Advanced hepatocellular carcinoma with hepatic vein tumor thrombosis and renal dysfunction after hepatic arterial infusion chemotherapy effectively treated by liver resection with active veno-venous bypass: report of a case.

BACKGROUND: Hepatocellular carcinoma (HCC) patients with hepatic vein tumor thrombosis (HVTT) extending to the inferior vena cava (IVC) have an extremely poor prognosis. Here we report a case of HCC with HVTT and renal dysfunction after hepatic arterial infusion chemotherapy (HAIC) successfully treated by liver resection and active veno-venous bypass. CASE PRESENTATION: A 77-year-old man was diagnosed to have a large HCC with intrahepatic metastases and HVTT extending to the IVC. Due to the advanced stage, HAIC with cisplatin was performed 13 times in a period of 17 months. As a consequence of this treatment, the size of the main HCC markedly decreased, and the advanced part of the HVTT went down to the root of the right hepatic vein (RHV). However, because of renal dysfunction, HAIC with cisplatin was discontinued and right hepatectomy with patch graft venoplasty of the root of the RHV was performed. Because progression of renal dysfunction had to be avoided, veno-venous bypass was activated during IVC clamping to prevent renal venous congestion and hypotension. Histological examination showed foci of a moderately differentiated HCC with extensive fibrosis and necrosis in the main HCC. Histologically, the HVTT in the RHV showed massive necrosis and tightly adhered to the vascular wall of the RHV. The postoperative function of the remnant liver was good, and no further deterioration of renal function was detected. The patient did not show signs of recurrence 15 month after surgery. CONCLUSION: In the present case, HAIC using cisplatin in combination with hepatic resection and patch graft venoplasty of the IVC provided a good long-term outcome with no HCC recurrence. Renal function was preserved by using active veno-venous bypass during IVC clamping to prevent renal venous congestion and hypotension.

Efficacy of sorafenib beyond first progression in patients with metastatic hepatocellular carcinoma.

AIM: We investigated whether continuous sorafenib administration keeps suppressing the growth of hepatocellular carcinoma (HCC) after first progressive disease (PD), and whether it prolongs patients' survival. METHODS: The size of metastatic lesions was measured in 36 patients with advanced HCC treated with sorafenib. The tumor growth rates before and after radiological PD as well as survival were compared between the patients who continued (n = 23) and stopped (n = 13) sorafenib at first radiological PD. RESULTS: The growth rate did not differ between before and after PD in patients who continued sorafenib, while it increased after PD in patients who stopped sorafenib at PD (P = 0.002). Survival beyond first progression was longer in patients who continued sorafenib than in those who stopped it at PD (P = 0.012), and this tendency was observed even when the analysis was limited to Child-Pugh class A patients (P = 0.085). CONCLUSION: Sorafenib administration beyond first radiological PD could continuously suppress HCC growth and may have survival benefit.

Hepatitis B virus core promoter mutations G1613A and C1653T are significantly associated with hepatocellular carcinoma in genotype C HBV-infected patients.

BACKGROUND: Hepatitis B virus (HBV) is a major cause of hepatocarcinogenesis.To identify mutations relevant to hepatocellular carcinoma (HCC) development, we compared the full genome sequences of HBV from the sera of patients with and without HCC. METHODS: We compared the full genome sequences of HBV isolates from 37 HCC patients (HCC group 1) and 38 patients without HCC (non-HCC group 1). We also investigated part of the core promoter region sequences from 40 HCC patients (HCC group 2) and 68 patients without HCC. Of the 68 patients who initially did not have HCC, 52 patients remained HCC-free during the follow-up period (non-HCC group 2), and 16 patients eventually developed HCC (pre-HCC group 2). Serum samples collected from patients were subjected to PCR, and the HBV DNA was directly sequenced. RESULTS: All patients had genotype C. A comparison of the nucleotide sequences of the HBV genome between HCC group 1 and non-HCC group 1 revealed that the prevalence of G1613A and C1653T mutations in the core promoter region was significantly higher in the HCC group. These mutations tended to occur simultaneously in HCC patients. Multivariate analysis with group 2 revealed that the presence of HCC was associated with aging and the double mutation. Future emergence of HCC was associated with aging and the presence of a single G1613A mutation. CONCLUSIONS: G1613A and C1653T double mutations were frequently found in patients with HCC. A single G1613A mutation was associated with future emergence of HCC. These mutations may serve as useful markers in predicting HCC development.

Efficacy and cost-effectiveness of consensus interferon monotherapy with high-dose induction for hepatitis C patients with genotype 2.

OBJECTIVE: Several treatment strategies for patients with chronic hepatitis C have been compared mainly in terms of their efficacy, and it has been found that pegylated interferon (IFN) plus ribavirin has become the standard therapy, but aged patients may not tolerate ribavirin and the cost-effectiveness of treatment should also be further considered. We conducted a study to evaluate the efficacy, safety, and cost-effectiveness of consensus IFN monotherapy with high-dose induction for patients with chronic hepatitis C in clinical practice. MATERIAL AND METHODS: We consecutively enrolled 104 patients with chronic hepatitis C. Patients were scheduled to receive 12 or 18 µg of consensus IFN daily for 2 weeks, then three times a week for 22 weeks. Efficacy, safety, and cost-effectiveness were assessed. A Markov model was developed to investigate cost-effectiveness in patients with chronic hepatitis C treated by different IFN-based treatment strategies. RESULTS: Of the 104 study patients, a sustained virological response (SVR) was achieved in 66 (63%). Logistic regression analysis revealed that genotype 2, lower hepatitis C virus RNA levels, and patient age were independently associated with SVR. The response rate was significantly higher in patients with genotype 2 (51/66, 77%) versus genotype 1 (15/38, 40%). Cost-effectiveness analysis in patients with genotype 2 revealed that high-dose induction with consensus IFN monotherapy was as highly cost-effective as pegylated IFN plus ribavirin. CONCLUSION: Consensus IFN monotherapy with high-dose induction shows high efficacy and cost-effectiveness in chronic hepatitis C patients with genotype 2 infection. Thus, it may be a reliable alternative in aged patients and for those excluded from standard combination therapy.

Mechanism of entecavir resistance of hepatitis B virus with viral breakthrough as determined by long-term clinical assessment and molecular docking simulation.

The mechanism by which entecavir resistance (ETVr) substitutions of hepatitis B virus (HBV) can induce breakthrough (BT) during ETV therapy is largely unknown. We conducted a cross-sectional study of 49 lamivudine (LVD)-refractory patients and 59 naïve patients with chronic hepatitis B. BT was observed in 26.8% of the LVD-refractory group during weeks 60 to 144 of ETV therapy. A line probe assay revealed ETVr substitutions only in the LVD-refractory group, i.e., in 4.9% of patients at baseline, increasing to 14.6%, 24.4%, and 44.8% at weeks 48, 96, and 144, respectively. Multivariate logistic regression analysis adjusted for age, gender, HBV DNA levels, and LVD resistance (LVDr) (L180M and M204V, but not M204I) indicated that T184 substitutions and S202G (not S202C) were a significant factor for BT (adjusted odds ratio [OR], 141.12, and 95% confidence interval [CI], 6.94 to 2,870.20; OR, 201.25, and 95% CI, 11.22 to 3608.65, respectively). Modeling of HBV reverse transcriptase (RT) by docking simulation indicated that a combination of LVDr and ETVr (T184L or S202G) was characterized by a change in the direction of the D205 residue and steric conflict in the binding pocket of ETV triphosphate (ETV-TP), by significantly longer minimal distances (2.2 A and 2.1 A), and by higher potential energy (-117 and -99.8 Kcal/mol) for ETV-TP compared with the wild type (1.3 A; -178 Kcal/mol) and LVDr substitutions (1.5 A; -141 Kcal/mol). Our data suggest that the low binding affinity of ETV-TP for the HBV RT, involving conformational change of the binding pocket of HBV RT by L180M, M204V plus T184L, and S202G, could induce BT.

Factors associated with adherence to combination therapy of interferon and ribavirin for patients with chronic hepatitis C: importance of patient's motivation and physician's treatment experience.

BACKGROUND/AIMS: Adherence to combination therapy with interferon (IFN) or pegylated IFN plus ribavirin for chronic hepatitis C patients is important for a better virological response. However, the impact of the patient's treatment experience and treatment centre on adherence to combination therapy has not been fully analysed. In this prospective study, we analysed the factors that might have an effect on adherence to therapy in patients who had initial or retreatment IFN therapy. PATIENTS AND METHODS: We consecutively enrolled 363 patients with chronic hepatitis C; 221 were IFN naïve and 142 were undergoing retreatment. The mean ages of the naïve and retreatment groups were 54.8 and 55.7 years respectively. IFN alpha-2b was administered daily for 2 weeks, followed by three times per week for 22 weeks, while ribavirin was administered daily. We evaluated the tolerability and response to combination therapy and analysed its relevant factors. RESULTS: Of the 363 patients, 189 (52%) achieved 80% adherence. The multivariate logistic regression analysis revealed that retreatment, centre with more patients treated, patient age (<55 years), male, genotype 2 and dosage of IFN per weight (<0.13 million units/kg) were associated with achievement of 80% adherence to combination therapy. Accordingly, the achievement of 80% adherence was more frequent in the retreatment (62%) than that in the naïve group (46%) (P<0.01) and in centres with more patients treated (57%) than in those with less patients treated (46%) (P=0.03). CONCLUSION: The present data suggest that the patient's motivation and the physician's treatment experience may be important for a better adherence to combination therapy for patients with chronic hepatitis C.

Feasibility and findings of colonoscopy for living-donor liver transplant candidates.

BACKGROUND AND AIMS: Living-donor liver transplantation (LDLT) has been widely performed in patients with end-stage liver disease and hepatocellular carcinoma in Japan. Although extrahepatic cancer survey for LDLT candidates is absolutely required, few reports have indicated the optimal surveillance method for colorectal cancer. The aim of this study is to investigate the feasibility and findings of colonoscopy before LDLT. PATIENTS AND METHODS: From January 2004 to August 2006, we prospectively enrolled all of the scheduled LDLT candidates of our hospital for pretransplant colonoscopy examination. RESULTS: A total of 81 patients were enrolled for colonoscopy. Of these patients, 67 (83%) could actually undergo colonoscopy. Patients who could not undergo colonoscopy exhibited more impaired liver function than those who could (median Model End-Stage Liver Disease score; 25.5 vs. 14.5, P=0.0003). Among patients who underwent colonoscopy, observation of total colon was attained in 64 (96%). Neoplasia was found in 28 (42%) patients, including 4 patients with adenomas > or =10 mm, 1 patient with adenomas with high-grade dysplasia, and 3 patients with invasive cancer. Patients who had advanced neoplasia (adenoma > or =10 mm, adenomas with high-grade dysplasia, or invasive cancer) were likely to have a lower performance status (PS) (7/8 were PS 3) than those who did not (P=0.054). CONCLUSIONS: Clinically significant tumors were found in a considerable portion of LDLT candidates, particularly in lower PS patients. Because immunosuppressive agents after transplantation may worsen malignant tumors, colonoscopy before transplantation is recommended in patients who can tolerate the procedure.

Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis.

AIM: Antinuclear antibodies (ANA) are the main serologic markers of type 1 autoimmune hepatitis (AIH); however 20-30% of patients are negative for ANA. We assessed the clinical features of ANA-negative patients. METHODS: A retrospective analysis was performed of 176 patients with type 1 AIH (153 females, median age 55 years). A diagnosis of AIH was made based on the revised scoring system proposed by the International Autoimmune Hepatitis Group. ANA titers were measured using a standard indirect immunofluorescence technique. RESULTS: Thirty-eight patients (22%) had low titers of ANA (1:40 or 1:80), and 114 (65%) had high titers (>/= 1:160). Of 24 ANA-negative patients, 15 were positive for smooth muscle antibodies (SMA). Three of nine both ANA- and SMA-negative patients developed ANA during follow-up. The other six were diagnosed based on histological characteristics. Thirteen ANA-negative patients relapsed after the normalization of serum alanine aminotransferase (ALT) levels. ANA-negative patients more frequently showed acute presentation and, at presentation, had lower serum immunoglobulin G levels, higher serum levels of bilirubin and transaminase, and higher frequencies of histological acute hepatitis and zone 3 necrosis than those with high titers. However, the frequency of advanced stage of fibrosis was similar. The response to corticosteroids was not different among the three groups. CONCLUSIONS: ANA-negative type 1 AIH shows acute-onset more frequently but may include not only acute autoimmune hepatitis, but also acute exacerbation of inactive chronic disease. Regarding the diagnosis of ANA-negative AIH, the determination of ANA during follow-up and the response to immunosuppressive treatment may be helpful.

Clinical features of type 1 autoimmune hepatitis in adolescence and early adulthood.

AIM: The peak age of the presentation of autoimmune hepatitis (AIH) is between 40 years and 50 years. Elderly patients have been reported to have higher frequencies of concurrent thyroid or rheumatic diseases and histological cirrhosis and a lower occurrence of treatment failure. In this study, we assessed the clinical features of Japanese type 1 AIH in adolescence and early adulthood. METHODS: Fifteen patients aged

Quantitative assessment of technical proficiency in performing needle-knife precut papillotomy.

BACKGROUND: Although needle-knife precut papillotomy (NKPP) is considered a useful alternative for achieving selective biliary cannulation, controversy remains regarding the technical proficiency needed to perform the procedure and its safety. This study evaluated whether procedural experience with NKPP predicted either successful cannulation or the development of complications. METHODS: This study retrospectively investigated 104 patients, out of 589 consecutive patients with native papillary, who underwent NKPP performed by a single endoscopist between October 2002 and July 2006. To demonstrate changes in NKPP, the 104 patients were divided chronologically into two groups according to periods: period A (October 2002 to September 2004) and period B (October 2004 to July 2006). RESULTS: Of the 104 consecutive patients who underwent NKPP, 41 (41/267, 15%) were treated in period A and 63 (63/322, 20%) in period B. There was no significant difference in the overall success rate between periods A (90%) and B (98%) (p = 0.08). However, the initial success rate was higher in period B (95%) than in period A (80%) (p < 0.05). The complication rates were not significantly different between the two groups (10% vs 16%; p = 0.56). Although all complications involved pancreatitis, severe pancreatitis was not observed. CONCLUSION: Whereas the initial success rate for NKPP can increase with procedural experience, the complication rate does not seem to decrease. Furthermore, the need for NKPP does not appear to decrease with increasing endoscopic retrograde cholangiopancreatography (ERCP) experience.

Endoscopic deployment of multiple JOSTENT SelfX is effective and safe in treatment of malignant hilar biliary strictures.

BACKGROUND & AIMS: For the treatment of unresectable biliary tract carcinoma with hilar biliary stricture, antitumor therapy and biliary stenting should be addressed in terms of prolonged survival with a good quality of life. However, the endoscopic management of malignant hilar biliary strictures is difficult even for an expert endoscopist. We evaluated the efficacy and safety of the endoscopic deployment of multiple JOSTENT SelfX units in patients with hilar biliary strictures treated with or without chemotherapy. METHODS: Between November 2003 and December 2006, endoscopic deployment of multiple JOSTENT SelfX units in hilar biliary strictures by using a partial stent-in-stent procedure was performed on 41 consecutive patients with primary cholangiocarcinoma (n = 34) and gallbladder carcinoma (n = 7) at a gastroenterologic center of Okayama University Hospital. Thirty-three patients were treated with gemcitabine (n = 25) or S-1 (n = 8). RESULTS: Metallic stent deployment was successfully accomplished in all cases via only endoscopic procedures. During the follow-up period (mean, 210 days), mean patency time was 150 days, and metallic stent obstruction occurred in 15 cases (37%). Although a repeat intervention was required in all metallic stent obstructed cases, the deployment of the second metallic or plastic stent was completed successfully. The remaining 26 cases (63%) required no interventions. The median overall survival period was only 235 days. However, that of the patients receiving chemotherapy was 392 days. CONCLUSIONS: Endoscopic partial stent-in-stent deployment with multiple JOSTENT SelfX prostheses is effective and safe for the treatment of malignant hilar biliary stricture even in patients receiving chemotherapy.

Fibrosis progression rates between chronic hepatitis B and C patients with elevated alanine aminotransferase levels.

BACKGROUND: We evaluated the annual rate of fibrosis progression in chronic hepatitis B and C patients with elevated alanine aminotransferase (ALT) levels. METHODS: Forty-nine chronic hepatitis B patients and 21 chronic hepatitis C patients, each of whom had undergone two or more liver biopsies at an interval of more than 1 year, were enrolled in this retrospective clinical research protocol. The annual rate of fibrosis progression was calculated by dividing the change in fibrosis stage between the first and second liver biopsies by the interval in years between them. RESULTS: The median interval in chronic hepatitis B and C was 3.4 (first and third quartiles, 1.8-4.7) and 3.2 (2.1-6.5) years, respectively. Overall, the mean fibrosis progression rate was 0.21 +/- 0.31 (mean +/- SD) fibrosis units (FU) per year in 49 patients with chronic hepatitis B, and 0.13 +/- 0.18 FU/year in 21 patients with chronic hepatitis C. The ALT level was an independent variable correlating with fibrosis progression. In patients whose median ALT level was 70 IU/l or more, the mean fibrosis progression rate was 0.28 +/- 0.32 FU/year in 36 patients with chronic hepatitis B, and 0.22 +/- 0.23 FU/year in eight patients with chronic hepatitis C. CONCLUSION: This paired-biopsy study of untreated chronic hepatitis B or C demonstrated that fibrosis progression occurred largely in patients with continuously elevated ALT levels even over a relatively short period, and that liver fibrosis might progress by one stage within an average of 4-5 years of follow-up in patients with elevated ALT of 70 IU/l or more.

Risk factors for high-grade dysplasia or carcinoma in colorectal adenoma cases treated with endoscopic polypectomy.

OBJECTIVE: Our aim is to establish the risk factors for carrying high-grade dysplasia or carcinoma by analyzing endoscopically treated adenoma cases. METHODS: Patients who underwent endoscopic polypectomy at our hospitals between January 2003 and August 2004 were analyzed. RESULTS: A total of 889 patients (mean age: 63+/-11 years), and 1486 adenomas resected from these patients, were included in the analysis. Seventy-five adenomas (5%) from 72 patients (8%) were found to have high-grade dysplasia or carcinoma. Among patient factors, female sex [odds ratio (OR) 2.25, 95% confidence intervals (CI)=1.34-3.76], presence of multiple adenomas (OR=2.15, 95% CI=1.15-4.00), older age (OR=1.02, 95% CI=1.00-1.04), and rectal bleeding as the indication for colonoscopy (OR=2.57, 95% CI=1.34-4.92) were identified as the significant risk factors for carrying high-grade dysplasia or carcinoma using the multivariate analysis. In addition, a size of > or = 10 mm (OR=10.83, 95% CI=5.86-20.0), flat appearance (OR=3.91, 95% CI=2.20-6.95), and location on the left side of the colon (OR=1.80, 95% CI=1.03-3.13) were identified as tumor risk factors. CONCLUSION: Distinct factors were proved to be associated with high-grade dysplasia or carcinoma. These results are useful to select lesions that require immediate treatment. Moreover, female sex as a risk factor raises an interesting problem regarding the progression from adenoma to carcinoma.

Clinical factors that impair health-related quality of life in ulcerative colitis patients vary with the disease duration.

BACKGROUND AND AIM: The health-related quality of life (HRQOL) of patients with ulcerative colitis (UC) can be impaired because of the chronic symptoms. Although UC patients suffer from such symptoms over the long term, there have been few reports on the changes of HRQOL with disease duration. The aim of this study was to clarify these changes. METHODS: The HRQOL of 331 Japanese UC patients was examined using the validated Japanese version of the Inflammatory Bowel Disease Questionnaire (J-IBDQ). HRQOL and factors affecting HRQOL identified using multiple linear regression analysis were stratified by disease duration. RESULTS: Of the 15 clinical factors examined, the clinical activity index score was the strongest determinant (P<0.0001) of all the scores of IBDQ regardless of disease duration. HRQOL did not differ significantly among patients with different disease durations. The factors, however, that affected HRQOL varied according to disease duration. In patients with disease duration of less than 5 years, the clinical activity index score was the predominant factor affecting HRQOL. Being 'on sick leave or hospitalized' was a significant factor impairing HRQOL in patients with disease duration of 5-9 years. Moreover, complications due to corticosteroids significantly impaired all of the IBDQ scores in patients with disease duration of 10 years or more. CONCLUSION: Factors that affected the HRQOL of UC patients varied according to the patients' disease duration. Our findings should assist in the development of a long-term strategy for the treatment of UC patients.

A model for estimating cirrhosis in patients with type 1 autoimmune hepatitis.

UNLABELLED: Longstanding cirrhosis has been recognized as a risk factor for the development of hepatocellular carcinoma in patients with autoimmune hepatitis (AIH). Thus, the accurate determination of cirrhosis is important for prognostication, decisions regarding treatment and monitoring of disease progression. The aim of this study was to identify independent predictors of cirrhosis and to develop a model for estimating cirrhosis in patients with type 1 AIH. METHODS: Using the training sample, consisting of 121 patients with type 1 AIH, we retrospectively examined independent predictors of cirrhosis and constructed a model for estimating cirrhosis. Validation was prospectively performed in the validation sample, consisting of 35 patients. RESULTS: Using a stepwise multiple linear regression analysis, three predictors of serum immunoglobulin A level, ratio of aspartate aminotransferase to alanine aminotransferase, and platelet count were elicited, and a model for estimating cirrhosis was determined as follows: risk score = -0.113 + 0.0006056 x immunoglobulin A (mg/dL) + 0.155 x ratio of aspartate aminotransferase to alanine aminotransferase - 0.007079 x platelet (x10(4)/mm(3)). In the training sample, the sensitivity and specificity were 90% and 83%, respectively, when patients presenting a risk score >/=0.20 were estimated to be cirrhotic. When this model was applied to the validation sample, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 83%, 97%, 83%, 97% and 94%, respectively. CONCLUSION: It is suggested that this model could be useful for the estimation of cirrhosis in patients with type 1 autoimmune hepatitis.

Human leukocyte antigen DR status and clinical features in Japanese patients with type 1 autoimmune hepatitis.

AIM: Human leukocyte antigen (HLA) DR status affects the clinical features of autoimmune hepatitis. In Caucasians, patients with DR3 have poorer outcomes. In Japan, the relationship between HLA DR status and clinical features has yet to be fully examined. METHODS: We investigated 79 patients with type 1 autoimmune hepatitis who underwent liver biopsy and were screened for HLA DR status by the polymerase chain reaction sequence specific oligonucleotide hybridization method. RESULTS: Fifty-five patients had DR4 and 23 had DR2. Thirteen patients had both DR2 and DR4. None had DR3. Of patients aged <30 years, 70% did not have DR4. A tendency toward higher serum levels of immunoglobulin G was seen in patients with DR4 compared to those without, while patients with neither DR2 nor DR4 had lower serum levels of immunoglobulin G than those with only DR2 and those with only DR4. Patients with DR2 had a lower frequency of concurrentautoimmune disease. Concurrence of thyroid disease was seen only in patients with DR4. The cumulative incidental rate of the normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was not associated with HLA DR status. CONCLUSION: HLA DR status is considered to affect the clinical features of Japanese patients with type 1 autoimmune hepatitis. Japanese patients with DR2 may have different clinical features from others. In addition, diagnoses of type 1 autoimmune hepatitis should be made carefully in Japanese patients with neither DR2 nor DR4 and in those aged <30 years.

Risk factors for local and distant recurrence of hepatocellular carcinomas after local ablation therapies.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) recurs frequently after local ablation therapies. Recurrence following the therapies may be of two types: local recurrence and distant recurrence. The aim of the current study is to separately elucidate the predisposing factors for each recurrence. METHODS: Among the 2141 consecutive patients with HCC who were admitted to our institute and affiliated hospital between May 1997 and April 2004, 621 patients who had undergone local ablation therapies as the initial treatment were enrolled. Correlations between the clinical backgrounds of the patients and the type of recurrence were analyzed by the Cox proportional hazard model. RESULTS: A multivariate analysis revealed that tumor size (>30 mm; risk ratio 2.80; 95% confidence interval, 1.77-4.45; P < 0.0001), tumor number (> or =2; 1.74, 1.23-2.47, P = 0.002), and the serum alpha-fetoprotein level (>100 ng/mL; (1.62, 1.09-2.41, P = 0.014), which were classified as "tumor factors", were significant predisposing factors for the local recurrence of HCC. In contrast, a low platelet count (<100,000/microL; 1.34, 1.04-1.74, P = 0.03) and the presence of ascites (1.73, 1.16-2.57, P = 0.008), which were classified as "background factors", as well as tumor size (1.83, 1.11-3.01, P = 0.02) and tumor number (2.23, 1.72-3.00, P < 0.0001) were predisposing factors for distant recurrence. CONCLUSION: The predisposing factors for local and distant recurrence of HCC differ and different precautions must be observed to prevent recurrence, depending on the HCC status and background liver functions.

A prospective and comparative cohort study on efficacy and drug resistance during long-term lamivudine treatment for various stages of chronic hepatitis B and cirrhosis.

BACKGROUND AND AIMS: A prospective, non-randomized cohort study on long-term lamivudine treatment, comparing efficacy, drug resistance, and prognosis for various stages of chronic hepatitis B virus (HBV)-related liver disease was performed to elucidate the significance and indication of lamivudine for individual patients at each stage of disease. METHODS: A total of 158 cases consisting of 87 chronic hepatitis, 28 compensated cirrhosis, and 43 decompensated cirrhosis, with serum HBV-DNA > 5 log(10) copies/mL and with elevated alanine aminotransferase (ALT) over twice the upper normal limit or complications of hepatic insufficiency, were administered 100 mg of lamivudine daily and monitored for HBV markers, biochemistry, and prognosis. RESULTS: Lamivudine reduced HBV-DNA and ALT equally in all groups. Serum albumin, prothrombin time (%), and platelet count increased in all groups. The increased margin of albumin was the highest in the decompensated cirrhosis and higher in the compensated cirrhosis than the chronic hepatitis groups. Cumulative incidence of virologic breakthrough was 16%, 42%, 49%, and 53% at 12, 24, 36, and 48 months, respectively, and the strongest predictive factor for lamivudine resistance was persistent HBV-DNA at 3 months. Ascites, encephalopathy, and jaundice improved in the majority of patients with decompensated cirrhosis. On the other hand, hepatic failure developed or deteriorated in 10 patients after virologic breakthrough, and nine of them had decompensated cirrhosis. CONCLUSIONS: Lamivudine was effective in reducing HBV-DNA and improving hepatic reserve at all stages and was most beneficial and significant for decompensated cirrhosis. Meanwhile, close monitoring of viral load and immediate rescue treatment for lamivudine resistance is necessary to prevent hepatic failure in decompensated cirrhosis.

Evaluation of needle-knife precut papillotomy after unsuccessful biliary cannulation, especially with regard to postoperative anatomic factors.

BACKGROUND: Biliary cannulation is the first step in therapeutic endoscopic retrograde cholangiopancreatography. This study aimed to evaluate unsuccessful cases of biliary cannulation in which the standard procedure was changed to a needle-knife precut papillotomy (NKPP), with particular attention given to postoperative anatomic factors. METHODS: Between October 2002 and February 2006, a total of 501 consecutive patients with an intact duodenal papilla were retrospectively investigated. After biliary cannulation using standard maneuvers was unsuccessful within 20 min, NKPP was performed in 80 cases (16%). The clinical backgrounds for difficult biliary cannulation were compared between patients who had standard maneuvers (n = 421, 84%) and those who underwent NKPP. RESULTS: For 76 difficult cannulation cases (95%), successful cannulation after NKPP was accomplished, and the total success rate reached 99% (497/501). Multivariate analysis indicated that female gender (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.34-3.79), left lobe hypertrophy after hepatectomy (OR, 6.25; 95% CI, 2.52-15.54), history of Billroth I reconstruction after gastrectomy (OR, 7.49; 95% CI, 2.55-22.02), and malignant biliary stricture (OR, 2.31; 95% CI, 1.21- 4.41) were significant risk factors associated with unsuccessful standard procedures used for biliary cannulation. Complications after NKPP were observed in nine cases (11%), all of which were pancreatitis. CONCLUSIONS: Difficult biliary cannulation was strongly associated with postoperative anatomic factors. In these situations, early introduction of NKPP should be recommended if the conventional biliary cannulation promises to be difficult.