Friday, December 15, 2017

Formulary exclusion lists make it harder for patients to get prescriptions

Formulary exclusion lists make it harder for patients to get prescriptions
By Ginger Christ, The Plain Dealer

CLEVELAND, Ohio - Getting a prescription these days requires more than just a visit to your doctor.

Insurance companies use formulary exclusion lists to dictate which prescriptions are covered, and the number of medications on those lists continues to grow as prescription insurers try to cut costs.

The excluded medications are often times ones that aren't prescribed very often or that have generic alternatives, but recently a couple of specialty drugs, including some for Hepatitis C, are also popping up on these lists...

Community Health Clinics Evolving HCV Programs

AGA Reading Room 12.14.2017

Community Health Clinics Evolving HCV Programs
by Pippa Wysong
Increasing importance in treating high-risk populations
Community health clinics (CHCs) are taking on greater roles in terms of screening and treating hepatitis C virus (HCV) patients, but new models of care are just starting to evolve to improve access and care for the high-risk, complex populations they tend to serve...

Expert Critique
Michelle Long
With the wide availability of highly effective treatments for hepatitis C (HCV) the challenges in treating HCV now lies in improving access for high-risk populations. Federally funded community health clinics are now a prime access point for screening and treating HCV, particularly for the uninsured or under-insured. HCV is highly prevalent in the patient population served by community health clinics, which make them a good place to identify high-risk patients. However, the infrastructure for coordinating screening and delivering treatments needs development in many community health clinics. Additional training programs for primary care physicians and telemedicine programs would be helpful as well, since access to sub-specialty care is often limited. Few centers have adapted existing programs with success, but this has not yet been adapted on a large scale, and funding for such efforts is limited.

8-week Harvoni cost-effective alternative to 12-week regimen

December 14, 2017
An 8-week course of Harvoni for hepatitis C virus infection in both black and nonblack patients was a cost-effective alternative to a 12-week course, according to researchers.

Shorter course therapy may be a viable option under a constrained budget and can benefit patients who are treatment-naive and noncirrhotic, they wrote in Open Forum Infectious Diseases.
Continue reading: https://www.healio.com/infectious-disease/hepatitis-c/news/in-the-journals/%7B0ad54f9e-eabf-4be3-9d1e-5cfdf2513ba1%7D/8-week-harvoni-cost-effective-alternative-to-12-week-regimen

SVR after HCV treatment improves liver stiffness in progressive fibrosis
December 14, 2017
Sustained virologic response after direct-acting antiviral treatment for hepatitis C significantly improved liver stiffness from baseline to end of treatment, and…
Continue reading: https://www.healio.com/hepatology/hepatitis-c/news/online/%7Bbbe95f7d-0dac-4db6-a05e-ccfe72d878e0%7D/svr-after-hcv-treatment-improves-liver-stiffness-in-progressive-fibrosis

Wednesday, December 13, 2017

HCV Prevention in Correctional Settings Is Good Medicine

Clinical Thought
HCV Prevention in Correctional Settings Is Good Medicine
Lara Strick MD, MS - 12/12/2017

Implementation of prevention services targeting incarcerated patients is possible. Let me tell you why. 
Although the United States lags far behind in public acceptance and implementation of harm reduction services like condoms, needle exchanges, and regulated tattooing in the correctional setting, it is important to note that other countries have successfully launched such programming. For now, we need to rely on risk reduction counseling to augment prevention ahead of full maturation of our harm reduction initiatives. For instance, medication assistance for drug addiction is steadily garnering more attention across the United States as the public profile of the opioid epidemic expands, increasing the political will to broaden efforts to correctional facilities. 
But perhaps the most important thing to remember is this: Implementation of prevention services targeting incarcerated patients is possible. Do not let the fact that you are serving a correctional population prevent you from practicing good medicine because, ultimately, prevention is good medicine.
Continue reading: Clinical Care Options  
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Related Discussions - Clinical Care Options

Dr. Gabor Maté on the Trauma Underlying the Stigma of Addiction: An Interview

Dr. Gabor Maté on the Trauma Underlying the Stigma of Addiction: An Interview
By John Lavitt 12/12/17

There are legitimate uses of opioids in the treatment of physical pain. There is no legitimate use in the treatment of emotional pain.

When commenting on the neurobiology of addiction, you write how, “addiction is related psychologically, in terms of both emotional pain relief and neurobiological development, to early adversity.”

If the neurobiological development of a child is affected by trauma, how can such physical changes set in place long ago be reversed? Is it possible for an adult to “renew” their brain, and if so, how long would such a process of renewal take? What tools would be required?

When we do brain scans on adult addicts, you see several neural systems that just don’t work very well, including the opiate pain relief, pleasure, reward, attachment, and love circuitry. Other problematic systems include the stress regulation circuitry, the impulse regulation circuitry, and especially the dopamine-driven incentive motivation circuitry. As a result, doctors often conclude that because these brain circuits aren’t working well, there has to be a brain disease and that addiction is that disease.....

View Part 1 of a 2 part interview

Video HCV Series from Medscape TV - Patient education and screening

Six Episode Series from Medscape TV - Hepatitis C Virus: Containing the Threat
In the past few years, a new class of direct-acting antiviral agents has made the treatment of HCV easier and more effective than ever before, with cure rates nearing 100%, even among HIV-positive patients. But not all patients with HCV who are eligible for antiviral treatment are identified, and even fewer are being referred for care. Thus, HCV infection remains a significant risk for progression to cirrhosis, liver failure, and hepatocellular carcinoma. Liver specialists at two prestigious Chicago medical centers confront the key issues in the management of patients with chronic HCV infection.

Medscape TV Final Episode
December 11, 2017
EPISODE 6 - Strategies for Prevention
Primary care physicians can help stem the spread of HCV infection through patient education and screening

November 8, 2017 
EPISODE 5 - Hepatitis C Virus: Dealing With Chronic Disease
Patients with advanced disease will need help beyond current therapy, including managing comorbidities and navigating transplant.

October 10, 2017

EPISODE 4 - The New Regimens
Liver specialists find that HCV patients who have comorbid conditions and treatment-resistant disease may still be candidates for combination therapies.

August 17, 2017
EPISODE 3 - Hope and Uncertainty
Patients who have not responded to previous HCV therapies often need support to continue therapy and testing, and to maintain health.

July 17, 2017
EPISODE 2 - Considerations Before HCV Therapy
Physicians assess such factors as performance status and risk for reinfection to determine whether a patient is a candidate to receive HCV treatments.

June 21, 2017
EPISODE 1 - Strides and Obstacles
HCV treatments are highly efficacious, but challenges remain in screening persons at risk of contracting and spreading infection, as well as in the treatment of liver diseases caused by HCV

Access to hepatitis C treatment for patients in drug substitution programmes: the fight is far from over

Viewpoint
Access to hepatitis C treatment for patients in drug substitution programmes: the fight is far from over
Francesco Negro, Liudmyla Maistat
DOI: 10.4414/smw.2017.14570
Swiss Med Wkly. 2017;147:w14570

Hepatitis C virus (HCV) is a parenterally transmitted human pathogen of global concern. Chronic HCV infection is associated with progressive liver disease culminating in an estimated yearly toll of around 400 000 deaths, mostly due to liver failure and hepatocellular carcinoma. Thus, in 2016, the World Health Organization issued a declaration aiming at the elimination of viral hepatitis as a global public health threat by 2030 [1]. Six indicators were identified to measure the progress in this ambitious effort: infant vaccination against hepatitis B virus (HBV), prevention of mother-to-child transmission of HBV by birth dose vaccination, blood and injection safety, harm reduction measures for people who inject drugs (PWID), identification of infected patients by means of appropriate screening strategies, and treatment of patients with potent antivirals.

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Tuesday, December 12, 2017

Impact of HCV eradication on insulin resistance (IR), and the control of type 2 diabetes.

What We Know
Achieving Sustained Virologic Response (SVR) in patients treated with direct-acting antivirals (DAAs) is associated with the reversal of fibrosis, reduces the risk of liver transplant, liver cancer, and risk of other complications of chronic liver disease, including extrahepatic manifestations of HCV. The hepatitis C virus is associated with various extrahepatic manifesations, some of these include systemic manifestations such as thyroid disease, cardiovascular disease, renal disease, eye disease (sicca syndrome), skin disease (PCT, vasculitis, and lichen planus), lymphomas, and type II diabetes mellitus. As for the latter, previous research has demonstrated a significant association between hepatitis C - type 2 diabetes - and insulin resistance.

The Stats
According to The World Health Organization (WHO) people infected with HCV are at risk for liver related complications, worldwide around 399 000 people die each year from hepatitis C, mostly from cirrhosis and hepatocellular carcinoma.

Extrahepatic Consequences of HCV
However, because these estimates do not included extrahepatic consequences of HCV infection the risks of morbidity and mortality are underestimated, according to a systematic review investigating the relationship between HCV infection and glucose abnormalities; Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review, published in World J Gastroenterol.

New In The Journals
Learn more about the impact of HCV eradication on insulin resistance (IR), and the control of type 2 diabetes by viewing this collection of recent articles.

Journal of Medical Virology
Volume 90, Issue 2 February 2018 Pages 320–327
RESEARCH ARTICLE
Authors Alessia Ciancio, Roberta Bosio, Simona Bo, Marianna Pellegrini, Marco Sacco, Edoardo Vogliotti, Giulia Fassio, Andrea G. F. Bianco Mauthe Degerfeld, Monica Gallo, Chiara Giordanino, Lodovico Terzi di Bergamo, Davide Ribaldone, Elisabetta Bugianesi, Antonina Smedile, Mario Rizzetto, Giorgio Maria Saracco
First published: 14 November 2017
Full publication history DOI: 10.1002/jmv.24954
Abstract
Many studies showed insulin resistance amelioration in HCV-patients achieving Sustained Virologic Response (SVR) but results on glycemic control in diabetic patients are unclear. This study aimed to assess fasting glucose (FG) and glycated hemoglobin (HbA1c) values before and after therapy with direct-acting antivirals (DAAs) in HCV-patients with type 2 diabetes mellitus (T2DM). Of the 122 consecutively recruited patients with chronic hepatitis C and T2DM, 110 patients were treated with DAAs and 12 remained untreated. Clinical, biochemical, virological, and metabolic features were collected both at baseline and at 12 weeks after the end of therapy (EOT) or after a comparable period of time in untreated patients. A total of 101 patients obtained a SVR (Group 1), while nine were relapsers. Group 2 (21 patients) was composed by the nine relapsers and the 12 untreated patients. A significant reduction of mean FG (134.3 ± 41.32 mg/dL vs 152.4 ± 56.40 mg/dL, P = 0.002) and HbA1c values (46.51 ± 16.15 mmoL/moL vs 52.15 ± 15.43 mmoL/moL, P <  0.001) was found in Group 1 but not in Group 2 (140.6 ± 47.87 mg/dL vs. 145.31 ± 30.18 mg/dL, P = 0.707, and 55.31 ± 20.58 mmoL/moL vs. 53.38 ± 9.49 mmoL/moL, P = 0.780). In Group 1, 20.7% of patients could reduce or suspend their antidiabetic therapy compared to none in Group 2 (P = 0.03), despite the significant weight increase observed in Group 1. SVR induced a significant amelioration of glycemic control in diabetic HCV-patients, despite a significant weight increase; larger prospective studies are needed to verify whether these results are maintained over the long-term.
View Full Text Article: Downloaded and shared by @HenryEChang on Twitter

Journal of Gastroenterology and Hepatology
Luigi E Adinolfi,Riccardo Nevola,Barbara Guerrera,Giovanni D’Alterio,Aldo Marrone,Mauro Giordano, Luca Rinaldi
Accepted manuscript online: 11 December 2017
DOI: 10.1111/jgh.14067
Abstract Background and Aim
Chronic hepatitis C (HCV), particularly genotype 1, is associated with insulin resistance (IR) and diabetes. We evaluated the impact of HCV clearance by all-oral direct-acting antiviral (DAAs) treatments on IR and glycemic control.

Methods
Included in this prospective case-control study were 133 consecutive HCV-genotype 1 patients with advance liver fibrosis (F3-F4) without type 2 diabetes. Sixty-eight treated with DAAs and 65 untreated. Liver fibrosis was assessed by transient elastography. Pre-, end- and 3 months post-treatment withdrawal IR homeostasis was assessed by HOMA-IR, QUICKI and HOMA-B.

Results
At baseline, treated and untreated patients showed similar liver fibrosis levels, HOMA-IR was 4.90±4.62 and 4.64±5.62, respectively. HOMA-IR correlated with HCV RNA levels. At the end of treatment, all patients cleared HCV RNA, regardless of liver fibrosis and BMI, a reduction in HOMA-IR at 2.42±1.85 was showed (p<0.001), in addition, increased insulin sensitivity, decreased insulin secretion, reduction of serum glucose and insulin levels were observed. Data were confirmed 3 months after treatment withdrawal in the 65 patients who cleared HCV. No variation occurred in untreated patients. Overall, 76.5% of SVR patients showed IR improvements, of which 41.2% normalized IR. Improvement of IR was strict associated with HCV clearance, however, patients with the highest levels of fibrosis remain associated with some degree of IR.

Conclusions
The data underline a role of HCV in development of IR and that viral eradication reverses IR and improves glycemic control and this could prevent IR-related clinical manifestations and complications.
Subscription required to view full text article

Diabetes Care
Diabetes Care 2017 Sep - Justine Hum,1 Janice H. Jou,1 Pamela K. Green,2 Kristin Berry,2 James Lundblad,3 Barbara D. Hettinger,3 Michael Chang,1 and George N. Ioannou2,4 1Division of Gastroenterology, Portland Veterans Affairs Medical Center, Portland, OR 2Health Services Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, WA 3Division of Endocrinology, Portland Veterans Affairs Medical Center, Portland, OR 4Division of Gastroenterology, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, WA

Hepatitis C virus (HCV) infection is associated with diabetes and may worsen glycemic control in patients with diabetes. We aimed to investigate whether eradication of HCV infection with direct-acting antiviral (DAA) agents is associated with improved glycemic control in patients with diabetes.

In summary, glycemic control improves in patients with diabetes after DAA-induced SVR. Patients not only have an improvement in HbA1c level after achieving SVR, they are also less likely to require insulin. These endocrine benefits of SVR provide additional justification for considering antiviral treatment in all patients with diabetes. ....hepatitis C virus (HCV) infection is associated with a higher prevalence of type 2 diabetes mellitus (T2DM) . In addition, HCV proteins increase the release of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α, which then upregulate gluconeogenesis and enhance lipid accumulation in the liver

Future studies are needed to confirm our findings, to determine how durable the SVR-induced improvement in glycemic control is over time, and to assess the long-term effect on complications of diabetes such as nephropathy, neuropathy, and cardiovascular disease.
View Full Text Article: Available at NATAP

Medpage Today
Commentary: Improvement in Glycemic Control of Type 2 Diabetes After Successful Treatment of Hepatitis C Virus
Researchers at the VA health system—the largest provider of integrated hepatitis C care in the country—recently tested the role of viral eradication on the control of type 2 diabetes
By Kristin Bundy
Researchers at the VA health system—the largest provider of integrated hepatitis C care in the country—recently tested the role of viral eradication on the control of type 2 diabetes (T2D). Previous data demonstrated that the risk of developing T2D is about 4 times higher in people infected with the hepatitis C virus (HCV) than those without. Investigators wanted to know: Could HCV suppression lead to better control of T2D?
Continue reading: Available at Medpage Today

Nature - Scientific Reports
Yun Soo Hong, Yoosoo Chang, Seungho Ryu, Miguel Cainzos-Achirica, Min-Jung Kwon, Yiyi Zhang, Yuni Choi, Jiin Ahn, Sanjay Rampal, Di Zhao, Roberto Pastor-Barriuso, Mariana Lazo, Hocheol Shin, Juhee Cho & Eliseo Guallar
doi:10.1038/s41598-017-04206-6
Published online:04 2017
In conclusion, in this large study of men and women at low risk of diabetes, we found that serologic evidence of HBV and HCV infection was associated with the prevalence of diabetes. In addition, HBV infection was associated with the risk of incident diabetes in prospective analyses, but we could not reliably evaluate the prospective association between HCV infection and diabetes due to the small number of infected participants. Our studies add to the growing body of evidence suggesting that diabetes is an additional metabolic complication of HBV and HCV infection.

On This Blog

Retreatment of patients with treatment failure of direct-acting antivirals: Focus on hepatitis C virus genotype 1b

World J Gastroenterol. Dec 14, 2017; 23(46): 8120-8127
Published online Dec 14, 2017. doi: 10.3748/wjg.v23.i46.8120

Retreatment of patients with treatment failure of direct-acting antivirals: Focus on hepatitis C virus genotype 1b
Tatsuo Kanda, Kazushige Nirei, Naoki Matsumoto, Teruhisa Higuchi, Hitomi Nakamura, Hiroaki Yamagami, Shunichi Matsuoka, Mitsuhiko Moriyama

Abstract
The recent development of direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection could lead to higher sustained virological response (SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions (RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1b (GT1b) is founded in 70% of HCV-infected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1b-infected patients with treatment failure.

Core tip: In this minireview, we focused on the retreatment of patients with treatment failure of direct-acting antiviral agents against hepatitis C virus genotype 1b (HCV GT1b) infection. We summarized the retreatment regimens for patients with failure of peginterferon and ribavirin plus HCV NS3/4A inhibitors and for those with failure of HCV NS5A inhibitors. We also demonstrated the resistance-associated substitutions of HCV NS5B nucleos(t)ide inhibitors. Attention should be paid when selecting both the initial treatment and retreat regimens to completely eradicate HCV infection.

Full Text Article
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Retreatment regimens for patients with hepatitis C virus infection for whom the initial combination of direct-acting antivirals has failed.

DAAs: Direct-acting antivirals; HCV GTs: Hepatitis C virus genotypes; RAS: Resistance-associated variants; N/A: Not available.

Monday, December 11, 2017

Haemopoietic stem cell therapy in cirrhosis: the end of the story?

In Case You Missed It

Lancet Gastroenterology & Hepatology
Volume 3, No. 1, p3–5, January 2018
DOI: http://dx.doi.org/10.1016/S2468-1253(17)30359-X

Comment
Haemopoietic stem cell therapy in cirrhosis: the end of the story?
Nicolas Lanthier
Chronic liver diseases can lead to cirrhosis, characterised by fibrous septa dissecting the liver parenchyma, affecting both liver function (due to reduced functional mass) and normal intrahepatic venous pressure (due to increased stiffness). Some specific treatments for the underlying causes of the disease exist, such as antiviral treatment for hepatitis B or C virus infection, alcohol abstinence for alcohol-related liver disease, or weight loss strategies for metabolic non-alcoholic fatty liver disease, whereas other causes remain difficult to treat (like genetic disorders or autoimmune problems). Despite existing strategies, some patients still progress towards end-stage liver disease and its associated complications, including ascites, peritonitis, variceal bleeding, or hepatocellular carcinoma. No treatment is available to specifically target fibrosis and cirrhosis, and liver transplantation remains the only curative option. To avoid progression towards end-stage liver disease ultimately requiring a rescue transplantation—which is not devoid of disadvantages (donor organ shortage, challenging surgery, and lifelong immunosuppression)—many researchers are investigating strategies to restore liver functionality.

Cell therapy is an emerging approach being tested in this setting. Hepatocytes are the principal cells of the liver parenchyma and are responsible for maintaining liver function. They can originate from three sources.1 In a normal liver, hepatocytes themselves can proliferate to restore the functional liver mass, a mechanism that could be compromised in cirrhosis. Second, the liver contains liver progenitor cells that can also proliferate and differentiate into hepatocytes. However, in some circumstances, this differentiation does not occur.2 Finally, blood-derived stem cells can infiltrate the liver and become hepatocytes, although the participation of this process in liver regeneration is poorly understood.3

In a randomised controlled trial,4 Philip Newsome and colleagues investigated whether granulocyte colony-stimulating factor (G-CSF) with or without haemopoietic stem cell transplantation could improve liver function and reduce complications related to liver cirrhosis. Indeed, it has been proposed that bone-marrow-derived stem cells can engraft the diseased liver and differentiate toward hepatocytes, while G-CSF can stimulate bone marrow cell recruitment and liver progenitor cell proliferation.5, 6 This study is of interest because of its rigorous design and evaluation, and it adds to the evidence from numerous case reports and small studies that have suggested a beneficial effect from both strategies on liver function and patient survival. Unfortunately, in this trial, neither G-CSF alone nor combined with three autologous stem-cell infusions (harvested from the peripheral blood) into patients' peripheral veins improved liver function as assessed by MELD score, which was calculated by a routine blood test, after 3 months. Complications of cirrhosis were even more common in the combined therapy group. Finally, liver stiffness evaluation by transient elastography did not show any effect of the treatment.4

Notably, these results are in line with those from a previous randomised controlled trial7—the only trial on this subject to be regarded as a high-quality study8—which also found that G-CSF and bone-marrow-derived cells injected into the hepatic artery had no effect in the context of severe decompensated alcoholic cirrhosis. The new data provided by Newsome and colleagues' study show that even in liver disease with relatively low levels of inflammation, the treatment stimulus is not sufficient to promote liver regeneration and subsequent recovery of liver function.

These results highlight the importance of not drawing premature and possibly hazardous conclusions before solid preclinical evidence becomes available and subsequent well conducted clinical trials are done. Future research into potential treatments for cirrhosis should also include a refined assessment of treatment response. First, cell tracking experiments in human beings are needed to establish whether cells infused by the peripheral route or directly injected into the hepatic circulation in the context of portal hypertension really do engraft the liver or not. Studies of the biodistribution of labelled cells in humans could answer this question.9 Second, more specific biomarkers or at least more precise liver imaging to assess fibrosis are probably needed. Patient survival, MELD score, and liver elasticity changes do not seem to be sufficient to detect any therapeutic effect of cell transplantation, if there is one. However, concomitantly, or before such experiments are done, progress is needed in basic research to discover the determining factors explaining why some patients with cirrhosis will have decompensation despite adequate control of the causes of the disease. In this context, predictive baseline patient factors need to be identified, which could originate from several sources. These factors could be from the liver itself (eg, hypoxia, low-grade inflammation, and microscopic thrombotic events), and assessment of the liver tissue before and after treatment to characterise regenerative pathways or side-effects should provide important data.10 Indeed, it could simply be the case that if the diseased liver itself is not able to develop its own efficacious repopulation mechanisms, external strategies will also fail. Alternatively, factors originating from outside the liver, such as from the gut (eg, altered barrier function and microbiome dysregulation), the muscles (characterised by sarcopenia), or the inflamed adipose tissue in obesity, could also play an important part. Future trials to address these questions in an era of emerging liver disease epidemics will be of great interest. Ideally, future trials should target one cause of cirrhosis at a time, given that the mechanisms could be different depending on the cause of the liver disease. For example, chronic active hepatitis C, which characterised some patients in Newsome and colleagues' trial, might not remain a problem because of existing efficacious viral eradication approaches, making cirrhosis due to non-alcoholic fatty liver disease the primary cause of end-stage liver disease.

In conclusion, the robust data provided by Newsome and colleagues do not support G-CSF with or without haemopoietic stem-cell infusion having any effect on liver function in patients with cirrhosis. With liver regeneration and anti-fibrotic strategies remaining fascinating subjects of research, further efforts will be needed to shed light on the complexity and interconnectedness of regeneration and cirrhosis before novel effective clinical strategies can be developed to overcome the problem of a failing liver.

Voisin/Phanie/Science Photo Library

References

  1. Lanthier, N, Rubbia-Brandt, L, and Spahr, L. Liver progenitor cells and therapeutic potential of stem cells in human chronic liver diseases. Acta Gastroenterol Belg. 2013; 76: 3–9
  2. Dubuquoy, L, Louvet, A, Lassailly, G et al. Progenitor cell expansion and impaired hepatocyte regeneration in explanted livers from alcoholic hepatitis. Gut. 2015; 64: 1949–1960
  3. Alison, MR, Poulsom, R, Jeffery, R et al. Hepatocytes from non-hepatic adult stem cells. Nature. 2000; 406: 257
  4. Newsome, PN, Fox, R, King, AL et al. Granulocyte colony-stimulating factor and autologous CD133-positive stem-cell therapy in liver cirrhosis (REALISTIC): an open-label, randomised, controlled phase 2 trial. (published online Nov 7.)Lancet Gastroenterol Hepatol. 2017;
  5. Forbes, SJ and Newsome, PN. New horizons for stem cell therapy in liver disease. J Hepatol. 2012; 56: 496–499
  6. Spahr, L, Lambert, JF, Rubbia-Brandt, L et al. Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial. Hepatology. 2008; 48: 221–229
  7. Spahr, L, Chalandon, Y, Terraz, S et al. Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial. PLoS One. 2013; 8: e53719
  8. Moore, JK, Stutchfield, BM, and Forbes, SJ. Systematic review: the effects of autologous stem cell therapy for patients with liver disease. Aliment Pharmacol Ther. 2014; 39: 673–685
  9. Sokal, EM, Lombard, CA, Roelants, V et al. Biodistribution of liver-derived mesenchymal stem cells after peripheral injection in a hemophilia a patient. Transplantation. 2017; 101: 1845–1851
  10. Lanthier, N, Lin-Marq, N, Rubbia-Brandt, L, Clement, S, Goossens, N, and Spahr, L. Autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns?. Stem Cell Res Ther. 2017; 8: 88