean age 56.7years) presented with UGIH during the study period. Seventy-four (4.8%) died, 223 (14.3%) had endoscopic or surgical intervention and 363 (23.3%) required transfusion. The GBS was similar at predicting death compared with both the admission Rockall (area under ROC curve 0.804 vs. 0.801) and full Rockall score (AUROC 0.741 vs. 0.790). In predicting endo-surgical intervention, the GBS was superior to the admission Rockall (AUROC 0.858 vs. 0.705; P<0.00005) and similar to the full Rockall score (AUROC 0.822 vs. 0.797). The GBS was superior to both admission Rockall (AUROC 0.944 vs. 0.756; P<0.00005) and full Rockall scores (AUROC 0.935 vs. 0.792; P<0.00005) in predicting need for transfusion. CONCLUSIONS: Despite not incorporating age, the GBS is as effective as the admission and full Rockall scores in predicting death after UGIH. It is superior to both the admission and full Rockall scores in predicting need for transfusion, and superior to the admission Rockall score in predicting endoscopic or surgical intervention.

Long-term follow-up of endoscopic Histoacryl glue injection for the management of gastric variceal bleeding.

BACKGROUND: Variceal bleeding is an acute medical emergency with high mortality. Although less common than oesophageal variceal haemorrhage, gastric variceal bleeding is more severe and more difficult to control. The optimal therapy for gastric variceal bleeding remains unclear although endoscopic injection of N-Butyl-2-Cyanoacrylate (Histoacryl) glue is often used. However, its long-term efficacy is poorly described. We studied the immediate and long-term effects of Histoacryl glue injection as treatment for bleeding gastric varices in a large UK hospital. METHOD: Endoscopy records and case notes were used to identify patients receiving Histoacryl injection for gastric variceal bleeding over a 4-year period. RESULTS: Thirty-one patients received Histoacryl for gastric variceal bleeding. Seventy-four per cent patients had alcohol-related liver disease and 61% of cirrhotics were Childs Pugh grade B or C. Fifty-eight per cent were actively bleeding during the procedure with 100% haemostasis rates achieved. Two patients developed pyrexia within 24 h of injection settling with antibiotics. No other complications were encountered. Mean overall follow-up was 35 months, with mean follow-up of survivors 57 months. Forty-eight per cent patients had endoscopic ultrasound assessment of varices during follow-up with no effect on rebleeding rates. Thirteen per cent required subsequent transjugular intrahepatic portosystemic shunt placement. Gastric variceal rebleeding rate was 10% at 1 year and 16% in total. One- and two-year mortality was 23% and 35%, respectively. CONCLUSION: Endoscopic injection of Histoacryl glue appears to be a safe and effective treatment for gastric variceal bleeding. Further data are required to compare it with other therapies in this situation.

The changing face of hepatitis B in greater Glasgow: epidemiological trends 1993-2007.

BACKGROUND AND AIMS: Whilst hepatitis B (HBV) is historically uncommon in Scotland, anecdotal experience suggests an increasing prevalence of chronic infection. We sought to establish whether the incidence of chronic HBV is increasing in Greater Glasgow, and whether patients are assessed in secondary care. METHODS: The regional virus centre database identified HBV surface antigen (HBsAg) positive samples. For adult patients tested in Glasgow between 1993-2007 the first positive test was identified and classified as acute or chronic infection serologically. Clinic referral and attendance data was then obtained. RESULTS: 1,672 patients tested HBsAg positive; 1051 with chronic infection, 421 acute and 200 indeterminate. New diagnoses of HBV remained stable over time, however falling numbers of acute cases were mirrored by a rise in chronic cases from 40 to 119 per annum between 2000 and 2007. Of 193 patients diagnosed in 2006 and 2007, 51% were not seen in secondary care due to non referral (43%) or non attendance (8%). CONCLUSION: Chronic HBV trebled in Glasgow between 2000 and 2007. Most patients were not assessed in secondary care. Improved levels of clinic referral and attendance are required to ensure best care for HBV patients in Glasgow.

Prevalence of genetic haemochromatosis and iron overload in patients attending rheumatology and joint replacement clinics.

BACKGROUND & AIMS: Genetic Haemochromatosis (GH) is common in North European and Celtic populations and is associated with arthropathy. We aimed to measure the frequency of the common GH mutations (C282Y and H63D), the carrier frequency of C282Y and markers of iron overload in patients who were referred to our rheumatology and joint replacement clinics. METHODS: Unselected patients attending these clinics were anonymously tested for the described mutations. Transferrin saturation and serum ferritin were also measured and if elevated, the patients had predictive counselling then named GH mutation testing. The carrier and mutation frequencies were also determined in 340 local controls. RESULTS: One hundred and sixty-one unselected patients attending these clinics were studied. The C282Y mutation carrier frequency was 1 in 5.2 in patients compared with 1 in 8.1 in controls (p < 0.005). The overall mutation frequencies were similar in patients and controls. One patient was found to be a homozygous for the C282Y mutation and eight were compound heterozygotes. Seven other patients had a raised ferritin, one of whom was a C282Y heterozygote. CONCLUSION: The C282Y carrier frequency is significantly higher in patients attending rheumatology and joint replacement clinics than in controls. Screening of these patients for GH should be considered.

The transjugular intrahepatic portosystemic shunt (TIPS).

The creation of an intrahepatic portosystemic shunt via a transjugular approach (TIPS) is an interventional radiological procedure used to treat the complications of portal hypertension. TIPS insertion is principally indicated to prevent or arrest variceal bleeding when medical or endoscopic treatments fail, and in the management refractory ascites. This review discusses the development and execution of the technique, with focus on its clinical efficacy. Patient selection, imaging surveillance, revision techniques, and complications are also discussed.

Impact of EUS-FNA in the management of patients with oesophageal cancer.

BACKGROUND AND AIM: Endoscopic Ultrasound (EUS) has increased the staging accuracy of oesophageal cancer. The addition of EUS guided fine needle aspiration (EUS-FNA) appears superior to standard EUS for nodal staging. Our aim was to study the impact of EUS-FNA in the management of patients with oesophageal cancer. METHODS: We studied patients undergoing EUS for this indication between May 2003 and May 2006. EUS was performed in patients who were candidates for radical therapy following CT scanning. If suspicious non-peritumoural nodes were seen on EUS, EUS-FNA was undertaken. Further staging was performed as appropriate and all cases were discussed at our multidisciplinary meeting. Results and decisions were prospectively recorded. RESULTS: One hundred and ninety one patients underwent EUS for staging of oesophageal cancer during this period and 44 EUS-FNA were performed in 42 patients (mean age 62.2 years). Sixty two per cent of patients had adenocarcinoma and 48% sampled nodes were <10 mm diameter. Overall, 48% nodes were positive and two "suspicious" for malignancy. Following a positive EUS-FNA and MDM discussions, 15 patients had palliative and two neoadjuvant therapy. Eleven patients with a negative EUS-FNA underwent radical therapy. Therefore, EUS-FNA appeared to alter management in 28 (67%) patients. CONCLUSION: EUS-FNA appears to help direct patients towards appropriate treatment strategies.

Outpatient management of patients with low-risk upper-gastrointestinal haemorrhage: multicentre validation and prospective evaluation.

BACKGROUND: Upper-gastrointestinal haemorrhage is a frequent reason for hospital admission. Although most risk scoring systems for this disorder incorporate endoscopic findings, the Glasgow-Blatchford bleeding score (GBS) is based on simple clinical and laboratory variables; a score of 0 identifies low-risk patients who might be suitable for outpatient management. We aimed to evaluate the GBS then assess the effect of a protocol based on this score for non-admission of low-risk individuals. METHODS: Our study was undertaken at four hospitals in the UK. We calculated GBS and admission (pre-endoscopy) and full (post-endoscopy) Rockall scores for consecutive patients presenting with upper-gastrointestinal haemorrhage. With receiver-operating characteristic (ROC) curves, we compared the ability of these scores to predict either need for clinical intervention or death. We then prospectively assessed at two hospitals the introduction of GBS scoring to avoid admission of low-risk patients. FINDINGS: Of 676 people presenting with upper-gastrointestinal haemorrhage, we identified 105 (16%) who scored 0 on the GBS. For prediction of need for intervention or death, GBS (area under ROC curve 0.90 [95% CI 0.88-0.93]) was superior to full Rockall score (0.81 [0.77-0.84]), which in turn was better than the admission Rockall score (0.70 [0.65-0.75]). When introduced into clinical practice, 123 patients (22%) with upper-gastrointestinal haemorrhage were classified as low risk, of whom 84 (68%) were managed as outpatients without adverse events. The proportion of individuals with this condition admitted to hospital also fell (96% to 71%, p<0.00001). INTERPRETATION: The GBS identifies many patients presenting to general hospitals with upper-gastrointestinal haemorrhage who can be managed safely as outpatients. This score reduces admissions for this condition, allowing more appropriate use of in-patient resources.

The patella as an unusual site of renal cell carcinoma metastasis.

We report a rare case of renal cell carcinoma with metastasis to the patella in a 49-year-old man, who presented with seven months of left knee pain after a fall. Only two similar cases have been reported. Patellar metastasis is rare because it has a relatively poor blood supply and microemboli would have been sieved out by the pulmonary circulation. Patellectomy is the usual treatment for such cases. We suspect that the preferential metastasis in our patient is a result of tropism. Our treatment for this patient is unique. We opted for a patella-preserving operation involving the use of cryotherapy, as this treatment modality preserved the quality of life. An opportunistic biopsy one year later confirmed the absence of active disease within the patella. This case uniquely provides human in vivo histological confirmation that an intralesional procedure with local and systemic adjuvant therapy effectively controls local disease.

Faecal calprotectin in the assessment of Crohn's disease activity.

BACKGROUND: Clinical and laboratory assessment of activity in Crohn's disease (CD) correlate poorly with endoscopic findings. Calprotectin is a calcium-binding protein abundant in neutrophil cytosol, and extremely stable in faeces. Faecal calprotectin (FC) is an excellent surrogate marker of neutrophil influx into the bowel lumen. AIM: To assess whether FC concentration from a spot stool sample reliably detects active inflammation in patients with CD. DESIGN: Cross-sectional comparative study. METHODS: Subjects had a previously confirmed diagnosis of CD and were suspected on clinical grounds to be in the midst of a relapse. Thirty-five entered the study; they underwent radiolabelled white cell scanning (WCS) and had a stool sample collected for calprotectin measurement on the same day. A Crohn's disease activity index (CDAI) was also calculated for each. The WCS scans were scored at six standard sites to give a mean total, 'extent', 'severity' and 'combined extent and severity' scores. RESULTS: FC was significantly and positively correlated with mean total (r = 0.73, p < 0.001), 'extent' (r = 0.71, p < 0.001), 'severity' (r = 0.64, p < 0.001) and combined 'extent and severity' WCS scores (r = 0.71, p < 0.001). A cut-off of faecal calprotectin > 100 microg/g gave a sensitivity of 80%, specificity of 67%, positive predictive value of 87% and a negative predictive value of 64% in identifying those with and without any inflammation on WCS. There was, however, no significant correlation between CDAI and mean total WCS score (r = 0.21, p = 0.24), nor between CDAI and FC (r = 0.33, p = 0.06). DISCUSSION: While the CDAI does not accurately reflect inflammatory activity in CD, a one-off FC reliably detects the presence or absence of intestinal inflammation in adult patients with CD, compared to WCS.