Prevalence of chronic HCV infection in EU/EEA countries in 2019 using multiparameter evidence synthesis.

Background: Epidemiological data are crucial to monitoring progress towards the 2030 Hepatitis C Virus (HCV) elimination targets. Our aim was to estimate the prevalence of chronic HCV infection (cHCV) in the European Union (EU)/European Economic Area (EEA) countries in 2019. Methods: Multi-parameter evidence synthesis (MPES) was used to produce national estimates of cHCV defined as: π = πrecρrec + πexρex + πnonρnon; πrec, πex, and πnon represent cHCV prevalence among recent people who inject drugs (PWID), ex-PWID, and non-PWID, respectively, while ρrec, ρex, and ρnon represent the proportions of these groups in the population. Information sources included the European Centre for Disease Prevention and Control (ECDC) national operational contact points (NCPs) and prevalence database, the European Monitoring Centre for Drugs and Drug Addiction databases, and the published literature. Findings: The cHCV prevalence in 29 of 30 EU/EEA countries in 2019 was 0.50% [95% Credible Interval (CrI): 0.46%, 0.55%]. The highest cHCV prevalence was observed in the eastern EU/EEA (0.88%; 95% CrI: 0.81%, 0.94%). At least 35.76% (95% CrI: 33.07%, 38.60%) of the overall cHCV prevalence in EU/EEA countries was associated with injecting drugs. Interpretation: Using MPES and collaborating with ECDC NCPs, we estimated the prevalence of cHCV in the EU/EEA to be low. Some areas experience higher cHCV prevalence while a third of prevalent cHCV infections was attributed to PWID. Further efforts are needed to scale up prevention measures and the diagnosis and treatment of infected individuals, especially in the east of the EU/EEA and among PWID. Funding: ECDC.

Combining cross-sectional survey and register data improved the estimate of hepatitis C prevalence among patients attending a psychiatric emergency department in Denmark.

BACKGROUND: The prevalence of hepatitis C (HCV) among psychiatric patients is elevated compared to the background population in many studies, but the prevalence among Danish psychiatric patients is unknown. The aim of the study was to determine the HCV prevalence and the proportion of the psychiatric patient population that remains to be diagnosed and treated in a Danish setting. METHODS: During a 5-month period, patients attending the psychiatric emergency room in Vejle, Denmark, were offered point-of-care anti-HCV testing. Previous hepatitis C tests for all patients attending the Psychiatric Department in the study period were extracted from the national laboratory database (DANVIR). We combined the survey and register data in a capture-recapture estimate of undiagnosed patients with HCV. RESULTS: During the study 24.9% (589 of 2364) patients seen at the psychiatric department attended the emergency room. The prevalence of anti-HCV among those tested in the emergency room was 1.6%. The laboratory register identified 595/2364 patients previously tested for anti-HCV with a positive prevalence of 6.1%. The undiagnosed anti-HCV positives among the 1483 never tested was estimated to 1.1%. Thus the total estimated prevalence of anti-HCV was 2.3% (54/2364, 95% CI 1.7%-3.0%) in the population, of whom 70.4% had been diagnosed, and 72.2% of diagnosed patients had received treatment or cleared HCV. CONCLUSION: Combining survey and register data showed that the WHO target of 90% diagnosed and 80% treated was not met. To eliminate HCV in the psychiatric population, both undiagnosed and untreated patients must be targeted.

Full-length sequence analysis of hepatitis C virus genotype 3b strains and development of an in vivo infectious 3b cDNA clone.

IMPORTANCE: HCV genotype 3b is a difficult-to-treat subtype, associated with accelerated progression of liver disease and resistance to antivirals. Moreover, its prevalence has significantly increased among persons who inject drugs posing a serious risk of transmission in the general population. Thus, more genetic information and antiviral testing systems are required to develop novel therapeutic options for this genotype 3 subtype. We determined the complete genomic sequence and complexity of three genotype 3b isolates, which will be beneficial to study its biology and evolution. Furthermore, we developed a full-length in vivo infectious cDNA clone of genotype 3b and showed its robustness and genetic stability in human-liver chimeric mice. This is, to our knowledge the first reported infectious cDNA clone of HCV genotype 3b and will provide a valuable tool to evaluate antivirals and neutralizing antibodies in vivo, as well as in the development of infectious cell culture systems required for further research.

Hepatitis C screening and linkage to care with a mobile clinic in Southern Denmark.

BACKGROUND: Knowing the prevalence of hepatitis C (HCV) in risk groups is essential for elimination. The aim of the study was to assess HCV prevalence among people with different risk profiles and the feasibility of linking people with HCV to care. METHODS: In Southern Denmark we tested people who were using shelters, cafés, and facilities for marginalized populations and the general population. We established a mobile clinic for HCV testing offering point-of-care HCV-antibody (HCV-Ab), point-of-care HCV RNA testing, and dried blood spot (DBS) testing. People with HCV infection were linked to care. RESULTS: Among 802 tested persons, we found an HCV-Ab /HCV RNA prevalence of 13% (n = 101) /3% (n = 24). We found a prevalence of 20% (n = 97)/5% (n = 24) among 475 persons tested at locations attended by people who inject drugs but 0%/0% when testing the general population. Of 24 people who were HCV RNA positive, 83% (n = 20) initiated treatment, 13% (n = 3) spontaneously cleared their infection, and one was lost to follow-up. CONCLUSION: General population testing has limited utility while focus on settings attended by people with increased HCV risk is more feasible. Linkage of people with a current HCV infection to care is feasible.

Retrieval of patients with hepatitis C who were lost to follow-up in Southern Denmark.

BACKGROUND: The goal of the C-Free-South project is to eliminate hepatitis C (HCV) in the Region of Southern Denmark (1.2 million inhabitants). One target group consists of people with HCV who had received care but were lost to follow-up. The study aim was to evaluate program efficacy in locating these patients and getting them into care. METHODS: Patients were contacted if they were HCV-RNA positive and age 18+ years, registered in the clinical hepatitis database as of November 1, 2019, and had no scheduled HCV-related appointment. They were contacted at 2-month intervals by phone or letter. For patients who did not respond, we asked their general practitioner to refer them, if possible. RESULTS: We identified 69 (7%) patients in the database who were listed as untreated and not being followed up. We successfully contacted 54 (78%), and the remaining 15 (22%) did not respond to our contacts. To date, 45 (65%) had initiated treatment, one (1%) had rejected treatment, and eight (12%) did not show up to their appointments. Among those receiving treatment, 20 (44%) responded after the first contact, 18 (40%) after the second contact, and 7 (16%) after informing the general practitioner. CONCLUSION: An intensified and persistent effort made it possible to reach most HCV patients lost to follow-up. All new contact attempts increased the possibility that patients would receive treatment. Nevertheless, 22% of HCV patients lost to follow-up did not respond to repeated contact attempts.

Increasing prevalence of chronic hepatitis B virus infection and low linkage to care in Denmark on 31 December 2016 - an update based on nationwide registers.

OBJECTIVES: We aimed to update the estimated prevalence of both diagnosed and undiagnosed chronic hepatitis B virus infection in Denmark. Moreover, we aimed to determine the number of people with chronic hepatitis B virus infection in specialised care and to assess the completeness of reporting to the national register of communicable diseases. METHODS: Using four registers with national coverage, we identified all individuals registered with chronic hepatitis B virus infection, aged 16 years or older, and alive in Denmark on 31 December 2016. The diagnosed population was then estimated using capture-recapture analysis. The undiagnosed population was estimated using data from the Danish pregnancy screening program. RESULTS: We estimated that 14,548 individuals were living with chronic hepatitis B virus infection corresponding to 0.3% of the Danish population. Of them, 13,530 (93%) were diagnosed and 7942 (55%) were registered in one or more of the source registers. Only 4297 (32%) diagnosed individuals had attended specialised care and only 3289 cases (24%) were reported to the Danish communicable disease register. CONCLUSION: The prevalence of chronic hepatitis B virus infection increased from 2007 to 2017. The majority that had been diagnosed did not receive care as recommended by national guidelines and were not reported to the communicable diseases register responsible for hepatitis B virus surveillance. Future efforts should focus on linking individuals diagnosed with chronic hepatitis B virus infection to specialised care and improving reporting to the hepatitis B virus surveillance system.

Ischemic Heart Disease in Chronic Hepatitis B: A Danish Nationwide Cohort Study.

Objective: Data on the risk of ischemic heart disease (IHD) in patients with chronic hepatitis B virus (CHB) are conflicting. Our objective was to address the rate of IHD in patients with CHB compared with individuals without CHB (control-persons) from the general population. Study Design and Setting: We conducted a cohort study of prospectively obtained data from Danish nationwide registries. We produced cumulative incidence curves and calculated the unadjusted incidence rate ratio (IRR) of IHD in persons with and without CHB. The adjusted association between having CHB and developing IHD was examined using a cause-specific Cox regression model. Results: In total, 6472 persons with CHB and 62,251 age- and sex-matched individuals from the general population were followed for 48,840 and 567,456 person-years, respectively, during which 103 (1,59%) with CHB and 1058 (1,70%) control-persons developed IHD. The crude IRR was 1.13 (95% CI: 0.91-1.39). CHB did not have a statistically significant effect on the rate of IHD after adjusting for several confounding factors (adjusted hazard ratio: 0.96, 95% CI: 0.76-1.21). Conclusion: In this nationwide cohort study, we did not find any difference between rate of IHD in persons with CHB in comparison with the general population.

Immunological Characteristics of Patients Receiving Ultra-Short Treatment for Chronic Hepatitis C.

Reducing the treatment duration for chronic hepatitis C could be an important tool in the effort to reach the elimination goals set by the World Health Organization. The current challenge is to predict the target group who will achieve sustained virological response at week 12 (SVR12) with shorter treatment duration. The aim of this exploratory study was to characterize immune subsets with focus on inhibitory receptors in patients who experienced SVR12 or virological relapse following four weeks treatment with glecaprevir/pibrentasvir with or without ribavirin. A total of 32 patients were included in this study of whom 21 achieved SVR12 and 11 had virological relapse. All available samples at baseline (n = 31) and end of treatment (EOT) (n = 30) were processed for flow cytometric analysis in order to measure the expression of PD-1, 2B4, BY55, CTLA-4, TIM-3 and LAG-3 on 12 distinct T cell subsets. At baseline, patients with SVR12 (n=21) had numerically lower frequencies of inhibitory receptors for 83% (60/72) of the investigated T-cell subtypes. The most significant difference observed between the two groups was a lower frequency of stem cell-like memory T-cells CD4+PD1+ in the SVR group (p = 0.007). Furthermore, we observed a significant positive correlation between baseline viral load and the expression of PD-1 on the total CD8+ T-cells and effector memory T-cells CD4+ and CD8+ for patients with virological relapse. This study suggests a measurable immunologic phenotype at baseline of patients achieving SVR12 after short treatment compared to patients with virological relapse.

A multi-level intervention to eliminate hepatitis C from the Region of Southern Denmark: the C-Free-South project.

Denmark has signed the WHO strategy to eliminate hepatitis C virus (HCV). In the absence of a national strategy for elimination, a local action plan was developed in the Region of Southern Denmark (RSD). The aim of the strategy is to diagnose 90% of HCV-infected persons and treat 80% of those diagnosed by 2025. The strategy was developed by reviewing Danish data on HCV epidemiology and drug use to identify key populations for screening, linkage to care, and treatment. Based on available published data from 2016, an estimated 3028 persons in the RSD were HCV-RNA positive (population prevalence 0.21%). Of these, 1002 were attending clinical care, 1299 were diagnosed but not in clinical care, and 727 were undiagnosed. Three different interventions targeting the HCV-infected population and two interventions for HCV surveillance are planned to achieve elimination. The "C-Free-South" strategy aims to eliminate HCV in our region by identifying (90%) and treating (80%) of infected persons by the end of 2025, 5 years earlier than the WHO elimination target date.

Soluble inflammatory mediators identify HCV patients who may be cured with four weeks of antiviral treatment.

Soluble inflammatory mediators (SIM) can be predictive of treatment outcome in antiviral treatment of chronic hepatitis C. Recently, it was shown that a subgroup of patients can be cured with four weeks of therapy. We here profiled patients for 70 SIM before and during treatment of hepatitis C with glecaprevir/pibrentasvir (GLE/PIB) +/- ribavirin. Proximity extension assay was performed in a total of 32 patients. Pre-treatment SIM profiles did not distinguish patients achieving an SVR (n = 21) from patients experiencing antiviral relapse (n = 11). However, after 4 weeks of therapy, eight markers were identified that could distinguish patients with SVR from the relapsed group, namely MMP-10, CCL20, CXCL11, FGF-23, TNF, MCP-2, IL-18R1 and CXCL10. Thus, this study shows that a distinct on-treatment immune profile is associated with cure of HCV infection after ultrashort treatment.

Hepatitis C time trends in reported cases and estimates of the hidden population born before 1965, Denmark and Sweden, 1990 to 2020.

BackgroundAccording to the World Health Organization, hepatitis C virus (HCV) infection should be under control by 2030.AimOur aim was to describe the size and temporal changes in reported cases of chronic HCV infection in Denmark and Sweden and to estimate the size of the hidden (undiagnosed) population born before 1965.MethodsWe extracted all HCV infections reported to national surveillance systems in Denmark and Sweden from 1990 to 2020. Prediction of the size of the hidden HCV-infected population was restricted to the cohort born before 1965 and cases reported up to 2017. We applied a model based on removal sampling from binomial distributions, estimated the yearly probability of diagnosis, and deducted the original HCV-infected population size.ResultsDenmark (clinician-based) reported 10 times fewer hepatitis C cases annually than Sweden (laboratory and clinician-based), peaking in 2007 (n = 425) and 1992 (n = 4,537), respectively. In Denmark, the birth year distribution was monophasic with little change over time. In recent years, Sweden has had a bimodal birth year distribution, suggesting ongoing infection in the young population. In 2017, the total HCV-infected population born before 1965 was estimated at 10,737 living persons (95% confidence interval (CI): 9,744-11,806), including 5,054 undiagnosed, in Denmark and 16,124 (95% CI: 13,639-18,978), including 10,580 undiagnosed, in Sweden.ConclusionsThe reporting of HCV cases in Denmark and Sweden was different. For Denmark, the estimated hidden population was larger than the current national estimate, whereas in Sweden the estimate was in line with the latest published numbers.

[From treating in the dark towards eliminating hepatitis C].

Before the hepatitis C virus (HCV) was identified, patients with hepatitis C were treated with interferon. Alanine aminotranferase levels decreased in 25-50% of treated patients, but only 10-20% had been cured, i.e. became HCV-RNA-negative. Cure rates were improved to 40-60% by prolonging the duration of therapy and adding ribavirin, but it was not until the introduction of direct acting antivirals, that a cure for all patients was achieved. The time is now to eliminate hepatitis C, and in this review we argue, that it will require outreach and point-of-care testing and treating, but we expect Denmark to fulfil the WHO elimination goals before 2030.

Emergency department testing is feasible but ineffective to eliminate hepatitis C in Denmark.

BACKGROUND: As direct-acting antiviral treatment for hepatitis C virus (HCV) is widely available in Denmark, the hindrance to achieving elimination lies in identifying infections. Effective identification relies on screening in high-risk populations. Here, we report the outcomes of a risk-based, point-of-care (POC) screening strategy in a Danish emergency department (ED). METHODS: During a three-month period, ED patients at Odense University Hospital were screened for risk factors and offered POC HCV-antibody (HCV-Ab) testing. Reactive results were followed up by confirmatory venepuncture testing. The main outcome measure was prevalence of HCV-antibodies. Secondary outcome measures were prevalence of risk factors and an evaluation of feasibility of ED screening. RESULTS: During study times, 1831 (55.7%) of 3288 presentations to the ED were eligible for screening. Six hundred and seventy-three (36.8%) were approached, of which 514 (28.1%) participated and 159 (8.7%) declined. Of 514 participants, 339 (66%) reported one or more risk factors, and 489 (95.1%) underwent HCV-Ab testing. Four (0.8%) had a reactive HCV-Ab test. No active infections of HCV were found. The risk factor of having injected drugs was present in all HCV-Ab positive patients. Compared to participants, patients who could not be approached had a lower prevalence of previously diagnosed hepatitis C- and risk-factor-associated diagnoses. CONCLUSIONS: The risk factor of injecting drug use had the highest yield for HCV-Ab positivity. Additional risk factors did not contribute to case-finding. This screening strategy was feasible but ineffective. Further testing strategies will be necessary to identify the remaining hepatitis C patients in Denmark.

Low incidence of HCC in chronic hepatitis C patients with pretreatment liver stiffness measurements below 17.5 kilopascal who achieve SVR following DAAs.

BACKGROUND AND AIMS: To evaluate the ability of pretreatment liver stiffness measurements (pLSM) to predict hepatocellular carcinoma (HCC), incident decompensation and all-cause mortality in chronic hepatitis C (CHC) patients who achieved sustained virological response (SVR) after treatment with direct-acting antivirals (DAAs). METHODS: 773 CHC patients with SVR after DAA treatment and no prior liver complications were identified retrospectively. Optimized cut-off of 17.5 kPa for incident HCC was selected by maximum Youden's index. Patients were grouped by pLSM: <10 kPa [reference], 10-17.4 kPa and ≥17.5 kPa. Primary outcomes were incident hepatocellular carcinoma and secondary outcomes were incident decompensated cirrhosis and all-cause mortality, analyzed using cox-regression. RESULTS: Median follow-up was 36 months and 43.5% (336) had cirrhosis (LSM>12.5 kPa). The median pLSM was 11.6 kPa (IQR 6.7-17.8, range 2.5-75) and pLSM of <10 kPa, 10-17.4 kPa and 17.5-75 kPa was seen in 41.5%, 32.2% and 26.3%. During a median follow-up time of 36 months, 11 (1.4%) developed HCC, 14 (1.5%) developed decompensated cirrhosis, and 38 (4.9%) patients died. A pLSM of 17.5 kPa identified patients with a high risk of HCC with a negative predictive value of 98.9% and incidence rate of HCC in the 17.5-75 kPa group of 1.40/100 person years compared to 0.14/100 person years and 0.12/100 person years in the 10-17.4 kPa and <10 kPa groups, p<0.001. CONCLUSION: Pretreatment LSM predicts risk of HCC, decompensation and all-cause mortality in patients with SVR after DAA treatment. Patients with a pLSM <17.5 kPa and no other risk factors for chronic liver disease appear not to benefit from HCC surveillance for the first 3 years after treatment. Longer follow-up is needed to clarify if they can be safely excluded from post treatment HCC screening hereafter.

Hepatitis C prevalence in Denmark in 2016-An updated estimate using multiple national registers.

BACKGROUND: Chronic hepatitis C (CHC) can be eliminated as a public health threat by meeting the WHO targets: 90% of patients diagnosed and 80% treated by 2030. To achieve and monitor progress towards elimination, an updated estimate of the size of the CHC population is needed, but Denmark has no complete national CHC register. By combining existing registers in 2007, we estimated the population living with CHC to be 16,888 (0.38% of the adult population). AIM: To estimate the population living with diagnosed and undiagnosed CHC in Denmark on 31 December 2016. Among additional aims were to estimate the proportion of patients attending specialised clinical care. METHODS: People with diagnosed CHC were identified from four national registers. The total diagnosed population was estimated by capture-recapture analysis. The undiagnosed population was estimated by comparing the register data with data from two cross-sectional surveys. RESULTS: The population living with diagnosed CHC in Denmark was 7,581 persons (95%CI: 7,416-12,661) of which 6,116 (81%) were identified in the four registers. The estimated undiagnosed fraction was 24%, so the total CHC infected population was 9,975 corresponding to 0.21% of the adult population (95%CI: 9,758-16,659; 0.21%-0.36%). Only 48% of diagnosed patients had received specialised clinical care. CONCLUSION: CHC prevalence in Denmark is declining and 76% of patients have been diagnosed. Linking diagnosed patients to care and increasing efforts to test people with former or current drug use will be necessary to achieve CHC elimination.

Incidence, prevalence and risk factors for hepatitis C in Danish prisons.

Hepatitis C virus (HCV) infection is prevalent among people in prison and prisons could therefore represent a unique opportunity to test risk groups for HCV. The aim of this sero-epidemiological study was to determine the incidence and prevalence of HCV infection and the corresponding risk factors in Danish prisons. Participants, recruited from eight Danish prisons, were tested for HCV using dried blood spots and filled out a questionaire with demographic data and risk factors for HCV infection. In total, 76.9% (801/1041) of all eligible prisoners consented to participate. The prevalence of HCV RNA positive prisoners was 4.2% (34/801) and the in-prison incidence rate was 0.7-1.0 per 100PY overall and 18-24/100PY among PWIDs. Infected prisoners were older than the overall population with a mean age of 42 years and only 17.6% (6/34) were younger than 35 years. The prevalence of PWID was 8.5% (68/801) and only 3% (2/68) of PWID were younger than 25 years. Among the PWID, 85.3% (58/68) had ever received opioid substitution therapy (OST) and 47.1% (32/68) were currently receiving OST. Risk factors associated with HCV infection were intravenous drug use, age ≥ 40 years, and being incarcerated ≥ 10 years. In conclusion, the prevalence of PWID in Danish prisons is low, possibly reflecting a decrease in injecting among the younger generation. This together with OST coverage could explain the low prevalence of HCV infection. However among PWIDs in prison the incidence remains high, suggesting a need for improved HCV prevention in prison.

Combining liver stiffness with hyaluronic acid provides superior prognostic performance in chronic hepatitis C.

BACKGROUND: Non-invasive methods are the first choice for liver fibrosis evaluation in chronic liver diseases, but few studies investigate the ability of combined methods to predict outcomes. METHODS: 591 chronic hepatitis C patients with baseline liver stiffness (LSM) by FibroScan and hyaluronic acid measurements were identified retrospectively. The patients were grouped by baseline LSM: < 10kPa, 10-16.9kPa, and 17-75kPa. Primary outcomes were all-cause mortality and liver-related mortality, analyzed using cox regression and competing risk regression models, respectively. RESULTS: Median follow-up was 46.1 months. Prevalence of cirrhosis at baseline was 107/591 (18.1%). Median LSM was 6.8kPa (IQR 5.3-11.6) and divided into groups, 404/591 (68.4%) had a LSM < 10kPa, 100/591 (16.9%) had a LSM between 10-16.9kPa and 87/591 (14.7%) had a LSM between 17-75kPa. There were 69 deaths, 27 from liver-related disease. 26 patients developed cirrhosis and 30 developed complications of cirrhosis. The mortality rate in the 17-75kPa group was 9.7/100 person-years, compared to 2.2/100 person-years and 1.1/100 person-years in the 10-16.9kPa and <10kPa groups (p<0.005). Liver-related mortality increased 10-fold for each group (p<0.005). Cirrhotic complications occurred almost exclusively in the 17-75kPa group, with an incidence of 10.3/100 person-years, compared to 1.8/100 person-years and 0.2/100 person-years in the 10-16.9kPa and <10kPa groups (p<0.005). Median hyaluronic acid in the 17-75kPa group was approximately 200ng/mL. Patients with a LSM 17-75kPa had significantly higher risks of death, liver-related death, and complications to cirrhosis if their hyaluronic acid measurement was more than or equal to 200ng/mL at baseline, with hazard ratios of 3.25 (95% CI 1.48-7.25), 7.7 (95% CI 2.32-28), and 3.2 (95% CI 1.35-7.39), respectively. CONCLUSIONS: The combination of LSM and circulating hyaluronic acid measurements significantly improved prognostic ability, relative to LSM alone. Combined static and dynamic markers of liver fibrosis could provide superior risk prediction.

[Controlled attenuation parameter is a novel technique in screening for non-alcoholic fatty liver disease].

Non-alcoholic fatty liver disease afflicts 30% of the population and is tightly linked to the metabolic syndrome and development of cardiovascular disease and chronic liver disease. Regular ultrasound is currently used in liver steatosis diagnosing, but it is operator-dependent, fails to detect lower grades of steatosis, and is unable to graduate the degree of steatosis. Controlled attenuation parameter is a novel, ultrasound-based technique to accurately detect and grade steatosis. Further studies are needed to establish cut-offs, before it can be implemented in clinical practice.

Liver-related morbidity and mortality in patients with chronic hepatitis C and cirrhosis with and without sustained virologic response.

BACKGROUND: Chronic hepatitis C (CHC) causes liver cirrhosis in 5%-20% of patients, leading to increased morbidity and mortality. This study aimed to estimate liver-related morbidity and mortality among patients with CHC and cirrhosis in Denmark with and without antiviral treatment and sustained virologic response (SVR). Furthermore we aimed to estimate the rate of hepatocellular carcinoma (HCC) and decompensation associated with certain prognostic factors. MATERIALS AND METHODS: Patients with CHC and cirrhosis registered in the Danish Database for Hepatitis B and C were eligible. Cirrhosis was based on liver biopsy, transient elastography, and clinical cirrhosis. Data were extracted from nationwide registries. The study period was from 2002 until 2013. RESULTS: Of 1,038 patients included, 716 (69%) were male and the median age was 52 years. Median follow-up was 3.8 years, 360 patients died, and 233 of 519 treated patients achieved SVR. Alcohol overuse and hepatitis C virus genotype 3 were associated with an increased incidence rate (IR) of HCC, whereas diabetes and alcohol overuse were associated with increased IRs of decompensation. Achieving SVR reduced all-cause mortality (adjusted mortality rate ratio 0.68 [95% CI 0.43-1.09]) and liver-related mortality (mortality rate ratio 0.6 [95% CI 0.36-1]), as well as liver-related morbidity with adjusted IR ratios of 0.37 (95% CI 0.22-0.62) for HCC and 0.31 (95% CI 0.17-0.57) for decompensation. The IRs of HCC and decompensation remained elevated in patients with alcohol overuse after SVR. CONCLUSION: Alcohol overuse, hepatitis C genotype 3, and diabetes were associated with liver-related morbidity in patients with CHC and cirrhosis. SVR markedly reduced liver-related morbidity and mortality; however, special attention to patients with alcohol overuse should continue after SVR.

Feasibility of transient elastography versus real-time two-dimensional shear wave elastography in difficult-to-scan patients.

BACKGROUND AND AIMS: Transient elastography (TE) is hampered in some patients by failures and unreliable results. We hypothesized that real time two-dimensional shear wave elastography (2D-SWE), the FibroScan XL probe, and repeated TE exams, could be used to obtain reliable liver stiffness measurements in patients with an invalid TE examination. METHODS: We reviewed 1975 patients with 5764 TE exams performed between 2007 and 2014, to identify failures and unreliable exams. Fifty-four patients with an invalid TE at their latest appointment entered a comparative feasibility study of TE vs. 2D-SWE. RESULTS: The initial TE exam was successful in 93% (1835/1975) of patients. Success rate increased from 89% to 96% when the XL probe became available (OR: 1.07, 95% CI 1.06-1.09). Likewise, re-examining those with a failed or unreliable TE led to a reliable TE in 96% of patients. Combining availability of the XL probe with TE re-examination resulted in a 99.5% success rate on a per-patient level. When comparing the feasibility of TE vs. 2D-SWE, 96% (52/54) of patients obtained a reliable TE, while 2D-SWE was reliable in 63% (34/54, p < 0.001). The odds of a successful 2D-SWE exam decreased with higher skin-capsule distance (OR = 0.77, 95% CI 0.67-0.98). CONCLUSIONS: Transient elastography can be accomplished in nearly all patients by use of the FibroScan XL probe and repeated examinations. In difficult-to-scan patients, the feasibility of TE is superior to 2D-SWE.