Comparing clinical presentations, treatments and outcomes of hepatocellular carcinoma due to Hepatitis C and Non Alcoholic Fatty Liver Disease

Comparing clinical presentations, treatments and outcomes of hepatocellular carcinoma due to Hepatitis C and Non Alcoholic Fatty Liver Disease

Nwe Ni Than, Anwar Ghazanfar, James Hodson, Nadeem Tehami, Chris Coldham, Hynek Mergental, Derek Manas, Tahir Shah, Philip N Newsome, Helen Reeves, Shishir Shetty 

DOI: http://dx.doi.org/10.1093/qjmed/hcw151

First published online: 10 September 2016

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Abstract

Introduction: Hepatocellular carcinoma (HCC) is increasing in incidence in the UK and globally. Liver cirrhosis is the common cause for developing HCC. The common reasons for liver cirrhosis are viral hepatitis C (HCV), viral hepatitis B and alcohol. However, HCC caused by non-alcoholic fatty liver disease (NAFLD)-cirrhosis is now increasingly as a result of rising worldwide obesity.

Aim: To compare the clinical presentation, treatment options and outcomes of hepatocellular carcinoma due to HCV and NAFLD patients.

Methods: Data were collected from two liver transplant centres in the United Kingdom (Birmingham and Newcastle upon Tyne) between 2000 and 2014. We compared 275 patients with HCV-related HCC against 212 patients with NAFLD- related HCC.

Results: Patients in the NAFLD group were found to be significantly older (p<0.001) and more likely to be Caucasian (p<0.001). They had lower rates of cirrhosis (p<0.001) than those in HCV-HCC group. The NAFLD group presented with significantly larger tumours (p=0.009), whilst HCV patients had a higher alpha fetoprotein (AFP) (p=0.018). NAFLD patients were more commonly treated with TACE (p=0.005) than the HCV patients, whilst the HCV group were significantly more likely to be transplanted (p<0.001). In patients selected for liver transplantation, 5-year survival rates in NAFLD were not significantly different from HCV-HCC (44% and 56% respectively, p=0.102).

Conclusion: In this study NAFLD patients presented with larger tumours that were less likely to be amenable to curative therapy, as compared with HCV patients. Despite this disadvantage, patients with NAFLD had similar overall survival compared to patients with HCV.

Keywords: hepatocellular carcinoma, hepatitis C, non-alcoholic fatty liver disease, survival, liver
transplantation. 

ILCA Annual Conference Coverage - Conflicting Evidence Surfaces on Anti-HCV Drugs for Liver Cancer

The 2016 International Liver Cancer Association Annual Conference took place in Vancouver, Canada from September 9 to 11, 2016.

The 10th ILCA Annual Conference welcomed over 600 participants from 46 different countries and proved to be a great success!

This multidisciplinary meeting is an outstanding scientific forum for all clinical, translational and basic researchers, physicians and allied professionals across liver cancer related disciplines to exchange their experiences and best practices.

Conference articles and multimedia coverage is available online at OncLive.

Conference Articles

Conflicting Evidence Surfaces on Anti-HCV Drugs for Liver Cancer
A new generation of drugs has proved highly effective against the hepatitis C virus but there is conflicting evidence about whether the therapies promote cancer recurrence in infected patients with hepatocellular carcinoma who already have responded to curative treatment.

Expert Describes Potential Therapeutic Vaccine for Advanced HCC
Ghassan K. Abou-Alfa, MD, discusses research into the use of the immunotherapeutic vaccinia virus Pexa-Vec as a frontline treatment for advanced hepatocellular carcinoma.

New Roles May Evolve for Competing Embolization Techniques in HCC
Two competing methods of delivering locoregional therapy to patients with hepatocellular carcinoma both have advantages and may be most successful in subgroups of individuals with intermediate-stage disease.

Large Analysis Sheds Light on Risk Factors for Non-Cirrhotic NASH-Associated HCC
About one quarter of patients with nonalcoholic steatohepatitis-associated hepatocellular carcinoma present without cirrhosis at diagnosis, suggesting a crucial subset of patients for future research with implications for HCC screening and surveillance.

Nivolumab Maintains Positive Results in Latest HCC Findings
Nivolumab continues to post durable responses in patients with advanced hepatocellular carcinoma regardless of whether they had hepatitis B or C or whether they had received prior treatment with sorafenib.

Regorafenib Moves Ahead of Field With Success in Advanced HCC
After 9 years of failed trials for once-promising drugs, regorafenib (Stivarga) has emerged as the clear choice for second-line therapy in advanced hepatocellular carcinoma after demonstrating survival improvements for patients whose disease has progressed after systemic treatment.

Regorafenib Poised as Second-Line Standard of Care in HCC
Although regorafenib is not currently approved, Morris Sherman, MD, PhD, already views the agent as the standard second-line therapy, with hopes for moving the agent into the frontline setting.

Early Signals Positive for Immunotherapy Plus Standard Therapy in HCC
Early evidence suggests that the combination of locoregional therapy with an immune checkpoint inhibitor is a safe and effective strategy to pursue for patients with advanced hepatocellular carcinoma.

Liver Cancer Experts Mark a Decade of Milestones in HCC
Although it has been nearly 10 years since a new drug was approved for the treatment of patients with hepatocellular carcinoma, the past decade has been marked by advances on the scientific and radiology fronts and the prospects for the development of new therapies are bright.

View all updates, here....

CLD Updates: Velpatasvir/Sofosbuvir, Serum markers for hepatocellular carcinoma and Type 2 diabetes

View recently published articles in the latest issue of Clinical Liver Disease (CLD).

Volume 8 Issue 2  Issue Publication: August 2016

CLD is the official digital educational resource from the American Association for the Study of Liver Diseases.

Category Reviews New Treatments for HCV

Velpatasvir and sofosbuvir: How will we use a new drug when the old agents work well?
The rapid development of highly efficacious and well-tolerated regimens for treatment of chronic hepatitis C virus (HCV) infection has been a remarkable advance. Direct-acting antiviral combinations are available for each of the six HCV genotypes (GTs). Because sustained virological response (SVR) rates are greater than 95% for most patient populations, it may be questioned why new regimens are under development.​
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Biomarkers in Liver Disease
Serum markers for hepatocellular carcinoma
Authors Paul ClarkFirst Published: 29 August 2016
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Biomarkers of immunosuppression

Authors Tiong Yeng Lim, Michael HeneghanFirst Published: 29 August 2016
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Hepatocellular Carcinoma and Nonalcoholic Steatohepatitis
Statins and metformin for chemoprevention of hepatocellular carcinoma

Authors Jonggi Choi, Lewis R. RobertsFirst Published: 29 August 2016
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Type 2 diabetes–associated hepatocellular carcinoma: A molecular profile

Authors Manon Allaire, Jean Charles NaultFirst Published: 29 August 2016
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Begin here...

Liver Cancer is one of eight cancers linked to overweight and obesity

Liver Cancer is one of eight cancers linked to overweight and obesity

A Working Group of 21 independent international experts met at the International Agency for Research on Cancer (IARC) on 5–12 April 2016 to assess the cancer-preventive effects of the absence of excess body fatness. A summary of the evaluations has now been published in The New England Journal of Medicine.

The systematic review which involved more than 1000 studies on the link between overweight/obesity and cancer found obesity is linked to the following types of cancer: stomach, gall bladder, liver, pancreas, meningioma (a brain tumor), ovary, multiple myeloma (a blood cancer) and thyroid.

The detailed assessments will be published as Volume 16 of the IARC Handbooks of Cancer Prevention. Also available is a Q&A on the Handbooks Volume 16 evaluations.

IARC identifies eight additional cancer sites linked to overweight and obesity

Press Release
Lyon, France, 25 August 2016 – A new evaluation carried out by the IARC Handbooks of Cancer Prevention programme has concluded that overweight/obesity is a risk factor for more cancer sites than previously established. Based on a systematic review of the published scientific literature, the Working Group for IARC Handbooks of Cancer Prevention Volume 16: Body Fatness provided the latest evaluation of the cancer-preventive effects of the absence of excess body fatness. A summary of the results is published today in The New England Journal of Medicine.

A Working Group of 21 independent international experts, convened by the International Agency for Research on Cancer (IARC), assessed more than 1000 studies, including intervention trials, cohort and case–control studies, studies in experimental animals, and studies on the mechanisms linking excess body fatness and cancer.

“This comprehensive evaluation reinforces the benefits of maintaining a healthy body weight in order to reduce the risk of several different types of cancer,” says Dr Béatrice Lauby-Secretan, lead author of the new article.

Link between overweight/obesity and cancer

The experts confirmed the previous evaluation of the IARC Handbooks (Volume 6, published in 2002) that the absence of excess body fatness reduces the risk of cancers of the colon and rectum, oesophagus (adenocarcinoma), kidney (renal cell carcinoma), breast in postmenopausal women, and endometrium of the uterus.

In addition, the review of the available literature for middle-aged adults showed that there is sufficient evidence in humans that the absence of excess body fatness reduces the risk of cancers of the gastric cardia, liver, gallbladder, pancreas, ovary, and thyroid, and meningioma, and multiple myeloma. There is also limited evidence that the absence of excess body fatness reduces the risk of fatal cancer of the prostate, cancer of the breast in men, and diffuse large B-cell lymphoma.

The Working Group also reviewed data pertaining to body fatness in children, adolescents, and young adults (aged up to 25 years) to assess whether obesity at earlier periods of life is linked with cancer in adult life. For several cancer sites, including the colon and the liver, associations between excess body weight and cancers were observed that were similar to those reported in adults.

It is well established that overweight in experimental animals increases the incidence of several types of cancer. Studies in overweight animals showed that caloric or dietary restriction reduces the risk of cancers of the mammary gland, colon, liver, pancreas, skin, and pituitary gland.

Global burden of overweight and obesity Body fatness is assessed primarily by body mass index (BMI), defined as a person’s weight in kilograms divided by the square of their height in metres (kg/m2). In adults, overweight is defined as BMI ≥ 25 kg/m2, and obesity as BMI ≥ 30 kg/m2. Worldwide, an estimated 640 million adults were obese in 2014 (a 6-fold increase since 1975) and 110 million children and adolescents were obese in 2013 (a 2-fold increase since 1980).

The estimated age-standardized prevalence of obesity in 2014 was 10.8% in men, 14.9% in women, and 5.0% in children, and globally more people are overweight or obese than are underweight.

In 2013, an estimated 4.5 million deaths worldwide were attributable to overweight and obesity. The identification of new obesity-related cancer sites will add to the number of deaths worldwide attributable to obesity.

“The new evidence emphasizes how important it is to find effective ways, at both the individual and societal level, to implement World Health Organization recommendations on improving diets and physical activity patterns throughout life if the burden of cancer and other noncommunicable diseases is to be tackled,” says IARC Director Dr Christopher Wild.

Rewind: HCV in elderly patients, liver cancer during/after interferon-free therapy and dietary supplements

Rewind: HCV in elderly patients, liver cancer during/after interferon-free therapy and dietary supplements

Hello everyone, here is a look back at this weeks research and headlines.

HCV treatment in elderly patients

Hepatitis C and Aging

Lucinda Porter RN

August 11

The age that hepatitis C was acquired may have an impact on prognosis. A number of studies have reported that individuals who are infected with hep C at older ages tend to have a worse prognosis than those who acquire hep C while young. People over age 40 more likely to develop HCV-related liver cancer. Age can also have a negative impact on liver transplantation survival; older liver transplant recipients have a significantly lower survival rate than younger patients...

Related:

July 27
Battling hepatitis C in the elderly
Plenty of studies have been done globally for younger adults, but seniors have different risk factors and comorbidities, notes an article in Clinical Gastroenterology and Hepatology journal. “Although the safety and efficacy of hepatitis C therapies have been extensively studied in patients between ages of 18 and 65, patients who are over 65 still remain an understudied and difficult to treat population,” the authors write...

July 17
Treatment of Chronic Hepatitis C in the Aged – Does It Impact Life Expectancy? A Decision Analysis
Since currently complications of HCV mostly affect members of the elderly population, they are in urgent need of effective HCV treatment. The approach we suggest for the treatment of patients over 70 with chronic HCV is illustrated in Fig 3. For those patients who have no major co-morbidities, more than moderate fibrosis, and a life expectancy greater than one year, there is a possibility of offering treatment. This needs to be presented to the patient and discussed before a final decision...

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*Commentary on this article is available in the August issue of HCV Advocate.

Fibrosis

Study Explores Marijuana Use and Fibrosis in Women with HIV and Hepatitis C

Aug 12

Catherine Kolonko

A study in women coinfected with hepatitis C and HIV found that use of marijuana was not associated with progression to advanced liver fibrosis...

DEA declines to loosen restrictions on medical marijuana

Aug 12
CNN‎
Marijuana will remain a Schedule l controlled substance, which declares it has "no currently accepted medical use and a high potential for abuse," the Drug Enforcement Administration said Thursday. This keeps the drug in the same category as heroin, LSD and Ecstasy...

Why the US decision to expand marijuana supply for research matters
Aug 12

Policy change could accelerate development of treatments derived from the drug.

Study finds clues to fibrosis progression in chronic HCV infection
Aug 11
Fibrosis progression in hepatitis C virus–infected individuals is not linear, is associated with alanine aminotransferase–related flares, and varies according to stage, with those who are least fibrotic tending to have the highest progression, according to a study...

Facebook

Hemp Fest - A Cry for Help AL/TN

Non-Profit Organization · Iron City, Tennessee

A annual festival to raise money , promote awareness of natural healing plants and support legalization of them. This event is held @ Sycamore campground .

Liver Cancer

Unexpected high incidence of hepatocellular carcinoma in patients with hepatitis C in the era of DAAs: too alarming?
Aug 12

As a terminator of hepatitis C virus (HCV) infection, sofosbuvir-based direct-acting antiviral agent (DAA) regimens have achieved great success in the eradication of HCV in patients with hepatitis C and related end stage liver diseases[[1], [2]]. Recently, we read with interest the studies by Reig et al.[3 and Kozbial et al.[4 on the surprisingly high incidence of hepatocellular carcinoma (HCC) recurrence and occurrence in patients with advanced liver diseases during interferon-free therapy and after sustained virologic response (SVR), respectively. Notably, the time interval between the initiation of DAAs (or SVR) and tumour occurrence is very short. These studies promote the current awareness and understanding of the risk for hepatocarcinogenesis in the era of DAAs. However, similar episodes have not frequently been observed in Chinese patients until now...

Related
Alcohol Intake Increases Risk for HCC in Patients With HCV-Related Cirrhosis
July
Alcohol consumption — including light-to-moderate — was associated with an increased risk for hepatocellular carcinoma among patients with hepatitis C virus infection-related cirrhosis, according to published findings.

Liver Transplant

National proposal aims for fairer liver transplant distribution
August 11, 2016 by Sean D. Hamill, Pittsburgh Post-Gazette
The organization that oversees the nation's transplant system said Wednesday that it believes a new proposal would greatly reduce geographic disparities that make getting a liver transplant harder in some areas of the country and easier in others...

Hospitals are throwing out organs and denying transplants to meet federal standards

Aug 13

Hospitals across the United States are throwing away less-than-perfect organs and denying the sickest people lifesaving transplants out of fear that poor surgical outcomes will result in a federal crackdown..

Healthy You

Video
Is There a Special Diet for Liver Disease Patients?
Aug 10
by Dr. Joe Galati
Probably the most common question I am asked, is regarding a special diet to follow if you have liver problems. Here is an updated answer to these questions...

Aflatoxin Alert: Moldy Nuts and Corn Increases Your Liver Cancer Risk 60-Times If You Have Hepatitis B
August 10

One of the biggest health threats to people living with chronic hepatitis B is a toxic, nearly invisible mold called aflatoxin found in corn, peanuts, peanut butter, almonds, Brazil nuts, walnuts and pistachios. People with hepatitis B who eat food with high levels of aflatoxins face a liver cancer risk that is 60-times above average. In addition to nuts and grains like quinoa, aflatoxin can be found in figs, milk and cheese, soybeans, dried spices and cottonseed. It is less common in rice, as long as rice is hulled, which removes aflatoxin mold.....

​Summertime Foods to Help Hepatitis C
July 28
By Karen Hoyt
When it’s summertime and the weather is high, you need to eat good food to stay strong with hepatitis C. Since the garden goods are easy to find, use this time to...

Herbal and Dietary Supplements

Many liver disease patients use complementary/alternative medicines

Aug 8

Many patients with liver disease use complementary and alternative medicines (CAMs) despite some being potentially hepatotoxic, often don’t tell their healthcare providers.

These were the findings of researchers at Duke University School of Medicine who analysed data from the 2012 [US] National Health Interview Survey. Of 647 adults with liver disease, 41% reported using CAMs in the prior year, compared with 33% of adults without liver disease. The most common modality was herbs and supplements (23%), and 3% of respondents reported consumption of a potentially hepatotoxic substance in the previous 30 days. Only a small proportion of CAM therapies were used specifically for liver disease, with milk thistle being the most common. Among respondents with liver disease, CAMs were used more commonly for anxiety or depression, fatigue, and substance use. The majority believed that these therapies improved health. Nearly one-third of therapies were not reported to healthcare providers, mostly because they don’t ask...
Reference - Complementary and alternative medicine use in United States adults with liver disease. Henson JB, Brown CL, Chow SC et al. J Clin Gastroenterol. 2016 Jul 29. [Epub ahead of print]

FDA Updates Draft Guidance for Dangerous Dietary Supplements
Aug 12
The U.S. Food and Drug Administration issued a revised draft guidance to improve dietary supplement companies’ new dietary ingredient premarket safety notifications to the agency. These notifications help the agency identify safety concerns before products reach consumers...

Related
15 Supplement Ingredients to Always Avoid
July
With the help of an expert panel of independent doctors and dietary-supplement researchers, Consumer Reports identified 15 supplement ingredients that are potentially harmful. The risks include organ damage, cancer, and cardiac arrest. The severity of these threats often depends on such factors as pre-existing medical conditions as well as the quantity of the ingredient taken and the length of time a person has been exposed to the substance....

Liver injury due to herbal and dietary supplements: A review of individual ingredients
Authors Elizabeth Zheng, Victor Navarro

First Published: 27 April 2016 Vol: 7, Pages: 80–83 DOI: 10.1002/cld.541

Often, it is difficult to identify the culprit ingredient that is responsible for liver damage among a multitude of different components within a particular supplement. However, some ingredients have been associated with hepatotoxicity. We aim to review those ingredients that have been implicated in liver injury and, in doing so, give the practitioner a rationale to implicate a supplement containing them as a cause for injury...

Abstract
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Watch the interview with the author

Research - Hepatitis C Therapy

Elbasvir-grazoprevir
August

Elbasvir-grazoprevir works effectively against HCV despite current drug use

New, highly curative hepatitis C therapy is both safe and effective as a treatment option for people who inject drugs receiving opioid substitution therapy according to the results of a world-first clinical trial led by professor Gregory Dore at the Kirby Institute at UNSW Australia and published today in the Annals of Internal Medicine...

NEJM Journal Watch
Elbasvir–Grazoprevir Is Effective in HCV-Infected Patients Who Abuse Drugs
Atif Zaman, MD, MPH reviewing Dore GJ et al. Ann Intern Med 2016 Aug 8.
Ongoing illicit drug use did not reduce adherence to the HCV regimen nor efficacy...

Sofosbuvir, velpatasvir, and GS-9857

July
NEJM Journal Watch

A Regimen for HCV-Infected Patients Who Fail Direct-Acting Antiviral Therapy
Atif Zaman, MD, MPH reviewing Lawitz E et al. Gastroenterology 2016 Jul 30. Gane E et al. Gastroenterology 2016 Jul 30.

Combination fixed-dose sofosbuvir-velpatasvir plus GS-9857 was highly effective in phase II studies.

Although infrequently, direct-acting antiviral agents (DAAs) fail in treating chronic hepatitis C virus (HCV) infection and treatment-induced resistance can develop. Treatment options are limited for this population.

In companion phase II, industry-funded studies, researchers evaluated the safety and efficacy of daily triple therapy with sofosbuvir (an NS5B inhibitor; 400 mg), velpatasvir (a second-generation NS5A inhibitor with a high barrier to resistance; 100 mg), and GS-9857 (an investigational, next-generation NS3/4A protease inhibitor; 100 mg) in treatment-naive and treatment-experienced (i.e., previously failed DAAs) patients with HCV genotypes 1–6 infections.

In one open-label trial involving 197 HCV genotype 1 patients, all treatment-naive patients without cirrhosis who received 8 weeks of triple therapy achieved sustained virologic response at 12 weeks posttreatment (SVR12). Among treatment-naive patients with cirrhosis, treated for 8 weeks, SVR12 rates were 81% with added weight-based ribavirin and 94% without ribavirin. A small cohort without cirrhosis receiving 6 weeks of therapy achieved an SVR12 of 71%. Treatment-experienced patients with or without cirrhosis received 12 weeks of triple therapy, and all achieved SVR12.

Another open-label trial involved 128 patients with different HCV genotypes (58% genotype 3, 26% genotype 2). Among treatment-naive patients without cirrhosis, who received 6 weeks of triple therapy, SVR12 was 88%; among those with cirrhosis, treated for 8 weeks, SVR12 was 93%. Among treatment-experienced patients with or without cirrhosis, who received therapy for 12 weeks, SVR12 was 100% with cirrhosis and 97% without.

In both studies, the most common adverse effects were headache, fatigue, nausea, and diarrhea. Discontinuation rates due to adverse events were ≤2%.

Comment
This triple-DAA regimen was highly effective across HCV genotypes when given for 8 weeks in treatment-naive patients and 12 weeks in treatment-experienced patients with and without cirrhosis. A 6-week regimen was less effective, and adding ribavirin added no benefit. If subsequent phase III trials produce similar results, we might soon have a simple and effective 8–12-week regimen that is pangenotypic and ribavirin-free.

Note to readers: At the time NEJM Journal Watch reviewed these papers, their publisher noted that they were not in final form and that subsequent changes might be made.

Editor Disclosures at Time of Publication
Disclosures for Atif Zaman, MD, MPH at time of publication Nothing to disclose

Citation(s):
Lawitz E et al. Efficacy of sofosbuvir, velpatasvir, and GS-9857 in patients with genotype 1 hepatitis C virus infection in an open-label, phase 2 trial. Gastroenterology 2016 Jul 30; [e-pub]. (http://dx.doi.org/10.1053/j.gastro.2016.07.039)

Full Text PDF download

Gane E et al. Efficacy of sofosbuvir, velpatasvir, and GS-9857 in patients with HCV genotype 2, 3, 4, or 6 infections in an open-label, phase 2 trial. Gastroenterology 2016 Jul 30; [e-pub]. (http://dx.doi.org/10.1053/j.gastro.2016.07.038)

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GS-9857 in Patients With Chronic Hepatitis C Virus Genotype 1–4 Infection
A Randomized, Double-blind, Dose-ranging Phase 1 Study
In summary, administration of multiple doses of GS-9857 was well tolerated and resulted in a robust decline of HCV RNA levels in patients with genotype 1–4 HCV infection. Notably, the potent antiviral activity of GS-9857 was preserved in the presence of commonly observed NS3 mutations associated with resistance to protease inhibitors. GS-9857 demonstrated linear PK when administered at doses ranging from 50 to 300 mg under fasting conditions. The median half-life of GS-9857 ranged from 29 to 42 h, conducive to once-daily dosing. Lastly, GS-9857 has demonstrated additive antiviral activity when evaluated in vitro in combination with sofosbuvir or velpatasvir.^[5] Together, these data support the further development of once-daily GS-9857 in combination with other DAAs for the treatment of patients with chronic HCV infection....

Hepatitis outlook: July 2016

By: RICHARD PIZZI

Aug 3

If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.

In Case You Missed It

HCV Therapy of Genotype 3: Is It Still a Challenge?
Published on 07/22/2016
By Ramakrishna Behara and Nancy Reau
Hepatitis C genotype 3 accounts for 30 percent of all infections secondary to hepatitis C and is the second most common genotype worldwide, behind genotype 1. Estimates report that in the U.S., it accounts for 8 to 13 percent of infections. Historically, genotype 3 has been uniquely challenging to manage in large part due to lower response to therapy combined with high rates of steatosis, fibrosis progression and a disproportionately high rate of hepatocellular carcinoma. With the launch of the first wave of interferon-free treatment, many of the direct-acting antivirals (DAA) had higher overall sustained virologic response (SVR) to genotype 3 but did not compare to the SVR rate for treatments approved for genotype 1. Thus, recent drug development has focused on pan-genotypic agents to equalize efficacy across all genotypes...

Weekend Video

A cure at what cost? More states easing restrictions on Hepatitis C treatments  
Published on Aug 12, 2016

NewsWorks

The new Hepatitis C drugs have come with a big catch: the price tag. It's difficult to know the exact cost — public and private payers negotiate private agreements with drug companies — but one of the main drugs, Sofosbuvir (the brand name is Sovaldi), has been listed at $1,000 a pill before discounts. It's taken once a day for up to three months, often in combination with other drugs, making the cost of a cure upwards of $100,000.

Have a safe and healthy weekend.

Tina

Direct-acting antivirals in hepatitis C do not reduce hepatocellular carcinoma occurrence

Lauren Biscaldi

Assistant Digital Content Editor

Clinical Advisor                       

Direct-acting antivirals in hepatitis C do not reduce hepatocellular carcinoma occurrence
Patients with HCV-related cirrhosis treated with direct-acting antivirals (DAA) do not have reduced rates of hepatocellular carcinoma (HCC), according to research published in the Journal of Hepatology.

Fabio Conti, MD, PhD student, Research Center for the Study of Hepatitis, Department of Medical and Surgical Sciences, University of Bologna, Italy, and colleagues analyzed 344 cirrhotic patients without HCC who had been treated with DAA; of these patients, 59 had previous HCC. Patients were followed for 24 weeks.

During the 24-week follow-up, 26 patients had HCC; 17 of 59 patients had previous HCC, and 9 of 285 patients did not. Among the 59 patients with previous HCC, younger age and severe liver fibrosis were significantly associated with HCC recurrence.

“Child-Pugh Class B, more severe liver fibrosis, lower platelet count, and previous HCC were significantly associated with HCC development,” said Dr Conti. “In patients with HCV-related cirrhosis, DAA-induced resolution of HCV infection does not seem to reduce the occurrence of HCC, and patients previously treated for HCC still have a high risk of tumor recurrence in the short term.”
Reference

Conti F, Buonfiglioli F, Scuteri A, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct acting antivirals. J Hepatol. 2016; pii:S0168-8278(16)30303-8; doi: 10.1016/j.jhep.2016.06.015. Epub ahead of print.

Journal of Hepatology

Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct acting antivirals

Abstract
Background & Aims
Hepatocellular carcinoma (HCC) represents a serious complication of HCV-related cirrhosis. New direct-acting antivirals (DAA) cure HCV infection in over 90% of patients. Aim of this study was to evaluate the early occurrence and recurrence of HCC in cirrhotic patients treated with DAA.
Methods

We analysed 344 consecutive cirrhotic patients, without HCC, who were treated with DAA, and followed for 24 weeks. Fifty-nine patients had previous HCC.
Results

DAA therapy induced sustained virological response in 91% of patients. During 24-week follow-up, HCC was detected in 26 patients (7.6%, 95% CI: 4.99-10.84): 17 of 59 patients (28.81%, 95% CI: 17.76-42.07) with previous HCC and 9 of 285 patients (3.16%, 95% CI: 1.45-5.90) without previous HCC. Child-Pugh Class B, more severe liver fibrosis, lower platelet count, and previous HCC were significantly associated with HCC development, at univariate analysis. At multivariate analysis, Child Pugh class (p= 0.03, OR: 4.18, 95% CI: 1.17-14.8) and history of HCC (p< 0.0001, OR: 12.0, 95% CI: 4.02-35.74) resulted independently associated with HCC development. Among the 59 patients with previous HCC, younger age and more severe liver fibrosis were significantly associated with HCC recurrence, both at univariate and at multivariate analysis.

Conclusions
In patients with HCV-related cirrhosis, DAA-induced resolution of HCV infection does not seem to reduce occurrence of HCC, and patients previously treated for HCC have still a high risk of tumour recurrence, in the short term. For these reasons, all cirrhotic patients should be closely monitored and followed during and after antiviral therapy.

Lay Summary
New direct-acting antivirals are able to eradicate HCV infection in over 90% of patients with advanced liver disease. Unfortunately, the occurrence of liver cancer is not reduced in effectively treated cirrhotic patients. In addition, patients previously treated for HCC have still a high risk of tumour recurrence in the short term, despite DAA treatment.

Blood-born molecules could predict those who will develop liver cancer

Blood-born molecules could predict those who will develop liver cancer

(PHILADELPHIA) - Hepatocellular carcinoma, the most common type of liver cancer, is increasing in incidence in the United States, and infection with the Hepatitis B virus (HBV) causes about 50 percent of cases. However, it can be difficult to identify who is most likely to develop this cancer. Although earlier research had discovered molecular signatures associated with HBV-driven liver cancer, new research from Thomas Jefferson University has proven that this panel of microRNAs can also predict the patients at high risk for developing the disease before the cancer develops, via a blood test.

The researchers, led by Hushan Yang, Ph.D., an Associate Professor of Medical Oncology and researcher at the Sidney Kimmel Cancer Center at Jefferson studied a large cohort of HBV-infected patients, some of whom eventually developed liver cancer, and analyzed their molecular signature from blood samples. Of the 373 HBV patients who were originally cancer free, 40 developed cancer over a median follow up of 4.5 years. The researchers analyzed a panel of 24 microRNAs -- small molecules that regulate gene activity -- and showed that 15 of these microRNAs had changed their normal gene expression pattern before patients developed cancer, suggesting these molecules could be used to predict patients with a high likelihood of developing cancer. The study was published in the journal Oncotarget,

Earlier studies had identified the 24 microRNAs that Dr. Yang and colleagues studied. However, it was unclear whether those microRNAs caused the cancer, or were a result of already occurring cancerous processes. By following this cohort of patients prospectively, and using blood samples taken at least one year before liver cancer diagnosis, the researchers were able to answer that question for the first time. In addition, prior studies analyzed samples taken from patient biopsies, which require invasive procedures, whereas the current study showed that microRNAs circulating in the blood could predict disease.

"This research confirms previous work on microRNAs and liver cancer and goes further to show that these microRNAs may be able to predict the development of liver cancer through a non-invasive blood test," says first author Chun Wang, a visiting scholar in the Department of Medical Oncology.

The current non-invasive test for determining cancer risk among HBV patients is a diagnostic for the molecule alpha-fetoprotein (AFP). It is also associated with Hepatitis C infections, but it isn't always a good predictor of disease. In fact, the Jefferson researchers identified 15 out of 16 patients, or 94 percent of patients who were misclassified as cancer-free by AFP. Likewise, in the 57 patients who were deemed at high risk of developing liver cancer by AFP, the microRNA testing correctly reclassified 33, or 58 percent, as low risk.

Although the panel of 15 microRNAs was useful, it wasn't perfect. "We need to find more microRNAs that may predict liver cancer in order to sharpen this tool for identifying high risk patients," says Dr. Yang. "Through collaboration with Dr. Hann in the Department of Medicine at Jefferson, we continue to work on improving this diagnostic method."

The work was supported by a Tobacco Grant from the Pennsylvania Department of Health, National Cancer Institute Grant CA159047, American Cancer Society Research Scholar Grant 123741-RSG-13-003-01-CCE, and a V Scholar Grant from the V Foundation for Cancer Research. The authors report no conflicts of interest.

Source: Thomas Jefferson University

FDA Grants Fast Track Designation to Can-Fite's CF102 in the Treatment of Liver Cancer

U.S. Food and Drug Administration Grants Fast Track Designation to Can-Fite's CF102 in the Treatment of Liver Cancer

PETACH TIKVA, Israel, Sept. 17, 2015 /PRNewswire/ -- Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory and cancer diseases, today announced the U.S. Food and Drug Administration (FDA) has granted the Company's drug candidate CF102 Fast Track designation as a second line treatment for hepatocellular carcinoma (HCC), the most common form of liver cancer. CF102 had already received the FDA's Orphan Drug designation.

Can-Fite is currently conducting a Phase II study for this indication in the U.S., Europe and Israel. The randomized, double blind, placebo controlled study is expected to complete enrollment by the end of the first half of 2016 in 78 patients with Child-Pugh Class B cirrhosis who failed the only FDA approved drug on the market, Nexavar® (sorafenib). Patients are treated twice daily with 25 mg of oral CF102, which has been found to be the most efficacious dose in Can-Fite's earlier Phase I/II study resulting in the longest overall survival time, with excellent safety results.

Fast Track, aimed at getting important new drugs that meet an unmet need to patients earlier, is expected to expedite the development of CF102. Drugs that receive Fast Track designation benefit from more frequent meetings and communications with the FDA to review the drug's development plan to support approval. It also allows the Company to submit parts of the New Drug Application (NDA) on a rolling basis for review as data becomes available. Since the Fast Track Program started, from March 1998through June 30, 2015 a total of 318 Fast Track applications have been received by the FDA. The FDA has granted 202 of them, and denied 110, with 6 more pending.

"We are very pleased that the FDA recognizes the potential for CF102 to treat HCC patients who have tried, and not been responsive to Nexavar, the only FDA approved drug currently on the market for this indication," stated Can-Fite CEO Dr. Pnina Fishman. "We consider Fast Track designation to be a major catalyst for our CF102 development program and we believe it could shorten our time to market for CF102, thereby making a considerable difference for patients."

According to Global Industry Analysts, the global market for liver cancer drugs is projected to exceed $2 billion in 2015. Nexavar® annual sales, as reported by Bayer, were €773 million in 2014.

About CF102
CF102 is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). A3AR is highly expressed in tumor cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug. In Can-Fite's pre-clinical and clinical studies, CF102 has demonstrated a robust anti-tumor effect via deregulation of the Wnt signaling pathway, resulting in apoptosis of liver cancer cells.

Steroid Use and Liver Cancer

Anabolic steroids have their legitimate uses, but abusing them can bring on a variety of health problems - some of which are connected to liver cancer.


Although well-documented reports linking steroids to liver cancer are rare, as more athletes use drugs to improve their performance or build their bodies, many types of dangerous side effects from the abuse of anabolic steroids are becoming known — and events are becoming more frequent.

Recently, there have been many instances in the news about famous athletes and performance-enhancing drugs, sometimes referred to as "doping." In most cases, the drugs that are being used are anabolic steroids. These drugs are manufactured steroids that behave like the male hormone testosterone. In the United States, it is illegal to use anabolic steroids without a prescription.

"Anabolic steroids are male-related hormones that can be used to increase muscle mass. When these drugs are abused they can have many side effects, including liver damage.

Liver Cancer: What Anabolic Steroids Can Treat

Anabolic steroids, under a doctor's prescription, will treat certain conditions in which increasing bone strength and muscle mass are required for health reasons. These medications can be helpful in the following types of cases:

    Delayed puberty
    Testosterone deficiency
    AIDS-related weakness

Liver Cancer: Anabolic Steroid-Related Liver Damage

Liver damage from anabolic steroids can cause a condition called cholestasis. With this condition, bile, a digestive fluid made in your liver, cannot get to where it needs to go and leaks out into your blood. Symptoms include:

    Itching
    Nausea
    Loss of appetite
    Dark urine
    Jaundice — the yellow discoloration of your eyes and skin

Damage to the liver is evident when enzymes called aminotransferases leak out of damaged liver cells into your bloodstream.

Another important point about anabolic steroids: They can be addictive. These steroids can cause steroid craving that leads to the need for more frequent and higher drug doses. Liver damage has been shown to be related to the cumulative effects of higher and more frequent use.

Liver Cancer: Can Anabolic Steroids Cause It?

Reports exist showing a slightly increased risk of developing liver cancer with long-term use of high-dose anabolic steroids. However,  the scientific evidence supporting a cause-and-effect relationship is weak.

But these steroids are known to cause tumors that form in your liver. Called hepatic adenomas, these tumors are not cancerous. However, they are dangerous because they can rupture and cause serious bleeding in the liver. There have been several reported deaths caused by bleeding from ruptured hepatic adenomas. The link between hepatic adenomas and anabolic steroid use in athletes is increasing. Recently, a case of a hepatic adenoma turning into liver cancer was reported.

Liver Cancer: Anabolic Side Effects

While there is not a strong link between liver cancer and anabolic steroids, there is strong evidence for serious liver damage. Other side effects of anabolic steroids include:

    High blood pressure
    Increased levels of bad cholesterol
    Mood swings
    Aggressive behavior
    Infertility in men
    Menstrual abnormalities in women

If you are an athlete or a body-builder and you are tempted to use anabolic steroids, consider that besides the legal and social risks involved, these drugs can and do cause life-theatening medical complications.