Showing posts with label HCV-Education. Show all posts
Showing posts with label HCV-Education. Show all posts

Monday, August 13, 2018

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

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

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

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

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

Listen here...…

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

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

Friday, August 3, 2018

Long–term effect of liver fibrosis after SVR in patients with HCV

Journal of Viral Hepatitis, July 27, 2018 

Cirrhosis, High Age and High Body Mass Index Are Risk Factors for Persisting Advanced Fibrosis After Sustained Virological Response in Chronic Hepatitis C
M. Hedenstierna; A. Nangarhari; A. El-Sabini; O. Weiland; S. Aleman
J Viral Hepat. 2018;25(7):802-810.

The aim of this study was to investigate the long–term effect of achieved SVR on liver fibrosis, measured as liver stiffness with transient elastography, in a cohort with pretreatment advanced chronic HCV infection. We also aimed to identify risk factors associated with persisting fibrosis.

Abbreviations
BMI, body mass index; CI, confidence interval; DM, diabetes mellitus; FU, follow-up; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; LSM, liver stiffness measurement; OR, odds ratio; SVR, sustained virological response.

Discussion Only
View Complete article: https://www.medscape.com/viewarticle/898758_1
The long–term effect of achieved SVR on liver fibrosis in patients with HCV–induced advanced fibrosis has not been extensively investigated. To study this, fibrosis in our patients was assessed by LSM during long–term follow–up over more than 5–10 years. Our study shows that the vast majority of our 269 patients with pretreatment advanced fibrosis or cirrhosis improved their fibrosis during long–term follow–up after SVR. A minority, however, continued to have advanced fibrosis even after more than 5–10 years of follow–up. In this subset of patients, a point of no return for advanced liver fibrosis might have been reached, where improvement is not possible. Other possible explanations are contributing cofactors such as liver steatosis with inflammation and alcohol use as driving forces to maintain or even progress liver fibrosis. In this study, we identified pretreatment cirrhosis, high age and high BMI as the main risk factors for lack of improvement. The proportion of patients who maintained advanced fibrosis decreased among patients with longer follow–up time, indicating that fibrosis regression is a slow process that continues over time.

Several studies with varying follow–up times have compared pre– and post–treatment fibrosis stages.[10,19–27] Studies based on liver biopsies have all shown that fibrosis and also cirrhosis can improve after achievement of SVR in a majority of patients, but also that fibrosis will persist or progress after SVR in a subset of 1%–14%, confirming the results in our study.[19–23] In a large study including more than 3000 biopsied patients with a mean follow–up time of 20 months, a low baseline fibrosis stage, age below 40 and BMI below 27 were all factors strongly associated with lack of significant fibrosis at follow–up in patients with SVR.[19] The risk factors identified to be associated with persisting fibrosis found were the same as in our long–term study.

More recent studies have investigated fibrosis regression after SVR with LSM and biochemical markers. The diagnostic accuracy of these methods to detect persisting cirrhosis after SVR, however, has been questioned.[10,24] In a study comparing LSM with follow–up biopsies 61 months after achieved SVR, the sensitivity of LSM to detect cirrhosis after SVR was only 61% when standard pretreatment cut–offs were used.[10] On the other hand, the specificity for diagnosing cirrhosis with LSM after treatment reached 95%. As LSM measures both fibrosis and inflammation, rapid early improvement of liver stiffness after SVR could be explained by a reduction in liver inflammation, and not by fibrosis regression. This could suggest that patients with pretreatment cirrhosis defined by LSM, including some with severe inflammation and less advanced fibrosis, would have lower liver stiffness at follow–up than patients with biopsy–proven cirrhosis. Surprisingly, in our study, we observed the opposite. The difference was not significant, but could be explained by the fact that patients with cirrhosis defined by LSM had shorter follow–up times. This supports our conclusion that cirrhosis regression is a process that continues over time. Recently published studies with repeated LSM up to 2 years after achieved SVR have shown a rapid initial improvement of liver stiffness, but also a continued slower reduction, better reflecting true fibrosis regression.[25–27] The follow–up times in these studies were relatively short, but the findings support the results generated in our study. Another possible explanation for the initial rapid and later slower improvement of liver stiffness levels after SVR could be the remaining presence of nodular architecture in the liver, despite decreased amount of fibrosis.[21] Nodules are the hallmark for a histopathological definition of cirrhosis.[5] This implies that the persisting advanced fibrosis in our study, measured by LSM, probably is accurate, while we might have misclassified the stage of fibrosis in some of the cirrhotic patients that still had nodular architecture.

Although this study was not designed to assess the correlation between LSM and the risk to develop HCC, there were patients in our study with improved fibrosis who later developed HCC up to 15 years after SVR. This finding supports that surveillance for HCC should continue even in patients where cirrhosis has regressed after achieved SVR. The duration for such surveillance needs to be further studied. We have earlier found that diabetes and the presence of pretreatment cirrhosis were risk factors for the development of HCC after SVR had been achieved.[13] No direct correlation between diabetes mellitus and persisting advanced fibrosis was noted in this study. On the other hand, high BMI, known to be associated with diabetes, was found to be a risk factor for persisting advanced fibrosis.

There are several limitations to this study. It had a cross–sectional and retrospective design and lacked sequential LSMs for the included patients. However, in a preliminary prospective study on LSM data collected at 6–month intervals after SVR in 100 patients with F3–F4 fibrosis at baseline, 31% had persisting advanced fibrosis, similar to the results in our study.[28] Furthermore, in our study, a third of the eligible patients were excluded or lost to follow–up, which could introduce a selection bias. Baseline characteristics for the nonincluded patients were, however, comparable to the studied patients, reducing this bias. The clinical outcome was worse in the excluded group with higher occurrence of HCC and death, but the causes of death were not liver related in a majority of the cases.

Assessment of fibrosis after SVR with transient elastography and not liver histology may have caused us to underestimate the extent of advanced fibrosis at follow–up. However, the identified patients with maintained advanced fibrosis are probably correctly classified. As all our patients were treated with IFN–based regimens, we do not know if our findings are relevant for patients treated with IFN–free regimens. One recently published study, however, showed a statistically similar median change in LSM levels 24 weeks after the end of treatment in patients with SVR after IFN–containing and IFN–free regimens.[25]

To conclude, we found that the liver fibrosis after achievement of SVR improved in the vast majority of our patients after long–term follow–up. Our data indicate that fibrosis regression is an ongoing long–term process over years. Risk factors for lack of such improvement during follow–up were pretreatment cirrhosis, older age and high body mass index. Lifestyle intervention to decrease weight in obese persons and treatment before establishment of cirrhosis at a younger age should therefore be recommended to avoid persistence of advanced fibrosis after SVR.

Free registration may be required to view article.
Abstract and Introduction
Patients and Methods
Results
Discussion

Thursday, August 2, 2018

Liver Cancer After Treatment For Hepatitis C


Page updated: Aug 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.

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?

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...

Friday, July 27, 2018

The thrill of curing hepatitis C and the pain of watching the disease surge with opioid abuse

World Hepatitis Day — July 28th
For World Hepatitis Day, learn more about the different types of viral hepatitis that impact millions worldwide and what CDC is doing to help eliminate hepatitis.

The following article was originally published on The Conversation.
Read the original article.

The thrill of curing hepatitis C and the pain of watching the disease surge with opioid abuse
Anna Suk-Fong Lok, Professor of Internal Medicine, University of Michigan
When I began my medical career in Hong Kong in the early 1980s, I chose to focus on hepatitis B, in part because it was very common and because the hepatitis C virus had not yet been discovered. I witnessed the devastation that this virus caused – cirrhosis, liver failure and liver cancer – and the lack of treatments we could offer to patients. Back then, scientists knew there was another type of hepatitis but no one could identify it, so we called it non-A, non-B hepatitis. I would never have imagined that during the course of my career I would witness the discovery of what came to be known as hep C and the development of a cure for nearly all patients with chronic hepatitis C in 2014.

The development of treatments other researchers and I have seen over the past 30 years reflects the amazing progress the field has made in tackling hepatitis C in a relatively short period of time. Initially, in the late 1980s, before a diagnostic test became available, some physicians started treating well-characterized cases of non-A, non-B hepatitis (hep C) with interferon, a natural protein that the body makes to fight virus, and ribavirin, an antiviral drug. These medications were not specifically developed for hepatitis C, had to be given as injections for 6-12 months, had many side effects and resulted in a cure in only half of the patients who received treatment. It took more than two decades for the first direct-acting antiviral drugs to be approved by the FDA. 

I remember the excitement when I and my colleagues tested one of the new drug combinations in patients and saw the virus count drop from more than 1 million to less than 20 within two weeks. We published the results of our pilot study in the New England Journal of Medicine in 2012. Although the study involved only 21 patients, it was considered a watershed moment because it was the first study to prove that a combination of oral pills without interferon can cure hepatitis C.

World Hepatitis Day is celebrated on July 28, the birthday of Dr. Baruch S. Blumberg, a Philadelphia researcher who shared the 1976 Nobel Prize in physiology or medicine for his discovery of the hepatitis B virus. 

Effective treatment for hepatitis C has become even more relevant today in light of the recent surge in new cases of hepatitis C due to rising opioid use.
A pricey drug and new generics

The first combo pill with two drugs that inhibits different steps in hepatitis C replication was approved by the FDA in 2014. This pill is taken once a day for 8-12 weeks, has little to no side effects and improved the cure rate to 90-95 percent. It was hailed as a magical cure, but it came with a price tag of US$94,500 for a 12-week course of treatment. That led many insurers in the United States and national health departments in other countries to limit access to treatment.

Since then, several other combo pills with similar cure rates that are equally well-tolerated have become available, and the cost has markedly decreased. In addition, low-cost generics and special pricing arrangements are available in many resource-limited countries.

While the current price of hepatitis C virus drugs is still very high, one needs to remember that for 95 percent of patients, this is a cure. It is unlike medicines for many illnesses that need to be taken for a long time, sometimes for the rest of the patients’ lives. Indeed, a cure for hepatitis C virus has allowed some patients who were on the liver transplant waiting list to reverse their liver failure, making transplantation unnecessary. This is good news not only for these patients but also for others on the waiting list.

The remarkable success of hepatitis C treatment has reenergized efforts to find a cure for hepatitis B. Current treatments can suppress hepatitis B virus replication but do not eliminate it. Most patients need to be on long-term treatment to prevent flares of hepatitis when the virus reemerges after treatment is stopped. 

Deaths from hepatitis B and C infections rising worldwide
Learning from the hepatitis C experience and with better understanding of the biology of hepatitis B virus and improved animal models, drugs that target different steps of the hepatitis B virus life cycle are being developed. While cure for hepatitis B will be more challenging because it can integrate into the patient’s DNA, enabling it to evade the patient’s immune response, I am optimistic that we will witness the availability of new combination of drugs that will move us nearer the goal of an hepatitis B virus cure.

Members of Delhi Network of Positive People, a support group for HIV-positive people, shout slogans during a protest in New Delhi, India, Friday, March 21, 2014. The activists urged the Indian government to allow production of generic versions of direct-acting antivirals, that can help thousands get affordable oral doses of medicine to control hepatitis C. Infection progresses more rapidly to damage the liver in HIV-positive patients, and co-infection of HIV and hepatitis C virus is common among HIV-infected injection drug users. 
Saurabh Das/AP Photo 

But the news is not all positive. While we’ve seen mortality rates from HIV, TB and malaria decline in recent years, mortality from hepatitis B and C has risen. Globally, an estimated 257 million people have chronic hepatitis B virus infection, and 71 million have chronic hepatitis C virus. Together hepatitis B and C caused 1.34 million deaths in 2015. This led the World Health Organization to challenge countries around the world to develop national plans to eliminate these two viruses by 2030.

Hepatitis B virus and hepatitis C virus are usually spread through contact with blood or body secretions such as semen from infected persons by sharing needles or sexual exposure. But they can also be spread through contaminated needles used for medical treatment, which continues to happen in many parts of the world. In addition, hepatitis B virus can be spread from infected mothers to newborn babies unless vaccination is given immediately after birth.

For hepatitis C virus, roughly two-third suffer chronic infection. For hepatitis B virus, the chance of chronic liver infection decreases the later the patient encounters the virus: 90 percent if infected during infancy; 20-30 percent if infected during childhood; and 2-5 percent if infected in adult life. Some people infected with hepatitis B virus or hepatitis C virus can recover on their own, but many go on to chronic infection (lasting more than six months and often years or lifelong). Those with chronic infection are at risk of cirrhosis (severe liver damage), liver failure and liver cancer.

Opioid epidemic, homeless lead to rise in hepatitis B and C infections
In this Nov. 8, 2017, photo, Christine Wade sits among her children in front of their donated tent in the city-sanctioned encampment on a parking lot in San Diego. The Wade family is among several hundred people living in the city’s first campground open for the homeless, set up to curb the worst hepatitis A outbreak in the United States in decades. 

In the United States, the number of new hepatitis B virus and hepatitis C virus infections has been decreasing for many years, but this trend has been reversed during recent years due to the opioid epidemic as more people use injection drugs, share needles or other paraphernalia and practice high-risk sexual behavior. This is particularly true for hepatitis C, where the number of new cases in the past 10 years has more than doubled, highlighting the need for a preventive vaccine, which is a vital tool if we want to eliminate hepatitis C. The increase in number of new cases of hepatitis B is smaller and mainly seen in adults in their 30s because most younger persons have benefited from hepatitis B virus vaccination.

When we talk about viral hepatitis, the focus is on hepatitis B and C because they can cause chronic infection, while hepatitis A causes only acute infection and will not lead to cirrhosis or liver cancer. However, starting late 2016, many states in the U.S. have witnessed outbreaks of hepatitis A. The Centers for Disease Control and Prevention (CDC) received more than 2,500 reports of hepatitis A between January 2017 and April 2018 associated with person-to-person transmission, with risk factors in two-thirds of these cases being drug use or homelessness or both. In the state of Michigan, where I live, 859 cases of hepatitis A including 27 deaths were reported between July 2016 and June 2018. We can prevent hepatitis A through vaccination and improved hygienic conditions.

As we celebrate World Hepatitis Day on July 28, a day chosen in honor of the late Dr. Baruch Blumberg, who received a Nobel Prize for discovering the hepatitis B virus, I marvel at how much progress we have made in the last three decades and am delighted to be not just an observer but also a contributor to the progress. Our work is not finished. Much more needs to be done to completely eliminate new cases of viral hepatitis and deaths from chronic hepatitis B and C.

Thursday, July 12, 2018

Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection

Journal of Hepatology
Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection
JohannesVermehren, James S. Park, Ira Jacobson, StefanZeuzem

https://doi.org/10.1016/j.jhep.2018.07.002

Full-Text

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The following full-text articles downloaded and shared by Henry E. Chang.

Abstract
Treatment of chronic hepatitis C virus (HCV) infection has been revolutionized with the development of direct-acting antiviral agents (DAAs). Eight to twelve weeks of all-oral, once-daily treatments is now the standard of care and viral eradication can be achieved in >95% across different patient populations. Despite these advances, several unresolved issues remain, including treatment of HCV genotype 3, chronic kidney disease, and in patients in whom DAA therapy has failed. Glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) are the most recently approved DAA regimens. Given the overwhelming success of modern DAA-based therapies, GLE/PIB and SOF/VEL/VOX are also likely to represent the last DAAs to be approved. Both are pangenotypic, once-daily, all-oral DAA combinations that have the potential to close the gaps in the current DAA treatment portfolio. Here, we review the challenges associated with current DAAs and how these two regimens may be implemented in existing treatment algorithms.

Of Special Interest
Commentary
Hepatitis C Management Simplification From Test to Cure:A Framework for Primary Care Providers
SOF/VEL or GLE/PIB), both highly tolerated and effective for all genotypes.

Sofosbuvir and Ledipasvir is Associated with High Sustained Virologic Response and Improvement of Health-Related Quality of Life in East Asian Patients with Hepatitis C Virus Infection
In summary, our data clearly show the superiority of IFN-free RBV-free LDV/SOF in East Asian patients with chronic HCV genotype 1 infection. The advantages of that regimen are related not only to its high efficacy and excellent tolerability but also to significantly better quality of life during treatment and after achieving SVR. These data provide evidences up porting the comprehensive benefit of LDV/SOF for eligible patients which should inform all stakeholders, including providers, payers, and policy makers in East Asian countries

Absolute denials of DAA regimens by insurers in the U.S. have remained high & increased over time, regardless of type of insurance.

Tuesday, July 10, 2018

July Updates: Hep C Symptoms – How Do Yours Compare?

In The Journals - Catch up with what you may has missed.

Hep C Symptoms – How Do Yours Compare?
Welcome to this months hand-picked hepatitis newsletters, and recommended blogs from around the web. We start over at HepatitisC.net, where you can read about an array of hepatitis C symptoms, review a poll on the subject, and finally scan all the new blog entries.

Blog Updates Around The Web 
Check out the following articles from your favorite bloggers, along with this months viral hepatitis newsletters.

Lucinda K. Porter
Lucinda Porter is a nurse, speaker, advocate and patient devoted to increasing awareness about hepatitis C.
Latest: Freedom from Worry

Hep 
Hep is an award-winning print and online brand for people living with and affected by viral hepatitis.
Latest: Remember Your “Bear” Story When Fighting Hepatitis C and Liver Disease
Liver Health: Yet Another Reason to Avoid Alcohol

Life Beyond Hepatitis C
Life Beyond Hep C is where faith, medical resources and patient support meet, helping Hep C patients and their families navigate through the entire journey of Hep C.
Latest: Feeling Depleted with Hepatitis C?

I Help C
Your Best Friend’s Guide to Hepatitis C and Cirrhosis
Latest: All Shook Up with PTSD from Liver Disease

CATIE Blog
A comprehensive website for HIV and hepatitis C information
Latest: What it will take to eliminate hepatitis C in Canada

Canadian Liver Foundation 
We strive to improve prevention and the quality of life of those living with liver disease by advocating for better screening, access to treatment, and patient care.
Latest: ‘HepBeware’ It begins with a diagnosis.

AGA Journals
Latest: Can Nonlytic T cells be Engineered to Fight HBV Infection?

Hepatitis B Foundation 
The Hepatitis B Foundation is a national nonprofit organization dedicated to finding a cure and improving the quality of life for those affected by hepatitis B worldwide.
Latest: - Finding the Missing Millions in Ghana

An ongoing dialogue on HIV/AIDS, infectious diseases, all matters medical, and some not so medical.
Latest: Surgeon Who Was Denied Disability Insurance for Taking PrEP Tells His Story

The Hepatitis C Mentor and Support Group 
Latest: Needle exchanges have been proved to work against opioid addiction. They’re banned in 15 states.

Newsletters
HCV Advocate
The HCV Advocate newsletter is a valuable resource designed to provide the hepatitis C community with monthly updates on events, clinical research, and education.
July Issue
In this month’s HCV Advocate newsletter we have a plethora of articles for your reading and learning pleasure:
HealthWise: Avoiding Fatty Liver by Lucinda Porter, RN. 
Lucinda shares her personal and professional tips to help you avoid or reduce fatty liver disease.

Hepatitis Headlines:
AASLD and IDSA Announce Updates to HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C
The Canadian Association for the Study of the Liver recommends that Canadians born between 1945 and 1975 should be tested for hepatitis C

Evaluation of Instruments used to Measure Hepatitis C Patient-Reported
Symptoms by Alan Franciscus. 
This is the first in a series of studies from a PCORI funded study. The first one was to evaluate the reliability and validity of several survey instruments.

SnapShots 
by Alan Franciscus. 
In this month’s column I write about the following studies:
Prognostic value of viral eradication for major adverse cardiovascular events in hepatitis C cirrhotic patients
Evaluation of the Xpert HCV Viral Load Finger-Stick Point-of-Care Assay
Gut dysbiosis associated with hepatitis C virus infection
Briefly:
Hepatocellular carcinoma incidence and survival among people with hepatitis C an international study
Hepatitis C care in the Department of Veterans Affairs: Building a foundation for success
Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis
Viral hepatitis screening in transgender patients undergoing gender identity hormonal therapy 

We have updated our entire series of Easy C Facts
View all newsletters here....

Weekly Bull
HepCBC is a Canadian non-profit organization offering awareness with basic information about HCV and a weekly digest of news.
Read the latest issue of the highly successful Weekly Bull.

Hep - Your Guide to Hepatitis
Hep is an award-winning print and online brand for people living with and affected by viral hepatitis. Offering unparalleled editorial excellence since 2010, Hep and HepMag.com are the go-to source for educational and social support for people living with hepatitis.
View - all issues
Read the news
Check out the talented people who blog at Hep.

The National Viral Hepatitis Roundtable
The National Viral Hepatitis Roundtable (NVHR) is national coalition working together to eliminate hepatitis B and C in the United States.
July Newsletter

The New York City Hepatitis C Task Force
The New York City Hepatitis C Task Force is a city-wide network of service providers and advocates concerned with hepatitis C and related issues. The groups come together to learn, share information and resources, network, and identify hepatitis C related needs in the community. Committees form to work on projects in order to meet needs identified by the community.
View: Hep Free NYC Newsletters
Review all news updates.

HCV Action
HCV Action brings together hepatitis C health professionals from across the patient pathway with the pharmaceutical industry and patient representatives to share expertise and good practice.
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World Hepatitis Alliance
We run global campaigns, convene high-level policy events, build capacity and pioneer global movements, ensuring people living with viral hepatitis guide every aspect of our work.
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World Hepatitis Alliance (WHA) presents hepVoice, a monthly magazine with updates on the latest projects, news from WHA members and key developments in the field of hepatitis.

GI & Hepatology News
Over 17,000 gastroenterologists and hepatologists rely on GI & Hepatology News every month to cover the world of medicine with breaking news, on-site medical meeting coverage, and expert perspectives both in print and online.
View all updates here....

CATIE
CATIE strengthens Canada’s response to HIV and hepatitis C by bridging research and practice. We connect healthcare and community-based service providers with the latest science, and promote good practices for prevention and treatment programs.
Updates - News
What's New?
Continuing care needed for HIV-positive people after hospitalization for mental health issues
HepCinfo Update 9.13: Half with HIV/HCV untreated for HCV; HCV cure improves fatty liver; community-based liver screening feasible

Hepatitis Victoria
Hepatitis Victoria is the peak not-for-profit community organisation working across the state for people affected by or at risk of viral hepatitis.
July Newsletter - Download We also produced short podcasts interviewing health experts and practioners on topics related to viral hepatitis - come have a listen!

British Liver Trust
The British Liver Trust is the leading UK liver disease charity for adults – we provide information and support; increase awareness of how liver disease can be prevented and promote early diagnosis; fund and champion research and campaign for better services.
View Recent Newsletters, here.

Hepatitis B Foundation
Hepatitis B Foundation is a national nonprofit dedicated to finding a cure and improving the quality of life for people affected by hepatitis B worldwide.
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Blog & News

National Institutes of Health
A monthly newsletter from the National Institutes of Health, part of the U.S. Department of Health and Human Services
Read: July Newsletter

Thanks for stopping by!
Tina