Switching to tenofovir vs continuing entecavir for hepatitis B virus with partial virologic response to entecavir: a randomized controlled trial.

Entecavir 0.5 mg (ETV) is widely used among treatment-naïve chronic hepatitis B (CHB) patients. However, 10%-30% of patients show partial virologic response (PVR) to the drug. If the hepatitis B virus (HBV) continues to replicate, the underlying liver disease may progress. Herein, we compared the efficacy of switching to tenofovir disoproxil fumarate (TDF) with that of continuing ETV in CHB patients with PVR to ETV. This was an open-label randomized controlled trial including CHB patients who had been receiving 0.5 mg of ETV for >12 months, but who still had detectable HBV DNA levels of >60 IU/mL without known resistance to ETV. Sixty patients were enrolled and 45 qualified for the study: Twenty-two patients were randomly assigned into the TDF group and 23 into the ETV group. After 12 months of treatment, the virologic response rate (HBV DNA <20 IU/mL) was significantly higher in the TDF group than in the ETV group, as measured using per-protocol analysis (55% vs 20%; P = .022) and intention-to-treat analysis (50% vs 17.4%; P = .020). The reduction in HBV DNA was greater (-1.13 vs -0.67 log10 IU/mL; P = .024), and the mean HBV DNA level was lower (1.54 vs 2.01 log10 IU/mL; P = .011) in the TDF group than in the ETV group. In conclusion, to achieve optimal response in CHB patients with PVR to ETV, switching to TDF would be a better strategy than continuing ETV. Appropriate modification of therapy would further improve the outcome of chronic HBV infection.

A phase 3b study of sofosbuvir plus ribavirin in treatment-naive and treatment-experienced Korean patients chronically infected with genotype 2 hepatitis C virus.

In Korea, patients with chronic hepatitis C virus (HCV) infection are typically treated with pegylated interferon-alpha plus ribavirin, but interferons are contraindicated in many patients and are often poorly tolerated, particularly by the elderly and those with advanced liver disease. No interferon-free treatment regimens are approved in Korea. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV nonstructural 5B RNA polymerase. It is approved in the USA, European Union and Japan for treating a number of HCV genotypes, including genotype 2. Genotype 2 has a seroprevalence of 38-46% in Korea. This single-arm, phase 3b study (NCT02021643) examined the efficacy and safety of sofosbuvir plus ribavirin (12-week duration) in chronic genotype 2 HCV-infected treatment-naive and treatment-experienced Korean patients with and without cirrhosis. The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 97% (125/129), with 96% (101/105) of treatment-naive and 100% (24/24) of treatment-experienced patients achieving SVR12. Two patients experienced virologic failure (n = 1, on-treatment failure; n = 1, relapse). No patient discontinued study treatment due to an adverse event (AE). The most common treatment-emergent AEs were headache (18%, 23/129) and pruritus (15%, 19/129). Few patients had grade 3 AEs (5%, 6/129) or grade 3 laboratory abnormalities (12%, 15/129). No grade 4 AE was reported. These data suggest that 12 weeks of treatment with the all-oral, interferon-free regimen of sofosbuvir plus ribavirin is effective and well tolerated in Korean patients with chronic genotype 2 HCV infection.

Classification by causes of dark circles and appropriate evaluation method of dark circles.

BACKGROUND: Dark circles refer to a symptom that present darkness under the eyes. Because of improvement in the quality of life, the dark circles have been recognized as one of major cosmetic concerns. However, it is not easy to classify the dark circles because they have various causes. METHODS: To select suitable instruments and detailed evaluation items, the dark circles were classified according to the causes through visual assessment, Wood's lamp test, and medical history survey for 100 subjects with dark circles. After the classification, were newly recruited for instrument conformity assessment. Through this, suitable instruments for dark circle evaluation were selected. We performed a randomized clinical trial for dark circles, a placebo-controlled double-blind study, using effective parameters of the instruments selected from the preliminary test. RESULTS: Dark circles of vascular type (35%) and mixed type (54%), a combination of pigmented and vascular types, were the most common. Twenty four subjects with the mixed type dark circles applied the test product (Vitamin C 3%, Vitamin A 0.1%, Vitamin E 0.5%) and placebo on randomized split-face for 8 weeks. The effective parameters (L*, a, M.I., E.I., quasi L*, quasi a* and dermal thickness) were measured during the study period. Result showed that the L* value of Chromameter(®) , Melanin index (M.I.) of Mexameter(®) and quasi L* value obtained by image analysis improved with statistical significance after applying the test product compared with the placebo product. CONCLUSION: We classified the dark circles according to the causes of the dark circles and verified the reliability of the parameter obtained by the instrument conformity assessment used in this study through the efficacy evaluation. Also based on this study, we were to suggest newly established methods which can be applied to the evaluation of efficacy of functional cosmetics for dark circles.

A study on seasonal variation of skin parameters in Korean males.

OBJECTIVE: The physiological characteristics of the skin are varied greatly, depending on gender, age, region and race, and many dermatologic researches have been performed through various research methods. This study aimed to examine how Korean men's skin conditions were influenced by temperature or humidity changes caused by seasonal rotations. METHODS: A total of 100 healthy Korean men, age range 20-59 years, participated in the study for both summer and winter. We compared on the characteristics of skin between summer and winter. The skin hydration, skin pH and TEWL were evaluated on the forehead, cheek and forearm. The skin sebum content of the glabella, nasal ala and cheek was measured using Sebumeter(®) (SM810, Courage+Khazaka, Germany). Cutometer(®) (MPA 580 Courage+Khazaka, Germany) the elasticity was measured by on the cheeks, and PRIMOS lite(®) (Phase shift Rapid in vivo Measurement of Skin, GFMesstechnik GmbH, Germany) was used to evaluate wrinkles on crow's feet. Lastly, in addition, the skin pore of the face was measured using the Janus(®) (PSI, Korea) which is a facial analysis system. RESULTS: The results were as follows: the comparison of hydration in summer and winter shows significant differences in their forehead, cheeks and forearm. The pH values of the skin surface were generally higher in winter, and significantly different on each site, and the sebum content was higher in summer than in winter. As a result of the pore measurement, the summer showed more pores compared to the winter, and there was a statistically significant difference in skin pores between summer and winter. The sensitivity measured by stinging test increases significantly more in winter than in summer. However, there were no seasonal differences in wrinkles and skin brightness. CONCLUSION: The skin surface pH, TEWL, sebum content, hydration, elasticity, wrinkles, skin pore and skin sensitivity vary with seasons and body regions in Korean men.

Virologic and biochemical responses to clevudine in patients with chronic HBV infection-associated cirrhosis: data at week 48.

Clevudine shows high rates of virologic and biochemical responses in patients with chronic hepatitis B. However, the efficacy and safety of clevudine in patients with cirrhosis are unknown. The aims of this study were to evaluate the safety and to assess the virologic and the biochemical responses to clevudine in patients with cirrhosis with chronic hepatitis B virus (HBV) infection. We reviewed data from treatment-naïve patients with chronic hepatitis B with and without cirrhosis who started clevudine between April 2007 and March 2008 (n = 52, hepatitis B without cirrhosis n = 21 and chronic hepatitis B with cirrhosis n = 31) at Korea University Ansan/Guro Hospital. All of the patients were treated for more than 48 weeks. The mean age was older in the patients with cirrhosis. Baseline HBV DNA levels were 6.9 and 7.78 log copies/mL (P = 0.042), and alanine aminotransferase (ALT) levels were 104.9 and 147.4 IU/L (P = 0.204), for those with and without cirrhosis, respectively. Virologic response (HBV DNA <1000 copies/mL) (87.1%vs 71.4%, P = 0.24) and biochemical response (83.9%vs 80.9%, P = 0.99) at week 48 were not significantly different between the two groups. Early virologic response at week 12 was even higher in the patients with cirrhosis (61.3%vs 28.6%, P = 0.026). Neither ALT flare nor newly onset hepatic decompensation was found in the patients with cirrhosis, whereas ALT flare was transiently observed in 14.3% of the chronic hepatitis group. In conclusion, although clevudine may produce a transient elevation of ALT during the early treatment period, such findings were not observed in patients with cirrhosis and the virologic and biochemical responses of the groups were comparable.

Differences in the prevalence of colorectal polyps in patients undergoing endoscopic removal of gastric adenoma or early gastric cancer and in healthy individuals.

BACKGROUND AND AIMS: We compared the prevalence of adenomatous and cancerous colon polyps in patients who underwent endoscopic removal of gastric neoplasms and in healthy controls. MATERIALS AND METHODS: This retrospective study reviewed the medical records of 186 patients with gastric neoplasms and 186 healthy subjects from January 2002 to October 2008. The gastric neoplasm group was comprised of patients undergoing endoscopic removal of gastric adenomas or early gastric cancers and serial fiberoptic colonoscopy (FCS) for checkups. The control group was comprised of subjects undergoing fiberoptic esophagogastroduodenoscopy (FEGD) and FCS for general checkup and was matched for age and sex with the gastric neoplasm group. Advanced colonic neoplasm was defined by any of the following: (1) the presence of three or more polyps; (2) polyp size at least 1.0 cm; (3) high-grade dysplasia or adenocarcinoma confirmed by histopathologic examination. RESULTS: Of the 372 persons, colorectal polyps were detected in 124 (33.3 %), advanced colonic neoplasms in 44 (11.8 %), and adenocarcinomas in 10 (2.7 %). The overall prevalence of adenomatous or cancerous polyps ("all polyps") and the prevalence of advanced colonic neoplasms were significantly higher in the gastric neoplasm group than in the control group (all polyps: 40.9 % in the gastric neoplasm group vs. 25.8 % in the control group, P = 0.002; advanced colonic neoplasms: 15.6 % vs. 8.1 %, P = 0.025). The risk factors for all polyps were age, male sex, diabetes mellitus, and being assigned to the gastric neoplasm group, and those for advanced colonic neoplasms were age and being assigned to the gastric neoplasm group. Confining the analysis to the gastric neoplasm group, the risk factors for all polyps were identical with those for the total group; however, those for advanced colonic neoplasm were different (age vs. diabetes and hypertriglyceridemia). CONCLUSION: Endoscopists should consider performing routine FCS in patients undergoing endoscopic removal of gastric neoplasms.

Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE).

Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naïve hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE). 129 patients were randomly assigned 2:1 to Pexa-Vec plus BSC vs. BSC alone. Pexa-Vec was given as a single intravenous (IV) infusion followed by up to 5 IT injections. The primary endpoint was OS. Secondary endpoints included overall response rate (RR), time to progression (TTP) and safety. A high drop-out rate in the control arm (63%) confounded assessment of response-based endpoints. Median OS (ITT) for Pexa-Vec plus BSC vs. BSC alone was 4.2 and 4.4 months, respectively (HR, 1.19, 95% CI: 0.78-1.80; p = .428). There was no difference between the two treatment arms in RR or TTP. Pexa-Vec was generally well-tolerated. The most frequent Grade 3 included pyrexia (8%) and hypotension (8%). Induction of immune responses to vaccinia antigens and HCC associated antigens were observed. Despite a tolerable safety profile and induction of T cell responses, Pexa-Vec did not improve OS as second-line therapy after sorafenib failure. The true potential of oncolytic viruses may lie in the treatment of patients with earlier disease stages which should be addressed in future studies. ClinicalTrials.gov: NCT01387555.

Risk Factors for Dropout From the Liver Transplant Waiting List of Hepatocellular Carcinoma Patients Under Locoregional Treatment.

BACKGROUND: In new organ allocation policy, patients with hepatocellular carcinoma (HCC) experience a 6-month delay in being granted Model for End-Stage Liver Disease exception points. However, it may not be fair for patients at risk of early progression of HCC. METHODS: All patients who were diagnosed as United Network for Organ Sharing (UNOS) stage 1 or 2 of HCC between January 2004 and December 2012 were included. Patients who received surgical resection or liver transplant (LT) as a primary treatment and who did not receive any treatment for HCC were excluded. Patients with baseline Model for End-Stage Liver Disease score ≥22 were also excluded because they have a higher chance of receiving LT. Patients who developed extrahepatic progression within 1 year were considered as high-risk for early recurrence after LT. RESULTS: A total of 586 patients were included. Mean (SD) age was 59.9 (10.3) years and 409 patients (69.8%) were men. The cumulative incidence of estimated dropout was 8.9% at 6 months; size of the maximum nodule (≥3 cm) and nonachievement of complete response were independent factors. Extrahepatic progression developed in 16 patients (2.7%) within 1 year; size of the maximum nodule (4 cm) and alpha-fetoprotein level (>100 ng/mL) were independent predictors. CONCLUSIONS: The estimated dropout rate from the waiting list within 6 months was 8.9%. Advantage points might be needed for patients with maximum nodule size ≥3 cm or those with noncomplete response. However, in patients with maximum nodule size ≥4 cm or alpha-fetoprotein level >100 ng/mL, caution is needed.

Resistance to adefovir dipivoxil in lamivudine resistant chronic hepatitis B patients treated with adefovir dipivoxil.

BACKGROUND: Adefovir dipivoxil (ADV) is a potent nucleotide analogue against both the wild-type and lamivudine (LMV) resistant hepatitis B virus (HBV). The cumulative incidence of ADV resistant mutations in the nucleoside/-tide treatment naive chronic hepatitis B patient (CHB) at weeks 48, 96, and 144 was 0, 0.8-3%, and approximately 5.9%, respectively. AIMS: The aim of this study was to characterise the genotypic and phenotypic mutation profiles to ADV in 67 LMV resistant CHB patients who were treated with ADV. METHODS: Serum HBV DNA was quantified by real time polymerase chain reaction. The ADV mutant was detected using matrix assisted laser desorption/ionisation time of flight mass spectrometry based genotyping assays, termed restriction fragment mass polymorphism (RFMP). RESULTS: RFMP analysis revealed that a total of 11 amino acid substitutions developed in the rt domain of the HBV polymerase in nine patients. The cumulative incidence of genotypic ADV resistance at months 12 and 24 was 6.4% and 25.4%, respectively. The rtA181V, rtN236T, and rtA181T mutations were detected in five, four, and two of the 67 patients at treatment months 12-17, 3-19, and 7-20, respectively. Serial quantification of serum HBV DNA revealed that two patients with the rtA181V mutation, with or without the rtN236T mutation, and one patient with the rtA181T mutation displayed HBV DNA rebound. CONCLUSION: Emergence of the ADV mutation in LMV resistant patients who are treated with ADV appeared to present earlier and more frequently than was reported in previous studies on nucleoside/-tide treatment naive patients.

Systematic review with meta-analysis: the efficacy and safety of tenofovir to prevent mother-to-child transmission of hepatitis B virus.

BACKGROUND: Preventing mother to child transmission of chronic hepatitis B infection in the setting of a high maternal viral load is challenging. The idea has emerged from antepartum tenofovir treatment with combination immunoprophylaxis. AIMS: To demonstrate the efficacy and safety of tenofovir to prevent mother to child transmission of hepatitis B virus. METHODS: PubMed, EMBASE, and Cochrane databases were searched through August 16, 2016. Comparative trials of second or third trimester tenofovir administration vs. controls for patients with chronic hepatitis B infection and non-comparative case series assessing mother to child transmission rates and evaluating maternal and foetal safety outcomes were included. RESULTS: Ten studies (one randomised controlled trial, four non-randomised controlled trials and five case series) that enrolled 733 women were included. The pooled results from comparative trials (599 pregnancies) showed that tenofovir significantly reduced the risk of infant hepatitis B surface antigen seropositivity by 77% (odds ratio=0.23, 95% confidence intervals=0.10-0.52, P=.0004) without heterogeneity (I2 =0%). In the case series analysis (134 pregnancies), only two cases (1.5%) of mother to child transmission with extremely high maternal viral load and non-compliance to treatment were identified. Maternal and foetal safety parameters including congenital malformation and foetal death were re-assuring. CONCLUSIONS: For pregnant women with high hepatitis B virus DNA levels, tenofovir administration in the second or third trimester can prevent mother to child transmission when combined with hepatitis B immunoglobulin and the hepatitis B vaccine. Tenofovir is safe and tolerable for both the mother and foetus.

Endoscopic treatment in a case with extensive spontaneous intramural dissection of the oesophagus.

Spontaneous intramural dissection of the oesophagus has been recognized as a separate clinical entity between a transmural oesophageal rupture (Boerhaave syndrome) and an oesophageal mucosal tear (Mallory-Weiss syndrome). It is important to differentiate this condition from myocardiac infarction, dissecting aneurysm and other acute surgical conditions. Conservative management is usually thought to be adequate. We report a case of spontaneous intramural oesophageal dissection, in which the symptom of dysphagia did not improve with the conservative management and an endoscopic incision of the septum between true and false lumens using a needle-type diathermy knife was done safely and effectively.

Invasive pulmonary aspergillosis after living donor liver transplantation should be eradicated or not? A case report.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a rare complication with a high mortality rate after organ transplantation. Early antifungal therapy improves survival. In some cases, surgical resection is necessary for a complete remission. We have reported herein a case of sustained (but stationary) IPA cured by the modulation of immunosuppression with discontinuation of antifungal therapy. CASE: A 34-year-old man underwent liver transplantation experiencing are early bile leak and an acute rejection episode. Steroid pulse therapy was accompanied by intensified immunosuppression. After a week he developed intermittent hemoptysis, which was treated with antibiotics due to a diagnosis of pneumonia by chest X ray. Meanwhile the bile leak progressed to a huge biloma at reoperation 3 weeks after the initial operation he was converted from a choledochocholedochostomy to a hepaticojejunostomy. After 1 week, follow-up chest X ray showed the lesion had progressed to form an abscess. Subsequent chest computed tomography (CT) detected a pulmonary mass with internal necrosis and CT-guided lung biopsy revealed Aspergillus fumigatus on isolation. Antifungal therapy with voriconazole and/or amphotericin B for 3 months stopped disease progression but the lesion was sustained. We stopped antifungal therapy due to side effects and reduced the intensity of immunosuppression. Follow-up chest CT 5 months later showed improvement with a persistent cavitary lesion containing a fungal ball. However, after 9 months, there was no focal lesion in either lung. This unusual case of IPA was cured by reducing immunosuppression without antifungal therapy. CONCLUSION: IPA should be eradicated with prompt antifugal therapy, but stationary IPA can be observed cautiously while reducing immunosuppression.

Spinal cord injury subsequent to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma.

Transcatheter arterial chemoembolization is one of the most common treatment modalities for hepatocellular carcinoma. Transcatheter arterial chemoembolization is considered to be a relatively safe procedure, but transcatheter arterial chemoembolization is associated with a number of disastrous complications. Among the ischaemic complications caused by transcatheter arterial chemoembolization, spinal cord injury is very rare, but can occur via the intercostal or lumbar arteries. We report two cases of extremely rare spinal cord injuries after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. The patients had sensory loss below the T9 or T10 dermatomes and paraparesis or paraplegia within 6-8h after transcatheter arterial chemoembolization. One patient sustained paraplegia until death 2 months after transcatheter arterial chemoembolization and the other patient recovered almost completely 2 months after transcatheter arterial chemoembolization.

Cryoglobulinaemia and rheumatic manifestations in patients with hepatitis C virus infection.

OBJECTIVES: To investigate the association of cryoglobulinaemia and rheumatic manifestations in Korean patients with hepatitis C virus (HCV) infection. METHODS: Forty nine Korean patients with HCV infection were recruited. The prevalence, concentration, and type of cryoglobulin (by immunofixation), rheumatoid factor (RF), antinuclear antibody (ANA), and various rheumatological symptoms were investigated and HCV genotype was determined by polymerase chain reaction with genotype specific primer. RESULTS: The prevalence of cryoglobulin was 59% in Korean HCV patients and the concentration of cryoglobulin was 9.8 (7.9) g/l (mean (SD)). The type of cryoglobulinaemia was identified in 23 (80%) of 29 HCV patients with cryoglobulinaemia and they were all type III. There were no differences in age, sex, history of operation and transfusion, proportion of liver cirrhosis between the patients with cryoglobulinaemia and those without cryoglobulinaemia. The frequencies of RF and ANA were 14% and 3.4% respectively in HCV patients with cryoglobulinaemia. There was no difference in HCV genotype between the patients with cryoglobulinaemia and those without cryoglobulinaemia. Clinical features of HCV patients were as follows: arthralgia/arthritis (35%), cutaneous manifestation (37%), Raynaud's phenomenon (8%), paresthesia (44%), dry eyes (22%), dry mouth (10%), oral ulcer (33%), and abdominal pain (14%). However, these rheumatological symptoms did not differ between the two groups. CONCLUSION: Although the rheumatological symptoms were not different between HCV patients with and without cryoglobulinaemia, HCV patients showed various rheumatological manifestations. These result suggests that HCV infection could be included as one of the causes in patients with unexplained rheumatological symptoms.

Chronic liver disease in central Harlem: the role of alcohol and viral hepatitis.

For reasons not yet determined, chronic liver disease (CLD) has been a leading cause of excess morbidity and mortality in central Harlem. We conducted a case series and case-control analysis of demographic, clinical, epidemiological, and alcohol-intake-related information from patients with CLD and age- and sex-matched hospitalized control patients. Patients' sera were tested for markers of viral hepatitis. The presumed etiology of CLD among case-patients was as follows: both alcohol abuse and hepatitis C virus (HCV) infection, 24 persons (46% of case-patients); alcohol abuse alone, 15 (29%); HCV infection alone, 6 (12%); both alcohol abuse and chronic hepatitis B virus (HBV) infection, 3 (6%); and 1 each (2%) from: 1) schistosomiasis, 2) sarcoidosis, 3) unknown causes, and 4) alcohol abuse, chronic HBV, and HCV combined. In the case-control analysis, patients who had both alcoholism and either HBV (odds ratio [OR]: 6.3; 95% CI: 0. 5-334) or HCV (OR: 2.9; 95% CI: 1.3-6.2) were at increased risk for CLD, whereas patients who had only one of these three factors were not at increased risk for CLD. Patients who tested positive for the hepatitis G virus (HGV) did not have a significantly increased risk of CLD, and neither severity of CLD nor mortality was greater among these patients. Most patients in central Harlem who had CLD had liver damage from a combination of alcohol abuse and chronic viral hepatitis. Alcohol and hepatitis viruses appear to be synergistically hepatotoxic; this synergy appears to explain both the high rate of CLD in central Harlem and the recent reductions in this rate. Persons at risk for chronic HBV and HCV infection should be counseled about their increased risk of CLD if they consume excessive alcohol. Morbidity and mortality from liver disease could be decreased further by a reduction in alcohol consumption among persons who have chronic HBV and HCV infection, avoidance of needle sharing, and hepatitis B vaccination.

Jejunal inflammatory fibroid polyp presenting as intussusception--a case report with review of the literature.

A 52-year-old woman was presented with intermittent abdominal pain and vomiting for 10 days. Abdominal CT scan disclosed a dilated small bowel loop with a round solid mass in the right anterior supravesical space. The clinical impression was intussusception caused by small bowel tumor. She underwent an exploratory laparotomy. The macroscopic and microscopic findings confirmed an inflammatory fibroid polyp of jejunum causing intussusception. To the best of our knowledge, this was the 5th reported case of such a presentation in English medical literature.

A clinical study of hemorrhagic fever with renal syndrome caused by Seoul virus infection.

The clinical findings of 29 patients with hemorrhagic fever with renal syndrome (HFRS) caused by Seoul virus were evaluated and compared with the previously reported clinical findings of classic Korean hemorrhagic fever (KHF). The diagnoses of these patients were made by hemagglutination inhibition test. The results were as follows: 1) The disease occurred predominantly in males with a high incidence in the third and fourth decades of life. 2) The highest incidence of the disease occurred in October-December. 3) Major symptoms were fever, abdominal or flank pain, vomiting and myalgia. 4) Major signs were petechia, CVA tenderness, pharyngeal injection, and conjunctival infection, but these signs were much less common than in patients with classic KHF. 5) The treatments were mainly conservative and there was no fatal case in the study subjects. These findings suggest that the clinical course of Seoul virus infection may be much milder than that of classic KHF and the outcome may be more favorable.

Detection of hepatitis A viral RNA in sera of patients with acute hepatitis A.

BACKGROUND AND AIMS: The Detection of hepatitis A virus (HAV) is important for diagnosis and epidemiological studies of hepatitis A. The polymerase chain reaction (PCR) technique is a sensitive test to detect HAV-RNA in specimens. The aims of the present study were to clarify the detection rate of serum HAV-RNA by PCR and the natural history of HAV viraemia, and to determine the correlation between viraemia and the clinical characteristics in patients with acute hepatitis A. METHODS: Hepatitis A virus RNA was tested in 74 serum samples which were serially collected from 27 patients with acute hepatitis A. A nested reverse transcription (RT)-PCR for HAV-RNA was performed with primer sets located at the VP1 region of the HAV genome and the PCR products were electrophoresed on a 1.5% agarose gel. RESULTS: Hepatitis A virus RNA was found in 18 of 27 (67%) patients with hepatitis A. There were no significant differences between groups positive and negative for HAV-RNA in clinical and laboratory data, except the time interval between clinical onset and initial serum sampling for RT-PCR (10 +/- 6 vs 19 +/- 14 days) and the alanine aminotransferase (ALT) level at initial serum sampling for RT-PCR (1436 +/- 1416 vs 518 +/- 432 IU/L). The mean duration of HAV viraemia was 30 +/- 19 days (range, 5-59 days). The duration of HAV viraemia and duration of abnormal ALT levels from clinical onset were positively correlated (r = 0.685, P = 0.007). CONCLUSION: In conclusion, HAV-RNA RT-PCR is a useful tool to detect HAV viraemia and to study the molecular epidemiology of HAV infection.

Molecular epidemiology of hepatitis A virus in Korea.

BACKGROUND: The prevalence of antibodies for hepatitis A virus (anti-HAV) in adolescents and young adults has decreased remarkably following the economic growth in Korea. As a result, this age group has a high risk for HAV infection paradoxically, and over 1500 cases of clinically overt hepatitis A occurred in 1998. Human isolates of hepatitis A virus (HAV) are categorized within four genotypes (I, II, III, and VII). In some geographic regions, closely related isolates cluster, suggesting endemic spread of the virus, while in other regions multiple genotypes circulate. Virtually no data are available with regard to the genetic relatedness of Korean strains of HAV. METHODS AND RESULTS: A 168 base pair segment encompassing the putative VP1/2A junction of the HAV genome was amplified by RT-PCR and sequenced in sera of 18 Korean patients with a sporadic form of acute hepatitis A. Pairwise comparisons of the nucleic acid and amino acid sequences of 18 Korean isolates with one another revealed that the Korean isolates showed > 94.6% and > 96.4% identity, respectively. All of the 18 Korean isolates clustered within genotype IA, irrespective of the geographic locations and the time that hepatitis occurred. Unique amino acid sequence changes that had never been reported in genotype IA were found in nine of the 18 isolates. These changes were Gln-->Ser and Lys-->Arg in 2A-19 and 2A-10 amino acid positions. CONCLUSION: The presence of single genotype and unique mutations may be related with the circulation of endemic HAV over a long period of time in Korea.