Recent advances in alcoholic hepatitis.

Alcoholic hepatitis (AH) is an acute deterioration in liver function seen in the context of prolonged excessive alcohol consumption and is characterised by the rapid onset of jaundice. The diagnosis of AH has been controversial for many years: it is now accepted that there are clear clinical criteria which can be used to diagnose AH without the need for a liver biopsy. Corticosteroids remain the only treatment proven to be effective in reducing short-term mortality in severe AH; abstinence from alcohol is the most important factor in determining long-term survival. It is recommended a trial of corticosteroid therapy is considered only in those patients with high baseline 'static' scores (Glasgow Alcoholic Hepatitis score and model for end-stage liver disease). Response to corticosteroid therapy should be assessed using a 'dynamic' score such as the Lille score at day 7, with corticosteroids continuing only in patients with a favourable score. Infection and acute kidney injury are associated with poorer outcomes in AH. Early screening for and treatment of infection is recommended with antibiotic therapy overlapping with any subsequent corticosteroid treatment. A biomarker which predicts benefit from corticosteroids at baseline would avoid a trial of therapy to determine response. More efficacious therapeutic options for AH patients are required with N-acetylcysteine, granulocyte colony stimulating factor, faecal microbiota transplantation and routine antibiotics showing promise, but adequate controlled trials are needed to confirm efficacy. Liver transplant has an emerging role for some patients with severe AH not responding to corticosteroids and is likely to become more acceptable with improved methods of patient selection.

Review article: recent insights into clinical decision-making in severe alcoholic hepatitis.

BACKGROUND: Alcoholic hepatitis is a severe acute manifestation of alcoholic liver disease with a high mortality. Management of patients with this condition has been a matter of controversy for many years; however, recent clinical studies have sought to improve the clinical approach to these patients. AIM: To use these recent studies in order to guide clinical management. METHODS: A MeSH search of Medline was performed to specifically identify recent studies which influenced clinical diagnosis, assessment and management of alcoholic hepatitis. RESULTS: Fulfilment of clear clinical criteria including a minimum threshold of bilirubin, defined periods of jaundice and alcohol ingestion negates the need for liver biopsy in most patients. Corticosteroids improve short-term mortality only (28 day) with other factors such as abstinence likely to be significant in long-term outcome. Pentoxifylline is not an effective treatment. The Glasgow Alcoholic Hepatitis Score (GAHS) score can identify those patients likely to benefit from corticosteroids, but scores that include the evolution of bilirubin over 1 week of such treatment (such as the Lille Score) define "response". Underlying infection may contribute towards corticosteroid nonresponse and needs to be actively sought out and treated. Liver transplant remains controversial; however, it has been shown to be feasible in alcoholic hepatitis. CONCLUSIONS: Recent studies have helped to define patients who may benefit from corticosteroid treatment. However, there remains a need for more accurate scores of prognosis and treatment response, and a clear need for alternative treatments for those patients not responding to corticosteroid therapy.

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 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.

Appraisal of the Glasgow assessment and management of alcohol guideline: a comprehensive alcohol management protocol for use in general hospitals.

BACKGROUND: Guidelines exist for the management of alcohol withdrawal syndrome (AWS) but few have been assessed as to their suitability for general hospitals. The Glasgow Assessment and Management guideline for alcohol has been specifically developed for use in this context. AIM: To determine if this alcohol assessment guideline aids the management of AWS in general hospitals. DESIGN: The four components of the Glasgow Assessment and Management of Alcohol guideline were evaluated. This included the use of the Fast Alcohol Screening Test (FAST) to identify at risk patients, a risk stratification strategy to indicate fixed dose or symptom-triggered benzodiazepine treatment, the Glasgow Modified Alcohol Withdrawal Scale (GMAWS) for symptom-triggered treatment and a clear recommendation for vitamin prophylaxis of Wernicke's encephalopathy. METHODS: FAST scores were assessed along with the CAGE (cut down, annoyed, guilty and eye-opener) screening tool to ascertain if a single screening tool could identify hazardous and dependent drinking. The GMAWS and Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) were compared between two medical units. A staff survey of the two AWS tools was also carried out. RESULTS: FAST was able to identify both probable hazardous and dependent drinking. The GMAWS was reliable and gauged both physical and cognitive aspects of AWS. Staff generally preferred the GMAWS-based treatment as opposed to CIWA-Ar management and welcomed the Guideline as a whole. CONCLUSION: The Glasgow Guideline aids the management of patients with AWS in an acute hospital setting. It allows early identification of at risk patients and directs effective therapeutic 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.

The Glasgow alcoholic hepatitis score identifies patients who may benefit from corticosteroids.

INTRODUCTION: There is no consensus on the pharmacological treatment of alcoholic hepatitis. The Glasgow alcoholic hepatitis score (GAHS) has been shown to be more accurate than the modified Maddrey's discriminant function (mDF) in the prediction of outcome from alcoholic hepatitis. This study aimed to determine whether the GAHS was able to identify those patients who would benefit from corticosteroids. METHODS: 225 patients with an mDF greater than or equal to 32 from five hospital centres in the United Kingdom were reviewed. Patient survival relative to the GAHS and the use of corticosteroids was recorded. RESULTS: 144 patients with an mDF greater than or equal to 32 (64%) also had a GAHS greater than or equal to 9. There was no difference in survival between untreated or corticosteroid-treated patients for those with a GAHS less than 9. For patients with a GAHS greater than or equal to 9 the 28-day survival for untreated and corticosteroid-treated patients was 52% and 78% (p = 0.002), and 84-day survival was 38% and 59% (p = 0.02), respectively. CONCLUSIONS: Among patients with an mDF greater than or equal to 32, there was no appreciable benefit from treatment with corticosteroids in patients with a GAHS less than 9. Patients with a GAHS greater than or equal to 9 have an extremely poor prognosis if they are not treated with corticosteroids, or if such treatment is contraindicated.

The prevalence of alcohol misuse among acute admissions: current experience and historical comparisons.

BACKGROUND: Over the last 25 years there has been a large increase in alcohol related deaths in Scotland. Medical patients who misuse alcohol may have overt alcohol related disease, but may also present with other unrelated illness. AIM: We examined alcohol misuse amongst acute medical admissions to compare this with other similar studies at the same hospital since 1974. PATIENTS AND METHODS: 850 consecutive admissions to the medical receiving unit of Victoria Infirmary were assessed. They were assessed using the modified Michigan Alcohol Screening Test (MAST) and also by a medical consultant. 414 patients also had their blood ethanol levels measured on admission. RESULTS: 18.6% admissions had a MAST greater than 5 and were considered to misuse alcohol (24.8% male and 12.2% female; p < 0.0001). Patients from socio-economic group V and patients presenting with gastro-intestinal haemorrhage or self-poisoning were more likely to misuse alcohol. The sensitivity and specificity of consultant opinion regarding alcohol misuse were 0.55 and 0.97 compared with the MAST. There was an increase in the alcohol misuse amongst women admitted (12.2%) compared to 1977 (5.5%; p = 0.0026) and 1981/2 (6.3%; p = 0.004). CONCLUSION: Alcohol misuse is common amongst acute medical admissions. Since 1979, there has been a particular increase in female medical admissions who misuse alcohol. Medical opinion regarding alcohol misuse lacks sensitivity in identifying at risk individuals compared with a validated.

Polymorphisms of the renin-angiotensin system and the severity of fibrosis in chronic hepatitis C virus infection.

SUMMARY: Patients with chronic hepatitis C virus (HCV) infection vary in their rates of fibrosis progression. The renin-angiotensin system (RAS) regulates fibrosis. Polymorphisms in the genes of the RAS may contribute to the outcome of renal and cardiovascular disease. We studied four RAS gene polymorphisms in 195 patients with chronic HCV infection. Patients were grouped by Ishak stage of fibrosis on liver biopsy: group 1 (fibrosis score 0 or 1; n = 97), group 2 (fibrosis score 2 or 3; n = 73) and group 3 (fibrosis score 4-6; n = 25). Polymorphisms of the angiotensinogen (AGT) gene (M235T and AT-6), the angiotensin I converting enzyme gene and the type 1 angiotensin II receptor gene were assayed. There was no difference in the distribution of these polymorphisms of the RAS between the fibrosis groups. There did not appear to be any increased prevalence of fibrosis if two or even three of the polymorphisms associated with increased RAS effect were present. On multivariate analysis factors significantly associated with fibrosis were necroinflammatory activity (P < 0.001) and age (P < 0.001). No association was identified between these four RAS polymorphisms and fibrosis in chronic HCV infection.

Analysis of factors predictive of mortality in alcoholic hepatitis and derivation and validation of the Glasgow alcoholic hepatitis score.

INTRODUCTION: Alcoholic hepatitis is associated with a high short term mortality. We aimed to identify those factors associated with mortality and define a simple score which would predict outcome in our population. METHODS: We identified 241 patients with alcoholic hepatitis. Clinical and laboratory data were recorded on the day of admission (day 1) and on days 6-9. Stepwise logistic regression was used to identify variables related to outcome at 28 days and 84 days after admission. These variables were included in the Glasgow alcoholic hepatitis score (GAHS) and its ability to predict outcome assessed. The GAHS was validated in a separate dataset of 195 patients. RESULTS: The GAHS was derived from five variables independently associated with outcome: age (p = 0.001) and, from day 1 results, serum bilirubin (p<0.001), blood urea (p = 0.019) and, from day 6-9 results, serum bilirubin (p<0.001), prothrombin time (p = 0.002), and peripheral blood white blood cell count (p = 0.001). The GAHS on day 1 had an overall accuracy of 81% when predicting 28 day outcome. In contrast, the modified discriminant function had an overall accuracy of 49%. Similar results were found using information at 6-9 days and when predicting 84 day outcome. The accuracy of the GAHS was confirmed by the validation study of 195 patients The GAHS was equally accurate irrespective of the use of the international normalised ratio or prothrombin time ratio, or if the diagnosis of alcoholic hepatitis was biopsy proven or on the basis of clinical assessment. CONCLUSIONS: Using variables associated with mortality we have derived and validated an accurate scoring system to assess outcome in alcoholic hepatitis. This score was able to identify patients at greatest risk of death throughout their admission.

Acute hepatitis C in a nursing home resident.

Elderly patients commonly present with jaundice from a multitude of causes. We present an unusual case of acute hepatitis C in an elderly nursing home resident who had no risk factors. Possible causes and treatment are discussed.

The impact of specialist management of jaundiced alcoholic liver disease patients.

BACKGROUND: Patients with alcoholic liver disease (ALD) presenting with jaundice have advanced chronic ALD and/or acute alcoholic hepatitis. Their prognosis is poor. These patients may be managed by General Medical physicians (GM) or by Gastroenterologists (GE). AIM: This study aimed to retrospectively assess the differences in management and outcome of jaundiced ALD between GM and GE. PATIENTS AND METHODS: Patients with a serum bilirubin greater than 80 mmol/l on admission and a history of alcohol excess until within three weeks of admission were identified retrospectively. In particular the use of corticosteroids (CS), nutritional support (N) and the use of broad-spectrum antibiotics (A/b) were noted. RESULTS: 97 patients were identified, 62 managed by GE. Differences were apparent between GE and GM managed patients with respect to CS (p = 0.017), N (p < 0.001) and A/b (p < 0.001). The overall mortality was 27.8%, 34.0%, and 37.1% at 28, 56, and 84 days respectively. Mortality for patients with a Discriminant Function approximately 32 was greater in GM managed patients compared with GE at 28 (p = 0.006), 56 (p = 0.013), and 84 days (p = 0.036). CONCLUSION: Differences exist between the management of jaundiced ALD between GM and GE. Such differences may translate into improved outcomes.

Helicobacter pylori eradication for peptic ulceration: an observational study in a Scottish primary care setting.

Despite being established for the treatment of peptic ulcer (PU) disease, few studies have assessed the long-term effectiveness and economic benefits of Helicobacter pylori (Hp) eradication in primary care. Our aim was to investigate the effect of community based Hp eradication for patients with chronic peptic ulcer disease requiring maintenance acid suppression. The endpoints used were the patients dyspeptic symptoms and the requirement for the prescription of maintenance acid suppression therapy. The study area covered seven general practices in the Glasgow area. Patients with previously diagnosed peptic ulcer disease receiving prescribed acid suppression therapy were invited to a dyspepsia clinic. Hp status was assessed by Helisal rapid blood test (HRBT). Positive patients received Hp eradication therapy and were reviewed six weeks later. At six months a review of practice records was carried out, and two years after eradication a postal questionnaire was sent to participating patients. A total of 243 patients attended the initial clinic of which 81.9% were HRBT positive. 156 of 196 patients offered Hp eradication re-attended at six weeks. The per protocol eradication rate was 91.7%. After six months patients who had received eradication therapy were less likely to require maintenance acid suppression therapy compared with those to whom eradication was not given. Two years after treatment 76.5% of patients felt their symptoms were improved, but 42.2% were still receiving maintenance therapy. The estimated cost of treatment per month per patient had fallen from 20.23 Pounds to 9.39 Pounds after eradication. In conclusion we felt that community based Hp eradication for patients with chronic PU disease is effective, however it does not completely alleviate dyspepsia. Predictors of symptomatic response or of no longer requiring acid suppression therapy after two years were younger age of onset of PU disease and absence of pre-documented gastro-oesophageal reflux disease or hiatus hernia. Hp eradication improves patients symptoms, reduces the requirement for maintenance acid suppression and is cost-effective after two years follow-up in this targeted group.