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

Friday, June 15, 2018

Liver Cancer a Big Threat to U.S., Other Developed Nations

Liver Cancer a Big Threat to U.S., Other Developed Nations

FRIDAY, June 15, 2018 (HealthDay News) -- Liver cancer cases in several developed countries have doubled in the past 25 years, due to the continuing obesity epidemic and a spike in hepatitis infections, new research suggests.

Even worse, the sharp rise in liver cancer cases is starting to swamp the limited number of liver specialists in those nations, the researchers added.

In the four countries -- the United States, the United Kingdom, Australia and Canada -- liver cancer is the only major cancer for which death rates are rising.

The findings were to be presented Friday at the Global Hepatitis Summit, in Toronto. Research presented at meetings is considered preliminary until published in a peer-reviewed journal.


Global Hepatitis Summit
Toronto June 14th – 17th, 2018 
Twitter
#GHS2018 

Thursday, June 14, 2018

Diagnosis and Treatment of HCC Varies by Race

Diagnosis and Treatment of HCC Varies by Race
Blacks and Hispanics less likely to get surveillance, early diagnosis, and curative treatment
by Diana Swift, Contributing Writer June 14, 2018

A large retrospective study of hepatocellular (HCC) patients in Texas found racial and ethnic differences in outcomes, with blacks and Hispanics less likely than whites to get early diagnosis and curative treatment, and blacks less likely to survive.

"Our findings have important implications for health policy and highlight the need for further study on racial-ethnic disparities in HCC, including identification of additional actionable intervention," wrote Amit Singal, MD, MS, of the University of Texas (UT) Southwestern Medical Center's Simmons Cancer in Dallas, and colleagues in Clinical Gastroenterology and Hepatology
Continue reading: 

Free registration may be required

Wednesday, June 13, 2018

Liver Cancer After Treatment For Hepatitis C


Page updated: June 2018

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?

This page offers an index of links to current data investigating the possible risk of developing liver cancer (hepatocellular carcinoma, or HCC) during and after direct-acting antiviral therapy in patients with hepatitis C.

June 2018
June 15 2018
Alimentary Pharmacology & Therapeutics
Direct-acting Antiviral Treatment for Hepatitis C Virus Infection and Risk of Incident Liver Cancer
Does DAA-based HCV treatment reduce the risk of incident liver cancer compared to untreated HCV or interferon-based treatment?

May 2018
May 12, 2018
Nature reviews gastroenterology & hepatology
HCV therapy and risk of liver cancer recurrence: who to treat?
Article shared and download by Henry E. Chang on Twitter

May 4, 2018
This large real-life study proves that the efficacy of DAA in cirrhotic patients is not impaired by successfully treated HCC.

April 2018
April 21, 2018
Editorial
Hepatocellular carcinoma as a consequence of hepatitis C direct-acting anti-virals-the great urban myth of hepatology
Aliment Pharmacol Ther. 2018 May;47(10):1418-1419. doi: 10.1111/apt.14634.

April 17, 2018
Does interferon-free therapy for hepatitis C after curative treatment for hepatocellular carcinoma lead to unexpected recurrences of HCC?
PLOS ONE | https://doi.org/10.1371/journal.pone.0194704

April 11, 2018
New At Healio: 8 reports on liver cancer outcomes with HCV, DAA therapy

April 5, 2018
Hepatitis C - Interferon-free therapy did not increase the risk of liver cancer
LAY SUMMARY: We examined the risk of liver cancer among 857 patients with cirrhosis in Scotland who received hepatitis C antiviral therapy and achieved a cure. We compared the risk of first-time liver cancer in patients treated with the newest interferon-free regimens, to patients treated with interferon. After accounting for the different characteristics of these two treatment groups, we found no evidence that interferon-free therapy is associated with a higher risk of liver cancer.

Mar 19, 2018
Patients with hepatitis C who are successfully treated with direct-acting antiviral agents experience a dramatic reduction in their risk for liver cancer, new data show. However, the decrease is much lower for those diagnosed with cirrhosis before starting a DAA.

Mar 13, 2018
Persistence of hepatocellular carcinoma risk in hepatitis C patients with a response to IFN & cirrhosis

Stagnation of fibrosis regression is associated with a high risk for HCC after SVR

Mar 3, 2018

Feb 12, 2018
Hepatocellular carcinoma - Updated and evidence-based review
Alejandro Forner, MD, MD Alejandro Forner
Published: 04 January 2018
DOI: http://dx.doi.org/10.1016/S0140-6736(18)30010-2

Full Text
Hepatocellular carcinoma appears frequently in patients with cirrhosis. Surveillance by biannual ultrasound is recommended for such patients because it allows diagnosis at an early stage, when effective therapies are feasible. The best candidates for resection are patients with a solitary tumour and preserved liver function. Liver transplantation benefits patients who are not good candidates for surgical resection, and the best candidates are those within Milan criteria (solitary tumour ≤5 cm or up to three nodules ≤3 cm). Image-guided ablation is the most frequently used therapeutic strategy, but its efficacy is limited by the size of the tumour and its localisation. Chemoembolisation has survival benefit in asymptomatic patients with multifocal disease without vascular invasion or extrahepatic spread. Finally, sorafenib, lenvatinib, which is non-inferior to sorafenib, and regorafenib increase survival and are the standard treatments in advanced hepatocellular carcinoma. This Seminar summarises the scientific evidence that supports the current recommendations for clinical practice, and discusses the areas in which more research is needed....

Future perspectives
In the past 10 years, treatment of hepatocellular carcinoma has evolved considerably. Nowadays, patients with hepatocellular carcinoma can benefit from effective options that improve their survival whatever the evolutionary stage of disease at diagnosis. However, improvement can still be made in several areas. Prevention of the acquisition of the risk factors for development of hepatocellular carcinoma is the best strategy for decreasing mortality. The high efficacy of direct acting antivirals in elimination of chronic hepatitis C virus infection is expected to have an impact on the incidence of hepatocellular carcinoma, but further information about disease evolution in the patients after viral cure needs to be collected.......

Article Downloaded & shared by @HenryEChang via Twitter.
View Article: https://jumpshare.com/v/La5WS4Mn8Uwpi927nbeU

December 2017
Healio - December 8, 2017
Liver cancer incidence after HCV therapy linked to risk factors, not treatment
Li DK, et al. Hepatol. 2017;doi:10.1002/hep.29707. 
Direct-acting antiviral treatment for hepatitis C did not correlate with an increased risk for hepatocellular carcinoma in a large cohort study of both treated and untreated patients with or without cirrhosis. Those with incident HCC after DAA treatment had higher risk factors at baseline. “There was no increased risk for HCC as a result of having received DAA therapy whatsoever,” Raymond T. Chung, PhD, director of Hepatology and Liver Center at Massachusetts General Hospital, told Healio Gastroenterology and Liver Disease. “The risk was related to their preexisting likelihood of developing HCC. The fact that HCC developed post-DAA, we think, is more likely to be an accident of timing than the idea that it's related to receipt of DAA — these persons were at risk for HCC whether they received DAAs or not.”

Innes H, et al. J Hepatol. 2017;doi:10.1016/j.jhep.2017.10.033.
Recently published data suggest that higher hepatocellular carcinoma incidence after sustained virologic response with interferon-free hepatitis C treatment correlates to patient baseline risk factors, such as age, Child-Turcotte Pugh score and prior treatment, rather than IFN-free therapy.

HCV Clearance Lowers Liver Cancer Risk by 70% no Matter Drug of Choice
Reaching sustained virologic response with direct-acting antivirals reduced the occurrence of hepatocellular carcinoma by 71%, but all treatments that cleared the virus saw a similar reduction in risk, according to a presenter at The Liver Meeting 2017.


November 2017
HCV Advocate – Direct-Acting Antiviral Treatment & Decrease a Incidence of Liver Cancer
The studies on this blog looked at treatment with DAAs to find out if curing hepatitis C (HCV) with DAAs improved HCV disease progression and reduced the risk of liver cancer.

October 2017
Oct 23, 2017
The Liver Meeting® 2017 - Vets with HCV Might Settle Cancer Controversy
In the largest cohort analyzed to date -- some 62,000 patients in the VA system -- there is no evidence that therapy with newer agents that act directly against the virus (DAAs) increases the risk of hepatocellular carcinoma (HCC), according to George Ioannou, BMBCh, of the Veterans Affairs Puget Sound Health Care System in Seattle.

Oct 20, 2017
The Liver Meeting® - Direct‐Acting Antiviral Therapy Cuts Liver Cancer Risk By 71%
The study’s findings showed that DAA‐induced sustained virological response is associated with a 71 percent reduction in patients’ liver cancer risk, and showed treatment with DAAs is not associated with increased liver cancer risk compared to treatment with interferon.

Oct 16, 2017
Short-term risk of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting anti-viral treatment
In conclusion, our data showed no evidence of an increased risk of de novo HCC or recurrence by patients treated with interferon-free SOF-based regimens. However, cirrhosis was strongly associated with the short-term development of HCC after HCV eradication. Moreover, our findings underscore the fact that the serum EOT-AFP level is a useful marker for predicting de novo HCC for cirrhotic patients and that close HCC surveillance should be required for patients with a past history of HCC, especially for patients treated with noncurative procedures. Going forward, further studies will be required to elucidate the risk of HCC development over the long-term.....

Oct 3, 2017
HCV Treatment Not Associated with Liver Cancer, New Evidence Suggests
Kenneth Bender
An assessment of over 62,000 patients treated for hepatitis C (HCV) revealed no evidence to support the suggestion that direct acting antiviral (DAA) agents promote recurrence of hepatocellular carcinoma (HCC), and found instead that successful treatment with or without DAAs is associated with reduced risk of HCC.

September 2017
Sep 18, 2017
Coverage OncLive - 2017 International Liver Cancer Association Annual Conference
Study Shows DAAs Are Not Associated With Increased HCC Recurrence Risk
Angelica Welch
Published Online: Monday, Sep 18, 2017
Direct acting antivirals (DAA) are a novel and completely oral hepatitis C therapy that is associated with a high response rate. DAAs are used in most patients being treated for hepatitis C, including those with decompensated cirrhosis.

Sep 12, 2017
Full Text Article Provided by NATAP
"Most HCV-infected patients in the United States will undergo DAA-based antiviral treatment in the next few years and the vast majority of them will achieve SVR. Our results suggest that DAA-induced SVR is associated with a 71% reduction in HCC risk (AHR 0.29, 95% CI 0.23-0.37) compared to treatment failure. The reduction in HCC risk associated with SVR was similar irrespective of whether SVR was achieved by DAA-ONLY, DAA+IFN or IFN-ONLY regimens. This suggests that eradication of HCV reduces HCC risk independently of how it is achieved. In contrast to prior reports that suggested an increased HCC risk in patients treated with DAAs[[3], [7]], we found that receipt of DAA-ONLY antiviral treatment was not associated with increased risk of HCC when compared to receipt of IFN-ONLY antiviral treatment.....We found no evidence that treatment with DAAs was associated with increased risk of HCC compared to treatment with IFN.

Sept 5, 2017
Risk for hepatocellular carcinoma after HCV antiviral therapy with DAAs: case closed?
Several studies of patients treated with interferon -based therapy nicely documented that the risk for hepatocellular carcinoma (HCC) was markedly lower in patients who achieved SVR compared to those without SVR. 5-7 As a result, it was naturally assumed that with higher cure rates with DAAs, cancer rates would start to decline. It was therefore surprising and unsettling in 2016 to see a series of reports of unexpectedly high rates of ‘early’ HCC recurrence after ‘curative’ therapy as well as higher than expected rates of de novo HCC in patients who achieved SVR with DAAs.
PDF Full Text Article - Provided by @HenryEChang via Twitter

August 2017
Aug 15, 2017
How Do Direct-Acting Antivirals for HCV Affect HCC Risk?
The latest data on the controversial hepatitis C-hepatocellular carcinoma treatment link are examined.

Aug 10, 2017
The risks of hepatocellular carcinoma development after HCV eradication are similar between patients treated with peg-interferon plus ribavirin and direct-acting antiviral therapy
The risk of hepatocellular carcinoma (HCC) development is reduced following viral elimination by interferon therapy in chronic hepatitis C patients. However, the risk in patients treated with interferon-free direct-acting antivirals (DAAs) is unknown. We evaluated chronic hepatitis C patients who achieved viral eradication by pegylated-interferon plus ribavirin (PEG-IFN/RBV, n = 244) or daclatasvir plus asunaprevir (DCV/ASV, n = 154) therapy...

Aug 4, 2017
Liver cancer, mortality risks decrease with SVR after direct-acting antivirals
Patients who achieved sustained virologic response after direct-acting antiviral treatment also had significantly lower all-cause mortality and lower incident rates of…

July 2017
July 26, 2017
Medscape
With Hepatitis C Virus on the Run, Meet the New Challenge: Hepatocellular Carcinoma
Significant advances in the clinical practice of hepatology were addressed during this year's Digestive Disease Week. This review focuses on the concerns related to the apparent increase in the incidence of hepatocellular carcinoma (HCC).

July 16
Hepatitis C virus eradication with direct antiviral agents and liver cancer recurrence: Is the best the enemy of the good? Antiviral therapy has long been perceived as an adjuvant treatment modality worth to be offered to patients with chronic hepatitis C virus (HCV) infection after successful removal of a hepatocellular carcinoma (HCC), an approach dating more than two decades since interferon was first employed to treat non-A, non-B hepatitis.

July 10
DAAs do not affect HCC risk, SVR reduces risk
July 10, 2017
Recently published data showed a link between sustained virologic response and a reduced risk for hepatocellular carcinoma among patients treated with direct-acting…

July 3
Sustained response to direct-acting HCV antivirals tied to lower HCC risk
July 3, 2017
by Marilynn Larkin
NEW YORK (Reuters Health) - A sustained virologic response to direct-acting antiviral treatment of hepatitis C (HCV) is associated with a “considerable” reduction in the risk of hepatocellular carcinoma (HCC), researchers say. Dr. Fasiha Kanwal of Baylor College of Medicine in Houston, Texas and colleagues analyzed data on 22,500 HCV patients (mean age 62) from 129 Veterans Health Administration hospitals who filled more than one prescription of sofosbuvir, simeprevir, ledipasvir, a combination of paritaprevir/ritonavir or ombitasvir and dasabuvir, and daclatasvir in 2015.

June 2017
June 26, 2017
Challenges in Treatment of Hepatitis C among Patients with Hepatocellular Carcinoma

June 3, 2017
Medscape Coverage from the International Liver Congress (ILC) 2017
Navigating the Hep C Treatment and Cancer Risk Minefield

May 2017
May 26
Hepatocellular carcinoma and direct- acting antivirals: A never ending story?
Vincenza Calvaruso* andAntonio Craxì Version of Record online: 24 MAY 2017 DOI: 10.1111/liv.13421
Liver International
Volume 37, Issue 6, pages 812–814, June 2017

Key Points
• The benefit of SVR is higher in patients without clinically significant portal hypertension
• HCC occurrence in patients with compensated cirrhosis is comparable to historical controls of patients who achieved SVR after interferon-based therapy.
• Patients who achieve SVR with DAAs had a lower risk of developing liver cancer than those patients whose HCV infection was not cured.
• Data available on patients with previous HCC do not show an increased risk of HCC recurrence and report a comparable rate of reappearance of cancer among DAA-treated and untreated patients.

Full Text

Link Provided By
Henry E. Chang via Twitter

May 26
Summary Of  Available Data:
New Hep C Treatment Not Linked to Liver Cancer
Contrary to some earlier research, most recent studies see no association between response to DAAs and HCC

Do HCV DAAs Increase HCC Recurrence Risk or Not?
Does the administration of direct-acting antiviral (DAA) therapy increase a patient’s risk of hepatocellular carcinoma (HCC) recurrence?

Direct-acting-antivirals (DAA) can cure patients of the life-threating hepatitis C virus (HCV) infection, with cure rates exceeding 95%. However, questions have been raised about the long-term consequences of curing patients with DAAs, including a potential link between DAA treatment and the development of hepatocellular carcinoma (HCC).

Improved survival of patients with hepatocellular carcinoma and compensated HCV-related cirrhosis who attained SVR
Few studies examined the outcome of patients with HCV-related cirrhosis who developed hepatocellular carcinoma (HCC). The relative weight as determinant of death for cancer versus endstage-liver-disease (ESLD) and the benefit of HCV eradication remain undefined. This multicenter, retrospective analysis evaluates overall survival (OS), rate of decompensation and tumor recurrence in compensated HCC patients treated with IFN according to HCV status since HCC diagnosis.

Of Interest
HCC in presence of HCV decreases cure rate in DAA treatment
Patients with hepatocellular carcinoma and hepatitis C were less likely to achieve sustained virologic response while receiving direct-acting antiviral therapy compared with patients without HCC, according to results of a retrospective study.

International Liver Congress
April 21,2017
Direct-acting antivirals for hepatitis C not linked to higher liver cancer risk in most studies
People with hepatitis C who take treatment with direct-acting antivirals (DAAs) do not appear to have a higher risk of developing liver cancer compared to those treated with interferon, and the seemingly higher rates seen in some studies are attributable to risk factors such as older age and more advanced liver disease, according to a set of studies presented on Thursday at the International Liver Congress in Amsterdam. The congress is the annual meeting of the European Association for the Study of the Liver (EASL).

April 20, 2017
#ILC 2017: Is direct-acting antiviral therapy for Hepatitis C associated with an increased risk of liver cancer? The debate continues
Eight studies being presented at The International Liver Congress™ 2017 demonstrate contrasting evidence on the potential link between direct-acting antiviral treatment for Hepatitis C and liver cancer

Commentary on this study
Hepatitis C Patients At No Elevated Risk of Developing HCC Following DAA Compared To Interferon
Patients were at no elevated risk of developing hepatocellular carcinoma (HCC) after achieving sustained virologic response (SVR) following treatment with direct-acting antiviral therapy (DAA) for hepatitis C compared to interferon therapy, according to results of a meta-analysis reported at the 2017 International Liver Congress (ILC).

Timing of DAA therapy and HCC response may impact recurrence rate
April 20, 2017
AMSTERDAM — Unexpectedly high hepatocellular carcinoma recurrence rates were reported among patients who achieved sustained virologic response after receiving direct-acting antiviral therapy, according to data presented at the International Liver Congress.
“This update further supports our findings about an unexpected high recurrence rate associated in time with DAA, but also exposes a more aggressive pattern of recurrence and faster tumor evolution,” Maria Reig, MD, of the Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic Barcelona, at the University of Barcelona, said in her presentation.

Liver International
April 20, 2017
Download PDF - Full Text
Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C
Arrival of direct-acting antiviral (DAA) agents against hepatitis C virus (HCV) with high-sustained virological response (SVR) rates and very few side effects has drastically changed the management of HCV infection. The impact of DAA exposure on hepatocellular carcinoma (HCC) recurrence after a first remission in patients with advanced fibrosis remains to be clarified

Editorial - Healio
April 20, 2017
HCC After DAAs Requires More Study, but no Cause for Withheld Treatment
HCV Next, April 2017
As we continue to see the success of direct-acting antiviral therapy in treating hepatitis C virus, we must be aware of any potential complications from the underlying liver disease after successful treatment, especially hepatocellular carcinoma.

March 15, 2017
Full Text - Download PDF
Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals
Abstract
Hepatitis C virus infection is a major cause of hepatocellular carcinoma worldwide. Interferon has been the major antiviral treatment, yielding viral clearance in approximately half of patients. New direct-acting antivirals substantially improved the cure rate to above 90%. However, access to therapies remains limited due to the high costs and under-diagnosis of infection in specific subpopulations, e.g., baby boomers, inmates, and injection drug users, and therefore, hepatocellular carcinoma incidence is predicted to increase in the next decades even in high-resource countries. Moreover, cancer risk persists even after 10 years of viral cure, and thus a clinical strategy for its monitoring is urgently needed. Several risk-predictive host factors, e.g., advanced liver fibrosis, older age, accompanying metabolic diseases such as diabetes, persisting hepatic inflammation, and elevated alpha-fetoprotein, as well as viral factors, e.g., core protein variants and genotype 3, have been reported. Indeed, a molecular signature in the liver has been associated with cancer risk even after viral cure. Direct-acting antivirals may affect cancer development and recurrence, which needs to be determined in further investigation.
Download PDF

Feb 27, 2017
People with HIV and hepatitis C virus (HCV) co-infection who are successfully treated for hepatitis C using interferon-free direct-acting antiviral (DAA) therapy do not appear to have an increased likelihood of developing hepatocellular carcinoma (HCC), according to a study presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2017) this month in Seattle.

Accepted Manuscript
Gastroenterology Accepted Date: 23 January 2017
Genome-wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection

Media Coverage of this Article
Feb 22, 2017
Genetic variant linked to risk of liver cancer after hep C eradication
NEW YORK (Reuters Health) – A single nucleotide polymorphism (SNP) in the tolloid-like 1 (TLL1) gene is associated with the development of hepatocellular carcinoma (HCC) after eradication of hepatitis C virus (HCV) infection, researchers from Japan report.
“When we constructed different models for predicting HCC in patients with mild as opposed to advanced hepatic fibrosis by combining this TLL1 variant with other distinct risk factors, these proposed models including TLL1 variant could be useful for predicting the occurrence of HCC after achieving sustained virological response (SVR) in the clinical practice,” Dr. Yasuhito Tanaka from Nagoya City University Graduate School of Medical Sciences told Reuters Health by email.
Continue reading...

Feb 8, 2017
High Rates of Hepatocellular Carcinoma After Hepatitis C Treatment
NEW YORK (Reuters Health) - Patients treated with direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV)-related cirrhosis appear to have high rates of hepatocellular carcinoma (HCC).

"If these findings are confirmed from other centers, studies are suggested to examine mechanisms of these findings," Dr. Ashwani Singal from University of Alabama at Birmingham told Reuters Health by email.

Some studies have shown unexpectedly high HCC recurrence rates after DAA therapy, whereas others have shown no such association.

Dr. Singal and colleagues examined the occurrence of de novo HCC in their retrospective study of 66 patients with HCV-related cirrhosis who received DAA between 2015 and 2016.

Typically, patients with HCV cirrhosis have an HCC incidence of 3%-5% per year, the researchers say.

But six of these patients (9.1%) developed HCC during or within six months after treatment, and two additional patients (3%) developed indeterminate liver lesions, according to their letter online February 1st in Gastroenterology.

They note that another study showed a reduced risk of HCC occurrence among DAA-treated patients who achieved sustained viral responses (SVR) versus those not achieving SVR, so they suggest prospective multicenter studies to confirm these findings.

"Be aware of this potential issue and consider more intensive HCC surveillance of HCV cirrhotics during and after HCV therapy," Dr. Singal concluded.

Dr. Gaetano Serviddio from University of Foggia, Italy, who has reported on the outcomes of DAA therapy, told Reuters Health by email, "DAAs have completely changed the prognosis of chronic hepatitis C patients who have a unique possibility to be cured definitively. To discover that such drugs have some tumor risks is particularly terrible. In any case, the number of events is small, and the data are not enough to support the hypothesis that the risk is directly related to the drugs."

"DAAs are safe and powerful drugs; millions of lives will be saved with such drugs," he said. "Studies should be supported to completely define patients at risk of HCC recurrence."
SOURCE: http://bit.ly/2lmDbXa
Gastroenterol 2017.

January 2017
In Press, Corrected Proof
Digestive and Liver Disease
Available online 21 January 2017
HCV clearance by direct antiviral therapy and occurrence/recurrence of hepatocellular carcinoma: A “true-or-false game”
Three years ago, the new direct antiviral therapies (DAAs) were approved for HCV treatment and the scenario completely changed. The share of patients in whom eradication is obtained raised to over 90% [7], the limits in the stage of the disease that can be treated disappeared, but solid data on the long-term outcome of cirrhotics treated with these new drugs are lacking.

A totally unexpected, intriguing and somehow hard-to-believe report of an increased incidence of HCC with rapid recurrence after HCV eradication with DAAs was first presented at the 2016 EASL meeting and then published in the Journal of Hepatology.....
Continue to full text article...

2016
AASLD 2016 and International Liver Congress 2016
Two studies presented at The Liver Meeting® 2016, and research presented in April at the International Liver Congress 2016.

Patients With HCV Who Treated With Interferon-based Therapy  
We begin with a study presented at AASLD 2016; The impact of sustained virological response to HCV infection on long term risk of hepatocellular carcinoma: the BC Hepatitis Testers Cohort, that suggested patients achieving SVR were still at risk for hepatocellular carcinoma, more specifically older patients and those with cirrhosis, commentary on the study is available over at Healio; SVR post–interferon-based therapy reduces, not eliminates risk for HCC, below is a summary of the study followed by slides @ NATAP 

Liver cancer risk reduced in patients cured of HCV
A large study found that the risk of hepatocellular carcinoma was reduced by 80% in people cured of HCV compared to those who were not cured.

This was a study of the entire population of people treated for HCV in British Columbia province, Canada, between 1990 and 2013. The study identified 8147 people treated with interferon-based regimens, 57% of whom were cured. Treated individuals were followed for a median of 5.6 years.

The liver cancer incidence was highest among those with cirrhosis who did not achieve a SVR (21 cases per 1000 patient-years of follow-up). In comparison, the liver cancer incidence was 6.4 per 1000 patient-years in those with cirrhosis who achieved SVR, 7.2 in those without cirrhosis who did not achieve SVR12 and 1.1 per 1000 patient-years in those without cirrhosis who achieved SVR12.

In a multivariable analysis liver cancer was associated with cirrhosis, age over 50 years, genotype three infection versus genotype one, alcohol consumption and being male in those who were not cured. In those who were cured of hepatitis C, only cirrhosis, age over 50 and being male were associated with an increased risk of liver cancer.

The researchers concluded that although curing HCV greatly reduces the risk of developing liver cancer, it does not eliminate the risk entirely. Older people and those with cirrhosis are at higher risk than others, underlining the importance of early diagnosis and treatment.

Reference
The impact of sustained virological response to HCV infection on long term risk of hepatocellular carcinoma: the BC Hepatitis Testers Cohort. Janjua NZ et al. The 67th Meeting of the American Association for the Study of Liver Diseases, Boston 2016. Abstract 175
Summary Source - https://www.basl.org.uk/

Review Slides

Patients With HCV Who Treated With Oral DAAs
In a prospective study presented at the 2016 AASLD; Incidence and pattern of "de novo" hepatocellular carcinoma in HCV patients treated with oral DAAs, reported that treatment with direct-acting antiviral therapy did not increase the risk of developing hepatocellular carcinoma in patients with HCV, but patients with advanced liver disease should continue to be monitored for liver cancer after treatment, here is the AASLD press release, followed by slides @ NATAP.

AASLD Press Release;
AASLD 2016 - Is There an Increased Risk of Cancer After Taking Direct-Acting Antiviral Medication?
BOSTON, Nov. 11, 2016
A new study presented this week at The Liver Meeting® — held by the American Association for the Study of Liver Diseases — found patients with hepatitis C who take direct-acting antiviral medication are at no higher risk for developing liver cancer than those who do not take the medication. However, they might be at an increased for more aggressive, infiltrative patterns of cancer, should they develop it.

"Data on clinical outcomes in cirrhotic patients with hepatitis C treated with direct-acting antiviral agents (DAAs) are still scanty and somehow controversial, and this is particularly true for development of a liver cancer, one of the most frequent and deadly complications of the disease," says Alfredo Alberti; professor of gastroenterology at University of Padova in Padova, Italy, and lead investigator in the study.

Recent studies have suggested the possibility of increased risk of developing liver cancer (hepatocellular carcinoma, or HCC) during and after DAA treatment in patients with hepatitis C (HCV). Dr. Alberti's team recently looked at the incidence of new cases of liver cancer among 3,075 HCV patients with advanced liver disease who were treated with DAAs. Almost 70 percent of the patients studied were men, and nearly 86 percent had cirrhosis (scarring of the liver). HCV genotypes one through four were all represented in the study, and patients with a past history of liver cancer were excluded.

All participants were treated with oral DAA therapy and monitored monthly. At the time of Dr. Alberti's team's analysis, patients had an average follow up of nearly 305 days from the time they started DAA therapy. During this period, the researchers found 41 patients had developed liver cancer, and the overall incidence (per 100 patient years) was 1.64.

Dr. Alberti's team further noted an incidence rate of 0.23 in patients without cirrhosis and of 1.93 in those with cirrhosis (1.93 for men and 1.94 for women). Incidence rates varied among HCV genotypes as well, with HCV-1 at the low end (1.70) and HCV-3 at the high end (2.44). Finally, cirrhotic patients with a Child-Pugh score of 'A' had an incidence rate of 1.64 and those with more advanced disease and a score of 'B' had a rate of 2.92.

"These rate incidences were not significantly different from those observed in historical control cohorts of similar patients from the same geographic area, not receiving antiviral therapy, indicating that the risk of developing HCC is not increased by oral DAAs, being closely dependent on stage of disease as in untreated cases," says Dr. Alberti.

Liver cancer was diagnosed four weeks after starting DAA therapy in three patients, at week eight in three patients, week 12 in six patients, between week 12 and 24 in thirteen patients, and after treatment ended in sixteen patients. Fifty percent of patients who developed liver cancer developed a single nodular cancer with a typical vascular pattern, while 50 percent had a more aggressive pattern. Finally, 28 out of the 41 patients who developed cancer were successfully cured of HCV (reaching a sustained virological response at 12 weeks), while the remaining 13 relapsed.

In different analyses of the data, Dr. Alberti's team found elevated liver enzymes and low platelet count to be associated with liver cancer risk, while gender, age, HCV genotype and DAA regimen were not. The best baseline predictor of liver cancer risk was APRI scores (which calculate scarring in the liver). The researchers find the risk of developing liver cancer increased linearly by 10 percent at each one-point increase in APRI value.

"The results of this study, while confirming that DAAs treatment doesn't increase the overall risk of HCC, indicate that there is no pharmacological prevention of HCC even with successful antiviral therapy, at least during the first six to 12 months after initiation of treatment when microscopic and therefore initially invisible HCC foci might even be boosted in their growth as consequence of the profound immunological and molecular changes in the liver microenvironment following abrupt cessation of HCV replication," explains Dr. Alberti. "Therefore, it is mandatory that patients treated with DAAs with advanced liver disease should continue to be monitored for HCC."

This release contains updated data. Dr. Alberti will present these findings at AASLD's press conference in Room 313 at John B. Hynes Veterans Memorial Convention Center in Boston on Saturday, November 12 at 4pm. The study entitled "Incidence and pattern of "de novo" hepatocellular carcinoma in HCV patients treated with oral DAAs" will be presented by Antonietta Romano, MD in Ballroom A on Sunday, November 13 at 10am. The corresponding abstract (number 19) can be found in the journal, Hepatology – Special Issue: The 67th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2016.

View the slides @ NATAP Reported by Jules Levin
"Incidence and pattern of "de novo" hepatocellular carcinoma in HCV patients treated with oral DAAs"
Another look at both studies;  Incidence and pattern of `de novo` hepatocellular carcinoma in HCV patients treated with oral DAAs and The impact of sustained virological response to HCV infection on long term risk of hepatocellular carcinoma: the BC Hepatitis Testers Cohort.

Liver cancer risk reduced after hepatitis C treatment, but vigilance needed for aggressive cancers in months after treatment
Keith Alcorn
People who are cured of hepatitis C after a course of direct-acting antiviral treatment do not have a higher risk of developing liver cancer (hepatocellular carcinoma), and probably have a reduced risk, studies from Italy and Canada presented at The Liver Meeting this week in Boston have shown. However, Italian researchers also found that those people who did develop liver cancer during or shortly after antiviral treatment were more likely to develop an aggressive form of liver cancer, perhaps because of changes in immune surveillance in the liver as a result of treatment.

Patients With HCV And History Of Liver Cancer Who Treated With New Antivirals
As a reference point two studies presented in April at the International Liver Congress 2016 found; patients with a history of hepatocellular carcinoma have the highest risk of developing a tumor after direct-acting antiviral therapy, but new diagnoses were also reported. ​​Read the report; Liver Cancer Found in Hepatitis C Patients on New Antivirals provided below, or over at Medscape.

Liver Cancer Found in Hepatitis C Patients on New Antivirals
Kate Johnson
April 15, 2016
BARCELONA, Spain — In a surprising number of patients with hepatitis C and cirrhosis, hepatocellular carcinoma develops within weeks of starting treatment with direct-acting antivirals, new research suggests.

"I do not think that direct-acting antivirals are directly responsible," said lead investigator Stefano Brillanti, MD, from the University of Bologna, Italy.

"The hypothesis is that immune surveillance may be reduced too rapidly," he told Medscape Medical News. "You have an immediate drop in viremia, but also attenuation of inflammation. I think inflammation is a bad thing in terms of hepatitis progression, but it may be a good thing in terms of controlling cancer."

The study by Dr Brillanti's team, presented here at the International Liver Congress 2016, suggests that patients with hepatitis C should be closely monitored after treatment with direct-acting antivirals. Two days earlier, a study conducted by a team from the University of Barcelona in Spain suggested the same thing (J Hepatol. Published online April 12, 2016).

Both studies indicate that patients with a history of hepatocellular carcinoma have the highest risk of developing a tumor after direct-acting antiviral therapy, but new diagnoses were also reported.

The EMA has extended the scope of its review of the six direct-acting antivirals approved for use in the European Union for the treatment of chronic hepatitis  C infection to include the risk for early liver cancer recurrence, the agency reported.

Tumor Risk
"Patients with previous hepatocellular carcinoma are, of course, at risk of recurrence anyway," Dr Brillanti said. "A 30% rate over 3 years from initial surgery or ablation is normal. What was surprising to us was that we were observing 4 cm lesions after 12 weeks."

The retrospective cohort study involved 344 consecutive patients with hepatitis C and cirrhosis who were treated with one or two direct-acting antivirals and followed for 24 weeks after therapy. Median age was 63 years.
In this cohort, 237 patients were infected with hepatitis C genotype 1, 191 had received previous antiviral treatment, and 59 had been successfully treated for hepatocellular carcinoma.

Contrast-enhanced ultrasonography and CT scans or MRIs were performed at baseline to exclude active hepatocellular carcinoma, and then again 12 and 24 weeks after treatment.
During the follow-up period, 26 of the 344 patients (7.6%) were diagnosed with hepatocellular carcinoma. This included 17 of the 59 patients previously treated for hepatocellular carcinoma, and nine of the 285 patients (3.2%) with no history of carcinoma.

There was no association between recurrence and hepatitis C genotype, direct-acting antiviral regimen, or treatment response for patients who did not develop hepatocellular carcinoma or for those who did. The sustained viral response rate at 12 weeks was 89% in the two groups.
For patients with a history of hepatocellular carcinoma, those who developed a recurrence were significantly younger than those who did not (56 vs 73 years), were more frequently treatment-experienced (88.2% vs 61.9%), and had more advanced liver fibrosis at baseline.

More patients who developed hepatocellular carcinoma during the follow-up period, regardless of history, had advanced cirrhosis than those who did not, indicated by a Child-Pugh class B score (26.9% vs 10.1%; P =.02). They also had more liver stiffness, indicated by a measure above 21.3 Kpa (61.5% vs 31.8%; P = .005), and fewer platelets at baseline (102.3 vs 124.4 × 1000/mm³; P = .02).

Second Study
In the Spanish study, all 58 hepatitis C patients had a history of hepatocellular carcinoma (with complete radiologic response), and all but three were cirrhotic at the start of direct-acting antiviral therapy. After a median follow-up of 5.7 months, the rate of tumor recurrence was 27.6%, with a median time to recurrence of 3.5 months. The sustained viral response rate at 12 weeks was 97.5%.

In their publication, the Spanish authors note that these findings "raise a concern about the benefits" of direct-acting antiviral therapy in the subgroup of hepatitis C patients with a history of hepatocellular carcinoma. Although the therapies "offer a major hope for current and future patients, we may face a drawback that may change these predictions in specific groups of patients," they point out.

Dr Brillanti said he is less concerned. "Clones of the hepatocellular carcinoma were present before the therapy," he pointed out, suggesting that direct-acting antivirals simply accelerated their inevitable progression. Either way, he said, an increased risk for hepatocellular carcinoma should not deter clinicians or patients from pursuing treatment with direct-acting antivirals when it is needed.

"This is a different cancer than elsewhere in oncology — it is a cancer within an advanced chronic disease — so the prognosis, the life expectancy, is related not only to the liver cancer but also to the liver disease and liver function," he explained. "If you don't treat these patients and ameliorate their liver function, and if hepatocellular carcinoma occurs, you have no chance of curing them. But if you ameliorate liver function and they develop hepatocellular carcinoma, you can cure it better because their improved liver function will allow an ablation."

This finding is "quite striking and unexpected, but we have to be cautious," said Laurent Castera, MD, PhD, from Hôpital Beaujon in Clichy, France, who is vice-secretary of the European Association for the Study of the Liver, and was not involved with the research.

"It is potentially worrying, but these are retrospective studies, with possible referral bias, and no long-term follow-up," he told Medscape Medical News.

Dr Brillanti reports receiving research grants from Gilead Sciences and being on the advisory board for Janssen and Gilead Sciences. Dr Castera reports serving on the speaker's bureau for Echosens.
International Liver Congress (ILC) 2016: Abstract LBP506. Presented April 14, 2016.
Source - Medscape

Feb 2017
Of Interest - In The News
Risk of liver cancer low in patients with cirrhosis, study finds
01 Feb 2017
The results of a study by researchers at The University of Nottingham suggest that the risk of liver cancer in patients with cirrhosis may be much lower than previously thought.

Liver cancer – or hepatocellular carcinoma (HCC) – is one of the most serious complications of cirrhosis, or scarring of the liver, caused by long-term liver damage.

However, an analysis of health records, published in the academic journal Alimentary Pharmacology and Therapeutics, found that the 10-year incidence of HCC in UK patients with cirrhosis is actually only four per cent, or lower.

Joe West, Professor of Epidemiology in the University’s School of Medicine, led the study and believes that the results could better inform doctors on how best to focus resources for the benefit of patients with liver damage.

He said: “This very low incidence of HCC occurrence in people with cirrhosis caused by alcohol or of unknown origin suggests that surveillance for HCC among these groups is likely to benefit patients little.

“As surveillance incurs substantial cost, it is therefore unlikely to represent value for money for the NHS. There may well be other ways of spending this money that would benefit patients far more.”

Cirrhosis is caused by long-term damage to the liver, which leads to a build-up of scar tissue which replaces healthy tissue and eventually can result in liver failure.

The researchers identified more than 3,000 patients with cirrhosis of the liver using the UK’s General Practice Research Database between 1987 and 2006 and then cross-referenced this information with diagnoses of HCC on linked national cancer registries.

The study found that only 1.2 per cent of patients with alcoholic cirrhosis and 1.1 per cent of patients with cirrhosis of unknown cause will develop HCC within a decade. The highest 10-year incidence of HCC was among those with cirrhosis due to chronic viral hepatitis (four per cent).
http://www.nottingham.ac.uk/news/pressreleases/2017/january/risk-of-liver-cancer-low-in-patients-with-cirrhosis-study-finds.aspx

March 2017
Antiviral medication successful for treating HCV in hepatocellular carcinoma

Hepatocellular Carcinoma Decreases the Chance of Successful Hepatitis C Virus Therapy with Direct-Acting Antivirals
The new medications for hepatitis C have excellent cure rates. However, our study shows that in patients with both liver cancer and hepatitis C, they do not achieve these cure rates. Patients with liver cancer are almost 6 times more likely to fail hepatitis C treatment than patients without liver cancer

AGA Institute Clinical Practice Update: Care of Patients Who Have Achieved a Sustained Virologic Response (SVR) Following Antiviral Therapy for Chronic Hepatitis C Infection
Ira M. Jacobson M.D., Joseph K. Lim, M.D., and Michael W. Fried, M.D.
ACCEPTED MANUSCRIPT
DOI: http://dx.doi.org/10.1053/j.gastro.2017.03.018

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Abstract
Chronic hepatitis C virus (HCV) infection is well-recognized as a common blood borne infection with global public health impact, affecting 3 to 5 million persons in the U.S. and over 170 million persons worldwide. Chronic HCV infection is associated with significant morbidity and mortality due to complications of liver cirrhosis and hepatocellular carcinoma (HCC). Current therapies with all-oral directly acting antiviral agents (DAAs) are associated with high rates of sustained virologic response (SVR), generally exceeding 90%. SVR is associated with a reduced risk of liver cirrhosis, hepatic decompensation, need for liver transplantation, and both liver-related and all-cause mortality. However, a subset of patients who achieve SVR will remain at long-term risk for progression to cirrhosis, liver failure, HCC, and liver-related mortality. Limited evidence is available to guide clinicians on which post-SVR patients should be monitored versus discharged, how to monitor and with which tests, how frequently should monitoring occur, and for how long. In this clinical practice update, available evidence and expert opinion are used to generate best practice recommendations on the care of patients with chronic HCV who have achieved SVR.

Index
Assessment of HCV RNA after SVR12 has been attained
With the initiation of trials of DAA regimens, initially in combination with interferon and later without it, the attainment of SVR 12 weeks after completion of treatment replaced SVR24 as the primary endpoint, defined as undetectable HCV RNA on a highly sensitive PCR assay (lower limit of detection <12 IU/mL). This transition was based upon the rarity of relapse after follow up week 12, and it helped move the field ahead by shortening the intervals between successive trials in development programs (22). It has become apparent that late relapse beyond this time point is no more common, and perhaps less so, than it was after interferon-based therapy
Ongoing surveillance for hepatocellular carcinoma after SVR Is HCC risk after SVR exclusive to patients with advanced fibrosis and cirrhosis?
Can HCC surveillance ever be discontinued?
How should screening for, and management of, varices be affected by SVR?
Should patients be routinely monitored for regression of advanced fibrosis or
cirrhosis?
Recurrent HCC After SVR
Reinfection
Lifestyle Measures
Conclusions
Continue reading...

Wednesday, June 6, 2018

Mayo Clinic researchers take a step closer to developing a DNA test for liver cancer

WASHINGTON, D.C. - A group of researchers from Mayo Clinic and Exact Sciences Corporation have completed a phase II study comparing a set of DNA markers to alpha fetoprotein as a method to test for liver cancer. The researchers presented their findings today at the 2018 Digestive Disease Week conference in Washington, D.C.

"We currently test for liver cancer using ultrasound and a blood protein marker called alpha fetoprotein," says John Kisiel, M.D., a gastroenterologist at Mayo Clinic. "Unfortunately, these tests are not very sensitive for curable stage liver cancers, and most patients who need this testing do not have it easily available or [are] not able to receive it often enough to be effective."

Dr. Kisiel and his colleagues developed a simple blood test using abnormal DNA markers that are known to exist in liver cancer tissues. They were able to confirm that the abnormal DNA markers were present in the overwhelming majority of blood samples that came from people with primary liver cancers. Simultaneously, these markers were absent in healthy individuals and individuals with cirrhosis of the liver but no evidence of tumors on their clinical follow-up.

"We were most excited that our DNA markers were able to detect more than 90 percent of patients with curable stage tumors," says Dr. Kisiel. "This is the main reason why we think a DNA test will make difference, compared to currently available tests." Dr. Kisiel says the next step will be to validate these markers in blood testing on much larger patient cohorts.

According to the National Cancer Institute, the number of new cases of liver and bile duct cancer in the U.S. was 8.8 per 100,000 men and women per year. Dr. Kisiel says primary liver cancer is a major cause of suffering and death for patients who have cirrhosis of the liver or patients with hepatitis B infections. Worldwide, liver cancer is the second most common cause of cancer death.

Tuesday, June 5, 2018

Gut microbes and liver cancer

NIH Research Matters
Gut microbes affect antitumor activity in liver

At a Glance
A study in mice revealed a connection between bacteria in the gut and antitumor immune responses in the liver.

The findings have implications for understanding the mechanisms that lead to liver cancer and developing approaches to treat it.


The microbiome is the community of bacteria and other microbes that live in or on the body. The greatest proportion of the human microbiome is in the intestine, or gut. Recent research has found that the gut microbiome can influence many conditions, including cancer growth.

Cancer is commonly found in the liver. Most of the time, it’s from a cancer that started somewhere else in the body, broke off, and spread to the liver. About 75% of the blood that reaches the liver travels through the portal vein from the digestive tract. That blood includes substances from the gut microbiome. To understand how certain gut bacteria may influence the development of tumors in the liver, a team led by Dr. Tim Greten at NIH’s National Cancer Institute (NCI) carried out a series of experiments in mice. Their study was published on May 25, 2018, in Science.

The scientists tested mouse models of liver cancer. They first depleted certain bacteria from the animals’ guts using antibiotics. Mice given the antibiotics developed fewer and smaller liver tumors.

To understand how the depletion of gut bacteria suppressed tumor growth, the investigators examined immune cells in the liver. They found that antibiotic treatment increased the numbers of natural killer T (NKT) cells, a type of immune cell. Further experiments showed that, in all the mouse models tested, the reduction in liver tumor growth from the antibiotic treatment was dependent on NKT cells.

NKT cells interact with a protein on cell surfaces called CXCL16. The team examined CXCL16 in the cells that line the inside of capillaries in the liver. They found that the accumulation of NKT cells in the liver resulted from an increase in CXCL16.

The scientists next searched for the link between gut microbes and CXCL16. Gut microbes are known to modify bile acids, which are made by the liver to help break down fats during digestion. Through a series of experiments, the team showed that altered bile acids from the gut reduced CXCL16 levels when they traveled back into the liver. Confirming this idea, the team fed different types of bile acids to the mice and found that they affected tumor growth differently in the liver.

The researchers identified a type of bacterium in the gut, Clostridium, that modifies bile acids. Antibiotics that kill Clostridium allow bile acids from the gut to increase levels of CXCL16 and NKT cells in the liver, which inhibits liver tumor growth.

“What we found using different tumor models is that if you treat mice with antibiotics and thereby deplete certain bacteria, you can change the composition of immune cells of the liver, affecting tumor growth in the liver,” Greten says. “This is a great example of how what we learn from basic research can give us insight into cancer and possible treatments.”

These findings in mice may also apply to people with liver cancer. In preliminary work, the researchers showed that different bile acids can also control CXCL16 levels in human liver samples. Further work will be needed to understand the significance of these mechanisms in people.

https://www.nih.gov/news-events/nih-research-matters/gut-microbes-affect-antitumor-activity-liver

Wednesday, May 30, 2018

FDA Accepts Supplemental New Drug Application for Cabozantinib in Advanced HCC

Exelixis Announces U.S. FDA Accepts Supplemental New Drug Application for CABOMETYX® (cabozantinib) in Previously Treated Advanced Hepatocellular Carcinoma

– U.S. Food and Drug Administration assigns Prescription Drug User Fee Act action date of January 14, 2019 –

– The supplemental New Drug Application is based on the CELESTIAL phase 3 pivotal trial, in which CABOMETYX provided a statistically significant and clinically meaningful improvement versus placebo in overall survival –

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--May 29, 2018-- Exelixis, Inc. (Nasdaq:EXEL) today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the company’s supplemental New Drug Application (sNDA) for CABOMETYX® (cabozantinib) tablets as a treatment for patients with previously treated advanced hepatocellular carcinoma (HCC). The FDA has completed its filing review and has determined that the application is sufficiently complete to permit a substantive review. The filing has been assigned a Prescription Drug User Fee Act (PDUFA) action date of January 14, 2019.

“Patients with this aggressive form of advanced liver cancer urgently need new treatment options after they progress on first-line therapy,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “The acceptance of our sNDA filing for CABOMETYX is a critical step forward as we work to help address this unmet need, and we intend to work closely with the FDA as they review the application.”

An sNDA is an application to the FDA that, if approved, will allow a drug sponsor to make changes to a previously approved product label, including modifications to the indication. Exelixis announced they submitted the sNDA for the treatment of previously treated advanced HCC to the FDA in March 2018 based on results from the CELESTIAL phase 3 pivotal trial of CABOMETYX in patients with advanced HCC who received prior sorafenib.

About the CELESTIAL Study
CELESTIAL is a randomized, double-blind, placebo-controlled study of cabozantinib in patients with advanced HCC conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who received prior sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms during the blinded treatment phase of the trial. The primary endpoint for the trial is overall survival, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.

In October 2017, Exelixis announced that the independent data monitoring committee for the CELESTIAL study recommended that the trial be stopped for efficacy following review at the second planned interim analysis, with cabozantinib providing a statistically significant and clinically meaningful improvement in overall survival compared with placebo in patients with previously treated advanced HCC. In March 2017, the FDA granted orphan drug designation to cabozantinib for the treatment of advanced HCC.

Please see Important Safety Information below and full U.S. prescribing information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf

Tuesday, May 22, 2018

Overall cancer mortality continues to decline, liver cancer increasing

Press Release
The latest Annual Report to the Nation on the Status of Cancer finds that overall cancer death rates continue to decline in men, women, and children in the United States in all major racial and ethnic groups. Overall cancer incidence, or rates of new cancers, decreased in men and were stable in women from 1999 to 2014. In a companion study, researchers reported that there has been an increase in incidence of late-stage prostate cancer and that after decades of decline, prostate cancer mortality has stabilized....

American Cancer Society
Stacy Simon Senior Editor, News
The death rate from cancer in the United States is continuing to fall among men, women, and children, according to the latest Annual Report to the Nation on the Status of Cancer. Part 1 of the report shows the rate of death from cancer in the United States is decreasing for all major racial and ethnic groups, and for the most common types of cancer, including lung, colorectal, breast, and prostate. However, the report identified some cancer types with increasing death rates, including liver, pancreas, and brain cancer in men and women; oral cavity, throat, soft tissue, non-melanoma skin cancer in men; and uterine cancer in women.

The American Cancer Society, the North American Association of Central Cancer Registries, the Centers for Disease Control and Prevention, and the National Cancer Institute work together to create the report, which has been published each year since 1998. It provides an update of new cancer cases, death rates, and trends in the United States.

Black men and non-Hispanic women in various racial groups had the highest overall cancer incidence rates, and black men and black women had the highest overall cancer death rates.

“There continue to be significant declines in the cancer death rate with significant differences in rate by gender, race and ethnicity,” said Otis W. Brawley, M.D., chief medical officer for the American Cancer Society. “We need to continue working to understand the reasons for the disparities and how to most efficiently continue supporting and if possible accelerate these declines.”

In a companion study—Part 2 of this year’s report—researchers reported that there has been an increase in incidence of late-stage prostate cancer and that after decades of decline, the prostate cancer death rate has stabilized.

Parts 1 and 2 of the report were published May 22, 2018 in the American Cancer Society’s journal Cancer. 

Among the findings:
Overall cancer death rates from 1999 to 2015 decreased by 1.8% per year in men, and by 1.4% per year in women. 

Cancer death rates decreased during 2011-2015 for 11 of the 18 most common cancers in men and for 14 of the 20 most common cancers in women. 

Rates of new cancer cases from 1999 to 2014 decreased in men but stayed about the same for women
Survival rates increased significantly for several cancer types for both early- and late-stage disease, but varied by race and ethnicity, and state.

Behind the numbers
The declining cancer death rates have resulted largely from improvements in early detection and treatment, and reductions in tobacco use. However cigarette smoking still accounts for more than 25% of cancer deaths in the United States.

Increasing death rates were reported for several cancer types. Researchers attribute the increase in liver cancer death rates to the high prevalence of hepatitis C virus infection among Baby Boomers, as well as to the high prevalence of obesity in the United States. Obesity is also thought to have contributed to the increase in death rates from cancers of the uterus and pancreas.

The recent increase in oral cavity and pharynx cancer death rates among white men is thought to be attributable to human papillomavirus (HPV) infection.

Trends in prostate cancer 
In the companion study, researchers explored prostate cancer trends in more detail. They found that overall rates of new prostate cancers declined about 6.5% per year from 2007 to 2014. However, the rate of new advanced prostate cancers increased between 2011 and 2014. In addition, after declining between 1993 and 2013, prostate cancer death rates leveled off between 2013 and 2015.

This study also reports a decline in recent prostate-specific antigen (PSA) screening in the population based on a series of national surveys. The reported decline in screening occurred between the 2010 and 2013 surveys, for men between 50 and 74 years of age, and after the 2008 survey, for men age 75 and older.

“There are many factors that contribute to incidence and mortality such as improvements in staging and treating cancer,” said Serban Negoita, M.D., Dr.P.H., of NCI’s Surveillance Research Program and lead author of the prostate cancer report. “Additional research is needed to get a more comprehensive understanding of the recent trends and the possible relationship with PSA screening, as well as the relationship with other factors that may be associated with these trends.”

Related Resources
NIH/National Cancer Institute
View the Current Report:
Annual Report to the Nation on the Status of Cancer, part I: National cancer statistics
Annual Report to the Nation on the Status of Cancer, part II: Recent changes in prostate cancer trends and disease characteristics
Archive of Previous Reports

Monday, May 21, 2018

Hepatocellular Carcinoma Incidence and Survival Among People With Hepatitis C An International Study

This study assessed trends in HCC diagnosis rates, contribution of risk factors to HCC diagnosis, and survival after HCC diagnosis among people with HCV infection.

Trends in Hepatocellular Carcinoma Incidence and Survival Among People With Hepatitis C An International Study 
M. Alavi; N. Z. Janjua; M. Chong; J. Grebely; E. J. Aspinall; H. Innes; H. Valerio; B. Hajarizadeh; P. C. Hayes; M. Krajden; J. Amin; M. G. Law; J. George; D. J. Goldberg; S. J. Hutchinson; G. J. Dore

J Viral Hepat. 2018;25(5):473-481
Volume 25, Issue 5 May 2018
Full Text
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Abstract
This study evaluates trends in hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct–acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995–2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001–2012/2013/2014, respectively) and mortality (1995–2013/2014/2015, respectively). Age–standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid–2000s, HCC diagnosis numbers increased in all jurisdictions. Age–standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8 years in 2001–2006 and 2007–2011) and NSW (0.9 years in 2001–2006 and 2007–2013) and improved in Scotland (0.7 years in 2001–2006 to 1.5 years in 2007–2014). Across the settings, HCC burden increased, individual–level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon–based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years.

In conclusion, this international comparison of population–level data provides evidence for the rising burden of HCV–related advanced liver disease in BC, NSW and Scotland, highlighting the combined impact of ageing, suboptimal HCV treatment efficacy and uptake, and low levels of HCC screening and early diagnosis. Over the coming years, the population–level burden and individual–level risk of HCC would be expected to decline, given the potential impact of well–tolerated and effective DAA treatments. In addition, enhanced HCC screening could enable early diagnosis and better management options. The use of administrative databases for surveillance, particularly with the addition of individual–level antiviral treatment data, will be a valuable tool for evaluation and monitoring trends of HCV and HCC burden in relation to public health intervention strategies across the three settings.


Saturday, May 12, 2018

HCV therapy and risk of liver cancer recurrence: who to treat?

Article shared and download by Henry E. Chang on Twitter

Nature reviews gastroenterology & hepatology
HCV therapy and risk of liver cancer recurrence: who to treat?
Massimo Colombo and Vincenzo Boccaccio
The advent of potent and user-friendly direct- acting antiviral agents (DAAs) to treat HCV infection has inflated the expectations that the control of such a potentially lethal disease is now possible. The scrutiny of the huge database of the Veterans Affairs practice has provided unequivocal proof that eradication of HCV with DAAs is attainable in almost all patients with any stage of infection, even in the presence of multiple comorbidities (such as obesity, alcohol abuse and diabetes), resulting in a substantial decline of short- term mortality and de novo hepatocellular carcinoma (HCC) development 1 , 2 . Yet, an area of uncertainty remains regarding the safety and efficacy of these innovative therapies in patients with liver cancer who have already received anticancer therapy.

View the article: https://jumpshare.com/v/PAnSunSpBpEcc4ByR5EK

Recommended Reading
May 4, 2018
High efficacy of direct-acting anti-viral agents in hepatitis C virus-infected cirrhotic patients with successfully treated hepatocellular carcinoma
This large real-life study proves that the efficacy of DAA in cirrhotic patients is not impaired by successfully treated HCC.

Tuesday, May 8, 2018

Higher risk of hepatocellular carcinoma in Hispanic patients with hepatitis C cirrhosis and metabolic risk factors

Published:08 May 2018
nature.com - scientific reports

Higher risk of hepatocellular carcinoma in Hispanic patients with hepatitis C cirrhosis and metabolic risk factors
Alina Wong, An Le, Mei-Hsuan Lee, Yu-Ju Lin, Pauline Nguyen, Sam Trinh, Hansen Dang & Mindie H. Nguyen

Full-Text

In summary, this study shows that patients with CHC cirrhosis and super-imposed metabolic syndrome have increased risk of liver-related complications including both hepatic decompensation and HCC. Hispanic patients with two or more metabolic risks are at especially increased risk of developing liver-related complications. As the prevalence of obesity and metabolic syndrome increase across the world, targeted health interventions will be needed to help curb the effects of metabolic syndrome in chronic hepatitis C patients.

Abstract
The effect of metabolic syndrome on chronic liver diseases other than non-alcoholic fatty liver disease has not been fully elucidated. Our goal was to evaluate if metabolic syndrome increased the risk of liver-related complications, specifically hepatocellular carcinoma (HCC) and decompensation, in cirrhotic chronic hepatitis C (CHC) patients. We conducted a retrospective cohort study of 3503 consecutive cirrhotic CHC patients seen at Stanford University from 1997–2015. HCC developed in 238 patients (8-year incidence 21%) and hepatic decompensation in 448 patients (8-year incidence 61%). The incidence of HCC and decompensation increased with Hispanic ethnicity, diabetes, and number of metabolic risk factors. Multivariate Cox regression analysis demonstrated that, independent of HCV therapy and cure and other background risks, Hispanic ethnicity with ≥2 metabolic risk factors significantly increased the risk of HCC and hepatic decompensation. There was no interaction between Hispanic ethnicity and metabolic risk factors. All in all, metabolic risk factors significantly increase the risk of liver-related complications in cirrhotic CHC patients, especially HCC among Hispanics. As the prevalence of metabolic syndrome increases globally, targeted health interventions are needed to help curb the effects of metabolic syndrome in CHC patients.