Tuesday, April 24, 2018

Radiotherapy offers new treatment option for liver cancer

Radiotherapy offers new treatment option for liver cancer

Radiological Society of North America

OAK BROOK, Ill. - A novel technique that delivers high doses of radiation to tumors while sparing the surrounding normal tissue shows promise as a curative treatment option for patients with early-stage liver cancer, according to a study published online in the journal Radiology.

Curative treatment options for early-stage hepatocellular carcinoma (HCC), the most common type of liver cancer, include surgery, liver transplantation and radiofrequency ablation. However, many patients are not candidates for these therapies due to the presence of other conditions. In addition, these treatments carry significant costs and potential complications.

Radiation segmentectomy (RS) is a minimally invasive option that uses the radioisotope yttrium-90 (Y90) to destroy tumors. The isotope is embedded into tiny beads that are delivered through a catheter into a blood vessel in the liver. They then travel to the site of the tumor, where they come to rest and deliver their radioactive effect while sparing much of the surrounding healthy tissue.

The procedure's name derives from the fact that surgeons divide the liver into a number of segments. Using an imaging approach called cone beam CT, interventional radiologists gain a detailed view of the complex liver vasculature and can focus delivery of the Y90 to the relevant segment.

"Cone beam CT has revolutionized our ability to perform segmental injections isolated to very small tumors, sparing the majority of normal tissue," said study senior author Riad Salem, M.D., chief of vascular interventional radiology in the Department of Radiology at the Northwestern University Feinberg School of Medicine in Chicago. "Before cone beam CT, we had the ability to focus radiation, but not with this level of accuracy."

Dr. Salem and colleagues studied long-term outcomes in 70 early-stage HCC patients who had undergone RS between 2003 and 2016. They analyzed the patients' responses to treatment based on two commonly used sets of criteria.

Based on one criteria, 90 percent of patients showed positive response to the therapy, of which 59 percent showed complete response. Based on a second criteria, 71 percent achieved positive response, of which 16 percent achieved complete response.

RS controlled the target tumor, slowed the time to disease progression and improved survival outcomes at rates comparable to radiofrequency ablation, surgery and transplantation for early-stage HCC patients.

Almost three-quarters of patients had no progression of cancer in the target tumor five years after treatment. Median overall survival was 6.7 years, and one-, three-, and five-year survival probabilities were 98 percent, 66 percent and 57 percent, respectively. One-, three-, and five-year overall survival probability was 100 percent, 82 percent and 75 percent in patients with a baseline tumor size of 3 centimeters or less.

"The results show that we are able to impart curative outcomes to these patients," Dr. Salem said. "Our numbers with radiation segmentectomy match or outperform those of other curative treatments in terms of tumor control, survival rate and recurrence."

RS is performed on an outpatient basis, is minimally invasive and has a low toxicity profile, Dr. Salem said. Given the potency of the radiation, RS outperforms transarterial chemoembolization, another minimally invasive procedure in which cancer-killing drugs are injected into the liver's main artery under imaging guidance and travel to the tumor microvasculature. Transarterial chemoembolization has the additional disadvantage of requiring hospitalization.

The researchers continue to follow the patients from the study group as they work on ways to optimize the treatment.

"We want to see these outcomes validated in patients over the longer term," Dr. Salem said. "We also want to minimize the time from clinic visit to treatment, and fine-tune dosimetry so that we can find the optimal dose that will kill the tumor. In the right patient setting, RS can be considered curative."

Implementation of hepatitis C cure in Australia: one year on

J Virus Erad. 2018 Apr 1;4(2):115-117.
Implementation of hepatitis C cure in Australia: one year on.
Richmond JA, Wallace J1.

Full Article
View Online

Direct-acting antivirals (DAAs) for the treatment of hepatitis C (HCV) became universally available in Australia in March 2016, with an aim to achieve HCV elimination. Fourteen per cent of Australians with HCV have initiated treatment. The objective of this study was to explore and identify challenges and enablers that have emerged during this initial phase of HCV cure implementation.

Key stakeholders (KS) in primary care, non-government and government sectors were recruited to participate in a telephone-based semi-structured interview to describe challenges and enablers facing individuals with HCV and the healthcare system in implementing HCV cure. Data were thematically analysed.

Eleven KS participants were interviewed with each commending the significantly increased numbers of people accessing HCV treatment since March 2016. There was concern that this momentum was waning and that targeted interventions to normalise HCV treatment within primary care were needed. Furthermore, workforce development activities needed to acknowledge the priority of HCV elimination, and develop training and resources for clinicians, most of whom had limited HCV experience. The role of professional champions and multidisciplinary teams of both clinical and non-clinical workers was identified as critical for services that had cured a significant number of people with HCV.

Australia has many of the essential elements necessary to eliminate HCV, including universally funded DAA access and multiple treatment access points through primary care. Additional systematic activity is needed to ensure that the DAA-access momentum is maintained and HCV elimination achieved.

Monday, April 23, 2018

HCV, type 2 diabetes & fatty liver disease - Importance of diet and exercise

Importance of diet and exercise 

This Michigander is announcing winter might just be over. I am so done walking on my ugly, hated, overrated treadmill, looking forward to moving my morning routine outside.

If you too are feeling a bit of spring fever, or preparing for a lifestyle change, check out the links provided below and learn about the importance of diet and exercise for people with HCV, type 2 diabetes or fatty liver disease.

On The Radio
To get you started we begin with Dr Norman Swan, the host of Health Report, along with his guest Professor Mike Lean, lead author in a study investigating the impact of weight loss on type 2 diabetes, published in the Lancet 10 February 2018; Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The study found after a year, participants who lost weight (around 30 pounds) on a 800 calorie diet, no longer had type 2 diabetes. The diet may be too difficult or not recommended for some people, in the trial patients were followed closely, however, the outcome is amazing. The interview starts at 8:29, listen to the program, here, read the transcript below or visit Health Report.

Norman Swan: There's good news, for once, from the west of Scotland where a trial in general practice of an extremely low calorie diet has reversed type 2 diabetes in a large percentage of participants. Mike Lean is Professor of Human Nutrition at the University of Glasgow and is on the line. Welcome to the Health Report.

Mike Lean: Hello, how are you?

Norman Swan: Fine. You say in the paper that this is the first trial of its kind in type 2 diabetes, which is extraordinary.

Mike Lean: We've known about type 2 diabetes and thought of it as a distinct disease growing enormously in numbers and costing perhaps more than any other single disease for about 100 years, and it has been noted in a number of studies that some people if they lose enough weight will get rid of their diabetes. But no study has previously gone out to actually try and do that, to actually get as many people as possible to become non-diabetic, to get rid of their diabetes completely.

Norman Swan: So what did you do in this study?

Mike Lean: Well, this is not rocket science. What we did was we recruited people in primary care, in general practice, who were overweight, BMI over 27, so not enormously overweight but overweight, with type 2 diabetes. And we ask them to follow a formula diet, not a very low calorie but and 800-odd calorie diet for as long as it took, and it took quite a long time in some cases, to lose enough weight to become non-diabetic. And we aimed to get 15 kg weight loss because we knew from other observations that that was likely to do it. And of course not everybody managed, sadly, a lot of people found it really hard. A lot of people did manage. In the end we got about a quarter of our patients to lose that amount of weight. And those who lost 15 kg, almost 90% were no longer diabetic after a year, they were off all their medication, they were off all their diabetic medication and their antihypertensive medication, and they felt a lot better, their quality of life went up.

The remainder who didn't lose 15 kg, none of them got worse. Of those who lost over 10 kg, over half of them were non-diabetic. So you don't need to lose 15 kg but it's much better if you do. And I think what we've learnt from this is what we've regarded as a distinct disease, type 2 diabetes, is actually all part and parcel of obesity when you think about obesity as a disease process…

Norman Swan: We'll come back to the diet in a minute. And what was the recidivism rate, if you want to call it that, in terms of people gaining weight again and returning to diabetes?

Mike Lean: Yes, so that is of course…we've only published the one-year results and there's a lot more to find out. What we did find out was that the proportion of people with diabetes who wanted to have a go at this was very high. It was probably no great surprise because being diabetic is a penalty and it carries terrible medical risks as well as financial. The number within a year who put on any weight was really quite small, but we know very well from earlier studies that it's hard to maintain…the biggest problem is not losing the weight, it's actually maintaining it long term, and that's where our big research effort needs to go.

Norman Swan: So the diet itself…an 800 calorie diet is not something you try yourself at home because you can go into nutritional deficiency. This was a shakes and bars diet, wasn't it, it was a meal plan diet.

Mike Lean: That's correct, it was a formula diet which made sure it had all the vitamins and minerals, everything that was necessary, provided the patients actually followed this. And they didn't have to pay for it, they were given it for the study. And so they did that, so it was perfectly safe, there was no…

Norman Swan: That's my point, so it's one of these things you can buy in the chemist and it comes in various boxes, but we won't talk about the branding.

Mike Lean: The branding doesn't matter, all these things are pretty much the same. What matters is not what comes in the box or out of the packet, it's the support that is given with it, because people who go and get these type of diets from the chemist or from a supermarket generally do it for two or three or four weeks and then they peel off. If you are going to get rid of your diabetes you've got to stick in for probably 12 weeks if you do it full time. There are plenty of people who do it off and on for 12 weeks and need to carry on doing it off and on for a bit longer to lose their 10 or 15 kg. So there are different routes to getting there, you don't half to lose it all in one go but it works better if you do.

Norman Swan: What about complications, like if you lose weight fast when you are overweight you can get gallbladder disease…

Mike Lean: Ah, you're well informed!

Norman Swan: You can low blood sugar if you're on insulin, or diabetes complications. What sort of complications did people get?

Mike Lean: Well, the first thing was for this particular study we didn't include people who were already on insulin, partly because their likelihood of getting a remission is much lower. It had probably done damage to their pancreas by that stage. And what we did on day one was that we stopped all our anti-diabetes medication, so there's no risk of hypoglycaemia at all, and nobody had hypoglycaemia. And the same thing went for the blood pressure tablets, we stopped all their blood pressure tablets on day one because otherwise if you lose weight there is a risk of possible hypotension, and just to pick up your other point, there was one patient amongst the 150 who started, one who developed abdominal pains and we think that was probably by gallstones. That's a common complication of obesity, very common in people with diabetes anyway, and it can be made worse during weight loss.

Norman Swan: These are similar findings to bariatric surgery.

Mike Lean: Oddly the remission rate was actually a tiny bit better than bariatric surgery if you can lose 15 kg. If you lose 15 kg you will almost certainly get rid of your diabetes, whether or not it's done with surgery. There are of course many fewer hazards doing it without surgery. They produce very similar results, yes.

Norman Swan: Mike, thanks very much for joining us, a fascinating study.

Mike Lean: Thank you very much.

Norman Swan: Mike Lean is Professor of Human Nutrition at the University of Glasgow.

Fatty Liver Disease & Type 2 Diabetes 
"Given the increasing worldwide incidence of obesity and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease. Recent developments in the field have shown that NAFLD not only is a “liver disease” but also is the underlying cause of an increasing number of extrahepatic manifestations; thus, it should be treated as a multisystem disease. NAFLD is most prominently linked to chronic kidney disease, mellitus type 2 and cardiovascular disease, as well as a number of other severe chronic diseases. These findings demonstrate that NAFLD ranks amongst the most serious public health problems of our time."

Also noted in the article; The prevalence of Nonalcoholic Steatohepatitis (NASH), in people who are obese and have type 2 diabetes may be as high as 40%, whereas it is less than 5% in people without type 2 diabetes.
Read the article, here.

Presented at Liver Congress 2018
Alcoholic liver disease replaces hepatitis C infection as leading cause of liver transplantation in patients without hepatocellular carcinoma in the USA
Two independent studies presented at the conference reported; that alcoholic liver disease has now replaced hepatitis C virus (HCV) infection as the leading cause of liver transplantation in the USA in patients without HCC. Non-alcoholic steatohepatitis (NASH) is also on the increase, now ranking second as a cause of liver transplantation due to chronic liver disease.
Read the article, here.

Hepatitis C & Diabetes
Several studies have demonstrated the risk for development of diabetes is increased in people with chronic hepatitis C infection (HCV), for instance people with HCV have a 2.3 fold increased chance of having type 2 diabetes. According to a 2013 study published in Alimentary Pharmacology Therapeutics; Chronic hepatitis C virus infection is independently associated with presence of metabolic conditions (insulin resistance, type 2 diabetes mellitus and hypertension) and congestive heart failure.

HCV Treatment & Type 2 Diabetes
The good news is with today's high sustained viral response rates using direct antiviral medications to treat HCV, people who successfully reach SVR, or achieve a cure, lower their risk for the development of type 2 diabetes, the recent study was published in the Journal of Viral Hepatitis [published online February 25, 2018]. A quick overview of the study can be found online, here.

Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR
This particular study may be of interest to people with HCV, according to data published Mar 21, 2018 in the online journal World J Gastroenterology, evidence of steatosis was reported to be found in close to half of patients who achieve a sustained virologic response after treating with direct-acting antivirals. Full-text, here....

Tips - Eating Right

The Liver Loving Diet
"The Liver Loving Diet" is a book that will help you learn to eat well during all phases of liver disease. Karen Hoyt, the author, also blogs about living with and treating hepatitis C, cirrhosis, liver cancer and liver failure.

Mediterranean diet reduces liver fat, risk for NAFLD
March 30, 2018
Improved diet quality based on the Mediterranean-style diet score and Alternative Healthy Eating Index score correlated with less liver fat accumulation and a reduced risk for new-onset nonalcoholic fatty liver, according to a recently published study.
Continue reading @ Healio

Bottom Line
Spring is a great time to start again, experts agree two key elements in the prevention and management of type 2 diabetes and fatty liver disease is weight loss and exercise. In the end, its all good for your liver!

See you soon,

Saturday, April 21, 2018

Albumin predicts cirrhosis improvement after SVR with DAAs

Albumin predicts cirrhosis improvement after SVR with DAAs
April 20, 2018

PARIS — Rapid improvement in albumin levels after 4 weeks of treatment with direct-acting antivirals for hepatitis C significantly predicted long-term clinical and biochemical improvements among patients with advanced liver disease, according to a presentation at the International Liver Congress 2018.

“The introduction of DAAs has completely changed the HCV setting in clinical practice,” Chiara Mazzarelli, MD, from King’s College Hospital, United Kingdom, said in her presentation. “As hepatologists, we know that HCV clearance ... is associated with improvement and normalization of liver function.”

On This Blog

Hepatocellular carcinoma as a consequence of hepatitis C direct-acting anti-virals-the great urban myth of hepatology

Aliment Pharmacol Ther. 2018 May;47(10):1418-1419. doi: 10.1111/apt.14634.

Linked Content
This editorial is linked to Singer et al paper; Direct‐acting antiviral treatment for hepatitis C virus infection and risk of incident liver cancer: a retrospective cohort study, published 7 March 2018  https://doi.org/10.1111/apt.14593.

Editorial: hepatocellular carcinoma as a consequence of hepatitis C direct‐acting anti‐virals—the great urban myth of hepatology
Hussaini T1,2, Zhu J2,3, Yoshida EM2,3.

Achieving sustained virologic response (SVR), the surrogate marker for the cure of chronic hepatitis C virus (HCV) infection, has long been associated with decreased all‐cause and liver‐related mortality including progression to end stage liver disease or development of hepatocellular carcinoma.1 During the interferon (IFN) era, many studies demonstrated decreased incidence of HCC after HCV eradication, although the risk was not eliminated, especially in patients with advanced hepatic fibrosis or cirrhosis.2-4 With the availability of direct acting antiviral agents (DAAs), offering high SVR rates of greater than 90%, a dramatic decrease in HCC incidence was expected. Single‐center observational studies, however, reported an unexpected increase in both HCC occurrence and recurrence following DAA associated SVR.5-8 The majority of these studies were limited by methodological flaws: small sample size, lack of control groups and short follow‐up time, resulting in a suspicion of selection bias and other potential confounders. Nonetheless, these reports raised concern that DAA therapy may promote HCC recurrence by altering immune surveillance after HCV eradication.

Recently, the results of a large retrospective cohort trial studying 62 352 HCV infected patients treated with IFN, DAAs, or a combination of both, challenged the findings of the earlier studies.9 Based on HCV treatment regimens, patients were divided into three groups; IFN only (N = 35 871), DAAs + IFN (N = 4535), and DAA only (N = 21 948). Although the HCC incidence was higher with DAA only therapy, after adjusting for important baseline confounders, there was no difference in HCC incidence between the groups. In fact, SVR was associated with significantly lower incidence of HCC regardless of regimen utilised.

In a recent issue of Alimentary Pharmacology & Therapeutics, Singer and colleagues, report the results of another large population based study that further dispels the myth of increased HCC occurrence after DAA associated SVR. They studied 30 183 patients treated with DAAs, 12 948 patients treated with IFN‐based therapy and 137 502 treatment‐naïve patients.10 The unadjusted incidence rate of HCC was higher in DAA treated group as compared to both IFN treated (unadjusted HR = 1.22, 95% CI: 1.04‐1.42) and treatment naïve patients (unadjusted HR of 1.84 (95% CI: 1.65‐2.05). However, after adjusting for known baseline risk factors for HCC such as older age, male gender and advanced liver disease, DAA therapy was associated with reduced incidence of HCC as compared to untreated (adjusted HR = 0.84, 95% CI: 0.73‐0.96) and IFN treated individuals (adjusted HR = 0.84, 95% CI: 0.73‐0.96).

The introductions of DAA regimens have revolutionised HCV therapy, both in terms of outstanding SVR rates and excellent tolerability profiles. They offer a chance for virological cure in those with few treatment options due to age or advanced liver disease. Therefore, it is not surprising that the unadjusted incident rate of HCC is higher in cohorts treated with DAAs as compared to IFN based therapy. The results of the recent large studies that were designed to control for known HCC risk factors such as older age and advanced liver disease have again demonstrated that HCV eradication reduces the risk of HCC regardless of anti‐viral regimen. We are therefore confident that DAAs do not increase the risk of HCC.

Declaration of personal: Drs. Hussaini and Zhu have no conflict of interest to declare Dr. Eric Yoshida has been an investigator of clinical trials sponsored by Gilead, Merck, Abbvie, Janssen, Intercept, Genfit, Springbank. He has received honoraria for CM/ad board lectures from Gilead Canada, Abbvie Canada, Merck Canada, Celgene Canada, Intercept Canada.


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Clinical Insights in NAFLD and NASH for 2018

Clinical Liver Disease (CLD) is a digital educational resource published on behalf of the American Association for the Study of Liver Diseases (AASLD). CLD publishes easy to read reviews on relevant topics for clinicians diagnosing and managing patients with liver disease.

LATEST ISSUE > Volume 11, Issue 4
Pages: 81-104
April 2018

Clinical Insights in NAFLD and NASH for 2018
Guest Edited by Arun Sanyal, MD

An update on the pharmacological treatment of nonalcoholic fatty liver disease: Beyond lifestyle modifications
Naim Alkhouri M.D.
Andrea Scott B.S.
Pages: 82-86
First Published:20 April 2018
Watch a video presentation of this article
Full text

Kara Wegermann M.D.
Anna Mae Diehl M.D.
Cynthia A. Moylan MD, MHS
Pages: 87-91
First Published:20 April 2018

Watch a video presentation of this article
Full text

Free Access
The epidemiology of nonalcoholic steatohepatitis

Zobair M. Younossi M.D., M.P.H., F.A.A.S.L.D.
Pages: 92-94
First Published:20 April 2018
Watch a video presentation of this article
Watch the interview with the author
Full text

Pediatric nonalcoholic fatty liver disease

Tania Mitsinikos M.D.
Rohit Kohli M.B.B.S., M.S.
Pages: 95-97
First Published:20 April 2018
Watch a video presentation of this article
Watch the interview with the author
Full text

Diagnostic challenges of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis
Erin Cleveland M.D.
Andrew Bandy M.D.
Lisa B. VanWagner M.D., M.Sc.
Pages: 98-104
First Published:20 April 2018
Watch a video presentation of this article
Watch the interview with the author
Full text

Friday, April 20, 2018

International Liver Congress 2018 - Webinars covering critical studies on viral hepatitis and NAFLD/NASH

Clinical Care Options 
Program Overview
2018 Annual Meeting of the European Association for the Study of the Liver*
April 11-15, 2018 | Paris, France

Review Capsules Summaries, download slides, and listen to audio commentary from expert-led Webinars covering critical studies on viral hepatitis and NAFLD/NASH from Paris.
Link: https://www.clinicaloptions.com/Hepatitis/Conference%20Coverage/Paris%202018.aspx

Free registration required

Viral Hepatitis
Capsule Summaries (6)
Addition of RBV Associated With Increased Efficacy of 12 Weeks Sofosbuvir/Velpatasvir in Patients With Genotype 3 HCV Infection and Compensated Cirrhosis

Retreatment of Patients Who Failed Glecaprevir/Pibrentasvir Treatment for Hepatitis C Virus Infection

A Phase 3b, Open-Label, Randomized, Pragmatic Study of Glecaprevir/Pibrentasvir +/- Ribavirin (RBV) for HCV Genotype 1 Subjects Who Previously Failed an NS5A Inhibitor + Sofosbuvir (SOF) Therapy

8 Weeks Sofosbuvir/Velpatasvir in Genotype 3 Patients With Significant Fibrosis: Highly Effective Amongst an OST Cohort (Coming soon)

Safety and Efficacy at 1 Year After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in Chronic HBV Patients With Risk Factors for TDF Use

High Efficacy and Safety of Grazoprevir and Elbasvir for 8 Weeks in Treatment-Naive, Nonsevere Fibrosis HCV GT1B-Infected Patients: Interim Results of the STREAGER Study

Capsule Summaries (4) 
Low-Moderate Alcohol Use Is Associated With a Lower Prevalence of Nonalcoholic Fatty Liver Disease in Hispanics/Latinos Living in the US: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Substantial Comorbidities and Rising Economic Burden In Real-World Nonalcoholic Fatty Liver Disease (NAFLD)/Nonalcoholic Steatohepatitis (NASH) Patients With Compensated Cirrhosis (CC): A Large German Claims Database Study (Coming soon)

Nonalcoholic Fatty Liver Disease and Relative Risk of Incident Steatohepatitis, Cirrhosis and Hepatocellular Carcinoma Events in 4 European Primary Care Databases

Prevalence and Stratification of NAFLD/NASH in a UK and US Cohort Using Noninvasive Multiparametric MRI

Begin here.......

Thursday, April 19, 2018

Life of a liver awaiting transplantation - Machine that preserves livers might offer a way forward

18 April 2018

Life of a liver awaiting transplantation
Stefan Schneeberger
People waiting for a liver transplant can die before an organ is found, or, if one is available but of poor quality, there is a risk of transplant failure. A machine that preserves livers might offer a way forward.

The concept of machine perfusion of an organ awaiting transplantation is not new. Indeed, machine-assisted perfusion was in use before cold storage became the method of choice owing to its simplicity and reproducibility2. However, interest in revisiting perfusion as a transplant approach has been gaining momentum.

The main outcome monitored in the latest trial was the post-transplantation level of the enzyme aspartate transaminase in patients’ blood. This measurement is commonly used to assess liver damage and to estimate the risk of transplant failure. The authors found that the use of NMP was associated with less liver damage than that found in livers preserved on ice. Moreover, preservation by NMP reduced the number of organs that were discarded as unsuitable for transplantation compared with livers preserved on ice, and was associated with a better blood-flow profile in the recipient.

Scientific guidelines for using cannabis to treat stress, anxiety and depression

Scientific guidelines for using cannabis to treat stress, anxiety and depression

Washington State University

PULLMAN, Wash.--In a first-of-a-kind study, Washington State University scientists examined how peoples' self-reported levels of stress, anxiety and depression were affected by smoking different strains and quantities of cannabis at home.

Their work, published this month in the Journal of Affective Disorders, suggests smoking cannabis can significantly reduce short-term levels of depression, anxiety, and stress but may contribute to worse overall feelings of depression over time.

It marks one of the first attempts by U.S. scientists to assess how cannabis with varying concentrations of the chemical compounds tetrahydrocannabinol (THC) and cannabidiol (CBD) affect medicinal cannabis users' feelings of wellbeing when smoked outside of a laboratory.

"Existing research on the effects of cannabis on depression, anxiety and stress are very rare and have almost exclusively been done with orally administered THC pills in a laboratory," said Carrie Cuttler, clinical assistant professor of psychology at WSU and lead author of the study. "What is unique about our study is that we looked at actual inhaled cannabis by medical marijuana patients who were using it in the comfort of their own homes as opposed to a laboratory."

For example, the WSU research team found that one puff of cannabis high in CBD and low in THC was optimal for reducing symptoms of depression, two puffs of any type of cannabis was sufficient to reduce symptoms of anxiety, while 10 or more puffs of cannabis high in CBD and high in THC produced the largest reductions in stress.

"A lot of consumers seem to be under the false assumption that more THC is always better," Cuttler said. "Our study shows that CBD is also a very important ingredient in cannabis and may augment some of the positive effects of THC."

The researchers also found that while both sexes reported decreases in all three symptoms after using cannabis, women reported a significantly greater reduction in anxiety following cannabis use.

Data for the study were taken from the trademarked app Strainprint, which provides medical cannabis users a means of tracking how different doses and types of cannabis affect a wide variety of symptoms of wellbeing.

Strainprint users rate the symptoms they are experiencing before using cannabis on a scale of 1-10 and then input information about the type of cannabis they are using. Twenty minutes after smoking, they are prompted to report how many puffs they took and to rerate the severity of their symptoms.

Cuttler and WSU colleagues Alexander Spradlin and Ryan McLaughlin used a form of statistical analysis called multilevel modeling to analyze around 12,000 anonymous Strainprint entries for depression, anxiety and stress. The researchers did not receive any of the Strainprint users personally identifying information for their work.

"This is to my knowledge one of the first scientific studies to provide guidance on the strains and quantities of cannabis people should be seeking out for reducing stress, anxiety and depression," Cuttler said. "Currently, medical and recreational cannabis users rely on the advice of bud tenders whose recommendations are based off of anecdotal not scientific evidence."

The study is among several cannabis-related research projects currently underway at WSU, all of which are consistent with federal law and many of which are funded with Washington state cannabis taxes and liquor license fees.

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Hepatic Steatosis and its Effects on Fibrosis in Patients With Chronic Hepatitis B Virus Infection

Clinical Gastroenterology and Hepatology (CGH)
April 2018 Volume 16, Issue 4, Pages 491–494

Hepatic Steatosis and its Effects on Fibrosis in Patients With Chronic Hepatitis B Virus Infection
Mauricio Garcia-Saenz-de-Sicilia, MD, Andres Duarte-Rojo, MD, MS, DSC

Read Online
Download PDF

Obesity rising prevalence has reawakened interest in the potential interactions between chronic viral hepatitis and hepatic steatosis. The metabolic syndrome and its components are independent risk factors associated with fibrosis progression, development of cirrhosis,1 and potentially with lack of fibrosis reversal following antiviral therapy in chronic viral hepatitis.2 However, the particular role of hepatic steatosis, the hallmark of nonalcoholic fatty liver (NAFLD), has been less of a focus of attention in chronic hepatitis B virus (HBV) infection when compared with chronic hepatitis C, in part because of the lack of proper evaluation tools.3

Liver biopsy is considered to be the gold standard for steatosis grading. However, it is invasive, has potential life-threatening complications, can result in sampling errors particularly when fatty infiltration is unevenly distributed (typical biopsy represents 1/50,000 of liver), and interpretation reaches only moderate interobserver or intraobserver agreement.4 Furthermore, repeated monitoring following a therapeutic intervention is hard to justify because of the invasive nature of the procedure and cost, and the fact that noninvasive options are now available. Imaging techniques provide reliable noninvasive alternatives to assess steatosis. Proton density fat fraction from magnetic resonance is perhaps the most accurate method for steatosis quantification; however, it is not a point-of-care method, and has associated high costs and limited availability, making it impractical for routine clinical care at most institutions. All of these limitations are at least partially overcome by the controlled attenuated parameter (CAP) feature from FibroScan (Echosens, Paris, France). This technique, based on the principle that fat affects ultrasound propagation, quantifies variations in M-mode (unidimensional) ultrasound attenuation during liver stiffness measurement (LSM) with vibration-controlled transient elastography, to yield a steatosis estimate. When testing CAP against steatosis grading by liver biopsy, fair to excellent performance has been reported across studies, and discrepancies are likely explained by variations in liver disease etiology, population body composition, and spectrum bias (Table 1). Although CAP interpretation has been limited by uncertainty as to the optimal cutoff values between grades of steatosis, Karlas et al5 have recently brought some certainty to this issue. In a meta-analysis including 2735 cases with histology and CAP analysis, the authors defined cutoff values and variables influencing the output, such as body mass index (BMI), diabetes, and etiology.

Risk factors for hepatocellular carcinoma by age, sex, and liver disorder status

Cancer. 2018 Apr 18. doi: 10.1002/cncr.31406. [Epub ahead of print]
Risk factors for hepatocellular carcinoma by age, sex, and liver disorder status: A prospective cohort study in Korea.
Yi SW1,2, Choi JS3, Yi JJ4, Lee YH5, Han KJ3.

First published: 18 April 2018

Personal or institutional subscription required to read full text article.

To the authors' knowledge, relatively little is known regarding the interaction of risk factors for hepatocellular carcinoma (HCC) with age, sex, and liver disorder status.

The authors followed 504,646 Korean patients aged 40 to 80 years who underwent routine health checkups between 2002 and 2003 until 2013 via linkage to national hospital discharge records.

HCC occurred in 2744 individuals. In the sex-adjusted and age-adjusted analysis, cirrhosis increased the incidence of HCC by 42-fold, followed by hepatitis B virus (21-fold), hepatitis C virus (HCV; 19-fold), male sex (4.3-fold), and each 5-year age increment (1.24-fold). In the multivariable adjusted analysis, diabetes increased the risk of HCC by 80%, alcohol consumption ≥80 g/day increased the risk by 75%, alcohol consumption of 40 to 79 g/day increased the risk by 37%, and being a current smoker increased the risk by 25%. The multivariable adjusted hazard ratios of male sex and HCV were 6.27 and 5.72, respectively, at age <50 years, but were 2.09 and 22.51, respectively, at age ≥70 years. Each 20 g/day of alcohol consumption increased the risk of HCC by 6% (P = .11), 8% (P = .02), 16% (P<.001), and 30% (P<.001), respectively, in individuals aged <50 years, 50 to 59 years, 60 to 69 years, and 70 to 80 years. In individuals without a liver disorder, body mass index was found to be positively associated with HCC, whereas patients with a liver disorder demonstrated an inverse association. Women had higher adjusted hazard ratios associated with age and cirrhosis compared with men.

With advancing age, the effects of alcohol use and HCV on the development of HCC become stronger, whereas the effect of male sex weakens. Lifetime moderate alcohol consumption may cause HCC in the elderly. Smoking increases the risk of HCC irrespective of viral hepatitis, and diabetes increases the risk of HCC independent of cirrhosis. Cancer 2018. © 2018 American Cancer Society.

© 2018 American Cancer Society.

European Food Safety Authority Warns Green Tea Extracts May Be Associated With Liver Damage

According to new research from the European Food Safety Authority (EFSA) consuming more than 800mg of green tea catechins per day may lead to higher health risks, including liver damage.

Scientific opinion on the safety of green tea catechins EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS)
Maged Younes Peter Aggett Fernando Aguilar Riccardo Crebelli Birgit Dusemund Metka Filipič Maria Jose Frutos Pierre Galtier David Gott Ursula Gundert‐Remy Claude Lambré Jean‐Charles Leblanc Inger Therese Lillegaard Peter Moldeus Alicja Mortensen Agneta Oskarsson Ivan Stankovic Ine Waalkens‐Berendsen Rudolf Antonius Woutersen Raul J Andrade Cristina Fortes Pasquale Mosesso Patrizia Restani Davide Arcella Fabiola Pizzo Camilla Smeraldi Matthew Wright

First published: 18 April 2018 https://doi.org/10.2903/j.efsa.2018.5239


The EFSA ANS Panel was asked to provide a scientific opinion on the safety of green tea catechins from dietary sources including preparations such as food supplements and infusions. Green tea is produced from the leaves of Camellia sinensis (L.) Kuntze, without fermentation, which prevents the oxidation of polyphenolic components. Most of the polyphenols in green tea are catechins. The Panel considered the possible association between the consumption of (‐)‐epigallocatechin‐3‐gallate (EGCG), the most relevant catechin in green tea, and hepatotoxicity. This scientific opinion is based on published scientific literature, including interventional studies, monographs and reports by national and international authorities and data received following a public ‘Call for data’. The mean daily intake of EGCG resulting from the consumption of green tea infusions ranges from 90 to 300 mg/day while exposure by high‐level consumers is estimated to be up to 866 mg EGCG/day, in the adult population in the EU. Food supplements containing green tea catechins provide a daily dose of EGCG in the range of 5–1,000 mg/day, for adult population. The Panel concluded that catechins from green tea infusion, prepared in a traditional way, and reconstituted drinks with an equivalent composition to traditional green tea infusions, are in general considered to be safe according to the presumption of safety approach provided the intake corresponds to reported intakes in European Member States. However, rare cases of liver injury have been reported after consumption of green tea infusions, most probably due to an idiosyncratic reaction. Based on the available data on the potential adverse effects of green tea catechins on the liver, the Panel concluded that there is evidence from interventional clinical trials that intake of doses equal or above 800 mg EGCG/day taken as a food supplement has been shown to induce a statistically significant increase of serum transaminases in treated subjects compared to control.

In The Media
Green tea supplements may cause liver damage, warns EU watchdog
The European Food Safety Authority assessed the safety of the supplements
More than 800mg of green tea catechins each day may pose health concerns
Officials at the EU funded organisation were unable to confirm a safe dose
It today called for further scientific trials into the effect of green tea catechins

Tuesday, April 17, 2018

Every Cloud Has a Silver Lining: Overdose-Death Donors in Organ Transplantation

HIV and ID Observations
Hepatitis C Positive Organ Donors — Coming Soon to a Transplant Center Near You
There’s one immutable fact in solid organ transplantation — the number of patients awaiting transplant exceeds the number of available organs.
Continue reading...

Reuters Health
Organs from overdose-death donors a viable option for transplant
Last Updated: 2018-04-16
By Marilynn Larkin
NEW YORK (Reuters Health) - Transplantation with overdose-death donor (ODD) organs has increased dramatically in the U.S., with equivalent outcomes to non-ODD organs, and therefore these organs should not be routinely discarded, researchers in Maryland say.

"Most Americans know that the U.S. faces an epidemic of deaths due to drug overdose, and many are also aware that there is a critical shortage of organs available for transplant," Dr. Christine Durand of Johns Hopkins University School of Medicine in Baltimore told Reuters Health.

"Perhaps less widely known is that today, more than one in every 10 deceased organ donors died from a drug overdose," she said by email.

"Patients who received transplants from these donors had excellent outcomes; patient survival and organ function were similar to cases when donors died due to trauma, and similar or better than cases when the donor died due to medical causes of death like heart attack or stroke," she added.

Dr. Durand and colleagues examined data from January 2000 to September 2017 on 138,565 deceased donors and 337,934 transplant recipients at 297 transplant centers in the U.S.

Ann Intern Med 2018
Editorial |17 April 2018
Nearly 115 000 candidates currently await organ transplantation in the United States (mostly kidneys [81%] and livers [12%]) (1). Because of the profound organ shortage, many candidates awaiting transplant experience significant morbidity and mortality each year. In this issue, Durand and colleagues (2) review the use of overdose-death donor (ODD) organ transplants involving 138 565 deceased donors and 337 934 solid organ transplant recipients from 2000 to 2017. The study used the Scientific Registry of Transplant Recipients, which includes U.S. national data collected by the Organ Procurement and Transplantation Network (OPTN). The authors found that ODD transplants increased 24-fold, from 149 in 2000 (1.1% of donors) to 3533 in 2016 (12.7% of donors). For the most part, outcomes with ODD organs were noninferior to those with organs from trauma-death donors (TDDs) and medical-death donors (MDDs). Compared with MDDs, ODDs were less likely to have hypertension, diabetes, or prior myocardial infarction but had slightly higher creatinine levels and were more likely to donate after circulatory death. Cold ischemic time of transplanted kidneys was similar across all donor types. In an adjusted analysis, recipients of ODD kidneys and livers had a lower risk for death than recipients of MDD organs and a similar risk for death and graft loss compared with recipients of TDD organs.

Does interferon-free therapy for hepatitis C after curative treatment for hepatocellular carcinoma lead to unexpected recurrences of HCC?

PLOS ONE | https://doi.org/10.1371/journal.pone.0194704
April 16, 2018

Does interferon-free direct-acting antiviral therapy for hepatitis C after curative treatment for hepatocellular carcinoma lead to unexpected recurrences of HCC? A multicenter study by the Japanese Red Cross Hospital Liver Study Group
Toshie Mashiba, Kouji Joko , Masayuki Kurosaki, Hironori Ochi, Yukio Osaki, Yuji Kojima, Ryo Nakata, Tohru Goto, Akahane Takehiro, Hiroyuki Kimura, Akeri Mitsuda, Chiharu Kawanami, Yasushi Uchida, Chikara Ogawa, Atsunori Kusakabe, Ryuichi Narita, Yasushi Ide, Takehiko Abe, Keiji Tsuji, Tadashi Kitamura, Kazuhiko Okada, Tetsuro Sohda, Masaya Shigeno, Takashi Satou, Namiki Izumi

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Since the era in which interferon (IFN) was the standard treatment for hepatitis C, attempts have been made to eliminate hepatitis C virus (HCV) following hepatocellular carcinoma (HCC) treatment, but it could be achieved in only a limited number of patients due to side effects. Recently, dramatic progress has been made in anti-HCV therapies. It is now feasible to achieve a sustained virological response (SVR) rate of ≥95% even in older patients or cirrhosis patients with IFN-free direct-acting antiviral (DAA) therapy that has minimal side effects in older patients and in cirrhosis patients [1], and antiviral therapy can now be performed easily in patients who have undergone HCC treatment. It has been reported that the elimination of HCV with IFN after curative treatment for HCV-associated HCC suppresses HCC recurrences [25]. We have also found that it dramatically extends patients’ survival [6]. However, whether a similar effect can be achieved with DAA therapy is unclear. Furthermore, potential increases in unexpected early recurrence of HCC after HCV elimination have been reported with DAA therapy [7,8]. With this background, the HCC recurrence rate was compared between those who underwent IFN therapy and those who underwent IFN-free therapy after HCC treatment in a large-scale cohort.

Background and aim
This study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort.

This multicenter study was conducted by the Japanese Red Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and 347 IFN-free DAA-treated patients achieved sustained virological response (SVR). The recurrence rate of HCC was compared between the antiviral therapies. Logistic analysis and Cox proportional hazards analysis identified factors associated with early recurrence of HCC within 24 weeks of antiviral therapy and recurrence throughout the observation period, respectively.

AFP at the completion of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors associated with early recurrence of HCC. Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC. For recurrence throughout the observation period in SVR patients, AFP at completion of antiviral therapy, duration between last HCC treatment to antiviral therapy, and the number of treatments were independent factors. There was no significant difference in the rate of early recurrence of HCC or recurrence throughout the observation period between IFN and IFN-free DAA treated patients.

There were no differences in the early recurrence rate of HCC between patients who underwent IFN and those who underwent IFN-free DAA as antiviral therapies.

Monday, April 16, 2018

DAA therapy effective in patients with HCV and advanced cirrhosis - Real World Experience from the HCV-TARGET Cohort

The International Liver Congress 2018

Healio Coverage
DAA therapy effective in patients with HCV and advanced cirrhosis
April 16, 2018
PARIS — Direct-acting antiviral therapy effectively treated hepatitis C virus in patients with high MELD scores, producing a high rate of sustained viroloic response, according to a presentation at the International Liver Congress 2018.

“Real-life SVR rates with DAAs in patients with advanced liver disease ranged from 85% to 100% and were comparable to clinical trial experience. Ribavirin did not influence SVR in this cohort,” Elizabeth C. Verna, MD, of Columbia University, said in her presentation. “Over the year following treatment, stabilization or marginal improvement is seen in those with low MELDs while greater degree of improvement may occur in patients with MELD greater than 16.”

Verna and colleagues used the HCV-TARGET database of patients to cull patients with cirrhosis and MELD higher than 10. Patients initiated DAA therapy between March 2014 and June 2017. Patients with prior liver transplant were excluded. The researchers enrolled 488 patients in the safety cohort and 412 patients in the efficacy cohort; of those, 373 achieved SVR12 and 39 failed treatment. Patients received a variety of approved regimens.

On This Blog

Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?

World J Gastroenterol. Apr 14, 2018; 24(14): 1491-1506
Published online Apr 14, 2018. doi: 10.3748/wjg.v24.i14.1491

Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?
Ivana Mikolasevic, Tajana Filipec-Kanizaj, Maja Mijic, Ivan Jakopcic, Sandra Milic, Irena Hrstic, Nikola Sobocan, Davor Stimac, Patrizia Burra

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a primary cause of macrovesicular steatosis and has several impacts on liver transplantation (LT), which is transmitted to transplant recipients and organ donors. Current data indicate a new trend in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome (MetS) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT.

Sunday, April 15, 2018

Long term follow up of HCV pts with F2-F3 fibrosis who had achieved SVR with DAA therapy

Shared on Twitter today by @HenryEChang

Liver-related & HCC events were rare after up to 144 weeks of follow-up in patients with F2-F3 fibrosis who had achieved SVR with DAA therapy: Results from the Gilead Sciences SVR Registry

Sustained & continued improvement in hepatic fibrosis beyond the first-year (& in the subsequent 3 years) following HCV treatment

Shared on Twitter today by @HenryEChang

Sustained & continued improvement in hepatic fibrosis beyond the first-year (& in the subsequent 3 years) following HCV treatment

Download here.... https://jumpshare.com/v/H2I1i5H2NNVi5Xp2vXbM

Michael Kirsch, M.D. - Why I Now Treat Hepatitis C Patients

Michael Kirsch, MD, a full time practicing physician who blogs at “MD Whistleblower ,” in the past has written about the controversies surrounding hepatitis C; from weighing in on the value of HCV screening strategies, treatment risks and benefits, to the price of a cure. After reviewing his previous articles over the years its clear he did not recommend treating HCV patients, today he explains why he has changed his mind, he writes;
Patients come to my office already informed about current HCV treatment. Many are referred to me by physicians expecting me to treat them. The drugs are safe and effective and approved by the F.D.A. Although I still feel we are overtreating, my arguments for holding back have been somewhat dismantled by the new pharmaceutical developments. Am I now at the vanguard of the Medical Industrial Complex?
Check out previous articles, followed by his current take on treating HCV.


April 15, 2018
Why I Now Treat Hepatitis C Patients
Michael Kirsch, M.D.
In a prior post, I shared my heretofore reluctance to prescribe medications to my Hepatitis C (HCV) patients. In summary, after consideration of the risks and benefits of the available options, I could not persuade myself – or my patients – to pull the trigger. These patients were made aware of my conservative philosophy of medical practice. I offered every one of them an opportunity to consult with another specialist who had a different view on the value of HCV treatment.

I do believe that there is a medical industrial complex that is flowing across the country like hot steaming lava. While I have evolved in many ways professionally over the years, I have remained steadfast that less medical care generally results in better outcomes.

Saturday, April 14, 2018

JIAS - Special Issue: Towards global viral hepatitis elimination for all patients in all income settings

Journal of the International AIDS Society
Published on behalf of the International AIDS Society

Special Issue: Towards global viral hepatitis elimination for all patients in all income settings
Guest Editors: Marina B Klein, Karine Lacombe

The complete supplement file is available at

First Published: 10 April 2018
Full text

Open Access
How far are we from viral hepatitis elimination service coverage targets?

Yvan J‐F Hutin Marc Bulterys Gottfried O Hirnschall e25050
First Published: 10 April 2018
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Research Articles
Open Access
Hep‐CORE: a cross‐sectional study of the viral hepatitis policy environment reported by patient groups in 25 European countries in 2016 and 2017

Jeffrey V Lazarus Samya R Stumo Magdalena Harris Greet Hendrickx Kristina L Hetherington
Mojca Maticic Marie Jauffret‐Roustide Joan Tallada Kaarlo Simojoki Tatjana Reic Kelly Safreed‐Harmon the Hep‐CORE Study Group e25052
First Published: 10 April 2018
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Open Access
Approaches for simplified HCV diagnostic algorithms

Slim Fourati Jordan J Feld Stéphane Chevaliez Niklas Luhmann e25058
First Published: 10 April 2018
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Open Access
Linkage and retention in HCV care for HIV‐infected populations: early data from the DAA era

Rachel Sacks‐Davis Joseph S Doyle Andri Rauch Charles Beguelin Alisa E Pedrana Gail V Matthews Maria Prins Marc van der Valk Marina B Klein Sahar Saeed Karine Lacombe
Nikoloz Chkhartishvili Frederick L Altice Margaret E Hellard e25051
First Published: 10 April 2018
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Open Access
Treatment advocate tactics to expand access to antiviral therapy for HIV and viral hepatitis C in low‐ to high‐income settings: making sure no one is left behind

Céline Grillon Priti R Krishtel Othoman Mellouk Anton Basenko James Freeman Luís Mendão
Isabelle Andrieux‐Meyer Sébastien Morin e25060
First Published: 10 April 2018
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Open Access
Is hepatitis C virus elimination possible among people living with HIV and what will it take to achieve it?

Natasha K Martin Anne Boerekamps Andrew M Hill Bart J A Rijnders e25062
First Published: 10 April 2018
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Open Access
Research gaps in viral hepatitis

Anders Boyd Léa Duchesne Karine Lacombe e25054
First Published: 10 April 2018
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