The aim of this review is to outline emerging biomarkers that can serve as early diagnostic tools to identify patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis ...(NASH) and, among them, the subgroup of best candidates for clinical trials on emerging compounds. Regarding possible predictors of NAFLD, a number of studies evaluated a combination of serum biomarkers either available in routine practice (or investigational) or proprietary and expensive. So far, magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) appears to be the most accurate for fatty liver diagnosis. In clinical practice, the main question is how to diagnose NASH early. There are new promising biomarkers that can help in diagnosing early stages of NASH, yet they include variables not routinely tested. In the setting of NASH, most studies confirm that, in spite of several well-known limitations, transient elastography or point shear wave elastography can help in enriching the pool of patients that should be screened for investigational treatments. Newer multiomics biomarkers including those focusing on microbiota can be useful but require methods to be standardized and implemented. To date, one biomarker alone is not able to non- or minimally invasively identify patients with NASH and mild to moderate fibrosis.
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Biomarkers can be defined as measurable characteristics to be evaluated as indicators of normal or pathogenic biological processes, or as predictors of treatment response ....
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In two studies of sofosbuvir for previously untreated HCV infection, patients with genotype 1, 4, 5, or 6 had a 90% rate of sustained virologic response in a single-group study. In a study of ...sofosbuvir–ribavirin versus peginterferon–ribavirin for patients with genotype 2 or 3, the response rate was 67% in each group.
As many as 170 million persons are chronically infected with the hepatitis C virus (HCV) worldwide, and more than 350,000 die annually from liver disease caused by HCV.
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Estimates of the number of persons in the United States who have chronic HCV infection range from 2.7 million to 5.2 million.
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For previously untreated cases of HCV genotype 1 infection (representing more than 70% of all cases of chronic HCV infection in the United States), the current standard of care is 12 to 32 weeks of an oral protease inhibitor combined with 24 to 48 weeks of peginterferon alfa-2a . . .
Sofosbuvir and Ribavirin in HCV Genotypes 2 and 3 Zeuzem, Stefan; Dusheiko, Geoffrey M; Salupere, Riina ...
New England journal of medicine/The New England journal of medicine,
05/2014, Volume:
370, Issue:
21
Journal Article
Peer reviewed
Open access
In patients with HCV genotypes 2 and 3, sofosbuvir plus ribavirin was administered for 12 weeks in patients with genotype 2 and for 24 weeks in those with genotype 3. Rates of sustained virologic ...response were 93% in patients with genotype 2 and 85% in those with genotype 3.
Of the six main genotypes of the hepatitis C virus (HCV), genotypes 2 and 3 account for approximately 30% of chronic infections worldwide.
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Although these two genotypes have historically been grouped together in treatment guidelines and clinical trials,
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accumulating evidence suggests that there are important clinical differences between them.
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HCV genotype 3 infection is associated with a higher incidence of hepatic steatosis, more rapid progression of fibrosis, and possibly a greater risk of hepatocellular carcinoma than is HCV genotype 2 infection.
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Moreover, patients with HCV genotype 3 infection are less responsive to peginterferon-based treatment than are patients . . .
Hepatitis C virus micro-elimination: Where do we stand? Mangia, Alessandra; Cotugno, Rosa; Cocomazzi, Giovanna ...
World journal of gastroenterology,
2021-Apr-28, 2021-4-28, 20210428, Volume:
27, Issue:
16
Journal Article
Open access
Hepatitis C virus (HCV) elimination by 2030, using direct-acting antiviral treatments, has been promoted by the World Health Organization. This achievement is not attainable, however, particularly ...after the 2020 pandemic of the coronavirus disease 2019. Consequently, the more realistic objective of eliminating HCV from population segments for which targeted strategies of prevention and treatment are easily attained has been promoted in Europe, as a valid alternative. The underlying idea is that micro-elimination will ultimately lead to macro-elimination. The micro-elimination strategy may target different specific populations and at-risk groups. Different settings, including prisons and hospitals, have also been identified as micro-elimination scenarios. In addition, dedicated micro-elimination strategies have been designed that are tailored at the geographical level according to HCV epidemiology and individual country's income. The main elements of a valid and successful micro-elimination project are reliable epidemiological data and active involvement of all the stakeholders. Community involvement represents another essential component for a successful program.
Background and aims
Achieving sustained virological response (SVR; cure) in hepatitis C patients using a simple regimen is key to making elimination by 2030 possible. In the largest real‐world ...analysis to date, the effectiveness of pangenotypic, panfibrotic, single‐tablet, sofosbuvir/velpatasvir (SOF/VEL) once‐daily for 12 weeks was assessed in 12 clinical real‐world cohorts from various geographical areas, settings and treatment practices. Factors affecting risk of not achieving SVR were assessed.
Methods
Adults treated with SOF/VEL 400/100 mg, without ribavirin, were included. All HCV patients reaching Week 12 or 24 post‐treatment were assessed for SVR12/24. Factors associated with not achieving SVR12/24 for virological reasons were evaluated using logistic regression analysis.
Results
Overall, 5552 patients were included: 13.3% treatment‐experienced; 20.7% compensated cirrhotic; 30.2% genotype 1; 29.5% genotype 2; 32.9% genotype 3; 4.7% genotype 4; 3.7% HIV coinfection; 13.4% current/former intravenous drug use. Of the 5196 patients evaluated for effectiveness, 98.9% achieved SVR12/24. High SVR12/24 rates occurred in all genotypes including genotype 3 (98.3%; 1649/1677) and in those with compensated cirrhosis (97.9; 1055/1078). Only 55 patients did not achieve SVR12/24 due to a virological reason; the only factor statistically significantly associated with an increased risk of not achieving SVR12/24 was compensated cirrhosis (P = .002). Overall, 6% (332/5552) of patients did not achieve SVR12/24 for non‐virological reasons (67% lost to follow‐up; 26.5% early treatment discontinuation).
Conclusions
In this large cohort, representative of clinical practice, a simple 12‐week regimen of SOF/VEL without ribavirin resulted in high SVR12/24 rates in diverse patient populations, even among those with compensated cirrhosis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Ramos-Casals et al present evidence-based recommendations on the management of extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. The objective of this international consensus ...is to provide therapeutic recommendations for HCV patients with extrahepatic manifestations. The current therapeutic armamentarium against HCV has been recently expanded with an explosion of new molecules (DAAs) with high virological efficacy. B cell depletion with rituximab is the established biologic approach to cryo-globulinaemic vasculitis (CV) employed to date.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Elderly subjects have been historically underrepresented in clinical trials involving antiviral hepatitis C therapies. The aim of this analysis was to retrospectively evaluate the safety and efficacy ...of ledipasvir/sofosbuvir (LDV/SOF) by age groups of <65 years versus ≥65 years among subjects enrolled in phase 3 trials. Four open‐label phase 3 clinical trials evaluated the safety and efficacy of LDV/SOF with or without ribavirin (RBV) for the treatment of genotype 1 chronic hepatitis C virus. Sustained virological response at 12 weeks, treatment‐emergent adverse events (AEs), and graded laboratory abnormalities were analyzed according to age group. Of the 2293 subjects enrolled in four phase 3 trials, 264 (12%) were ≥65 years of age, of whom 24 were aged ≥75 years. Sustained virological response at 12 weeks was achieved by 97% (1965/2029) of subjects aged <65 years and 98% (258/264) of subjects aged ≥65 years. The most common AEs in both LDV/SOF groups that occurred in ≥10% of subjects were headache and fatigue. The rate of study discontinuation due to AEs was similar in the two age cohorts. The use of RBV in 1042 (45%) subjects increased the number of AEs, treatment‐related AEs, and AEs leading to study drug modification/interruption, particularly among elderly subjects. Conclusions: LDV/SOF with or without RBV was highly effective for treatment of genotype 1 chronic hepatitis C virusin subjects aged 65 and older. Addition of RBV did not increase sustained virological response at 12 weeks rates but led to higher rates of AEs, especially in elderly subjects. (Hepatology 2016;63:1112–1119)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated ...with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis.
It has been estimated that the incidence of chronic hepatitis C virus (HCV) will not decline over the next 10 years despite the improved efficacy of antiviral therapy because most patients remain ...undiagnosed and/or untreated. This study aimed to investigate the opinion of relevant target populations on the practicability, effectiveness and best modalities of the test-and-treat approach in the fight against HCV in Italy.
A survey was delivered to patients with HCV from the general population, patients from drug addiction services, hospital physicians and healthcare providers for drug addiction services.
For both hospital clinicians and SerD HCPs, tolerability is shown as the most important feature of a suitable treatment. Time to treatment (the time from first contact to initiation of treatment) is deemed important to the success of the strategy by all actors. While a tolerable treatment was the main characteristic in a preferred care pathway for general patients, subjects from drug addiction services indicated that a complete Meet-Test-Treat pathway is delivered within the habitual care center as a main preference. This is also important for SerD HCPs who are a strong reference for their patients; hospital clinicians were less aware of the importance of the patient-HCP relationship in this process.
The health system is bound to implement suitable pathways to facilitate HCV eradication. A Meet-Test-Treat program within the drug addiction services may provide good compliance from subjects mainly concerned with virus transmission.
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