2.Management of Antiviral-Resistant Chronic Hepatitis B Virus Infection.
The Korean Journal of Gastroenterology 2008;51(6):346-359
Substantial progress has been made in the treatment of chronic hepatitis B during the past decade. Nucleos(t)ide analogues are now widely used due to their convenience, less side effects, and considerable response rates. However, development of antiviral resistance is a major problem being considered as the most important factor for the treatment failure. Viral breakthrough associated with selection of antiviral-resistant hepatitis B virus (HBV) is usually followed by biochemical breakthrough, clinical deterioration, and even progressive liver failure. Therefore, appropriate management of antiviral resistance is critical for improving treatment outcomes. Strategies for the management of antiviral-resistant chronic HBV infection are described herein considering recently published guidelines. Lamivudine/telbivudine resistance can be managed by adding adefovir. Switching to adefovir or entecavir is also a viable option. However, careful follow-up of viral load is mandatory to detect any primary or secondary treatment failure in case of sequential monotherapy. Interferon or peg-interferon therapy can also be considered in case of young patients with compensated liver disease. For adefovir resistance, lamivudine can be added, but adding or switching to entecavir is a more reasonable option. Likewise, adding or switching to adefovir can be considered for entecavir resistance. Adding or switching to tenofovir needs to be considered upon availability. Experiences for clevudine resistance are still lacking, and need to be studied further upon the isolation of clinically resistant strains. To avoid emergence of resistant mutations, antiviral therapy should be initiated after careful balance of risk and benefit, and the most potent antiviral agent with the lowest resistance rate should be selected.
Adenine/analogs & derivatives/therapeutic use
;
Antiviral Agents/therapeutic use
;
Arabinofuranosyluracil/analogs & derivatives/therapeutic use
;
*Drug Resistance, Multiple, Viral
;
Guanine/analogs & derivatives/therapeutic use
;
Hepatitis B virus/*drug effects/isolation & purification
;
Hepatitis B, Chronic/*drug therapy
;
Humans
;
Lamivudine/therapeutic use
;
Mutation
;
Nucleosides/therapeutic use
;
Phosphonic Acids/therapeutic use
;
Practice Guidelines as Topic
;
Pyrimidinones/therapeutic use
;
Treatment Outcome
3.Hepatitis B virus genetic diversity and mutant.
The Korean Journal of Hepatology 2008;14(4):446-464
Hepatitis B virus (HBV) is a partially double stranded DNA virus with genetic diversity represented by eight genotypes (A to H). Natural course and response to treatment could be affected by HBV genotypes. HBV shows high rates of turn over in the absence of proof-reading ability. As a result, large amounts of quasispecies are produced naturally or antiviral-associated. HBV consists of four open reading frames, namely preS/S gene, precore/core gene, polymerase gene, and X gene. Mutations on preS gene can result in undetectable HBsAg even in case that HBV is replicating. Surface gene mutation leads to decreased binding affinity to anti-HBs, which is associated with a vaccine escape mutant. Precore mutation abolishes HBeAg whereas mutations on basal core promoter gene down-regulate the HBeAg production. Mutations on basal core promoter are associated with increased HBV replication and high incidence of progressive liver diseases such as liver cirrhosis and hepatocellular carcinoma. Mutations on polymerase genes are often induced by antiviral therapy. Emergence of antiviral-resistant mutation is the major cause of treatment failure. Furthermore, existence of prior antiviral-resistant mutations limits the options of subsequent antiviral agents. Therefore, judicious use of antivirals and selection of the most potent drug with the lowest resistance rate are of the utmost importance for the prevention of antiviral-associated mutants. Detailed knowledge and understanding of HBV genetic diversity and mutant would be critical to establish strategies for the diagnosis and management of HBV infection.
Drug Resistance, Viral
;
*Genetic Variation
;
Genotype
;
Hepatitis B/diagnosis/drug therapy/virology
;
Hepatitis B virus/classification/*genetics
;
Humans
;
*Mutation
;
Serotyping
;
Virus Replication/genetics
5.An experimental study on tissue reactions of allogeneic sciatic nerve graft in rat
Hyung Bai CHUNG ; Chang Joon YIM ; Dong Keun LEE ; Jae Deok SE
Journal of the Korean Association of Maxillofacial Plastic and Reconstructive Surgeons 1991;13(2):203-216
No abstract available.
Animals
;
Rats
;
Sciatic Nerve
;
Transplants
7.Reversal of liver cirrhosis: current evidence and expectations.
Young Kul JUNG ; Hyung Joon YIM
The Korean Journal of Internal Medicine 2017;32(2):213-228
In the past, liver cirrhosis was considered an irreversible phenomenon. However, many experimental data have provided evidence of the reversibility of liver fibrosis. Moreover, multiple clinical studies have also shown regression of fibrosis and reversal of cirrhosis on repeated biopsy samples. As various etiologies are associated with liver fibrosis via integrated signaling pathways, a comprehensive understanding of the pathobiology of hepatic fibrogenesis is critical for improving clinical outcomes. Hepatic stellate cells play a central role in hepatic fibrogenesis upon their activation from a quiescent state. Collagen and other extracellular material components from activated hepatic stellate cells are deposited on, and damage, the liver parenchyma and vascular structures. Hence, inactivation of hepatic stellate cells can lead to enhancement of fibrolytic activity and could be a potential target of antifibrotic therapy. In this regard, continued efforts have been made to develop better treatments for underlying liver diseases and antifibrotic agents in multiple clinical and therapeutic trials; the best results may be expected with the integration of such evidence. In this article, we present the underlying mechanisms of fibrosis, current experimental and clinical evidence of the reversibility of liver fibrosis/cirrhosis, and new agents with therapeutic potential for liver fibrosis.
Biopsy
;
Collagen
;
Fibrosis
;
Hepatic Stellate Cells
;
Liver Cirrhosis*
;
Liver Diseases
;
Liver*
8.Options for the management of antiviral resistance during hepatitis B therapy: reflections on battles over a decade.
Hyung Joon YIM ; Seong Gyu HWANG
Clinical and Molecular Hepatology 2013;19(3):195-209
Although much advancement has been achieved in the treatment of chronic hepatitis B, antiviral resistance is still a challenging issue. Previous generation antiviral agents have already developed resistance in a number of patients, and it is still being used especially in resource limited countries. Once antiviral resistance occurs, it predisposes to subsequent resistance, resulting in multidrug resistance. Therefore, prevention of initial antiviral resistance is the most important strategy, and appropriate choice and modification of therapy would be the cornerstone in avoiding treatment failures. Until now, management of antiviral resistance has been evolving from sequential therapy to combination therapy. In the era of tenofovir, the paradigm shifts again, and we have to decide when to switch and when to combine on the basis of newly emerging clinical data. We expect future eradication of chronic hepatitis B virus infection by proper prevention and optimal management of antiviral resistance.
Adenine/analogs & derivatives/pharmacology/therapeutic use
;
Antiviral Agents/pharmacology/*therapeutic use
;
Drug Resistance, Viral/drug effects
;
Drug Therapy, Combination
;
Hepatitis B virus/genetics
;
Hepatitis B, Chronic/*drug therapy/prevention & control
;
Humans
;
Mutation
;
Nucleosides/*chemistry/pharmacology/therapeutic use
;
Organophosphonates/pharmacology/therapeutic use
;
Virus Replication/drug effects
9.Clinical Application of the Delayed Procedure in the Distally Based Sural Flap.
Hyung Woo YIM ; Yong Joon PARK
Journal of the Korean Society of Plastic and Reconstructive Surgeons 2010;37(6):775-778
PURPOSE: Reconstruction of soft tissue defects with osteomyelitis in the lower third of the leg represents a challenge to plastic surgeons. Moreover, it is more arduous in multimorbid patients. One excellent option for reconstruction of these defects is to use a delayed distally based sural flap. METHODS: We successfully used delayed distally based sural flap with a two-step procedure. During the first operation, radical debridement and elevation of flap were performed. The raised flap was fixed again at the donor site. The delay period ranged from seven to ten days. Between August 2008 and July 2009, we underwent operations for five patients using this technique. The size of flap varied from 10 x 6 cm to 12 x 14 cm. RESULTS: All flaps successfully survived. Partial skin loss of the grafted site was seen in two patients but no further surgical procedure was required for wound healing. Complaints of hypoesthesia on the lateral part of the foot was observed. In a three month follow-up period, hypoesthesia was resolved spontaneously. CONCLUSION: Delayed procedure improves the viability of distally based sural flap in high risk, critically multimorbid patients. We recommend that, if a two-stage operative approach is required, the delayed procedure should be considered.
Debridement
;
Follow-Up Studies
;
Foot
;
Humans
;
Hypesthesia
;
Leg
;
Organic Chemicals
;
Osteomyelitis
;
Skin
;
Tissue Donors
;
Transplants
;
Wound Healing
10.The Association of Carbon Disulfide Poisoning with Heart Rate Variability.
Hyung Joon JHUN ; Sang Hyuk YIM ; Do Myung PAEK
Korean Journal of Occupational and Environmental Medicine 2004;16(1):48-56
OBJECTIVES: Mass poisoning by carbon disulfide (CS2) occurred in a viscose rayon factory in Korea. Up until 1998, 830 employees, including 38 who had died, were diagnosed with CS2 poisoning. Among the CS2 poisoned subjects, heart rate variability (HRV) was evaluated to investigate whether the toxic effect of CS2 persists after the exposure has ceased. The dose-response relationship between carbon disulfide exposure and HRV was also evaluated. METHODS: The case group was comprised of 71 retired male workers diagnosed as being CS2 poisoned. The control group was comprised of 127 males of same age-range who had no history of CS2 exposure and cardiovascular diseases. Information on individual age, height, weight, cigarette smoking, alcohol drinking, regular exercise, medical and occupational history, chest x-ray, and ECG recording of the two groups were collected through a self-administered questionnaire and with a medical examination. Time (maximum, average, minimum RR interval) and frequency domain measures (low frequency - LF, high frequency - HF, total power spectrum TPS, and LF/HF ratio) of the two groups were analyzed. CS2 exposure indices of the case group (duration of employment, exposure level per work department, cumulative exposure index and duration of retirement) were investigated. RESULTS: Using a univariate analysis, the frequency domain measures for the case group were significantly lower than those in the control group, except for HF. In the multivariate analysis, previous history of CS2 poisoning was inversely related to all frequency domain parameters and it significantly affected the LF (p<0.05) and the LF/HF ratio (p<0.05). There was no significant dose-response relationship between CS2 exposure indices and HRV parameters in the case group. CONCLUSION: This study suggests that further studies are necessary to evaluate the residual effects of CS2 poisoning even after the CS2 exposure has ceased.
Alcohol Drinking
;
Carbon Disulfide*
;
Carbon*
;
Cardiovascular Diseases
;
Electrocardiography
;
Employment
;
Heart Rate*
;
Heart*
;
Humans
;
Korea
;
Male
;
Multivariate Analysis
;
Poisoning*
;
Questionnaires
;
Smoking
;
Thorax