Showing posts with label Liver Fibrosis. Show all posts
Showing posts with label Liver Fibrosis. Show all posts

Thursday, August 9, 2018

Even light drinking may make fatty liver disease worse

Even light drinking may make fatty liver disease worse 
Study In Hepatology
July 17, 2018
Non‐heavy drinking and worsening of non‐invasive fibrosis markers in nonalcoholic fatty liver disease: A cohort study

Reuters Health
Lisa Rapaport
For the current study, researchers examined data on 58,927 Korean young and middle aged adults with NAFDL who had low levels of fibrosis, or scarring on the liver. After following half of these patients for at least 8.3 years, 5,630 people had progressed from low to more advanced levels of fibrosis.

Moderate drinkers were 29 percent more likely to have worse fibrosis by the end of the study than people who didn’t drink at all. Men were considered moderate drinkers when they had up to about two drinks a day, while women could have up to about 1.5 drinks daily.

But “light drinkers” who averaged less than 10 grams of alcohol (less than one drink) daily, were also 6 percent more likely to have their fibrosis become more advanced than people who avoided alcohol altogether, the study team reports in Hepatology.
Continue reading: https://in.reuters.com/article/us-health-liver-drinking/even-light-drinking-may-make-fatty-liver-disease-worse-idINKBN1KT2V7

Sunday, August 5, 2018

Hepatitis C-Diabetes associated w-advanced fibrosis and progression in HCV non-genotype 3 patients

In case you missed it

Dig Liver Dis. 2018 Jul 17. pii: S1590-8658(18)30814-4. doi: 10.1016/j.dld.2018.07.003. 
[Epub ahead of print]

Diabetes is associated with advanced fibrosis and fibrosis progression in non-genotype 3 chronic hepatitis C patients.

Researchers investigated if diabetes is associated with progression from the non-cirrhotic liver to cirrhosis in non-genotype 3 chronic hepatitis C (CHC) patients. In the study 976 non-genotype 3 patients with HCV were studied, out of the 976 participants, 684 did not have cirrhosis. According to ultrasound findings, 60 patients developed cirrhosis during the follow-up period. In non-genotype 3 CHC patients, diabetes was correlated with progression from the non-cirrhotic liver to cirrhosis.

Abstract
BACKGROUND:
Diabetes is a risk factor of fibrosis progression in chronic hepatitis C (CHC). However, only one longitudinal study exploring whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in CHC patients has been conducted.

AIMS: 
We investigated whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients.

METHODS: 
A cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC was studied. After excluding patients with biopsy-proven or ultrasound-identified cirrhosis, there were 684 patients without cirrhosis. All 684 patients underwent hepatocellular carcinoma surveillance using ultrasound every 6 months, with a median duration of follow-up evaluation of 102.4 months. During the follow-up period, 60 patients developed cirrhosis according to ultrasound findings.

RESULTS: 
For the subgroup of 684 patients without cirrhosis, Kaplan-Meier survival analyses showed no significantly different cumulative incidences of cirrhosis (log-rank test; P = 0.71) among the patients with diabetes as compared to those without. However, after making adjustments for age, gender, fibrosis, steatosis, sustained virological response status, and obesity using Cox's proportional hazard model, diabetes was found to be an independent predictor for cirrhosis (HR = 1.9; 95% CI = 1.05-3.43, P = 0.03).

CONCLUSIONS: 
Diabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients.

KEYWORDS:
Diabetes; Genotype 3; Hepatitis C virus; Liver cirrhosis; Ultrasound
PMID: 30076015 DOI: 10.1016/j.dld.2018.07.003 
Full text article requires payment 

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, July 12, 2018

Northwestern Medicine study has newly identified a trigger of some fibrotic diseases

Why internal scars won't stop growing Rogue molecules provoke out-of-control scar tissue, strangle organs 
Northwestern University

-New compound discovered that halts some fibrotic diseases
-Fibrosis accounts for up to 40 percent of all global deaths
-Human fibrotic cells reveal immune abnormality 

CHICAGO --- Normal scar tissue forms to heal an internal wound and quietly retreats when the job is done. But in many common diseases - kidney, liver and lung fibrosis -- the scar tissue goes rogue and strangles vital organs. These diseases are largely untreatable and ultimately fatal.

A new Northwestern Medicine study has newly identified a trigger of some fibrotic diseases and an experimental compound to treat it.

Fibrosis - a progressive scarring and hardening of internal organs - is estimated to cause 35 to 40 percent of deaths in the world. Fibrotic diseases include diabetic kidney fibrosis, alcoholic liver cirrhosis, hepatitis C, pulmonary fibrosis and nonalcoholic fatty liver disease, which may lead to fibrosis of the liver, the leading cause of liver transplant.

In one subset of human fibrosis cells, scientists discovered a delinquent gang of molecules that continually shouted at an immune receptor - the antennae on the cell -- to produce scar tissue instead of quieting down and allowing the scar tissue to go back to sleep.

Scientists collaborated with a University of Colorado researcher who used crystallography and computer modeling to predict a molecule that could block the receptor that leads to the uncontrolled scarring. When they tested the molecule, T53, in three different mouse models of fibrosis, the abnormality was significantly reversed.

"Our study opens a new door into fibrosis by looking at it as an aberrant innate immune response and suggesting a novel approach to treat it," said senior author Dr. John Varga, director of the Northwestern Scleroderma Program and the John and Nancy Hughes Distinguished Professor of Rheumatology at Northwestern University Feinberg School of Medicine.

The paper will be published July 12 in the Journal of Clinical Investigation Insight.

"The leading cause of liver failure in western world is obesity and that's because of liver fibrosis," Varga said. "In the U.S., many of these diseases are lifestyle or age dependent. As we get fatter or older, they get worse."

Most fibrotic disease likely begins as normal repair of an injury, scientists said. "But if the immune system produces too much of an initial scar, it can't go back to normal," Varga said. "You have an unhealed scar that keeps growing and can wipe out the entire organ."

Not everyone's fibrosis is caused by the same abnormality, Varga said. If the compound, T53, is eventually developed into an approved drug, it would be targeted to patients with the specific genetic signature identified in the study.

"There is an emerging direction for treating fibrosis with precision medicine," said first author Swati Bhattacharyya, research associate professor of medicine in rheumatology and scientific director of the Scleroderma Research Laboratory at Feinberg. "Some people live with fibrotic disease for 30 years while others die in two years. We need to identify the rapid progressors from the slow progressors. That's where precision medicine becomes really critical."

"The results of this study are encouraging," Varga said. "We are not saying this compound is ready to be a drug. It's an initial compound that would need to be developed and tweaked. It would need significant funding to go to the next step."

Varga has spent more than a decade researching the cause and treatment of scleroderma, a type of fibrosis that simultaneously affects multiple organs. He directs the Northwestern Scleroderma Program, a clinical and research effort that follows 1,500 patients with scleroderma.

Tuesday, May 29, 2018

Can anti-viral therapy reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus

Available on Medscape
Viral Eradication Reduces Both Liver Stiffness and Steatosis in Patients With Chronic Hepatitis C Virus Infection Who Received Direct-acting Anti-viral Therapy
In this study, we investigated changes in liver stiffness and steatosis as determined by MRI in patients with chronic HCV genotype 1 or 2 infection who received direct-acting anti-viral therapy and achieved SVR.
May 29, 2018 

Viral Eradication Reduces Both Liver Stiffness and Steatosis in Patients With Chronic Hepatitis C Virus Infection Who Received Direct-acting Anti-viral Therapy
T. Tada; T. Kumada; H. Toyoda; Y. Sone; K. Takeshima; S. Ogawa; T. Goto; A. Wakahata; M. Nakashima; M. Nakamuta; J. Tanaka

Abstract
Background Whether direct-acting anti-viral therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection is unclear.

Aims To evaluate changes in liver stiffness and steatosis in patients with HCV who received direct-acting anti-viral therapy and achieved sustained virological response (SVR).

Methods A total of 198 patients infected with HCV genotype 1 or 2 who achieved SVR after direct-acting anti-viral therapy were analysed. Liver stiffness as evaluated by magnetic resonance elastography, steatosis as evaluated by magnetic resonance imaging-determined proton density fat fraction (PDFF), insulin resistance, and laboratory data were assessed before treatment (baseline) and at 24 weeks after the end of treatment (SVR24).

Results Alanine aminotransferase and homeostatic model assessment-insulin resistance levels decreased significantly from baseline to SVR24. Conversely, platelet count, which is inversely associated with liver fibrosis, increased significantly from baseline to SVR24. In patients with high triglyceride levels (≥150 mg/dL), triglyceride levels significantly decreased from baseline to SVR24 (P = 0.004). The median (interquartile range) liver stiffness values at baseline and SVR24 were 3.10 (2.70–4.18) kPa and 2.80 (2.40–3.77) kPa respectively (P < 0.001). The PDFF values at baseline and SVR 24 were 2.4 (1.7–3.4)% and 1.9 (1.3–2.8)% respectively (P < 0.001). In addition, 68% (19/28) of patients with fatty liver at baseline (PDFF ≥5.2%; n = 28) no longer had fatty liver (PDFF <5.2%) at SVR24.

Conclusion Viral eradication reduces both liver stiffness and steatosis in patients with chronic HCV who received direct-acting anti-viral therapy (UMIN000017020).

Saturday, May 26, 2018

Quick blood test can detect liver damage before symptoms appear

UMass Amherst Chemists, International Team Develop New Blood Test to Detect Liver Damage in Under an Hour 
May 24, 2018
Vincent Rotello

AMHERST, Mass. – Chemist Vincent Rotello at the University of Massachusetts Amherst, with colleagues at University College London (UCL), U.K., announce today that they have developed a “quick and robust” blood test that can detect liver damage before symptoms appear, offering what they hope is a significant advance in early detection of liver disease. Details appear in Advanced Materials.

Their new method can detect liver fibrosis, the first stage of liver scarring that can lead to fatal disease if left unchecked, from a blood sample in 30-45 minutes, the authors note. They point out that liver disease is a leading cause of premature mortality in the United States and U.K., and is rising. It often goes unnoticed until late stages of the disease when the damage is irreversible.

For this work, Rotello and his team at UMass Amherst’s Institute of Applied Life Sciences (IALS) designed a sensor that uses polymers coated with fluorescent dyes that bind to blood proteins based on their chemical processes. The dyes change in brightness and color, offering a different signature or blood protein pattern.

He says, “This platform provides a simple and inexpensive way of diagnosing disease with potential for both personal health monitoring and applications in developing parts of the world.” Rotello and colleagues hope the new test can be used routinely in medical offices, clinics and hospitals to screen people with elevated liver disease risk so they can be treated “before it’s too late.”

The UCL team tested the sensor by comparing results from small blood samples equivalent to finger-prick checks from 65 people, in three balanced groups of healthy patients and among those with early-stage and late-stage fibrosis. This was determined using the Enhanced Liver Fibrosis (ELF) test, the existing benchmark for liver fibrosis detection. They found that the sensor identified different protein-level patterns in the blood of people in the three groups. The ELF test requires samples to be sent away to a lab.

Co-author William Peveler, a chemist now at the University of Glasgow, adds, “By comparing the different samples, the sensor array identified a ‘fingerprint’ of liver damage. It’s the first time this approach has been validated in something as complex as blood, to detect something as important as liver disease.”

The investigators report that the test distinguished fibrotic samples from healthy blood 80 percent of the time, reaching the standard threshold of clinical relevance on a widely-used metric and comparable to existing methods of diagnosing and monitoring fibrosis. The test distinguished between mild-moderate fibrosis and severe fibrosis 60 percent of the time. The researchers plan further tests with larger samples to refine the method’s effectiveness.

Peter Reinhart, director of UMass Amherst’s IALS says, “These exciting findings epitomize the mission of IALS to translate excellent basic science into diagnostics, therapeutic candidates and personalized health monitoring devices to improve human health and well-being.”

Peveler adds, “This may open the door to a cost-effective regular screening program thanks to its simplicity, low cost and robustness. We’re addressing a vital need for point-of-care diagnostics and monitoring, which could help millions of people access the care they need to prevent fatal liver disease.”

Rotello explains that the sensing strategy uses a “signature-based” approach that is highly versatile and should be useful in other areas. “A key feature of this sensing strategy is that it is not disease-specific, so it is applicable to a wide spectrum of conditions, which opens up the possibility of diagnostic systems that can track health status, providing both disease detection and monitoring wellness.”

In addition to UMass Amherst, UCL and the University of Glasgow, the U.K.-based research and development firm iQur Ltd. took part in the study. The work was supported by the U.K. Royal Society, the U.K. Engineering and Physical Sciences Research Council, the U.S. National Institutes of Health and the U.K. National Institute for Health Research UCLH Biomedical Research Centre.

Link
Advanced Materials article
Source

Friday, May 11, 2018

Patients with stage 3 compared to stage 4 liver fibrosis have lower frequency of and longer time to liver disease complications

As a side note, according to the HCV treatment guidelines published by the American Association for the Study of Liver Diseases, the Infectious Diseases Society of America and the International Antiviral Society, the only contraindication to current chronic HCV treatment is in a patient with a short life expectancy that cannot be lengthened with treatment, with liver transplant, or with any other treatments. Overtime we have learned that treating people with lower-stage fibrosis increases SVR rates, and for persons who inject drugs, adherence and efficacy rates are comparable to those of patients who do not use injected drugs. In other words, treat all.

Patients with stage 3 compared to stage 4 liver fibrosis have lower frequency of and longer time to liver disease complications
Page Axley, Sandhya Mudumbi, Shabnam Sarker, Yong-Fang Kuo, Ashwani Singal
Published: May 10, 2018
https://doi.org/10.1371/journal.pone.0197117

Full-Text

Abstract
Background and aims
Advanced liver fibrosis is an important predictor of liver disease progression and mortality, and current guidelines recommend screening for complications of cirrhosis once patients develop F3 fibrosis. Our study compared liver disease progression and survival in patients with stage 3 (F3) and stage 4 (F4) fibrosis on liver biopsy.

Methods
Retrospective study of patients with F3 or F4 on liver biopsy followed for development of liver disease complications (variceal bleeding, ascites, and hepatic encephalopathy); hepatocellular carcinoma, and survival (overall and transplant free survival).

Results
Of 2488 patients receiving liver biopsy between 01/02 and 12/12, a total of 294 (171 F3) were analyzed. Over a median follow up period of 3 years, patients with F4 (mean age 53 years, 63% male) compared to F3 (mean age 49 years, 43% male) had higher five year cumulative probability of any decompensation (38% vs. 14%, p<0.0001), including variceal bleed (10% vs. 4%, p = 0.014), ascites (21% vs. 9%, p = 0.0014), and hepatic encephalopathy (14% vs. 5%, p = 0.003). F4 patients also had lower overall 5-year survival (80% vs. 93%, p = 0.003) and transplant free survival (80% vs. 93%, p = 0.002). Probability of hepatocellular carcinoma in 5 years after biopsy was similar between F3 and F4 (1.2% vs. 2%, p = 0.54).

Conclusions
Compared to F4 stage, patients with F3 fibrosis have decreased risk for development of liver disease complications and better survival. Prospective well designed studies are suggested with large sample size and overcoming the limitations identified in this study, to confirm and validate these findings, as basis for modifying guidelines and recommendations on follow up of patients with advanced fibrosis and stage 3 liver fibrosis.

Discussion Only
View full text article @ PLOS ONE

The main findings of our study are that patients with F4 fibrosis compared to those with F3 stage have a) higher probability of developing decompensation of liver disease including ascites, variceal bleeding, and hepatic encephalopathy and b) lower overall and transplant-free survival.

In patients with chronic HCV infection, several previous studies have reported increased rate of liver disease complications related to advanced fibrosis stage. In a study of 1050 HCV patients, 57% with Ishak stage 4 to 6, there was cumulative incidence of first liver-disease complication of 19.3% for stage 4, 37.8% for stage 5, and 49.3% for stage 6 in the 6 year follow up period.[8] The probability of liver disease complication, death, or liver transplant increased with successive fibrosis stages. Stages 4 and 5 of the Ishak system represent advanced bridging fibrosis and/or early nodule formation and have shown excellent correlation with F3 in the METAVIR system.[9]

Another study based on four large US-integrated health systems retrospectively examined 917 chronic HCV patients with F3 and F4 fibrosis for 5 years after liver biopsy.[10] For liver disease related complications comparing F4 vs. F3 fibrosis, there was increased risk for ascites (14 vs. 7.1%), esophageal varices with bleeding (4.4 vs. 1.2%), and hepatic encephalopathy (3.9 vs. 1.4%) in the 5 year observation period after liver biopsy. The 5-year survival was 77% in F4 fibrosis compared to 91% in F3 fibrosis. The 5-year probability for HCC development was 3.1% in F3 fibrosis and 8.8% in F4 fibrosis.

Huang et al. evaluated 153 patients with F3 fibrosis (mean age 45, 54% male) and F4 fibrosis (mean age 51, 54% male) over a mean follow up period of 9 years and found that F4 had significantly higher risk of liver-related complications, hepatocellular carcinoma, and death than F3 (p < 0.001).[11] Very similar to our findings, the 5-year survival in patients with F4 fibrosis was 83% compared to 96% in patients with F3 fibrosis. The 5-year probability for development of HCC patients with F3 fibrosis was 0% compared to 6% in F4 patients. At year 7, probabilities for HCC development jumped to 16% in patients with F4 fibrosis and increased to 2% in patients with F3 fibrosis. Unlike these previous 2 studies described, our study failed to show a difference in the risk for development of HCC in F3 compared to F4 fibrosis, likely because of the shorter follow up period of only 5 years and the inclusion of non-HCV patients who have lower risk for HCC development.

In NAFLD, advanced fibrosis has also been identified as leading to higher rates of liver-disease related complications and mortality.[12, 13] In a recent study of 646 patients (mean age 48, 62% male) with well-defined NAFLD followed for a mean of 20 years, patients with F4 fibrosis had a 3-fold increase in liver disease related complications and a 2-fold increase in overall mortality compared to those with F3 fibrosis.[14] The average time for patients with F3 fibrosis to develop severe liver disease as defined by the ICD-code diagnosis of cirrhosis, liver failure, HCC, or decompensated liver disease was 6 years (95% CI 2.3–9.6), however the study did not differentiate between these outcomes or provide data on HCC incidence. In another large multi-center cohort study of 619 NAFLD patients (11.5% with stage 3 or 4 fibrosis) followed for a median of 12.6 years, F4 patients compared to F3 patients had a four-fold increased probability for liver disease related complications overall and two-fold increased risk of liver-related mortality.[13] Only 3 patients in the study developed HCC, and fibrosis stage for these patients was not reported.

To our knowledge, this is the first study showing that patients with F3 compared to F4 fibrosis have lower frequency of and longer time to development of liver disease complications irrespective of liver disease etiology. Our large cohort is also well characterized with liver fibrosis stage confirmed by two separate pathologists. Further, studies have shown good inter- and intraobserver reproducibility on the fibrosis staging using any classification including the Metavir fibrosis staging system.[5] Also, potential confounders of alcohol use and HCV treatment were equally distributed in the two groups ruling out to a great extent their impact on the outcomes. However, apart from inherent limitations of a retrospective study design, our study does suffer from potential selection bias as not everyone presenting for liver disease evaluation at our center underwent a liver biopsy examination. Further, our study excluded patients with F2 fibrosis, which could be used as a control group and compare with F3 fibrosis on development of outcomes. Although for analysis on decompensation and liver disease complications, we only analyzed patients developing the respective event after 30 days from liver biopsy, it is possible that some of the F3 patients may have transitioned to F4 on follow up, and it is difficult to ascertain the stage of fibrosis at which the decompensation occurred. Repeat liver biopsy or non-invasive imaging with transient elastography was not performed and limits us from identifying the patients that may have progressed from F3 to F4 fibrosis stage.

Regardless of underlying liver disease etiology, advanced hepatic fibrosis portends increased liver-associated complications and mortality.[1013, 1521] However, physicians need to be vigilant as these patients unpredictably may transition to F4 stage. In this regard, data are needed on the use of non-invasive serum and radiological markers including fibroscan and transient elastography, as basis for cost-effective management of these patients in clinical practice.

In summary, our study shows lower rate of and slower development of decompensation and liver disease complications, with better overall and transplant free survival among patients with biopsy conformed bridging or advanced fibrosis (F3) as compared to patients with cirrhosis (F4) irrespective of liver disease etiology. We suggest larger multicenter prospective studies overcoming the limitations identified in this study, to confirm and validate these findings as basis for modifying guidelines and recommendations on follow up of patients with advanced fibrosis and stage 3 liver fibrosis.

Saturday, April 21, 2018

Albumin predicts cirrhosis improvement after SVR with DAAs

Albumin predicts cirrhosis improvement after SVR with DAAs
April 20, 2018

PARIS — Rapid improvement in albumin levels after 4 weeks of treatment with direct-acting antivirals for hepatitis C significantly predicted long-term clinical and biochemical improvements among patients with advanced liver disease, according to a presentation at the International Liver Congress 2018.

“The introduction of DAAs has completely changed the HCV setting in clinical practice,” Chiara Mazzarelli, MD, from King’s College Hospital, United Kingdom, said in her presentation. “As hepatologists, we know that HCV clearance ... is associated with improvement and normalization of liver function.”

On This Blog

Thursday, April 19, 2018

Hepatic Steatosis and its Effects on Fibrosis in Patients With Chronic Hepatitis B Virus Infection

Clinical Gastroenterology and Hepatology (CGH)
April 2018 Volume 16, Issue 4, Pages 491–494

Hepatic Steatosis and its Effects on Fibrosis in Patients With Chronic Hepatitis B Virus Infection
Mauricio Garcia-Saenz-de-Sicilia, MD, Andres Duarte-Rojo, MD, MS, DSC

Full-Text
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Obesity rising prevalence has reawakened interest in the potential interactions between chronic viral hepatitis and hepatic steatosis. The metabolic syndrome and its components are independent risk factors associated with fibrosis progression, development of cirrhosis,1 and potentially with lack of fibrosis reversal following antiviral therapy in chronic viral hepatitis.2 However, the particular role of hepatic steatosis, the hallmark of nonalcoholic fatty liver (NAFLD), has been less of a focus of attention in chronic hepatitis B virus (HBV) infection when compared with chronic hepatitis C, in part because of the lack of proper evaluation tools.3

Liver biopsy is considered to be the gold standard for steatosis grading. However, it is invasive, has potential life-threatening complications, can result in sampling errors particularly when fatty infiltration is unevenly distributed (typical biopsy represents 1/50,000 of liver), and interpretation reaches only moderate interobserver or intraobserver agreement.4 Furthermore, repeated monitoring following a therapeutic intervention is hard to justify because of the invasive nature of the procedure and cost, and the fact that noninvasive options are now available. Imaging techniques provide reliable noninvasive alternatives to assess steatosis. Proton density fat fraction from magnetic resonance is perhaps the most accurate method for steatosis quantification; however, it is not a point-of-care method, and has associated high costs and limited availability, making it impractical for routine clinical care at most institutions. All of these limitations are at least partially overcome by the controlled attenuated parameter (CAP) feature from FibroScan (Echosens, Paris, France). This technique, based on the principle that fat affects ultrasound propagation, quantifies variations in M-mode (unidimensional) ultrasound attenuation during liver stiffness measurement (LSM) with vibration-controlled transient elastography, to yield a steatosis estimate. When testing CAP against steatosis grading by liver biopsy, fair to excellent performance has been reported across studies, and discrepancies are likely explained by variations in liver disease etiology, population body composition, and spectrum bias (Table 1). Although CAP interpretation has been limited by uncertainty as to the optimal cutoff values between grades of steatosis, Karlas et al5 have recently brought some certainty to this issue. In a meta-analysis including 2735 cases with histology and CAP analysis, the authors defined cutoff values and variables influencing the output, such as body mass index (BMI), diabetes, and etiology.

Friday, April 13, 2018

Eight weeks of treatment with Epclusa cured almost all people receiving opioid substitution therapy

Conference news @infohep
Eight weeks of treatment with Epclusa cured almost all people receiving opioid substitution therapy
Keith Alcorn
Published: 12 April 2018
An eight-week course of sofosbuvir/velpatasvir (Epclusa) cured almost all people with hepatitis C genotype 3 without cirrhosis receiving treatment alongside opioid substitution therapy through community pharmacies or prisons in the Greater Glasgow area, Alison Boyle of Gartnavel Hospital, Glasgow, reported at the 2018 International Liver Congress in Paris on Thursday. Genotype 3 is especially common in people who inject drugs and former drug users. It has been considered 'harder to cure' although recent studies of newer agents in people with genotype 3 have shown high cure rates.
Continue reading......

Slides @ NATAP
8 weeks sofosbuvir/velpatasvir in genotype 3 patients with significant fibrosis: Highly effective amongst an OST cohort - (04/13/18)

New @infohep
New Hepatocellular carcinoma (HCC)
EASL updates liver cancer guidelines at International Liver Congress
Liz Highleyman / 7 hours ago
The European Association for the Study of the Liver (EASL) presented updated clinical practice guidelines for the management of hepatocellular carcinoma (HCC) during a special session at the 2018 International Liver Congress yesterday

New NAFLD
Cenicriviroc treatment improves liver fibrosis in people with NASH
Liz Highleyman / 7 hours ago
Cenicriviroc, a drug that blocks both CCR5 and CCR2 receptors on immune cells, continued to show an anti-fibrotic effect in people with non-alcoholic steatosis (NASH) after two years of follow-up, according to a

New Treatment for people who use drugs
Eight weeks of treatment with Epclusa cured almost all people with HCV receiving opioid substitution therapy
Keith Alcorn / 18 hours ago
An eight-week course of sofosbuvir/velpatasvir (Epclusa) cured almost all people with hepatitis C genotype 3 without cirrhosis receiving treatment alongside opioid substitution therapy through community pharmacies or prisons in the Greater Glasgow area...

Pan-genotypic regimens
New affordable hepatitis C combination shows 97% cure rate
Keith Alcorn / 12 April 2018
The combination of sofosbuvir and the new NS5A inhibitor ravidasvir cured 97% of people with hepatitis C in a study carried out in Malaysia, and could provide a safe and

Thursday, April 12, 2018

The Benefits of Hepatitis C Virus Cure via DAAs: Every Rose Has Thorns

In case you missed it

The Benefits of Hepatitis C Virus Cure: Every Rose Has Thorns
D. Salmon; M. U. Mondelli; M. Maticic; J. E. Arends

J Viral Hepat. 2018;25(4):320-328.

The advent of DAAs has revolutionized the treatment of HCV infection, enabling a cure for most patients. This will result in declining mortality rates due to HCC and to fewer extrahepatic manifestations. However, it will require early treatment of HCV at an individual and population level, with broad access to DAAs. To achieve the collective targets, a radical change is needed, with highly motivated national policies to improve screening and access to care, particularly in high–risk populations.

Abstract
To examine mid–term benefits on hepatic complications, extrahepatic clinical syndromes and quality of life associated with HCV cure; to review the few safety issues linked to oral direct–acting antivirals (DAAs); and to discuss the potential population benefits of reducing the burden of HCV infection. DAAs cure HCV infection in more than 95% of patients. The halting of liver inflammation and fibrosis progression translates into both hepatic and extrahepatic benefits and reduces the need for liver transplantation. A reduction in the frequency of extrahepatic manifestations such as mixed cryoglobulinaemia and vasculitis and improvements in quality of life and fatigue have also been described. A few safety issues linked to DAAs such as the potential recurrence of aggressive HCC, the flares of hepatitis B virus in patients with overt or occult HBV infection are been discussed. Curing HCV infection also has a high potential to reduce the burden of HCV infection at the population level. With widespread scaling up of HCV treatment, several modeling studies suggest that major reductions in HCV prevalence and incidence are possible, and that elimination of viral hepatitis is an achievable target by 2030.

*Free registration may be required 

Liver Congress™ 2018 Scotland: Direct-acting antiviral agent therapy reduces the burden of HCV-related decompensated cirrhosis

Related
Early-stage HCV treatment saves money, improves QOL
April 12, 2018
PARIS — Treating hepatitis C virus in the early stage of disease saves money in drug and medical costs while lowering risk for decompensated cirrhosis, hepatocellular carcinoma, liver transplant and liver-related death, according to a presentation at the International Liver Congress 2018.

“For all these outcomes, the best outcome is experienced by those who started at [fibrosis stage 0 and 1] and the worst by those who have advanced disease,” Scott Johnson, PhD, MHA, an economist with Medicus Economics LLC, said during a press conference. “The advanced patients have ten-sixteenths of the lifespan and quality of life of those who were treated when they were mild.”
Continue reading: https://www.healio.com/hepatology/hepatitis-c/news/online/%7Bbe1e33fe-348d-4b39-a390-05bee966a6d1%7D/early-stage-hcv-treatment-saves-money-improves-qol

Earlier HCV Tx May Lower Complication Rate, Save Money

PARIS -- Treating patients with hepatitis C virus (HCV) at earlier stages of fibrosis may be reduce both complications and cost, a commercially sponsored modeling study showed here.

There was a lower risk of decompensated cirrhosis, hepatocellular carcinoma, liver transplant, and liver-related death among patients who started treatment at the mild, F0-F1 stage compared to those who started treatment at advanced/compensated cirrhosis (F4/CC).
Continue reading: https://www.medpagetoday.com/meetingcoverage/easl/72308

Scotland: Direct-acting antiviral agent therapy reduces the burden of HCV-related decompensated cirrhosis 
European Association for the Study of the Liver

12 April 2018, Paris, France: Two presentations given this week at The International Liver Congress™ 2018 in Paris, France illustrate the impact that DAAs can have in averting HCV-related liver disease, and reducing the clinical and economic burden of this chronic infection. The first presentation summarized data from Scottish national records providing country-level evidence of a reduction in HCV-related decompensated cirrhosis since the introduction of DAAs in 2014. The second presentation described modelling data based on clinical trials of glecaprevir/pibrentasvir and UK patient tracker data, and suggested that the health and economic benefits of DAAs may be increased if treatment is initiated at an earlier stage of disease.

Rapid advances in the field of HCV treatment have led to the availability of several DAAs that now offer a cure, in the form of a sustained virological response (SVR), for more than 90% of people with chronic HCV infection.15,16 The impact of DAAs on the incidence and cost of liver morbidity and mortality at the population level is not yet known.17 Scotland is home to an estimated 34,500 people chronically infected with HCV and is regarded as a world leader in facing this problem.18 The Hepatitis C Action Plan (2006-2011) and the Sexual Health and Blood Borne Virus Framework (2011-2020)19 have resulted in significant increases in HCV diagnosis and treatment over the past decade.18-6 Informed by modelling work, Scotland set the ambitious target of reducing the incidence of HCV-related decompensated cirrhosis by 75% between 2015 and 2020.7,8

The Scottish HCV Clinical and Diagnosis databases, linked with the national inpatient hospital database, provided data on the use of HCV therapy up to March 2017 and on the numbers of patients with a chronic HCV diagnosis that had presented and been admitted to hospital for the first time with decompensated cirrhosis during 2000-2016. Among 4,800 people initiated on HCV therapy in Scotland between April 2014 and March 2017, 83% were treated with DAAs and 94% achieved SVR. This scale up of therapy, compared with the 3 preceding years, was associated with a 29% and 39% reduction in first-time presentations for decompensated cirrhosis among those previously diagnosed with chronic HCV and those with chronic HCV at the time of admission, respectively.

'Scotland's national surveillance of HCV treatment and disease means we are ideally placed to examine the early impact of DAA treatment on HCV-related disease progression at a population level', explained Professor Sharon Hutchinson from Glasgow Caledonian University, UK. 'We have been able to show that scale up of therapy has resulted in substantially fewer patients presenting with decompensated cirrhosis but has highlighted the need to address comorbidities that pose a continued risk of liver disease progression in those clear of the virus'.

In the second study, a health state transition model of the natural history of HCV was developed to forecast liver-related clinical and economic outcomes over a lifetime. The model population and treatment efficacy data were based on clinical trials of glecaprevir/pibrentasvir. Genotype, fibrosis distribution and costs were based on Scottish patient tracker data and on literature review. Rates of decompensated cirrhosis, hepatocellular carcinoma, liver transplant and liver-related death were predicted to be lower if treatment was initiated when disease was mild (F0-1) rather than delayed until compensated cirrhosis was present. As a consequence, early versus delayed treatment resulted in lower lifetime costs, including those associated with extrahepatic manifestations (F0-1: £33,297; compensated cirrhosis: £61,204), and greater lifetime quality-adjusted life years (F0-1: 16.20; compensated cirrhosis: 10.05).

'This study shows the impact that delayed treatment can have on a patient's life, including consequences such as liver morbidity and mortality, as well as extrahepatic complications', said Dr Sammy Saab, Professor of Medicine and Surgery at the University of California, Los Angeles. 'Beyond benefits to the patients, early treatment can generate significant savings by reducing clinical risks and allowing for a shorter, 8-week duration of treatment across all genotypes'.

'The studies from Scotland are important because they discuss the impact of HCV therapy and cure on patient-relevant outcomes', said Prof. Markus Cornberg from the Hannover Medical School, Germany, and EASL Governing Board Member. 'Recently, the value of DAA therapies has been challenged by a Cochrane review. These data are therefore very important in documenting not only sustained virological response, but also the prevention of morbidity and mortality'.

Author disclosures
Abstract 4515: Outside the submitted work: Sharon Hutchinson reports personal fees from Gilead Sciences; Hamish Innes reports personal fees from Gilead Sciences; John Dillon reports grants and personal fees from Gilead, Merck Sharp & Dohme, AbbVie, and Janssen; Peter Hayes reports personal fees from Merck Sharp & Dohme, Gilead, AbbVie, Janssen, Bristol-Myers Squibb, and Pfizer, and grants and personal fees from Roche; Raymond Fox is an Advisory Board member for AbbVie, Gilead, and Merck Sharp & Dohme, and reports personal fees from Gilead, AbbVie, and Merck Sharp & Dohme; Stephen Barclay reports personal fees from Gilead and Merck Sharp & Dohme, and grants and personal fees from AbbVie; Nicholas Kennedy is an Advisory Board member for AbbVie, Gilead, and Merck Sharp & Dohme, and reports personal fees from Gilead, AbbVie, and Merck Sharp & Dohme.

Abstract 1184: Design, study conduct and financial support for the study were provided by AbbVie, Inc. AbbVie Inc. participated in the interpretation of data, and review and approval of the abstract. All authors contributed to the development of the publication and maintained control over the final content. Brett Pinsky and Yuri Sanchez Gonzalez are employees of AbbVie Inc. and may own stocks and/or options in the company. Dominic Mitchell and Scott J Johnson are employees of Medicus Economics, LLC. Dominic Mitchell is a contractor to Medicus Economics, LLC. Medicus Economics, LLC received consulting fees for research from AbbVie. Sammy Saab is a consultant to and serves on speaker bureaus for AbbVie Inc., Bristol-Myers Squibb, Gilead, Janssen, and Merck.

References
15. World Health Organization. Global health sector strategy on viral hepatitis 2016-2021. June 2016. Available from: http://www.who.int/hepatitis/strategy2016-2021/ghss-hep/en/. Last accessed: March 2018.

16. Scottish National Clinical Guidelines for the treatment of HCV in adults. Version 4.0, November 2017. Available from: http://www.hps.scot.nhs.uk/resourcedocument.aspx?resourceid=1598. Last accessed: March 2018.

17. Jakobsen JC, et al. Direct-acting antivirals for chronic hepatitis C. Cochrane Database Syst Rev. 2017;18:9.

18. The Hepatitis C Trust. Eliminating hepatitis C in Scotland: a call to action, 2018. Available from: http://www.hcvaction.org.uk/sites/default/files/resources/Eliminating%20Hepatitis%20C%20FINAL.pdf. Last accessed: March 2018.

19. Scottish Sexual Health and Blood Borne Virus Framework (2015-2020). Available from: http://www.gov.scot/Resource/0048/00484414.pdf. Last accessed: March 2018.

20. Hutchinson S, et al. Expansion of HCV treatment access to people who have injected drugs through effective translation of research into public health policy: Scotland's experience. Int J Drug Policy. 2015;26(11):1041-9.

21. Innes H, et al. Strategies for the treatment of hepatitis C in an era of interferon-free therapies: what public health outcomes do we value most? Gut. 2015;64(11):1800-9.

22. The Scottish Government hepatitis C treatment & therapies group report. Revised February 2017. Available from: http://www.gov.scot/Resource/0051/00515075.pdf. Last accessed March 2018.

For Patients: The International Liver Congress 2018

International Liver Congress

April 11, 2018 - April 15, 2018
Paris, France
Congress Website

Whether your liver is infected with a virus, injured by alcohol, or you have the most common liver disease in the United States - non-alcoholic fatty liver disease (NAFLD) - you need accurate information to make an intelligent decision about both treatment and care. From April 11-15, the 53rd annual meeting of the European Association for the Study of the Liver (EASL) will present key developments in the world of hepatology.

Viral Hepatitis & Fatty Liver Disease
Viral hepatitis highlights include; current and emerging treatments for hepatitis B virus (HBV), current data on effective drugs to treat hepatitis C virus (HCV), with research into the importance of early HCV treatment, follow up care, testing and linkage to care. As well as current research on liver cancer, alcoholic liver disease, fatty liver disease (information on screening, noninvasive tests, follow-up care, diet, and new drugs on the horizon), fibrosis, cirrhosis and liver transplantation.

Practice Guidelines
The European Association for the Study of the Liver (EASL) will also release four major clinical practice guidelines; hepatocellular carcinoma, decompensated cirrhosis, alcoholic liver diseases and updated recommendations on hepatitis C, view the guidelines below.

Download: Recommendations on Treatment of Hepatitis C 2018
April 11, 2018
EASL just released Updated EASL Recommendations on Treatment of Hepatitis C 2018.
*Shared by @HenryEChang via Twitter.

You can view the following guidelines online in the Journal of Hepatology;
EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma

Overview: EASL updates liver cancer guidelines at International Liver Congress
April 13. 2018
Liz Highleyman
The European Association for the Study of the Liver (EASL) presented updated clinical practice guidelines for the management of hepatocellular carcinoma (HCC) during a special session at the 2018 International Liver Congress yesterday ...


EASL Clinical Practice Guidelines on hepatitis E virus infection

Practice Guidelines - Download Slide Decks

Clinical Care Options
April 27, 2018
Practice-Changing Data From EASL 2018
Listen to downloadable audio from a live Webinar in which Stefan Zeuzem, MD, assessed the clinical impact of new data reported at the Paris meeting and answered case questions from participants.
Free Registration Required 

Conference News
April 28, 2018
On This Blog
Updates before, during and after the meeting.

Hepatitis C Treatment
May 17, 2018
HCV Next, May/June 2018
Nancy S. Reau, MD
As we in the United States look ahead to Digestive Disease Week coming up and further to our fall meetings, the International Liver Congress gives us an opportunity to…

May 4, 2018
Available online @ NATAP
Summary from EASL 2018 for Hepatitis C (HCV)
HCV in 2018: Success stories and remaining challenges?
With the more recent introduction of the pangenotypic regimens sofosbuvir/velpatasvir and glecaprevir/pibrentasvir, two new fix dose combinations have become available which may even overcome the need for baseline HCV genotype assessment. Larger data sets however, from real-life cohorts still are missing but this gap has been filled at this year EASL.

May 1, 2018
Download HCV Advocates' May Newsletter
In this edition of the HCV Advocate we have devoted nearly the entire issue to the 2018 International Liver Congress. Lucinda Porter, RN and I cover some of our favorite posters and presentations in the current issue and in the upcoming June 2018 issue...

April 28, 2018
April "infohep bulletin" - Overview of EASL's 2018 International Liver Congress
Patients looking for an overview of EASL's 2018 International Liver Congress can find it in this month's "infohep bulletin".

International Liver Congress Sees Shift in Liver Diseases
I’ve been covering this conference since 2012, at the dawn of the era of direct-acting antivirals for hepatitis C. For about five years a large proportion of content—and the lion’s share of excitement—at this meeting was devoted to these new therapies.

April 21, 2018
Slides @ NATAP


Liver Fibrosis


Mavyret (glecaprevir/pibrentasvir)
The results of the first real-world studies assessing the effectiveness and safety of glecaprevir/pibrentasvir (G/P) in patients with chronic hepatitis C virus (HCV) infection have confirmed high rates of viral suppression and a favourable safety profile in patients receiving 8-16 weeks of treatment.

Commentary - Real-world experience confirms Mavyret efficacy in HCV
Two real-world studies presented at the International Liver Congress 2018 confirmed the efficacy and safety of Mavyret in Italy and Germany even in the face of multiple comorbidities.

Slides - Real-life effectiveness & safety of G/P among 723 Italian patients with chronic HCV: interim analysis of data from the NAVIGATOR-II study


NATAP Slides - FIRST REAL-WORLD DATA ON SAFETY AND EFFECTIVENESS OF GLECAPREVIR/PIBRENTASVIR FOR THE TREATMENT OF PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION: DATA FROM THE GERMAN HEPATITIS C-REGISTRY - (04/13/18)

Integrated Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients With Psychiatric Disorders - (04/13/18)



RETREATMENT OF HEPATITIS C VIRUS INFECTION IN PATIENTS WHO FAILED GLECAPREVIR/PIBRENTASVIR - (04/12/18)

Time to Viral Suppression Does not Impact SVR in Patients Treated With Glecaprevir/Pibrentasvir for 8 Weeks - (04/23/18)

Clinical Care Options CCO - Review Capsules Summaries, download slides, and listen to audio commentary from expert-led Webinars covering critical studies on viral hepatitis.

Zepatier (elbasvir/grazoprevir)
Commentary - Zepatier Yields High Hepatitis C Cure Rates in U.S. Veterans
April 13, 2018
Cure rates were near 100 percent even though the population in the study’s analysis had high rates of other health conditions.




Effectiveness of Elbasvir/Grazoprevir in Patients with Cirrhotic Genotype 1 or 4 Chronic Hepatitis C: Updated Retrospective Data Analyses from the TRIO Network - (04/13/18)

Clinical Care Options CCO - Review Capsules Summaries, download slides, and listen to audio commentary from expert-led Webinars covering critical studies on viral hepatitis.
Second Interim Analysis of STREAGER: High Rate of SVR With 8 Weeks of Elbasvir/Grazoprevir in Treatment-Naive Patients With Nonsevere Fibrosis and Genotype 1b HCV Infection
Summary of Key Conclusions
In analysis of first 90 patients enrolled on a single-arm, open-label trial of treatment-naive patients with nonsevere fibrosis and genotype 1b HCV infection, 8 weeks of elbasvir/grazoprevir associated with sustained virologic response rate at 12 weeks post treatment (SVR12) of 97%
No grade 3/4 adverse events observed
Relapse observed in 4 patients (1 patient relapsed after achieving SVR12), including 1 patient with genotype 1e HCV infection wrongfully included in study

Harvoni (ledipasvir/sofosbuvir)
Slides @ NATAP
An eight-week course of sofosbuvir/velpatasvir (Epclusa) cured almost all people with hepatitis C genotype 3 without cirrhosis receiving treatment alongside opioid substitution therapy through community pharmacies or prisons in the Greater Glasgow area, Alison Boyle of Gartnavel Hospital, Glasgow, reported at the 2018 International Liver Congress in Paris on Thursday. Genotype 3 is especially common in people who inject drugs and former drug users. It has been considered 'harder to cure' although recent studies of newer agents in people with genotype 3 have shown high cure rates.

Clinical Care Options CCOReview Capsules Summaries, download slides, and listen to audio commentary from expert-led Webinars covering critical studies on viral hepatitis.
High SVR12 Rate With 8 Weeks of Sofosbuvir/Velpatasvir in Real-World Retrospective Analysis of Treatment-Naive Patients With Genotype 3 HCV and Fibrosis
Main Findings
In ITT population, 93% (84/90) of noncirrhotic, treatment-naive patients with genotype 3 HCV infection achieved SVR12 following 8 weeks of sofosbuvir/velpatasvir
Lost to follow-up: n = 2
Premature discontinuation: n = 2
Death: n = 1
Reinfection without subsequent spontaneous clearance: n = 1
In mITT population, 100% of patients achieved SVR12
High rates of SVR12 observed across selected subgroups
Subgroup, n/N (%)
SVR
ITT Population
mITT Population
F3 fibrosis
23/28 (82.1)
23/23 (100)*†‡§
HCV RNA > 6,000,000 IU/mL
5/6 (83.3)
5/5 (100)
HIV coinfected
2/3 (66.6)
2/2 (100)
Quantifiable HCV RNA at end of treatment
7/7 (100)
7/7 (100)
Daily supervised methadone
35/38 (92.1)
35/35 (100)†‡
IVDU
8/8 (100)
8/8 (100)
Non-IVDU
14/15 (93.3)
14/14 (100)
Positive screen for drugs of abuse
4/4 (100)
4/4 (100)

Clinical Care Options CCO
Addition of RBV Associated With Increased Efficacy of 12 Weeks Sofosbuvir/Velpatasvir in Patients With Genotype 3 HCV Infection and Compensated Cirrhosis
Summary of Key Conclusions
In NS5A-naive patients with genotype 3 HCV infection and compensated cirrhosis, sustained virologic response at 12 weeks posttreatment (SVR12) rate numerically higher in those receiving sofosbuvir (SOF)/velpatasvir (VEL) with ribavirin (RBV) vs SOF/VEL alone
SVR12 rate 96% vs 91%, respectively
Fewer relapses observed with use of RBV
In both treatment arms, NS5A resistance associated substitutions (RAS) at baseline associated with reduced SVR12 rate, particularly Y93H
Treatment well tolerated
Few grade 3/4 adverse events (AEs), serious AEs, discontinuations for AEs in both treatment arms
Use of RBV associated with increased toxicities


Safety and Efficacy of Sofosbuvir/Velpatasvir with and without Ribavirin in Genotype 3 HCV-Infected Patients with Cirrhosis - (04/13/18)

Vosevi (Sofosbuvir/Velpatasvir/Voxilaprevir) 
Clinical and virological characteristics of DAA-experienced patients with chronic HCV infection treated with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX): results from the Frankfurt Resistance Database - (04/20/18)

Ravidasvir combined with sofosbuvir
Video Healio:
$300 HCV combination reaches 97% cure rates in Malaysia, Thailand
April 13, 2018
PARIS — Using a new medication and generic sofosbuvir, researchers reached 97% sustained virologic response in patients with hepatitis C both with and without…

Commentary - New affordable hepatitis C combination shows 97% cure rate
April 12, 2018
The combination of sofosbuvir and the new NS5A inhibitor ravidasvir cured 97% of people with hepatitis C in a study carried out in Malaysia, and could provide a safe and effective cure for hepatitis C in low- and middle-income countries for $300 or less, researchers of the Drugs for Neglected Diseases Initiative reported on the opening day of the 2018 International Liver Congress in Paris.

April 12, 2018
New affordable hepatitis C combination treatment shows 97% cure rate
An affordable hepatitis C combination treatment including the new drug candidate ravidasvir has been shown to be safe and effective, with extremely high cure rates for patients, including hard-to-treat cases, according to interim results from the Phase II/III STORM-C-1 trial presented by the non-profit research and development organisation Drugs for Neglected Diseases initiative (DNDi) at the International Liver Conference in Paris.

Commentary - The Latest Hepatitis C News From the 2018 International Liver Congress
April 13, 2018
By Lucinda K. Porter, RN
The 2018 International Liver Congress (ILC) began yesterday in Paris. This annual meeting is hosted by the European Association for the Study of the Liver (EASL). It is an important event for liver specialists, and people gather from all over the world to share their latest findings. In the next week, I’ll post more frequently with highlights from some posters and presentations. (Note: Conference presentations represent part of the story and unless and until these studies are published in a peer-reviewed journal, these data and conclusions are considered preliminary.)

Treat Early
(at earlier stages of fibrosis)
EASL Press Release - Liver Congress™ 2018 Scotland: Direct-acting antiviral agent therapy reduces the burden of HCV-related decompensated cirrhosis
April 12, 2018
Two presentations given this week at The International Liver Congress™ 2018 in Paris, France illustrate the impact that DAAs can have in averting HCV-related liver disease, and reducing the clinical and economic burden of this chronic infection.

Slides @ NATAP
EASL: Early versus Delayed Hepatitis C Treatment Provides Increased Health Benefits at Lower Costs: A Pan-Genotypic Cost-Effectiveness Analysis Set in Scotland -

The early treatment of hepatitis C infection with a pan-genotypic drug combination is more effective and less expensive than if therapy is delayed until liver fibrosis develops, health economists report. A health state-transition model of the natural history of hepatitis C shows that early therapy with the combination of glecaprevir and pibrentasvir (Mavyret, AbbVie) results in lower lifetime costs because of reductions in the risk for decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related mortality, said researcher Scott Johnson, PhD, from Medicus Economics in Boston.

Commentary - Early-stage HCV treatment saves money, improves QOL
April 12, 2018
Treating hepatitis C virus in the early stage of disease saves money in drug and medical costs while lowering risk for decompensated cirrhosis, hepatocellular carcinoma, liver transplant and liver-related death.

Commentary - Earlier HCV Tx May Lower Complication Rate, Save Money
April 12, 2018
PARIS -- Treating patients with hepatitis C virus (HCV) at earlier stages of fibrosis may be reduce both complications and cost, a commercially sponsored modeling study showed here. There was a lower risk of decompensated cirrhosis, hepatocellular carcinoma, liver transplant, and liver-related death among patients who started treatment at the mild, F0-F1 stage compared to those who started treatment at advanced/compensated cirrhosis (F4/CC).

Cirrhosis
NATAP Slides

Commentary - DAA therapy effective in patients with HCV and advanced cirrhosis
April 16, 2018
PARIS — Direct-acting antiviral therapy effectively treated hepatitis C virus in patients with high MELD scores, producing a high rate of…
Slides @ NATAP - Direct Acting Antiviral HCV Therapy is Safe and Effective in Patients with Decompensated Cirrhosis: Real World Experience from the HCV-TARGET Cohort - (04/12/18)

EASL Press Release - Liver Congress™ 2018 - Mediterranean-style diet improves gut microbial diversity reduces hospitalization in liver cirrhosis
April 12, 2018
'Our hypothesis for this study was that diet and the severity of cirrhosis might interact to determine microbiota composition and, ultimately, clinical outcomes in patients with liver cirrhosis'.

Press Release - Liver Congress™ 2018 A third of bacterial infections in patients with cirrhosis across the world are multi-drug resistant 
April 12, 2018
'The finding that over one in three of bacterial infections occurring in hospitalized patients with cirrhosis are induced by multidrug resistance microorganisms is very worrisome', said Prof. Annalisa Berzigotti from the University of Bern, Switzerland, and EASL Governing Board Member.

Commentary - 'Alarming' New Numbers on Bacterial Infection in Cirrhosis
April 12, 2018
PARIS — Infections caused by multidrug-resistant bacteria, which are common in patients with cirrhosis, are associated with a significant elevation in risk for in-hospital mortality, results from a global study show.

Liver Transplant
April 15. 2018
Therapies also appear to reduce liver-related mortality
Since use of direct acting antiviral combination therapies for hepatitis C virus (HCV) infection became widespread, the need for liver transplantation for patients with the infection has plummeted, researchers reported here.

Scale-up of HCV diagnosis and treatment
EASL Press Release - Linkage to care specialist facilitates access to HCV treatment for people who inject drugs
April 12, 2018
'Based on our analysis', said Sarah Robbins from the Polaris Observatory, 'we predict that given the current standard of care for the next 15 years, the total HCV-infected population in Europe would increase by an estimated 1% by 2030 and that, in order to meet WHO goals, the number of individuals diagnosed annually would need to increase to at least 800,000 by 2022, with 900,000 being treated each year by 2025. Improving linkage to care coupled with increased access to DAA therapy is needed to achieve such goals'.


Liver Cancer
Liver-related & HCC events were rare after up to 144 weeks of follow-up in patients with F2-F3 fibrosis who had achieved SVR with DAA therapy: Results from the Gilead Sciences SVR Registry


Slides @ NATAP
Commentary - EASL updates liver cancer guidelines at International Liver Congress
Liz Highleyman
The European Association for the Study of the Liver (EASL) presented updated clinical practice guidelines for the management of hepatocellular carcinoma (HCC) during a special session at the 2018 International Liver Congress yesterday ...

April 12, 2018
'HCC surveillance in HCV patients after sustained virological response is a matter of debate', said Prof. Markus Cornberg from the Hannover Medical School, Germany, and EASL Governing Board Member. 'This study is important because it emphasizes the importance of HCC surveillance by ultrasound in patients with cirrhosis, even if HCV has been eliminated. However, the study also challenges the need for surveillance in patients with advanced fibrosis but without cirrhosis'.

Video Healio:
April 13, 2018
“Long-term follow-up studies and data will be required to identify those who are at risk for tumor development and also to better tailor surveillance guidelines,” Zangneh concluded. – by Talitha Bennett
April 12, 2018
Celsion’s Phase III OPTIMA Study is expected to enroll up to 550 patients in up to 70 clinical sites in the United States, Europe, China and Asia Pacific, and will evaluate ThermoDox® in combination with optimized RFA, which will be standardized to a minimum of 45 minutes across all investigators and clinical sites for treating lesions three to seven centimeters, versus optimized RFA alone.

WHO’s 2030 hepatitis C elimination goals
April 12, 2018
New research presented at this year’s International Liver Congress in Paris, France (11-15 April) shows that while several European countries are now on target to meet WHO’s 2030 hepatitis C elimination goals, many others are off track and problems screening and diagnosing enough patients threaten the progress of all countries.

Hepatitis B
Press Release - Assembly Biosciences Presents Positive Interim Data from Phase 1a and 1b Studies of ABI-H0731 in HBV Patients in a Late-Breaker Session at the EASL Conference
April 12, 2018
The Phase 1b patient study enrolled both HBeAg positive and negative patients. Potent antiviral activity was observed across patient cohorts in a dose dependent manner. Specifically, in the ongoing 300 mg dose cohort, the mean overall decline from baseline is currently ≥2.8 log10 IU/mL, with ≥2.9 and 2.5 log10 IU/mL mean declines in HBeAg positive and negative patients, respectively. Maximal viral load declines of 3.6 to 4.0 log10 IU/mL were observed in certain HBeAg negative patients treated at all dose levels (100 to 400 mg). The company intends to report complete results from this study at a scientific conference later this year.

Slides @ NATAP

View all HBV coverage at NATAP

Fatty Liver Disease: NAFLD/NASH




April 13, 2018
'We demonstrated that German patients with NAFLD/NASH who develop compensated cirrhosis have a substantial burden of comorbidities and that their healthcare costs jump with the development of cirrhosis', said Dr Canbay. 'Novel treatment options are needed to improve patient outcomes'. 'This study highlights the burden of NASH cirrhosis on healthcare systems and reinforces the need for new therapies to tackle the epidemic currently affecting many European countries', said Prof. Phil Newsome from the Queen Elizabeth Hospital and University of Birmingham, UK, and EASL Governing Board Member.

Press Release - Gilead Presents Data on Multiple Investigational Regimens for the Treatment of Patients With Nonalcoholic Steatohepatitis (NASH) and Advanced Fibrosis at The International Liver CongressTM 2018
Gilead Presents Data on Multiple Investigational Regimens for the Treatment of Patients With Nonalcoholic Steatohepatitis (NASH) and Advanced Fibrosis at The International Liver CongressTM 2018

Commentary - Low food security increases risk for advanced fibrosis
Food insecurity an increased risk for advanced fibrosis, particularly among patients with diabetes, according to a presentation at the International Liver Congress 2018. According to a presentation by Russell Rosenblatt, MD, from the New York Presbyterian Hospital, food insecurity is the state of being without reliable access to a sufficient quantity of affordable, nutritious food, often in the form of low-cost, energy-dense, nutritionally poor foods. “Food insecurity’s risk for diabetes doesn’t stop there,” Rosenblatt said. “We know that diabetes increases the risk for NAFLD, and diabetes is also an increased risk factor for advanced fibrosis.”

April 13, 2108
Deep-learning approaches to pattern recognition in liver biopsy samples have moved one step closer to clinical application, with a new study reporting a good correlation between an automated image analysis system and an expert reviewer for the identification of key markers of disease activity in a pre-clinical model of non-alcoholic steatohepatitis (NASH).

April 13, 2018
presented the positive results from the interim analysis of the Phase 2 clinical trial of MN-001 (tipelukast) in NASH (non-alcoholic steatohepatitis) and NAFLD (non-alcoholic fatty liver disease) with hypertriglyceridemia

April 12. 2018
The research demonstrated that adding fructose (sugar) and fatty acids to three-dimensional bioprinted human liver tissue produced NASH-type liver pathology, including steatosis, inflammation, ballooning and fibrosis. Addition of MSDC-0602K to the tissue showed evidence of reduced disease progression, including reductions in collagen deposition and stellate cell activation, in the liver model.

Commentary - Cenicriviroc shows safe long-term antifibrotic activity in adults with NASH
April 12, 2018
PARIS — Cenicriviroc, an oral C-C chemokine receptor type 2 and type 5 antagonist also known as CVC, was well-tolerated and provided…

April 11, 2018
Two independent studies have today reported that alcoholic liver disease has now replaced hepatitis C virus (HCV) infection as the leading cause of liver transplantation in the USA in patients without HCC. Non-alcoholic steatohepatitis (NASH) is also on the increase, now ranking second as a cause of liver transplantation due to chronic liver disease.

Primary sclerosing cholangitis
April 13, 2018
'Studies like this one are key, since they investigate possible novel treatments for PSC, a disease that currently has no effective therapies', said Prof. Marco Marzioni from the University Hospital of Ancona, Italy, and EASL Governing Board Member. 'Although this trial did not achieve fully positive results in terms of reduction of markers of disease progression, it certainly indicates that the manipulation of key molecules involved in the pathophysiology of PSC is the route to cure for our patients'.

April 12, 2018
PARIS — Patients with primary sclerosing cholangitis who took statins – likely for another indication – showed reduced risk for transplant and morbidity, according to a presenter at the International Liver Congress 2018. - View Press Release

April 10, 2018
Animated short created to raise public awareness about liver failure European Association for the Study of the Liver
The ad highlights the innovative DIALIVE technology, a novel 'liver dialysis device' which after 25 years of research is undergoing two clinical trials which will assess its safety and efficacy. View the ad, here..... Press release, here....

Healio live from EASL’s 2018 International Liver Congress
Guidelines, Expanded Opportunities Mark EASL's Liver Congress
Liver Cancer on the Rise in Backdrop of Undiagnosed Hep C

Conference Coverage

Websites
Link: Practice Point 
Independent Conference Coverage from the 53rd Annual Congress of the European Association for the Study of the Liver (EASL)*
In this video series, Dr. Brown will present ‘what you need to know in 5‐minutes’ regarding today's presentations from The International Liver Congress EASL 2018 in Paris, France. These educational Clinical Clips will spotlight the latest advances in the prevention and treatment of hepatitis C through a series of daily, ‘what you need to know in 5-minutes’ videos each day from the conference.
Free registration required

To learn more, or view highlights see: Liver Congress 2018 - ‘what you need to know in 5-minutes’ video clips each day from the conference

EASL LiverTree - Open To All
This year webcasts and congress materials are open access! Watch freely the conferences and ePosters
*Free registration required

Link: NATAP
The National AIDS Treatment Advocacy Project - NATAP
Slide decks, press updates, commentary, and full-text articles
About NATAP

Link: Healio
Coverage of the meeting will include, videos, perspectives and interviews with leading researchers and clinicians.
About Healio

Link: infohep
Patient-friendly coverage

News, with patient-friendly commentary
About NAM

Link: MedPage Today
Commentary and news updates

Link: Medscape 
Read clinically focused news coverage of key developments from ILC 2018.
*Free registration may be required
About Medscape

Link: Clinical Care Options CCO
Review Capsules Summaries, download slides, and listen to audio commentary from expert-led Webinars covering critical studies on viral hepatitis and NAFLD/NASH from Paris.About CCO

Link: Liz Highleyman @ Cancer Health

Newsletters
Link: HCV Advocate
Download HCV Advocate's - May Newsletter
In this edition of the HCV Advocate we have devoted nearly the entire issue to the 2018 International Liver Congress. Lucinda Porter, RN and I cover some of our favorite posters and presentations in the current issue and in the upcoming June 2018 issue...

Blogs
HCV Advocate Greg Jefferys blogs from the conference.
Inside the convention hall were display stands for Zepatier, Mavyret and Epclusa and many other products related to treating liver diseases. The three DAA stands were by far the biggest but Gilead easily won the “Biggest and Most Number of display stands” award with three huge and separate stands.

Follow On Twitter
@EASLnews
@HenryEChang 
@JMPawlotsky 
@DonaldJensenMD
Liz Highleyman‏ @LizCancerHealth
@Homie_Razavi
@rixwolff
@JVLazarus
@HepatitisEurope

Abstract Book
Start by reviewing the first abstracts of the meeting, and embargo policy, available online and shared via Twitter by Henry E. Chang.
Download Here: https://jumpshare.com/v/rz9OhagvCF0FEPy7zwHQ

HEPAHEALTH Project Report
EASL report on the burden of liver disease across Europe
April 12, 2017
Link: Watch - Liver Congress™ 2018 - First Press Conference HEPAHEALTH Project Report
The European region is the highest consumer of alcoholic beverages in the world and efforts to reduce alcohol consumption are stalling in many countries. Likewise, rates of obesity have risen across almost every country the report surveyed since 2013 and the rates of Non-Alcoholic Fatty Liver Disease (NAFLD) are increasing accordingly. In Southern and Eastern Europe viral hepatitis is the leading cause of liver disease mortality.
Twitter #Hepahealth

Watch - Daily Press Conference

*Page updated May 5, 2018