Results of a Model of Delivering Hepatitis C Care in a Homeless Metropolitan Population in England.

INTRODUCTION: Given the hepatitis C virus (HCV) burden and despite curative treatments, more efforts focused on scaling-up testing and treatment in homeless populations are needed. This project aimed to implement education and flexible on-site HCV testing, treatment, and follow-up for a homeless population in south London and to evaluate engagement, therapy initiation, and cure rates. METHODS: A mobile unit (van) for on-site HCV education, screening, treatment, and follow-up was placed on the street in a well-known homeless population areas from January 2018 to September 2021. Homeless was defined as living in temporary housing (hostel/hotel-based) or living on the street (street-based). Sociodemographic status, risk factors, comorbidities, concomitant medication, and data related with HCV treatment were recorded. Univariable and multivariable modeling were performed for treatment initiation and sustained virological response (SVR). RESULTS: Nine hundred forty homeless people were identified and 99.3% participated. 56.2% were street-based, 243 (26%) tested positive for HCV antibody, and 162 (17.4%) were viremic. Those with detectable HCV RNA had significantly more frequent psychiatric disorders, active substance use disorders, were on opioid agonist treatment, had advanced fibrosis, and had lower rates of previous treatment in comparison with undetectable HCV RNA. Overall treatment initiation was 70.4% and SVR was 72.8%. In the multivariable analysis, being screened in temporary housing (odds ratio [OR] 3.166; P = 0.002) and having opioid agonist treatment (OR 3.137; P = 0.004) were positively associated with treatment initiation. HCV treatment adherence (OR 26.552; P < 0.001) was the only factor associated with achieving SVR. DISCUSSION: Promoting education and having flexible and reflex mobile on-site testing and treatment for HCV in the homeless population improve engagement with the health care system, meaning higher rates of treatment initiation and SVR. However, street-based homeless population not linked with harm reduction services are less likely to initiate HCV treatment, highlighting an urgent need for a broad health inclusion system.

Successful liver transplantation for drug-induced vanishing bile duct syndrome.

Drug-induced cholestasis has a wide range of clinical presentations, and in a small number of patients, it can progress to severe ductopenia. A 63-year-old woman was referred to our department with progressive cholestasis and hyperbilirubinaemia following a course of flucloxacillin. Despite the comprehensive laboratory, imaging and genetic investigations, no other cause for the cholestasis was demonstrated. Sequential liver biopsies confirmed the development of vanishing bile duct syndrome. She developed significant cachexia and pruritus that did not respond to medical therapy, and hence she was listed for liver transplantation. She underwent liver transplantation 6 months after the initial drug-induced injury. She has remained well with good graft function at 1-year follow-up. The case highlights an extreme form of drug-induced ductopenia and underscores the need for meticulous hepatology input and consideration of liver transplantation in some patients.

Faldaprevir for the treatment of genotype-1 hepatitis C virus.

Historically, pegylated interferon in combination with ribavirin was the standard of care in hepatitis C virus; however, this combination is often poorly tolerated, has a significant side-effect profile and is of limited efficacy in hepatitis C virus genotype-1. More recently, pegylated interferon/ribavirin has been combined with direct acting antiviral agents such as the first generation NS3/4A protease inhibitors. Faldaprevir, a first generation, second-wave protease inhibitor, when used with a pegylated interferon/ribavirin regimen, has also been shown to increase treatmentsuccess while shortening treatment duration; however, second generation direct acting antiviral agents offer even betterefficacy and tolerability. Various direct acting antiviral agent combinations in interferon-free regimens have been effective in over 95% of patients and are now in licensed use. While faldaprevir was a pioneering drug, by the time it reached late phase development it was superseded by newer agents.

Repeat endoscopic retrograde cholangiopancreaticography after failed initial precut sphincterotomy for biliary cannulation.

AIM: To investigate the outcome of repeating endoscopic retrograde cholangiopancreaticography (ERCP) after initially failed precut sphincterotomy to achieve biliary cannulation. METHODS: In this retrospective study, consecutive ERCPs performed between January 2009 and September 2012 were included. Data from our endoscopy and radiology reporting databases were analysed for use of precut sphincterotomy, biliary access rate, repeat ERCP rate and complications. Patients with initially failed precut sphincterotomy were identified. RESULTS: From 1839 consecutive ERCPs, 187 (10%) patients underwent a precut sphincterotomy during the initial ERCP in attempts to cannulate a native papilla. The initial precut was successful in 79/187 (42%). ERCP was repeated in 89/108 (82%) of patients with failed initial precut sphincterotomy after a median interval of 4 d, leading to successful biliary cannulation in 69/89 (78%). In 5 patients a third ERCP was attempted (successful in 4 cases). Overall, repeat ERCP after failed precut at the index ERCP was successful in 73/89 patients (82%). Complications after precut-sphincterotomy were observed in 32/187 (17%) patients including pancreatitis (13%), retroperitoneal perforations (1%), biliary sepsis (0.5%) and haemorrhage (3%). CONCLUSION: The high success rate of biliary cannulation in a second attempt ERCP justifies repeating ERCP within 2-7 d after unsuccessful precut sphincterotomy before more invasive approaches should be considered.

Treatment of chronic hepatitis C virus infection after liver transplantation.

Chronic hepatitis C virus infection is a leading cause of end stage liver disease and one of the leading indications for liver transplantation. Furthermore, hepatitis C virus recurrence is universal post-transplant leading to decreased graft and patient survival. Recurrent disease related to hepatitis C virus can lead to between 20 and 30% of patients developing recurrent cirrhosis within 5 years. Treatment options with antiviral therapy are limited and are associated with a significant side-effect profile, suboptimal tolerability and inferior response rates. Attention has therefore turned to strategies that can reduce hepatitis C virus recurrence rates post-transplant. Approximately only 30% of patients will achieve a sustained virologic response with current therapy with pegylated interferon and ribavirin. Successful hepatitis C virus eradication is the only factor associated with improved graft and patient survival post liver transplantation. Here we provide an overview of antiviral treatment in patients in the transplant arena and the potential opportunities and challenges with the introduction of new directly acting antivirals in G1 patients.

Primary sclerosing cholangitis: is any treatment worthwhile?

While many therapeutic agents have been evaluated in Primary Sclerosing Cholangitis (PSC), none have been shown in controlled trials to modify the course of disease. The bile acid ursodeoxycholic acid (UDCA) has been widely used in the treatment of PSC but its use remains controversial. It may have a role in providing chemoprotection against the development of colonic dysplasia/cancer in patients with associated inflammatory bowel disease. The exclusion of IgG4-associated cholangitis, which generally responds to immunosuppressant agents, is essential prior to deciding on an appropriate therapeutic strategy in PSC. In the absence of proven therapeutic agents, treatment strategies are usually aimed at minimizing the complications of the biliary disease. Endoscopic management of dominant strictures may improve long-term outcomes. Orthotopic liver transplantation has a good outcome in patients with end stage PSC.

Gastrointestinal symptoms in patients with end-stage renal disease undergoing treatment by hemodialysis or peritoneal dialysis.

OBJECTIVES: The aim of this study was to determine the prevalence of gastrointestinal symptoms in patients with end-stage renal disease undergoing hemodialysis (HD) or peritoneal dialysis (PD) treatment. METHODS: Patients undergoing HD or chronic ambulatory PD in the Department of Renal Medicine of our hospital were asked to complete a locally validated Rome II questionnaire. The same questionnaire was also administered to age- and gender-matched medical outpatients without renal failure, and community subjects. Patients on HD and their outpatient controls also completed the Hospital Anxiety and Depression Scale. RESULTS: A total of 148 patients with end-stage renal disease (HD 100, PD 48) completed the study. Their results were compared with those of 148 age- and gender-matched medical outpatients without renal failure and 148 randomly selected community controls. Patients on dialysis treatment were more likely to have abdominal pain, use laxatives, and report symptoms consistent with functional vomiting and irritable bowel syndrome (IBS) (70%, 55%, 16%, and 25%) than age- and gender-matched medical outpatients without renal failure (21%, 11%, 1%, and 6%) and community controls (16%, 4%, 0%, and 8%). Among HD patients and their outpatient controls, the differences appeared to be unrelated to anxiety or depression. CONCLUSIONS: Abdominal pain, laxative use, functional vomiting, and IBS were more common in uremic individuals than in controls without renal failure. Our data have not shown whether these differences are due to the uremic state itself, or, alternatively, its treatment.