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 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 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.

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.

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.

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.

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 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.

Pseudohermaphrodite rat: end organ insensitivity to testosterone.

The pseudohermaphrodite rat is characterized by lack of androgen-dependent differentiation. Treatment of these rats with testosterone failed to produce the expected changes in preputial and adrenal gland weights and hexobarbital metabolism. This insitivity of the end organ to testosterone could not be explained by defective formation of dihydrotestosterone.

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.

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.

Structural and functional factors related to testicular neoplasia in feminized rats.

Testicular tumors in King-Holtzman hybrid rats with testicular feminization (tfm) were seen as firm, rounded masses of tissue consisting of Leydig cells, myoid cells, and fibroblast-like cells. The cytoplasm of Leydig cells contained well-developed smooth endoplasmic reticulum, pleomorphic mitochondria with numerous cristae, and many lipid droplets. Mitochondria were numerous and varied in size and shape. Their cristae were in the form of tubules, and lipid-like inclusions were frequently seen in the mitochondrial matrix. Lysosomes, rough endoplasmic reticulum, and Golgi bodies were also scattered in the cytoplasm. An in vitro study showed that more testosterone was produced in the tumor than in the testes of rats with tfm; however, the amount in both was less than normal. Testicular tumor-bearing rats with tfm exhibited slightly higher levels of plasma testosterone than did non-tumor-bearing animals with tfm. Levels in both were significantly higher than normal. Testicular tumor cells growing in culture medium supplemented with luteinizing hormone (LH) contained more protein and synthesized more androgen and DNA than did those growing in culture medium without LH. Observed under the scanning and transmission electron microscopes, the LH-stimulated cells had well-developed cytoplasmic organelles and inclusions and surface specializations such as numerous microvilli, large blebs, and other microextensions. They adhered well to the glass surface. These results indicated that Leydig cells in testicular tumors of rats with tfm had morphologic characteristics of steroid-producing cells. In addition these cells were capable of producing steroids, and this capability was enhanced by the presence of LH.

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.

Primary hyperparathyroidsm, amyloid and multiple myeloma: an unusual association.

We report the case of a 76-year-old woman with a diagnosis of Primary Hyperparathyroidsm and Systemic Amyloidosis, in whom subsequent investigations revealed the presence of Multiple Myeloma. We discuss the relationship between these conditions and the implications for management.

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.

Review article: spontaneous bacterial peritonitis--diagnosis, treatment and prevention.

Spontaneous bacterial peritonitis is a serious complication of cirrhotic ascites, arising most frequently in those with advanced liver disease. Its development leads to a further reduction in the effective arterial blood volume, and it has a mortality rate equivalent to that of a variceal bleed. However, problems remain with regard to the identification and optimal treatment of spontaneous bacterial peritonitis. Several important studies and consensus documents on the condition have recently been published which aid in the identification of patients at risk and help to guide therapy. In this review, we discuss these publications and address the issues of diagnosis, treatment and both primary and secondary prophylaxis of spontaneous bacterial peritonitis in the light of recent data.

Review article: update on the role of transjugular intrahepatic portosystemic stent-shunt (TIPSS) in the management of complications of portal hypertension.

In the 8 years since its introduction into clinical practice, initial enthusiasm for the transjugular intrahepatic portosystemic stent-shunt (TIPSS) has been tempered by a more critical appraisal of its role in the management of portal hypertension. TIPSS has established its role as a rescue procedure for variceal haemorrhage uncontrolled by endoscopic means and as a treatment for ectopic or recurrent variceal bleeding. Randomized trials comparing TIPSS with endoscopic methods in the secondary prophylaxis of oesophageal variceal haemorrhage have shown reduced rebleeding after TIPSS but no effect on survival. Its exact role in this situation awaits further assessment, including quality of life and cost analyses, and consideration of the current limited availability of the technique. Experience of TIPSS in patients with refractory ascites or hepatorenal syndrome has been disappointing. Little data currently exist, but results of further randomized studies comparing TIPSS with paracentesis for refractory ascites are awaited. Ideally these should be multicentre studies, and should include quality of life data for this poor prognostic group. Development of shunt insufficiency remains a major problem and occurs in approximately 50% patients at 1 year. The need for continued shunt surveillance by Doppler sonography and direct portography is the major limitation of TIPSS, but hopefully the development of covered stents will address this problem.

Haemodynamic effects of acute and chronic administration of low-dose carvedilol, a vasodilating beta-blocker, in patients with cirrhosis and portal hypertension.

BACKGROUND: Carvedilol is a non-selective vasodilating beta-blocker with weak alpha1 receptor antagonism. Recent studies have demonstrated its potential as a portal hypotensive agent. AIM: To assess the haemodynamic effects and patient tolerability of the acute and chronic administration of low-dose carvedilol. METHODS: Haemodynamic measurements were performed in ten cirrhotic patients before and 1 h after the administration of 12.5 mg oral carvedilol. The study was repeated 4 weeks after daily administration of 12.5 mg carvedilol. RESULTS: After acute administration of carvedilol, there was a 23% reduction in the hepatic venous pressure gradient from 16.37 +/- 2.14 to 12.56 +/- 3.91 mmHg (P < 0.05), with significant falls in the heart rate, mean arterial pressure and cardiac output. Chronic administration resulted in a further fall in the hepatic venous pressure gradient from a baseline of 16.37 +/- 0.71 to 9.27 +/- 1.40 mmHg (P < 0.001) with the mean arterial pressure being unaffected. The drug was well tolerated with only one patient experiencing asymptomatic hypotension. CONCLUSIONS: The results show that low-dose carvedilol is an extremely potent portal hypotensive pharmacological agent, and is worthy of further investigation in large randomized trials to assess its effect in preventing variceal haemorrhage.