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Management of viral hepatitis in liver transplant recipients.

Soung Won JEONG ; Youngrok CHOI ; Jin Wook KIM

Clinical and Molecular Hepatology.2014;20(4):338-344. doi:10.3350/cmh.2014.20.4.338

Recurrence of viral hepatitis after liver transplantation (LT) can progress to graft failure and lead to a decrease in long-term survival. Recently, there have been remarkable improvement in the treatment of chronic hepatitis B (CHB) using potent antiviral agents. Combination of hepatitis B immunoglobulin and potent antiviral therapy has brought marked advances in the management of CHB for liver transplant recipients. Post-transplant antiviral therapy for hepatitis C virus infection is generally reserved for patients showing progressive disease. Acheiving a sustained virological response in patients with LT greatly ameliorates graft and overall survival, however this only occurs in 30% of transplant recipient using pegylated interferon and ribavirin (RBV). Direct acting antivirals such as protease inhibitors, polymerase or other non-structural proteins inhibitors are anticipated to establish the new standard of care for transplant recipients. In liver transplant recipients, hepatitis E virus infection is an uncommon disease. However, it can lead to chronic hepatitis and cirrhosis and may require retransplantation. Recently, 3-month course of RBV monotherapy has been reported as an effective treatment. This review focuses on the recent management and therapeutic approaches of viral hepatitis in liver transplant recipient.
Antiviral Agents/therapeutic use ; Hepatitis B/drug therapy/pathology/surgery ; Hepatitis C/drug therapy/pathology/surgery ; Hepatitis E/drug therapy/pathology/surgery ; Hepatitis, Viral, Human/drug therapy/pathology/*surgery ; Humans ; *Liver Transplantation ; Recurrence

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Cost-of-illness studies: concepts, scopes, and methods.

Changik JO

Clinical and Molecular Hepatology.2014;20(4):327-337. doi:10.3350/cmh.2014.20.4.327

Liver diseases are one of the main causes of death, and their ever-increasing prevalence is threatening to cause significant damage both to individuals and society as a whole. This damage is especially serious for the economically active population in Korea. From the societal perspective, it is therefore necessary to consider the economic impacts associated with liver diseases, and identify interventions that can reduce the burden of these diseases. The cost-of-illness study is considered to be an essential evaluation technique in health care. By measuring and comparing the economic burdens of diseases to society, such studies can help health-care decision-makers to set up and prioritize health-care policies and interventions. Using economic theories, this paper introduces various study methods that are generally applicable to most disease cases for estimating the costs of illness associated with mortality, morbidity, disability, and other disease characteristics. It also presents concepts and scopes of costs along with different cost categories from different research perspectives in cost estimations. By discussing the epidemiological and economic grounds of the cost-of-illness study, the reported results represent useful information about several evaluation techniques at an advanced level, such as cost-benefit analysis, cost-effectiveness analysis, and cost-utility analysis.
*Cost of Illness ; Costs and Cost Analysis ; Delivery of Health Care/economics ; Humans ; Liver Diseases/*economics/pathology

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Elevated red cell distribution width is associated with advanced fibrosis in NAFLD.

Hwa Mok KIM ; Bum Soo KIM ; Yong Kyun CHO ; Byung Ik KIM ; Chong Il SOHN ; Woo Kyu JEON ; Hong Joo KIM ; Dong Il PARK ; Jung Ho PARK ; Kwan Joong JOO ; Chang Joon KIM ; Yong Sung KIM ; Woon Je HEO ; Won Seok CHOI

Clinical and Molecular Hepatology.2013;19(3):258-265. doi:10.3350/cmh.2013.19.3.258

BACKGROUND/AIMS: The red-blood-cell distribution width (RDW) is a newly recognized risk marker in patients with cardiovascular disease, but its role in nonalcoholic fatty liver disease (NAFLD) has not been well defined. The aim of the present study was to determine the association between RDW values and the level of fibrosis in NAFLD according to BARD and FIB-4 scores. METHODS: This study included 24,547 subjects who had been diagnosed with NAFLD based on abdominal ultrasonography and questionnaires about alcohol consumption. The degree of liver fibrosis was determined according to BARD and FIB-4 scores. The association between RDW values and the degree of fibrosis in NAFLD was analyzed retrospectively. RESULTS: After adjusting for age, hemoglobin level, mean corpuscular volume, history of hypertension, history of diabetes, and high-sensitivity C-reactive protein, the RDW values were 12.61+/-0.41% (mean+/-SD), 12.70+/-0.70%, 12.77+/-0.62%, 12.87+/-0.82%, and 13.25+/-0.90% for those with BARD scores of 0, 1, 2, 3, and 4, respectively, and 12.71+/-0.72%, 12.79+/-0.66%, and 13.23+/-1.52% for those with FIB-4 scores of <1.30, 1.31-2.66, and > or =2.67, respectively (P<0.05). The prevalence of advanced fibrosis (BARD score of 24 and FIB-4 score of > or =1.3) increased with the RDW [BARD score: 51.1% in quartile 1 (Q1) vs. 63.6% in Q4; FIB-4 score: 6.9% in Q1 vs. 10.5% in Q4; P<0.001]. After adjustments, the odds ratio of having advanced fibrosis for those in Q4 compared to Q1 were 1.76 (95%CI=1.55-2.00, P<0.001) relative to BARD score and 1.69 (95%CI=1.52-1.98, P<0.001) relative to FIB-4 score. CONCLUSIONS: Elevated RDW is independently associated with advanced fibrosis in NAFLD.
Adult ; Alcohol Drinking ; C-Reactive Protein/analysis ; Diabetes Mellitus/pathology ; Erythrocyte Indices ; Fatty Liver/complications/*diagnosis/ultrasonography ; Female ; Humans ; Hypertension/pathology ; Liver Cirrhosis/*diagnosis/epidemiology/etiology ; Male ; Middle Aged ; Odds Ratio ; Prevalence ; Questionnaires ; Severity of Illness Index

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Chasing after novel non-invasive markers to identify advanced fibrosis in NAFLD.

Wonseok KANG ; Seung Up KIM

Clinical and Molecular Hepatology.2013;19(3):255-257. doi:10.3350/cmh.2013.19.3.255

No abstract available.
Fatty Liver/*diagnosis ; Female ; Humans ; Liver Cirrhosis/*diagnosis ; Male

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Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis.

Seung Hoi KOO

Clinical and Molecular Hepatology.2013;19(3):210-215. doi:10.3350/cmh.2013.19.3.210

Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.
Acetyl Coenzyme A/metabolism ; Fatty Acids/metabolism ; Fatty Liver/*metabolism/pathology ; Humans ; Lipogenesis ; Mitochondria/metabolism ; Triglycerides/metabolism

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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. doi:10.3350/cmh.2013.19.3.195

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

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Comparison of hepatic MDCT, MRI, and DSA to explant pathology for the detection and treatment planning of hepatocellular carcinoma.

Lauren M LADD ; Temel TIRKES ; Mark TANN ; David M AGARWAL ; Matthew S JOHNSON ; Bilal TAHIR ; Kumaresan SANDRASEGARAN

Clinical and Molecular Hepatology.2016;22(4):450-457. doi:10.3350/cmh.2016.0036

BACKGROUND/AIMS: The diagnosis and treatment plan for hepatocellular carcinoma (HCC) can be made from radiologic imaging. However, lesion detection may vary depending on the imaging modality. This study aims to evaluate the sensitivities of hepatic multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) in the detection of HCC and the consequent management impact on potential liver transplant patients. METHODS: One hundred and sixteen HCC lesions were analyzed in 41 patients who received an orthotopic liver transplant (OLT). All of the patients underwent pretransplantation hepatic DSA, MDCT, and/or MRI. The imaging results were independently reviewed retrospectively in a blinded fashion by two interventional and two abdominal radiologists. The liver explant pathology was used as the gold standard for assessing each imaging modality. RESULTS: The sensitivity for overall HCC detection was higher for cross-sectional imaging using MRI (51.5%, 95% confidence interval [CI]=36.2-58.4%) and MDCT (49.8%, 95% CI=43.7-55.9%) than for DSA (41.7%, 95% CI=36.2-47.3%) (P=0.05). The difference in false-positive rate was not statistically significant between MRI (22%), MDCT (29%), and DSA (29%) (P=0.67). The sensitivity was significantly higher for detecting right lobe lesions than left lobe lesions for all modalities (MRI: 56.1% vs. 43.1%, MDCT: 55.0% vs. 42.0%, and DSA: 46.9% vs. 33.9%; all P<0.01). The sensitivities of the three imaging modalities were also higher for lesions ≥2 cm vs. <2 cm (MRI: 73.4% vs. 32.7%, MDCT: 66.9% vs. 33.8%, and DSA: 62.2% vs. 24.1%; all P<0.01). The interobserver correlation was rated as very good to excellent. CONCLUSIONS: The sensitivity for detecting HCC is higher for MRI and MDCT than for DSA, and so cross-sectional imaging modalities should be used to evaluate OLT candidacy.
Adult ; Aged ; Angiography, Digital Subtraction ; Carcinoma, Hepatocellular/*diagnostic imaging/pathology/therapy ; Female ; Humans ; Liver Neoplasms/*diagnostic imaging/pathology/therapy ; Liver Transplantation ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; Tomography, X-Ray Computed

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Efficacy of switching from adefovir to tenofovir in chronic hepatitis B patients who exhibit suboptimal responses to adefovir-based combination rescue therapy due to resistance to nucleoside analogues (SATIS study).

Hye Won LEE ; Jun Yong PARK ; Beom Kyung KIM ; Moon Young KIM ; Jung Il LEE ; Young Suk KIM ; Ki Tae YOON ; Kwang Hyub HAN ; Sang Hoon AHN

Clinical and Molecular Hepatology.2016;22(4):443-449. doi:10.3350/cmh.2016.0037

BACKGROUND/AIMS: It remains to be determined whether switching from adefovir (ADV) to tenofovir (TDF) provides better virological outcomes in patients exhibiting suboptimal responses to ADV plus nucleoside analogue (ADV+NA) therapy for NA-resistant chronic hepatitis B (CHB). METHODS: In this prospective trial, patients who showed partial responses (defined as serum hepatitis B virus [HBV] DNA >60 IU/mL) to ADV+NA therapy for NA resistance were randomly allocated to receive TDF plus NA (TDF+NA group, n=16) or to continue their current therapy (ADV+NA group, n=16). The primary end point was the proportion of patients with complete virological response (CVR, defined as serum HBV DNA <60 IU/mL) at 48 weeks. RESULTS: The median age was 52 years (16 men), and 28 were positive for hepatitis B e antigen (HBeAg). The baseline characteristics did not differ significantly between the two groups. The proportion with CVR was significantly higher in the TDF+NA group than in the ADV+NA group at 24 weeks (81.3% vs. 25.0%, P=0.001) and 48 weeks (87.5% vs. 37.5%, P=0.002). Furthermore, a decrease in the serum HBV DNA level of >2log10 IU/mL was more likely in the TDF+NA group at both 24 and 48 weeks (68.8% vs. 56.3%, P=0.014 vs. 81.3% vs. 56.3%, P=0.001, respectively). During the follow-up, the rate of HBeAg seroconversion was higher in the TDF+NA group than the ADV+NA group (12.5% vs. 6.25%, P=0.640), as was that for the hepatitis B surface antigen (6.25% vs. 0%, P=0.080). No serious adverse events due to antiviral agents occurred. CONCLUSIONS: In patients exhibiting suboptimal responses to ADV+NA therapy for NA-resistant CHB, switching from ADV to TDF might provide better virological outcomes.
Adenine/*analogs & derivatives/therapeutic use ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Genotype ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/*drug therapy ; Humans ; Lamivudine/therapeutic use ; Male ; Middle Aged ; Organophosphonates/*therapeutic use ; Prospective Studies ; Tenofovir/*therapeutic use ; Treatment Outcome

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Switch to tenofovir-based therapy or to continue adefovir-based therapy in CHB patients with suboptimal response to adefovir-based combination?.

Byung Cheol SONG

Clinical and Molecular Hepatology.2016;22(4):439-442. doi:10.3350/cmh.2016.0108

No abstract available.

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Management of direct antiviral agent failures.

María BUTI ; Rafael ESTEBAN

Clinical and Molecular Hepatology.2016;22(4):432-438. doi:10.3350/cmh.2016.0107

The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). Most HCV patients treated with these drugs achieve viral elimination, but 1% to 15% fail to attain this objective. Treatment failures are usually related to relapse, and less often to on-treatment viral breakthrough. HCV drug resistant associated substitutions are detected in most patients who do not eliminate the virus. The risk of developing these variants depends on host- and virus-related factors, the properties of the drugs used, and the treatment strategies applied. Patients who carry Resistant Associated Substitutions (RASs) may not obtain benefits from treatment, and are at a risk of disease progression. Whether HCV RASs persist depends on their type: NS3-4A variants often disappear gradually after DAA therapy is stopped, whereas NS5A variants tend to persist for more than 2 years. The best way to prevent emergence of resistant variants is to eliminate the virus at the first treatment using highly potent DAAs with genetic barriers to resistance. For those who fail an NS5A inhibitor, deferral of treatment is recommended pending the availability of additional data if they do not have cirrhosis or reasons for urgent re-treatment. If re-treatment is needed, the most commonly used strategy is sofosbuvir as backbone therapy plus a drug from a class other than that previously used, for 24 weeks. Unless it is contraindicated, weight-based ribavirin should also be added. If available, nucleotide-based (eg, sofosbuvir) triple or quadruple DAA regimens may be considered. The optimal treatment for patients who fail an NS5A inhibitor and those with multidrug-resistant variants remains to be defined, and research efforts should continue to focus on treatment for these patients.
Antiviral Agents/*therapeutic use ; Drug Resistance, Viral ; Drug Therapy, Combination ; Genotype ; Hepacivirus/genetics ; Hepatitis C, Chronic/*drug therapy ; Humans ; Recurrence ; Ribavirin/therapeutic use ; Sofosbuvir/therapeutic use

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