Sulleman Moreea

The Diversity and Management of Chronic Hepatitis B Virus Infections in the United Kingdom: A Wake-up Call

BACKGROUND Through migration, diversity of chronic hepatitis B virus (HBV) infection has changed, affecting disease burden and control. We describe clinical and viral characteristics of chronic HBV in the United Kingdom. METHODS A total of 698 individuals with chronic HBV infection were recruited from referral liver centers. Demographic, clinical, and laboratory data were collected. RESULTS Sixty-one percent of patients were male, 80% were not born in the United Kingdom, and the largest ethnicity was East/Southeast Asian (36%). Twenty-two percent were hepatitis B e antigen (HBeAg) seropositive; 20.4% (59/289) had cirrhosis and 10 (1.7%) had hepatocellular carcinoma. Genotype D was most common (31%) followed by A, C, B, and E (20%, 20%, 19%, and 9%, respectively). Genotype was significantly associated with country of birth, length of time in the United Kingdom, HBeAg status, and precore and basal core promoter mutations. One-third were on treatment, with men independently more likely to be treated. Only 18% of those on treatment were on recommended first-line therapies, and 30% were on lamivudine monotherapy. Among treated individuals, 27% had antiviral drug resistance. Testing rates for human immunodeficiency virus, hepatitis C virus, and delta coinfections were low. CONCLUSIONS We demonstrated diversity of chronic HBV infections in UK patients, suggesting that optimal management requires awareness of the variable patterns of chronic HBV in countries of origin. We also found less-than-optimal clinical management practices, possible gender-based treatment bias, and the need to improve testing for coinfections.

The Diversity and Management of Chronic Hepatitis B Virus Infections in the UK – A Wake up Call

BACKGROUND Through migration, diversity of chronic hepatitis B virus (HBV) infection has changed, affecting disease burden and control. We describe clinical and viral characteristics of chronic HBV in the United Kingdom. METHODS A total of 698 individuals with chronic HBV infection were recruited from referral liver centers. Demographic, clinical, and laboratory data were collected. RESULTS Sixty-one percent of patients were male, 80% were not born in the United Kingdom, and the largest ethnicity was East/Southeast Asian (36%). Twenty-two percent were hepatitis B e antigen (HBeAg) seropositive; 20.4% (59/289) had cirrhosis and 10 (1.7%) had hepatocellular carcinoma. Genotype D was most common (31%) followed by A, C, B, and E (20%, 20%, 19%, and 9%, respectively). Genotype was significantly associated with country of birth, length of time in the United Kingdom, HBeAg status, and precore and basal core promoter mutations. One-third were on treatment, with men independently more likely to be treated. Only 18% of those on treatment were on recommended first-line therapies, and 30% were on lamivudine monotherapy. Among treated individuals, 27% had antiviral drug resistance. Testing rates for human immunodeficiency virus, hepatitis C virus, and delta coinfections were low. CONCLUSIONS We demonstrated diversity of chronic HBV infections in UK patients, suggesting that optimal management requires awareness of the variable patterns of chronic HBV in countries of origin. We also found less-than-optimal clinical management practices, possible gender-based treatment bias, and the need to improve testing for coinfections.

Extended duration therapy with pegylated interferon and ribavirin for patients with genotype 3 hepatitis C and advanced fibrosis: Final results from the STEPS trial

BACKGROUND & AIMS Patients with genotype 3 hepatitis C virus (HCV) infection and cirrhosis have poor response rates after 24 weeks treatment with pegylated interferon and ribavirin. Treatment for 48 weeks is therefore recommended, although the benefits of this are untested. We examined extended therapy in patients with genotype 3 HCV and advanced fibrosis. METHODS Multicentre, open labelled randomized trial comparing therapy with 24 weeks pegylated interferon and ribavirin to 48 weeks of the same therapy. RESULTS 136 patients completed the study. 67 received 24 weeks therapy and the SVR rate (48%) did not differ from that seen in the 69 patients who received 48 weeks therapy (42%). The response rates in patients with biopsy proven cirrhosis (13 patients treated for 24 weeks, 18 patients treated for 48 weeks) or cirrhosis proven on imaging (28 patients treated for 24 weeks and 25 patients treated for 48 weeks) were 46% in those treated for 24 weeks and 40% in those treated for 48 weeks. The differences were not significantly different. Treatment failure was due to relapse in the majority of patients. CONCLUSIONS Patients with genotype 3 HCV and advanced fibrosis do not benefit from extended therapy with pegylated interferon and ribavirin.

Coeliac disease and hereditary haemochromatosis: association and implications.

Coeliac disease and hereditary haemochromatosis are genetic disorders paradoxically associated with altered intestinal absorption of iron. Hereditary haemochromatosis is the most common autosomal recessive disease in the Caucasian population and is characterised by an iron overload state. Coeliac disease, or gluten sensitive enteropathy, on the other hand is frequently associated with iron deficiency anaemia. We report the cases of two patients who developed both coeliac disease and hereditary haemochromatosis. We review the literature of this rare association and examine how the clinical presentation is modified by their co-existence and the potential genetic linkage of these two disorders.

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.

Modern management of acute non-variceal upper gastrointestinal bleeding

An acute upper gastrointestinal bleed (AUGIB) often represents a life-threatening event and is recognised universally as a common cause of emergency hospitalisation. Large observational studies have improved our understanding of the disease characteristics and its impact on mortality but despite significant advancement in endoscopic management, mortality remains high, particularly in elderly patients and those with multiple comorbidities. Skilled assessment, risk stratification and prompt resuscitation are essential parts of patient care, with endoscopy playing a key role in the definitive management. A successful outcome partly relies on the clinicians familiarity with current guidelines and recommendations, including the National Institute for Clinical Excellence guidelines published in 2012. Validated risk stratification scores, such as the Blatchford and Rockall score, facilitate early discharge of low-risk patients as well as help in identifying those needing early endoscopic intervention. Major advances in therapeutic endoscopy, including more recently, the development of non-toxic proprietary powders (Hemospray and EndoClot), have resulted in the development of effective treatments of bleeding lesions, reduction in rebleeding rates and the need for emergency surgery. The role of proton-pump inhibitor therapy prior to endoscopy and the level of optimum red cell transfusion in the setting of AUGIB remain fields that require further research.

Use of the haemostatic agent TC-325 in the treatment of bleeding secondary to endoscopic retrograde cholangiopancreatography sphincterotomy

A 71-year-old man presented to secondary care with a 2-week history of right upper quadrant pain associated with rigors. Obstructive jaundice was demonstrated on blood sampling, and subsequent magnetic resonance cholangiopancreatography imaging revealed an 8-mm obstructing calculus within the common bile duct. An endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and balloon trawl was subsequently performed. Twenty-four hours post-ERCP the patient was diagnosed with an upper gastrointestinal haemorrhage characterized by passage of melaena, haemodynamic compromise and a 50 g/l drop in haemoglobin. An emergency gastroscopy was performed, which identified an active bleeding point in the region of the previous sphincterotomy site. This …

Response to clopidogrel with proton pump inhibitors: safe or not?

The authors conducted literature research on bothprospective and retrospective data and concluded thatthere is little evidence to suggest an interaction betweenclopidogrel and proton pump inhibitors (PPIs). We wish toshare the findings at our unit.We undertook an observational retrospective study of188 consecutive patients (122 non–ST-segment elevationmyocardial infarction, 66 ST-segment elevation myocardialinfarction) treated with dual antiplatelet therapy (DAT)following acute coronary syndrome (ACS) over a period of1 year.Patientsweredividedin2groups:PPIgroup(patientsonDATandPPI,n=96)andcontrolgroup(patientsonDATonly, n=88). The end point was recurrence of ACS or death12 months after the index coronary event.Clopidogrel and aspirin were discontinued in 4 patientsdue to gastrointestinal bleeding, and these patients weretherefore excluded from the study. Data were analyzedin 184 patients. There were 66% males and 34% females;73% were Caucasian and 27% Asian. The mean age ofthe patients was 67 years (range, 24–96 years). In the PPIgroup, 10 patients (10/96, 10.4%) were readmitted withfurther myocardial infarction (6 on lansoprazole and 4 onpantoprazole). In the control group, 2 patients (2/88, 2.3%)were readmitted with a further myocardial infarction. Usingthe test of independent proportion, this difference in the rateof recurrence of coronary event was statistically significant(

Elbasvir/grazoprevir and sofosbuvir for hepatitis C virus genotype 3 infection with compensated cirrhosis: A randomized trial

Many direct‐acting antiviral regimens have reduced activity in people with hepatitis C virus (HCV) genotype (GT) 3 infection and cirrhosis. The C‐ISLE study assessed the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) plus sofosbuvir (SOF) with and without ribavirin (RBV) in compensated cirrhotic participants with GT3 infection. This was a phase 2, randomized, open‐label study. Treatment‐naive participants received EBR/GZR + SOF + RBV for 8 weeks or EBR/GZR + SOF for 12 weeks, and peginterferon/RBV treatment‐experienced participants received EBR/GZR + SOF ± RBV for 12 weeks or EBR/GZR + SOF for 16 weeks. The primary endpoint was HCV RNA <15 IU/mL 12 weeks after the end of treatment (sustained virologic response at 12 weeks [SVR12]). Among treatment‐naive participants, SVR12 was 91% (21/23) in those treated with RBV for 8 weeks and 96% (23/24) in those treated for 12 weeks. Among treatment‐experienced participants, SVR12 was 94% (17/18) and 100% (17/17) in the 12‐week arm, with and without RBV, respectively, and 94% (17/18) in the 16‐week arm. Five participants failed to achieve SVR: 2 relapsed (both in the 8‐week arm), 1 discontinued due to vomiting/cellulitis (16‐week arm), and 2 discontinued (consent withdrawn/lost to follow‐up). SVR12 was not affected by the presence of resistance‐associated substitutions (RASs). There was no consistent change in insulin resistance, and 5 participants reported serious adverse events (pneumonia, chest pain, opiate overdose, cellulitis, decreased creatinine). High efficacy was demonstrated in participants with HCV GT3 infection and cirrhosis. Treatment beyond 12 weeks was not required, and efficacy was maintained regardless of baseline RASs. Conclusion: Data from this study support the use of EBR/GZR plus SOF for 12 weeks without RBV for treatment‐naive and peginterferon/RBV–experienced people with GT3 infection and cirrhosis (ClinicalTrials.gov NCT02601573). (Hepatology 2018;67:2113‐2126)

PTH-100 Nice Guidance on The Treatment of Hepatitis C (HCV) Genotype 3 (G3) – Have We Forgotten The Past? Single Centre Experience of Biopsy Proven Fibrosis in HCV G3 Suggests Slower Progression than Previously Suggested

Introduction NICE guidance in 2000 (TA14) only recommended treatment of patients with moderate/severe HCV. NICE now advises that patients with G3 early disease should not be given DAAs but be treated with pegylated interferon/ribavirin, which is a longer treatment with lower SVR and more side effects. Methods Our databases were used to obtain: demographics, age at point of liver biopsy, stage of fibrosis and SVR in relation to all genotypes. We aim to plot the rate of progression of fibrosis in HCV G3 patients to ensure NICE guidance isn’t disadvantageous to this group. Results Between 1998–2015 we biopsied 477 patients: G1 112(81 males average 40 years, 31 females average 42 years) SVR 48%; G2 16(10 males; average 39 years, 6 females average 43 years) SVR75%; G3 337(194 males average 39 years, 143 females average 40 years) SVR 68%; G4 12(10 males average 38 years, 2 females average 45 years) SVR 42%. The point prevalence of fibrosis in HCV G3 at the time of liver biopsy is shown on the graph along with the SVR in relation to the stage of fibrosis. This confirms that fibrosis progresses with age but not in an exponential way and also recognises the well described fall in SVR with increasing fibrosis.Abstract PTH-100 Figure 1 Progression of fibrosis in HCV G3 and SVR in relation to stage of fibrosis. A second-order polynomial trend line shows the association of increasing age to stage of fibrosis. Conclusion We confirm HCV G3 progresses in both males and females from the mid-40s. Our SVR data strongly suggests that we should provide all of our HCV G3 patients with the new potent DAAs to prevent progression of disease and subsequent consequences. We urge for a change in the current guidance. Disclosure of Interest None Declared