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

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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.

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Risk factors for hepatocellular carcinoma by age, sex, and liver disorder status

Cancer. 2018 Apr 18. doi: 10.1002/cncr.31406. [Epub ahead of print]
Risk factors for hepatocellular carcinoma by age, sex, and liver disorder status: A prospective cohort study in Korea.
Yi SW1,2, Choi JS3, Yi JJ4, Lee YH5, Han KJ3.

First published: 18 April 2018

https://doi.org/10.1002/cncr.31406

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Abstract

BACKGROUND:
To the authors' knowledge, relatively little is known regarding the interaction of risk factors for hepatocellular carcinoma (HCC) with age, sex, and liver disorder status.

METHODS:
The authors followed 504,646 Korean patients aged 40 to 80 years who underwent routine health checkups between 2002 and 2003 until 2013 via linkage to national hospital discharge records.

RESULTS:
HCC occurred in 2744 individuals. In the sex-adjusted and age-adjusted analysis, cirrhosis increased the incidence of HCC by 42-fold, followed by hepatitis B virus (21-fold), hepatitis C virus (HCV; 19-fold), male sex (4.3-fold), and each 5-year age increment (1.24-fold). In the multivariable adjusted analysis, diabetes increased the risk of HCC by 80%, alcohol consumption ≥80 g/day increased the risk by 75%, alcohol consumption of 40 to 79 g/day increased the risk by 37%, and being a current smoker increased the risk by 25%. The multivariable adjusted hazard ratios of male sex and HCV were 6.27 and 5.72, respectively, at age <50 years, but were 2.09 and 22.51, respectively, at age ≥70 years. Each 20 g/day of alcohol consumption increased the risk of HCC by 6% (P = .11), 8% (P = .02), 16% (P<.001), and 30% (P<.001), respectively, in individuals aged <50 years, 50 to 59 years, 60 to 69 years, and 70 to 80 years. In individuals without a liver disorder, body mass index was found to be positively associated with HCC, whereas patients with a liver disorder demonstrated an inverse association. Women had higher adjusted hazard ratios associated with age and cirrhosis compared with men.

CONCLUSIONS:
With advancing age, the effects of alcohol use and HCV on the development of HCC become stronger, whereas the effect of male sex weakens. Lifetime moderate alcohol consumption may cause HCC in the elderly. Smoking increases the risk of HCC irrespective of viral hepatitis, and diabetes increases the risk of HCC independent of cirrhosis. Cancer 2018. © 2018 American Cancer Society.

© 2018 American Cancer Society.

https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.31406

European Food Safety Authority Warns Green Tea Extracts May Be Associated With Liver Damage

According to new research from the European Food Safety Authority (EFSA) consuming more than 800mg of green tea catechins per day may lead to higher health risks, including liver damage.

Scientific opinion on the safety of green tea catechins EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS)

Maged Younes Peter Aggett Fernando Aguilar Riccardo Crebelli Birgit Dusemund Metka Filipič Maria Jose Frutos Pierre Galtier David Gott Ursula Gundert‐Remy Claude Lambré Jean‐Charles Leblanc Inger Therese Lillegaard Peter Moldeus Alicja Mortensen Agneta Oskarsson Ivan Stankovic Ine Waalkens‐Berendsen Rudolf Antonius Woutersen Raul J Andrade Cristina Fortes Pasquale Mosesso Patrizia Restani Davide Arcella Fabiola Pizzo Camilla Smeraldi Matthew Wright

First published: 18 April 2018 https://doi.org/10.2903/j.efsa.2018.5239

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Abstract
The EFSA ANS Panel was asked to provide a scientific opinion on the safety of green tea catechins from dietary sources including preparations such as food supplements and infusions. Green tea is produced from the leaves of Camellia sinensis (L.) Kuntze, without fermentation, which prevents the oxidation of polyphenolic components. Most of the polyphenols in green tea are catechins. The Panel considered the possible association between the consumption of (‐)‐epigallocatechin‐3‐gallate (EGCG), the most relevant catechin in green tea, and hepatotoxicity. This scientific opinion is based on published scientific literature, including interventional studies, monographs and reports by national and international authorities and data received following a public ‘Call for data’. The mean daily intake of EGCG resulting from the consumption of green tea infusions ranges from 90 to 300 mg/day while exposure by high‐level consumers is estimated to be up to 866 mg EGCG/day, in the adult population in the EU. Food supplements containing green tea catechins provide a daily dose of EGCG in the range of 5–1,000 mg/day, for adult population. The Panel concluded that catechins from green tea infusion, prepared in a traditional way, and reconstituted drinks with an equivalent composition to traditional green tea infusions, are in general considered to be safe according to the presumption of safety approach provided the intake corresponds to reported intakes in European Member States. However, rare cases of liver injury have been reported after consumption of green tea infusions, most probably due to an idiosyncratic reaction. Based on the available data on the potential adverse effects of green tea catechins on the liver, the Panel concluded that there is evidence from interventional clinical trials that intake of doses equal or above 800 mg EGCG/day taken as a food supplement has been shown to induce a statistically significant increase of serum transaminases in treated subjects compared to control.

Continue reading online: https://efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5239

In The Media
Green tea supplements may cause liver damage, warns EU watchdog
The European Food Safety Authority assessed the safety of the supplements
More than 800mg of green tea catechins each day may pose health concerns
Officials at the EU funded organisation were unable to confirm a safe dose
It today called for further scientific trials into the effect of green tea catechins

Every Cloud Has a Silver Lining: Overdose-Death Donors in Organ Transplantation

HIV and ID Observations
Hepatitis C Positive Organ Donors — Coming Soon to a Transplant Center Near You
There’s one immutable fact in solid organ transplantation — the number of patients awaiting transplant exceeds the number of available organs.
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Reuters Health

Organs from overdose-death donors a viable option for transplant
Last Updated: 2018-04-16
By Marilynn Larkin
NEW YORK (Reuters Health) - Transplantation with overdose-death donor (ODD) organs has increased dramatically in the U.S., with equivalent outcomes to non-ODD organs, and therefore these organs should not be routinely discarded, researchers in Maryland say.

"Most Americans know that the U.S. faces an epidemic of deaths due to drug overdose, and many are also aware that there is a critical shortage of organs available for transplant," Dr. Christine Durand of Johns Hopkins University School of Medicine in Baltimore told Reuters Health.

"Perhaps less widely known is that today, more than one in every 10 deceased organ donors died from a drug overdose," she said by email.

"Patients who received transplants from these donors had excellent outcomes; patient survival and organ function were similar to cases when donors died due to trauma, and similar or better than cases when the donor died due to medical causes of death like heart attack or stroke," she added.

Dr. Durand and colleagues examined data from January 2000 to September 2017 on 138,565 deceased donors and 337,934 transplant recipients at 297 transplant centers in the U.S.

Continue reading: http://www.chronicliverdisease.org/reuters/article.cfm?article=20180416Other2030196131

Ann Intern Med 2018

Editorial |17 April 2018

Every Cloud Has a Silver Lining: Overdose-Death Donors in Organ Transplantation

Nearly 115 000 candidates currently await organ transplantation in the United States (mostly kidneys [81%] and livers [12%]) (1). Because of the profound organ shortage, many candidates awaiting transplant experience significant morbidity and mortality each year. In this issue, Durand and colleagues (2) review the use of overdose-death donor (ODD) organ transplants involving 138 565 deceased donors and 337 934 solid organ transplant recipients from 2000 to 2017. The study used the Scientific Registry of Transplant Recipients, which includes U.S. national data collected by the Organ Procurement and Transplantation Network (OPTN). The authors found that ODD transplants increased 24-fold, from 149 in 2000 (1.1% of donors) to 3533 in 2016 (12.7% of donors). For the most part, outcomes with ODD organs were noninferior to those with organs from trauma-death donors (TDDs) and medical-death donors (MDDs). Compared with MDDs, ODDs were less likely to have hypertension, diabetes, or prior myocardial infarction but had slightly higher creatinine levels and were more likely to donate after circulatory death. Cold ischemic time of transplanted kidneys was similar across all donor types. In an adjusted analysis, recipients of ODD kidneys and livers had a lower risk for death than recipients of MDD organs and a similar risk for death and graft loss compared with recipients of TDD organs.

Abstract
The Drug Overdose Epidemic and Deceased-Donor Transplantation in the United States: A National Registry Study  

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 16, 2018

Does interferon-free direct-acting antiviral therapy for hepatitis C after curative treatment for hepatocellular carcinoma lead to unexpected recurrences of HCC? A multicenter study by the Japanese Red Cross Hospital Liver Study Group

Toshie Mashiba, Kouji Joko , Masayuki Kurosaki, Hironori Ochi, Yukio Osaki, Yuji Kojima, Ryo Nakata, Tohru Goto, Akahane Takehiro, Hiroyuki Kimura, Akeri Mitsuda, Chiharu Kawanami, Yasushi Uchida, Chikara Ogawa, Atsunori Kusakabe, Ryuichi Narita, Yasushi Ide, Takehiko Abe, Keiji Tsuji, Tadashi Kitamura, Kazuhiko Okada, Tetsuro Sohda, Masaya Shigeno, Takashi Satou, Namiki Izumi

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Since the era in which interferon (IFN) was the standard treatment for hepatitis C, attempts have been made to eliminate hepatitis C virus (HCV) following hepatocellular carcinoma (HCC) treatment, but it could be achieved in only a limited number of patients due to side effects. Recently, dramatic progress has been made in anti-HCV therapies. It is now feasible to achieve a sustained virological response (SVR) rate of ≥95% even in older patients or cirrhosis patients with IFN-free direct-acting antiviral (DAA) therapy that has minimal side effects in older patients and in cirrhosis patients [1], and antiviral therapy can now be performed easily in patients who have undergone HCC treatment. It has been reported that the elimination of HCV with IFN after curative treatment for HCV-associated HCC suppresses HCC recurrences [2–5]. We have also found that it dramatically extends patients’ survival [6]. However, whether a similar effect can be achieved with DAA therapy is unclear. Furthermore, potential increases in unexpected early recurrence of HCC after HCV elimination have been reported with DAA therapy [7,8]. With this background, the HCC recurrence rate was compared between those who underwent IFN therapy and those who underwent IFN-free therapy after HCC treatment in a large-scale cohort.

Abstract

Background and aim
This study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort.

Methods
This multicenter study was conducted by the Japanese Red Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and 347 IFN-free DAA-treated patients achieved sustained virological response (SVR). The recurrence rate of HCC was compared between the antiviral therapies. Logistic analysis and Cox proportional hazards analysis identified factors associated with early recurrence of HCC within 24 weeks of antiviral therapy and recurrence throughout the observation period, respectively.

Results
AFP at the completion of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors associated with early recurrence of HCC. Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC. For recurrence throughout the observation period in SVR patients, AFP at completion of antiviral therapy, duration between last HCC treatment to antiviral therapy, and the number of treatments were independent factors. There was no significant difference in the rate of early recurrence of HCC or recurrence throughout the observation period between IFN and IFN-free DAA treated patients.

Conclusions
There were no differences in the early recurrence rate of HCC between patients who underwent IFN and those who underwent IFN-free DAA as antiviral therapies.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194704

DAA therapy effective in patients with HCV and advanced cirrhosis - Real World Experience from the HCV-TARGET Cohort

The International Liver Congress 2018

NATAP Coverage:
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)

All Updates @ NATAP Coverage: International Liver Congress

Healio Coverage

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 sustained viroloic response, according to a presentation at the International Liver Congress 2018.

“Real-life SVR rates with DAAs in patients with advanced liver disease ranged from 85% to 100% and were comparable to clinical trial experience. Ribavirin did not influence SVR in this cohort,” Elizabeth C. Verna, MD, of Columbia University, said in her presentation. “Over the year following treatment, stabilization or marginal improvement is seen in those with low MELDs while greater degree of improvement may occur in patients with MELD greater than 16.”

Verna and colleagues used the HCV-TARGET database of patients to cull patients with cirrhosis and MELD higher than 10. Patients initiated DAA therapy between March 2014 and June 2017. Patients with prior liver transplant were excluded. The researchers enrolled 488 patients in the safety cohort and 412 patients in the efficacy cohort; of those, 373 achieved SVR12 and 39 failed treatment. Patients received a variety of approved regimens.

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Coverage: International Liver Congress

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For Patients: The International Liver Congress 2018 

Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?

World J Gastroenterol. Apr 14, 2018; 24(14): 1491-1506
Published online Apr 14, 2018. doi: 10.3748/wjg.v24.i14.1491

Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?
Ivana Mikolasevic, Tajana Filipec-Kanizaj, Maja Mijic, Ivan Jakopcic, Sandra Milic, Irena Hrstic, Nikola Sobocan, Davor Stimac, Patrizia Burra

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a primary cause of macrovesicular steatosis and has several impacts on liver transplantation (LT), which is transmitted to transplant recipients and organ donors. Current data indicate a new trend in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome (MetS) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT.

Continue to article: https://www.wjgnet.com/1007-9327/full/v24/i14/1491.htm

Long term follow up of HCV pts with F2-F3 fibrosis who had achieved SVR with DAA therapy

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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

Link: https://jumpshare.com/v/nmtqInYoY8yOinSGe6Xk