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

Thursday, November 29, 2018

Balancing Efficacy With Toxicity Among the Agents for HCC

Balancing Efficacy With Toxicity Among the Agents for HCC
Catherine Frenette, MD
Published Online:Nov 29, 2018

Catherine Frenette, MD: The 2 groups of lenvatinib [Lenvima] versus sorafenib [Nexavar] in the REFLECT trial were not stratified by AFP [alpha-fetoprotein] level. They were also not stratified by their underlying cause of liver disease. The patients in the lenvatinib group did have a slightly higher AFP than the patients in the sorafenib group. This may actually have resulted in a favorable imbalance in the positive for sorafenib. Additionally, hepatitis C patients were more frequent in the sorafenib group as compared with the lenvatinib group. This may have given a benefit to sorafenib. The reason for this discussion is that we recall, in the SHARP trial, when they broke out a subgroup of patients who were treated with sorafenib and had hepatitis C, had quite a longer median survival. In the SHARP trial, the overall survival [OS] in the subgroup was 10.7 months. In the hepatitis C–treated population with sorafenib, there may have been a longer OS than would have been seen in patients who were stratified for that risk factor.....


Transcript
Continue reading
https://www.targetedonc.com/case-based-peer-perspectives/hepatocellular-carcinoma/frenette-unresectable-hcc/balancing-efficacy-with-toxicity-among-the-agents-for-hcc

Thursday, November 15, 2018

In Older Hep B Patients, Carcinoma Surveillance Is Advised

Medscape Medical News > Conference News > AASLD 2018
In Older Hep B Patients, Carcinoma Surveillance Is Advised
Laird Harrison
November 15, 2018 

SAN FRANCISCO — Surveillance for hepatocellular carcinoma (HCC) should continue in patients older than 50 years, even after they have undergone 5 years of therapy for chronic hepatitis B, according to an analysis of the PAGE-B cohort.

But the risk for the cancer is low enough in younger patients — except for those with cirrhosis — that surveillance might not be warranted, said George Papatheodoridis, MD, PhD, from Athens University Medical School in Greece.

"It will save monitoring in some patients," he told Medscape Medical News.

Long-term monotherapy with entecavir (Baraclude, Bristol-Myers Squibb) or tenofovir disoproxil fumarate (Viread, Gilead) suppresses the hepatitis B virus and improves liver lesions, so the survival rate in patients without compensated cirrhosis is comparable to that in the general population, Papatheodoridis explained here at The Liver Meeting 2018...

Free registration may be required

Meeting Coverage
Twitter @Medscape

Recommended Coverage 
Updates on this blog (LINK), recommended coverage elsewhere (LINK). 

Tuesday, November 13, 2018

Osteopontin: A new emerging role in HCV-related hepatocellular carcinoma

Published: 03 September 2018 in scientific reports; https://www.nature.com/articles/s41598-018-31421-6
https://doi.org/10.1038/s41598-018-31421-6

Osteopontin: A new emerging role in HCV-related hepatocellular carcinoma

Kanazawa University
Hepatitis C virus (HCV) infection is the major cause of hepatocellular carcinoma (HCC) and was estimated to be responsible for 745,000 deaths in 2012. Recently, highly efficient and direct-acting antiviral agents (DAAs) have been able to eliminate HCV from infected livers in more than 90% of cases. However, emergence of HCC at a rate of about 1% per year is now reported in HCV-infected livers. Therefore, new therapeutic strategies are needed to prevent HCV infection, HCC recurrence, and hepatocarcinogenesis.

Osteopontin (OPN) is a multifunctional cytokine and is involved in normal physiological processes, as well as in numerous pathological conditions, including inflammation, fibrogenesis, and carcinogenesis. In liver diseases, OPN plays an important role in acute liver injury, viral replication, liver repair, fibrosis, and HCC.

Recent work has identified CD44 as the most common marker for cancer stem cells (CSCs) in several human cancers. CD44 has a pivotal role in regulating the properties of CSCs, including their self-renewal, tumor initiation, metastasis, and chemoradioresistance, and OPN reportedly interacts with CD44.

In HCC, enrichment of several stem cell markers, including CD133, CD90, CD13, epithelial cell adhesion molecule (EpCAM), CD44, CD24, and oval cell marker OV6, is reported in certain side populations of CSCs. However, CSCs represent only a minor population of the cancer cells and there is currently no evidence for a role for CSCs in supporting HCV replication. Therefore, identifying the underlying mechanism of HCV pathogenesis and its relationship to CSCs is an important research challenge.

In this study, a group from Kanazawa University evaluated the significance of the OPN-CD44 axis for HCV replication in EpCAM+/CD44+ CSCs, and investigated the role of OPN in the regulation and maintenance of EpCAM+/CD44+ CSCs.

[Results]

EpCAM+/CD44+ CSCs showed marked HCV replication when compared with EpCAM?/CD44? cells. In addition, the levels of OPN mRNA and protein were higher in EpCAM+/CD44+ CSCs than in EpCAM?/CD44? cells. OPN significantly enhanced HCV replication in EpCAM+/CD44+ CSCs and markedly suppressed interferon (IFN)-stimulated gene expression. Glycogen synthase kinase-3β inhibitor 6-bromoindirubin-3-oxime increased the EpCAM+/CD44+ CSC population and OPN expression and impaired IFN signaling via signal transducer and activator of transcription 1 (STAT1) degradation. Furthermore, OPN regulated stemness of EpCAM+/CD44+ CSCs, which led to inactivation of IFN signaling and enhanced HCV replication.

[Significance and future prospects]

The Kanazawa University group focused its attention on CSCs, as HCC is proposed to develop from CSCs, even though they represent a small part of the HCC cell population. However, HCV replication in CSCs is still poorly understood. This study showed the significance of the OPN-CD44 axis for HCV replication in EpCAM+/CD44+ CSCs.

The results of the Kanazawa University group highlight a new role for OPN in supporting HCV replication in EpCAM+/CD44+ CSCs through a reduction in STAT1 activation. They also provide evidence that OPN has the potential to maintain CSC phonotypes, and identify the OPN-CD44 pathway as a potential target for regulating HCV replication and stemness in HCC cells. 

Saturday, November 10, 2018

Five Years of Regular Aspirin Use Helps Prevent Common Liver Cancer - The Liver Meeting®

Five Years of Regular Aspirin Use Helps Prevent Common Liver Cancer
November 9, 2018
Data from a new study presented this week at The Liver Meeting® found that taking a regular aspirin is associated with a dose-dependent reduction in the risk of hepatocellular carcinoma, one of the most common liver cancers.

SAN FRANCISCO – Data from a new study presented this week at The Liver Meeting® – held by the American Association for the Study of Liver Diseases – found that taking a regular aspirin is associated with a dose-dependent reduction in the risk of hepatocellular carcinoma, one of the most common liver cancers. The cancer risk reduction is apparent after at least five years of aspirin use, the study showed.

Evidence suggests that aspirin may prevent hepatocellular cancer – commonly called HCC – but it’s still unclear what dose and duration of aspirin is needed to prevent this liver cancer. To examine aspirin’s influence on HCC incidence and risk, a group of researchers from Massachusetts General Hospital and Harvard Medical School in Boston conducted two nationwide, prospective cohort studies of men and women in the United States.

“Given the limitations of existing therapies and the growing mortality [due to] HCC in the U.S., there is an urgent and growing need to identify effective strategies for primary prevention,” says Tracey G. Simon, MD, a research fellow at Massachusetts General Hospital and the study’s co-author. “Previous studies have suggested that aspirin is associated with a lower risk for developing incident HCC, but the optimal dose and duration of aspirin use to achieve clinical benefit was unknown. Understanding the optimal dose and duration of aspirin use to effectively reduce the risk for developing HCC may inform future clinical guidelines and facilitate the planning of clinical trials. We know that HCC has a very long latency, and that the impact of a preventive therapy, such as aspirin, will likely require long-term use.”

The study included 133,371 individuals from both the Nurses’ Health Study and the Health Professionals Follow-Up Study who reported aspirin use, dosage and duration every two years from 1980 (for the NHS) and 1986 (for the HPFS) until 2012. The study defined regular aspirin use as two or more standard (325 mg) aspirin tablets per week. The researchers updated all data prospectively at each biennial follow-up. Cases of incident HCC were reported by study participants (or their next-of-kin or through death certificates) and were subsequently confirmed by physician review of the individuals’ medical records.

In over 4.2 million person-years of follow-up, the study found 108 incident cases of HCC in 65 women and 43 men. Compared to non-regular aspirin use, regular aspirin use was associated with significantly lower HCC risk in this population. The relationship appeared to be closely related to the dose of aspirin a person was taking: compared to non-use, the multivariable adjusted hazard ratio (HR) was 0.87 for 1.5 or less standard aspirin tablets a week, 0.51 for more than 1.5 up to five tablets a week, and 0.49 for more than five tablets a week.

This inverse association also appeared to be duration-dependent, the study found. Among former aspirin users, an increase in time since the discontinuation of aspirin was associated with progressively increased risk of HCC. When both dose and duration were analyzed together, significant HCC risk reduction was found when patients took 1.5 or more standard aspirin tablets per week for five or more years, compared to non-use. Importantly, non-aspirin NSAID (nonsteroidal anti-inflammatory drug) use was not associated with HCC risk compared to non-NSAID use – suggesting the apparent benefit was specific to aspirin.

“We still need to define the impact of aspirin use in various types of chronic liver disease, including nonalcoholic fatty liver disease, which is now the leading cause of chronic liver disease in the U.S.,” explains Dr. Simon of next steps. “We also need to understand the impact of aspirin in various stages of liver disease, since there is some data to suggest that aspirin may be most effective if it is taken before the development of cirrhosis. Finally, we need to carefully understand the risks of using aspirin for the primary prevention of HCC, including the risk of bleeding. We need to understand which patients stand to achieve the greatest benefit from aspirin use, with the lowest possible bleeding risks.”

Dr. Simon will present the study entitled “The Association between Aspirin Use and Risk of Hepatocellular Carcinoma: Results from Two Perspective U.S. Cohort Studies” on Sunday, November 11 at 10:30 AM in Room 306/308. The corresponding abstract (number 0091) can be found in the journal, HEPATOLOGY (link is external).
About AASLD

AASLD is the leading organization of clinicians and researchers committed to preventing and curing liver disease. The work of our members has laid the foundation for the development of drugs used to treat patients with viral hepatitis. Access to care and support of liver disease research are at the center of AASLD’s advocacy efforts.

Press releases and additional information about AASLD are available online at www.aasld.org.

The Liver Meeting® Liver Cancer Combined with Other Liver Diseases Driving Higher Death Rate and Health Care Costs for US Seniors

Liver Cancer Combined with Other Liver Diseases Driving Higher Death Rate and Health Care Costs for US Seniors
November 9, 2018
Data from a new study presented this week at The Liver Meeting® found that hospitalizations and death are increasing among Medicare recipients with hepatocellular carcinoma, mainly due to co-existing alcoholic liver disease, hepatitis C virus infection (commonly called HCV) and nonalcoholic fatty liver disease (commonly called NAFLD). 

SAN FRANCISCO – Data from a new study presented this week at The Liver Meeting® – held by the American Association for the Study of Liver Diseases – found that hospitalizations and death are increasing among Medicare recipients with hepatocellular carcinoma, mainly due to co-existing alcoholic liver disease, hepatitis C virus infection (commonly called HCV) and nonalcoholic fatty liver disease (commonly called NAFLD).

Liver cancer is the fifth most common cancer and the second most common cause of cancer-related deaths worldwide. Hepatocellular carcinoma, or HCC, is the primary liver cancer, and its incidence is increasing in the United States. Researchers at the Inova Fairfax Hospital and the Betty and Guy Beatty Center for Integrated Research at Inova Health System in Falls Church, Va., conducted a study to assess recent trends in HCC-related deaths and health care utilization for US Medicare recipients.

“Both HCV and nonalcoholic steatohepatitis are expected to become more advanced with age,” says Zobair M. Younossi, MD, MPH, chairman, Department of Medicine, Inova Fairfax Medical Campus and professor of medicine at Virginia Commonwealth University. Dr. Younossi is a co-author of the new study. “In this context, an important complication of advanced liver disease is HCC. We believe that HCC is driven by NAFLD, which is increasing in prevalence, and will continue to place a financial burden on Medicare and should be addressed proactively.”

The study included a random sample of Medicare beneficiaries from 2005 to 2014. The researchers established diagnoses of HCC, HCV, hepatitis B virus (or HBV), alcoholic liver disease and NAFLD using ICD-9 codes. They analyzed trends in HCC rates, patient demographics, clinical features and utilization parameters.

The researchers examined 13,648 cases of HCC patients who sought inpatient or outpatient care. The average age of the patients in the study was 70; 62.8 percent were male; and 76 percent were white. The one-year death rate for this patient cohort was 45 percent. An increase in death rates was similar between males and females. The length of hospital stay duration decreased from 9.23 to 8.81 days over the study period, and the number of outpatient visits increased 1.86 to 3.18. In the inpatient care setting, one-year mortality was 64.4 percent, with an average length of stay of 8.6 days. In the outpatient care setting, the death rate was 40.6 percent.

Total charges for HCC care in the inpatient setting increased from $67,679 to $98,902 over the study period, and increased from $11,933 to $32,084 in the outpatient setting. People with HCC, HCV and alcoholic liver disease treated in the inpatient setting had a higher risk of death than patients with HCV alone – followed by those with HCC and NAFLD. Patients with HCC who also had other liver diseases – including HCV, alcoholic liver disease and NAFLD – also had higher health care charges than those with HCV alone, the study found.

“HCC has been one of the only solid tumors with increasing incidence in the U.S. Given the ongoing epidemic of NAFLD and its complications, this clinical picture is expected to get worse. HCC is also an expensive cancer with significant direct and indirect medical costs,” says Dr. Younossi. “Therefore, all payers, especially Medicare, will be affected by this increase in HCC. Hepatologists are not only involved in understanding the pathogenic pathways of HCC and developing treatment regimens, but also must educate all stakeholders, including payers and policymakers, about the importance of HCC.”

Dr. Younossi will present the study entitled “In Medicare Patients with Hepatocellular Carcinoma, Nonalcoholic Fatty Liver Disease is Among the Top Causes of Morality and Resource Utilization” on Monday, November 12 at 4:00 PM in Room 206/208. The corresponding abstract (number 0273) can be found in the journal, HEPATOLOGY (link is external).
About AASLD

AASLD is the leading organization of clinicians and researchers committed to preventing and curing liver disease. The work of our members has laid the foundation for the development of drugs used to treat patients with viral hepatitis. Access to care and support of liver disease research are at the center of AASLD’s advocacy efforts.

Press releases and additional information about AASLD are available online at www.aasld.org.

Updates
On This Blog
Link to key data from the meeting with a focus on viral hepatitis, NASH, liver cancer and liver transplantation.

Friday, November 9, 2018

FDA Approves Merck’s KEYTRUDA® for Patients with Hepatocellular Carcinoma Previously Treated with Sorafenib

FDA Approves Merck’s KEYTRUDA® (pembrolizumab) for the Treatment of Patients with Hepatocellular Carcinoma (HCC) Who Have Been Previously Treated with Sorafenib

Approval Marks 14th Indication for KEYTRUDA 

November 09, 2018 04:21 PM Eastern Standard Time
KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Merck’s anti-PD-1 therapy, for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

“Hepatocellular carcinoma is the most common type of liver cancer in adults, and while we have seen recent therapeutic advancements, there are still limited treatment options for advanced recurrent disease,” said Dr. Andrew X. Zhu, lead investigator and director of liver cancer research at Massachusetts General Hospital and professor of medicine at Harvard Medical School. “Today’s approval of KEYTRUDA is important, as it provides a new treatment option for patients with hepatocellular carcinoma who have been previously treated with sorafenib.”

Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see “Selected Important Safety Information” below.

“The approval of KEYTRUDA for advanced hepatocellular carcinoma marks the second FDA approval for hepatocellular carcinoma in Merck’s oncology portfolio this year, underscoring our commitment to help bring forward new treatment options for cancers that have historically been very challenging to treat,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “We look forward to continuing to advance research for hepatocellular carcinoma across our portfolio with the goal to help even more patients affected by this type of cancer.” 

Tuesday, November 6, 2018

HCC recurrence rates do not differ after interferon vs. DAA therapy

HCC recurrence rates do not differ after interferon vs. DAA therapy 
November 6, 2018
Hepatocellular carcinoma recurrence rates and patterns did not differ between patients who underwent interferon-based antiviral therapy for hepatitis C and those who received direct-acting antiviral therapy, according to a recently published study.

“With the development of direct-acting antivirals (DAA), patients with a history of HCC can achieve a high sustained viral response (SVR) rate with favorable tolerability,” Mizuki N. Kinoshita, MD, from the University of Tokyo, and colleagues wrote. “However, a high rate of early tumor recurrence has been reported in patients with a prior history of HCC treatment who were starting DAA treatment, for which we have presented counterevidence.”
Read More: https://www.healio.com/hepatology/hepatitis-c/news/online/%7Be554943e-f94f-4688-8069-fe88a24f854b%7D/hcc-recurrence-rates-do-not-differ-after-interferon-vs-daa-therapy

On This Blog
Liver Cancer After Treatment For Hepatitis C​
This page offers an index of  research articles investigating the possible risk of developing liver cancer (hepatocellular carcinoma, or HCC) during or after direct-acting antiviral therapy in patients with hepatitis C.

Monday, November 5, 2018

Study Suggests Risk of Cancer Death Increases With Each Generation of Latinos Born in the United States

Study Suggests Risk of Cancer Death Increases With Each Generation of Latinos Born in the United States
By Jo Cavallo
Posted: 11/5/2018 3:30:12 PM
Last Updated: 11/5/2018 3:30:12 PM

Key Points
Latinos in the United States experience an increased risk of cancer death with each generation born in the United States. 

The highest cancer death rate occurred among third-generation U.S.-born Latinos, followed by second-generation Latinos with one or both parents born in Mexico. The lowest cancer death rate occurred among first-generation immigrants.

The risk of dying from certain cancers, including lung, colorectal and liver cancers, was significantly higher among third-generation U.S.-born Latinos compared with the first-generation Mexico-born immigrants

According to the U.S. Census Bureau, as of July 2016, the Hispanic population in the United States had grown to 57.5 million, making people of Hispanic origin the nation’s largest ethnic or racial minority group. Studies have shown that U.S.-born Latinos have a higher incidence of cancer than foreign-born Latinos. To better understand the influence that acculturation and environmental factors have on cancer risks in Latinos in the United States, Setiawan et al launched a large observational study examining the cancer mortality patterns across first-generation immigrants and second- and third-generation U.S.-born Mexican Americans.

Sunday, November 4, 2018

Liver Cancer After Treatment For Hepatitis C


Page updated: November 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.

November 2018
Nov 6, 2018
Kinoshita MN, et al. J Hepatol. 2018;doi:10.1016/j.jhep.2018.09.029.
Hepatocellular carcinoma recurrence rates and patterns did not differ between patients who underwent interferon-based antiviral therapy for hepatitis C and those who received direct-acting antiviral therapy, according to a recently published study. Free registration required 

October 2018
Research continues to invalidate link between DAA treatment, liver cancer

August 2018
Aug 4, 2018
Direct Antiviral Therapy of Hep C May Not Boost Hepatocellular-Carcinoma Risk
Treatment of hepatitis C (HCV) with direct-acting antiviral agents does not appear to increase the risk of hepatocellular carcinoma (HCC) in individuals with cirrhosis, researchers from France report.
Reuters Health Information, August 2018

June 2018
June 28, 2018
Washington—Eradication of chronic infection with the hepatitis C virus with the new class of antiviral agents is associated with a 71% reduction in the risk for de novo liver cancer, according to a large retrospective cohort study involving the Veterans Affairs health care system. The findings should provide some assurance for patients taking direct-acting antivirals (DAAs), according to lead study author George Ioannou, BMBCh, MS, the director of hepatology at Veterans Affairs Puget Sound Health Care System, in Seattle.

June 27, 2018
Should we cure HCV in patients with hepatocellular carcinoma while treating cancer?

Syed T, Fazili J, Ali I, et al. (June 19, 2018)
Hepatocellular Carcinoma Occurrence and Recurrence in Hepatitis C-infected Patients Treated with Direct-acting Antivirals.
Cureus 10(6): e2843. doi:10.7759/cureus.2843
This work was presented as poster presentation at Digestive Disease Week 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

View Full Text
PDF Download

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, October 31, 2018

Potential markers identified for early detection and prevention of liver cancer

Potential markers identified for early detection and prevention of liver cancer
A shift in glucose metabolism hails progression from liver cirrhosis to liver cancer, finds a new study

Liver cancer is the second leading cause of cancer-related mortality worldwide, claiming 700,000 lives each year. Most cases are discovered too late for a cure -- but now a study offers hope of early detection, and targets for new treatments. Published in Frontiers in Cell and Developmental Biology, the results show a dramatic increase in expression of sugar-burning 'glycolytic' enzymes in precancerous cirrhotic livers. This increase is associated with a significantly higher risk of developing hepatocellular carcinoma (HCC) -- the main type of liver cancer -- and could lead to a biomarker which identifies those at risk of malignancy.

"We know that 90% of all hepatocellular carcinoma cases start with liver cirrhosis," explains study senior authors Dr Salvatore Papa of the University of Leeds and Dr Concetta Bubici of Brunel University London, UK. "So by pinpointing when cirrhosis progresses to cancer, we could improve early detection and treatment -- with surgery, chemo and radiotherapy, but perhaps also with new treatments which reverse the transition."

Metabolic changes in cancer cells
In cirrhosis, chronic damage caused by hepatitis viruses B or C, alcohol, or obesity leads to scarring and formation of regenerative nodules in the liver. High cell turnover in these nodules, with accumulation of genetic damage, can eventually produce cancerous cells.

"We set out to find features of cirrhotic cells that might predict cancerous change," says Papa.

For nearly a century, scientists have recognized that cancer cells shift the way they generate energy. Normally the body obtains energy from macronutrients -- sugars, fats, proteins and their intermediaries -- primarily using oxygen. But our cells can also extract energy from sugars without using oxygen. This anaerobic process, called glycolysis, produces the lactate that 'burns' our muscles during intense exercise -- and is also used by cancers to fuel their rampant growth.

"Like virtually all cancers, highly-proliferating HCC cells seem to readjust their energy metabolism towards glycolysis, irrespective of oxygen availability."

The cause of this shift in glucose metabolism -- known as the Warburg effect -- remains unknown, but inflammation is thought to play a role.

"Given that cirrhosis is an inflammatory process, we decided to look at whether the metabolic shift to glycolysis is present already in cirrhotic cells -- and whether this predicts progression to hepatocellular carcinoma."

Cancer metabolic changes are present in cirrhotic cells

Papa and colleagues analyzed normal, cirrhotic and cancerous (HCC) liver samples from patients followed up over 10 years following a liver biopsy.

"To have a complete overview of energy metabolism changes in HCC and premalignant stages of disease, we measured the expression of genes encoding enzymes involved in glycolysis and other metabolic pathways."

They found that glycolysis-related genes -- including hexokinase 2 (HK2), aldolase A (ALDOA) and pyruvate kinase M2 (PKM2) -- are highly expressed not only in HCC, but also in cirrhosis as compared to normal liver samples.

"In other words: the shift to glycolysis occurs in the precancerous stage," says Bubici.

Even more striking, the level of expression of glycolysis-related genes showed positive correlation with progression of cirrhosis to HCC -- and with poor outcome in those with HCC already at the time of biopsy.

"This suggests expression of glycolytic enzymes could be used as a new biomarker to predict the risk of later development of HCC in patients with cirrhosis," claims Bubici.

Towards early detection
The team stresses the study is preliminary: "Further studies are needed to establish whether these changes in gene expression are borne out as changes in glycolytic activity."

Nevertheless, the findings reveal a promising means to improve HCC survival through early detection and treatment. According to Papa, the shift to a glycolytic expression profile in cirrhotic cells could even be a target for new HCC therapies.

"For example, clinical trials are currently underway to explore the effect of statins -- which are used to help prevent cardiovascular disease -- on HCC development in cirrhotic patients or HCC recurrence following surgical removal.

"It is very likely that by blocking cholesterol synthesis, statins would also suppress glycolysis as these chemical pathways overlap. If these trials show that statins reduce HCC risk, further studies would be necessary to establish whether inhibition of glycolysis in cirrhotic cells is responsible," says Papa.

Original research article: