Comorbidities and concomitant medications in patients with chronic hepatitis C virus infection receiving second-generation direct-acting antiviral regimens in Belgium: an observational study.

Objective: To describe comorbidities and concomitant medications in patients initiating treatment for hepatitis C virus (HCV) infection with direct-acting antiviral (DAA) regimens in Belgium. Methods: This was a noninterventional, observational, multicenter study of data from patient charts. Adult patients with HCV infection receiving second-generation DAA therapy were included. Comorbidities were assessed at the time of HCV treatment initiation. Concomitant medications were recorded at the time of diagnosis and at treatment initiation. Potential clinically relevant drug-drug interactions (DDIs) were assessed based on information available at www.hep-druginteractions.org. The primary objective was to describe concomitant medication use ; secondary objectives were to describe modifications in concomitant therapies and comorbidities. Results: 405 patients were included. A total of 956 comorbidities were reported by 362 patients (median, 2 ; range, 0-15). The most common comorbidities were hypertension (27.2%) ; HIV coinfection (22.5%), and type 2 diabetes mellitus (14.3%). Overall, 1455 concomitant medications were being taken by 365 patients (90.1% ; median, 3 ; range 0-16). The most common concomitant medications were psycholeptics (28.6%), antiviral agents (24.2%), and medications for acid-related disorders (21.0%) Overall, 74/365 (20.3%) patients receiving a concomitant medication required an adaptation to their concomitant medication. The medications that most frequently required change were drugs for acid-related disorders (n = 14) and antiviral drugs (n = 5) ; those that were most frequently stopped were lipid-modifying drugs (n = 25) and drugs for acid-related disorders (n = 13). Conclusion: Physicians are aware of the potential for DDIs with DAAs, but improved alignment between clinical practice and theoretical recommendations is required.

A multicentre, observational study on demographic and disease characteristics of patients seeking care for chronic hepatitis C in Belgium in 2016.

BACKGROUND AND STUDY AIMS: Direct-acting antivirals provide interferon-free treatments for chronic hepatitis C (CHC) virus infection. In Belgium, in 2016, access to these agents was limited to patients with advanced liver fibrosis stages F3 and F4. This study is the first to describe Belgium's patient population ineligible for interferon-free treatment. PATIENTS AND METHODS: This was an observational, cross-sectional, multicentre study that enrolled adult patients with CHC ineligible for interferon-free treatment. Patient data recorded at a single visit included demographic data, disease characteristics, comorbidities, co-medications, treatment status, and laboratory data. RESULTS: Three hundred and three patients from 16 centres in Belgium were included in the statistical analysis. On average, patients were aged 53.5 years and 50.2% were women ; 94.1% had health insurance and 99.0% resided in Belgium. The current hepatitis C virus (HCV) infection was the first infection for 96.0% of patients and the mean time since infection was 20.0 years. Liver fibrosis stage was F0 for 23.7%, F0/F1 or F1 for 38.3%, F1/F2 or F2 for 25.8%, F3 for 7.1%, and F4 for 5.1% of patients ; 28.4% of patients were CHC treatment-experienced. The main reason for ineligibility for interferon-free treatment was lack of reimbursement (84.8%). Other reasons included no treatment urgency or medical decision to wait (27.1%), waiting for future treatment option (8.3%), and no social insurance coverage (3.6%). CONCLUSIONS: This study provides recent data on the CHC patient population and disease characteristics in Belgium that could help medical communities and government agencies manage CHC disease burden.

The risk of early occurrence and recurrence of hepatocellular carcinoma in hepatitis C-infected patients treated with direct-acting antivirals with and without pegylated interferon: A Belgian experience.

Recently, concerns were raised of high rates of HCC recurrence in patients treated with direct-acting antivirals (DAA) for hepatitis C infection. We investigated the HCC occurrence and recurrence rates within 6 months after treatment with DAA with or without pegylated interferon (PEG-IFN) in real life. This is a retrospective, multicenter cohort trial, executed in 15 hospitals distributed across Belgium. Populations were matched based on fibrosis score (Metavir F3-F4). Patients with a Child-Pugh score ≥ B were excluded. In total, 567 patients were included, of whom 77 were treated with PEG-IFN+DAA between 2008 and 2013 and 490 with DAA without PEG-IFN between 2013 and 2015. Patients treated with PEG-IFN+DAA (53±9y) were younger than patients treated with DAA without PEG-IFN (59±12y) (P=.001). 47% of patients treated with PEG-IFN+DAA were in the F4 stage vs 67% of patients treated with DAA without PEG-IFN (P=.001). Screening was inadequate in 20% of both patient groups (P=.664). The early occurrence rate of HCC was 1.7% and 1.1% in patients treated with DAA with and without PEG-IFN, respectively (P=.540). The early recurrence rate was 0% in patients treated with PEG-IFN+DAA and 15.0% in patients treated with DAA without PEG-IFN (P=.857). There is no difference in early occurrence of new HCC between patients treated with DAA with and without PEG-IFN. We did observe a high early recurrence rate of HCC in patients treated with DAA without PEG-IFN. However, these patients were at baseline more at risk for HCC. Finally, in 20%, screening for HCC was inadequate.

Nodular Regenerative Hyperplasia in HIV-positive patients : a case series and review of the literature.

Nodular regenerative hyperplasia (NRH) is a well-described condition that leads to non-cirrhotic portal hypertension and is histologically characterised by a nodular transformation of the liver without fibrosis. It seems to be a consequence of obliterative portal venopathy of small hepatic veins. Its precise aetiology remains to be clearly determined. NRH was reported to occur in HIV-positive patients ten years ago. In this article, three consecutive clinical cases of HIV-related NRH were identified in a high volume reference centre of HIV positive patients and are presented. Clinical, diagnostic aspects and strategies for management of this under-diagnosed medical condition in the HIV population are also developed.

Mitigating the burden of hepatitis C virus among people who inject drugs in Belgium.

BACKGROUD AND AIMS: In 2010, there were an estimated 10 100 PWID in Belgium and 43% (34%-57%) were HCV infected. Understanding HCV transmission dynamics in high-risk populations and assessing the potential impact of improved HCV treatment strategies requires robust epidemiological data and mathematical modeling. METHODS: CV transmission was modeled using cohorts to track HCV incidence and prevalence among active PWID in the general PWID population, OST and NSP. Model assumptions were derived from published literature and expert consensus. The relative impact of increasing the number of PWID treated with new oral DAAs was considered. RESULTS: If the current transmission paradigm continues, there will be 2645 HCV-infected PWID in 2030. Annually treating 30 (1% of 2015 population) or 120 (4% of 2015 population) HCV-infected PWID with oral DAAs will result in 5% and 25% reductions, respectively, in HCV-infected PWID by 2030. Treating 370 PWID annually (12.5% of 2015 population) will result in a > 90% reduction by 2030. CONCLUSION: Treating a small number of PWID can result in substantial reduction in HCV prevalence in this population ; however, high levels of treatment are necessary to reduce the viral pool and thus the risk of secondary infections. This analysis supports implementation of a screening and treatment strategy among PWID when combined with an expansion of harm reduction programs.

Achieving WHO recommendations for Hepatitis C Virus Elimination in Belgium.

BACKGROUD: The World Health Organization (WHO) released updated guidelines for the screening, care and treatment of patients with chronic hepatitis C virus (HCV) infection. METHODS: A previously described HCV disease burden model was used to develop a "WHO scenario" to achieve the WHO recommendations of a 90% reduction in incidence and 65% reduction in liver-related deaths. After determining the steps necessary to achieve this goal, the impact of realistic constraints was modeled. RESULTS: In 2015, there were 66.200 viremic infections, with 43% diagnosed and 1.350 treated. In order to reduce new infections, treatment must be extended to ≥ F0 patients, including people who inject drugs and other individuals at risk of transmitting HCV. -Additionally, diagnosis and treatment of 3.030 and 4.060 patients, respectively, would be required. The largest attenuation of the WHO scenario would occur if no new cases were diagnosed after 2018 (300% more viremic infections by 2030). Limiting treatment to ≥ F2 patients or treating fewer patients (3.000) would result in 220% or 140% more viremic cases, respectively, compared with the WHO scenario. CONCLUSION: Achieving the WHO guidelines in Belgium requires a coordinated effort to scale up treatment and prevention efforts and to allow treatment access to patients of all fibrosis stages. A scale-up of treatment, however, requires patients to be both diagnosed and linked to care, suggesting a need for increased awareness and expanded screening efforts. Finally, prevention of new HCV infections requires a comprehensive understanding of the population at risk of transmitting HCV.

Characteristics, treatment, and virologic responses of chronic hepatitis C patients treated with peginterferon alfa-2a and ribavirin in belgium: a sub-analysis of the PROPHESYS study.

BACKGROUND AND STUDY AIMS: PROPHESYS was a prospective, international cohort study of monoinfected, treatment-naive chronic hepatitis C patients treated with a combination of peginterferon alfa-2a or alfa-2b and ribavirin.It included worldwide 7,163 patients from 19 countries (including 384 patients from Belgium alone) and demonstrated that sustained virologic response rates in the real world were similar to those achieved in well-controlled clinical trials. The objective of this sub-analysis was to present an overview of the baseline characteristics, anti-hepatitis C drug treatment, and virologic responses of the patients treated in Belgium, infected with HCV genotype 1, 2, 3, or 4, and administered pegin-terferon alfa-2a. Moreover, the impact of ribavirin dosage on the response to treatment was studied. PATIENTS AND METHODS: 356 patients were included in this sub-analysis. All variables were summarized using descriptive statistics. RESULTS: Compared to the published data of the whole study population (1), the Belgian data presented some significant differences in terms of genotype distribution and response to treatment (e.g. lower prevalence of HCV genotype 1 infection, lower virologic response rates in HCV genotype 2 patients). Deviations from existing recommendations were identified (e.g. higher dose of ribavirin in HCV genotype 2 or 3 patients). Patients who received less than 80% of the target dose of ribavirin experienced a significantly weaker response to treatment. CONCLUSION: This sub-analysis provided an interesting profile of the Belgian experience in the treatment of chronic hepatitis C.

A non-interventional phase IV Belgian survey to assess the antiviral effectiveness of pegylated interferon-alpha-2b and ribavirin treatment according to the stage of liver fibrosis in previously untreated patients with genotype 1/4/5/6 chronic hepatitis C (PRACTICE).

BACKGROUND AND STUDY AIMS: This was an observational, non-interventional, multicenter, phase IV study, in patients with genotype 1/4/5/6 chronic hepatitis C (CHC). The primary objectives were to evaluate SVR in patients with no or minimal fibrosis (METAVIR F0-F1) versus well established fibrosis (F2-F4), and to estimate response on Weeks 12, 24 and 48 on treatment in previously untreated patients with genotypes 1/4/5/6 CHC. PATIENTS AND METHODS: 538 patients treated with pegylated interferon alfa 2b 1.5 mcg/kg in combination with ribavirin 800-1200 mg/day were enrolled in 55 sites in Belgium and Luxembourg, 505 being considered for the analysis. 40% of the patients were female and 60% male, the average age was 47.5 years, 10.5% were 65 or older. RESULTS: SVR was observed in 35% of the patients, EVR in 68%, of which pEVR in 33% and cEVR in 35%. SVR was observed in 43% of the low fibrosis group (F0, F1) and 30% of the high fibrosis group (F2, F3, F4) (p = 0.005). SVR rates were 34% for genotype 1, 37% for genotype 4, and 47% for genotype 5 (NS). Multivariate analysis showed that EVR and baseline METAVIR score are independent prognostic factors for SVR. CONCLUSIONS: This trial confirms that fibrosis stage and early viral response are the most important key-factors to predict sustained response, suggesting that the earlier patients are treated, the better the outcome. Non-invasive techniques enable us to closely monitor progression of fibrosis, allowing a better selection of patients for antiviral treatment in the DAA-era.

Response of Black African patients with hepatitis C virus genotype 4 to treatment with peg-interferon and ribavirin.

AIM: To compare responses to therapy of Black African (BA) and non-Black African (non- BA) patients with hepatitis C virus genotype 4 (HCV-4) residing in Belgium. METHODS: In this retrospective multicenter study, 473 patients with HCV-4 were selected from databases at 7 Belgian centers; 209 treatment-naive patients (154 BA) had received treatment with peg-interferon (peg-IFN) plus ribavirin (RBV) and were included in the study. RESULTS: There was a greater percentage of female patients in the BA group than in the non- BA group; BA patients were also older, had a greater body mass index, and more frequently had abnormal glucose metabolism. The route of contamination was more frequently unknown in BA than in non-BA patients and BA patients had more HCV-4 subtypes. There were no differences in other demographic factors between the groups. Sustained viral response (SVR) and complete early viral response rates were significantly lower and relapse rates significantly higher in BA than in non-BA patients. There were no differences between groups in rates of dose modification or in drug tolerance. CONCLUSION: In our cohort, treatment-naive BA patients with HCV-4 who were treated with peg-IFN and ribavirin had a much lower SVR rate than treatment-naive non-BA patients with HCV-4 who were treated with peg-IFN and ribavirin, and a higher relapse rate, possibly related to a weaker response to interferon-based therapy. Treatment may need to be adapted in this population.

Barriers to liver transplantation in HIV infected patients.

OBJECTIVES: Liver disease is one of the most frequent causes of non AIDS related deaths in HIV patients and transplantation has become a therapeutic option. In spite of this progress, no liver transplantation has ever been recorded for the patients of the Brussels Saint-Pierre HIV Cohort. The aim of this study is to identify the barriers to liver transplantation in HIV patients that arise in our practice. METHODS: All patients enrolled in the Brussels Saint-Pierre HIV Cohort presenting a theoretical indication for liver transplantation, as recommended by the AASLD, between 01/01/2002 and 01/07/2010 were considered. The reasons for not retaining these patients as candidates for liver transplantation were classified as HIV or non-HIV related. RESULTS: Nineteen patients were identified. All patients presented an HBV and/or HCV co-infection. Indication for liver transplantation was based on first severe complication of cirrhosis for 15 patients, hepatocellular carcinoma fulfilling the Milan criteria for 2 and chronic liver failure for 2 others. Three patients could have been transplantation candidates but only one was enlisted and died prior to transplantation whilst alternative treatments were chosen for the remaining two. Among the non candidates, 5 couldn't be enlisted for HIV-related reasons, 3 for non HIV related reasons and 8 on multifactorial grounds; non adherence to treatment, alcohol abuse, psychiatric disease and hepatotoxicities playing key roles. Eleven patients died, all within 12 months of their first major complication of cirrhosis. CONCLUSIONS: The undeniable medical progress that liver transplantation represents for HIV-infected individuals is, in practise, limited; only a minority of patients with an indication of liver transplant will fulfill the necessary criteria for enlistment. General awareness of this issue and early referral are essential to optimize pre-transplant management and increase the number of HIV patients developing ESLD that will be able to benefit from this cure.

[Hepatitis B: screening and treatment]. / Hépatite B: dépistage et traitement.

Hepatitis B virus infection is more prevalent than human immunodeficiency virus (HIV) infection and hepatitis C virus infection. Chronic hepatitis B (CHB) is a serious disease that can lead to severe complications as cirrhosis and hepatocellular carcinoma. The vast majority of people with chronic HBV infection are asymptomatic and as many as 2 in 3 people do not know they are infected. This is an indication of under screening by healthcare professionals. However, early treatment and intervention can prevent progression of liver disease. HBV infection is a vaccine-preventable disease. Until recently, there were few treatment options for patients with CHB, but now there are a number of antiviral agents available that are both effective against hepatitis B virus (HBV) and tolerable for the patient. This review paper attempts to provide some answers regarding the prevention, diagnosis and treatment of hepatitis B.

Effectiveness and tolerability of pegylated interferon alfa-2b in combination with ribavirin for treatment of chronic hepatitis C: the PegIntrust study.

BACKGROUND AND STUDY AIMS: Large international clinical trials conducted in the past 5 years rapidly improved the treatment of chronic hepatitis C; however, it is unclear whether the advances seen in clinical trials are being paralleled by similar improvements in routine clinical practice. PegIntrust is a Belgian community-based trial evaluating the sustained virological response. PATIENTS AND METHODS: Observational study of 219 patients receiving pegylated interferon alfa-2b (1.5 microg/kg/wk) and weight-based ribavirin (800-1200 mg/day) for 48 weeks. Primary study end point was sustained virological response (SVR), defined as undetectable HCV RNA 6 months after the completion of treatment. RESULTS: In total, 108 patients (49.3 %) had undetectable HCV RNA at the end of therapy, 91 (41.6%) attaining SVR. Of the 111 patients without an end-of-treatment response, 28 were non-responders, and 21 had virological breakthrough. In total, 134 patients attained early virological response (EVR); 88 (65.7%) of those patients attained SVR. In contrast, 82 (96.5 %) of the 85 patients who did not attain EVR also did not attain SVR. Age, fibrosis score and baseline viral load were identified as important predictors of treatment outcome. The most frequently reported serious adverse events resulting in treatment discontinuation were anemia (n = 10), fatigue/asthenia/malaise (n = 6) and fever (n = 3). CONCLUSION: Our data indicate that treatment of chronic hepatitis C with PEG-IFN alfa-2b plus weight-based ribavirin results in favourable treatment outcomes in a Belgian cohort of patients treated in community-based clinical practice.

Clinical trial: a randomized trial of pegylated-interferon-alpha-2a plus ribavirin with or without amantadine in treatment-naïve or relapsing chronic hepatitis C patients.

BACKGROUND: The combination therapy of pegylated-interferon-alpha2a plus ribavirin is considered as the standard of care for patients with chronic hepatitis C. A sustained viral response is obtained in 40-50% of naïve patients with genotype 1 and in around 80% of naïve patients with genotype 2 or 3. AIM: To assess whether amantadine, added to the conventional combination therapy, could improve the treatment efficacy. METHODS: In all, 630 patients (intent-to-treat population) with chronic hepatitis C were randomized into two groups: 316 patients (treatment group) received pegylated-interferon-alpha2a (180 microg once weekly) plus ribavirin (1000-1200 mg/daily) with amantadine (200 mg/daily); 314 patients (control group) received pegylated-interferon-alpha2a (180 microg once weekly) plus ribavirin (1000-1200 mg/daily) without amantadine. The duration of the treatment was 48 weeks for genotypes 1, 4, 5 and 6, and 24 weeks for genotypes 2 and 3. RESULTS: There was no statistically significant difference between treatments groups for any of the variables tested for. Subgroups of patients likely to take advantage of the addition of amantadine were not identified. CONCLUSIONS: This large study definitely excludes the role of amantadine in addition of conventional combination therapy in the treatment of chronic hepatitis C patients.

Issues in managing patients with chronic hepatitis C in public hospitals.

Public hospitals in Belgium are taking care of a disfavoured people such as drug addicts, alcoholics, patients with low income and people referred by refugee centres. Many of these patients are at risk of hepatitis C. The medical and paramedical staff is facing numerous problems in taking care of these patients. Requests of hepatologists from public hospitals are a more effective psychosocial management, an increase of the framing in these hospitals, and a more rapid process of reimbursement of medication for treatment of hepatitis C, allowing to treat the patients according to international standards.

Long-term terlipressin administration improves renal function in cirrhotic patients with type 1 hepatorenal syndrome: a pilot study.

BACKGROUND: Hepatorenal syndrome (HRS) is a severe complication of liver cirrhosis. Recently, ornipressin, a potent splanchnic vasoconstrictor, was reported to improve renal function in patients with HRS. However, this treatment is associated with a high incidence of vascular complications. Terlipressin is thought to be as effective as ornipressin with less systemic complications. AIMS: To evaluate the effectiveness and safety of terlipressin administration in cirrhotic patients with type 1 HRS. PATIENTS: Twelve consecutive patients fulfilling HRS criteria of the International Ascites Club were included in the study. Median plasma creatinine and sodium, urine volume and sodium before treatment were 3.4 mg% (2.5-4.0); 127 mEq/l (124-130), 500 ml/24 h (100-1031) and 7 mEq/24 h (1-17). METHODS: Terlipressin was administered i.v. 2 mg bid in 8 patients and tid in 4 others for at least one week and up to 2 months. RESULTS: After one week of treatment median plasma creatinine decreased to 1.8 mg% (1.3-2.1) together with an increase in urine volume, sodium excretion, creatinine and free-water clearance. Three patients underwent successful liver transplantation with a near normal renal function after 34, 36 and 111 days. The 9 other patients died during follow-up (4 from sepsis, 2 from digestive bleeding and 3 from liver failure). No ischaemic complications were encountered during the treatment. CONCLUSIONS: Long-term terlipressin administration is safe and effective to control type 1 HRS. However, it does not cure the underlying disease and therefore, may only be considered as a bridge to a definitive treatment as liver transplantation.