Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
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We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
IntechOpen is proud to announce that 179 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\n
Throughout the years, the list has named a total of 252 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
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As written above, this book will help its readers to expand their knowledge on this biopolymer with vast application in the industry worldwide.",isbn:"978-1-78984-072-8",printIsbn:"978-1-78984-071-1",pdfIsbn:"978-1-83968-550-7",doi:"10.5772/intechopen.78880",price:119,priceEur:129,priceUsd:155,slug:"pectins-extraction-purification-characterization-and-applications",numberOfPages:178,isOpenForSubmission:!1,hash:"ff1acef627b277c575a10b3259dd331b",bookSignature:"Martin Masuelli",publishedDate:"January 22nd 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8504.jpg",keywords:null,numberOfDownloads:6205,numberOfWosCitations:8,numberOfCrossrefCitations:7,numberOfDimensionsCitations:23,numberOfTotalCitations:38,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 12th 2018",dateEndSecondStepPublish:"November 26th 2018",dateEndThirdStepPublish:"January 25th 2019",dateEndFourthStepPublish:"April 15th 2019",dateEndFifthStepPublish:"June 14th 2019",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"99994",title:"Dr.",name:"Martin",middleName:"Alberto",surname:"Masuelli",slug:"martin-masuelli",fullName:"Martin Masuelli",profilePictureURL:"https://mts.intechopen.com/storage/users/99994/images/system/99994.jpg",biography:"Martin Masuelli is an Inv. Adj. of Instituto de Física Aplicada (INFAP) – CONICET – UNSL and Associate Professor at the National University of San Luis (UNSL), Argentina. He holds a Master’s degree and a Ph.D. and Master's thesis in Membrane Technology from the National University of San Luis. He is the Director of Physics Chemistry Service Laboratory at UNSL. He is an expert in polysaccharides and physics chemistry of macromolecules. He is an author or co-author of more than 30 peer-reviewed international publications, 8 book chapters, 75 communications in national and international congresses and editor of 8 books. He is a member of the Sociedad Argentina de Ciencia y Tecnología Ambiental, Asociación Argentina de Fisicoquímica y Química Inorgánica and Asociación Argentina de Tecnólogos Alimentarios. Since July 2013, he is the Editor in Chief and Founder of the Journal of Polymer and Biopolymers Physics Chemistry, Science and Education Publishing. He is on the Editorial Board of numerous journals.",institutionString:"National University of San Luis",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"National University of San Luis",institutionURL:null,country:{name:"Argentina"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"333",title:"Food Chemistry",slug:"food-science-food-chemistry"}],chapters:[{id:"69850",title:"Extraction and Characterization of Pectins From Peels of Criolla Oranges (Citrus sinensis): Experimental Reviews",slug:"extraction-and-characterization-of-pectins-from-peels-of-criolla-oranges-em-citrus-sinensis-em-exper",totalDownloads:771,totalCrossrefCites:1,authors:[{id:"99994",title:"Dr.",name:"Martin",surname:"Masuelli",slug:"martin-masuelli",fullName:"Martin Masuelli"}]},{id:"66671",title:"Extraction and Purification of Pectin from Agro-Industrial Wastes",slug:"extraction-and-purification-of-pectin-from-agro-industrial-wastes",totalDownloads:1560,totalCrossrefCites:0,authors:[null]},{id:"66458",title:"Pectin - Extraction, Purification, Characterization and Applications",slug:"pectin-extraction-purification-characterization-and-applications",totalDownloads:556,totalCrossrefCites:0,authors:[null]},{id:"65793",title:"Role of Pectin in Food Processing and Food Packaging",slug:"role-of-pectin-in-food-processing-and-food-packaging",totalDownloads:1878,totalCrossrefCites:5,authors:[null]},{id:"65638",title:"Pectins as Emulsifying Agent on the Preparation, Characterization, and Photocatalysis of Nano-LaCrO3",slug:"pectins-as-emulsifying-agent-on-the-preparation-characterization-and-photocatalysis-of-nano-lacro-su",totalDownloads:350,totalCrossrefCites:1,authors:[null]},{id:"66396",title:"Properties of Wine Polysaccharides",slug:"properties-of-wine-polysaccharides",totalDownloads:598,totalCrossrefCites:0,authors:[{id:"207851",title:"Dr.",name:"Zenaida",surname:"Guadalupe",slug:"zenaida-guadalupe",fullName:"Zenaida Guadalupe"},{id:"207853",title:"Dr.",name:"Belén",surname:"Ayestarán",slug:"belen-ayestaran",fullName:"Belén Ayestarán"},{id:"207854",title:"Dr.",name:"Leticia",surname:"Martínez-Lapuente",slug:"leticia-martinez-lapuente",fullName:"Leticia Martínez-Lapuente"}]},{id:"65895",title:"Flavonoids and Pectins",slug:"flavonoids-and-pectins",totalDownloads:497,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"278926",firstName:"Ivana",lastName:"Barac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/278926/images/8058_n.jpg",email:"ivana.b@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"2828",title:"Fiber Reinforced Polymers",subtitle:"The Technology Applied for Concrete Repair",isOpenForSubmission:!1,hash:"4922c593466cc822b281fe7cc7d7fef6",slug:"fiber-reinforced-polymers-the-technology-applied-for-concrete-repair",bookSignature:"Martin Alberto Masuelli",coverURL:"https://cdn.intechopen.com/books/images_new/2828.jpg",editedByType:"Edited by",editors:[{id:"99994",title:"Dr.",name:"Martin",surname:"Masuelli",slug:"martin-masuelli",fullName:"Martin Masuelli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1408",title:"Scientific, Health and Social Aspects of the Food Industry",subtitle:null,isOpenForSubmission:!1,hash:"e683dc398eabec0db3a88e891209a406",slug:"scientific-health-and-social-aspects-of-the-food-industry",bookSignature:"Benjamin Valdez",coverURL:"https://cdn.intechopen.com/books/images_new/1408.jpg",editedByType:"Edited by",editors:[{id:"65522",title:"Dr.",name:"Benjamin",surname:"Valdez",slug:"benjamin-valdez",fullName:"Benjamin Valdez"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5060",title:"Milk Proteins",subtitle:"From Structure to Biological Properties and Health Aspects",isOpenForSubmission:!1,hash:"4a7d2e5f38e97aaea90bb3fec55b3751",slug:"milk-proteins-from-structure-to-biological-properties-and-health-aspects",bookSignature:"Isabel Gigli",coverURL:"https://cdn.intechopen.com/books/images_new/5060.jpg",editedByType:"Edited by",editors:[{id:"175679",title:"Dr.",name:"Isabel",surname:"Gigli",slug:"isabel-gigli",fullName:"Isabel Gigli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6761",title:"Generation of Aromas and Flavours",subtitle:null,isOpenForSubmission:!1,hash:"32cb87c823ee53fcbff7ecb2e944d4b9",slug:"generation-of-aromas-and-flavours",bookSignature:"Alice Vilela",coverURL:"https://cdn.intechopen.com/books/images_new/6761.jpg",editedByType:"Edited by",editors:[{id:"181011",title:"Prof.",name:"Alice",surname:"Vilela",slug:"alice-vilela",fullName:"Alice Vilela"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8311",title:"Nutraceuticals",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"51994c7d3887b9ecd6926b4967a4fdfb",slug:"nutraceuticals-past-present-and-future",bookSignature:"María Chávarri Hueda",coverURL:"https://cdn.intechopen.com/books/images_new/8311.jpg",editedByType:"Edited by",editors:[{id:"150285",title:"Dr.",name:"María",surname:"Chávarri Hueda",slug:"maria-chavarri-hueda",fullName:"María Chávarri Hueda"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8625",title:"Whey",subtitle:"Biological Properties and Alternative Uses",isOpenForSubmission:!1,hash:"449a36f43c9a30ae4d43f9775599e8ac",slug:"whey-biological-properties-and-alternative-uses",bookSignature:"Isabel Gigli",coverURL:"https://cdn.intechopen.com/books/images_new/8625.jpg",editedByType:"Edited by",editors:[{id:"175679",title:"Dr.",name:"Isabel",surname:"Gigli",slug:"isabel-gigli",fullName:"Isabel Gigli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7332",title:"Some New Aspects of Colloidal Systems in Foods",subtitle:null,isOpenForSubmission:!1,hash:"0dd822267e027684bd3ff53da4f2ef41",slug:"some-new-aspects-of-colloidal-systems-in-foods",bookSignature:"Jafar M. 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\n
1. Introduction
\n
About 257 million people were infected chronically with hepatitis B (HBsAg positive), and 887,000 deaths were recorded in 2015 due to hepatitis B virus (HBV)-related liver diseases, mostly from complication with cirrhosis and hepatocellular carcinoma (HCC) indicating an urgent necessity for better ways to prevent such complication of HBV [1]. HBV infection is the tenth leading cause of death and main contributor of HCC, which is ranked the fifth leading cause of cancer in man [2, 3]. HBV can be differentiated from other hepatitis viruses by genotype and subgenotype. HBV sequence differs by >8% form other genotypes and 4–8% nucleotide differences for subgenotypes. Including newly identified genotypes I and J, there are 10 genotypes A–J. Some HBV genotypes are further classified into subgenotypes.
\n
About 30 subgenotypes are available till date. Many studies have reported that different genotypes and subgenotypes show different geographical distribution and are related to disease progression, clinical progression, response to antiviral treatment, and prognosis [4].
\n
As shown in Figure 1, genotype A is widespread in sub-Saharan Africa, Northern Europe, and Western Africa; genotypes B and C are common in Asia; genotype C is primarily observed in Southeast Asia and China; genotype D is dominant in Africa, Europe, Mediterranean countries, and India including Nepal. Genotype E is dominant in South Africa. As a minor genotype, genotype G is reported in France, Germany, and the United States; and genotype H is commonly encountered in Central and South America and genotype I in Vietnam and Laos. The newest HBV genotype, genotype J, has been identified in the Ryukyu Islands in Japan [5].
\n
Figure 1.
Global distribution of HBV genotype.
\n
However, geographical distribution is still incomplete as data was based on very small numbers of patients and from only few countries.
\n
Nepal is sandwiched between India and China, two countries with high prevalence of hepatitis B surface antigen (HBsAg) positive cases; 30% of the world’s HBsAg carriers are in China and 10% in India. Nevertheless, Nepal has a low prevalence (around 1%) of hepatitis B virus (HBV) infection in general population [6]. Hepatitis virus A and D genotypes are dominant in India, while Band C is dominant in China. The prevalence of HBV infection is low in Nepal, but still it is widely common among intravenous drug users, PLHA, and HCV-positive populations. Although our previous study revealed only A, D, and C/D recombinant genotype [8], in the locality of Nepal, all four common genotypes (A, B, C, and D) were reported in the previous study [7].
\n
Phylogenetic tree (Figure 2) was obtained from the aligned sequences combining with all human hepatitis B subgenotypes. The Nepal 10 strain was a C/D recombinant genotype, and it is differed from the genotypes A and D or other Nepalese strains. Genotype A1 in Nepal was more similar to that of Bangladesh and the Philippines, while A2 was more similar to the genotype A2 of Japan, Germany, Canada, and Russia. Genotype A1 (Nepal 31, 41, 24, 64, 50, 6, 9, 7, 47 strains) is similar to the A1 genotype of the Philippines, while strain 36, 16, and 18 are more similar to Bangladesh A1 strain. Almost all A1 strains of Nepal showed 88% similarity with Malawi A1 strain. Basically, HBV E genotype of Ghana and Sweden is nearby the genotype D of Nepal. Even some sequences from Germany and Italy are similar to the genotype D of Nepal.
\n
Figure 2.
Phylogenetic tree of Nepal study 2012.
\n
Among genotype D, Nepal 12 and 55 isolates are similar with German D genotype isolates, while Nepal 60 and 57 isolates are more similar with D isolates of Italy and France and Russian isolates of D genotype. These isolates are 93% similar with Nepal 21 f isolates from where the strain Nepal 28 was evolved. Nepal 28 isolates of D genotype is evolved to more similar isolates 22, 32, and 14. Nepal isolates 40, 38 1, 53, 11, 42, and 73 are more similar. Nepal 73 is more similar with 81, 79, and 72, while Nepal 81 and 79 is 88% similar with Nepal 72 isolates [8].
\n
\n
\n
2. Clinical importance of HBV genotypes
\n
As different regions have different serotypes and different clinical spectrum and different molecular epidemiological patterns, different HBV genotypes, but not different rashes, may influence clinical outcome, HBeAg seroconversion rate, mutational patterns in the precore and core promoter regions, and response to interferon therapy [9].
\n
Determination of genotypes: detection of the sequence differences in pre-S or S gene can be done by several methods, e.g., direct sequencing, restriction fragment length polymorphism, line probe assay, genotype-specific PCR, and mass spectrometry.
\n
\n
\n
3. Treatment: noncirrhotic patients
\n
Cirrhosis is defined as distortion of the hepatic architecture and the formation of regenerative nodules. It is generally irreversible in its late stage. It can progress even to hepatocellular carcinoma (HCC). The recommendation for the treatment initiation for cirrhotic patients are available as three different guidelines (EASL 2017, Asia pacific 2015, AASLD 2018) shown in Table 1 [4, 10, 11].
\n
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
Guideline
\n
HBeAg positive
\n
HBeAg negative
\n
ALT
\n
Family history
\n
\n
\n
\n
HBV DNA copies/ml
\n
ALT
\n
\n
HBV DNA copies/ml
\n
\n
Cirrhosis, HCC
\n
\n\n\n
\n
EASL2017
\n
>20,000
\n
Double (40)
\n
30 years
\n
>2000
\n
Double + mod. fibrosis
\n
Cirrhosis, HCC
\n
\n
\n
Asia Pacific 2015
\n
>2000
\n
Double (40)
\n
\n
>2000
\n
Double
\n
\n
\n
\n
AASLD 2018
\n
>2000
\n
Double (m/F 35/25)
\n
40 years
\n
>2000
\n
Double
\n
Cirrhosis, HCC
\n
\n\n
Table 1.
Comparison of the recommendation of different guideline treatments of noncirrhotic HBV patients.
\n
All patients with compensated cirrhosis HBeAg positive and HBV DNA level >20,000 U/ml with increased ALT twice higher than the normal limit are recommended to be treated by all three regional guidelines. However, AASLD guideline recommends different upper limit of normal (ULN) of ALT in male and female, i.e., 35 and 25, respectively, although EASL and APSL guidelines recommend 40 as ULN of ALT. HBeAg-negative patients with cirrhosis and HBV DNA > 2000 U/ml and the ALT twice higher than normal or the family history of cirrhosis and HCC are also recommended for treatment. EASL recommended to treat patients if fibrosis is present [10, 11, 12]. Different guideline recommendations are shown in Table 1.
\n
\n
\n
4. Treatment: cirrhotic patients
\n
Patients with compensated cirrhosis and HBV DNA level >2000 U/ml are treated per recommendations for immune-active chronic hepatitis B (CHB). All three guidelines recommend to treat patients with decompensated cirrhosis and detectable viral load. In cases of compensated cirrhosis, there is discrepancy among the guidelines. In cases of HBV DNA <2000 copy/ml, AASLD and EASL both recommend to treat irrespective to ALT, whereas APSL recommended to such cases to treat only when ALT is above normal [10, 11, 12]. Treatment guideline is shown in Table 2.
\n
Table 2.
Comparison of the recommendation of treatment of different guideline of cirrhotic HBV patients.
\n
\n
\n
5. Clinical characteristics of different genotype are important
\n
Genotype B is a common genotype in Asia. Some characteristics of genotype B are as follows [13, 14, 15, 16]:
Is commonly seen in young age less than 35 years as it is generally transmitted by perinatal or vertical route.
The conversion from acute to chronic phase is less in this genotype.
HBeAg seroconversion occurs earlier than genotype C.
HBsAg seroclearance is faster than genotype C.
Less patients develop cirrhosis.
HCC development is less.
Hepatic decompensation is less.
HBV DNA is high in number.
Less chance of getting fulminant hepatitis.
\n\n
Genotype C is also a common genotype in Southeast Asia and China. Characteristics of genotype care are as follows [13, 14, 15, 16]:
Is commonly seen in young age less than 35 years generally transmitted by perinatal or vertical route.
The conversion from acute to chronic phase is higher in this genotype.
HBeAg seroconversion is less percentage and takes time than genotype B.
HBsAg seroclearance is less than genotype B.
High chance of getting cirrhosis.
HCC development is more likely.
Hepatic decompensation is higher in this genotype.
HBV DNA is less in copy number.
Less chance of getting fulminant hepatitis.
\n\n
Genotype A is distributed worldwide. Characteristics of genotype A are as follows [13, 14, 15, 16]:
It is generally transmitted by horizontal route.
The conversion from acute to chronic phase is frequent in this genotype.
HBeAg seroconversion is earlier than genotype D.
HBsAg seroclearance is also more frequent than genotype D.
Less patients get cirrhosis.
HCC development is less.
Hepatic decompensation is higher.
HBV DNA is high in copy number.
Less chance of getting fulminant hepatitis.
\n\n
Genotype D also has worldwide distribution. Characteristics of genotype D are as follows [13, 14, 15, 16].
Transmitted by horizontal route.
The conversion from acute to chronic phase is less frequent in this genotype.
HBeAg seroconversion takes longer time than genotype A.
HBsAg seroclearance is less than genotype A.
HCC development is most frequent.
Hepatic decompensation is higher.
HBV DNA is low in copy number.
Higher chance of getting fulminant hepatitis.
\n\n
Different HBV genotype clinical characteristics are compared in Table 3.
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
Genotype clinical characteristics
\n
B
\n
C
\n
A
\n
D
\n
E–J
\n
\n\n\n
\n
Age
\n
Common <35
\n
>35
\n
—
\n
—
\n
\n
\n
\n
Modes of transmission
\n
Perinatal/vertical
\n
Perinatal/vertical
\n
Horizontal
\n
Horizontal
\n
Horizontal
\n
\n
\n
Chronicity
\n
Lower
\n
Higher
\n
Higher
\n
Lower
\n
—
\n
\n
\n
HBeAg seroconversion
\n
Earlier
\n
Later
\n
Earlier
\n
Later
\n
Earlier
\n
\n
\n
HBeAg seroclearance
\n
\n
\n
Earlier
\n
Later
\n
\n
\n
\n
HBsAg seroclearance
\n
More
\n
Less
\n
More
\n
Less
\n
_
\n
\n
\n
Cirrhosis
\n
Less active
\n
Active
\n
\n
\n
\n
\n
\n
HCC
\n
Better
\n
Worse
\n
Better
\n
Worse
\n
Worse in genotype F
\n
\n
\n
HBV DNA level
\n
Higher
\n
Lower
\n
Higher
\n
Lower
\n
_
\n
\n
\n
Hepatic decompensation
\n
Lower
\n
Higher
\n
Higher
\n
Higher
\n
_
\n
\n
\n
Fulminant hepatitis
\n
Less
\n
Less
\n
Less
\n
Higher
\n
\n
\n\n
Table 3.
Clinical characteristics of different genotypes of HBV.
\n
\n
\n
6. Antiviral treatment
\n
The goal of therapy
Decrease ALT—decrease necrotic inflammation in the liver
Decrease viral load to the undetectable level
HBeAg seroconversion to generate anti-HBeAg—to minimize the replication of virus
To reduce HBsAg and seroconversion and anti-HBS
Prevent development of new esophageal varices
\n\n
Long-term goal is to reduce the risk of HCC and chronic liver diseases.
\n
Peg-IFN alfa-2a or alfa-2b is recommended before starting peg-IFN therapy to HBeAg-positive patients; good responders should be identified; i.e., low viral load, HBV genotypes A and B, high serum ALT levels (above 2–5 times ULN) and high activity scores on liver biopsy are the predictors for better responding patients.
\n
As the baseline predictor of response for the therapy to HBeAg-negative patient, HBV genotype, HBV DNA, ALT, HBsAg levels, and age are the crucial factors [17].
\n
When to terminate Peg-IFN therapy: if low probability of response for HBeAg positive.
\n
Or
\n
No decline of HBsAg level for HBV genotype A and D at week 12 of treatment.
\n
\n
6.1 HBeAg loss
\n
HBeAg loss with HBV DNA <2000 IU/ml for 6 months after treatment. Genotype D HBeAg-negative patient decreasing <2log decline in HBV DNA at week 12 of peg-IFN therapy [18].
\n
Either entecavir or tenefovir is recommended for HIV
\n
\n
\n
6.2 No response
\n
HBeAg-positive patient with HBsAg level >20,000 IU/ml predicted no response after treatment. HIV positive, TNF + entecavir (lamivudine) + EFV is recommended. Other drugs are recommended as the second-line therapy if the first-line drug treatment is failed (if HBV DNA > log10 IU/ml in 3-month period [19].
\n
\n
\n
6.3 Response to lamivudine
\n
Genotype B has sustain responsiveness to lamivudine followed by genotype C. Genotype A is more resistant than genotype D so that virological responses to the drug are better in genotype D than genotype A. Pediatric patients have good tolerance to lamivudine. The younger the age at diagnosis, the longer consolidation treatment period [20].
\n
\n
\n
6.4 Response to adefovirdipivoxil
\n
Patients infected with genotypes A and D equally respond to 48-week treatment of adefovirdipivoxil, but there could be the adefovir resistance in patients having genotype D.
\n
\n
\n
6.5 Response to entecavir or telbivudine
\n
The relationship of HBV genotypes on drug resistance to entecavir was evaluated in lamivudine-refractory patients. Two-year therapy of telbivudine showed that HBeAg seroconversion, ALT normalization, and HBV negativity were comparable among different genotypes. Entecavir treatment has a chance of HBsAg seroloss in genotypes A and D, and the efficacy is better in Caucasian than in Asian population [20].
\n
\n
\n
6.6 Tenefovir (TDF)
\n
HBsAg loss in genotype A patient followed by genotype D (20 and 10%, respectively) was reported after completion of 144 weeks of treatment of TDF. The therapeutic effect was less in genotypes B and C [20].
\n
\n
\n
6.7 Management of incomplete responder
\n
Incomplete responder should be checked for the drug adherence.
\n
Patients who have previous exposure to lamivudine should be considered for entecavir resistance.
\n
EASL recommend to switch to NA or combination therapy if detectable HBV DNA in 12 weeks of therapy. Combination of TDF + ETV has resulted in undetectable DNA even after 4 years, which is better than TDF alone [21]. Most of the study and the guideline do not recommend peg-IFN + nucleot(s)ide therapy, but recommend to use peg-IFN after NA therapy. Antiviral drugs and their continuation recommended by different guideline are illustrated in Table 4.
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
Nucleotide analogue
\n
Dose
\n
Adverse
\n
EASL
\n
ASL
\n
APSL
\n
\n\n\n
\n
Lamivudine
\n
100 mg/day
\n
\n
Undetectable DNA For 3 years
\n
1–3 years after HBeAg-negative patient
\n
Undetectable DNA For 2 years
\n
\n
\n
Adefovir
\n
10 mg/day
\n
\n
\n
\n
Entecavir
\n
0.5 mg/day
\n
\n
\n
\n
Telbivudine
\n
600 mg/day
\n
\n
\n
\n
Tenofovir
\n
300 mg/day
\n
Bone and renal impairment
\n
\n
\n
Emcitrabine
\n
200 mg/day
\n
\n
\n
\n
Tenofovir alafenamide
\n
25 mg/day
\n
\n
\n\n
Table 4.
Antiviral treatment doses and period of recommendation by different guidelines.
\n
\n
\n
\n
7. Conclusion
\n
HBV genotyping is important for the proper management of chronic HBV patients. Clinical characteristics may be helpful to estimate the genotype and initiate antiviral therapy.
\n
\n\n',keywords:"hepatitis B, genotyping, distribution, clinical implication, management",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/65469.pdf",chapterXML:"https://mts.intechopen.com/source/xml/65469.xml",downloadPdfUrl:"/chapter/pdf-download/65469",previewPdfUrl:"/chapter/pdf-preview/65469",totalDownloads:508,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,dateSubmitted:"September 13th 2018",dateReviewed:"November 12th 2018",datePrePublished:"February 4th 2019",datePublished:"April 8th 2020",dateFinished:null,readingETA:"0",abstract:"Hepatitis B is one of the killer diseases and distributed globally. Nepal sandwiched between India and China. China is the country with high prevalence of hepatitis B surface antigen (HBsAg) account 30% of the world’s HBsAg carriers, and India which has intermediate HBsAg prevalence accounts 10% of the world’s carriers. Nepal has a low prevalence (around 1%) of hepatitis B virus (HBV) infection in general population. A and D genotypes are more prevalent in India, while band C is in China. The survey done in 2012 elaborated the common genes that are A and D and recombinant C/D in Nepal, but the clinical consequences are unclear. The prevalence of hepatitis B is low in Nepal, but it is widely common in intravenous drug users, PLHA, and HCV positive. The implication of HBV genotyping has clinical implication for the treatment. Basically, response of peginterféron, and antiviral drugs (adefovir, lamivudine, telbivudine) in hepatitis B.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/65469",risUrl:"/chapter/ris/65469",book:{slug:"hepatitis-b-and-c"},signatures:"Damodar Paudel and Sushma Suvedi",authors:[{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",fullName:"Damodar Paudel",slug:"damodar-paudel",email:"damodarpaudel@gmail.com",position:null,institution:null},{id:"284282",title:"MSc.",name:"Sushma",middleName:null,surname:"Suvedi",fullName:"Sushma Suvedi",slug:"sushma-suvedi",email:"dr@kumarpokhrel.np.com",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Clinical importance of HBV genotypes",level:"1"},{id:"sec_3",title:"3. Treatment: noncirrhotic patients",level:"1"},{id:"sec_4",title:"4. Treatment: cirrhotic patients",level:"1"},{id:"sec_5",title:"5. Clinical characteristics of different genotype are important",level:"1"},{id:"sec_6",title:"6. Antiviral treatment",level:"1"},{id:"sec_6_2",title:"6.1 HBeAg loss",level:"2"},{id:"sec_7_2",title:"6.2 No response",level:"2"},{id:"sec_8_2",title:"6.3 Response to lamivudine",level:"2"},{id:"sec_9_2",title:"6.4 Response to adefovirdipivoxil",level:"2"},{id:"sec_10_2",title:"6.5 Response to entecavir or telbivudine",level:"2"},{id:"sec_11_2",title:"6.6 Tenefovir (TDF)",level:"2"},{id:"sec_12_2",title:"6.7 Management of incomplete responder",level:"2"},{id:"sec_14",title:"7. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'\nWHO, WHO Key facts; 2018\n'},{id:"B2",body:'\nZamor PJ, deLemos AS, Russo MW. Viral hepatitis and hepatocellular carcinoma: Etiology and management. Journal of Gastrointestinal Oncology. 2017;8(2):229-242\n'},{id:"B3",body:'\nRaihan R et al. Hepatocellular carcinoma in Malaysia and its changing trend. Euroasian Journal of Hepato-Gastroenterology. 2018;8(1):54-56\n'},{id:"B4",body:'\nLin CL, Kao JH. Hepatitis B virus genotypes and variants. Cold Spring Harbor Perspectives in Medicine. 2015;5(5):a021436\n'},{id:"B5",body:'\nSunbul M. Hepatitis B virus genotypes: Global distribution and clinical importance. World Journal of Gastroenterology. 2014;20(18):5427-5434\n'},{id:"B6",body:'\nShrestha SM, Shrestha S. Chronic hepatitis B in Nepal: An Asian country with low prevalence of HBV infection. Tropical Gastroenterology. 2012;33(2):95-101\n'},{id:"B7",body:'\nHuy TT et al. High prevalence of hepatitis B virus pre-s mutant in countries where it is endemic and its relationship with genotype and chronicity. Journal of Clinical Microbiology. 2003;41(12):5449-5455\n'},{id:"B8",body:'\nPaudel D et al. Diversity of hepatitis B genotypes in Nepal and updated phylogenetic tree: A pilot survey in 2012. JNMA; Journal of the Nepal Medical Association. 2014;52(196):982-991\n'},{id:"B9",body:'\nFurusyo N et al. Relationship of genotype rather than race to hepatitis B virus pathogenicity: A study of Japanese and Solomon islanders. The American Journal of Tropical Medicine and Hygiene. 2004;70(5):571-575\n'},{id:"B10",body:'\nAssociation, E. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. Journal of Hepatology. 2017;67(2):370-398\n'},{id:"B11",body:'\nTerrault NA et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-1599\n'},{id:"B12",body:'\nSarin SK et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: A 2015 update. Hepatology International. 2016;10(1):1-98\n'},{id:"B13",body:'\nKramvis A. The clinical implications of hepatitis B virus genotypes and HBeAg in pediatrics. Reviews in Medical Virology. 2016;26(4):285-303\n'},{id:"B14",body:'\nLiaw YF. HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B. Hepatology International. 2009;3(3):425-433\n'},{id:"B15",body:'\nKmet Lunacek N, Poljak M, Maticic M. Distribution of hepatitis B virus genotypes in Europe and clinical implications: A review. Acta Dermatovenerologica Alpina Pannonica et Adriatica. 2018;27(3):141-146\n'},{id:"B16",body:'\nLin CL, Kao JH. The clinical implications of hepatitis B virus genotype: Recent advances. Journal of Gastroenterology and Hepatology. 2011;26(Suppl 1):123-130\n'},{id:"B17",body:'\nLiu LZ et al. Improvements in the management of chronic hepatitis B virus infection. Expert Review of Gastroenterology & Hepatology. 2018;12(11):1-14\n'},{id:"B18",body:'\nRijckborst V et al. Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B using HBsAg and HBV DNA levels. Hepatology. 2010;52(2):454-461\n'},{id:"B19",body:'\nWHO. Guidelines for the Prevention Care and Treatment of Persons with Chronic Hepatitis B Infection; 2015. Available in https://www.who.int/hiv/pub/hepatitis/hepatitis-b-guidelines/en/\n\n'},{id:"B20",body:'\nMan Cho S, Choe BH. Treatment strategies according to genotype for chronic hepatitis B in children. Annals of Translational Medicine. 2016;4(18):336\n'},{id:"B21",body:'\nChan HLY et al. Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive patients with normal levels of alanine aminotransferase and high levels of hepatitis B virus DNA. Gastroenterology. 2014;146(5):1240-1248\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Damodar Paudel",address:"damodarpaudel@gmail.com",affiliation:'
Department of Medicine, Internal Medicine Unit, National Academy of Health Science, Nepal Police Hospital, Nepal
Department of Microbiology, Nepalgunj Medical College, Nepal
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1. Introduction
Radiofrequency-assisted liposuction (RFAL) has been performed since 2008 [1].
Early devices were used to heat tissue prior to lipoaspiration, and the early cannulas performed both tissue heating and liposuction. Users gradually changed the order of the steps in the procedure, as it became clear that removing some of the adipose insulation prior to heating enhanced soft tissue contraction. Original versions of cannulas contained heating elements in a bipolar configuration that are allowed for treatment at multiple depths. A new, smaller version of radiofrequency was introduced in 2014. This device was monopolar and utilized a 10 or 15 cm wand-like cannula that was placed under the skin. Best suited for smaller areas, the device was capable of targeted nerve ablation as well as soft tissue coagulation. Both devices are considered “bulk heaters” as the subcutaneous cannula tip heats the soft tissue in gradients, hotter near the cannula tip and cooler away from the device tip [2]. The mechanism of action was the coagulation of the lax stromal collagen fibers, which resulted in overlying skin contraction as an indirect effect. In 2016, a helium plasma-driven radiofrequency device created for laparoscopic cutting and coagulation was used externally for skin resurfacing. An esthetic surgeon then placed the device under the skin, causing soft tissue coagulation and subsequent skin tightening in this region. Instead of targeting a large area of soft tissue, this device emits very small multidirectional pulses of RF energy that are impedance driven. The energy is delivered in a fractional manner. All subdermal RF devices cause mild soft tissue contraction initially, followed by gradual ingrowth of a new stromal collagen scaffold over time in the treated region. Safety is optimized with the helium plasma device, as the external skin temperature rarely reaches 39 degrees C. The treatment target is the fibroseptal stroma, not the overlying dermis.
Nanofat has been used for many purposes including enrichment of traditional fat grafts, in combination with myostimulation, and intradermal injection in patients who desire skin resurfacing without epidermal ablation. While the FDA considers nanofat or SVF produced with collagenase a drug, mechanical instead of chemical tissue manipulation does not fall into the “drug” or maximally manipulated category [3]. Mechanical devices must obtain a 510(k) clearance and are single use only. However, the individual devices cost quite a bit less per use than a tissue processing laboratory within the operating room would. Examples of nanofat processing units include the Nanocube (Lipocube, London) and Tulip devices (Tulip Medical, San Diego, CA). Nanofat is created from fatty lipoaspirate, and the cells that remain are fragile, prone to death when desiccated or roughly handled. The solution can be combined with particulate fat in order to enhance the quality of fat grafts. It can be injected intramuscularly following myostimulation. Nanofat can be injected into regions with radiation damage in order to lessen the deterioration of the skin and soft tissue. Also injected directly into the skin, nanofat can improve the quality of aging skin by stimulating dermal fibroblasts. It is not recommended to apply nanofat topically as very few cells will survive in this environment.
While either procedure alone has benefit, the combination of helium plasma-driven RF to treat soft tissue for localized volume reduction plus nanofat-enriched grafts for focal volumetric enhancement corrects most deformities in the subdermal region. The addition of intradermal nanofat injection helps to enhance the appearance of aging skin without creating any superficial injury.
2. Background
Initially, the purpose of adding radiofrequency energy to traditional liposuction was to prevent the inevitable postoperative skin laxity in cases of moderate to large volume reduction. The Vectra measurement of skin surface area contraction [4] showed 26% surface area reduction at 6 weeks posttreatment and 36% at 1 year. Corresponding measurements of skin contraction obtained with mechanical stimulation after SAL showed contraction of 10% at 6 weeks and only 8% at 1 year. While laser-assisted liposuction did tighten the skin surface area more effectively than SAL at 13–17% measured skin tightening [5, 6], none of the other energy assists generated significant measured associated skin tightening. As patient expectations continue to grow, these also drive both technical and clinical development. Demands for a smooth, taut contour following treatment have encouraged surgeons to adopt techniques that will result in better outcomes than were common a decade ago. Changes that have been noted during this development phase include lower power settings, fewer passes—but passes at multiple depths—and more contouring in regions that need more attention. As with other energy-based devices, the RFAL procedure has evolved from a basic company guideline of three to five passes per region to more of a sculpting approach. Because most surgeons also perform excisional techniques, the ability to visualize which region needs 33% skin contraction or less is a good guideline for treatment. If there is a localized region with extreme pendulosity, skin excision might be recommended. In order to transition from simple skin tightening to directional shaping, both vision and experience help to guide the practitioner in the therapeutic application of RF energy.
The popularity of using nanofat has grown rapidly over the past several years. With FDA-cleared devices for mechanical production of progenitor cells, the process has become affordable for most physicians and patients. Nanocube TM has been cleared for mechanical adipose tissue processing. This device produces millifat, microfat, and nanofat. The harvested macrofat is serially transferred through a cutting screen. The cube is rotated between ports 1 and 2 to produce millifat. Microfat is produced following several passes through the screen between ports 2 and 3. Nanofat production requires passage of the adipose tissue through ports 3 and 4. There is an average of between 50,000 and 70,000 MSCs in each cc of this particular nanofat, though no adipocytes remain.
3. Materials and methods
The Apyx Renuvion device has recently obtained a 510(k) clearance for a new handpiece that is significantly smaller in diameter than the original footprint (Figure 1). A bullet nose contour at the tip aids in a precise placement, and the two-side firing ports achieve a 360-degree directional energy placement. The handpieces are slightly flexible for ease of use in curved regions. As the energy is emitted just proximal to the handpiece tip, end hits are prevented. At a 3 mm diameter, instead of the previous 5 mm, the device can now be introduced through a small port created with a 16-gauge needle. Erythema and mechanical abrasion at the access port are reduced due to a graduated indicator system near the handpiece tip, warning the user that the device tip is near. More access points can now be placed without concern for pronged visible erythema. Also, more regions can be easily treated with the redesigned handpiece. The lower face, arms including the elbows, knees, and ankles are excellent targets for HPDRF treatment. There is no requirement for liposuction; soft tissue contraction in such areas as the neck, breast, arms, knees, and axilla can be performed following tumescent infusion.
Figure 1.
New handpiece is approved by the FDA for soft tissue coagulation: side port configuration of tip—testing demonstrated that the first locations of highest external tissue temperatures were treatment transition areas (i.e., transitions from treated tissue to untreated areas) when energy was delivered distally from tip of the device. Based on the results of this testing, the APR handpiece was designed to have plasma discharged radially from the side ports of the tip as opposed to distally; indicator lines on tip of device—the second location where the external tissue temperatures were the highest was areas within approximately 40 mm from the incision site providing access to the subdermal plane. There is a risk of this area being overtreated since the treatment strokes of the device converge at the incision site. In order to prevent overtreatment of this area, indicator lines were included on the shaft of the Renuvion APR device to provide awareness to the user that the tip is nearing the incision site. The user is also instructed to stop activation of the device when the indicator line becomes visible at the incision site; and epidermal marking templates—provided in device packaging as a mean for the user to mark 40 mm from the incision site on the patient. This will prevent possible overtreatment where treatment passes converge at the incision site.
Optimal settings range from 60 to 80% power and 1.5 to 3 L/min helium flow rate. While a minimum of three passes per region is recommended for the average treatment region, thin areas such as the nonfatty neck, upper arms, decollette, and knees should be treated with no more than two passes per region in order to avoid postoperative fibrosis.
While general anesthesia reduces the need for large volumes of tumescent fluid infusion, small areas can be treated under local anesthesia. Patients may find that the inhalation of nitrous oxide can reduce perceived discomfort during tumescent infusion. The limitations of local/ tumescent anesthesia include possible lidocaine toxicity and increased sensitivity to discomfort when the second region is being treated.
Following sterile prep and draping, access ports that were pre-marked in the upright position are injected with local anesthetic. A small 20-gauge infusion cannula is used to infuse standard Klein’s solution into the treatment region at multiple levels. The recommended fluid ratio is 1:1, meaning that approximately 1 cc of lipoaspirate is planned for each cc of tumescent infused. Because helium plasma RF is impedance driven, too little fluid creates a high-resistance field, while too much fluid does not allow the tissues to heat optimally. Liposuction is performed prior to RF heating in cases where it is indicated. If no liposuction is performed, pre-tunneling with a 3 mm cannula is recommended in order to establish the proper planes prior to application of RF energy. It is strongly recommended that at least three communicating access ports be created, so that helium gas is allowed to escape. Postoperative crepitus can be reduced by aspirating from each access port following RF heating. Three to five passes are recommended in each treatment region if the area is moderately lipodystrophic. In patients with very thick fat layers, up to eight passes can be performed at multiple varying depths. It is possible to create a seroma if depths are not varied. If energy is applied only superficially, the lax adipose layer will not reattach to the underlying fascia, and an optimal correction will not be achieved. It is important not to scrape the underside of the skin in an effort to achieve skin contraction. This can cause linear depressions that are very difficult to correct. Recommendations to stay at least 5 mm under the base of the dermis will improve the possibility of a smooth skin surface postoperatively. When performing a secondary case, marking of any preoperative depressions in the standing position is ideal. Following any revisional liposuction of the protruding areas, any treatment with RF heating should remain at the Scarpa’s fascia or below in order to avoid creating more superficial fibrosis. After the use of RF heat, fat grafting should be performed with slight overcorrection in the depressed regions. Specific regional contouring descriptions are given below.
Nanofat was processed following the harvest of fat using traditional liposuction techniques with negative pressure of only 10 mm Hg. In order to reduce extravasated free fatty acid contents, filtration rather than centrifugation was used for initial fat processing. Macrofat (particles measuring >3 mm) was then processed in the Nanocube in order to produce millifat, microfat, and nanofat (Figure 2). Macrofat was injected in regions needing more structure, such as the bra roll depression, chin, and the prejowl sulcus. Millifat was injected in the infraorbital hollows in order to avoid lumpiness. Microfat can be injected with a 25-gauge needle and is used for supporting the deep dermis or for mixing with biostimulatory agents such as hydroxyapatite.
Figure 2.
(a) Macrofat: Best for structural repair and contains stroma and fat >2 mm particle size. (b) Millifat: Obtained with first pass through Nanocube. 2 mm particle size. (c) Microfat: Obtained with second pass through Nanocube. Able to inject into the dermis. (d) Nanofat: This solution has progenitor cells but no adipose and can inject intradermally with a 30-gauge needle.
Nanofat can be combined with all types of particulate fat and also can be injected by itself with a 30-gauge needle. The stimulation of dermal fibroblasts is the primary purpose with superficial nanofat injection.
4. Results
The combination of using helium-driven plasma in the subcutaneous space for contouring has been enhanced with the development of a new handpiece. Ease of use, especially in areas with thin skin, striae, and small surface areas, has made the operative procedure more straightforward. Due to the slightly flexible nature of the cannula, directional shaping in regions such as the jawline, neck, lateral breast and axilla, upper arm, and knees has become possible.
The use of Renuvion is no longer limited to skin surface area contraction, though this use is off-label. The ability to shape soft tissue is difficult, even with traditional surgical techniques. If the fibroseptal network can be manipulated in such a way that a new form with defined shape is possible without skin excision, the stage is set for optimized outcomes.
The addition of fat grafting in certain regions also enhances results. For example, many women have skin pendulosity as well as localized lipodystrophy in the bra roll region. Frequently, there is an associated depression, due to the tethering of the dermis to the midlevel Scarpa’s fascia. By releasing the tether and creating a superficial subdermal tunnel that is then filled with transferred fat, the deformity can be fully corrected without surgical skin excision (Figure 3).
Figure 3.
(a) 38-year-old before surgery. (b) 3 months post-Renuvion treatment of bra roll and flanks.
Other areas that benefit from this combination are the lower face and jawline. A common problem with aging is bony resorption of the maxilla and mandible. This process causes visible jowling due to skin and stromal laxity as well as hollowing of the prejowl sulcus and gonial notch. The process of soft tissue aging is characterized by gradual loss of the scaffold, or fibroseptal network, in the fatty layer (Figure 4). The use of radiofrequency energy in the multiple levels of adipose stroma will regenerate this framework over the period of 1 year.
Figure 4.
(a) SEM of aging adipose tissue. Note the lack of collagen support network. (b) 3 months post-RF treatment of the adipose layer; the collagen binding network is restored.
Hollow regions tend to be focal instead of diffuse. Known regions of accelerated aging include the prejowl sulcus, gonial notch, oral commissures, distal nasolabial folds, and medial infraorbital regions. Temporal hollowing, also known as the “old horse” phenomenon, also creates an aged appearance even in younger patients. By restoring the smooth and full contour of the face and jawline, apparent age reduction can be accomplished with a process known as microlifting [7].
A third novel use of combined RF energy plus nanofat-enriched grafting is in male body contouring. Formerly reserved for liposuction plus etching [8], the addition of myostimulation plus fat transfer to the male contouring armamentarium has broadened the scope of male body contouring. By combining electromagnetic energy [9] with stem cell tissue enrichment, muscle volume can be enhanced in ways not achievable in the gym. Figure 5 shows results of a man treated 2 years ago with Renuvion and his 2-year result.
Figure 5.
(a) 38-year-old before surgery. (b) Early result 6 weeks post-op. (c) Result at 2 years post-op.
Myostimulation with radiofrequency energy combined with nanofat injection can also enhance the small muscles of the face. As we age, the combination of bone atrophy, muscle thinning and atrophy, and soft tissue volume loss [10] can lead to the development of a negative facial expression [11]. The combination of RF myostimulation at subcoagulative levels combined with intramuscular injection of progenitor cells can result in shortening of the long, attenuated upper lip by 3 mm or more without a “bullhorn” skin excision (Figure 6). The addition of erbium laser resurfacing can definitively optimize the long-term outcome in patients ≥60 years of age. In patients with mild to moderate neck laxity, the use of plasma-driven radiofrequency in the neck and submental region can be an alternative to a surgical neck lift, even with patients over 60 (Figure 7).
Figure 6.
(Above) 73-year-old woman before surgery. (Below) 6 months post-laser resurfacing, fat grafting, and RF myostimulation to the upper lip.
Figure 7.
(Above) 61-year-old before treatment. (Below) Same patient 3 months post-Renuvion-assisted neck lift. No skin was excised.
5. Discussion
Regenerative medicine is rapidly gaining a large market share of the esthetic market [12]. The procedures that utilize the patient’s own tissues make sense to most people, and the ability to generate a prolonged improvement without significant temporary deformity or downtime resonates with potential customers. As the popularity of minimally invasive or noninvasive procedures soars [13], esthetic practices are enthusiastically seeking solutions that are safe and effective. By understanding the causes of apparent aging as well as minimally or noninvasive options for skin and soft tissue restoration, esthetic practitioners are able to address these concerns in ways that patients identify with. The optimal combination of electromagnetic and RF energy plus nanofat-enriched fat transfer can optimize long-term outcomes of rejuvenative procedures.
The use of subdermal RF energy can restore the framework or scaffold that supports the overlying skin. With commonly used liposuction techniques, especially superficial liposuction, the integrity of that framework can be compromised, and a cannula defect or localized depression can result. Even with subdermal radiofrequency devices, if the cannula is used to scrape the underside of the dermis, interrupting the subdermal fibroseptal network, the adjacent soft tissue contraction will paradoxically amplify the defect as the soft tissue near the injury contracts. A uniform network of contractile hypodermis is needed for a smooth postoperative surface.
The combination of subcutaneous tissue contraction and stabilization and regeneration of the overlying skin will provide the optimal outcome in most facial and body contouring efforts. If underlying muscle laxity is a contributing factor to the deformity, electromagnetic stimulation of the affected muscle is recommended. Restoration of the stromal/skin complex’s attachment to the underlying fascia can be achieved by applying RF energy at the junction of these two layers. Figure 8 shows a patient treated with plasma-driven RF in the abdominal region. Treatment of the lower diastasis can improve the midline gap up to 5 cm. This is a minimally invasive alternative to an abdominoplasty in suitable patients.
Figure 8.
(a) 35-year-old mom with diastasis recti. She declined abdominoplasty. (b) 3 months post-Renuvion-assisted liposuction. Significant improvement of her rectus diastasis was obtained.
Care must be taken to not overtreat here in the abdominal region, as a seroma can develop. Overtreatment can also cause fibrosis which can compromise the gliding of the skin surface.
The use of fat grafting in facial, neck, and body contouring is well established [14]. Coleman is considered the father of fat grafting, popularizing the technique in the early 1990s [15]. He notes that the range of “take” of the fat grafts can range from 10 to 90% [16], depending on the technique and postoperative compliance of the recipient. The enhancement of graft take can be achieved by avoiding large-volume injections, by stratifying the fat injections at multiple levels, and by pulsing small volumes at a time so that a “string of pearls” effect is achieved. If there is a significant component of liquefied fat in the injectable fat, this will reduce graft take. The traumatized fat or desiccated fat is less viable than the fat harvested at low pressure and kept in a closed container. A current common practice is the topical application of nanofat following nonthermal microneedling, RF microneedling, or fractional laser resurfacing. There is little uptake of progenitor cells with these methods, as the aDSCs are prone to desiccation and traumatic death. A recent publication [17] advocates the use of a biocreme to enhance cell viability. Future development of the novel use of nanofat for skin enhancement will no doubt optimize the technique so that consistent outcomes can be achieved.
An interesting use of nanofat is the injection of the substance intradermally. Figure 9 shows a patient treated in the infraorbital region using this method. Since the particulate size is very small, the solution can be injected with a 30-gauge needle. The effect of intradermal nanofat improves with time, so that outcomes at 1-year post-injection are much more remarkable than early changes [18]. Regions that can be significantly improved with intradermal nanofat include the upper lip and the infraorbital region. By adding nanofat to the traditional macrofat grafts, the outcomes, especially in facial regions, are enhanced. By milling macrofat into millifat, lumpiness in regions with skin can be reduced.
Figure 9.
(a) 58-year-old before treatment. (b) 3 months following laser resurfacing, fat grafting, and intradermal injection of nanofat.
6. Conclusion
Regenerative medicine has become a popular antiaging resource that patients are actively seeking. Helium plasma-driven fractional radiofrequency energy can restore the lost fibroseptal scaffold in many regions of the face, neck, and body. While FSN contraction can reconstruct a framework of cohesive fatty stroma upon which the skin can rest, aged skin will not be appreciably improved as it is not directly addressed. Instead of using damaging resurfacing techniques such as laser ablation or thermal microneedling, the regenerative restoration of dermal fibroblasts as well as the generation of a new blood supply helps to thicken the dermis as well as improve the tone, texture, and wrinkles. Little downtime is seen with the use of nanofat injections, and there is very little temporary deformity. The addition of nanofat to traditional fat for grafting enhances both structural and vascular response. As with most esthetic procedures, combination therapy is superior to the use of a single modality when an optimal outcome is desired. The use of helium plasma-driven radiofrequency energy for soft tissue contouring and skin tightening is an excellent approach for the restoration of the supportive fibroseptal network. Nanofat plus more traditional approaches can optimize the correction of volume deficiencies as well as the correction of thin, structurally deficient skin. As research and development of both of these techniques evolves, biological restoration of the aging soft tissues is predicted to become more popular than other surgical or injectable approaches.
\n',keywords:"radiofrequency, plasma, nanofat, minimally invasive, neck, facial contouring",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/71649.pdf",chapterXML:"https://mts.intechopen.com/source/xml/71649.xml",downloadPdfUrl:"/chapter/pdf-download/71649",previewPdfUrl:"/chapter/pdf-preview/71649",totalDownloads:142,totalViews:0,totalCrossrefCites:0,dateSubmitted:"November 22nd 2019",dateReviewed:"February 4th 2020",datePrePublished:"April 3rd 2020",datePublished:"February 10th 2021",dateFinished:"April 3rd 2020",readingETA:"0",abstract:"Many energy sources have been utilized to optimize tissue behavior following traditional liposuction. Peer-reviewed data to date show that radiofrequency has been shown to cause more skin and soft tissue contraction than other energy sources. While external RF can improve skin quality and create new collagen formation, tissue contouring has not been successful with topical energy application. However, the use of subdermal RF has been utilized to generate directional shaping and contouring in addition to skin tightening. An understanding of the way soft tissue contracts over time as collagen fibers develop is based on both the science of soft tissue energy response and experience in treating large numbers of patients. The Apyx Renuvion device is 510(k) cleared for soft tissue coagulation. In most cases of facial and body contouring, the ability to add volume in specific regions is as important as the skill to remove it. Since some liposuction is commonly performed as a part of the Renuvion contouring process, frequently this lipoaspirate is used to augment focal depressions or areas of soft tissue atrophy. The recent development of mechanical processing of macrofat into smaller particles, as well as nanofat, has widened the scope of the use of adipose-derived tissue.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/71649",risUrl:"/chapter/ris/71649",signatures:"Diane Irvine Duncan",book:{id:"9122",title:"Cosmetic Surgery",subtitle:null,fullTitle:"Cosmetic Surgery",slug:"cosmetic-surgery",publishedDate:"February 10th 2021",bookSignature:"Yueh-Bih Tang",coverURL:"https://cdn.intechopen.com/books/images_new/9122.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"202122",title:"Prof.",name:"Yueh-Bih",middleName:null,surname:"Tang",slug:"yueh-bih-tang",fullName:"Yueh-Bih Tang"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"279869",title:"Dr.",name:"Diane Irvine",middleName:null,surname:"Duncan",fullName:"Diane Irvine Duncan",slug:"diane-irvine-duncan",email:"momsurg@aol.com",position:null,institution:{name:"University of Colorado Health",institutionURL:null,country:{name:"United States of America"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Background",level:"1"},{id:"sec_3",title:"3. Materials and methods",level:"1"},{id:"sec_4",title:"4. Results",level:"1"},{id:"sec_5",title:"5. Discussion",level:"1"},{id:"sec_6",title:"6. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Paul M, Mulholland RS. A new approach for adipose tissue treatment and body contouring using radiofrequency-assisted liposuction. Aesthetic Plastic Surgery. 2009;33:687-694'},{id:"B2",body:'Chen SS, Wright NT, Humphrey JD. Heat-induced changes in the mechanics of a collagenous tissue: Isothermal free shrinkage. Journal of Biomechanical Engineering. 1997;109:372-378'},{id:"B3",body:'Cohen SR, Tiryaki T, et al. Cellular optimization of nanofat: Comparison of two nanofat processing devices in terms of cell count and viability. Aesthetic Surgery Journal Open Forum. December 2019;1(4):ojz028. DOI: 10.1093/asjof/ojz028'},{id:"B4",body:'Duncan DI. Improving outcomes in upper arm liposuction: Adding radiofrequency-assisted liposuction to induce skin contraction. Aesthetic Surgery Journal. 2012;32(1):84-95'},{id:"B5",body:'DiBernardo BE, Reyes J. Evaluation of skin tightening after laser-assisted liposuction. Aesthetic Surgery Journal. 2009;29:400-407'},{id:"B6",body:'McBean J, Katz B. Laser Lipolysis: an update. The Journal of Clinical and Aesthetic Dermatology. 2011;4(7):25-34'},{id:"B7",body:'Tiryaki T. Micro-shuttle lifting of the neck: A percutaneous loop suspension method using a novel double-ended needle. Aesthetic Surgery Journal. 2016;36(6):629-638. DOI: 101093/asj/swj001. Epub: 23 February 2016'},{id:"B8",body:'Hurwitz D et al. Enhancing masculine features after massive weight loss. Aesthetic Plastic Surgery. 2016;40:245-255. DOI: 10.1007/s00266-016-0617-x. Published online: 18 February 2016. PMCID: PMC481945'},{id:"B9",body:'Duncan DI, Dinev I. Noninvasive induction of muscle fiber hypertrophy and hyperplasia: Effects of high-intensity focused electromagnetic field evaluated in an in-vivo porcine model: A pilot study. Aesthetic Surgery Journal. 26 October 2019:sjz244. DOI: 10.1093/asj/sjz244'},{id:"B10",body:'Cotofana S, Fratila AA, Schenck TL, Redka-Swoboda W, Zilinsky I, Pavicic T. The anatomy of the aging face: A review. Facial Plastic Surgery. 2016;32(3):253-260. DOI: 10.1055/s-0036-1582234. Epub: 01 June 2016. Review'},{id:"B11",body:'Duncan DI. Restoring a pleasant facial expression with minimally invasive techniques. Aesthetic Surgery Journal. 2004;24:574-579'},{id:"B12",body:'Dobke M, Hauch A. Targeting facial aging with nano and regenerative technologies and procedures. Plastic and Aesthetic Research. 2020;7:1. DOI: 10.20517/2347-9264.2019.65. Received: 30 November 2019; First Decision: 02 January 2020; Revised: 02 January 2020. https://parjournal.net/article/view/3320'},{id:"B13",body:'https://www.plasticsurgery.org/documents/News/Statistics/2018/plastic-surgery-statistics-full-report-2018.pdf [Accessed: 21 December 2019]'},{id:"B14",body:'Kaufman MR, Miller TA, Huang C, et al. Autologous fat transfer for facial recontouring: Is there science behind the art? Plastic and Reconstructive Surgery. 2007;119:2287-2296'},{id:"B15",body:'Coleman SR et al. Facial recontouring with lipostructure. Clinics in Plastic Surgery. 1997;24:347-367'},{id:"B16",body:'Strong AL, Cederna PS, et al. The current state of fat grafting: A review of harvesting, processing, and injection techniques. Plastic and Reconstructive Surgery. 2015;136(4):912. DOI: 10.1097/PRS.0000000000001590. PMCID: PMC4833505. Author manuscript; available in PMC October 1, 2016; Published in final edited form as: Plast Reconstr Surg. 2015; 897-913'},{id:"B17",body:'Cohen SR. Topical nanofat biocrème improves aesthetic outcomes of nonablative fractionated laser treatment: A preliminary report. Aesthetic Surgery Journal. 05 September 2019:sjz240. DOI: 10.1093/asj/sjz240'},{id:"B18",body:'Trivisonno A, Alexander R, et al. Intraoperative Strategies for minimal manipulation of autologous adipose tissue for cell- and tissue-based therapies: Concise review. Stem Cells Translational Medicine. 2019;8(12):1265-1271. DOI: 10.1002/sctm.19-0166. PMCID: PMC6877766'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Diane Irvine Duncan",address:"momsurg@aol.com",affiliation:'
Private Practice in Fort Collins, Colorado, USA
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Kjeld has implemented various projects in the \nareas of quality and patient safety and spearheaded, among \nother projects, the introduction of lean thinking and lean \nprocesses in the operating rooms.\nKjeld has previously conducted research into leadership and \nsuccessful change in organizations, with a special focus on \nthe role of middle management. Since 2010, he has served as \na member of the project committee for the Dutch Operating \nRoom Benchmarking Collaborative, whose objective is \nto improve operating room performance through mutual \nlearning from best practices. In 2010, he was appointed as a \nresearch member of the Lean Healthcare Research Consortium \nof Stanford University in Palo Alto, California, USA. Since \n2013, he has also been a member of the Center for Lean \nHealthcare Research at Ohio State University. He got his PhD \nin 2015, investigating the leadership behaviors essential to \nthe successful, sustainable implementation of lean principles \nin hospitals. He also teaches at VU University and several Business Schools and is a popular speaker at conferences.",institutionString:null,institution:{name:"VU University Amsterdam",institutionURL:null,country:{name:"Netherlands"}}},{id:"190488",title:"Prof.",name:"Sevgi",surname:"Şar",slug:"sevgi-sar",fullName:"Sevgi Şar",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"194238",title:"Dr.",name:"Reem",surname:"Al-Dossary",slug:"reem-al-dossary",fullName:"Reem Al-Dossary",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"194887",title:"Dr.",name:"Beatriz",surname:"Peña-Acuña",slug:"beatriz-pena-acuna",fullName:"Beatriz Peña-Acuña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/194887/images/system/194887.jpg",biography:"Beatriz Peña-Acuña enjoys discovering scientific and human\naspects of reality. She is an assistant professor accredited by the\nSpanish Quality Agency ANECA (2015). She teaches in the Faculty\nof Education of the University of Huelva. Her interests are\nHispanic philology, and she has a diploma in religious studies and\njournalism. She has produced several doctoral theses, and has an\nextraordinary doctorate award (2012) with European mention\nin English. Her scientific production is prolific. Beatriz is an expert evaluator of\nErasmus plus programs in the SEPIE agency. She participates as a reviewer in several\njournals of impact. She has visited several international universities (New York\nUniversity, UEA, University of London, etc.). She also gives international conferences\nand has been awarded the President’s Lifetime Achievement Award (2015),\nand received an Honoris Causa from UFA University (Russia, 2016) and Catholic\nUniversity of New Spain (USA, 2019).",institutionString:"University of Huelva",institution:{name:"University of Huelva",institutionURL:null,country:{name:"Spain"}}}]},generic:{page:{slug:"OA-publishing-fees",title:"Open Access Publishing Fees",intro:"
The Open Access model is applied to all of our publications and is designed to eliminate subscriptions and pay-per-view fees. This approach ensures free, immediate access to full text versions of your research.
As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 118,000 international scientists and researchers.
\\n\\n
The Open Access Publishing Fee (OAPF) is payable only after your full chapter, monograph or Compacts monograph is accepted for publication.
\\n\\n
OAPF Publishing Options
\\n\\n
\\n\\t
1,400 GBP Chapter - Edited Volume
\\n\\t
10,000 GBP Monograph - Long Form
\\n\\t
4,000 GBP Compacts Monograph - Short Form
\\n
\\n\\n
*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\\n\\n
Services included are:
\\n\\n
\\n\\t
An online manuscript tracking system to facilitate your work
\\n\\t
Personal contact and support throughout the publishing process from your dedicated Author Service Manager
\\n\\t
Assurance that your manuscript meets the highest publishing standards
\\n\\t
English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
\\n\\t
XML Typesetting and pagination - web (PDF, HTML) and print files preparation
\\n\\t
Discoverability - electronic citation and linking via DOI
\\n\\t
Permanent and unrestricted online access to your work
What isn't covered by the Open Access Publishing Fee?
\\n\\n
If your manuscript:
\\n\\n
\\n\\t
Exceeds 20 pages (for chapters in Edited Volumes), an additional fee of 40 GBP per page will be required
\\n\\t
If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
\\n
\\n\\n
Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\\n\\n
Open Access Funding
\\n\\n
To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at oapf@intechopen.com for further details or assistance.
\\n\\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\\n\\n
Added Value of Publishing with IntechOpen
\\n\\n
Choosing to publish with IntechOpen ensures the following benefits:
\\n\\n
\\n\\t
Indexing and listing across major repositories, see details ...
\\n\\t
Long-term archiving
\\n\\t
Visibility on the world's strongest OA platform
\\n\\t
Live Performance Metrics to track readership and the impact of your chapter
\\n\\t
Dissemination and Promotion
\\n
\\n\\n
Benefits of Publishing with IntechOpen
\\n\\n
\\n\\t
Proven world leader in Open Access book publishing with over 10 years experience
\\n\\t
+4,800 OA books published
\\n\\t
Most competitive prices in the market
\\n\\t
Fully compliant with OA funding requirements
\\n\\t
Optimized processes, enabling publication between 8 and 12 months
\\n\\t
Personal support during every step of the publication process
\\n\\t
+146,150 citations in Web of Science databases
\\n\\t
Currently strongest OA platform with over 130 million downloads
As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 118,000 international scientists and researchers.
\n\n
The Open Access Publishing Fee (OAPF) is payable only after your full chapter, monograph or Compacts monograph is accepted for publication.
\n\n
OAPF Publishing Options
\n\n
\n\t
1,400 GBP Chapter - Edited Volume
\n\t
10,000 GBP Monograph - Long Form
\n\t
4,000 GBP Compacts Monograph - Short Form
\n
\n\n
*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\n\n
Services included are:
\n\n
\n\t
An online manuscript tracking system to facilitate your work
\n\t
Personal contact and support throughout the publishing process from your dedicated Author Service Manager
\n\t
Assurance that your manuscript meets the highest publishing standards
\n\t
English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
\n\t
XML Typesetting and pagination - web (PDF, HTML) and print files preparation
\n\t
Discoverability - electronic citation and linking via DOI
\n\t
Permanent and unrestricted online access to your work
What isn't covered by the Open Access Publishing Fee?
\n\n
If your manuscript:
\n\n
\n\t
Exceeds 20 pages (for chapters in Edited Volumes), an additional fee of 40 GBP per page will be required
\n\t
If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
\n
\n\n
Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\n\n
Open Access Funding
\n\n
To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at oapf@intechopen.com for further details or assistance.
\n\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\n\n
Added Value of Publishing with IntechOpen
\n\n
Choosing to publish with IntechOpen ensures the following benefits:
\n\n
\n\t
Indexing and listing across major repositories, see details ...
\n\t
Long-term archiving
\n\t
Visibility on the world's strongest OA platform
\n\t
Live Performance Metrics to track readership and the impact of your chapter
\n\t
Dissemination and Promotion
\n
\n\n
Benefits of Publishing with IntechOpen
\n\n
\n\t
Proven world leader in Open Access book publishing with over 10 years experience
\n\t
+4,800 OA books published
\n\t
Most competitive prices in the market
\n\t
Fully compliant with OA funding requirements
\n\t
Optimized processes, enabling publication between 8 and 12 months
\n\t
Personal support during every step of the publication process
\n\t
+146,150 citations in Web of Science databases
\n\t
Currently strongest OA platform with over 130 million downloads
\n
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