Identification of 19 Novel Hepatitis C Virus Subtypes-Further Expanding HCV Classification

Open Forum Infectious Diseases

https://doi.org/10.1093/ofid/ofz076

Published: 22 February 2019 

Accepted Manuscript

Identification of 19 Novel Hepatitis C Virus Subtypes-Further Expanding HCV Classification 

Charlotte Hedskog1, Bandita Parhy1, Silvia Chang1, Stefan Zeuzem2, Christophe Moreno3, Stephen D.Shafran4, Sergio M. Borgia5, Tarik Asselah6, Laurent Alric7, Armand Abergel8, Jyh-Jou Chen9, Jane Collier10,Dharmesh Kapoor11, Robert H. Hyland1, Peter Simmonds12, Hongmei Mo1, Evguenia S. Svarovskaia

Full-text only available as a PDF: Download 

Abstract

Background

The hepatitis C virus (HCV) is currently classified into 8 genotypes and 86 subtypes. The objective of this study was to characterize novel HCV subtypes and to investigate the impact of subtypes on treatment outcome. 

Methods

Full genome sequencing was performed on HCV plasma samples with <85% sequence homology of NS3, NS5A and/or NS5B to HCV genotype (GT) 1 to 8 reference strains.

Results

14,653 patients with GT1 to 6 HCV infection were enrolled in clinical studies of sofosbuvir-based regimens. For the majority of the patients, a specific subtype could be assigned based on a close genetic relationship to previously described subtypes. However for 19 patients, novel subtypes were identified with <85% homology compared to previously described subtypes. These novel subtypes had the following genotypes; 9 in GT2, 5 in GT4, 2 in GT6 and one each in GT1, GT3 and GT5. Despite presence of polymorphisms at resistance-associated substitutions (RAS) positions, 18 of the 19 patients treated with sofosbuvir-containing therapy achieved SVR12. 

Conclusions

Nineteen novel HCV subtypes were identified, suggesting an even greater genetic diversity of HCV subtypes than previously recognized. 

Full-text only available as a PDF: Download 

Treatment for Advanced Liver Cancer: Current Standard and the Future

Clinical Liver Disease (CLD) 

Clinical Liver Disease is an official digital educational learning resource from the American Association for the Study of Liver Diseases. Visitors are able to view videos, access full text articles, and download files in either HTML or PDF formats.

Special Issue on HCC 
Volume13, Issue1

January 2019
Pages 13-19

Treatment for Advanced Hepatocellular Carcinoma: Current Standard and the Future 
Alisa Likhitsup M.D. Nataliya Razumilava M.D. Neehar D. Parikh M.D.
First published: 21 February 2019
https://doi.org/10.1002/cld.782

Watch a video presentation of this article

Download PDF

Hepatocellular carcinoma (HCC) is the third leading cause of death worldwide with increasing incidence and mortality in the United States.1, 2 High HCC‐associated mortality is in part due to the high proportion of patients diagnosed with advanced stage HCC and historical lack of effective systemic therapies for HCC.

HCC staging is unique because liver function and functional status, in addition to tumor burden, are integral determinants of stage and prognosis. Although staging systems vary, parameters that define advanced stage HCC eligible for therapy include presence of portal vein tumor invasion and/or extrahepatic metastases, with relatively preserved liver function and functional status. Generally, systemic therapy trials excluded patients with Child Pugh class B and C cirrhosis, largely because of the competing risk for mortality with cirrhosis. Thus, for many therapies, there are little data on efficacy and tolerability in patients with more advanced liver disease. Systemic therapies may also be appropriate in those patients with unresectable HCC who are not eligible for or are unlikely to benefit from locoregional therapies, although the decision on timing of when to initiate systemic therapy in a patient with intermediate HCC who is eligible for recurrent locoregional therapy remains an open question. In this review, we discuss contemporary approaches and ongoing studies for the treatment of patients with advanced HCC.
Continue to full-text article : https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/cld.782

or Download PDF

Review all articles in this special issue online:
https://aasldpubs.onlinelibrary.wiley.com/journal/20462484

On This Blog
Read All Posts With The Label Liver Cancer
Review a collection of current research articles extracted from peer-reviewed journals, liver meetings/conferences, and learning activities investigating the natural history of liver cancer, approved therapies, risk factors associated with chronic viral hepatitis, cancer-prevention, including diet, nutrition and physical activity, and trends associated with the rising rate of hepatocellular carcinoma in the U.S.

Begin, here.....

Liver Cancer After Treatment For Hepatitis C:

Research demonstrates that while SVR markedly reduced liver-related complications and liver cancer, some long-term risk for liver cancer remained in those who were cured of Hepatitis C. But after direct-acting antiviral therapy does the risk of developing liver cancer increase? Research is saying no, check out an index of articles here..... 

No need to discontinue hepatitis C virus therapy at the time of liver transplantation

PLoS One. 2019
No need to discontinue hepatitis C virus therapy at the time of liver transplantation
Catarina Skoglund, Martin Lagging, Maria Castedal

Published: February 22, 2019 https://doi.org/10.1371/journal.pone.0211437

Full-text
Download PDF
View Online

Abstract
Objectives
Direct antiviral agents (DAA) has dramatically improved the therapy outcome of hepatitis C-virus (HCV) infection, both on the waiting-list and post liver transplantation (LT). DAA are generally well-tolerated in patients with mild to moderate liver and kidney failure, but some DAAs are contraindicated in patients with severe dysfunction of these organs. Today there are few studies of peri-LT DAA use and treatment is commonly discontinued at the time of LT. We report here our experience of DAA therapy given continuously in the perioperative LT period in a real-life setting in Sweden.

Material
In total 10 patients with HCV-cirrhosis, with or without hepatocellular carcinoma, and a median age of 60.5 years (range, 52–65) were treated with DAAs on the waiting list for LT, and continued in the early postoperative period without any interruption, on the basis of not having reached a full treatment course at the time of LT. Sofosbuvir and a NS5A inhibitor with or without ribavirin, or sofosbuvir and ribavirin only, were given. The distribution of genotypes was genotype 1 and 3, in 4 and 6 patients, respectively. Six of the 10 patients had previously been treated with IFN-based therapy.

Results
There were no adverse events leading to premature DAA discontinuation. All recipients achieved a sustained viral response 12 weeks after end-of-treatment (SVR12). At the time of LT the median MELD-score was 16.5 (range 7–21), CTP-score 9.0 (range 5–10), creatinine 82.5 μmol/L (range 56–135, reference 60–105), bilirubin 33 μmol/L (range 16–79, reference 5–25) and PK-INR 1.5 (range 1.1–1.8). The median duration of DAA therapy was 60 days (range 18–132) pre-LT, 54 days post-LT (range 8–111 days) and in total 15.5 weeks (range 12–30 weeks).

Conclusion
Interferon-free DAA therapy of HCV-infection given in the immediate pre- and post-operative LT period is safe, well-tolerated and yields high SVR rates.

Full-text: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211437

Real impact of liver cirrhosis on the development of hepatocellular carcinoma in various liver diseases—meta‐analytic assessment

Cancer Med. 2019 Feb 21. doi: 10.1002/cam4.1998. [Epub ahead of print]
Real impact of liver cirrhosis on the development of hepatocellular carcinoma in various liver diseases-meta-analytic assessment.
Tarao K1, Nozaki A2, Ikeda T3, Sato A4, Komatsu H5, Komatsu T6, Taguri M7, Tanaka K8.

Abstract BACKGROUND:
It is well known that the incidence of developing hepatocelluler carcinoma (HCC) is increased in liver cirrhosis of different etiologies. However, comparison of HCC incidence in various liver diseases has not yet been estimated. We surveyed this comparison.

METHODS: The PubMed database was examined (1989-2017) for studies published in English language regarding the prospective follow-up results for the development of HCC in various liver diseases. A meta-analysis was performed for each liver disease.

RESULTS: The annual incidence (%) of HCC in the non-cirrhotic stage and cirrhotic stage, and the ratio of HCC incidence in the cirrhotic stage/non-cirrhotic stage were as follows. (a) hepatitis B virus liver disease: 0.37%→3.23% (8.73-fold), (b) hepatitis C virus liver diseases: 0.68%→4.81% (7.07-fold), (c) primary biliary cholangitis (0.26%→1.79%, 6.88-fold), (d) autoimmune hepatitis (0.19%→0.53%, 2.79-fold), and (e) NASH (0.03%→1.35%, 45.00-fold). Regarding primary hemochromatosis and alcoholic liver diseases, only follow-up studies in the cirrhotic stage were presented, 1.20% and 2.06%, respectively.

CONCLUSIONS: When the liver diseases advance to cirrhosis, the incidence of HCC is markedly increased. The development of HCC must be closely monitored by ultrasonography, magnetic resonance imaging, and computed tomography, irrespective of the different kinds of liver diseases.

DISCUSSION
--Download Full-text--
It is known that cirrhosis is present in 80～90% of HCC patients with any underlying liver disease,119 and it is the most important risk factor for HCC. However, comparison of the incidence of HCC in various liver diseases was not accurately and precisely evaluated in previous studies. In this study, we found that the incidence of HCC is highest in HCV LC (4.81%/year) and second highest in HBV LC (3.23%), followed by alcoholic LC (2.06%), PBC LC (1.79%), NASH LC (1.35%), primary hemochromatosis (1.20%), and AIH (0.53%).
        
The incidence of HCC has been wildly studied in patients with HBV LC and HCV LC, and was reported to be 3% and 5%,29, 120 which was almost the same as that in our study.

In this study, we also demonstrated that the incidence of HCC is markedly increased (2.79‐ to 45.00‐fold) in the cirrhotic state compared with non‐cirrhotic state, irrespective of the etiology of liver disease. Why this increase in HCC development occurs in the cirrhotic state must be considered.

First, chronic inflammation may be a key mechanism for HCC development in the cirrhotic state. In this respect, we made clinical observation in the HCV LC patients (Child A) in the past. The LC patients were divided into three groups: Group A: 28 patients whose annual average serum alanine aminotransferase (ALT) level was persistently high (≧80 IU; high‐ALT group); Group B: 28 patients whose annual average serum ALT levels was persistently low (<80 IU; low‐ALT group), and Group C: 13 unclassified patients. The patients had been followed up prospectively. The 5‐year incidence rate of HCC in the high‐ALT group was as high as 53.6% compared with only 7.1% in the low‐ALT group (P < 0.001).120 Thus, this clinical observation demonstrated the importance of chronic inflammation in the development of HCC in HCV LC.
        
The same tendency was demonstrated in HBV LC. Chen et al121 reported that high serum levels of HBV DNA and ALT were independent risk factors for HCC development in HBV infection. Ishikawa et al20 also reported that serum aminotransferase are one of predictive factor for the development of HCC. One important mechanism for high incidence of HCC in HCV LC and HBV LC as compared with the incidence of HCC in LC caused by other etiologies may be the sustained high‐grade inflammation.
        
Furthermore, in autoimmune hepatitis, persistent elevation of serum aminotransaminase was reported to lead to the development of HCC.78 This suggests a role for inflammation in the development of HCC, but this hypothesis has not been confirmed solidly.
         
Second, increases in DNA synthesis in the hepatocytes of cirrhotic patients is suspected as a possible mechanism of HCC development. In our previous study, we demonstrated that in the high DNA synthetic group [BrdU (thymidine analog) labeling index ≧1.5%] 64.3% of patients developed HCC in 5 years, in contrast to 14.3% in the low DNA synthesis (Brd U LI <1.5%) group in HCV LC patients (P < 0.05).122 We further demonstrated that in HCV‐associated cirrhosis patients who showed nodular formation on ultrasound, the cell cycle of hepatocytes was markedly accelerated, as estimated by the bromodeoxyuridine (thymidine analog) uptake into hepatocytes in vitro, and the incidence of HCC was greatly increased.123

Third, accumulated genomic change was also important factor for HCC development. In this respect, Hiatt et al124 reported that C282Y mutation itself may increase the risk of HCC development in hereditary hemochromatosis. In addition, in alcoholic LC, the genetic effect of long‐term alcoholic intake may influence the development of HCC.125

Fourth, obesity, and diabetes are suspected to increase the incidence of developing HCC. In a large epidemiologic study, patients with BMI >35 had an increased risk of cancer, especially HCC, with hazard ratio (HR) of 4.52.126 In addition, diabetes is associated with HCC occurrence, with a HR of 2.39 in a US cohort.127 It is generally accepted that NASH is associated with obesity and diabetes in high percentages.

Notably, in 2014, Flemming et al128 predicted the risk of HCC in patients with cirrhosis, using the ADRESS‐HCC risk model. They examined the l‐year probability of HCC in various liver diseases in 34 932 patients in the national transplantation waitlist database. HCC developed in 1960 patients (5.6%) during a median follow‐up of 1.3 years. Six baseline clinical variables including age, diabetes, race, etiology of cirrhosis, sex, and severity (ADRESS) of liver dysfunction were independently associated with HCC. They settled ADRESS‐HCC risk model from these data and the risk model well‐coincided with the clinical observation. They concluded that the risk model was clinically useful tool for predicting the risk of HCC in patients with diverse etiologies.

In addition, the aging of the patients must be taken into the consideration, as the cirrhotic patients were considered to be older than the non‐cirrhotic patients in almost all liver diseases. In this regard, Asahina et al129 investigated the difference of HCC incidence in aging in HCV‐associated liver disease, and found that the incidence of HCC was higher in the older patients (>65 years old) than the younger patients (<65 years old). The same tendency was observed by Taura et al130 However, the difference in incidence was approximately twofold. So, it is difficult to explain the marked difference in HCC incidence between the cirrhotic state and non‐cirrhotic state found in this meta‐analysis. Regarding other liver diseases, there were very few reports which demonstrated a difference between patients in the non‐cirrhotic and cirrhotic states concerning age.

The next consideration is the prevention of patients not to become cirrhosis state. We demonstrated that the incidence of HCC in the cirrhotic state and that in the non‐cirrhotic state were markedly different in many liver diseases; therefore, efforts to prevent patients with liver diseases from progressing to the cirrhotic state by all means is very important.

In HBV infection, the effort to diminish HBV‐DNA by pegylated interferon (Peg IFN)19 or oral antiviral agents, such as entecavir (ETV), tenofovir, and tenofovir anafenamide, is important. Indeed, ETV and tenofovir were reported to prevent the occurrence of HCC.131, 132In HCV infection, Peg IFN plus ribavirin or direct‐acting antivirals (DAAs) are effective to eliminate HCV, and may be prevent the progression of the disease, resulting in prevention of HCC development.

In primary biliary cholangitis, administration of ursodeoxycholic acid is important. Indeed, the risk of HCC in UDCA‐treated PBC patients was reported to be relatively low.59, 63

In autoimmune hepatitis, well‐designed corticosteroid therapy is important to prevent HCC development, and persistent elevation of serum aminotransaminase is reported to lead the development of HCC.78 It seems that alleviation of serum ALT levels might prevent HCC development, but this hypothesis is not confirmed solidly.
        
In NASH patients, improvement in metabolic syndrome, especially improvement in diabetes mellitus and obesity, is important.

Next, we mentioned whether the treatment of underlying liver diseases substantially modulates the HCC risk or not. We restricted the survey chiefly to the cirrhotic patients because they are at high risk of HCC development.

Continue to full-text article:
https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.1998

© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

KEYWORDS: hepatocellular carcinoma; liver cirrhosis; liver diseases; meta-analysis; risk of HCC

MAVIRET - AbbVie reaches an agreement with the pan-Canadian For HCV Drug

AbbVie reaches an agreement with the pan-Canadian Pharmaceutical Alliance (pCPA) for its hepatitis C treatment MAVIRET™

Feb. 21, 2019, 12:09 PM

Ontario will be the first province to reimburse MAVIRET as of February 28, 2019

MAVIRET is the first and only 8-week, pan-genotypic treatment for chronic hepatitis C patients without cirrhosis and who are new to treatment*1

MAVIRET previously received positive reimbursement recommendations from the CADTH Canadian Drug Expert Committee (CDEC)2 in January 2018 and the Institut national d'excellence en santé et services sociaux (INESSS) in February 2018

MAVIRET is the only pan-genotypic treatment approved for use in patients across all stages of chronic kidney disease

MONTREAL, Feb. 21, 2019 /CNW/ - AbbVie (NYSE: ABBV), a global, research and development-based biopharmaceutical company, announced an agreement was reached with the pan-Canadian Pharmaceutical Alliance (pCPA) regarding MAVIRET™ (glecaprevir/pibrentasvir tablets), a once-daily, ribavirin-free treatment for adults with chronic hepatitis C virus (HCV) infection across all major genotypes (GT1-6)2. MAVIRET is the only 8-week, pan-genotypic treatment for patients without cirrhosis and who are new to treatment,* who make up a large portion of HCV patients in Canada. 

Following the positive conclusion with the pCPA, Ontario will be the first province to reimburse MAVIRET on its public formulary as of February 28, 2019. As listed on the Ontario Drug Benefit (ODB)3 Formulary as a Limited Use product, MAVIRET will be covered for treatment-naïve and treatment-experienced adult patients with chronic hepatitis C infection (regardless of fibrosis stage)3:

Laboratory confirmed hepatitis C genotype 1,2,3,4,5,6
HCV RNA value within the last six months

***Prescription by a hepatologist, gastroenterologist or an infectious disease specialist (or other physician experienced in treating hepatitis C).

"After more than 20 years of treating hepatitis C, I am hopeful that soon we will successfully eliminate this virus. But in order to reach this goal in Canada and across the world, we need to work together to test, diagnose and bring these high curative treatments to every individual, regardless of their genotype, fibrosis stage and background," explains Dr. Magdy Elkhashab, Gastroenterologist/Hepatologist, Director of the Toronto Liver Centre. "As a hepatologist, MAVIRET offers me the opportunity to put my patients on an effective, short duration therapy that has a proven track record."

Approximately 300,000 Canadians are infected with hepatitis C.4 Over time chronic hepatitis C can lead to chronic liver diseases, with a risk of developing cirrhosis of up to 30 per cent within 20 years5 of infection. Additionally, HCV is common among people with severe chronic kidney disease (CKD), and some of these patients previously did not have a direct-acting antiviral (DAA)-based treatment option.6

"The Canadian Liver Foundation is committed to seeing Canada meet the target set by the World Health Organization's Global Strategy on Viral Hepatitis. And that target is to eliminate hepatitis C by 2030. It is within our reach, but all our elimination efforts require support, plans and concrete actions at the local level to combat the increasing burden of HCV infection and the associated stigma," says Dr. Morris Sherman, Chairman of the Canadian Liver Foundation and Toronto-based hepatologist. "To be successful, we need a comprehensive screening strategy based on risk factors, plus a one-time test for all Canadians born 1945 – 19757, as well as adapted linkage to care to allow access to all available treatment options for all Canadians."

The efficacy and safety of MAVIRET was evaluated in nine Phase 2-3 clinical trials, in over 2,300 patients with genotype 1, 2, 3, 4, 5 or 6 HCV infection and with compensated liver disease (with or without cirrhosis).

"AbbVie is committed to the World Health Organization's targets and looks forward to working with governments, health care professionals and patient associations in their concerted efforts to achieve HCV elimination in Canada," explains Stéphane Lassignardie, General Manager, AbbVie Canada. "MAVIRET brings value in order to achieve elimination and all Canadians should have access to innovative and curative therapies."

https://markets.businessinsider.com/news/stocks/abbvie-reaches-an-agreement-with-the-pan-canadian-pharmaceutical-alliance-pcpa-for-its-hepatitis-c-treatment-maviret-1027973100

Targeted and immune therapies for hepatocellular carcinoma: Predictions for 2019 and beyond

World J Gastroenterol. Feb 21, 2019; 25(7): 789-807

Published online Feb 21, 2019. doi: 10.3748/wjg.v25.i7.789 

Full-text: View Online

Targeted and immune therapies for hepatocellular carcinoma: Predictions for 2019 and beyond

Masatoshi Kudo, Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka 589-8511, Japan.  Author contributions: Kudo M designed the research and wrote the paper.

Core tip: Systemic therapy for hepatocellular carcinoma (HCC) has markedly advanced since sorafenib was approved in 2007. Since then, there was no active drug for 10 years that prolong overall survival, however, in 2017 and 2018, clinical trials of 4 more molecular targeted agents including lenvatinib as first line agent, regorafenib, cabozantinib and ramucirumab as second line agent have shown their survival benefit. In addition, immune check point inhibitors, nivolumab and pembrolizumab, were approved by Food and Drug Administration. Combination cancer immunotherapy, that combines immune checkpoint inhibitors and molecular targeted agents show great promise in the treatment of HCC.

Abstract
Systemic therapy for hepatocellular carcinoma (HCC) has markedly advanced since the survival benefit of a molecular targeted agent, sorafenib, were demonstrated in the SHARP and Asia Pacific trials in 2007. Treatment options for patients with advanced HCC increased by sorafenib, and long-term survival for patients with advanced stage HCC has become possible to some extent. However, development of a more potent first-line novel molecular targeted agent replacing sorafenib and a potent second-line agent after disease progression on or intolerant to sorafenib has been warranted because sorafenib lacks tumor shrinking/necrotizing effects and induces relatively severe adverse events such as hand foot skin reaction. Many agents in the 1st line and 2nd line setting were attempted to develop between 2007 and 2016, but all of these clinical trials failed. On the other hand, clinical trials of 4 agents (regorafenib, lenvatinib, cabozantinib, and ramucirumab) succeeded in succession in 2017 and 2018, and their use in clinical practice is possible (regorafenib and lenvatinib) or underway (cabozantinib and ramucirumab). Furthermore, all of 5 clinical trials of combination therapy with transcatheter chemoembolization (TACE) plus a molecular targeted agent failed to date, however, the combination of TACE and sorafenib (TACTICS trials) was reported to be successful and presented at ASCO in 2018. Phase 3 clinical trials of immune checkpoint inhibitors and a combination therapy of immune checkpoint inhibitors and molecular targeted agents are also ongoing, which suggests treatment paradigm of HCC in all stages from early, intermediate and advanced stage, is expected to be changed drastically in the very near future.

Full-Text 

View Online

Download PDF

On This Blog
Read All Posts With The Label Liver Cancer
Review a collection of current research articles extracted from peer-reviewed journals, liver meetings/conferences, and learning activities investigating the natural history of liver cancer, approved therapies, risk factors associated with chronic viral hepatitis, cancer-prevention, including diet, nutrition and physical activity, and trends associated with the rising rate of hepatocellular carcinoma in the U.S. Begin, here.....

Is high intake of whole grains associated with lower risk of developing liver cancer?

Media
Whole grains might help ward off liver cancer
Linda Carroll

(Reuters Health) - Yet another benefit of eating a diet containing high amounts of whole grains may be a reduced risk of liver cancer, a new U.S. study suggests. 

“Consumption of whole grains and dietary fiber, especially cereal fiber, have been associated with lower risk of obesity, type 2 diabetes, and nonalcoholic fatty liver disease, which are known predisposing factors for (liver cancer),” Zhang said. “Besides improving insulin sensitivity, metabolic regulation, and decreasing systemic inflammation, intake of whole grains and dietary fiber may improve gut integrity, and alter gut microbiota composition, thereby leading to increased production of microbiota-related metabolites including short-chain fatty acids, particularly butyrate.” 

Read more: https://in.reuters.com/article/us-health-grains-liver-cancer/whole-grains-might-help-ward-off-liver-cancer-idINKCN1QA2BE

Original Investigation 

JAMA Network OpenFebruary 21, 2019
Association of Intake of Whole Grains and Dietary Fiber With Risk of Hepatocellular Carcinoma in US Adults 
Wanshui Yang, PhD1,2; Yanan Ma, PhD2,3; Yue Liu, MD2,4; et al Stephanie A. Smith-Warner, PhD5,6; Tracey G. Simon, MD7,8,9; Dawn Q. Chong, MD10; Qibin Qi, PhD11; Jeffrey A. Meyerhardt, MD, MPH12; Edward L. Giovannucci, MD, ScD2,5,6; Andrew T. Chan, MD, MPH2,8,9; Xuehong Zhang, MD, ScD2 Author Affiliations JAMA Oncol.

Published online February 21, 2019.
doi:10.1001/jamaoncol.2018.7159

Key Points
Question Is high intake of whole grains and dietary fiber associated with lower risk of developing hepatocellular carcinoma (HCC)?

Findings In this cohort study of 125 455 participants in the United States, including 141 patients with HCC, with an average follow-up of 24.2 years, increased intake of whole grains was associated with a reduced risk of HCC. A nonsignificant inverse HCC association was observed for total bran but not for germ; increased intake of cereal fiber but not fruit or vegetable fiber was associated with a nonsignificant lower risk of HCC.

Meaning Increased intake of whole grains and possibly cereal fiber and bran could be associated with reduced risk of HCC among US adults.

Abstract
Importance Increased intake of whole grain and dietary fiber has been associated with lower risk of insulin resistance, hyperinsulinemia, and inflammation, which are known predisposing factors for hepatocellular carcinoma (HCC). Therefore, we hypothesized that long-term intake of whole grains and dietary fiber may be associated with lower risk of HCC.

Objective To assess the associations of whole grain and dietary fiber intake with the risk of HCC.

Design, Setting, and Participants Cohort study of the intake of whole grains, their subcomponents (bran and germ), and dietary fiber (cereal, fruit, and vegetable) in 125 455 participants from 2 cohorts from the Nurses’ Health Study and the Health Professionals Follow-up Study.

Exposures Intake of whole grains, their subcomponents (bran and germ), and dietary fiber (cereal, fruit, and vegetable) were collected and updated almost every 4 years using validated food frequency questionnaires.

Main Outcomes and Measures Multivariable hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression model after adjusting for most known HCC risk factors.

Results After an average follow-up of 24.2 years, we identified 141 patients with HCC among 125 455 participants (77 241 women and 48 214 men (mean [SD] age, 63.4 [10.7] years). Increased whole grain intake was significantly associated with lower risk of HCC (the highest vs lowest tertile intake: HR, 0.63; 95% CI, 0.41-0.96; P = .04 for trend). A nonsignificant inverse HCC association was observed for total bran (HR, 0.70; 95% CI, 0.46-1.07; P = .11 for trend), but not for germ. Increased intake of cereal fiber (HR, 0.68; 95% CI, 0.45-1.03; P = .07 for trend), but not fruit or vegetable fiber, was associated with a nonsignificant reduced risk of HCC.

Conclusions and Relevance Increased intake of whole grains and possibly cereal fiber and bran could be associated with reduced risk of HCC among adults in the United States. Future studies that carefully consider hepatitis B and C virus infections are needed to replicate our findings, to examine these associations in other racial/ethnic or high-risk populations, and to elucidate the underlying mechanisms.
https://jamanetwork.com/journals/jamanetworkopen

Nine-year distribution pattern of hepatitis C virus (HCV) genotypes in Southern Italy

Nine-year distribution pattern of hepatitis C virus (HCV) genotypes in Southern Italy
Arnolfo Petruzziello , Rocco Sabatino, Giovanna Loquercio, Annunziata Guzzo, Lucia Di Capua, Francesco Labonia, Anna Cozzolino, Rosa Azzaro, Gerardo Botti
Published: February 20, 2019
https://doi.org/10.1371/journal.pone.0212033

Full-text available online

Download PDF 

In conclusion, the epidemiological framework of Hepatitis C infection in Southern Italy, particularly interesting for the high prevalence of this virus in the general population, seems to highlight the "returning" role of the iatrogenic transmission as risk factor for the diffusion of HCV infection. Furthermore, the small increase of genotype 3a among young people should be more investigated, with a support of a phylogenetic analysis. At support of our hypothesis, some studies report small HCV outbreaks in Europe due to breaches in standards of health and safety practices among health-care workers [56]. Indeed, an interesting case–control study highlighted some unconventional routes of diffusion of Hepatitis C infection such as digestive endoscopy, beauty treatments and professional pedicure/manicure [57]. This suggest not only a necessary evaluation of the safety practices in surgery, but the fundamental importance of not lowering the safety levels, especially among all health-care professionals.

Abstract
Introduction
It has been greatly described that different hepatitis C virus (HCV) genotypes are strictly correlated to various evolution, prognosis and response to therapy during the chronic liver disease. Aim of this study was to outline the changes in the epidemiology of Hepatitis C genotypes in Southern Italy regions from 2006 to 2014.

Material/Methods
Prevalence of HCV genotypes was analyzed in 535 HCV-RNA positive patients with chronic Hepatitis C infection, selected during the period 2012–2014, and compared with our previous data, referred to periods 2006–2008 and 2009–2011.

Results
In all the three periods analyzed, genotype 1b is predominant (51.8% in 2006–08, 48.3% in 2009–11 and 54.4% in 2012–14) while genotype 2 showed an increase in prevalence (27.9% in 2006–08, 31.7% in 2009–11 and 35.2% in 2012–14) and genotypes 3a and 1a a decrease during the same period (6.8% in 2006–08, 4.7% in 2009–11 and 3.2% in 2012–14 and 7.9% in 2006–08, 4.7% in 2009–11 and 2.6% in 2012–14, respectively). Subtype 1b seems to be equally distributed between males and females (52.7% vs 56.6%) and the prevalence in the age range 31–40 years is significantly higher in the 2012–14 period than in both previous periods (53.8% vs. 16.6% in 2009–11, p< 0.001 and 13.4% in 2006–08, p < 0.001).

Conclusions
Genotype 1b is still the most prevalent, even if shows a significantly increase in the under 40 years old population. Instead, genotype 3a seems to have a moderate increase among young people. Overall, the alarming finding is the “returning” role of the iatrogenic transmission as risk factor for the diffusion of Hepatitis C infection.