Pilot implementation of a home-care programme with chlamydia, gonorrhoea, hepatitis B, and syphilis self-sampling in HIV-positive men who have sex with men.

BACKGROUND: Not all men who have sex with men (MSM) at risk for sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) infection currently receive sexual healthcare. To increase the coverage of high-quality HIV/STI care for MSM, we developed a home-care programme, as extended STI clinic care. This programme included home sampling for testing, combined with treatment and sexual health counselling. Here, we pilot implemented the programme in a hospital setting (HIV-positive MSM) to determine the factors for the successful implementation of STI home sampling strategies. METHODS: Healthcare providers from the HIV hospital treatment centre (Maastricht) were invited to offer free STI sampling kits (syphilis, hepatitis B, [extra]genital chlamydia and gonorrhoea laboratory testing) to their HIV-positive MSM patients (March to May 2018). To evaluate implementation of the program, quantitative and qualitative data were collected to assess adoption (HIV care providers offered sampling kits to MSM), participation (MSM accepted the sampling kits) and sampling-kit return, STI diagnoses, and implementation experiences. RESULTS: Adoption was 85.3% (110/129), participation was 58.2% (64/110), and sampling-kit return was 43.8% (28/64). Of the tested MSM, 64.3% (18/28) did not recently (< 3 months) undergo a STI test; during the programme, 17.9% (5/28) were diagnosed with an STI. Of tested MSM, 64.3% (18/28) was vaccinated against hepatitis B. MSM reported that the sampling kits were easily and conveniently used. Care providers (hospital and STI clinic) considered the programme acceptable and feasible, with some logistical challenges. All (100%) self-taken chlamydia and gonorrhoea samples were adequate for testing, and 82.1% (23/28) of MSM provided sufficient self-taken blood samples for syphilis screening. However, full syphilis diagnostic work-up required for MSM with a history of syphilis (18/28) was not possible in 44.4% (8/18) of MSM because of insufficient blood sampled. CONCLUSION: The home sampling programme increased STI test uptake and was acceptable and feasible for MSM and their care providers. Return of sampling kits should be further improved. The home-care programme is a promising extension of regular STI care to deliver comprehensive STI care to the home setting for MSM. Yet, in an HIV-positive population, syphilis diagnosis may be challenging when using self-taken blood samples.

Beneficial effect of successful HCV treatment in patients with inherited bleeding disorders, assessed by liver stiffness measurements.

Hepatitis C infection is a major comorbidity in patients with inherited bleeding disorders. Successful antiviral treatment leads to a reduction in liver fibrosis, as shown by liver biopsies. Liver stiffness measurement (LSM) is a non-invasive method of assessing liver fibrosis. The aim of this cohort study was to evaluate the long-term effect of successful antiviral treatment, using LSM, in HCV-infected patients with inherited bleeding disorders. The LSM were performed in 2005 (LSM 1) and 2009 (LSM 2) in 39 patients who were successfully treated for HCV. The change in liver fibrosis between LSM 1 and 2 was assessed. The median duration of HCV infection was 28.8 years. A total of 22 patients (56%) underwent successful antiviral treatment before LSM 1 (group 1), and 17 patients between LSM 1 and LSM 2 (group 2). The median time since antiviral treatment was 8.8 years in group 1 and 2.5 years in group 2. In group 1, the median results of LSM 1 and 2 were similar (6.0 vs. 5.6 kPa, P-value 0.36), so overall, patients remained stable. In three patients in this group, all treated more than 15 years ago, an increase of liver stiffness was shown. Group 2 showed a significant improvement in median LSM results (10.3 vs. 6.1 kPa, P-value <0.01), with decrease of liver stiffness in 82%. Even after a long HCV infection duration, successful antiviral treatment led to a significant improvement of fibrosis, measured by LSM, mainly in the first few years after completing treatment.

The burden of HCV treatment in patients with inherited bleeding disorders.

Many patients with inherited bleeding disorders are infected with hepatitis C virus (HCV). Antiviral treatment, consisting of pegylated interferon and ribavirin, has many side-effects. The aim of the study was to prospectively assess the occurrence and course of side-effects and changes in health-related quality of life (HRQoL) during antiviral treatment in patients with inherited bleeding disorders and chronic HCV. Forty-seven patients were followed during antiviral treatment. Side-effects of treatment were recorded, and the Beck Depression Inventory and the RAND-36 HRQoL questionnaire were administered at regular intervals. Frequently reported side-effects were fatigue (100%), headache (94%), pruritus and skin rash (94%), concentration problems (89%), decreased appetite (89%), fever, irritability and hair loss (all 85%). Many side-effects disappeared soon after end of treatment, but 4 weeks after cessation fatigue, concentration problems and sleeping problems were still present in more than 30% of patients. Dose reduction was necessary in 21 patients (45%), mostly because of decreasing weight or haemoglobin levels. Two patients stopped treatment prematurely because of side-effects. Depression was present in 28 patients (60%). HRQoL decreased significantly during treatment in all RAND-36 domains, and increased again within 4 weeks after treatment. Major side-effects were similar in patients with successful (n = 31, 66%) and unsuccessful antiviral treatment. In patients with inherited bleeding disorders and chronic HCV, antiviral treatment has many, but mostly transient side-effects and a significant impact on quality of life. Careful follow-up and management of side-effects will ensure optimal compliance and treatment results.

Liver stiffness measurements to assess progression of fibrosis in HCV-infected patients with inherited bleeding disorders.

Hepatitis C is a major co-morbidity in patients with inherited bleeding disorders, leading to progressive liver fibrosis and eventually cirrhosis. Liver stiffness measurement (LSM) is a non-invasive way of assessing the extent of liver fibrosis. This article describes our experience with serial LSM to assess prospectively progression of fibrosis in a cohort of patients with inherited bleeding disorders and chronic hepatitis C. A total of 84 patients underwent serial LSMs, with a median interval of 3.7 years. The change in LSM results over time was assessed. Overall, there was no significant difference between the median results of LSM 1 and LSM 2. The median result of LSM 2 was low (6.6 kPa), after a median duration of infection of 37 years. On the individual level, deterioration of LSM results of more than 2 kPa was seen in 13 patients (16%), 44 patients (52%) remained stable and 27 patients (32%) showed improvement of LSM results of more than 2 kPa. These results are comparable with those of paired liver biopsy studies. LSM appears to be a good alternative for liver biopsies in patients with hepatitis C and inherited bleeding disorders, although the interpretation of the unexpected improvement we found in some of our patients is not straightforward. LSMs will be repeated in our patient population in a few years to be able to better assess the value of serial LSM.

Cryoglobulinaemic vasculitis in a patient with chronic hepatitis C: favourable outcome due to direct-acting antivirals.

This case report describes a patient who presented with a debilitating hepatitis C virus-related cryoglobulinaemic vasculitis who was treated with immunosuppression and direct-acting antivirals. After returning symptoms revealed a relapse of the hepatitis C virus infection, treatment with direct-acting antivirals was repeated. Subsequently, he achieved a sustained virological response and his vasculitis subsided.

Is there a higher risk of a complicated course of hepatitis A in kidney transplant patients?

BACKGROUND: We describe a patient who was planned to receive a kidney transplant from his wife. Both were infected with Hepatitis A virus (HAV) two weeks prior to the planned transplantation. Due to prolonged shedding of HAV (up until 126 days) we decided to postpone the kidney transplant in order to prevent long term complications. OBJECTIVES: The main question in this case was is there a higher risk of a complicated course of HAV-infection after kidney transplantation? We discuss the need for upscale of preventative measures of HAV infections in solid organ transplant candidates. STUDY DESIGN: We performed a literature study on risks of a complicated course of HAV in solid organ transplant recipients and performed a seroprevalence study on anti-HAV in a cohort of 106 hemodialysis patients. RESULTS: Little is known whether HAV infection in solid organ transplant patients causes a more aggressive course of diseases. However, HAV infections in these populations are associated with increased risk of liver failure. CONCLUSIONS: This case highlights the need of scaling up preventative measures against HAV infections in solid organ transplant candidates.

Occurrence, course and risk factors of depression during antiviral treatment for chronic hepatitis C in patients with inherited bleeding disorders: a prospective study.

Treatment of hepatitis C virus (HCV) consists of pegylated interferon (IFN)-alpha and ribavirin for 24 or 48 weeks. An important side-effect of IFN-alpha is depression. The occurrence, course and risk factors of depression during antiviral treatment were studied prospectively in HCV patients with inherited bleeding disorders. The Beck Depression Inventory, indicating no, mild, moderate or severe depression, was administered to 47 patients before starting therapy, after 4, 12, 24 and 48 weeks of treatment, and 4 weeks after cessation of therapy. At baseline, five patients (11%) had mild depression. Depression worsened during treatment in three of these patients. In all five patients, (mild) depression persisted 4 weeks after treatment. Of the remaining 42 patients, 23 (55%) developed depression during treatment (14 mild, eight moderate and one severe), mostly (78%) during the first 12 weeks. Four weeks after cessation of treatment, three of 23 patients still had mild depression. The only independent risk factor for development of depression was a history of depression or other psychiatric problems (odds ratio 9.7). For patients with inherited bleeding disorders, depression is a significant, mostly transient, problem during HCV treatment. We recommend close monitoring of patients, especially those with previous psychiatric problems, to ensure adequate detection and treatment of depression during antiviral therapy.

Retrieval of chronic hepatitis C patients. A manifesto for action to eliminate hepatitis C in the Netherlands: the CELINE project.

Chronic hepatitis C virus (HCV) infection is a global public health issue, which is associated with high rates of morbidity and mortality. The development of direct acting antivirals (DAAs) has transformed treatment: they offer us highly-effective therapy with superior tolerability compared to interferon-containing regimens. In 2016, the World Health Organization (WHO) therefore adopted several ambitious viral hepatitis elimination targets, aiming for a 90% reduction in new infections and a 65% reduction in mortality by 2030. The ultimate goal is to eliminate HCV completely. It is reasonable that these goals may be achieved in the Netherlands due to the low prevalence of chronic HCV, the availability of DAAs, and excellent healthcare infrastructure. This paper describes a national effort to curtail the HCV epidemic in the Netherlands through an HCV retrieval and linkage to care project (CELINE: Hepatitis C Elimination in the Netherlands).

Horizontal hepatitis B virus transmission through non-sexual close contact in Turkish chronic hepatitis B patients living outside of Turkey.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) infection is a global threat and with the growing cultural diversity in Western Europe, knowledge on routes of infection in order to decrease HBV spreading is essential. This study assessed the risk of horizontal transmission through non-sexual close contact in the chronic hepatitis B (CHB) population in Maastricht (the Netherlands) and Genk (Belgium), with a main focus on the differences between ethnic groups. METHODS: In this multicenter retrospective study, 166 CHB patients, who were still under follow-up between December 2009 to December 2014, were recruited from the Hepatology Outpatient Departments of two hospitals, one in Maastricht and one in Genk. Ethnicity (defined as country of origin (COO)) and routes of transmission were collected from all patients. RESULTS: The CHB population in Maastricht and Genk consisted of 98 and 68 patients, respectively. In Maastricht, 31% were of Dutch and 16% of Chinese origin. In Genk, mainly Belgian (15%) and Turkish (50%) patients were included. The percentage of horizontal transmission in the total study cohort was 9%. Moreover, the COO groups Dutch/Belgian (n=40), Turkish (n=38) and Chinese (n=18) differed in the number of cases infected by horizontal transmission (4%, 30% and 6%, p=0.030). CONCLUSION: Although the prevalence of horizontal transmission in the total study cohort is low, non-sexual close contact may play a role in the migrant population, particularly the Turkish. This should be an important public health target with respect to the prevention of HBV spreading.

Significant liver damage in patients with bleeding disorders and chronic hepatitis C: non-invasive assessment of liver fibrosis using transient elastography.

BACKGROUND: Many patients with bleeding disorders have been infected with the hepatitis C virus (HCV), mainly with genotype 1. Antiviral treatment is only effective in 50% of these patients and is often accompanied by serious side effects. Consequently, careful selection of patients for treatment is warranted. Liver biopsies are generally not performed in these patients because of increased bleeding risk and high costs. We therefore assessed liver fibrosis and cirrhosis non-invasively using liver stiffness measurement (LSM). METHODS: We enrolled 124 patients with bleeding disorders and chronic hepatitis C. Liver fibrosis was assessed by LSM using Fibroscan. In order to assess the validity of LSM in our hands, a separate group of 63 patients without bleeding disorders infected with HCV were evaluated with both LSM and biopsy. RESULTS: In the validation study, liver elasticity was highly correlated with histological fibrosis stage (correlations coefficient 0.73, P < 0.001). Based on LSM, 18% of patients with bleeding disorders and chronic hepatitis C had severe fibrosis, and 17% had cirrhosis after 34 years of infection (range 14-40). However, the prevalence of cirrhosis based on laboratory and ultrasonographic findings was only 7%. Independent risk factors for an increase in LSM were older age at infection, higher body mass index, presence of viral co-infection, and male gender. Fifteen out of 59 patients (25%) with an apparent indication for treatment (significant fibrosis by LSM) agreed to start antiviral therapy within 3 months. CONCLUSIONS: We found an unexpected high number of patients with significant fibrosis and cirrhosis in patients with bleeding disorders and hepatitis C detected by LSM, with considerable impact on the management of the disease.

Antiviral therapy for chronic hepatitis C in patients with inherited bleeding disorders: an international, multicenter cohort study.

BACKGROUND: Hepatitis C is a major co-morbidity in patients with hemophilia. However, there is little information on the efficacy of antiviral therapy and long-term follow-up after treatment. OBJECTIVES: To assess the effect of interferon-based (IFN-based) therapy on hepatitis C virus (HCV) eradication, to identify determinants associated with treatment response, and to assess the occurrence of end-stage liver disease (ESLD) after completing antiviral therapy. PATIENTS AND METHODS: In a multicenter cohort study, 295 treatment-naïve hemophilia patients chronically infected with HCV were included. The effect of therapy was expressed as sustained virological response (SVR). Determinants associated with treatment response were expressed as odds ratios (ORs). Cumulative incidence of ESLD was assessed using a Kaplan-Meier survival table. RESULTS: Among human immunodeficiency virus (HIV) negative patients (n = 235), SVR was 29% (29/101) for IFN monotherapy, 44% (32/72) for IFN with ribavirin, and 63% (39/62) for pegylated IFN (PegIFN) with ribavirin. In patients co-infected with HIV (n = 60), IFN monotherapy, IFN with ribavirin, and PegIFN with ribavirin eradicated HCV in 7/35 (20%), 1/2 (50%), and 11/23 (48%), respectively. SVR increased with genotype 2 and 3 [OR 11.0, 95% CI: 5.8-20.5], and combination therapy (IFN and ribavirin OR 3.7, 95% CI: 1.7-8.4), PegIFN and ribavirin (OR 4.2, 95% CI: 1.8-9.5). Up to 15 years after antiviral treatment, none of the patients with a SVR relapsed and none developed ESLD. In contrast, among unsuccessfully treated patients the cumulative incidence of ESLD after 15 years was 13.0%. CONCLUSIONS: Successful antiviral therapy appears to have a durable effect and reduces the risk of ESLD considerably.

Acute hepatitis C in the Netherlands: characteristics of the epidemic in 2014.

Within the Dutch Acute HCV in HIV Study, a surveillance system was initiated to estimate the incidence of hepatitis C virus (HCV) infections in 2014. Following the Dutch HIV treatment guidelines, HIV-positive men having sex with men (MSM) in 19 participating centers were screened. Ninety-nine acute HCV infections were reported, which resulted in a mean incidence of 11 per 1000 patient-years of follow-up. Unfortunately, the HCV epidemic among Dutch HIV-positive MSM is not coming to a halt.

Favourable SVR12 rates with boceprevir or telaprevir triple therapy in HIV/HCV coinfected patients.

BACKGROUND: Recent publications have reported superior efficacy of telaprevir- or boceprevir-based triple therapy over conventional peginterferon-alfa/ribavirin therapy, albeit with varying rates of adverse events and treatment discontinuations in HIV/HCV coinfected patients. Therefore, the aim of this study is to describe the effectiveness of triple therapy in an HIV/HCV coinfection cohort in the Netherlands. METHODS: HIV-infected patients with chronic HCV genotype 1 starting triple therapy including either boceprevir or telaprevir were enrolled, 26% had F3-F4 fibrosis. Data were assessed at Week 4, 8, 12, 24, 48 and SVR12 (i.e. absence of detectable plasma HCV RNA 12 weeks after completion of treatment). Failure was defined as discontinuation of treatment due to virological failure, adverse events or loss to follow-up. RESULTS: A total of 53 HIV/HCV coinfected patients started peginterferon-alfa/ribavirin therapy with either boceprevir (n = 29) or telaprevir (n = 24). SVR12 was achieved in 19 (66%) of the boceprevir-treated and 15 (63%) of the telaprevir-treated patients. Both prior relapse and achievement of a rapid virological response were associated with a higher SVR12 rate. Non- response, breakthrough and relapse occurred in 4, 1 and 5 patients on boceprevir and 3, 2, 2 on telaprevir, respectively. One patient was lost to follow-up and one patient died due to progression of liver failure. Except for these two patients, no treatment discontinuations were observed due to adverse events. CONCLUSION: In HIV/HCV coinfected patients, boceprevir or telaprevir triple therapy was well tolerated and resulted in favourable SVR12 rates comparable with previous publications concerning HCV mono-infected patients.