The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Radiological response predicts survival following transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma.

BACKGROUND: It remains unclear whether initial compact lipiodol uptake after transarterial chemoembolisation (TACE) is associated with improved survival in patients with hepatocellular carcinoma (HCC). AIM: To reveal the clinical relevance of compact lipiodolisation after TACE. METHODS: We studied 490 patients with unresectable HCC who had first been treated with TACE. Compact lipiodolisation was defined as the absence of an arterial enhancing lesion, reflecting complete lipiodol uptake, as assessed by dynamic computed tomography (CT) 1 month after treatment. The rate of initial compact lipiodolisation was analysed according to multiplicity and size of tumour, and survival of patients who achieved compact lipiodolisation was compared to that of patients who did not. RESULTS: Of the 490 patients, 409 (83.5%) were in Child-Pugh class A and 81 (16.5%) in class B. The rate of initial compact lipiodolisation in single HCCs was higher than that in multinodular HCCs (33.7% vs. 14.6%, P < 0.001). Among single HCCs, the rate of compact lipiodolisation in tumours ≤5, 5-10 and >10 cm was 46.6%, 13.6%, and 0% respectively. The 1-, 3- and 5-year survival rates of patients with compact uptake were 92.7%, 70.7% and 52.4% compared to 60.8%, 28.0% and 16.9% in patients with noncompact lipiodolisation. Multivariate analysis revealed that Child-Pugh class, alpha-fetoprotein level, tumour node metastasis stage, portal vein thrombosis and initial compact lipiodolisation were independent predictors of survival. CONCLUSIONS: Initial compact lipiodol uptake after transarterial chemoembolisation is associated with improved survival in patients with unresectable hepatocellular carcinoma. Accordingly, initial complete lipiodolisation should be considered a relevant therapeutic target.

Results of up to 2 years of entecavir vs lamivudine therapy in nucleoside-naïve HBeAg-positive patients with chronic hepatitis B.

Entecavir is a potent inhibitor of hepatitis B virus (HBV) polymerase. The efficacy and safety of entecavir in nucleoside-naïve patients with hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B was established in a large, international, double-dummy study (ETV-022) where patients were randomized to entecavir 0.5 mg/day (n = 354) or lamivudine 100 mg/day (n = 355) once daily. ETV-022 had a 52-week blinded treatment phase, followed by an extended blinded treatment phase for up to 44 additional weeks (96 weeks total). Treatment was discontinued for patients achieving a protocol-defined response as determined by patient management criteria that intended to test the possibility of finite therapy, which has not previously been studied for entecavir or other anti-HBV agents in a large trial. Early results from this study have been previously presented/published separately. This paper compiles the results of up to 2 years of treatment for protocol-defined responders, virologic responders and nonresponders. For responders who discontinued therapy (per protocol), 24-week off-treatment evaluation is presented to provide a more 'complete picture' of what clinicians can expect when treating nucleoside-naïve HBeAg-positive patients with chronic hepatitis B. For patients who discontinued therapy because of nonresponse (nonresponders) and subsequently entered the rollover study ETV-901, follow-up results, including resistance profile, are provided.

The use of Q-switched Nd:YAG laser in the treatment of superficial pigmented lesions in Koreans.

AIM: There are still insufficient clinical reports concerning quality-switched Nd:YAG laser (QSNYL) in the treatment of superficial pigmented lesions in Asians. The purpose of this study was to analyse the efficacy and side effect profiles of QSNYL-assisted pigment removal in brown skin. METHODS: A total of 71 patients, presenting a wide gamut of superficial epidermal lesions, were treated with QSNYL. Clinical responses were assessed by comparing photographs that were taken serially in every treatment. RESULTS: Treatment using the QSNYL is reported individually for the various superficial pigmented lesions in the skin of Korean patients. CONCLUSION: QSNYL may be a beneficial alternative tool for the treatment of a number of benign pigmented lesions including freckles, lentigines and unilateral lentiginosis.

Clinical use of the Q-switched Nd:YAG laser for the treatment of acquired bilateral nevus of Ota-like macules (ABNOMs) in Koreans.

BACKGROUND: There are still insufficient clinical reports about quality-switched Nd:YAG laser (QSNYL) in the treatment of acquired bilateral nevus of Otalike macules (ABNOMs) in Asians. OBJECTIVE: To analyze the efficacy and side-effect profiles of QSNYL treatment of ABNOMs in Korean skin. METHODS: A prospective study was designed to follow 10 Korean patients with ABNOMs through laser treatment until maximal eradication of the lesions had been achieved. RESULTS: Five patients (50%) with ABNOMs were treated with excellent or good results. The more treatments a patient underwent, the greater the possibility of improvement. There were no cases of persistent skin textural change or persistent erythema. CONCLUSION: The clinical data support QSNYL being a beneficial alternative tool for treating ABNOMs in brown skin. This is, to the best of the authors' knowledge, the first report about laser treatment of ABNOMs using QSNNL.

Effects of red ginseng upon vascular endothelial function in patients with essential hypertension.

This study is to estimate the effect of Korean red ginseng on vascular endothelial cell dysfunction in patients with hypertension. Seventeen patients with hypertension who were divided into ginseng-treated (7) and non-treated (10) groups and 10 normotensive subjects were included. To assess the function of the vascular endothelial cell, changes of forearm blood flow to infusion of acetylcholine, sodium nitroprusside and bradykinin in incremental doses were measured by venous occlusion plethysmography. In the ginseng-treated hypertensive group, forearm blood flows at the highest dose of acetylcholine and bradykinin were significantly higher than those of the non-treated hypertensive group and were not different from those of the control group. In the case of sodium nitroprusside infusion, no significant differences were observed between the control, non-treated and treated groups. In conclusion, Korean red ginseng can improve the vascular endothelial dysfunction in patients with hypertension possibly through increasing synthesis of nitric oxide.

Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma.

PURPOSE: The best prognosis in hepatocellular carcinoma (HCC) can be achieved with surgical resection; however, the number of resected cases are limited due to advanced lesions or associated liver disease. The purpose of this study was to investigate the efficacy and toxicity of a prospective trial of combined transcatheter arterial chemoembolization (TACE) and local radiotherapy (RT) in unresectable HCC. METHODS AND MATERIALS: Patients with histologically proven unresectable HCC due to either advanced lesions or associated cirrhosis were eligible. From March 1992 to August 1994, 30 patients were entered into this study. TACE was performed with Lipiodol (5 ml) and doxorubicin (Adriamycin ; 50 mg), followed by gelatin sponge particle (Gelfoam) embolization. Local RT was started within 7-10 days following TACE. Mean tumor dose was 44.0+/-9.3 Gy in daily 1.8 Gy fractions. Response was assessed by computerized tomography (CT) scan 4-6 weeks following completion of the treatment and then at 1-3-month intervals. Survival was calculated from the start of TACE using the Kaplan-Meier method. RESULTS: An objective response was observed in 19 patients, giving a response rate of 63.3%. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone. Survival rates at 1, 2, and 3 years were 67%, 33.3%, and 22.2%, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Toxicity included transient elevation of liver function tests in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. CONCLUSION: Combined TACE and local RT is feasible and tolerable. It gives a 63.3% response rate with median survival of 17 months. We feel that this regimen would be a new promising modality in unresectable HCC. Further study is required to compare the therapeutic efficacy of this regimen to TACE alone.

Effect of red ginseng on blood pressure in patients with essential hypertension and white coat hypertension.

The objective of this study is to evaluate the changes of diurnal blood pressure pattern after 8 weeks of red ginseng medication (4.5 g/day) by 24 hour ambulatory blood pressure monitoring. In 26 subjects with essential hypertension, 24 hour mean systolic blood pressure decreased significantly (p = 0.03) while diastolic blood pressure only showed a tendency of decline (p = 0.17). The decrease in pressures were observed at daytime (8 A.M.-6 P.M.) and dawn (5 A.M.-7 A.M.). In 8 subjects with white coat hypertension, no significant blood pressure change was observed. We suggest that red ginseng might be useful as a relatively safe medication adjuvant to current antihypertensive medications.

Three naphthalenes from root bark of Hibiscus syriacus.

Three new naphthalenes, designated as syriacusins A-C, were isolated from the root bark of Hibiscus syriacus. These compounds were identified as 2,7-dihydroxy-6-methyl-8-methoxy-1-naphthalenecarbaldehyde, 2-hydroxy-6-hydroxymethyl-7,8-dimethoxy-1-naphthalenecarbaldehyde, 1-carboxy-2,8-dihydroxy-6-methyl-7-methoxynaphthalenecarbolactone (1-->8), respectively, on the basis of various spectral studies. The compounds inhibited lipid peroxidation with IC50s of 0.54, 5.90 and 1.02 micrograms ml-1, respectively. The first compound also showed cytotoxicity against some human cancer cell lines with an ED50 of 1.5-2.4 micrograms ml-1.

Combined treatment of radiotherapy and hyperthermia for unresectable hepatocellular carcinoma.

Eighty-four patients with unresectable primary hepatocellular carcinoma due either to locally advanced lesion or to association with liver cirrhosis were treated with combined radiotherapy and hyperthermia from April 1988 to January 1991. Purpose of this study was to assess thermometry, response rate, toxicity, and survival in those patients. External radiotherapy was given with a total of 30.6 Gy/3.5 wks. Hyperthermia was given twice a week with a total of 6 treatment sessions using an 8 MHz radiofrequency capacitive type heating machine. Each hyperthermia session was started within 30 min following radiotherapy and continued for 30-60 min. Thermal data were analysed with maximum, minimum, and average temperatures of the tumors. Thermal mapping was also done. In thermometry results, maximum, minimum, and average temperatures of the tumors were 41.9 +/- 1.3 degrees C, 39.9 +/- 1.0 degrees C, and 40.8 +/- 0.9 degrees C, respectively. The fraction over 40 degrees C was 73 +/- 32% with a wide variation from 15% to 100%. Among 67 assessable patients, 27 patients showed tumor regression of more than 50% of the original tumor volume (40.3% response rate). Symptomatic improvement was observed in 78.6% of the patients. Acute toxicities during the treatment were mostly acceptable local pain (51.2%) and local fat necrosis (13.1%). The actuarial 1-year, 2-year, and 3-year survival rates were 44.8%, 19.7%, and 15.6%, respectively. Median survival was 6 months. In view of acceptable toxicities and the current rate of survival, further evaluation of combined treatment of radiotherapy and hyperthermia for unresectable hepatocellular carcinoma is warranted.

Histological studies of surgically resected hepatocellular carcinoma following combined radiotherapy and hyperthermia.

Four cases of hepatocellular carcinoma (HCC) were surgically resected following combined radiotherapy (RT) and hyperthermia (HT). Complete necrosis of the tumor without viable tumor cell was found in one case and extensive tumor necrosis was observed in the other three cases; the percentage of necrosis in the specimens were 40%, 70%, and 80%, respectively. Histologic assessment showed mainly coagulative necrosis in the tumor with focal liquefactive necrosis. Cystic dilatation of sinusoids was observed in both tumor and nontumorous normal liver tissue. Other changes in normal liver tissue were unremarkable except for infiltration of inflammatory cells, fatty change, and proliferation of the bile ducts which can usually be seen beyond the area where any space occupying lesions are present. It is concluded that combined radiotherapy and hyperthermia can significantly induce coagulative necrosis of hepatocellular carcinoma with nonsignificant minimal histologic changes in adjacent nontumorous liver tissue.