R Marley

Prevalence of chronic viral hepatitis in people of south Asian ethnicity living in England: the prevalence cannot necessarily be predicted from the prevalence in the country of origin

Summary.  The prevalence of hepatitis B and hepatitis C in immigrant communities is unknown. Immigrants from south Asia are common in England and elsewhere, and the burden of viral hepatitis in these communities is unknown. We aimed to determine the prevalence of viral hepatitis in immigrants from south Asia living in England, and we therefore undertook a community‐based testing project in such people at five sites in England. A total of 4998 people attending community centres were screened for viral hepatitis using oral fluid testing. The overall prevalence of anti‐hepatitis C virus (HCV) in people of south Asian origin was 1.6% but varied by country of birth being 0.4%, 0.2%, 0.6% and 2.7% in people of this ethnic group born in the UK, India, Bangladesh and Pakistan, respectively. The prevalence of hepatitis B surface antigen was 1.2%–0.2%, 0.1%, 1.5% and 1.8% in people of this ethnic group born in the UK, India, Bangladesh and Pakistan, respectively. Analysis of risk factors for HCV infection shows that people from the Pakistani Punjab and those who have immigrated recently are at increased risk of infection. Our study suggests that migrants from Pakistan are at highest risk of viral hepatitis, with those from India at low risk. As prevalence varies both by country and region of origin and over time, the prevalence in migrant communities living in western countries cannot be easily predicted from studies in the country of origin.

Community-based treatment for chronic hepatitis C in drug users: high rates of compliance with therapy despite ongoing drug use

Background  Chronic hepatitis C infection is common in drug users. Treatment of injectors is possible under controlled conditions, but many have not yet been included in treatment programmes as there are concerns about their ability to comply with therapy. It is not known which factors influence compliance.

Assessment of Bone Mineral Density in Tenofovir-Treated Patients With Chronic Hepatitis B: Can the Fracture Risk Assessment Tool Identify Those at Greatest Risk?

BACKGROUND Tenofovir disoproxil fumarate (TDF) is an established nucleotide analogue in the treatment of chronic hepatitis B. Bone mineral density loss has been described in TDF-treated patients with human immunodeficiency virus infection, but limited data exist for patients with chronic hepatitis B. Dual X-ray absorptiometry (DEXA) was used to determine bone mineral density changes in TDF-exposed patients. We evaluated the accuracy of the Fracture Risk Assessment Tool (FRAX) as an alternative to DEXA in clinical practice. METHODS A total of 170 patients were studied: 122 were exposed to TDF, and 48 were controls. All patients underwent DEXA, and demographic details were recorded. FRAX scores (before and after DEXA) were calculated. RESULTS TDF was associated with a lower hip T score (P = .02). On univariate and multivariate analysis, advancing age, smoking, lower body mass index, and TDF exposure were independent predictors of low bone mineral density. In addition, the pre-DEXA FRAX score was an accurate predictor of the post-DEXA FRAX treatment recommendation (100% sensitivity and 83% specificity), area under the curve 0.93 (95% CI, .87-.97, P < .001). CONCLUSIONS TDF-treated patients with chronic hepatitis B have reduced bone mineral density, but the reduction is limited to 1 anatomical site. Age and advanced liver disease are additional contributing factors, underlining the importance of multifactorial fracture risk assessment. FRAX can accurately identify those at greatest risk of osteoporotic fracture.

Response to antiviral therapy in patients with genotype 3 chronic hepatitis C: fibrosis but not race encourages relapse.

Background and aims We completed a retrospective analysis of patients with genotype 3 hepatitis C virus (HCV) undergoing therapy in four UK centres with large populations of patients from the Indian subcontinent. Materials and methods Notes on all patients treated with pegylated interferon and ribavirin were reviewed and factors that influenced the response were examined. Results Six hundred and four patients with genotype 3 HCV were studied, of whom 299 were Asians. Median age was 43 years, 65% were men and 24% had cirrhosis. Overall, 457 (76%) patients achieved sustained virological response (SVR). By multivariable analysis it was found that ethnicity was not associated with an impaired response but age, cirrhosis and diabetes were significantly associated with a reduced SVR, the likelihood of a response was reduced by 25% per 10-year increment in age, by 59% among individuals with cirrhosis and by 62% among individuals with diabetes mellitus. Most patients who did not achieve an SVR relapsed (15%) rather than failing to achieve an end of treatment response. Conclusion The response to antiviral therapy in genotype 3 HCV is not affected by South Asian (vs. Caucasian) ethnicity, but age, cirrhosis and diabetes reduce the response. Treatment failure most often is due to relapse.

Recurrent ascites due to constrictive pericarditis

Constrictive pericarditis (CP) is a recognised, but unusual cause of chronic ascites.1 ,2 Patients with pericardial constriction may present to non-cardiological specialties,3 ,4 with the symptoms and signs leading to the diagnosis of congestive cardiac failure, lung disease or liver disease.5 ,6 It is important to suspect and rule out CP because with surgery it is treatable and potentially curable. Much of the difficulty in diagnosing CP can be attributed to its insidious course and the absence of typical cardiopulmonary symptoms. Over 50% of patients ending up with pericardiectomy lack symptoms of dyspnoea and orthopnoea.7 We present two cases, which highlight the potential difficulties in diagnosing CP in patients with chronic ascites. We review the key steps in diagnosis and management, emphasising that raised jugular venous pressure (JVP) is one of the crucial observations in making the diagnosis. A 77-year-old man presented with a 2-year history of recurrent ascites requiring serial paracentesis. He had been extensively investigated by both gastroenterological and respiratory physicians. Abdominal ultrasound scans revealed normal appearance of both liver and spleen. Paracentesis demonstrated a high ascitic total protein count of 39, an accompanying high serum-ascites albumin gradient (SAAG) with negative cytology and negative cultures and smears for tuberculosis (TB). Despite this, he received an empirical course of anti-TB therapy. Extensive investigations looking for causes of chronic liver disease were negative. A transthoracic echocardiogram (TTE) revealed normal biventricular function. The left atrium was reported as being dilated but no other abnormalities were detected, therefore a cardiac cause of the ascites was felt unlikely. During an elective admission for paracentesis, an elevated JVP was observed and CP was considered. On review of the echocardiogram, abnormal motion of the intraventricular septum (‘septal bounce’) was observed along with a dilated left atrium and dilated …

PWE-144 Frax Score in the Assessment of Bone Mineral Density Changes in Tenofovir Treated Chronic Hepatitis B Patients

Introduction Tenofovir Disoproxil Fumarate (TDF) is an established oral antiviral (OAV) in the treatment of Chronic Hepatitis B (CHB). Bone Mineral Density (BMD) loss has been described in TDF treated HIV patients, but limited data exist in CHB. We have used DEXA scanning to determine BMD changes in TDF treated patients and have reported the possibility of BMD loss. DEXA scanning, however, is costly and requires longitudinal follow-up. We assessed the value of the FRAX® score and of bone biochemistry to evaluate their utility in TDF treated patients. Methods The FRAX score is a WHO web-based tool, used to calculate 10-year fracture risk and the need for lifestyle modification, DEXA scanning or preventative treatment. CHB patients treated with TDF for a minimum of 12-months and a control group not exposed to TDF were studied. 122 TDF exposed patients (male = 89), median age 45 (range = 26–64) and 48 patients (male = 31), median age 36 (range = 20–62) not exposed to TDF were DEXA scanned and included in the study. We calculated FRAX scores and recorded bone biochemical markers, comprising serum Alkaline Phosphatase (sALP), Calcium (sCa) and Phosphate (sPO). Results TDF treated patients had lower hip T-scores compared to controls (p = 0.02). On univariate analysis factors associated with a hip T-score < 1 included older age, lower BMI, smoking and TDF exposure (p = < 0.05). On multivariate analysis the same factors were associated with a hip T-score < 1, but TDF lost significance. For the development of a major osteoporotic fracture the pre-DEXA FRAX score was 4.77% compared to 4.33% (post-DEXA FRAX) (p = 0.9) and for a hip fracture this was 0.54% (pre-DEXA FRAX) and 0.77% (post-DEXA FRAX) (p = 0.5). The pre-DEXA FRAX score was a significant predictor of the post-DEXA FRAX treatment recommendation (p = < 0.001). TDF therapy was associated with increased sALP after 12-months, but this was not significant. No change was observed in pre-treatment sCa and sPO levels compared to those after 12-months exposure (p = 0.5 & 0.09 respectively). Conclusion Our results demonstrate the FRAX score alone can accurately predict the risk of developing an osteoporotic fracture in TDF treated CHB patients. This potentially obviates the need for DEXA scanning and the associated costs. The relationship between sALP and TDF is noteworthy, but bone parameters are of limited use in predicting BMD changes. Although BMD loss in TDF treated CHB patients remains unproven, we demonstrate the use of the FRAX score may determine those at risk of osteoporotic fractures in CHB. Disclosure of Interest None Declared.

PMO-166 Early experience with telaprevir for patients with advanced fibrosis or cirrhosis

Introduction The direct-acting HCV protease inhibitor telaprevir has recently been licensed for treatment of chronic genotype 1 HCV infection, and promises significant improvements in sustained virological response for these patients. However the patients who may benefit most from novel HCV therapies, namely those with advanced fibrosis or cirrhosis who have previously failed to respond to pegylated interferon (pegIFN) and ribavirin treatment, are relatively poorly represented in the telaprevir clinical trials. Efficacy, safety and tolerability were assessed in patients with genotype 1 HCV and advanced fibrosis/cirrhosis who have received telaprevir-containing treatment at the Royal London Hospital. Methods Laboratory results and case notes were reviewed for all patients treated with pegIFN, ribavirin and telaprevir at the Royal London Hospital between September 2011 and January 2012. Results Eight patients with genotype 1 HCV had commenced telaprevir-containing treatment. All had advanced fibrosis/cirrhosis (median Ishak score 5, range 4–6). One was treatment-naïve, three had previously failed to respond to pegIFN/ribavirin and four had relapsed after therapy. All patients had completed at least 4 weeks of telaprevir-containing therapy. With one exception, all patients achieved undetectable HCV RNA at week 4 of treatment; the patient who did not had a viral load of 168 IU/ml at week 4 and undetectable HCV RNA at week 8. One patient had completed 12 weeks of therapy, with undetectable HCV RNA. The most common side effects were fatigue (8/8), pruritis (4/8), rash (3/8), anal pain (3/8), depression (3/8), nausea (3/8), gastrointestinal disturbance (2/8) and oral candidiasis (2/8). Most side effects were successfully managed, although telaprevir was stopped in two patients at week 8 due to worsening rash and one patient withdrew from all therapy at week 4 due to tolerability. The most common laboratory abnormality was an early, transient rise in bilirubin (3/8). Significant anaemia (Hb). Conclusion Telaprevir in combination with pegIFN and ribavirin appears efficacious in patients with advanced fibrosis or cirrhosis, who have previously failed treatment with pegIFN and ribavirin alone. However, the incidence of significant side effects in this subgroup of patients is high and necessitates frequent follow-up with medical support. Side effects, particularly rash, may limit duration of telaprevir treatment. Whether this impacts on sustained virological response remains to be seen. Competing interests M Cunningham: None declared, J Schulz: None declared, L Payaniandy: None declared, Y Kallis: None declared, P Kennedy: None declared, P Kooner: None declared, R Marley: None declared, G Foster grant/research Support from: Roche, Janssen, Tibotec, Novartis, Consultant for: Abbott, BI, BMS, Chughai, Janssen, Merck, Novartis, Roche, Tibotec.

PMO-176 Induction maintenance treatment in chronic hepatitis B; step-down from tenofovir and lamivudine to lamivudine monotherapy is effective

Introduction Tenofovir Disoproxil Fumarate (TDF) is a potent and effective oral antiviral used to treat Chronic Hepatitis B (CHB), but concerns remain about possible long-term toxicity and the costs of indefinite use. An induction-maintenance treatment strategy may allow the use of combination Lamivudine (LAM) and TDF, to avert the development of resistance, followed by maintenance of viral suppression with LAM. To date, there are no data on such a step-down strategy in HBeAg negative CHB. Here we report on patients in whom we safely discontinued TDF, while maintaining viral suppression and normal liver biochemistry. Methods We selected patients who were had received combination therapy for a minimum of 18 months. Selection criteria included HBeAg negative disease, fibrosis score of <4/6 on biopsy, undetectable HBV DNA and normal serum ALT for a minimum of 12 consecutive months. Patients meeting these criteria were invited to stop TDF and step-down to maintenance LAM monotherapy. Patients were followed at monthly intervals to determine whether viral suppression and ALT normalisation was maintained in the absence of TDF. Results 21 patients (13 male), median age 47, (range 39–62) discontinued TDF. Median follow-up was 3 months (range 1–10 months). During monthly follow-up biochemical and serological data have been measured. All patients had undetectable HBV DNA prior to step-down therapy to LAM and this remained undetectable during follow-up. Pre-discontinuation of TDF the median ALT was 27 (range 15–38) and during follow-up, on LAM monotherapy, was 22 (range 15–45), (p=NS). Median HBsAg level pre-discontinuation of TDF was log 3.48 (range 1.55–4.49) and 3.49 (range 1.55–4.55), (p=NS) on LAM monotherapy. Conclusion We demonstrate no viral breakthroughs or biochemical flares on discontinuing TDF. These data suggest that an induction-maintenance strategy may be pursued in selected CHB patients to avoid long-term exposure to TDF and reduce the burden on healthcare budgets in the context of lifelong oral antiviral therapy. Competing interests None declared.

PMO-175 Can a 3-month “stopping rule” for pegylated-interferon-α be applied to a UK population of chronic hepatitis B infected patients of mixed genotype?

Introduction Stopping rules have been proposed for the early discontinuation of Pegylated-Interferon-α (PEG-IFN-α) therapy in those patients who are considered unlikely to respond. Recent studies have shown that no reduction in quantitative HBsAg and the absence of >2 log decline in HBV DNA at 12 weeks therapy can predict non-response. However, these data are almost exclusively from genotype A and D cohorts. Here we test how robust this strategy would be in clinical practice and whether this rule could be applied to a UK population of diverse HBV genotypes. Methods 49 patients (male=35) were treated with PEG-IFNα for CHB over the course of the study. Ten patients remain on therapy and eight patients discontinued due to poor compliance or intolerance. 31 patients (male=20), HBeAg positive (n=24), median age 31 (range 18–55) completed 48 weeks PEG-IFNα and were included in the analysis. HBV genotype was recorded for all patients (A=6, B=5, C=10, D=9, E=1). ALT, HBV DNA and HBsAg was quantified at baseline and longitudinally at 12-week intervals. Results Of the 31 patients, 10 were considered responders; seven were HBeAg positive and seroconverted on therapy and three were HBeAg negative pre-therapy and considered responders with sustained immune control off treatment. The decline in HBV DNA and qHBsAg by 12 weeks was 3.99 log, 0.17 log (HBeAg positive group) and 2.9 log, 0.5 log (HBeAg negative group) respectively. 16/31 patients were non-genotype A or D. Of the responders from this group there was a decline in HBV DNA and qHBsAg of 4.10 log and 0.58 log respectively by 12 weeks. On sub-group analysis by genotype, there was no statistically significant difference in HBV DNA and qHBsAg decline at 12 weeks across all genotypes, when comparing HBV DNA and qHBsAg between genotype A and D and non A and D patients (p=0.40 and 1.0 respectively). More over adopting the rule of >2 log decline in HBV DNA and no decline in qHBsAg by 12 weeks, reveals we would not exclude those likely to respond; as all responders achieve the outlined viral response by 12 weeks therapy. Conclusion These data highlight the utility of this stopping rule for PEG-IFNα across all genotypes. The absence of >2 log decline in HBV DNA and reduction in qHBsAg at 12 weeks therapy makes a favourable response unlikely. This rule should be adopted in clinical practice to avoid poorly tolerated side effects and the cost of completing 48 weeks therapy. Furthermore, this 12-week milestone would allow the early switch to an oral antiviral in PEG-IFNα non-responders. Competing interests None declared.

PMO-148 Evaluation of liver fibrosis in young adult patients with chronic hepatitis B virus

Introduction Current guidelines do not recommend treatment of Chronic Hepatitis B (CHB) in young adults as they are believed to be immune tolerant with minimal liver damage. Recently we demonstrated that young CHB patients have evidence of immune activity comparable to older patients. Therefore, a proportion of young patients will develop fibrosis as a consequence of immune mediated liver injury. Despite this, the most appropriate modality to assess liver fibrosis remains controversial. We compare the utility of liver biopsy and digital image analysis with FibroScan for assessment of CHB in young adults. Methods Young adult CHB patients were followed in a dedicated clinic and seen 3-monthly. Liver biopsy was performed where indicated and compared with FibroScan scores. Digital image analysis was performed on a selected number of Sirius red stained sections to evaluate percentage fibrosis. 167 patients were assessed; 101/167 (male=63); median age 26 (range 16–30) underwent liver biopsy and were included for analysis. Results 47/101 patients were eAg+. Overall median ALT was 41IU/L (range 14–426) & HBV DNA was 5.22 logIU/ml (range 1.4–9.3). Median Ishak fibrosis score was 1 (range 0–6); median FibroScan score was 5.95 kPa (range 2.6–35.2). There was no difference in the FibroScan score in patients with advanced (F5/6) and minimal fibrosis (F0/1); median FibroScan scores were 6 and 5.95 respectively, (p=ns). The correlation co-efficient between fibrosis and FibroScan was not statistically significant (p=0.46). FibroScan scores were confounded by ALT; using Prati criteria to define normal ALT (female <19 IU/l, male <30 IU/l), we noted an ALT twice ULN revealed a higher FibroScan score, regardless of fibrosis (p=0.05 and 0.04; males and females respectively). On the contrary, digital image analysis more accurately reflected fibrosis stage irrespective of ALT. Conclusion A proportion of young adult patients with CHB have significant liver disease on biopsy. This study highlights the limitations of FibroScan in assessing liver fibrosis in this cohort. Our data demonstrates the utility of digital image analysis in benchmarking fibrosis in young patients, potentially providing a more accurate methodology to assess progression of fibrosis over time. Competing interests None declared.