Emergence of YMDD Motif Mutant Hepatitis B Virus during Short-term Lamivudine Therapy

Background/Aims: The emergence of lamivudine-resistant mutant hepatitis B virus (HBV), with aminoacid substitution in the YMDD motif of DNA polymerase, has been reported in the long-term lamivudine use group. However there is no report about the emergence of mutant viruses during the short-term lamivudine therapy. The objective of this study was to investigate the emergence of YMDD mutant HBV during short-term lamivudine therapy. Methods: We evaluated twenty-eight chronic hepatitis B patients who were HBeAg and HBV DNA positive and treated with lamivudine 100mg p.o. daily for 12 weeks. First, we investigated the emergence of YMDD mutants by nested polymerase chain reaction (PCR) method developed by Chayama et al in 19 patients who lost HBV DNA during lamivudine therapy but showed HBV DNA re-emergence 2 weeks after the end of therapy. Second, DNA subcloning and sequencing of HBV DNA polymerase including YMDD motif was undertaken in one patient's serial blood samples at 0, 8, 12 weeks to confirm the results of nested PCR. Results: YMDD motif mutation was detected in 17(90%) out of 19 patients at the end of therapy and the type of mutations were YIDD only. At the end of therapy, mutant was predominant in 5 patients, both mutant and wild type were similar in proportion in 3 patients, and wild type was predominant in 9 patients. When we carried out nested PCR serially with samples of 0, 2, 4, 8, 12, 14 weeks after initiation of therapy in 5 patients who were mutant predominant at 12 weeks, YIDD mutant began to be detected from 2 weeks in 4 patients and from 4 weeks in one patient. However, rapid turnover from mutant to wild type happened after the end of therapy, so only wild type was detected in 3 patients and wild type became predominant in 2 patients at 2 weeks after the end of therapy. All the sequencing results of serial blood samples in one patient were consistent with nested PCR data. Conclusions: The presence of YMDD motif HBV polymerase mutant may be possible before administration of lamivudine in Korean chronic hepatitis B patients. Nested PCR assay would be an useful method to detect YMDD mutant.ope

The Effect of Long-term Lamivudine Therapy for Chronic Liver Disease due to Hepatitis B Virus

Background/Aims : We studied to evaluate the virological and biochemical responses to lamivudine and to detect YMDD mutants in patients who received long-term lamivudine therapy. Method : We conducted a one-year trial of lamivudine in 45 Korean patients with chronic liver disease due to hepatitis B virus. The patients were treated with a single oral average dose of 100 mg of lamivudine every day for 12 months. Results : The suppression of serum HBV DNA was sustained in 77.8% of the patients and the normalization of serum ALT in 80%. The proportions of patients with HBeAg seroconversion were 25%. YMDD mutants were detected in 4 of 8 patients who showed sustained HBV DNA and serum ALT response (n=31) and in 3 of 8 patients who showed HBV DNA or serum ALT breakthrough (n=9). The response to lamivudine therapy in HBeAg-negative patients was excellent. Conclusion : Lamivudine therapy resulted in a significant virological and biochemical improvements and were well tolerated. But, YMDD mutants were detected during lamivudine therapy.ope

Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is a chronic cholestatic autoimmune liver disease that predominantly affects middle-aged women. It is characterized by slowly progressive destruction of the small intrahepatic bile ducts together with portal inflammation, and this initially leads to fibrosis and later to cirrhosis. It is currently accepted that the pathogenesis of PBC is multifactorial with genetic and environmental factors interplaying to determine the disease onset and progression. In addition to antimitochondrial antibody (AMA), which is the hallmark of PBC and is detected in at least 90% of the patients, other autoantibodies (antinuclear antibody, anti-smooth muscle antibody and rheumatoid factor, etc.) may also be found in the patients. There is no correlation between the titer of AMAs and the disease severity. Most patients are diagnosed either during the asymptomatic phase of PBC or after presenting with non-specific symptoms. Pruritus and fatigue are the most common symptoms of PBC. The prognosis of PBC has improved significantly during the last few decades. Patients are now diagnosed earlier in its clinical course, they are more likely to be asymptomatic at diagnosis and they are more likely to receive medical treatment. A wide variety of drugs have been assessed for the treatment of this condition: such immunosuppressive agents as corticosteroids, cyclosporine and azathioprine have a weak effect on the disease’s natural history. Ursodeoxycholic acid (UDCA) is the only currently approved medical treatment. For PBC patients with end-stage liver disease or an unacceptable quality of life, liver transplantation is the only accepted therapeutic option. Early diagnosis and treatment of PBC are important because effective treatment with UDCA has been shown to delay disease progression and improve rate survival in the early stage.ope

Prospective Study on Efficacy of Oral Supplement of Branched - Chain Amino Acid Granules on the Nutritional Status of the Cirrhotics

Background / Aims : A prospective comparative study was conducted to investigate the efficacy of orally administered branched-chain amino acids(BCAA) in cirrhotic patients. Methods : Forty-seven patients with liver cirrhosis of viral etiologies, whose hypoalbunemia could not be corrected with adequate protein intake, were randomly assigned to either the BCAA group(n=31) or the control group(n=16). The selection criteria were ages between 16 and 70 years, patients whose Child-Pugh scores were less than 13 points and who were willing to participate in the study. Most patients(87.1%) belonged to Child -Pugh class B. Patients in the BCAA group received oral supplementation with branced-chain amino acid granules(12g/day, each packet containing total 4g of BCAA , i.e.leucine, 1904 mg ; valine, 1144mg; isoleucine, 952mg) for 12 weeks. Patients had complete blood counts and chemistry at entry and once every month. Serum ferritin and amino acid concentrations in plasma were determined. Anthropometric parameters including body weight, body fat contents and body mass index were assessed at the beginning and at the end of the 3-month period. Results : In the BCAA group, there was a significant increment in plasma levels of isoleucine, valine(p<0.001) whereas levels of aromatic amino acids did not show substantial change. Total BCAA concentration and BCAA/AAA(aromatic amino acid) molar ratio(Fischer`s ratio) also increased significantly after administration of oral BCAA (p<0.02). In contrast, patients in the control group showed no significant change in assessed parameters. Conclusion : Oral supplementation of BCAA to or other serious adverse effects.ope

Simultaneous Isolation of Vibrio vulnificus and Vibrio parahaemolyticus in Blood from a Liver Cirrhosis Patient: Importance of Detection and Identification of Both Species

A 56-year-old woman with underlying liver cirrhosis was hospitalized with chief complaints of fever, which developed after eating raw fish on the previous day. On physical examination, she showed hypotension. Vibrio vulnificus and Vibrio parahaemolyticus strains were simultaneously isolated from blood cultures, and the patient recovered after treatment with antibiotics including cefotaxime. To our knowledge, simultaneous isolation of both V vulnificus and V parahaemolyticus from the blood has never been documented before in Korea or any other countries. When blood cultures from a patient with underlying disease such as liver disease show growth of gram-negative bacilli in the summer months, microbiologists in Korea, where Vibrio infection is prevalent, should be aware of the possi￢bility that V. vulnificus and other Vibrio spp. can be isolated simultaneously. An accurate identifica￢tion of all isolates is important, because antimicrobial susceptibility patterns. severity and prognosis of the infection are different significantly depending on species.ope

Clinical Characteristics of Gastroesophageal Reflux Diseases and Association with Helicobacter pylori Infection

Background/Aims: The prevalence of gastroesophageal reflux disease (GERD) in Korea was believed to be low until now. Korea is now believed to be on the evolving stage of GERD in its' prevalence. The aims of this study were to evaluate the epidemiologic and clinicopathologic characteristics among the subgroups of GERD i.e. non-erosive GERD (NERD), erosive GERD (ERD) and Barrett's esophagus (BE), and the role of Helicobacter pylori (H. pylori) infection in the pathogenesis of GERD. Methods: A total of 253 patients with typical symptoms of GERD who underwent EGD were enrolled from October 2002 to January 2004. Patients were grouped as NERD, ERD or BE based on the symptoms and endoscopic findings. BE was histologically confirmed if necessary. Various clinical parameters including the status of H. pylori infection were analyzed. Results: Among 253 patients, 106 patients were classified as NERD while 116 and 31 patients were classified as ERD and BE group respectively. BE and ERD group showed no gender predilection while NERD showed female preponderance (2.31:1, p＜0.05). NERD group were younger (49.57 y.o.) than BE (57.87 y.o.) and ERD (52.30 y.o.) group. About three quarters of the patients of erosive esophagitis were LA-A (74.2%) grade. This suggests the mild nature of erosive esophagitis in Korea. ERD showed significantly higher BMI (kg/m2) compared to NERD (p＜0.05). Hiatal hernia was frequently associated with BE and ERD (p＜0.05), but less frequently in NERD. Overall H. pylori positivity among GERD was significantly lower than the age and gender matched control group (p＜0.05). Conclusions: Subgroups of GERD in Korea showed different epidemiologic and clinical characteristics. Lower rate of H. pylori infection among GERD group may reflect the protective role of H. pylori infection regarding GERD prevalence in Korea.ope

Reappraisal of Risk Factors Predicting Liver Complications from Radiotherapy for Hepatocellular Carcinoma

Background/Aims: Determination of the optimal radiotherapeutic parameters for radiotherapy of hepatocellular carcinoma (HCC) is still under investigation. The purpose of this study is to identify the risk factors associated with radiation-related morbidity. Methods: We evaluated one hundred fifty-eight patients, who were given radiotherapy for HCC between January 1992 and March 2000. Radiation-induced liver disease (RILD) was defined as the development of nonmalignant ascites without disease progression and an anicteric elevation of the alkaline phosphatase level by at least twofold. Gastrointestinal toxicity was assessed by using the RTOG-EORTC scale. Results: Six patients (3.8%) displayed RILD. In these patients, three patients had not responded to other previous treatments. Two patients with portal vein thrombosis or huge sized mass, above 10 cm, showed liver toxicity and two other patients presented with Child-Pugh class B liver cirrhosis. Eight patients (5%) had gastro-duodenal ulcers. In one of these 8 patients, the left lobe close to the stomach was involved and two patients had been treated for gastro-duodenal ulcer. In two more patients, the radiation field, with using anterior/posterior radiation ports, covered a significant volume of the gastrointestinal tract. One of eight patients had been irradiated with a large fraction size (250 cGy). Conclusions: The efforts should be made to reduce the radiation-related complications for hepatocellular carcinoma by considering the volume and the function of remaining liver, the location of tumor, the tumor size and the severity of liver cirrhosisope

Recombinant interferon-Beta-1alpha plus ribavirin for the treatment of chronic HCV infection: a prospective, randomized, comparative pilot study

BACKGROUND/AIMS: Interferon beta (IFN-beta) has been shown to have antiviral activity, and thus could be useful in treating viral infections. Therefore, we compared the efficacy and safety of recombinant IFN-beta (IFN-beta-1a) plus oral ribavirin versus interferon alpha (IFN-alpha) plus ribavirin therapy for the treatment of chronic hepatitis C (HCV). METHODS: Twenty treatment-naïve patients were randomized into two equal-sized treatment groups. Both IFN-beta-1a (44 microg) and IFN-alpha (3 MIU) were given subcutaneously three times a week, while ribavirin was given orally at 1,000-1,200 mg/day. Patients were treated for 24 weeks and followed for an additional 24 weeks. RESULTS: After 24 weeks of treatment, six (60%) and four patients (40%) in the IFN-beta-1a group and IFN-alpha groups, respectively, achieved viral clearance. The sustained virological response (SVR) at the end of the observation period was similar in both groups (40%). However, the baseline viral load was significantly higher (p=0.034) in the IFN-beta-1a group than in the IFN-alpha group, and there were more HCV genotype 1 patients in the IFN-beta-1a group (eight versus seven). The IFN-beta-1a group was associated with similar adverse events in terms of frequency and severity. CONCLUSIONS: The SVR rate and safety profile were similar for the combination of IFN-beta-1a and ribavirin and that of IFN-alpha and ribavirinope

The effect of preoperative transcatheter hepatic arterial chemoembolization in the treatment of hepatocellular carcinoma

Background: Transcatheter hepatic arterial chemoembolization (TACE) is used for curative or palliative treatment of hepatocellular carcinoma (HCC). However, it is neither well known how much TACE induces tumor necrosis histologically, nor whether preoperative TACE has benefit for resectable HCC. The purpose of this study is to measure the degree of tumor necrosis induced by one session of TACE and to evaluate the effect of preoperative TACE for resectable HCC. Methods: Between January 1999 and January 2004, 20 HCC patients with one session of preoperative TACE (TACE group) and 36 HCC patients with only preoperative hepatic angiography, without TACE (angiography group) were enrolled. Results: In TACE group, 12 patients had tumor necrosis of 100%, 5 patients having between 80% and 99%, and 3 patients less than 50%. The mean tumor necrosis rate of HCC less than 5 cm in diameter were 84.7%, while 90.5% in larger size (>5 cm in diameter) of HCC (p>0.05). The mean tumor necrosis rate of the recurred patients in TACE group and in angiography group was 98.75 and 17.5% (p=0.02), respectively. Disease free survival time of the recurred patients in TACE and in angiography group was 16.75 and 20.25 months, respectively (p=0.77). Conclusions: The tumor size was not related with the degree of tumor necrosis and no relevant factors could be found. Although the mean tumor necrosis was greater in TACE group than in angiography group, the disease free survival time was not different between the two groups.ope

Curative Resection of Advanced Hepatocellular Carcinoma (TNM stage 4a) after Concurrent Chemo-Radiation Therapy: A Case Report

Hepatocellular carcinoma (HCC) with portal vein thrombosis is a difficult form of HCC to treat. Therefore, no specific treatment mordality has been absent. Here, we present a patient diagnosed as hepatocellular carcinoma with right portal vein thrombosis (stage IVa). The patient had been treated with concurrent chemo-radiation therapy (CCRT) for five weeks. After CCRR, tumor size was markedly decreased. Two courses of additional transcatheter arterial chemoembolization (TACE) and five courses of intraarterial 5-fluorouracil (5-FU)/cisplatin infusion were performed. Follow-up computerized tomography (CT) scan showed about 2cm-sized nodular lesion at lateral margin of right hepatic lobe. On angiography, it was shown that both the mass and intestine were commonly supplied by omental artery. For the treatment of the mass, right hepatic lobectomy was undertaken.ope