Peter C. Hayes

A population-based record linkage study of mortality in hepatitis C-diagnosed persons with or without HIV coinfection in Scotland

Infection with the hepatitis C virus (HCV) is known to increase the risk of death from severe liver disease and, because HCV status is strongly associated with a history of injecting drug use, the effect of a key disease progression cofactor, infection with human immunodeficiency virus (HIV), is of interest. We examined all-cause, liver-related and drug-related mortality and excess risk of death from these causes in a large cohort of HCV-monoinfected and HIV-coinfected persons in Scotland. The study population consisted of 20,163 persons confirmed to be infected with hepatitis C through laboratory testing in Scotland between 1991 and 2005. Records with sufficient identifiers were linked to the General Register Office for Scotland death register to retrieve associated mortality data, and were further linked to a national database of HIV-positive individuals to determine coinfection status. A total of 1715 HCV monoinfected and 305 HIV coinfected persons died of any cause during the follow-up period (mean of 5.4 and 6.4 years, respectively). Significant excess mortality was observed in both HCV monoinfected and HIV coinfected populations from liver-related underlying causes (standardised mortality ratios of 25, 95% CI = 23—27; and 37, 95% CI = 26—52 for the two groups, respectively) and drug-related causes (25, 95% CI = 23—27; 39, 95% CI = 28—53. The risk of death from hepatocellular carcinoma, alcoholic or non-alcoholic liver disease, or from a drug-related cause, was greatly increased compared with the general Scottish population, with the highest standardised mortality ratio observed for hepatocellular carcinoma in the monoinfected group (70, 95% CI = 57—85). This study has revealed considerable excess mortality from liver- and drug-related causes in the Scottish HCV-diagnosed population; these data are crucial to inform on the clinical management, and projected future public health burden, of HCV infection.

Peripheral vascular tone in patients with cirrhosis: role of the renin–angiotensin and sympathetic nervous systems

OBJECTIVEnThe aims of the study were to establish the roles of angiotensin II and of the cardiopulmonary baroreceptor reflex in the regulation of peripheral vascular tone in patients with cirrhosis.nnnMETHODSnForearm blood flow responses to subsystemic, locally active intrabrachial infusions were measured in patients with Childs Grade C cirrhosis and matched controls using bilateral venous occlusion plethysmography. Responses were determined to the angiotensin II type I receptor antagonist, losartan, noradrenaline, angiotensin II and the nitric oxide synthase inhibitor, L-NG-monomethyl arginine.nnnRESULTSnLosartan at 30 and 90 micrograms/min caused no significant change in blood flow in controls, but caused 23 +/- 6% and 27 +/- 5% increases in patients respectively (p < 0.001). Lower body negative pressure caused a mean bilateral reduction in forearm blood flow of 20 +/- 4% in controls (p < 0.001) but only tended to reduce flow (9 +/- 5%; p = 0.06) in patients (p < 0.001; controls vs. patients). Noradrenaline, angiotensin II and L-NG-monomethyl arginine caused significant vasoconstriction (p < 0.001) in both patients and controls although angiotensin II caused significantly less vasoconstriction in patients (p = 0.01).nnnCONCLUSIONSnWe conclude that angiotensin II makes an important contribution to basal peripheral vascular tone in patients with cirrhosis in the face of reduced vascular responses to its local administration. In addition, the vasoconstrictor response to cardiopulmonary baroreceptor unloading is attenuated despite normal vascular responses to noradrenaline. These responses are consistent with chronic activation of the renin-angiotensin and sympathetic nervous systems in patients with advanced cirrhosis.

Association of self‐reported alcohol use and hospitalization for an alcohol‐related cause in Scotland: a record‐linkage study of 23 183 individuals

AIMSnTo investigate the extent to which self-reported alcohol consumption level in the Scottish population is associated with first-time hospital admission for an alcohol-related cause.nnnDESIGNnObservational record-linkage study.nnnSETTINGnScotland, 1995-2005.nnnPARTICIPANTSnA total of 23,183 respondents aged 16 and over who participated in the 1995, 1998 and 2003 Scottish Health Surveys, followed-up via record-linkage from interview date until 30 September 2005.nnnMEASUREMENTSnRate of first-time hospital admission with at least one alcohol-related diagnosis. Cox proportional hazards regression analysis was applied to estimate the relative risk of first-time hospitalization with an alcohol-related condition associated with usual alcohol consumption level (1-7, 8-14, 15-21, 22-35, 36-49, 50+ units/week and ex-drinker, compared with <1 unit per week).nnnFINDINGSnOf the SHS participants, 527 were hospitalized for an alcohol-related cause during 135,313 person-years of follow-up [39 first admissions per 10,000 person-years, 95% confidence interval (CI) 36-42]. Alcohol-related hospitalization rates were considerably higher for males (61/10,000 person-years, 95% CI 54-67) than for females (22/10,000 person-years, 95% CI 18-26). Compared with the lowest alcohol consumption category (<1 unit per week), the relative risk of first-time alcohol-related admission increased with reported consumption: age-adjusted hazard ratios ranged from 3 (1-5) for 1-7 units/week to 19 (10-37) for 50+ units/week (males); and from 2 (1-3) for 1-7 units/week to 28 (14-56) for 50+ units/week (females). After adjusting for age and usual alcohol consumption, the relative risk of first-time alcohol-related admission remained significantly higher for males reporting binge drinking and for both males and females residing in the most deprived localities.nnnCONCLUSIONSnModerate and higher levels of usual alcohol consumption and binge drinking are serious risk factors for alcohol-related hospitalization in the Scottish population. These findings contribute to our understanding of the relationship between alcohol intake and alcohol-related morbidity.

Human thrombin for the treatment of gastric and ectopic varices

AIMnTo evaluate the efficacy of human thrombin in the treatment of bleeding gastric and ectopic varices.nnnMETHODSnRetrospective observational study in a Tertiary Referral Centre. Between January 1999-October 2005, we identified 37 patients who were endoscopically treated with human thrombin injection therapy for bleeding gastric and ectopic varices. Patient details including age, gender and aetiology of liver disease/segmental portal hypertension were documented. The thrombin was obtained from the Scottish National Blood Transfusion Service and prepared to give a solution of 250 IU/mL which was injected via a standard injection needle. All patient case notes were reviewed and the total dose of thrombin given along with the number of endoscopy sessions was recorded. Initial haemostasis rates, rebleeding rates and mortality were catalogued along with the incidence of any immediate complications which could be attributable to the thrombin therapy. The duration of follow up was also listed. The study was conducted according to the United Kingdom research ethics guidelines.nnnRESULTSnThirty-seven patients were included. 33 patients (89%) had thrombin (250 U/mL) for gastric varices, 2 (5.4%) for duodenal varices, 1 for rectal varices and 1 for gastric and rectal varices. (1) Gastric varices, an average of 15.2 mL of thrombin was used per patient. Re-bleeding occurred in 4 patients (10.8%), managed in 2 by a transjugular intrahepatic portosystemic shunt (TIPSS) (one unsuccessfully who died) and in other 2 by a distal splenorenal shunt; (2) Duodenal varices (or type 2 isolated gastric varices), an average of 12.5 mL was used per patient over 2-3 endoscopy sessions. Re-bleeding occurred in one patient, which was treated by TIPSS; and (3) Rectal varices, an average of 18.3 mL was used per patient over 3 endoscopy sessions. No re-bleeding occurred in this group.nnnCONCLUSIONnHuman thrombin is a safe, easy to use and effective therapeutic option to control haemorrhage from gastric and ectopic varices.

Pharmacokinetics of N-acetylcysteine are altered in patients with chronic liver disease

Background: The threshold plasma paracetamol concentration at which N‐acetylcysteine (NAC) treatment is recommended to treat paracetamol poisoning in a patient with induced liver enzymes (for example, with chronic liver disease or taking anticonvulsant drugs) is 50% lower than in a patient without induced liver enzymes. More patients with chronic liver disease might therefore be expected to be exposed to NAC treatment than previously. In addition, there is increasing use of NAC in patients with chronic liver disease for multiorgan failure or hepatorenal syndrome. Little is known of NACs pharmacokinetic properties in patients with cirrhosis.

Review article: hepatitis E—a concise review of virology, epidemiology, clinical presentation and therapy

Hepatitis E virus (HEV) is a leading cause of acute icteric hepatitis and acute liver failure in the developing world. During the last decade, there has been increasing recognition of autochthonous (locally acquired) HEV infection in developed countries. Chronic HEV infection is now recognised, and in transplant recipients this may lead to cirrhosis and organ failure.

Functional outcome following liver transplantation—A pilot study

Abstract Background/aims: We have previously shown that prior to liver transplantation, patients exhibit impairment in memory and psychomotor speed. Despite significant improvement following transplantation, recovery remained incomplete at 1 year post-transplant. This study aimed to investigate the effects of liver transplantation on a wider range of cognitive abilities, and to assess the impact of any impairment upon day-to-day functioning, particularly driving ability. Methods: This study was a between-group design involving three groups of participants: liver transplant candidates, liver transplant recipients and healthy controls. All participants completed measures of affective status, functional capacity, quality of life, neuropsychological status and driving ability. Results: For the majority of measures, healthy controls performed best, followed by liver transplant recipients and then liver transplant candidates, respectively. This pattern was most pronounced with respect to functional limitations, language and attention. No significant difference between the three groups was observed for simulated driving ability. Conclusions: The results suggest that while significant recovery occurs in many areas of psychosocial functioning following liver transplantation, this recovery may be incomplete, that is, many patients do not recover to their full pre-illness status. The measure we employed to assess driving ability was not a sensitive or discriminating measure in this study.

Excess morbidity in the hepatitis C-diagnosed population in Scotland, 1991-2006.

We estimated the excess risk of in-patient hospitalization in a large cohort of persons diagnosed with hepatitis C virus (HCV) infection, controlling for social deprivation. A total of 20 749 individuals diagnosed with HCV in Scotland by 31 December 2006 were linked to the Scottish hospital discharge database, and indirectly standardized hospitalization rates, adjusting for sex, age, year and deprivation were calculated. We observed significant excess morbidity considering episodes for: any diagnosis [standardized morbidity ratio (SMR) 3·4, 95% CI 3·3-3·5]; liver-related diagnoses (SMR 41·3, 95% CI 39·6-43·0); and only non-liver-related diagnoses (SMR 2·14, 95% CI 2·08-2·19). Cox regression analyses of the 2000-2006 data indicated increased relative risks of hospitalization for males [hazard ratio (HR) 1·1, 95% CI 1·0-1·2], older age (per 10 years) (HR 1·55, 95% CI 1·5-1·6), and those testing HIV-positive (HR 1·6, 95% CI 1·3-1·8). This study has revealed substantial excess all-cause and liver-related morbidity in the Scottish HCV-diagnosed population, even after allowing for deprivation.

Differential visceral blood flow in the hyperdynamic circulation of patients with liver cirrhosis

With advancing liver disease and the development of portal hypertension, there are major alterations in somatic and visceral blood flow. Using phase‐contrast magnetic resonance angiography, we characterised alterations in blood flow within the hepatic, splanchnic and extra‐splanchnic circulations of patients with established liver cirrhosis.

EUS-assisted thrombin injection for ectopic bleeding varices—a case report and review of the literature

Ectopic varices (EV) represent dilated porto-systemic collaterals located at sites other than the gastro-oesophageal junction. They mainly develop in cirrhotic patients following oesophageal variceal band ligation and more rarely secondary to abdominal surgical procedures or to abdominal venous thrombosis secondary to inflammation.1 Bleeding from EV is unusual and represents <5% of all variceal bleeds. Norton et al .2 reviewed 169 cases of bleeding from EV; 26% were from ileostomy varices in primary sclerosing cholangitis patients, 17% in the duodenum, 17% in the jejunum or ileum, 14% in the colon, 8% in the rectum, 9% in the peritoneum. Duodenal varices most commonly complicate portal or splenic vein thrombosis.2nnA 49-year-old male was diagnosed with coeliac disease 3 years prior to presentation. He was receiving iron supplements for severe iron deficiency anaemia; however, several investigations including, repeated upper and lower gastrointestinal (GI) endoscopies failed to identify a cause.nnPrior to transfer to our Unit, he was admitted to his regional hospital with melaena and a Hb of 66u2009g/l. An upper gastrointestinal endoscopy (UGIE) identified a polypoid mass in the second part of the duodenum (D2). Biopsies were taken but resulted in profuse bleeding requiring 6 U of red cell concentrate (RCC).nnA repeat endoscopy in our hospital showed a ‘C shaped’ non-bleeding polypoid lesion at the junction of D2/3 which was characterized further by endoscopic ultrasound (EUS); this was a vascular lesion at D2/3; the splenic vein was dilated and tortuous …