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The incidence of hepatocellular carcinoma (HCC) in patients co-infected with HIV and hepatitis B virus (HBV) or hepatitis C virus (HCV) is increasing. In patients with cirrhosis, guidelines recommend HCC screening every 6 months. We assessed compliance with HCC screening guidelines in cirrhotic HBV/HCV-HIV-co-infected patients. HBV/HCV-HIV-co-infected patients with cirrhosis were enrolled from 4 European prospective cohorts participating in the COHERE collaboration, followed from 1 January 2005-1 January 2015. Assessment of liver cirrhosis was based on clinical diagnosis and liver biopsy or Fibroscan. Compliance with HCC screening guidelines was defined as one ultrasound every 6 months. Generalized estimating equation models adjusted for repeated measurements were fitted to determine predictors of low compliance. Different sensitivity analyses were performed and validation of the data was carried out by randomly checking 10% of each cohort's data. 646 HIV-patients with the diagnosis of cirrhosis were included: 518 (80%) HCV-, 85 (13%) HBV- and 43 (7%) HBV/HCV-co-infected. Median age at cirrhosis diagnosis was 44 years, median follow-up time since diagnosis was 5.3 years. Screening

BACKGROUND: Successful treatment of chronic hepatitis C with direct-acting antiviral agents (DAAs) is expected to lead to improvement in liver fibrosis in most of the patients. However, limited data are available on the improvement of advanced liver fibrosis and cirrhosis, measured by transient elastography after treatment. This study assessed the change in liver stiffness measurements after successful treatment with DAAs in patients with pre-treatment advanced fibrosis or cirrhosis. METHODS: This observational retrospective cohort study included 514 mono-infected chronic hepatitis C patients, treated with all possible DAA-regimes in the Amsterdam region, the Netherlands. Liver stiffness was measured using FibroScan® at baseline and during follow-up. Cut-off values for staging liver fibrosis were ≥ 9.5 kPa for advanced fibrosis (F3) and ≥ 14.6 kPa for cirrhosis (F4). RESULTS: Liver stiffness decreased significantly from a median of 15.6 kPa (IQR 11.4-25.4) to 9.4 kPa (IQR 6.2-17.0) in 197 patients with pre-treated advanced fibrosis or cirrhosis. In 50.3% of these patients, liver stiffness improved to a value fitting with mild to moderate fibrosis (< 9.5 kPa, F0-F2) after successful treatment. Multivariate analysis demonstrated that a pre-treatment FibroScan® value of ≥ 20.0 kPa was associated with persisting advanced fibrosis or cirrhosis after treatment (OR 29.07, p < 0.001). CONCLUSION: Liver stiffness improves significantly after successful direct-acting antiviral agent treatment in chronic hepatitis C patients with advanced fibrosis or cirrhosis prior to DAA treatment. Long-term outcomes regarding occurrence of hepatocellular carcinoma (HCC) in these patients are required to determine whether they can be safely discharged from HCC surveillance.

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).

The incidence of hepatocellular carcinoma (HCC) in patients co-infected with HIV and hepatitis B virus (HBV) or hepatitis C virus (HCV) is increasing. In patients with cirrhosis, guidelines recommend HCC screening every 6 months. We assessed compliance with HCC screening guidelines in cirrhotic HBV/HCV-HIV-co-infected patients. HBV/HCV-HIV-co-infected patients with cirrhosis were enrolled from 4 European prospective cohorts participating in the COHERE collaboration, followed from 1 January 2005-1 January 2015. Assessment of liver cirrhosis was based on clinical diagnosis and liver biopsy or Fibroscan. Compliance with HCC screening guidelines was defined as one ultrasound every 6 months. Generalized estimating equation models adjusted for repeated measurements were fitted to determine predictors of low compliance. Different sensitivity analyses were performed and validation of the data was carried out by randomly checking 10% of each cohort's data. 646 HIV-patients with the diagnosis of cirrhosis were included: 518 (80%) HCV-, 85 (13%) HBV- and 43 (7%) HBV/HCV-co-infected. Median age at cirrhosis diagnosis was 44 years, median follow-up time since diagnosis was 5.3 years. Screening

MicroRNA-122 (miR-122) is an important host factor for the hepatitis C virus. Treatment with RG-101, a GalNAc conjugated anti-miR-122 oligonucleotide, resulted in a significant viral load reduction in patients with chronic hepatitis C (CHC) infection. Here, we analyzed the effects of RG-101 therapy on antiviral immunity. 32 CHC patients HCV genotype 1, 3 and 4 received a single subcutaneous administration with RG-101 at 2 mg/kg (n=14), 4 mg/kg (n=14) or placebo (n=2 per dosing group). Plasma and PBMCs were collected at multiple time points and comprehensive immunological analyses were performed. Following RG-101 administration, HCV RNA declined in all patients (mean decline at week 2: 3.27 log10 IU/mL). At week 8 HCV RNA was undetectable in 15/28 patients. Plasma IP-10 levels declined significantly upon dosing with RG-101. Furthermore, the frequency of NK cells increased, and the proportion of markers for NK cells expressing activating receptors activity and differentiation normalized and NK cell IFN-γ production decreased after RG-101 dosing. By week 8 post RG-101 injection, fFunctional HCV-specific IFN-γ-T cell responses did not declined significantly change in patients who had undetectable HCV RNA by week 8 post RG-101 injection. No increase in the magnitude of HCV-specific T cell responses was observed at later time points, including 3 patients who were HCV RNA negative 76 weeks post dosing.

Achtergrond: Bij een kind met een zwelling in de hals is een uitgebreide differentiaaldiagnose mogelijk. Chronische lymfadenopathie leidt bij kinderen dan ook niet zelden tot uitgebreid bloedonderzoek. Cervicofaciale non-tuberculeuze mycobacteriële lymfadenitis is echter niet met bloedonderzoek aan te tonen. Het is een zeldzame ziekte die met name bij jonge kinderenvoorkomt.Casus: Een 4-jarig meisje had sinds 9 weken een zwelling in haar hals; de laatste week zag de overliggende huid rood en schilferig. Uitgebreid bloedonderzoek gaf geen uitsluitsel over de diagnose en met echografie werden 3 abcederende, heterogene lymfeklieren met een fisteling naar de subcutis gezien. Dit maakte de diagnose ‘cervicofaciale NTM-lymfadenitis’ aannemelijk. Het geïnfecteerde klierpakket werd verwijderd en de microbiologische kweek waspositief voor Mycobacterium haemophilum.Conclusie: NTM-infecties bij jonge kinderen zijn hardnekkige infecties die voor het beste cosmetische en functionele resultaat in een vroeg stadium chirurgisch behandeld moeten worden.

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Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8666000 cases) and Russia (4162000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV-related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.

Prevalence of hepatitis C virus (HCV) infection in the Netherlands is low (anti-HCV prevalence 0.22%). All-oral treatment with direct-acting antivirals (DAAs) is tolerable and effective but expensive. Our analysis projected the future HCV-related disease burden in the Netherlands by applying different treatment scenarios. Using a modelling approach, the size of the HCV-viraemic population in the Netherlands in 2014 was estimated using available data and expert consensus. The base scenario (based on the current Dutch situation) and different treatment scenarios (with increased efficacy, treatment uptake, and diagnoses) were modelled and the future HCV disease burden was predicted for each scenario. The estimated number of individuals with viraemic HCV infection in the Netherlands in 2014 was 19,200 (prevalence 0.12%). By 2030, this number is projected to decrease by 4 5% in the base scenario and by 85% if the number of treated patients increases. Furthermore, the number of individuals with hepatocellular carcinoma and liver-related deaths is estimated to decrease by 19% and 27%, respectively, in the base scenario, but may both be further decreased by 68% when focusing on treatment of HCV patients with a fibrosis stage of ≥ F2. A substantial reduction in HCV-related disease burden is possible with increases in treatment uptake as the efficacy of current therapies is high. Further reduction of HCV-related disease burden may be achieved through increases in diagnosis and preventative measures. These results might inform the further development of effective disease management strategies in the Netherlands

Interferon-g-inducible protein-10 (IP-10) serum levels are associated with IL28B genotype and may predict response to interferon÷ribavirin-based therapy in chronic hepatitis C patients. Our aim was to relate IP-10 levels before and during treatment to treatment outcome, viral HCV-RNA kinetics and IL28B genotype. A cohort of chronic hepatitis C patients was treated with high-dose interferon for six weeks, followed by standard peginterferon÷ ribavirin for 24 or 48 weeks. IP-10 and HCV-RNA levels were frequently determined before, during and after treatment. IP-10 levels increased from log2.56 pg÷ml at baseline to log3.48 pg÷ml at Day 1 and gradually diminished thereafter. IP-10 levels at any time point were not statistically different between patients with or without sustained viral response (SVR). Patients with IL28B CC genotype had significantly lower baseline IP-10 levels (p = 0.019) and a higher increase of IP-10 levels from baseline to Day 1 than patients with IL28B non-CC genotypes (p = 0.015). Patients with HCV-RNA decline ≥ 2.28log10 at Day 1 had significantly lower baseline IP-10 levels (p = 0.016) and a higher increase of IP-10 levels from baseline to Day1 (p = 0.047) than patients with HCV-RNA decline of < 2.28log10 at Day 1. In patients treated with high induction dose interferon, IP-10 levels at any time point were not predictive for SVR. Low baseline IP-10 levels and a higher increase of IP-10 levels from baseline to Day 1 were associated with IL28B CC genotype and HCV-RNA decline ≥ 2.28log10 at Day 1. This suggests that, in our cohort, for prediction of SVR the added value of IP-10 to IL28B genotype and early viral kinetics is limited

Background: Successful treatment of chronic hepatitis C with direct-acting antiviral agents (DAAs) is expected to lead to improvement in liver fibrosis in most of the patients. However, limited data are available on the improvement of advanced liver fibrosis and cirrhosis, measured by transient elastography after treatment. This study assessed the change in liver stiffness measurements after successful treatment with DAAs in patients with pre-treatment advanced fibrosis or cirrhosis. Methods: This observational retrospective cohort study included 514 mono-infected chronic hepatitis C patients, treated with all possible DAA-regimes in the Amsterdam region, the Netherlands. Liver stiffness was measured using FibroScan® at baseline and during follow-up. Cut-off values for staging liver fibrosis were ≥ 9.5 kPa for advanced fibrosis (F3) and ≥ 14.6 kPa for cirrhosis (F4). Results: Liver stiffness decreased significantly from a median of 15.6 kPa (IQR 11.4-25.4) to 9.4 kPa (IQR 6.2-17.0) in 197 patients with pre-treated advanced fibrosis or cirrhosis. In 50.3% of these patients, liver stiffness improved to a value fitting with mild to moderate fibrosis (< 9.5 kPa, F0-F2) after successful treatment. Multivariate analysis demonstrated that a pre-treatment FibroScan® value of ≥ 20.0 kPa was associated with persisting advanced fibrosis or cirrhosis after treatment (OR 29.07, p < 0.001). Conclusion: Liver stiffness improves significantly after successful direct-acting antiviral agent treatment in chronic hepatitis C patients with advanced fibrosis or cirrhosis prior to DAA treatment. Long-term outcomes regarding occurrence of hepatocellular carcinoma (HCC) in these patients are required to determine whether they can be safely discharged from HCC surveillance.