Format
Sort by
Items per page

Send to

Choose Destination

Selected items

Items: 10

1.
Ann Intern Med. 2018 Mar 20;168(6):457-459. doi: 10.7326/L17-0698.

Expansion of Treatment for Hepatitis C Virus Infection.

Author information

1
University of Maryland School of Medicine, Baltimore, Maryland (B.E., S.K., S.K.).
2
National Institutes of Health, Bethesda, Maryland (H.M.).
PMID:
29554678
DOI:
10.7326/L17-0698
Icon for Silverchair Information Systems
2.
Ann Intern Med. 2018 Mar 20;168(6):456-457. doi: 10.7326/L17-0697.

Expansion of Treatment for Hepatitis C Virus Infection.

Author information

1
MedStar Franklin Square Medical Center and Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (M.J.R.).
PMID:
29554677
DOI:
10.7326/L17-0697
Icon for Silverchair Information Systems
3.
Ann Intern Med. 2018 Mar 20;168(6):457. doi: 10.7326/L17-0696.

Expansion of Treatment for Hepatitis C Virus Infection.

Author information

1
Royal Sussex County Hospital, Brighton, United Kingdom (D.K.).
PMID:
29554676
DOI:
10.7326/L17-0696
Icon for Silverchair Information Systems
4.
J Hepatol. 2018 Aug;69(2):278-285. doi: 10.1016/j.jhep.2018.02.032. Epub 2018 Mar 16.

Development of a scoring system to predict hepatocellular carcinoma in Asians on antivirals for chronic hepatitis B.

Author information

1
Big Data Research Center, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan; Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan; Division of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
2
Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong; Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong.
3
Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan.
4
Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
5
Section of Gastroenterology and Hepatology, Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX, USA.
6
Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medicine, Chung Shan Medical University, Taichung, Taiwan.
7
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
8
Big Data Research Center, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan; Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan.
9
Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong; Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong. Electronic address: wonglaihung@cuhk.edu.hk.
10
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine and Graduate Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Public Health, China Medical University, Taichung, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan. Electronic address: chun@vghtc.gov.tw.

Abstract

BACKGROUND & AIMS:

The risk of hepatocellular carcinoma (HCC) during antiviral therapy in patients with chronic hepatitis B (CHB) is inadequately predicted by the scores built from untreated patients. We aimed at developing and validating a risk score to predict HCC in patients with CHB on entecavir or tenofovir treatment.

METHODS:

This study analysed population-wide data from the healthcare databases in Taiwan and Hong Kong to identify patients with CHB continuously receiving entecavir or tenofovir. The development cohort included 23,851 patients from Taiwan; 596 (2.50%) of them developed HCC with a three-year cumulative incidence of 3.56% (95% CI 3.26-3.86%). The multivariable Cox proportional hazards model found that cirrhosis, age (cirrhosis and age interacted with each other), male sex, and diabetes mellitus were the risk determinants. These variables were weighted to develop the cirrhosis, age, male sex, and diabetes mellitus (CAMD) score ranging from 0 to 19 points. The score was externally validated in 19,321 patients from Hong Kong.

RESULTS:

The c indices for HCC in the development cohort were 0.83 (95% CI 0.81-0.84), 0.82 (95% CI 0.81-0.84), and 0.82 (95% CI 0.80-0.83) at the first, second, and third years of therapy, respectively. In the validation cohort, the c indices were 0.74 (95% CI 0.71-0.77), 0.75 (95% CI 0.73-0.78), and 0.75 (95% CI 0.72-0.77) during the first three years, and 0.76 (95% CI 0.74-0.78) and 0.76 (95% CI 0.74-0.77) in the extrapolated fourth and fifth years, respectively. The predicted and observed probabilities of HCC were calibrated in both cohorts. A score <8 and >13 points identified patients at distinctly low and high risks.

CONCLUSIONS:

The easily calculable CAMD score can predict HCC and may inform surveillance policy in patients with CHB during oral antiviral therapy.

LAY SUMMARY:

This study analyses population-wide data from the healthcare systems in Taiwan and Hong Kong to develop and validate a risk score that predicts hepatocellular carcinoma during oral antiviral therapy in patients with chronic hepatitis B. The easily calculable CAMD score requires only simple information (i.e. cirrhosis, age, male sex, and diabetes mellitus) at the baseline of treatment initiation. With a scoring range from 0 to 19 points, the CAMD score discriminates the risk of hepatocellular carcinoma with a concordance rate of around 75-80% during the first three years on therapy. The risk prediction can be extrapolated to five years on treatment with similar accuracy. Patients with a score <8 and >13 points were exposed to distinctly lower and higher risks, respectively.

KEYWORDS:

Health authority; Hepatitis B virus infection; National Health Insurance Research Database; Nucleos(t)ide analogues; Risk prediction

5.
J Hepatol. 2018 Aug;69(2):345-352. doi: 10.1016/j.jhep.2018.03.009. Epub 2018 Mar 16.

Newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with DAAs: A prospective population study.

Author information

1
Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy.
2
Department of Molecular Medicine, University of Padova, Padova, Italy.
3
Section of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
4
Section of General Medicine, Belluno Hospital, Belluno, Italy.
5
Section of Infectious Diseases, Treviso Hospital, Treviso, Italy.
6
Section of Infectious Diseases, Mestre Hospital, Venezia, Italy.
7
Section of Gastroenterology, Mestre Hospital, Venezia, Italy.
8
Section of Gastroenterology, Vicenza Hospital, Vicenza, Italy.
9
Section of Gastroenterology, Bussolengo Hospital, Verona, Italy.
10
Section of Infectious Diseases, Santorso Hospital, Vicenza, Italy.
11
Section of Internal Medicine, University of Verona, Verona Italy.
12
Section of Infectious Diseases, University of Verona, Verona Italy.
13
Regional Pharmaceutical Office, Veneto Region, Venice, Italy.
14
Department of Molecular Medicine, University of Padova, Padova, Italy. Electronic address: alfredo.alberti@unipd.it.

Abstract

BACKGROUND & AIMS:

Direct-acting antiviral agents (DAAs) are safe and effective in patients with hepatitis C. Conflicting data were reported on the risk of hepatocellular carcinoma (HCC) during/after therapy with DAAs. The aim of this study was to evaluate the incidence of newly diagnosed HCC and associated risk factors in patients with advanced hepatitis C treated with DAAs.

METHODS:

The study is based on the NAVIGATORE platform, a prospectively recording database of all patients with hepatitis C receiving DAAs in the Veneto region of Italy. The inclusion criteria were: fibrosis stage ≥F3. The exclusion criteria were: Child-Turcotte-Pugh (CTP)-C, liver transplantation before DAAs, history or presence of HCC, follow-up <4 weeks after starting DAAs. A total of 3,917 out of 4,234 consecutive patients were included, with a mean follow-up of 536.2 ± 197.6 days.

RESULTS:

Overall, HCC was diagnosed in 55 patients. During the first year, HCC incidence was 0.46% (95% CI 0.12-1.17) in F3, 1.49% (1.03-2.08) in CTP-A and 3.61% (1.86-6.31) in CTP-B cirrhotics; in the second year, HCC incidences were 0%, 0.2%, and 0.69%, respectively. By multivariate analysis, HCC was significantly associated with an aspartate aminotransferase to platelet ratio ≥2.5 (hazard ratio [HR] 2.03; 95% CI 1.14-3.61; p = 0.016) and hepatitis B virus infection (HR 3.99; 1.24-12.91; p = 0.021). Failure to achieve a sustained virological response was strongly associated with development of HCC (HR 9.09; 5.2-16.1; p = 0.0001). A total of 29% of patients with HCC had an aggressive tumor, often seen in the early phase of treatment.

CONCLUSIONS:

These data, obtained in a large, prospective, population-based study, indicate that in patients with advanced hepatitis C receiving DAAs, the risk of "de novo" hepatocarcinoma during the first year is not higher, and might be lower, than that of untreated patients. The risk further declines thereafter. Early hepatocarcinoma appearance may reflect pre-existing, microscopic, undetectable tumors.

LAY SUMMARY:

Hepatocellular carcinoma is one of the complications of hepatitis C related cirrhosis. Treating patients with advanced hepatitis C with the new interferon-free direct-acting antiviral agents has been associated with improvement in liver function and survival, while more conflicting data have been reported regarding the risk of hepatocellular carcinoma. We report the results of a prospective population study on the incidence of newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with direct-acting antiviral agents, clearly indicating that the residual hepatocellular carcinoma risk is reduced and declines progressively with time after a sustained virological response. Development of a liver tumor during/after therapy was associated with known risk factors and with virological failure.

KEYWORDS:

Advanced liver disease; Direct-acting antiviral agents; Hepatitis C; Hepatocellular carcinoma; Risk factor

6.
J Hepatol. 2018 Aug;69(2):293-300. doi: 10.1016/j.jhep.2018.03.007. Epub 2018 Mar 16.

High SVR12 with 8-week and 12-week glecaprevir/pibrentasvir therapy: An integrated analysis of HCV genotype 1-6 patients without cirrhosis.

Author information

1
AO Ospedale Niguarda Ca Granda, Milan, Italy. Electronic address: massimo.puoti@fastwebnet.it.
2
Queen Mary University of London, Barts Health, London, UK.
3
AbbVie Inc., North Chicago, IL, USA.
4
Queen Elizabeth Hospital and NIHR Liver Biomedical Research Unit, Birmingham, UK.
5
University of Auckland, Auckland, New Zealand.
6
CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
7
National Cheng Kung University Hospital, Tainan City, Taiwan.
8
University of Calgary, Calgary, AB, Canada.
9
Hospital S. Maria, Medical School of Lisbon, University of Lisbon, Portugal.
10
Hepatology, University Clinic for Visceral Surgery and Medicine, Bern University Hospital, Switzerland.
11
Université Paris Descartes and Hôpital Cochin, Paris, France.
12
Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France.
13
Henry Ford Health System, Detroit, MI, USA.
14
Royal Prince Alfred Hospital, Sydney, Australia.
15
Mercy Medical Center and University of Maryland School of Medicine, Baltimore, MD, USA.

Abstract

BACKGROUND & AIMS:

Glecaprevir plus pibrentasvir (G/P) is a pangenotypic, once-daily, ribavirin-free direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection. In nine phase II or III clinical trials, G/P therapy achieved rates of sustained virologic response 12 weeks after treatment (SVR12) of 93-100% across all six major HCV genotypes (GTs). An integrated efficacy analysis of 8- and 12-week G/P therapy in patients without cirrhosis with HCV GT 1-6 infection was performed.

METHODS:

Data were pooled from nine phase II and III trials including patients with chronic HCV GT 1-6 infection without cirrhosis who received G/P (300 mg/120 mg) for either 8 or 12 weeks. Patients were treatment naïve or treatment experienced with peginterferon, ribavirin, and/or sofosbuvir; all patients infected with HCV GT 3 were treatment naïve. Efficacy was evaluated as the SVR12 rate.

RESULTS:

The analysis included 2,041 patients without cirrhosis. In the intent-to-treat population, 943/965 patients (98%) achieved SVR12 when treated for eight weeks, and 1,060/1,076 patients (99%) achieved SVR12 when treated for 12 weeks; the difference in rates was not significant (p = 0.2). A subgroup analysis demonstrated SVR12 rates > 95% across baseline factors traditionally associated with lower efficacy. G/P was well tolerated, with one DAA-related serious adverse event (<0.1%); grade 3 laboratory abnormalities were rare.

CONCLUSIONS:

G/P therapy for eight weeks in patients with chronic HCV GT 1-6 infection without cirrhosis achieved an overall SVR12 rate of 98% irrespective of baseline patient or viral characteristics; four additional weeks of treatment did not significantly increase the SVR12 rate, demonstrating that the optimal treatment duration in this population is eight weeks.

LAY SUMMARY:

In this integrated analysis of nine clinical trials, patients with chronic HCV genotype 1-6 infection without cirrhosis were treated for either 8 or 12 weeks with the direct-acting antiviral regimen glecaprevir/pibrentasvir (G/P). The cure rate was 98% and 99% following 8 and 12 weeks of treatment, respectively; the difference in rates was not significant (p = 0.2), nor was there a significant difference in the cure rates across the two treatment durations on the basis of baseline patient or viral characteristics. These results, along with a favourable safety profile, indicate that G/P is a highly efficacious and well-tolerated pangenotypic eight-week therapy for most patients with chronic HCV infection.

KEYWORDS:

Direct-acting antiviral; Hepatitis C; Pangenotypic; Short duration

PMID:
29551706
DOI:
10.1016/j.jhep.2018.03.007
Free full text
Icon for Elsevier Science
7.
J Hepatol. 2017 Jun;66(6):1300-1312. doi: 10.1016/j.jhep.2017.02.026. Epub 2017 Mar 4.

Targeting hepatic macrophages to treat liver diseases.

Author information

1
Department of Medicine III, University Hospital Aachen, Aachen, Germany. Electronic address: frank.tacke@gmx.net.

Abstract

Our view on liver macrophages in the context of health and disease has been reformed by the recognition of a remarkable heterogeneity of phagocytes in the liver. Liver macrophages consist of ontogenically distinct populations termed Kupffer cells and monocyte-derived macrophages. Kupffer cells are self-renewing, resident and principally non-migratory phagocytes, serving as sentinels for liver homeostasis. Liver injury triggers Kupffer cell activation, leading to inflammatory cytokine and chemokine release. This fosters the infiltration of monocytes into the liver, which give rise to large numbers of inflammatory monocyte-derived macrophages. Liver macrophages are very plastic and adapt their phenotype according to signals derived from the hepatic microenvironment (e.g. danger signals, fatty acids, phagocytosis of cellular debris), which explains their manifold and even opposing functions during disease. These central functions include the perpetuation of inflammation and hepatocyte injury, activation of hepatic stellate cells with subsequent fibrogenesis, and support of tumor development by angiogenesis and T cell suppression. If liver injury ceases, specific molecular signals trigger hepatic macrophages to switch their phenotype towards reparative phagocytes that promote tissue repair and regression of fibrosis. Novel strategies to treat liver disease aim at targeting macrophages. These interventions modulate Kupffer cell activation (e.g. via gut-liver axis or inflammasome formation), monocyte recruitment (e.g. via inhibiting chemokine pathways like CCR2 or CCL2) or macrophage polarization and differentiation (e.g. by nanoparticles). Evidence from mouse models and early clinical studies in patients with non-alcoholic steatohepatitis and fibrosis support the notion that pathogenic macrophage subsets can be successfully translated into novel treatment options for patients with liver disease.

LAY SUMMARY:

Macrophages (Greek for "big eaters") are a frequent non-parenchymal cell type of the liver that ensures homeostasis, antimicrobial defense and proper metabolism. However, liver macrophages consist of different subtypes regarding their ontogeny (developmental origin), differentiation and function. Understanding this heterogeneity and the critical regulation of inflammation, fibrosis and cancer by macrophage subsets opens promising new options for treating liver diseases.

KEYWORDS:

Chemokine; Cholestasis; HBV; HCC; HCV; Kupffer cell; Liver fibrosis; Macrophage; Monocyte; NASH

PMID:
28267621
DOI:
10.1016/j.jhep.2017.02.026
[Indexed for MEDLINE]
Icon for Elsevier Science
8.
J Infect Dis. 2018 May 25;217(12):1897-1901. doi: 10.1093/infdis/jiy128.

Pathological Cerebrospinal Fluid Findings in Patients With Neuralgic Amyotrophy and Acute Hepatitis E Virus Infection.

Author information

1
Department of Neurology and Neurophysiology, Medical Center, Germany.
2
Faculty of Medicine, University of Freiburg, Germany.
3
Institute of Clinical Microbiology and Hygiene, Regensburg University Medical Centre, Germany.
4
Department of Psychiatry and Psychotherapy, Germany.
5
Institute for Virology, Medical Center, University of Freiburg, Germany.

Abstract

There is growing evidence that hepatitis E virus (HEV) infection can present with extrahepatic manifestations including neurological disorders. Among these, neuralgic amyotrophy (NA) has been reported to occur in some industrialized countries. We investigated 35 patients with NA and a control group for markers of HEV infection. Acute HEV infection was found in NA patients only and was associated with an inflammatory response in the central nervous system. Shedding of HEV RNA into the cerebrospinal fluid and intrathecal production of anti-HEV immunoglobulin M occurred in 1 patient, suggesting that HEV is neurotropic.

9.
Transplantation. 2018 Aug;102(8):1351-1357. doi: 10.1097/TP.0000000000002185.

Transmission of Hepatitis E Virus With Plasma Exchange in Kidney Transplant Recipients: A Retrospective Cohort Study.

Author information

1
Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
2
Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (Inserm), Paris, France.
3
Hepatology Service, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Cochin Port-Royal, Paris, France.
4
Assistance Publique-Hôpitaux de Paris, Centre Hospitalier Universitaire Necker Enfants Malades, Nephrology and Kidney Transplantation Service, Paris, France.
5
Assistance Publique-Hôpitaux de Paris, Centre Hospitalier Universitaire Paul Brousse, Virology Service, Villejuif, France.
6
Institut National de la Santé et de la Recherche Médicale (Inserm), Villejuif, France.
7
Assistance Publique-Hôpitaux de Paris, Centre Hospitalier Universitaire Cochin Port Royal, Hematology Service, Paris, France.
8
Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Virology Service, Paris France.
9
Etablissement Français du Sang Île-de-France, Unité de Gestion des Risques et de la Qualité, Centre Hospitalier Universitaire Européen Georges Pompidou, Paris, France.
10
Etablissement Français du Sang Île-de-France, Site Transfusionnel Pitié-Salpêtrière, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France.
11
INSERM UMR 1043-CNRS UMR 5282, Toulouse, France.
12
Department of Virology, CNR HEV, CHU Toulouse, France.
13
Université Paul Sabatier, Toulouse, France.

Abstract

BACKGROUND:

After observing a case of plasma exchange-mediated hepatitis E virus (HEV) infection in a kidney transplant recipient, we investigated the relationship between plasma exchange and HEV infection after kidney transplantation.

METHODS:

A cohort of 263 patients who underwent kidney transplantation from January 1, 2011, through December 31, 2012, was screened for HEV markers, including anti-HEV IgG and IgM antibodies and HEV ribonucleic acid (RNA), on 3 consecutive blood samples: 1 before, 1 with a mean (standard deviation) of 9.5 (9) months, and 1 with a mean (standard deviation) of 18.2 (6.6) months after transplantation, respectively. Transfusional investigation was performed in patients with detectable HEV RNA. We explored the relationships between plasma exchange, posttransplantation transaminase elevation and HEV markers acquisition.

RESULTS:

Overall, 24 (9.1%) patients had acquired HEV markers on the first posttransplantation sample, including 2 patients with detectable HEV RNA, and 7 (2.3%) patients had long-term persistent HEV markers on the second posttransplantation sample, including 3 patients with detectable HEV RNA without detectable anti-HEV antibodies. Plasma exchange was an independent risk factor for the acquisition of posttransplantation and long-term persistent HEV markers. Pathogen-reduced plasma-borne transmission of HEV was demonstrated. Plasma exchange and long-term persistent HEV markers were risk factors of posttransplantation transaminase elevation.

CONCLUSIONS:

Plasma exchange, including with pathogen-reduced plasma, is a risk factor for posttransplantation HEV infection and transaminase elevation. Screening for HEV RNA should be carried out in kidney transplant recipients treated with plasma exchange.

10.
Transplantation. 2018 Aug;102(8):1209-1210. doi: 10.1097/TP.0000000000002186.

E-xchange: Hepatitis E and the Risk of Plasma Products for Organ Transplant Recipients.

Author information

1
Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany.

Supplemental Content

Support Center