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.

Belgian experience with triple therapy with boceprevir and telaprevir in genotype 1 infected patients who inject drugs.

No data have been reported yet on treatment outcome in persons who inject drugs (PWID) infected with hepatitis C virus treated with boceprevir or telaprevir in combination with peginterferon (Peg IFN) and ribavirin (RBV). Additionally, there are concerns about the safety of boceprevir and telaprevir in some subgroups of patients with hepatitis C (HCV). In a cohort of HCV patients infected with genotype 1 in Belgium, treatment outcome of patients infected due to IV drug use was analyzed and compared with patients who have no history of substance use. The study population consisted of 179 patients: 78 PWID and 101 controls treated with boceprevir (n = 79) or telaprevir (n = 100) additional to Peg IFN and RBV; 53 (30%) had advanced disease (F3, F4) and 79 (44%) had an antiviral therapy previously. There were no significant differences in the baseline characteristics between both groups, except that PWID patients were more frequently infected with genotype 1a (67% vs 21%), were younger and were predominantly male. Psychiatric complaints during follow-up occurred more frequently in the PWID patients: 24% versus 11% (P = .02). Treatment failure for other reasons than absence of viral response was 70% and 64% in PWID and non-PWID respectively. The sustained viral response (SVR) rates were similar in both groups (71% in PWID vs 72% in non-PWID); with a non-inferiority test with -5% margin there is a difference of -1% (95% CI [-15%, 13%]) and P = 0.30. There are no reasons to exclude PWID from treatment with boceprevir, telaprevir and novel antiviral therapies.

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.

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.

High prevalence of advanced fibrosis in association with the metabolic syndrome in a Belgian prospective cohort of NAFLD patients with elevated ALT. Results of the Belgian NAFLD registry.

INTRODUCTION: Non-alcoholic Fatty Liver Disease (NAFLD) is increasingly recognised as a source of liver related morbidity and mortality. Hard data on epidemiology and natural history are scarce. AIM: To study demographic and metabolic characteristics of the NAFLD patients seen by Belgian hepatologists. METHODS: Belgian hepatologists filled in a questionnaire for every newly diagnosed NAFLD patient between January 1st and December 31st 2004. Liver biopsy was advised if ALT > 1.5 x ULN and if 3/5 of the criteria for the metabolic syndrome (MS) (ATPI-II) were present, but was not mandatory. Biopsy was scored using the Brunt classification. RESULTS: 230 patients were prospectively included in 9 centres; 54% were males; mean age was 49.4 +/- 13.9 y; mean BMI was 30.6 +/- 4.6 kg/m2. The MS was present in 53%. In 16% formerly undiagnosed diabetes was discovered. 51% had a liver biopsy: 25% met the criteria, 26% did not. Grading did not differ between patients with or without MS. Staging was significantly more severe in patients with MS (2.43 +/- 1.25 vs. 1.73 +/- 1.18, p < 0.001). A subgroup of patients with GGT > 5 x ULN were significantly older (55.9 vs. 47.64 y, p = 0.02), more frequently diabetic (53% vs. 23%, p = 0.01) and had more advanced fibrosis (3.42 vs. 1.08, p = 0.008). ALT levels were variable. CONCLUSIONS: The MS is highly prevalent in Belgian NAFLD patients and is associated with more severe disease. Mild to moderate fibrosis is frequent, and the proposed criteria for liver biopsy are not accurate in selecting these patients. Patients with elevated GGT constitute a subgroup with more advanced disease.

Hepatitis C genotype 4 response rate to pegylated interferon and ribavirin treatment in Belgium is similar to genotype 1.

BACKGROUND AND AIMS: Patients with genotype 4 (G4) chronic hepatitis C from the Middle East respond better to treatment than genotype 1 (G1) patients. There are few data on the response rates to treatment of G4 patients living in Western Europe. Many G4 patients in Belgium originate from Central Africa, and their response to treatment seems lower. METHODS: We analysed the data from 2 randomized phase III studies conducted in Belgium, BerNar-1 and BerNar-2, comparing the sustained virological response (SVR) to pegylated interferon and ribavirin of 78 G4 patients (34 Caucasians, 44 Blacks) and 477 G1 patients (455 Caucasians, 12 Blacks), and assessing the predictors of SVR. RESULTS: Baseline characteristics of G4 and G1 patients were similar except mainly for race. Complete early virological response (cEVR) was similar in G4 (73.2%) and G1 (68.1%). cEVR was also similar between Black and Caucasian G4 and between Black and Caucasian G1 patients. Partial early virological response was similar for G4 and G1. SVR was similar for G4 (51.3%) and G1 (51.8%). There was a trend for a higher SVR in Caucasians than in Blacks. In multivariate analysis, the only predictors for SVR were the presence of cirrhosis, HCV viral load, age < 40 vs > or = 40 yrs, and treatment status (relapsers vs naive). CONCLUSIONS: G4 patients in Belgium have the same SVR as G1 patients. It is lower than the SVR described in Arab countries, especially for Black G4 patients.

A pilot observational survey of hepatitis C in Belgium.

AIM OF THE STUDY: There is a lack of epidemiological data on hepatitis C (HCV) infected patients in Belgium. Therefore our purpose was to address this important question and to evaluate the feasibility of a national HCV observatory. PATIENTS AND METHODS: From November 2003 to November 2004, every new patient prospectively seen for HCV antibody positivity in 9 Belgian hospital centres was recorded and a standardised 10-items questionnaire was completed during the consultation, including a Quality of Live (QOL) visual analogue scale. RESULTS: Three hundred and eighteen consecutive patients were recruited. Fifty five percent were male with a median age of 45 y (11-87 y). The main risk factors for infection were IV drug use (27%), blood transfusion (23%), and invasive medical procedure (11%). On the QOL scale, ranging from 0 and 100, mean value was 61 +/- 31. Transaminases were abnormal in 66% with a median elevation 2 times above normal value. HCV RNA was positive in 87% with a viral load above 800 000 IU/ml in 42%. Genotype 1 was predominant (59%), followed by genotypes 3 (19%) and 4 (14%). A liver biopsy was performed in 190 patients, with minimal fibrosis (METAVIR F0-F1) in 43%, moderate fibrosis (F2) in 35% and advanced stages (F3-F4) in 22%. Antiviral treatment was not considered in 53% because of normal ALT (30%), old age (7%), minimal histological stage (6%) or patient refusal (4%). CONCLUSIONS: This study highlights the feasibility of a national HCV survey using a simple questionnaire. This pilot study could be generalised throughout Belgium, and, if repeated, could allow a regular assessment of the changes in epidemiology and management of HCV infection in our country.

Daily induction combination treatment with alpha 2b interferon and ribavirin or standard combination treatment in naive chronic hepatitis C patients. A multicentre randomized controlled trial.

The standard treatment for patients with chronic hepatitis C is a 6-12-month combination therapy with interferon alpha and ribavirin. Induction treatment could result in a faster early decline of the hepatitis C virus (HCV) load and a better response rate. Naive chronically infected HCV patients (n = 454) were randomized into two arms to receive either induction treatment with interferon alpha 2b 5 million units (MU) subcutaneously (s.c.) daily during a period of 8 weeks (arm A); or treatment with interferon alpha 2b 5 MU s.c. three times a week (TIW) for a period of 8 weeks (arm B). After week 8, interferon treatment in both arms was 3 MU s.c. TIW for a total period of 12 months. In both arms, ribavirin (1000-1200 mg orally per day) was added at week 4. Induction treatment resulted in a higher virological response at week 8 of treatment (66%vs 47%; P < 0.01). However, response at the end of treatment and at 6 months follow-up was not different (53%vs 50%, 41%vs 33%). The occurrence of adverse events and the drop-out rate were similar in both arms. Although an early virological response is observed more frequently in the induction treatment, end of treatment response and sustained responses did not differ.

Liver damage caused by therapeutic vitamin A administration: estimate of dose-related toxicity in 41 cases.

Clinical presentation, changes in liver function test results, and liver morphology were examined in 41 consecutive patients with vitamin A hepatoxicity. The cause of liver disease was suspected at initial interview in only 13 instances, whereas histological evidence of fat-storing cell hyperplasia with fluorescent vacuoles led to the diagnosis in the remaining cases. Cirrhosis was found in 17, mild chronic hepatitis in 10, noncirrhotic portal hypertension in 5, and "increased storage" alone in 9 cases. During a mean follow-up period of 4.6 years, 6 patients died of causes related to the liver disease. A precise appraisal of drug consumption was obtained in 29 cases. Among them the total cumulative intake was the highest in patients with cirrhosis (423 +/- 103 x 10(6) IU) and significantly lower in those with noncirrhotic liver disease (88.5 +/- 41; P less than 0.02). The smallest continuous daily consumption leading to cirrhosis was 25,000 IU during 6 years, whereas higher daily doses (greater than or equal to 100,000 IU) taken during 21/2 years resulted in similar histological lesions. It was concluded that at least in some western countries chronic vitamin A consumption might represent an appreciable cause of chronic liver disease, the recognition of which mainly relies on expert liver biopsy interpretation. The data also indicate that prolonged and continuous consumption of doses in the low "therapeutic" range can result in life-threatening liver damage.

Collagenous colitis: a transient condition? Report of two cases.

We have seen two patients with watery diarrhea whose work-up revealed a collagenous infiltration beneath the rectal epithelium. Within a year, symptoms disappeared in both. Repeated rectal biopsy revealed the disappearance of the collagen layer. Collagenous colitis may thus present as a transient condition.

Increased sensitivity to concanavalin A and a suppressor cell defect in chronic active hepatitis.

Suppressor T cell activity was studied serially in 11 patients with HBsAg-negative chronic active hepatitis when the disease was clinically and histologically inactive and during relapse using a short-lived suppressor cell assay. With a concentration of concanavalin A which gave a suboptimal proliferative response in normal subjects, the expected increase in thymidine incorporation was seen when the addition of the mitogen was delayed for 24 hr after the start of the lymphocyte culture period, a finding consistent with the disappearance of functional suppressor cells during the initial incubation. This effect was seen both in normal subjects and in patients with inactive disease, but was not observed at times of relapse. Further studies revealed a marked increase in lymphocyte sensitivity to concanavalin A at these times, a finding which might explain the apparent decrease in suppressor cell activity. When lower concentrations of mitogen were used in the assay, however, a significant reduction in suppressor cell activity was observed in the patients with chronic active hepatitis which was almost equal in magnitude in both the active and inactive groups, suggesting the presence of a true suppressor cell defect in this disease.