Showing posts with label liver cancer. Show all posts
Showing posts with label liver cancer. Show all posts

Monday, October 15, 2018

Liver Cancer Treatment Paradigm Undergoing Major Overhaul

Liver Cancer Treatment Paradigm Undergoing Major Overhaul
Christine Lehmann, MA
Published Online: Oct 15,2018

Until recently, few systemic therapies had been approved for the treatment of patients with liver cancer, as few agents could demonstrate significant benefit over placebo. Sorafenib (Nexavar) was the first systemic therapy that extended median overall survival (OS) over placebo by nearly 3 months (10.7 versus 7.9 months),1 and, in December 2007, it became the first systemic therapy approved by the FDA for patients with unresectable hepatocellular carcinoma (HCC).

Read the article:

Blog & News Updates: Link between viral hepatitis and liver cancer?

Save The Date
October 16th, 3 p.m. EST
In honor of Liver Cancer Awareness Month we have a few news and blog updates to share with you. On Tuesday, October 16th, join Hepatitis B Foundation for a Twitter chat to discuss the link between hepatitis and liver cancer. Representatives from Hepatitis B Foundation, CDC’s Division of Viral Hepatitis, and NASTAD will co-host the chat at 3 p.m. EST.

In addition check out this years Liver Cancer Awareness Campaign aimed at encouraging individuals with an increased risk for liver cancer to receive ongoing screening, launched by the American Liver Foundation (ALF) and Bayer Healthcare. Find out if you're at risk for liver cancer.

October 23, 2018 2:00 p.m. to 3:00 p.m. EST 

Webinar
Timothy M. Block, Ph.D.President and Director, Baruch S. Blumberg Institute and the Hepatitis B Foundation
Read More

November 29, 2018 (1:00-2:30 pm ET)
Strategies to Eliminate HCV in Veterans Webinar November 29
Join NVHR on November 29, 2018 (1:00-2:30 pm ET) for a webinar to discuss how government and community organizations are working to treat Veterans living with hepatitis C.
Read More

Blog & Journal Updates Around The Web
Oct 15, 2018 
Liver Cancer Awareness Month
• By Lucinda K. Porter, RN
While the incidence of most cancers are declining in the United States, the rate of hepatocellular carcinoma (HCC or liver cancer) is increasing. More than 40,000 people in this country will be diagnosed this year with primary liver cancer, facing a 5-year survival rate of only 18 percent. According to the National Cancer Institute, liver cancer is the fifth leading cause of cancer death. Worldwide, it is the second leading cause of cancer death.
Read More

Oct 14, 2018
VA Continues Hepatocellular Screening, but Study Questions the Value
by Annette Boyle 
SAN FRANCISCO—Although a recent study determined that screening veterans with cirrhosis for hepatocellular carcinoma did not reduce the risk of death associated with liver cancer, the VA has no plans to change its screening practices.

“The VA currently follows the American Association for the Study of Liver Diseases (AASLD) guidelines for HCC screening among patients with cirrhosis,” explained Maggie Chartier, PsyD, MPH, the VA’s deputy director of HIV, Hepatitis and Related Conditions and associate professor at the University of California, San Francisco. The AASLD recommends screening patients with cirrhosis for HCC using ultrasound (USS) with or without serum alpha fetoprotein measurement every six months
Read More

Oct 10, 2018
..positive impact on HRQoL with improvement in mobility, pain/discomfort, anxiety/depression...

Oct 9, 2018
Paul E. Sax, MD
There’s so much going on no one can cover it all, certainly not me. So here’s a sampling of some (emphasis on some) of the interesting research presentations from last week, a “Mini” Really Rapid Review™ of the conference. Use the comments section to chime in with your favorites.

Oct 9, 2018
What support do people with liver cirrhosis and their families need?
People with liver cirrhosis and their families need more information about their condition and prognosis and greater access to palliative care, a systematic review of studies on the needs of people with cirrhosis of the liver has concluded.

Oct 9, 2018
Malnutrition decreases quality of life, social function in cirrhosis
PHILADELPHIA — Malnutrition as measured by subjective global assessment correlated significantly with decreased health-related quality of life in patients with…

Do you know that the liver doesn’t have any nerve cells? Here are some facts about this amazing organ in honor of Liver Awareness Month...

Alcohol and Increased Cirrhosis-related Deaths
Many of us are well aware that excessive (particularly long-term) consumption of alcohol is not good for our body — and is especially not friendly to our liver. But a newly published research study might very well convince us that the effects of alcohol on our liver health are even worse than we may have initially imagined. What’s the sobering research finding? The likelihood that increased cirrhosis-related mortality rates from 1999 to 2016 may be due to alcohol abuse and alcohol-induced liver disease...

Hepatitis C affects more than just the liver- it can affect many parts of the body, and mental wellbeing... 

Stress is not good for any of us, it can lead to serious health issues and depression. Stress is the..

In a pilot study from the October issue of Clinical Gastroenterology and Hepatology, colony stimulating factor 3 (CSF3, also called GCSF) improved liver function and increased survival times in patients with severe alcohol-associated hepatitis (AH), compared with standard therapy. Addition of N-acetyl cysteine (NAC) to GCSF did not improve patient outcomes... 

To all of you with gluten intolerance, first, let me say: I’m sorry. You’re looking for good food for celiac and liver disease. I worked in the kitchen and saved my life with The Liver Loving Diet, I had no idea what celiac was....

In The News
HepCBC - Weekly Review
Here's the latest issue of the Weekly Bull.

Oct 15, 2018
Liver Cancer Treatment Paradigm Undergoing Major Overhaul

Oct 15, 2018
Study Casts Doubt on Connection Between DAAs and Liver Cancer Risk
“There are no significant differences between DAA regimens in HCC risk after antiviral treatment,” concluded the authors, led by Elijah J. Mun, MD, of the University of Washington.

Oct 10, 2018
Hepatitis C - Vosevi safe, effective in ‘triple-infected’ patients with HCV, HBV, HIV
PHILADELPHIA – The direct-acting antiviral Vosevi demonstrated an average sustained virologic response rate of 87% among patients who were “triple-infected” with hepatitis C genotype 3, hepatitis B and HIV, as presented at the American College of Gastroenterology Annual Meeting.

By Nguyen Quy October 8, 2018 
A report by the World Cancer Research Fund International, a leading organization on cancer-prevention research related to diet, nutrition and physical activity, ranks Vietnam fourth among 25 countries with the highest rates of liver cancer this year. The report is based on the latest statistics from Globocan, an interactive web-based platform with cancer statistics from 185 countries....

Mass. General-led study supports ability of regular aspirin use to reduce liver cancer risk
The results of a study led by Massachusetts General Hospital (MGH) investigators support evidence from previous studies suggesting the regular use of aspirin can reduce the risk of developing primary liver cancer – also called hepatocellular carcinoma (HCC). Their report analyzing data from two long-term epidemiologic studies appears in JAMA Oncology and finds that regular aspirin use – taking two or more 325 mg tablets a week for five years or more – led to a significantly reduced risk of developing HCC, which is the second leading cause of cancer death worldwide...

"Compelling" evidence of link between aspirin use, lower hepatoma risk
NEW YORK (Reuters Health) - Regular, long-term use of aspirin is associated with a reduced risk of developing hepatocellular carcinoma (HCC), according to pooled data from more than 133,000 people. "Animal studies have shown that aspirin can block primary liver cancers from developing. Although these studies have been promising, data in humans have been limited," said Dr. Andrew Chan from Massachusetts General Hospital, in Boston.

Scientists use CRISPR to treat genetic liver diseases in neonatal and adult mice
by Arlene Weintraub
The newest issue of the journal Nature Medicine features two animal studies that show progress is being made towards achieving the holy grail of gene editing: the ability to prevent or treat diseases that are caused by gene mutations. In both cases, the researchers used modified versions of CRISPR-Cas9, the most commonly used gene-editing system.

Recommended reading

Evidence does not support statin use for conditions other than heart …
Despite studies suggesting benefits for conditions beyond cardiovascular disease (CVD), the evidence does not support revising current statin …

Early liver disease detection during pregnancy key for improved outcomes
October 7, 2018
PHILADELPHIA — Early detection of liver-related complications and hepatic diseases in patients who are pregnant leads to reduced risks and improved outcomes for…

NAFLD has ‘bidirectional’ course in patients with type 2 diabetes
October 8, 2018
PHILADELPHIA – Nonalcoholic fatty liver disease may have a “bidirectional” nature in patients with type 2 diabetes as NAFLD regressed in 2.2% of patients without any NAFLD-specific interventions despite increase in the prevalence of risk factors, according to a presentation at the American College of Gastroenterology Annual Meeting.

Obesity, Weight Gain Linked to Fibrosis Progression in NAFLD
Medscape Medical News 
October 4, 2018
Obesity and weight gain are independently associated with an increased risk for fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD), a large cohort study has found. Weight loss was negatively associated with fibrosis progression...

At-Risk Teens and Young Adults Overlooked During Opioid Crisis Too Few Tested for Hepatitis C, Research Suggests 
SAN FRANCISCO – Teens and young adults who have injected drugs are at risk for contracting hepatitis C, but most aren’t tested and therefore don’t receive life-saving treatment, according to a national study being presented at IDWeek 2018. The study of more than 250,000 at-risk youth found only one-third of those with diagnosed opioid use disorder (OUD) were tested for hepatitis C...

NEW YORK (Reuters Health) - The risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) treated with tenofovir is lower than in those treated with entecavir, according to a nationwide study from South Korea. "Patients with CHB have about 1% risk of developing HCC," Dr. Young-Suk Lim from the University of Ulsan College of Medicine, in Seoul, told Reuters Health by email. "Once diagnosed with HCC, the overall prognosis of the patients is very poor, with 5-year survival rate of less than 30%. Therefore, prevention of HCC is of utmost importance in the management of CHB patients."

Healthy You
October 13, 2018
Dietary Supplements Can Contain Viagra, Steroids, or Worse
October 13, 2018
You know those sexual enhancement dietary supplements for sale at gas stations and markets across the country? Beware, they might actually be viagra. Or steroids. Or an antidepressant. Many supposed dietary supplements for weight loss, erectile dysfunction, and muscle building may contain actual pharmaceuticals—but you likely have no way of knowing what's in them...

October 13, 2018
Weekend Reading - Baby Boomers and the Flu
Did you know that you are more susceptible to flu-related complications if you're over 65, living with chronic liver disease, or viral hepatitis?

Recommended Reading
How Many Cases of Drug-Induced Liver Injury Are Caused by Herbal and Dietary Supplements?
September 2018
Herbal and dietary supplement-induced liver injury is more severe than other types of drug-induced liver injury (DILI), and re-exposure is more likely, researchers report in the September issue of Clinical Gastroenterology and Hepatology. Increasing awareness of the hepatoxic effects of herbal and dietary supplements could help physicians make earlier diagnoses
Read more

Recent Updates
Online learning activity
Screening and Diagnosis of Hepatitis C Infection
Topics; HCV Transmission FAQs, Risk Factors for Acquiring HCV, HCV Disease Burden and more...

Twitter Updates
Open To All
Watch the open access webcasts from #EASL #NAFLDsummit on : https://bit.ly/2NsZkzZ 

Check back for updates!
Tina

Study Casts Doubt on Connection Between DAAs and Liver Cancer Risk

Study Casts Doubt on Connection Between DAAs and Liver Cancer Risk
OCTOBER 15, 2018
Jared Kaltwasser

“There are no significant differences between DAA regimens in HCC risk after antiviral treatment,” concluded the authors, led by Elijah J. Mun, MD, of the University of Washington.

The finding is significant because it suggests that hepatocellular carcinoma risk does not need to be a determining factor in which DAA a physician prescribes. However, the authors say the takeaway from the study can extend even beyond the question of whether any particular DAA therapy is worse than another when it comes to cancer risk. They argue their study suggests DAAs broadly don’t increase the risk of hepatocellular carcinoma

On This Blog
Sift through current Liver Cancer and Hepatitis C research articles

Liver Cancer After Treatment For Hepatitis C:
Research demonstrates that while SVR markedly reduced liver-related complications and liver cancer, some long-term risk for liver cancer remained in those who were cured of Hepatitis C. But after direct-acting antiviral therapy does the risk of developing liver cancer increase? Research is saying no, check out an index of articles here..... 

Wednesday, October 10, 2018

Current noninvasive liver reserve models do not predict histological fibrosis severity in hepatocellular carcinoma

Nature Research Journal - Scientific Reports
Current noninvasive liver reserve models do not predict histological fibrosis severity in hepatocellular carcinoma 
Shu-Yein Ho , Po-Hong Liu, Teh-Ia Huo

...No study to date has specifically evaluated the relationship and accuracy between noninvasive liver reserve models and the severity of liver fibrosis in HCC. We aimed to investigate the correlation of the currently used noninvasive liver function models and histological fibrosis in HCC patients undergoing surgical resection...

Abstract
The Ishak scoring system has been used to stage liver fibrosis. Ten noninvasive liver reserve models were proposed to assess the severity of liver fibrosis, but their performance in hepatocellular carcinoma (HCC) is unknown. We aimed to evaluate the correlation between these models and severity of fibrosis in patients with HCC. A total 464 patients with HCC undergoing surgical resection were retrospectively analyzed. Multivariate logistic regression analysis was performed to determine independent factors associated with advanced fibrosis (Ishak score 4 or higher). There were no significant correlations between all noninvasive models and severity of fibrosis in HCC (p for trend all >0.1). In subgroup analysis, cirrhosis discriminant index (CDS) and Lok’s index in hepatitis B-, and fibrosis index based on 4 factors (FIB-4), CDS and Lok’s index in hepatitis C-associated HCC, best correlated with the severity of liver fibrosis. Low platelet count, prolonged prothrombin time, hepatitis C and multiple tumors were independently associated with advanced fibrosis. Among the 10 models, CDS was the best model to predict cirrhosis. Currently used noninvasive liver reserve models do not well correlate with severity of histological fibrosis in HCC. New noninvasive models are required to improve the predictive accuracy of liver fibrosis in HCC.

Read the full-text article:

Saturday, October 6, 2018

Genetic Variations Linked to Hepatocellular Carcinoma: Personalized Medicine Takes a Step Forward


Genetic Variations Linked to Hepatocellular Carcinoma: Personalized Medicine Takes a Step Forward 

Parul D. Agarwal MD & Michael R. Lucey MD
The American Journal of Gastroenterology (2018)

Hepatocellular carcinoma (HCC) remains a major global health problem, and is the third leading cause of cancer-related mortality worldwide. The vast majority of HCC emerges against the background of cirrhosis, often related to infection with chronic viral hepatitis, including hepatitis B and hepatitis C viral infection, which account for approximately 54% and 31%, respectively, of HCC cases worldwide [1]. The prevalence of HCC varies geographically, with the highest occurrences in Southeast Asia and sub-Saharan Africa, mirroring the endemic high prevalence of chronic viral hepatitis in these countries. In the West, cirrhosis related to both alcohol-associated and non-alcohol-associated steatohepatitis (NASH) represent common etiological pathways for development of HCC. Patients with alcohol-associated cirrhosis have an estimated risk of developing HCC of 1–2% annually [2]. Other factors, including older age, male sex, obesity and diabetes mellitus, and environmental exposure to aflatoxin represent additional independent predictors for development of HCC in cirrhosis [2].

However, up to recently, it has been a relative mystery why some patients with risk factors, such as excessive consumption of alcohol, progress to cirrhosis, whereas others with a similar risk profile do not; and similarly, why HCC arises in some but not most persons with cirrhosis. The mystery has started to clear since the completion of the human genome project was completed in 2003, with greater understanding of the role of inherited factors in the pathogenesis of cirrhosis and of HCC. The study of Stickel et al. [3] in the present edition of AJG is a valuable addition to this literature.

Epidemiology and Elimination of HCV-Related Liver Disease

In Case You Missed It

Received: 1 September 2018 / Accepted: 3 October 2018 / Published: 6 October 2018 
Viruses 2018, 10(10), 545; doi: 10.3390/v10100545

Review 
Epidemiology and Elimination of HCV-Related Liver Disease 
Pierre Pradat , Victor Virlogeux and Eric Trépo

Abstract:
Hepatitis C virus (HCV) infection, defined by active carriage of HCV RNA, affects nearly 1.0% of the worldwide population. The main risk factors include unsafe injection drug use and iatrogenic infections. Chronic HCV infection can promote liver damage, cirrhosis and hepatocellular carcinoma (HCC) in affected individuals. The advent of new second-generation, direct-acting antiviral (DAA) agents allow a virological cure in more than 90% of treated patients, and therefore prevent HCV-related complications. Recently, concerns have been raised regarding the safety of DAA-regimens in cirrhotic patients with respect to the occurrence and the recurrence of HCC. Here, we review the current available data on HCV epidemiology, the beneficial effects of therapy, and discuss the recent controversy with respect to the potential link with liver cancer. We also highlight the challenges that have to be overcome to achieve the ambitious World Health Organization objective of HCV eradication by 2030.

Read full-text article online

On This Blog
Sift through current Liver Cancer and Hepatitis C research articles

Liver Cancer After Treatment For Hepatitis C: 
Research demonstrates that while SVR markedly reduced liver-related complications and liver cancer, some long-term risk for liver cancer remained in those who were cured of Hepatitis C. But after direct-acting antiviral therapy does the risk of developing liver cancer increase? Research is saying no, check out an index of articles here..... 

Also see; HCV Newsletters & Blog Updates

Thursday, October 4, 2018

Lower liver-cancer risk seen with tenofovir treatment of chronic hepatitis B

Lower liver-cancer risk seen with tenofovir treatment of chronic hepatitis B
Last Updated: 2018-10-04

By Will Boggs MD
NEW YORK (Reuters Health) - The risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) treated with tenofovir is lower than in those treated with entecavir, according to a nationwide study from South Korea.

"Patients with CHB have about 1% risk of developing HCC," Dr. Young-Suk Lim from the University of Ulsan College of Medicine, in Seoul, told Reuters Health by email. "Once diagnosed with HCC, the overall prognosis of the patients is very poor, with 5-year survival rate of less than 30%. Therefore, prevention of HCC is of utmost importance in the management of CHB patients."

Entecavir and tenofovir disoproxil fumarate (TDF), first-line antiviral agents for CHB infection, have similar efficacy for intermediate-term virologic, biochemical, serologic and histologic outcomes. Their relative efficacy in reducing HCC risk remains uncertain.

During follow-up, the incidence of HCC was significantly lower in the tenofovir group (0.64 per 100 person-years) than in the entecavir group (1.06 per 100 person-years), the researchers report in JAMA Oncology, online September 27....

Read the complete article here: 

In The Journal
JAMA Oncology, online September 27:
doi:10.1001/jamaoncol.2018.4070

Editorial
doi:10.1001/jamaoncol.2018.4039 

Monday, October 1, 2018

Hepatocellular carcinoma treatment: hurdles, advances and prospects

Hepatic Oncology
Ahead of Print

Review
Hepatocellular carcinoma treatment: hurdles, advances and prospects 
Ratna Kumari, Manoj Kumar Sahu, Anindita Tripathy, Kanishka Uthansingh & Manas Behera Published Online:28 Sep 2018
https://doi.org/10.2217/hep-2018-0002

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related mortality and is particularly refractory to the available chemotherapeutic drugs. Among various etiologies of HCC, viral etiology is the most common, and, along with alcoholic liver disease and nonalcoholic steatohepatitis, accounts for almost 90% of all HCC cases. HCC is a heterogeneous tumor associated with multiple signaling pathway alterations and its complex patho-physiology has made the treatment decision challenging. The potential curative treatment options are effective only in small group of patients, while palliative treatments are associated with improved survival and quality of life for intermediate/advanced stage HCC patients. This review article focuses on the currently available treatment strategies and hurdles encountered for HCC therapy. The curative treatment options discussed are surgical resection, liver transplantation, and local ablative therapies which are effective for early stage HCC patients. The palliative treatment options discussed are embolizing therapies, systemic therapies, and molecular targeted therapies. Besides, the review also focuses on hurdles to be conquered for successful treatment of HCC and specifies the future prospects for HCC treatment. It also discusses the multi-modal approach for HCC management which maximizes the chances of better clinical outcome after treatment and identifies that selection of a particular treatment regimen based on patients’ disease stage, patients’ ages, and other underlying factors will certainly lead to a better prognosis.

Future perspective
The review presents an overview of treatment approaches available for early, intermediate, and advanced stage of HCC patients. Additionally, it summarizes hurdles to be encountered and future prospects for HCC treatment. As screening and surveillance has improved the diagnosis of HCC patients at early stages so curative treatments could be a potential therapeutic option in future for HCC patients. So improving over the barriers of liver transplantation has enormous potential, like use of cell therapies. On the other hand, the treatment of intermediate/advanced stage HCC in future would greatly be affected by targeting potential new molecules like HIf-1α and RAAS pathway.

Friday, September 28, 2018

Hepatocellular carcinoma among US and non-US-born patients with chronic hepatitis B: Risk factors and age at diagnosis

Research Article

Hepatocellular carcinoma among US and non-US-born patients with chronic hepatitis B: Risk factors and age at diagnosis 
Kaitlyn Kennedy, Susan M. Graham, Nayan Arora, Margaret C. Shuhart, H. Nina Kim
Published: September 25, 2018
https://doi.org/10.1371/journal.pone.0204031

Full-text
Download PDF
View Online 

Abstract
Background
Risk factors for hepatocellular carcinoma (HCC) have not been well characterized among African immigrants with chronic hepatitis B virus (HBV) infection. We conducted a case-control study to identify demographic and clinical factors associated with HCC among a diverse cohort of patients with chronic HBV infection seen in a large academic health setting.

Methods
We identified a total of 278 patients with HCC and chronic HBV seen at two medical centers in a 14-year span from January 2002 to December 2015. These cases were age- and sex-matched in a 1:3 ratio with 823 non-cancer control subjects with chronic HBV. Conditional logistic regression was used to estimate the odds of HCC by race, with black race stratified by African-born status, after adjusting for diabetes, HIV or HCV coinfection, alcohol misuse and cirrhosis.

Results
Of the 278 HCC cases, 67% were 60 years of age or older, 78% were male, 87% had cirrhosis and 72% were Asian. HIV infection was present in 6% of cases. Only 7% (19 of 278) of HCC cases were black, of whom 14 were African immigrants. The median age at HCC diagnosis was 44 years in Africans. Notably, nearly all (93%) of the African-born patients with HCC were diagnosed at an age younger than 60 years compared with 52% of Asian cases (P<0.001). The main factors independently associated with greater odds of HCC overall were Asian race (adjusted odds ratio [aOR] 3.3, 95% confidence interval [CI] 1.9–5.5) and cirrhosis (aOR 19.7, 95% CI 12.2–31.8).

Conclusion
African immigrants accounted for a small proportion of HBV-associated HCC cases overall compared with Asians but appeared to have greater likelihood of early-onset HCC. Optimal strategies for HCC prevention in these key subroups with chronic HBV warrant further study.

Differences in hepatocellular carcinoma risk, predictors and trends over time according to etiology of cirrhosis

Of Interest
Sci Rep. 2018; 8: 13651.
Published online 2018 Sep 12. doi: 10.1038/s41598-018-31839-y

Differences in hepatocellular carcinoma risk, predictors and trends over time according to etiology of cirrhosis 
George N. Ioannou , Pamela Green, Elliott Lowy, Elijah J. Mun, Kristin Berry
Published: September 27, 2018 https://doi.org/10.1371/journal.pone.0204412

Full-text Article 
Download PDF

Abstract
Background and aims
Hepatocellular carcinoma (HCC) risk is high in cirrhosis. We sought to describe differences in HCC risk, predictors and trends over time according to etiology of cirrhosis.

Methods
We identified 116,404 patients with cirrhosis diagnosed between 2001–2014 in the VA healthcare system and determined incident HCC cases occurring from the date of cirrhosis diagnosis until 01/31/2017. Patients were divided by cirrhosis etiology into hepatitis C virus (HCV, n = 52,671), alcoholic liver disease (ALD, n = 35,730), nonalcoholic fatty liver disease (NAFLD, n = 17,354), or OTHER (n = 10,649).

Results
During a mean follow-up of 4.3 years, 10,042 new HCC cases were diagnosed. Patients with HCV had >3 times higher incidence of HCC (3.3 per 100 patient-years) than patients with ALD (0.86/100 patient-years), NAFLD (0.90/100 patient-years) or OTHER (1.0/100 patient-years), an association that persisted after adjusting for baseline characteristics. HCC incidence was 1.6 times higher in patients with cirrhosis diagnosed in 2008–2014 (2.47/100 patient-years) than in 2001–2007 (1.55/100 patient-years). 

Independent predictors of HCC among all cirrhosis etiologies included: age, male sex, Hispanic ethnicity, high serum alpha fetoprotein, alkaline phosphatase and AST/√ALT ratio and low serum albumin and platelet count. Diabetes was associated with HCC in ALD-cirrhosis and NAFLD-cirrhosis, and BMI in ALD-cirrhosis.

Conclusions
HCC risk is 3 times greater in cirrhotic patients with HCV than ALD or NAFLD. HCC risk continues to increase over time in analyses extending to 2017 in cirrhosis of all etiologies. Multiple readily available risk factors for HCC were identified that were influenced by cirrhosis etiology and could be used to develop HCC risk estimation models.

Monday, September 24, 2018

Liquid biopsy shows promise for monitoring, detecting liver disease

Liquid biopsy shows promise for monitoring, detecting liver disease
Last Updated: 2018-09-24
By Anne Harding

NEW YORK (Reuters Health) - Diseased liver cells can be detected in the peripheral blood, and those from patients with hepatocellular carcinoma (HCC) have a different gene expression profile than those from patients with chronic liver disease (CLD) but no cancer, according to new findings in Gastroenterology.

The authors also found that patients with CLD and more severe fibrosis had significantly more hepatic circulating epithelial cells (CECs) in their blood. "We're identifying cells that haven't been identified before," Dr. Irun Bhan of Massachusetts General Hospital (MGH) Cancer Center in Boston, the study's first author, told Reuters Health by phone. "Perhaps in the future they could even be used as biomarkers for these diseases."

Published In Gastroenterology 
Abstract
Epithelial cells in the circulation (circulating epithelial cells, or CECs) are analyzed as a non-invasive method to detect cancers; we investigated whether analysis of hepatocytes in the circulation can identify patients with chronic liver disease or hepatocellular carcinoma (HCC). We previously developed a cell-sorting device to isolate CECs from patient blood samples and combined it with an mRNA analysis system to identify CECs with liver-specific markers. We tested the ability of this device to detect CECs of hepatocyte origin in blood samples from healthy individuals (n=10), patients with chronic liver disease without HCC (n=39), and patients with HCC (n=54), using immunofluorescence. We confirmed hepatocyte origin using RNA-sequencing analysis. We found a similar concentration of circulating hepatocytes in blood samples from patients with chronic liver disease and HCC but an increased concentration from patients with advanced fibrosis compared to those without advanced fibrosis. Circulating hepatocytes isolated from patients with HCC had a different gene expression profile than those from patients with chronic liver disease. This system for detecting and analyzing circulating hepatocytes might be used in the evaluation of benign and malignant liver disease.

Saturday, September 22, 2018

Video: Recognizing Liver Cancer Risk Factors

Hepatocellular carcinoma (HCC)
Hepatocellular carcinoma (HCC) is cancer that starts in the liver, it is not the same as metastatic liver cancer, which starts in another organ (such as the breast or colon) and spreads to the liver.

Practice Guidelines: Management of hepatocellular carcinoma
Journal of Hepatology
July 2018 Volume 69, Issue 1, Pages 182–236

Recognizing Hepatocellular Carcinoma (HCC) Risk Factors
Risk factors including viral hepatitis (hepatitis C, hepatitis B infection), alcoholic liver disease, and NASH from the metabolic syndrome—I think all of those can cause chronic inflammation, eventually leading to cirrhosis, which increases the risk of having HCC develop in the liver.



Recommended Reading
View a series of videos and articles about liver cancer available at OncLive:
https://www.onclive.com/

Steady Increase in Liver Cancer Death Rates Observed in Adults ...
OncLive
A National Center for Health Statistics (NCHS) briefing stratifies liver cancer mortality by sex, ethnicity, and age for adults aged 25 years and …

Diabetes drug may prevent liver cancer
by Liz Entman Sep. 21, 2018, 9:05 AM
A drug commonly used to treat type 2 diabetes might help prevent patients from developing liver cancers. In a study published this month in the journal Cancer Causes & Control, Harvey J. Murff, MD, MPH, and colleagues found that patients taking metformin had a reduced rate of liver cancer compared to patients taking an alternative anti-diabetes drug. 

Reuters-Sep 4, 2018
(Reuters Health) - People with advanced cases of nonalcoholic fatty liver disease (NAFLD) may need to be watched for liver cancer, a large …

Saturday, September 8, 2018

Risk of Liver Cancer in Patients with NAFLD

Severe NAFLD Boosts Liver Cancer Risk
By Ankur Banerjee

(Reuters Health) - People with advanced cases of nonalcoholic fatty liver disease (NAFLD) may need to be monitored for liver cancer, a large U.S. study suggests.

Fatty liver disease is known to be linked with a higher risk of hepatocellular carcinoma (HCC). But it hasn't been clear whether some patients are more at risk than others.

The new study showed that when NAFLD progresses to cirrhosis, the risk for HCC is dramatically higher.

The findings suggest that people with NAFLD and cirrhosis should be monitored for HCC, the authors wrote in Gastroenterology, online August 23.


Gastroenterology
Risk of HCC was higher in NAFLD patients than that observed in general clinical population. Most HCC cases in NAFLD developed in patients with cirrhosis. The absolute risk of HCC was higher than the accepted thresholds for HCC surveillance for most patients with NAFLD cirrhosis.

Monday, August 27, 2018

New target could prevent progression of liver damage to cancer

Journal of Clinical Investigation

New target could prevent progression of liver damage to cancer 
AUGUSTA, Ga. (Aug. 27, 2018) - Problems like obesity and alcoholism appear to chronically trigger in the liver a receptor known to amplify inflammation in response to invaders like bacteria, scientists report.

The relentless, increased activity of TREM-1 in turn accelerates injury and scarring of the liver, a first step toward cirrhosis and liver cancer, says Dr. Anatolij Horuzsko, reproductive immunologist in the Georgia Cancer Center and Department of Medicine at the Medical College of Georgia at Augusta University.

TREM-1, or triggering receptor expressed on myeloid cells-1, is known to help turn up inflammation short-term to help us deal with external invaders. It has increased activity immediately after an injury as well, when increased inflammation, damage cleanup and collagen production aid healing.

But Georgia Cancer Center scientists report in the Journal of Clinical Investigation the first evidence that when activated by chronic offending agents, like obesity and hepatitis, TREM-1 instead contributes to a destructive level of inflammation that results in liver damage and possibly cancer.

The unhealthy transformation can occur in five to 50 years, depending on factors like the level of insult, and may be largely reversible up to the point of cirrhosis, if the offending agent is stopped, and the liver's natural ability to regenerate takes over.

Horuzsko and his colleagues think TREM-1 could one day be another point of intervention, possibly with a drug that could return TREM-1 activation to normal levels on resident, garbage-eating, watchdog immune cells called Kupffer cells.

"Right now we have treatment for hepatitis C, for example, which is very efficient, if we treat it before too much damage is done. But we don't have treatment for alcohol- or obesity-related damage," Horuzsko says.

They already are doing experiments with a drug that, because of its structure, should enable tamping down of TREM-1, but long-term goals include a drug that would target this receptor on Kupffer cells.

It's known that inflammation is a key process in the thickening and scarring of the liver called fibrosis, and that tamping down inflammation can help prevent fibrosis progression. But just how inflammation and fibrosis happen at the cellular and molecular level is largely unknown, say Horuzsko, the study's corresponding author.

Their work in both animal models and human tissue indicate TREM-1 is essential to both.

In the liver, TREM-1 is found primarily on Kupffer cells, the liver's resident macrophages, as well as monocytes, a type of white blood cell that can also become garbage-eating macrophages.

TREM-1's expression is limited in a healthy human liver but its activation goes up short-term following an insult, like a laceration.

To look at what happens in the face of a chronic problem, the scientists created a model of chronic liver disease - like obesity or high alcohol consumption might - using carbon tetrachloride, a poisonous solvent found in oils, varnishes and resin. They found TREM-1 activation went up and stayed up on a larger number of Kupffer cells in the liver as well as other immune cells circulating in the body.

When they deleted TREM-1 from the model, it reduced inflammation, injury and subsequent fibrosis. When they gave TREM-1 back to the mice, inflammation and related damage came back with a vengeance, leading them to dub TREM-1 the main target that drives fibrogenesis.

They found TREM-1 even recruits other pro-inflammatory cells from the bone marrow to the liver, many of which could become macrophages as well, which further multiplies the inflammation, liver cell damage and death.

"This creates a loop," says Horuzsko, of increased activity on many fronts. "This creates chronic inflammation - with no bacterium or virus involved - which is important to the development of liver disease."

As liver cells die in the face of chronic inflammation, they release their innards, called damage associated molecular patterns, or DAMPs, when they get outside the cells. DAMPs further activate TREM-1 on the macrophages and the damaging momentum builds, he says.

That's where collagen and fibrosis set in. Stellate cells in the liver are normally quiescent and mainly store vitamin A. When TREM-1 gets activated on the macrophages, it also activates the macrophages themselves which, in turn, activate stellate cells.

Stellate cells literally change their shape, release vitamin A and start to make collagen. Collagen is a component of connective tissue that typically helps hold tissues and blood vessels together and aids wound healing. The liver already has some collagen, but in this scenario too much gets deposited and liver function suffers.

"Efficiency goes down and it causes additional damage to liver cells that already have been damaged by something like hepatitis or obesity," Horuzsko says. The liver of a patient with cirrhosis, for example, is overrun with collagen, he notes.

Blood levels of the enzymes alanine aminotransferase, or ALT, and aspartate aminotransferase, or AST, are indicators of liver injury and both went up and remained high in their models. However, in mice where TREM-1 was knocked out, rates went up only short- term before returning to pre-injury levels, another indicator of TREM-1's role in persistent inflammation and resulting damage, Horuzsko says.

They also found that while mice with and without TREM-1 both recruited additional immune cells, such as more macrophages and monocytes, from their bone marrow immediately after the injury, 72 hours later the levels were much higher both in the blood and livers of the mice that also still had TREM-1.

To look further at the role of Kupffer cells when TREM-1 is out of the picture, they first removed the cells from both mice models, then gave Kupffer cells that contained TREM-1 back to both, and both were able to cause localized damage and recruit immune cells from the marrow to further bolster inflammation. But when they put TREM-1-deficient Kupffer cells back in normal mice, the exaggerated inflammation and liver damage did not happen.

Likewise, they found markedly increased infiltration of TREM-1 expressing cells in patients with liver fibrosis.

"TREM-1 is a molecule that can be very dangerous and is normally very controlled in the body," Horuzsko says. In fact, one of the diagnostic criteria for body-wide infection, or sepsis, is the level of TREM-1 protein in the fluid portion of a patient's blood. And, in hepatitis B related liver cancer in humans, high levels of TREM-1 expression on stellate cells is considered an indicator of poor prognosis.

"The balance in our body is very, very tightly regulated and important. Alcohol, obesity, hepatitis viruses all change the balance," Horuzsko says.

The scientists suspect their findings of TREM-1 gone wild will hold true in other organs including the lungs, heart and kidneys, which also have TREM-1 on their macrophages.

Liver cancer rates have risen dramatically in the United States, 43 percent in men and 40 percent in women, from 2000-16, according to a report released this summer by the Centers for Disease Control and Prevention. In May 2017, the CDC reported that newly reported cases of hepatitis C tripled between 2010-15 and the American Cancer Society says liver cancer rose from ninth to the sixth leading cause of cancer death from 2000-16.

The most common causes of liver cancer include infection with the hepatitis B or C virus, heavy alcohol use, obesity and diabetes, according to the CDC.

The liver is part of the gastrointestinal tract and filters blood coming from the GI tract before the blood circulates to the rest of the body. Its myriad of functions include secreting bile, which helps us absorb fats and eliminate waste; producing cholesterol, triglycerides and blood clotting factors; and detoxifying chemicals. The liver is the heaviest solid organ in the body and sits on the right sight of the body behind the lower ribs. 

The research was funded by the National Institutes of Health.
https://www.augusta.edu/mcg/

Sunday, August 19, 2018

FDA approves LENVIMA® for first-line treatment of unresectable liver cancer

MedPage Today:
FDA OKs First-Line Tx for Unresectable Liver Cancer First new upfront treatment option in over a decade 
by Ian Ingram, Deputy Managing Editor, MedPage Today 
August 16, 2018
WASHINGTON -- The FDA on Thursday approved the kinase inhibitor lenvatinib (Lenvima) for the first-line treatment of hepatocellular carcinoma (HCC) patients with unresectable disease.

Approval was based on the REFLECT study, a multicenter non-inferiority trial, which randomized 954 HCC patients 1:1 to either 8 mg or 12 mg oral lenvatinib (depending on the patient's weight) versus 400 mg sorafenib twice daily until disease progression or unacceptable toxicity. The drug is approved at the 8 mg once-daily dose for patients <60 kg and at the 12 mg once-daily dose for those ≥60 kg.
Continue reading:
 https://www.medpagetoday.com/hematologyoncology/othercancers/74612

Press Release:
Eisai And Merck Announce FDA Approval Of LENVIMA® (lenvatinib) Capsules For First-line Treatment Of Unresectable Hepatocellular Carcinoma (HCC) 

- Approval was based on REFLECT, the first-ever positive Phase 3 trial against an active comparator in previously untreated patients with unresectable HCC 

- Marks second approval under Eisai-Merck global collaboration to co-develop and co-commercialize LENVIMA, following Japan in March 2018

Aug 16, 2018
WOODCLIFF LAKE, N.J. and KENILWORTH, N.J., Aug. 16, 2018 /PRNewswire/ -- Eisai Inc. and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) approved the kinase inhibitor LENVIMA® (lenvatinib) for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). This approval was based on results from REFLECT (Study 304), where LENVIMA demonstrated a proven treatment effect on overall survival (OS) by statistical confirmation of non-inferiority, as well as statistically significant superiority and clinically meaningful improvements in progression-free survival (PFS) and objective response rate (ORR) when compared with sorafenib in patients with previously untreated unresectable HCC.

"Unresectable hepatocellular carcinoma is an extremely difficult-to-treat cancer, with no new first-line systemic therapy options for more than a decade," said Dr. Ghassan Abou-Alfa, medical oncologist, Memorial Sloan Kettering Cancer Center. "REFLECT is the first-ever positive Phase 3 trial against an active comparator in unresectable HCC. The efficacy and safety data from REFLECT are important findings for oncologists and others in the multidisciplinary teams who treat liver cancer, as well as for our patients who are affected by it."

Adverse reactions, some of which can be serious or fatal, may occur with LENVIMA, including hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure or impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of thyroid stimulating hormone suppression/thyroid dysfunction, and wound healing complications. Based on the severity of the adverse reaction, LENVIMA should be monitored, withheld or discontinued. Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should be advised to use effective contraception. For more information, see "Important Safety Information" below.

REFLECT showed that LENVIMA achieved the primary endpoint, demonstrating a treatment effect on OS by statistical confirmation of non-inferiority to sorafenib. Patients treated with LENVIMA experienced a median OS of 13.6 months compared to 12.3 months with sorafenib (HR: 0.92; 95% CI: 0.79–1.06). The OS analysis was conducted when 351 events had occurred in the LENVIMA arm and 350 events had occurred in the sorafenib arm, as prespecified in the statistical analysis plan. In addition, LENVIMA showed statistically significant superiority and clinically meaningful improvements in the secondary efficacy endpoints of PFS and ORR, as confirmed by a blinded independent imaging review (IIR):

Median PFS was doubled with LENVIMA compared to sorafenib: 7.3 months versus 3.6 months (HR: 0.64; 95% CI: 0.55–0.75; p<0.001) per blinded independent imaging review based on mRECIST criteria, and 7.3 months with LENVIMA versus 3.6 months with sorafenib (HR: 0.65; 95% CI: 0.56–0.77) per RECIST 1.1.
LENVIMA showed nearly 3.5 times the ORR of sorafenib: 41% (95% CI: 36-45%) vs. 12% (95% CI: 10-16%) per blinded independent imaging review based on mRECIST criteria, respectively (p<0.001), and 19% (95% CI: 15-22%) with LENVIMA versus 7% (95% CI: 4-9%) with sorafenib per RECIST 1.1.
Per mRECIST: Treatment with LENVIMA resulted in complete response (CR) = 2.1% (n=10) vs. 0.8% (n=4) with sorafenib; treatment with LENVIMA resulted in partial response (PR) = 38.5% (n=184) vs. 11.6% (n=55) with sorafenib
Per RECIST 1.1: Treatment with LENVIMA resulted in CR = 0.4% (n=2) vs. 0.2% (n=1) with sorafenib; treatment with LENVIMA resulted in PR = 18.4% (n=88) vs. 6.3% (n=30) with sorafenib

In addition, median time to progression (TTP) was doubled with LENVIMA compared to sorafenib: 7.4 months versus 3.7 months (HR: 0.60; 95% CI: 0.51–0.71; p<0.0001) per blinded independent imaging review based on mRECIST criteria, and 7.4 months with LENVIMA versus 3.7 months with sorafenib (HR: 0.61; 95% CI: 0.51–0.72; p<0.0001) per RECIST 1.1. Time to progression is defined as time from randomization to radiological progression. Deaths during follow-up without evidence of radiological progression are censored. This differs from PFS and is less correlative to overall survival.

In REFLECT, the most common adverse reactions (≥20%) observed in patients treated with LENVIMA were hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism and nausea. The most common serious adverse reactions (≥2%) reported in patients treated with LENVIMA were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%) and decreased appetite (2%).

The most common adverse reactions (≥20%) observed in patients who received sorafenib were palmar-plantar erythrodysesthesia syndrome, diarrhea, fatigue, hypertension, abdominal pain, decreased appetite, rash, decreased weight and arthralgia/myalgia. The most common serious adverse reactions (≥2%) reported in patients who received sorafenib were ascites (2%) and abdominal pain (2%).

It is also important to note that the dose for LENVIMA for patients with unresectable HCC is based on the patient's weight (12 mg for patients weighing 60 kilograms or more, 8 mg for patients weighing less than 60 kilograms); the recommended dosage and dose adjustments are described in the full prescribing information.

"Eisai strives to be a leading global R&D-based pharmaceutical company, driven by our human health care (hhc) mission to improve the lives of patients and their loved ones," said Shaji Procida, President and Chief Operating Officer, Eisai Inc., and Commercial Head of the Oncology Business Group, Americas at Eisai. "That purpose is what has propelled us toward this win for patients with unresectable hepatocellular carcinoma. Our goal is to bring monumental solutions to patients and health care providers, changing expectations for the oncology landscape, and we look forward to continuing this work in our ongoing collaboration with Merck."

"We are pleased by the FDA approval of LENVIMA as it marks an important advancement in the treatment of unresectable hepatocellular carcinoma," said Dr. Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories. "With our shared mission to find solutions for difficult-to-treat cancers, we look forward to working with Eisai to help bring this needed option to patients and physicians."

LENVIMA, a kinase inhibitor, was first approved in the U.S. in February 2015 for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC). In May 2016, LENVIMA was approved in the U.S. in combination with everolimus, for patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy. Under the collaboration, Eisai and Merck initiated co-commercialization activities for LENVIMA in the U.S. in June 2018. Since the initial launch, more than 10,000 patients were treated with LENVIMA, which is approved in more than 50 countries worldwide.

About the REFLECT Trial (Study 304)
REFLECT was a large (N=954) phase 3, randomized, multicenter, open-label trial conducted by Eisai to compare the efficacy and safety of lenvatinib versus sorafenib as a first-line systemic treatment in patients with unresectable hepatocellular carcinoma (HCC). Patients at 154 trial sites in 20 countries were randomized to receive lenvatinib 12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was overall survival, tested first for non-inferiority to sorafenib, then for superiority. Patients randomized to the LENVIMA arm did not have a statistically significant improvement in OS compared to those in the sorafenib arm. The key secondary efficacy endpoints of this study included progression-free survival, time to progression and objective response rate, tested for superiority to sorafenib. The results of the REFLECT trial were published online in The Lancet (Vol 391(10126):1163-1173) on February 9, 2018.

About Unresectable Hepatocellular Carcinoma (HCC)
The prevalence and mortality rate of hepatocellular carcinoma have been rising steadily over the past decade. Hepatocellular carcinoma is the most common type of liver cancer, accounting for about 90% of cases of primary liver cancer. The stage of disease at diagnosis largely determines treatment approach, with potentially curative options, like resection or transplantation, only available for early stage HCC. Unresectable HCC, a type of liver cancer that cannot be removed by surgery, has a worse prognosis, with a median survival of less than one year. Unfortunately, approximately 70% of patients are diagnosed too late to be eligible for resection or transplantation, and there have been limited treatment options available for patients with unresectable disease.

About LENVIMA® (lenvatinib) capsules 10 mg and 4 mg
LENVIMA® (lenvatinib) is a kinase inhibitor that is indicated:

For the treatment of patients with locally recurrent or metastatic, progressive radioactive iodine-refractory differentiated thyroid cancer (DTC)
In combination with everolimus, for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)

LENVIMA, discovered and developed by Eisai, is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2α (FRS2α) phosphorylation.

Important Safety Information
Warnings and Precautions
Hypertension. In DTC, hypertension occurred in 73% of patients on LENVIMA (44% grade 3-4). In RCC, hypertension occurred in 42% of patients on LENVIMA + everolimus (13% grade 3). Systolic blood pressure ≥160 mmHg occurred in 29% of patients, and 21% had diastolic blood pressure ≥100 mmHg. In HCC, hypertension occurred in 45% of LENVIMA-treated patients (24% grade 3). Grade 4 hypertension was not reported in HCC.

Serious complications of poorly controlled hypertension have been reported. Control blood pressure prior to initiation. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at reduced dose when hypertension is controlled or permanently discontinue based on severity.

Cardiac Dysfunction. Serious and fatal cardiac dysfunction can occur with LENVIMA. Across clinical trials in 799 patients with DTC, RCC, and HCC, grade 3 or higher cardiac dysfunction occurred in 3% of LENVIMA-treated patients. Monitor for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Arterial Thromboembolic Events. Among patients receiving LENVIMA or LENVIMA + everolimus, arterial thromboembolic events of any severity occurred in 2% of patients in RCC and HCC and 5% in DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials.

Permanently discontinue following an arterial thrombotic event. The safety of resuming after an arterial thromboembolic event has not been established and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.

Hepatotoxicity. Across clinical studies enrolling 1,327 LENVIMA-treated patients with malignancies other than HCC, serious hepatic adverse reactions occurred in 1.4% of patients. Fatal events, including hepatic failure, acute hepatitis and hepatorenal syndrome, occurred in 0.5% of patients. In HCC, hepatic encephalopathy occurred in 8% of LENVIMA-treated patients (5% grade 3-5). Grade 3-5 hepatic failure occurred in 3% of LENVIMA-treated patients. 2% of patients discontinued LENVIMA due to hepatic encephalopathy and 1% discontinued due to hepatic failure.

Monitor liver function prior to initiation, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Renal Failure or Impairment. Serious including fatal renal failure or impairment can occur with LENVIMA. Renal impairment was reported in 14% and 7% of LENVIMA-treated patients in DTC and HCC, respectively. Grade 3-5 renal failure or impairment occurred in 3% of patients with DTC and 2% of patients with HCC, including 1 fatal event in each study. In RCC, renal impairment or renal failure was reported in 18% of LENVIMA + everolimus–treated patients (10% grade 3).

Initiate prompt management of diarrhea or dehydration/hypovolemia. Withhold and resume at reduced dose upon recovery or permanently discontinue for renal failure or impairment based on severity.

Proteinuria. In DTC and HCC, proteinuria was reported in 34% and 26% of LENVIMA-treated patients, respectively. Grade 3 proteinuria occurred in 11% and 6% in DTC and HCC, respectively. In RCC, proteinuria occurred in 31% of patients receiving LENVIMA + everolimus (8% grade 3).

Monitor for proteinuria prior to initiation and periodically during treatment. If urine dipstick proteinuria ≥2+ is detected, obtain a 24-hour urine protein. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Diarrhea. Of the 737 LENVIMA-treated patients in DTC and HCC, diarrhea occurred in 49% (6% grade 3). In RCC, diarrhea occurred in 81% of LENVIMA + everolimus–treated patients (19% grade 3). Diarrhea was the most frequent cause of dose interruption/reduction, and diarrhea recurred despite dose reduction.

Promptly initiate management of diarrhea. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Fistula Formation and Gastrointestinal Perforation. Of the 799 patients treated with LENVIMA or LENVIMA + everolimus in DTC, RCC, and HCC, fistula or gastrointestinal perforation occurred in 2%. Fistulas and gastrointestinal perforations have also been reported in other lenvatinib clinical trials and in post-marketing experience. Pneumothorax has been reported with and without clear evidence of a bronchopleural fistula. Some reports of gastrointestinal perforation, fistula, and pneumothorax occurred in association with tumor regression or necrosis. In most cases of fistula formation or gastrointestinal perforation, risk factors such as prior surgery or radiotherapy were present.

Permanently discontinue in patients who develop gastrointestinal perforation of any severity or grade 3-4 fistula.

QT Interval Prolongation. In DTC, QT/QTc interval prolongation occurred in 9% of LENVIMA-treated patients and QT interval prolongation of >500 ms occurred in 2%. In RCC, QTc interval increases of >60 ms occurred in 11% of patients receiving LENVIMA + everolimus and QTc interval >500 ms occurred in 6%. In HCC, QTc interval increases of >60 ms occurred in 8% of LENVIMA-treated patients and QTc interval >500 ms occurred in 2%.

Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold and resume at reduced dose upon recovery based on severity.

Hypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in 9% of LENVIMA-treated patients. In 65% of cases, hypocalcemia improved or resolved following calcium supplementation with or without dose interruption or dose reduction. In RCC, grade 3-4 hypocalcemia occurred in 6% of LENVIMA + everolimus–treated patients. In HCC, grade 3 hypocalcemia occurred in 0.8% of LENVIMA-treated patients.

Monitor blood calcium levels at least monthly and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity.

Reversible Posterior Leukoencephalopathy Syndrome. Across clinical studies of 1,823 patients who received LENVIMA as a single agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with MRI. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity and persistence of neurologic symptoms.

Hemorrhagic Events. Serious including fatal hemorrhagic events can occur with LENVIMA. In DTC, RCC, and HCC clinical trials, hemorrhagic events, of any grade, occurred in 29% of the 799 patients treated with LENVIMA as a single agent or in combination with everolimus. The most frequently reported hemorrhagic events (all grades and occurring in at least 5% of patients) were epistaxis and hematuria. In DTC, grade 3-5 hemorrhage occurred in 2% of LENVIMA-treated patients, including 1 fatal intracranial hemorrhage among 16 patients who received LENVIMA and had CNS metastases at baseline. In RCC, grade 3-5 hemorrhage occurred in 8% of LENVIMA + everolimus–treated patients, including 1 fatal cerebral hemorrhage. In HCC, grade 3-5 hemorrhage occurred in 5% of LENVIMA-treated patients, including 7 fatal hemorrhagic events.

Serious tumor-related bleeds, including fatal hemorrhagic events, occurred in LENVIMA-treated patients in clinical trials and in the postmarketing setting. In postmarketing surveillance, serious and fatal carotid artery hemorrhages were seen more frequently in patients with anaplastic thyroid carcinoma (ATC) than other tumors. Safety and effectiveness of LENVIMA in patients with ATC have not been demonstrated in clinical trials.

Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (eg, carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction. LENVIMA impairs exogenous thyroid suppression. In DTC, 88% of patients had baseline thyroid stimulating hormone (TSH) level ≤0.5 mU/L. In patients with normal TSH at baseline, elevation of TSH level >0.5 mU/L was observed post baseline in 57% of LENVIMA-treated patients. In RCC and HCC, grade 1 or 2 hypothyroidism occurred in 24% of LENVIMA + everolimus–treated patients and 21% of LENVIMA-treated patients, respectively. In patients with normal or low TSH at baseline, elevation of TSH was observed post baseline in 70% of LENVIMA-treated patients in HCC and 60% of LENVIMA + everolimus–treated patients in RCC.

Monitor thyroid function prior to initiation and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.

Wound Healing Complications. Wound healing complications, including fistula formation and wound dehiscence, can occur with LENVIMA. Withhold for at least 6 days prior to scheduled surgery. Resume after surgery based on clinical judgment of adequate wound healing. Permanently discontinue in patients with wound healing complications.

Embryo-fetal Toxicity. Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to pregnant women. In animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended clinical doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potential risk to a fetus; and advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 30 days after the last dose.

Adverse Reactions
In DTC, the most common adverse reactions (≥30%) observed in LENVIMA-treated patients were hypertension (73%), fatigue (67%), diarrhea (67%), arthralgia/myalgia (62%), decreased appetite (54%), decreased weight (51%), nausea (47%), stomatitis (41%), headache (38%), vomiting (36%), proteinuria (34%), palmar-plantar erythrodysesthesia syndrome (32%), abdominal pain (31%), and dysphonia (31%). The most common serious adverse reactions (≥2%) were pneumonia (4%), hypertension (3%), and dehydration (3%). Adverse reactions led to dose reductions in 68% of LENVIMA-treated patients; 18% discontinued LENVIMA. The most common adverse reactions (≥10%) resulting in dose reductions were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%); the most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were hypertension (1%) and asthenia (1%).

In RCC, the most common adverse reactions (≥30%) observed in LENVIMA + everolimus–treated patients were diarrhea (81%), fatigue (73%), arthralgia/myalgia (55%), decreased appetite (53%), vomiting (48%), nausea (45%), stomatitis (44%), hypertension (42%), peripheral edema (42%), cough (37%), abdominal pain (37%), dyspnea (35%), rash (35%), decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%). The most common serious adverse reactions (≥5%) were renal failure (11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea (5%). Adverse reactions led to dose reductions or interruption in 89% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and proteinuria (5%). Treatment discontinuation due to an adverse reaction occurred in 29% of patients.

In HCC, the most common adverse reactions (≥20%) observed in LENVIMA-treated patients were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%), arthralgia/myalgia (31%), decreased weight (31%), abdominal pain (30%), palmar-plantar erythrodysesthesia syndrome (27%), proteinuria (26%), dysphonia (24%), hemorrhagic events (23%), hypothyroidism (21%), and nausea (20%). The most common serious adverse reactions (≥2%) were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%), and decreased appetite (2%). Adverse reactions led to dose reductions or interruption in 62% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were fatigue (9%), decreased appetite (8%), diarrhea (8%), proteinuria (7%), hypertension (6%), and palmar-plantar erythrodysesthesia syndrome (5%). Treatment discontinuation due to an adverse reaction occurred in 20% of patients. The most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were fatigue (1%), hepatic encephalopathy (2%), hyperbilirubinemia (1%), and hepatic failure (1%).

Use in Specific Populations
Because of the potential for serious adverse reactions in breastfed infants, advise women to discontinue breastfeeding during treatment and for at least 1 week after last dose. LENVIMA may impair fertility in males and females of reproductive potential.

No dose adjustment is recommended for patients with mild (CLcr 60-89 mL/min) or moderate (CLcr 30-59 mL/min) renal impairment. LENVIMA concentrations may increase in patients with DTC or RCC and severe (CLcr 15-29 mL/min) renal impairment. Reduce the dose for patients with RCC or DTC and severe renal impairment. There is no recommended dose for patients with HCC and severe renal impairment. LENVIMA has not been studied in patients with end stage renal disease.

No dose adjustment is recommended for patients with HCC and mild hepatic impairment (Child-Pugh A). There is no recommended dose for patients with HCC with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment.

No dose adjustment is recommended for patients with DTC or RCC and mild or moderate hepatic impairment. LENVIMA concentrations may increase in patients with DTC or RCC and severe hepatic impairment. Reduce the dose for patients with DTC or RCC and severe hepatic impairment.

For more information about LENVIMA please see available full Prescribing Information.
http://eisai.mediaroom.com/2018-08-16-Eisai-And-Merck-Announce-FDA-Approval-Of-LENVIMA-R-lenvatinib-Capsules-For-First-line-Treatment-Of-Unresectable-Hepatocellular-Carcinoma-HCC

Monday, August 13, 2018

Listen: Fewer Australians are dying from hepatitis C, but thousands are still missing out on treatment

Article
Fewer Australians are dying from hepatitis C, but thousands are still missing out on treatment
By health reporter Olivia Willis
Monday 13 August 2018
The number of Australians dying from liver failure and liver cancer related to hepatitis C has dropped by 20 per cent in just two years, according to preliminary data released today by The Kirby Institute.
Read the article: http://www.abc.net.au/news/health/2018-08-13/fewer-australians-dying-from-hepatitis-c/10107326

ABC Radio Australia 
Deaths from Hep C liver failure and liver cancer improving
Listen to Monday's Health Report hosted by Dr. Norman Swan with guest Greg Dore discuss the latest hepatitis C-related liver failure and liver cancer figures in New South Whales.

Deaths from Hep C liver failure and liver cancer improving
New research is showing a return on the Federal Government's investment in free hepatitis C treatment aimed at curing blood-transmitted liver infection.

The latest figures from New South Wales show the number of people dying from hepatitis C-related liver failure and liver cancer has dropped 20 per cent in two years.

Listen here...…

Guest: Professor Greg Dore
Professor and Program Head, Viral Hepatitis Clinical Research Program, The Kirby Institute, University of New South Wales.

Monday 13 August 2018 5:45PM (full episode)