• MeSH
• antivirové látky aplikace a dávkování   klasifikace   škodlivé účinky   MeSH
• chronická hepatitida C * diagnóza   epidemiologie   farmakoterapie   komplikace   patofyziologie   přenos   MeSH
• diabetes mellitus 2. typu * komplikace   MeSH
• klinické rozhodování MeSH
• kombinovaná farmakoterapie metody   MeSH
• komorbidita MeSH
• lidé MeSH
• plošný screening MeSH
• riziko MeSH
• setrvalá virologická odpověď MeSH
• stupeň závažnosti nemoci MeSH
• výběr pacientů MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• Klíčová slova
• risankizumab,
• MeSH
• chronická hepatitida C komplikace   MeSH
• dospělí MeSH
• HIV infekce komplikace   MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• komorbidita MeSH
• lidé MeSH
• psoriáza * farmakoterapie   komplikace   MeSH
• sexuální a genderové menšiny MeSH
• syfilis diagnóza   komplikace   MeSH
• terapie neúspěšná MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Background and Objectives: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer with a highly unfavorable prognosis. Aims: Retrospective statistical analysis of patients with HCC in the field of liver cirrhosis treated at our center from the perspective of demography, and the effects of key changes in diagnostic and therapeutic procedures in the last 10 years on overall survival (OS) and earlier diagnosis. Materials and Methods: This study included 170 cirrhotic patients with HCC (136 men, 80%). Demographic and etiological factors and OS were analyzed based on distribution into three groups according to the period and key changes in diagnostic and therapeutic approaches (BCLC classification staging; standardization of protocol for transarterial chemoembolization (TACE) and the introduction of direct-acting antivirals (DAA) for the treatment of chronic viral hepatitis C (HCV); expansion of systemic oncological therapy). Results: The mean age at the time of diagnosis was 69.3 years (SD = 8.1), and etiology was as follows: non-alcoholic steatohepatitis (NASH) 39%, alcoholic liver disease (ALD) 36%, HCV 18%, cryptogenic liver cirrhosis 3%, chronic hepatitis B infection (HBV) 2%, and other etiology 2%. Distribution of stages according to the BCLC: 0 + A 36%, B 31%, C 22%, and D 11%. However, the distribution in the first studied period was as follows: 0 + A 15%, B 34%, C 36%, and D 15%; and in the last period: 0 + A 45%, B 27%, C 17%, and D 11%, and difference was statistically significant (p < 0.05). The median OS for stages 0 + A, B, C, and D was 58, 19, 6, and 2 months, respectively. During the monitored period, there was a visible increase in the etiology of ALD from 30% to 47% and a decrease in HCV from 22% to 11%. In patients treated with TACE (stage B), the median OS grew from 10 to 24 months (p < 0.0001) between the marginal monitored periods. Conclusions: We described a decreasing number of patients with HCV-related HCC during follow-up possibly linked with the introduction of DAA. In our cohort, an improvement in early-stage diagnosis was found, which we mainly concluded as a result of proper ultrasound surveillance, the institution of a HCV treatment center, and increased experience of our sonographers with an examination of cirrhotic patients. Lastly, we described significantly improved overall survival in patients with intermediate HCC treated by TACE, due to the increased experience of interventional radiologists with the method at our facility and an earlier switch to systemic therapy in case of non-response to TACE.

• MeSH
• antivirové látky terapeutické užití   MeSH
• chemoembolizace * škodlivé účinky   metody   MeSH
• chronická hepatitida C * komplikace   farmakoterapie   MeSH
• hepatocelulární karcinom * etiologie   terapie   MeSH
• jaterní cirhóza komplikace   diagnóza   MeSH
• lidé MeSH
• nádory jater * etiologie   terapie   MeSH
• retrospektivní studie MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Following the introduction of direct-acting antiviral therapy in 2013, WHO launched the first Global Health Sector Strategy on Viral Hepatitis. We describe a hepatitis C virus (HCV) cascade of care in people with HIV (PWH) across Europe in terms of reaching the WHO elimination targets of diagnosing 90% and treating 80% of HCV-infected individuals. METHODS: HIV/HCV-coinfected participants in the EuroSIDA cohort under prospective follow-up at October 1, 2019, were described using a nine-stage cascade of care. Care cascades were constructed across Europe, on a regional (n = 5) and country (n = 21) level. RESULTS: Of 4773 anti-HCV positive PWH, 4446 [93.1%, 95% confidence interval (CI) 92.4-93.9)] were ever tested for HCV RNA, and 19.0% (95% CI 16.4-21.6) were currently HCV RNA positive, with the highest prevalence in Eastern and Central-Eastern Europe (33.7 and 29.6%, respectively). In Eastern Europe, 78.1% of the estimated number of chronic infections have been diagnosed, whereas this proportion was above 95% in the other four regions. Overall, 3116 persons have ever started treatment (72.5% of the ever chronically infected, 95% CI 70.9-74.0) and 2404 individuals (55.9% of the ever chronically infected, 95% CI 53.9-57.9) were cured. Cure proportion ranged from 11.2% in Belarus to 87.2% in Austria. CONCLUSION: In all regions except Eastern Europe, more than 90% of the study participants have been tested for HCV-RNA. In Southern and Central-Western regions, more than 80% ever chronically HCV-infected PWH received treatment. The proportion with cured HCV infection did not exceed 80% in any region, with significant heterogeneity between countries. SUMMARY: In a pan-European cohort of PWH, all regions except Eastern Europe achieved the WHO target of diagnosing 90% of chronic HCV infections, while the target of treating 80% of eligible persons was achieved in none of the five regions.

• MeSH
• antivirové látky terapeutické užití   MeSH
• chronická hepatitida C * komplikace   farmakoterapie   epidemiologie   MeSH
• Hepacivirus genetika   MeSH
• hepatitida C * komplikace   farmakoterapie   epidemiologie   MeSH
• HIV infekce * komplikace   farmakoterapie   epidemiologie   MeSH
• koinfekce * farmakoterapie   MeSH
• lidé MeSH
• prospektivní studie MeSH
• RNA terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Intravenous drug use (IVDU) represents the major factor of HCV transmission, but the treatment uptake among people who inject drugs (PWID) remains low owing to a false presumption of low efficacy. The aim of our study was to assess treatment efficacy in PWID and factors determining adherence to therapy. METHODS: A total of 278 consecutive patients starting DAA (direct-acting antivirals) therapy were included, divided into two groups: individuals with a history of IVDU, PWID group (N = 101) and the control group (N = 177) without a history of IVDU. RESULTS: Sustained virological response 12 weeks after the end of therapy (SVR12) was achieved by 99/101 (98%) and 172/177 (98%) patients in the PWID and control group, respectively; in PWID group, two patients were lost to follow-up, and in the control group, four patients relapsed and one was lost to follow-up. PWID patients postponed appointments significantly more often, 29 (28.7%) in PWID versus 7 (4%) in the control group, p = 0.001. Thirteen of 101 (12.9%) and six of 177 (3.4%) patients in the PWID and in the control group, respectively, missed at least one visit (p < 0.01). However, postponing visits led to a lack of medication in only one PWID. In the PWID group, older age (p < 0.05; OR 1.07, 95% CI 1.00-1.20) and stable housing (p < 0.01; OR 9.70, 95% CI 2.10-56.20) were factors positively contributing to adherence. Contrarily, a stable job was a factor negatively influencing adherence (p < 0.05; OR 0.24, 95% CI 0.06-0.81). In the control group, none of the analyzed social and demographic factors had an impact on adherence to therapy. CONCLUSIONS: In PWID, treatment efficacy was excellent and was comparable with SVR of the control group. Stable housing and older age contributed to a better adherence to therapy.

• MeSH
• antivirové látky terapeutické užití   MeSH
• chronická hepatitida C * komplikace   farmakoterapie   MeSH
• hepatitida C * farmakoterapie   MeSH
• intravenózní abúzus drog * komplikace   farmakoterapie   MeSH
• léčivé přípravky * MeSH
• lidé MeSH
• senioři MeSH
• setrvalá virologická odpověď MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Hepatocelulární karcinom (HCC) je maligní onemocnění jater, které ve většině případů vzniká v terénu chronického jaterního onemocnění. Různá jaterní onemocnění mají různé riziko rozvoje karcinomu, na jeho vzniku se podílejí u jednotlivých onemocnění také rozdílné kancerogenní mechanizmy. Obecně se tyto mechanizmy mohou týkat přímého působení vlastní příčiny jaterního onemocnění (virové infekce, kumulace těžkých kovů) nebo návazných mechanizmů chronického zánětu a fibrogeneze, ke kterým můžeme řadit i procesy oxidativního stresu. Existují i případy HCC bez jaterní cirhózy a zde se pak uplatňují především zmíněné mechanizmy s přímým podílem etiologického faktoru (např. X protein u infekce virem hepatitidy B (HBV)). Klíčovou metodou, která prokazatelně umožňuje dosáhnout lepších léčebných výsledků HCC, je screening – surveillance HCC. Metodou screeningu je abdominální sonografie opakovaná kaž­dých 6 měsíců. Otázkou, která dosud nebyla jednoznačně vyřešena a která ve svém důsledku velmi významně ovlivňuje efektivitu, je definice cílové populace, která musí být screeningové metodě vystavena. V současné době jsou cílovou populací osoby s jaterní cirhózou a máme dostupnou pouze jedinou metodu primární prevence HCC. Jedná se o univerzální vakcinaci HBV. Za metody sekundární prevence můžeme považovat všechny metody léčby chronických jaterních onemocnění, zejména pak protivirovou léčbu infekce HBV a HCV (virus hepatitidy C). Terciární prevencí je pak vlastně adjuvantní terapie HCC po jeho terapii či ně­kte­ré další postupy snižující riziko rekurence HCC. Pro určení stupně pokročilosti HCC se nejčastěji v Evropě používá tzv. Barcelonská klasifikace kombinující vlastní rozsah nádoru s dalšími parametry, jako je stupeň pokročilosti jaterní dysfunkce a celkový stav. Její výhoda je v tom, že implikuje přímo volbu vhodné terapeutické metody. Za potenciálně kurativní metody jsou nyní považovány pouze metody chirurgické, transplantace jater a jaterní resekce. Radikální přístup lze použít u jedné třetiny pacientů. Základní paliativní metodou léčby HCC je transarteriální chemoembolizace.

Hepatocellular carcinoma (HCC) is one of the major complications of chronic liver disease, mostly of liver cirrhosis. Liver diseases from different causes differ in the risks of HCC development. Different mechanisms of carcinogenesis are involved in HCC development in different liver diseases as well. Generally, two main pathways are distinguished: the cause of liver disease itself (e. g. viral infections, accumulation of heavy metals etc.) and chronic liver inflammation and fibrogenesis, including mechanisms of oxidative stress. Rare cases of HCC in liver without underlying cirrhosis are likely the consequences of the mechanisms directly linked with particular etiological factor (e. g. protein X in chronic hepatitis B virus (HBV) infection). The key approach which can lead to significantly better results of any treatment used in HCC cases is HCC screening and surveillance. The appropriate method of HCC surveillance is abdominal ultrasonography in 6-month intervals. There is still one question to be solved: the correct definition of target population which should undergo this method of surveillance. Currently, the target population in the developed world is defined as all patients with liver cirrhosis. Unfortunately, the only method of primary prevention of HCC is available: universal HBV vaccination. Antiviral treatment of hepatitis B or C is considered as a method of secondary prevention. Adjuvant therapy of HCC after its primary therapy (antiviral therapy after HCC resection etc.) and other measures able to reduce HCC recurrence risk are usually mentioned as tertiary prevention approach. The BCLC staging system is the most common system used in Europe for the classification of HCC at the diagnosis. This classification combines the stage of HCC itself with other parameters, such as liver disease severity (Child - Pugh classification), portal hypertension etc. BCLC is a system which guides the physicians to optimal treatment options in every HCC stage. The only potentially curable approaches are surgical resection or liver transplantation. These options may be used in 1/3 of all HCC patients. Unfortunately, the vast majority of HCC patients can be treated only by palliative treatment options with transarterial chemoembolisation being the most common one.

• MeSH
• chronická hepatitida B komplikace   MeSH
• chronická hepatitida C komplikace   MeSH
• hepatocelulární karcinom * diagnóza   etiologie   MeSH
• lidé MeSH
• nealkoholová steatóza jater komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND & AIMS: Eight-week glecaprevir/pibrentasvir leads to high rates of sustained virological response at post-treatment week 12 (SVR12) across HCV genotypes (GT) 1-6 in treatment-naïve patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naïve patients with compensated cirrhosis. METHODS: EXPEDITION-8 was a single-arm, multicenter, phase IIIb trial. The primary and key secondary efficacy analyses were to compare the lower bound of the 95% CI of the SVR12 rate in i) patients with GT1,2,4-6 in the per protocol (PP) population, ii) patients with GT1,2,4-6 in the intention-to-treat (ITT) population, iii) patients with GT1-6 in the PP population, and iv) patients with GT1-6 in the ITT population, to pre-defined efficacy thresholds based on historical SVR12 rates for 12 weeks of glecaprevir/pibrentasvir in the same populations. Safety was also assessed. RESULTS: A total of 343 patients were enrolled. Most patients were male (63%), white (83%), and had GT1 (67%). The SVR12 rate in patients with GT1-6 was 99.7% (n/N = 334/335; 95%CI 98.3-99.9) in the PP population and 97.7% (n/N = 335/343; 95% CI 96.1-99.3) in the ITT population. All primary and key secondary efficacy analyses were achieved. One patient (GT3a) experienced relapse (0.3%) at post-treatment week 4. Common adverse events (≥5%) were fatigue (9%), pruritus (8%), headache (8%), and nausea (6%). Serious adverse events (none related) occurred in 2% of patients. No adverse event led to study drug discontinuation. Clinically significant laboratory abnormalities were infrequent. CONCLUSIONS: Eight-week glecaprevir/pibrentasvir was well tolerated and led to a similarly high SVR12 rate as the 12-week regimen in treatment-naïve patients with chronic HCV GT1-6 infection and compensated cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03089944. LAY SUMMARY: This study was the first to evaluate an 8-week direct-acting antiviral (DAA) regimen active against all major types of hepatitis C virus (HCV) in untreated patients with compensated cirrhosis. High virological cure rates were achieved with glecaprevir/pibrentasvir across HCV genotypes 1-6, and these high cure rates did not depend on any patient or viral characteristics present before treatment. This may simplify care and allow non-specialist healthcare professionals to treat these patients, contributing to global efforts to eliminate HCV.

• MeSH
• antivirové látky aplikace a dávkování   škodlivé účinky   MeSH
• benzimidazoly aplikace a dávkování   škodlivé účinky   MeSH
• chinoxaliny aplikace a dávkování   škodlivé účinky   MeSH
• chronická hepatitida C krev   komplikace   farmakoterapie   virologie   MeSH
• cyklopropany aplikace a dávkování   škodlivé účinky   MeSH
• fixní kombinace léků MeSH
• genotyp * MeSH
• Hepacivirus enzymologie   genetika   MeSH
• jaterní cirhóza komplikace   farmakoterapie   MeSH
• kyseliny aminoisomáselné aplikace a dávkování   škodlivé účinky   MeSH
• leucin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrocyklické laktamy aplikace a dávkování   škodlivé účinky   MeSH
• polymorfismus genetický MeSH
• prolin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• pyrrolidiny aplikace a dávkování   škodlivé účinky   MeSH
• RNA virová krev   genetika   MeSH
• senioři MeSH
• setrvalá virologická odpověď MeSH
• sulfonamidy aplikace a dávkování   škodlivé účinky   MeSH
• virové nestrukturální proteiny genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

BACKGROUND: Hepatitis C virus (HCV) infection has been associated with increased risk of chronic kidney disease (CKD). We investigated the impact of HCV cure on CKD in HIV-positive persons in the EuroSIDA study. METHODS: HIV-positive persons with known HCV status and at least three serum creatinine measurements after 1/1/2004 were compared based on time-updated HCV-RNA and HCV treatment: anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, and HCV-RNA positive after HCV treatment. Poisson regression compared incidence rates of CKD [confirmed (>3 months apart) eGFR <60 ml/min per 1.73 m] between HCV strata. RESULTS: Fourteen thousand, seven hundred and fifty-four persons were included; at baseline 9273 (62.9%) were HCV-Ab negative, 696 (4.7%) spontaneous clearers, 3021 (20.5%) chronically infected, 922 (6.2%) successfully treated and 842 (5.7%) HCV-RNA positive after treatment. During 115 335 person-years of follow-up (PYFU), 1128 (7.6%) developed CKD; crude incidence 9.8/1000 PYFU (95% CI 9.2-10.4). After adjustment, persons anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.59; 95% CI 0.46-0.75] and spontaneous clearers (aIRR 0.67; 95% CI 0.47-0.97) had significantly lower rates of CKD compared with those cured whereas persons chronically infected (aIRR 0.85; 95% CI 0.65-1.12) and HCV-RNA positive after treatment (aIRR 0.71; 95% CI 0.49-1.04) had similar rates. Analysis in those without F3/F4 liver fibrosis using a more rigorous definition of CKD showed similar results. CONCLUSION: This large study found no evidence that successful HCV treatment reduced CKD incidence. Confounding by indication, where those with highest risk of CKD were prioritized for HCV treatment in the DAA era, may contribute to these findings.

• MeSH
• antivirové látky * terapeutické užití   MeSH
• chronická hepatitida C * komplikace   farmakoterapie   MeSH
• chronická renální insuficience * komplikace   epidemiologie   MeSH
• Hepacivirus MeSH
• HIV infekce * komplikace   farmakoterapie   MeSH
• koinfekce * farmakoterapie   MeSH
• lidé MeSH
• prospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Long-term outcomes after face transplantation are rarely reported in the scientific literature. Here we present outcome data of a partial face allograft recipient 10 years after transplantation. METHODS: Medical records were reviewed for functional and psychosocial outcomes as well as complications. Histopathologic analyses of autopsy tissues and characterization of skin immune cells were performed. RESULTS: The patient retained long-term motor and sensory function, though with a noticeable drop in sensory function after year 5. Social reintegration of the patient was marked by reconnection with his family and participation in public social activities. Immunosuppressive therapy consisted of tacrolimus (target levels 6-8 ng/mL after the first year), mycophenolate, and prednisone, while steroids were completely weaned between years 1 and 7. One acute cellular rejection episode of grade II or higher occurred on average per year and led to chronic skin changes (papillary dermal sclerosis with superficial hyalinization, epidermal thinning with loss of rete ridges, perieccrine fibrosis), but the allograft vessels, muscles, adipose tissue, and bone were spared. Allograft skin was characterized by increased number of CD4+ TNF-α/IL17A producing T-cells as compared with native skin. Long-term kidney function was maintained at 60 mL/min estimated glomerular filtration rate. Unfortunately, the preexisting hepatitis C virus infection with liver cirrhosis was resistant to 3 treatments with new direct-acting antivirals and eventually hepatocellular carcinoma developed, causing the patient's death 10 years after transplantation. CONCLUSION: This report suggests that face transplants can maintain their function for at least 10 years. Chronic skin changes can occur independently of allograft vasculopathy.

• MeSH
• alografty MeSH
• antigeny CD4 metabolismus   MeSH
• chronická hepatitida C komplikace   MeSH
• hepatocelulární karcinom virologie   MeSH
• hodnoty glomerulární filtrace MeSH
• imunosupresiva terapeutické užití   MeSH
• interleukin-17 metabolismus   MeSH
• kůže metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory jater virologie   MeSH
• následné studie MeSH
• příjemce transplantátu * MeSH
• T-lymfocyty metabolismus   MeSH
• TNF-alfa metabolismus   MeSH
• transplantace obličeje * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

• Klíčová slova
• kryoglobulinemická vaskulitida,
• MeSH
• chronická hepatitida C farmakoterapie   komplikace   MeSH
• kryoglobulinemie * etiologie   farmakoterapie   MeSH
• lidé MeSH
• vaskulitida * terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH