Complications after Radiofrequency Ablation for Hepatocellular Carcinoma: A Multicenter Study Involving 9,411 Japanese Patients.

INTRODUCTION: Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is considered a safe and minimally invasive procedure. We previously reported that the mortality and complication rates for RFA were 0.038% (5/13,283 patients) and 3.54% (579 complications/16,346 procedures), respectively, from 1999 to 2010 (previous period). In this study, we investigated the clinical criteria for RFA and the mortality and complication rates from 2011 to 2015 (recent period). METHODS: Data were collected from 25 centers by using a questionnaire developed by the Chugoku-Shikoku Society for Local Ablation Therapy of HCC. The criteria for RFA, RFA modification, use of image-guidance modalities, mortality, and complications during the previous and recent periods were compared. RESULTS: We evaluated 11,298 procedures for 9,411 patients, including those that involved new devices (bipolar RFA and internally adjustable electrode system). The criterion of hepatic function for RFA increased from a Child-Pugh score ≤8 during the previous period to ≤9 during the recent period. The criteria regarding the tumor location and other risk factors have been expanded recently because of the increased use of several modifications of the RFA procedure and image-guidance modalities. The mortality rate was 0.064% (6/9,411 patients), and the complication rate was 2.92% (330 complications/11,298 procedures). There was no difference in mortality rates between the 2 periods (p = 0.38), but the complication rates was significantly lower during the recent period (p = 0.038). DISCUSSION AND CONCLUSIONS: Our findings confirmed that RFA, including the use of new devices, is a low-risk procedure for HCC, despite the expansion of the criteria for RFA during the recent period.

Morbidly obese patient with non-alcoholic steatohepatitis-related cirrhosis who died from sepsis caused by dental infection of Porphyromonas gingivalis: A case report.

Non-alcoholic steatohepatitis (NASH) is associated with increased risks of developing lifestyle-related diseases including type 2 diabetes, cardiovascular disease and cerebral vessel disease. While the two-hit hypothesis and, recently, multiple parallel hits hypothesis of NASH pathogenesis were proposed, further details have not emerged. Recently, dental infection of Porphyromonas gingivalis (P. gingivalis) has been reported as a critical risk factor for NASH progression, which acts as multiple parallel hits to induce inflammation and fibrogenic responses in steatosis. We describe here a 54-year-old woman who died from sepsis and was diagnosed with NASH. Briefly, her body mass index (BMI) at the age of 35 years old had been 25.6 kg/m(2) , but she became obese after withdrawing into her home at the age of 45 years. Severe obesity continued over 19 years without diabetes mellitus. She was admitted to our hospital due to a sudden disturbance of consciousness. On admission, her BMI was 48.5 kg/m(2) . Computed tomography revealed cirrhotic liver with massive ascites, and laboratory data indicated increased inflammatory responses, renal failure and C grade Child-Pugh classification, suggesting the diagnosis of sepsis. Also, severe periodontal disease was present, because the patient's front teeth fell out easily during intubation. Although the focus of infection was not specified, the oral flora Parvimonas micra, a periodontal pathogen, was detected in venous blood. In spite of intensive care including artificial respiration management and continuous hemodiafiltration, she died on the 43rd day after admission. Surprisingly, P. gingivalis was detected in her hepatocytes. This case may represent the significance of P. gingivalis in the progress to cirrhosis in NASH patients.

Effect of prolonged administration of pegylated interferon/ribavirin therapy in genotypes 2a and 2b: propensity score-matched analysis.

BACKGROUND AND AIM: Chronic hepatitis C genotype 2 patients show high susceptibility to pegylated interferon plus ribavirin therapy (PEG/RBV). However, the differences in response to therapy between genotypes 2a and 2b, and the efficacy of prolonged therapy for refractory patients have not been evaluated. We investigated the differences in response to PEG/RBV between each genotype and examined the efficacy of prolonged therapy. METHODS: A total of 343 chronic hepatitis patients infected with hepatitis C virus (HCV) genotype 2 (2a: n = 195; 2b: n = 148) were enrolled in this study. All patients received PEG/RBV for 24 (24 week group, n = 242) or more weeks (prolonged group, n = 101). We analyzed the differences in virological response between genotypes 2a and 2b. Clinical and virological factors of patients in the 24-week group and the prolonged treatment group were matched using propensity score analysis, and the efficacy of prolonged therapy established by comparing time of serum HCV disappearance for each genotype. RESULTS: Virological response tended to be higher for genotype 2a compared with genotype 2b; however, there was no significant difference in sustained virological response rates between genotypes (2a: 78.3%; 2b: 70.2%; P = 0.19). After propensity score matching, the adjusted P-value for sustained virological response rate was significantly different for genotype 2b patients with undetectable HCV-RNA between weeks 5 and 8, and for genotype 2a patients with detectable HCV-RNA at week 8. CONCLUSION: Prolonged therapy with PEG/RBV may be effective when serum HCV-RNA is detectable at week 4 and week 8 for genotype 2b and 2a patients, respectively.

Safety of hepatectomy for elderly patients with hepatocellular carcinoma.

The number of elderly patients with hepatocellular carcinoma (HCC) has been increasing. Characteristics of elderly HCC patients are a higher proportion of females, a lower rate of positive hepatitis B surface antigen, and a higher rate of positive hepatitis C antibodies. Careful patient selection is vital for performing hepatectomy safely in elderly HCC patients. Treatment strategy should be decided by not only considering tumor stage and hepatic functional reserve, but also physiological status, including comorbid disease. Various assessment tools have been applied to predict the risk of hepatectomy. The reported mortality and morbidity rates after hepatectomy in elderly HCC patients ranged from 0% to 42.9% and from 9% to 51%, respectively. Overall survival rate after hepatectomy in elderly HCC patients at 5 years ranged from 26% to 75.9%. Both short-term and long-term results after hepatectomy for strictly selected elderly HCC patients are almost the same as those for younger patients. However, considering physiological characteristics and the high prevalence of comorbid disease in elderly patients, it is important to assess patients more meticulously and to select them strictly if scheduled to undergo major hepatectomy.

Complications of radiofrequency ablation for hepatocellular carcinoma in a multicenter study: An analysis of 16 346 treated nodules in 13 283 patients.

AIM: We surveyed multiple centers to identify types and frequency of complications and mortality rate associated with radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). METHODS: We distributed a questionnaire developed by members of the Chugoku-Shikoku Society for the Local Ablation Therapy of Hepatocellular Carcinoma to 20 centers and analyzed types and frequency of complications and mortality rate. RESULTS: In total, 16 346 nodules were treated in 13 283 patients between January 1999 and November 2010. Five patients (0.038%) died: two from intraperitoneal hemorrhage, and one each from hemothorax, severe acute pancreatitis and perforation of the colon. In 16 346 treated nodules, 579 complications (3.54%) were observed, including 78 hemorrhages (0.477%), 276 hepatic injuries (1.69%), 113 extrahepatic organ injuries (0.691%) and 27 tumor progressions (0.17%). The centers that treated a large number of nodules and performed RFA modifications, such as use of artificial ascites, artificial pleural effusion and bile duct cooling, had low complication rates. CONCLUSION: This study confirmed that RFA is a low-risk treatment for HCC and that sufficient experience and technical skill can reduce complications.

Impact of ribavirin dose reduction on the efficacy of pegylated interferon plus ribavirin combination therapy for elderly patients infected with genotype 1b and high viral loads.

AIM: To examine the impact of ribavirin dose reduction on the efficacy of pegylated interferon (PEG IFN) plus ribavirin combination therapy for elderly patients infected with genotype 1b and high viral loads. METHODS: A total of 72 patients, over 65 years old, were recruited for this study. Patients were divided into groups receiving either 600-800 mg of ribavirin according to bodyweight (Group 1, n = 36) or 400 mg of ribavirin (Group 2, n = 36) plus 1.5 µg/kg (range: 1.3-2.0 µg/kg) of PEG IFN-α-2b for 48 weeks. RESULTS: Total ribavirin doses were administrated at 9.80 ± 2.39 mg/kg per day (3.29 ± 0.80 g/kg) for Group 1 and 5.87 ± 1.82 mg/kg per day (1.97 ± 0.61 g/kg) for Group 2 (P < 0.001). According to the total clearance (CL/F) of ribavirin, 34 of 36 patients in Group 1 received over-doses of ribavirin. In contrast, numbers of those receiving equivalent doses of ribavirin were two of 36 patients in Group 1 and 36 of 36 patients in Group 2, respectively (P < 0.001). End-of-treatment response (ETR) rates were observed in 23 of 36 patients (63.9%) in the standard ribavirin dose protocol and in 23 of 36 patients (63.9%) in the reduction ribavirin dose protocol (NS). Sustained virological response (SVR) rates were observed in 11 of 36 patients (30.6%) in the standard ribavirin dose protocol, and in 13 of 36 patients (36.1%) in the reduced ribavirin dose protocol (NS). CONCLUSION: Reduction of ribavirin doses for elderly patients did not affect the outcome for the 48-week combination therapy.

Transcatheter chemoembolization for unresectable hepatocellular carcinoma and comparison of five staging systems.

AIM: We compared the ability of five staging system to predict survival in patients with hepatocellular carcinoma (HCC) treated with chemoembolization. METHODS: The study subjects were 214 patients with HCC treated with repeated chemoembolization alone using cisplatin and lipiodol. Predictors of survival were assessed by multivariate analysis. Before chemoembolization was carried out, the modified Japan Integrated Staging (m-JIS), Japan Integrated Staging (JIS score), Barcelona (BCLC) stage, Liver Cancer Study Group of Japan/Tumor-Node-Metastasis (LCSGJ/TNM) and Italian score (CLIP score) were checked. To validate the prognostic value of these staging systems, the survival curve was obtained and analyzed by the Kaplan-Meier method. Discriminatory ability and predictive power were compared using Akaike's information criterion (AIC) score and the likelihood ratio (LR) χ(2) . RESULTS: Overall survival was 1 year in 82.9%, 3 years in 39.9% and 5 years in 15.1%. Multivariate analysis identified more than 90% lipiodol accumulation (grade I) after the first chemoembolization (P = 0.001), absence of portal vein tumor thrombosis (PVTT) (P < 0.001) and liver damage A (P = 0.012) as independent determinants of survival. AIC score and the LR χ(2) showed superior predictive power of the m-JIS system in 95 patients with grade I accumulation of lipiodol after first chemoembolization. CONCLUSION: The discriminate ability of the m-JIS score is substantially better than those of other staging systems and has better prognostic predictive power in patients with grade I accumulation of lipiodol after first chemoembolization.

[Usefulness of ultrasonography for diagnosis and treatment in case of superior mesenteric artery (SMA) syndrome].

A 37-year-old man, who had been admitted to another facility because of integration dysfunction syndrome suffered from postprandial epigastric pain, vomiting and weight loss. He was referred to our hospital for further examinations and treatment. Ultrasound examination revealed gastric and duodenal dilatation, reduction of the distance between the superior mesenteric artery (SMA) and aorta and to-and-fro movement in his duodenum, suggesting SMA syndrome. Computed tomography and upper gastrointestinal tract examination also showed findings typical of SMA syndrome. We measured the SMA-aorta distance and the passage of duodenal contents in various body positions using ultrasound. He had to-and-fro movements in his duodenum in a supine, sitting, and left recumbent position. However, when examined in the right recumbent position, the SMA-aorta distance became longest, and intestinal juice flowed from the duodenum to the jejunum. He underwent postural therapy, maintaining a right recumbent position for 30 minutes after every meal, which improved his clinical symptoms.

Regular surveillance by imaging for early detection and better prognosis of hepatocellular carcinoma in patients infected with hepatitis C virus.

PURPOSE: This study evaluated the usefulness of regular check-ups by ultrasonography and contrast-enhanced imaging for early detection of hepatocellular carcinoma (HCC) in a retrospective analysis. PATIENTS AND METHODS: From April 2001 to March 2007, 240 consecutive patients with HCC who were infected with hepatitis C virus (HCV) were divided into three groups. Patients diagnosed with HCC by repeated imaging constituted Group A (surveillance group). Group B comprised patients in whom HCC was detected during scheduled doctor visits for liver disease or other diseases such as diabetes. Group C comprised non-screened patients. RESULTS: The prevalence of solitary tumors decreased from Group A through Group B to Group C (66, 48 and 24%, respectively, P < 0.001). The proportion of patients in stages I and II decreased from 83% (103/124) in Group A to 53% (42/79) in Group B and 24% (9/37) in Group C (P < 0.001). The proportion of patients who were treated with curative procedures, such as resection or ablation, was highest at 80% (99/124) in Group A, and lower at 53% (42/79) in Group B and 27% (10/37) in Group C (P < 0.001). The cumulative survival rate was better in Group A than B (P < 0.05), and in Group B than C (P < 0.001). Periodical medical check-ups without imaging did not necessarily detect early-stage disease, even when HCC-related markers including des-gamma-carboxy prothrombin were tested. CONCLUSIONS: Regular surveillance with ultrasonography and contrast-enhanced imaging is useful for detecting early-stage HCC and increase chances for curative treatments in patients with HCV-related chronic liver disease.

[Large hepatocellular carcinoma successfully treated with transarterial chemoembolization using cisplatin].

A 83-year-old man was admitted to our hospital with a large hepatic tumor located in lateral segment. Alpha-fetoprotein was 7ng/ml, and protein induced by vitamin K deficiency and antagonist-II (PIVKA-II) was 50792mAU/ml. The tumor was diagnosed as hepatocellular carcinoma (HCC) by angiographically assisted CT. No ascites was detected and major serological findings were T-Bil 0.7mg/dl, Alb 4.2g/dl, and PT 129%. Because of advanced age and a history of heart disease, he was treated with transarterial chemoembolization using cisplatin (Lip-TACE). The total dose was 128mg of cisplatin and 15ml of lipiodol. No adverse effects appeared. After the third session of Lip-TACE, the levels of PIVKA-II became negative and continued within the normal range for 26 months. We confirmed a decrease of HCC with lipiodol accumulation by abdominal CT, and the response rate was PR. He has been well for 3 years since the first Lip-TACE procedure.

Magnifying colonoscopy used to predict disease relapse in patients with quiescent ulcerative colitis.

BACKGROUND: Many patients with quiescent ulcerative colitis (UC) experience relapse. However, clinical and conventional colonoscopic signs are inadequate for predicting relapse. This study's aim was to investigate the effectiveness of magnifying colonoscopy in predicting relapse in patients with quiescent UC and to evaluate the association of the findings of magnifying colonoscopy with the histological findings. METHODS: Magnifying colonoscopy was performed in 57 patients with clinical and endoscopic inactive UC. Patients were divided into 3 groups according to the findings of magnifying colonoscopy as MR (magnify-regular), MI (magnify-irregular), and MD (magnify-defect). Their subsequent clinical course was compared to assess the clinical usefulness of magnifying observation in predicting relapse. We also compared histological findings according to Riley's criteria to each finding of magnifying colonoscopy. RESULTS: Within 12 months, 1 of 18 patients (6.7%), 10 of 22 patients (45.5%), and 12 of 17 patients (70.6%) with findings of magnifying colonoscopy of MR, MI, and MD, respectively, experienced relapse. The MR group had a significantly low relapse rate compared with the MD and MI groups (P = 0.016, P = 0.002). When histological findings were compared with the findings of magnifying colonoscopy, the mean score of each variable, such as acute inflammatory cell infiltrate, chronic inflammatory cell infiltrate, and crypt architectural irregularities was significantly lower in the MR group than in the MD and MI groups. CONCLUSIONS: The findings of magnifying colonoscopy in patients with quiescent UC is useful for predicting relapse and is associated with histological grade of inflammation.

Predicting the response to 48-week combination therapy with peginterferon alpha-2b plus ribavirin from the estimated HCV RNA load index after negative serum change in genotype 1b hepatitis C patients.

AIM: We estimated viral dynamics after serum hepatitis C virus (HCV) RNA became negative and assessed the relation between the estimated viral load at the end of treatment (EVE) index and the response to the combination therapy with peginterferon alpha-2b plus ribavirin. METHODS: Patients with chronic HCV, genotype 1b, and a high viral load were treated with this combination therapy for 48 weeks, and serum HCV RNA was measured frequently during the treatment period. In the patients showing an end-of-treatment response (ETR), the viral load profile from the start of treatment until serum HCV RNA became negative was expressed by an approximate curve. Then the EVE index was calculated by using the expression obtained from the curve, and differences between the sustained virologic response (SVR) and relapse groups were investigated. RESULTS: The SVR rate increased as the EVE index became lower, and the EVE index was significantly lower in the SVR group than in the relapse group. The SVR rate was higher for those in whom the EVE index was below the cut-off point. CONCLUSION: Prediction of SVR and relapse from the EVE index is more useful than prediction from viral dynamics at the time when HCV RNA becomes negative or when HCV RNA shows a decrease of 2-log or more.

Dose comparison study of pegylated interferon-alpha-2b plus ribavirin in naïve Japanese patients with hepatitis C virus genotype 2: a randomized clinical trial.

BACKGROUND AND AIM: To compare the efficacy and safety of pegylated interferon (PEG-I) at 1 and 1.5 microg/kg, and in combination with ribavirin (RBV) for 24 weeks in naïve Japanese patients infected with hepatitis C virus genotype 2. METHODS: The present study was an open-label, randomized trial of 55 patients receiving PEG-I (1 or 1.5 microg/kg body weight [BW], subcutaneously, once a week) and RBV for 24 weeks. The patients were followed up for 24 weeks without treatment. RESULTS: The intention-to-treat analyses showed that the proportion of patients with a sustained virological response (SVR) in the 1-microg/kg PEG-I-RBV group (38.5%, 10/26) was lower than that of the 1.5-microg/kg PEG-I-RBV group (74.1%, 20/27; P = 0.013). The PEG-I dose was reduced in two of the 26 patients of the 1-microg/kg PEG-I-RBV group (one because of thrombocytopenia at 2 weeks, and one because of generalized fatigue at 20 weeks), and four of the 27 patients of the 1.5-microg/kg PEG-I-RBV group (one because of neutropenia at 20 weeks, and three because of generalized fatigue at 1, 5, and 8 weeks). The multivariate analysis identified age (< 60 years) and dose of PEG-I (1.5 microg/kg) as significant determinants of SVR. CONCLUSION: The dose of PEG-I to be used at the start of therapy should be 1.5-microg/kg BW in naïve Japanese patients infected with hepatitis C virus genotype 2.

Prospective study of short-term peginterferon-alpha-2a monotherapy in patients who had a virological response at 2 weeks after initiation of interferon therapy.

BACKGROUND AND AIMS: Long-term interferon (IFN) therapy is effective in eliminating hepatitis C virus (HCV). However, it carries the risk of adverse effects and reduced quality of life. To assess whether short-term IFN therapy effectively eliminates HCV, we performed a prospective pilot study of pegylated (peg)IFN-alpha-2a therapy for 8 or 24 weeks. METHODS: After excluding patients with high titers of genotype-1, 55 HCV patients received pegIFN-alpha-2a. Patients who became negative for HCV-RNA at week 2 were allocated to either an 8-week (n = 19) or 24-week (n = 15) course of IFN. We evaluated the efficacy of and tolerance to IFN therapy. RESULTS: The sustained virological response rate was excellent in the two groups (8 weeks, 89.5% [17/19]; 24 weeks, 100% [15/15], respectively,). IFN dose reduction was required in one patient of the 8-week group, but in six patients of the 24-week group (P = 0.028). Treatment was completed by all patients of the 8-week group, but discontinued in five patients of the 24-week group (P = 0.011). CONCLUSIONS: The 8-week IFN therapy is more tolerable than the 24-week therapy and had similar outcomes. Excluding the patients with high titers of genotype-1, we recommend switching to an 8-week course of pegIFN-alpha monotherapy once patients show an ultra rapid virological response at week 2 from the start of IFN therapy.

The long-term outcome of patients with bleeding gastric varices after balloon-occluded retrograde transvenous obliteration.

BACKGROUND: The purpose of our study was to evaluate the long-term outcome and complications of balloon-occluded retrograde transvenous obliteration (B-RTO) in patients with hemorrhage from gastric fundal varices. METHODS: Thirty-four consecutive patients with bleeding from gastric varices who were treated with B-RTO were enrolled in this study between December 1994 and September 2005 (urgent cases, n = 12; elective cases, n = 22). The long-term outcome, complications, and various liver functions were evaluated. RESULTS: Complete obliteration was achieved in 31 of 34 (91%) patients with an acute bleeding episode. In one of the remaining patients, there was a technical failure, and the other two had only partial obliteration. The two patients with partial obliteration did not obtain hemostasis. Thus, the rate of hemostasis was 94% (31/33). Gastric varices disappeared in all patients with complete obliteration during the treatment. The rate of gastric variceal eradication was 91%. Variceal rebleeding from esophageal varices occurred in three patients. The rate of rebleeding was 10% (3/31). Rebleeding from gastric varices was not observed after complete obliteration. None of the patients showed worsening of their Child-Pugh score. Although the 5-year cumulative worsening rate of esophageal varices was 52%, neither portal hypertensive gastropathy nor ectopic varices were observed. The patients with worsening esophageal varices were successfully treated with an endoscopic procedure. The 5-year survival rate was 68%. CONCLUSIONS: B-RTO is useful for treatment of bleeding gastric varices, achieving high eradication of gastric varices, a low rebleeding rate, and a fairly good prognosis with improved hepatic function.

Liver disease in hepatitis C virus carriers identified at blood donation and their outcomes with or without interferon treatment: Study on 1019 carriers followed for 5-10 years.

AIM: To portray liver disease and project outcomes in carriers of hepatitis C virus (HCV) in the general population. METHODS: Liver disease was evaluated in 1019 individuals who were found with HCV infection at blood donation, and they were followed for 5-10 years with or without receiving interferon (IFN). RESULTS: At baseline, chronic hepatitis was detected in 529 (51.9%) HCV carriers and more frequently in men than in women (62.6% [299/478]vs 42.5% [230/541], P < 0.01); cirrhosis was diagnosed in five (0.5% [three men included]) and hepatocellular carcinoma (HCC) in one (0.1% [man]). Of the carriers who were followed for 5 years or longer, loss of HCV-RNA from serum was achieved in 61 (31.0%) of the 197 treated with interferon (IFN) and only one of the 211 (0.5%) without IFN (P < 0.0001). HCC developed in 14 carriers including six ofthe 211 (2.8%) without IFN and eight of the 197 (4.1%) with IFN (six non-responders included). Follow ups of the 949 carriers identified age (P < 0.002), male gender (P < 0.01) and cirrhosis at the baseline (P < 0.0001) as factors contributing to the development of HCC. Cumulative incidence rates of HCC during 10 years among carriers found with chronic hepatitis increased in parallel with the age at the baseline. CONCLUSION: Identification of HCV carriers in the general population and treating those indicated with IFN would help decrease the development of HCC and lift its medical, as well as economic, burdens off society.

Eicosapentaenoic acid could permit maintenance of the original ribavirin dose in chronic hepatitis C virus patients during the first 12 weeks of combination therapy with pegylated interferon-alpha and ribavirin. A prospective randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of eicosapentaenoic acid (EPA) against ribavirin (RBV)-associated hemolytic anemia during the first 12 weeks in chronic hepatitis C virus (HCV) combination therapy. METHODS: This study was a prospective open-label, randomized controlled trial. 100 HCV patients were randomized to either the EPA group (n = 49) or non-EPA group (n = 51) who received combination therapy with or without EPA. We compared the changes in hemoglobin level and RBV plasma concentrations at week 12 in each group with RBV dose reduction rate and performed multivariate analysis to identify independent variables associated with RBV dose reduction. RESULTS: 8 patients (17%) in the EPA group and 20 patients (29%) in the non-EPA group required RBV dose reduction, respectively. The cumulative RBV reduction rate was significantly lower in the EPA group than in the non-EPA group (p = 0.017), while the decrease of hemoglobin and RBV plasma concentrations from baseline was not significantly different. However, in the multivariate analysis, treatment with EPA showed significant variables for the reduction of RBV dose (odds ratio 3.235, p = 0.023). CONCLUSION: EPA could prevent the RBV dose reduction during the first 12 weeks in combination therapy, although further large-scale double-blind randomized controlled trials are required.

Prolonged negative HCV-RNA status led to a good outcome in chronic hepatitis C patients with genotype 1b and super-high viral load.

OBJECTIVE: We examined whether a sustained negative HCV-RNA status for 48 weeks affects the outcome in patients with genotype 1b and super-high viral load, and also investigated whether the outcome is affected by the induction therapy of twice-daily pre-administrated interferon (IFN)-beta. METHODS: 78 eligible patients were divided into four groups. 40 were patients assigned to the short treatment protocol. 13 patients received 3 MU IFN-beta twice daily for 2 weeks followed by IFN-alpha2b+ribavirin for 22 weeks (beta-induction group: group 1). 27 patients received IFN-alpha2b+ribavirin for 24 weeks (standard combination group: group 2). 38 patients were assigned to the maintenance treatment protocol. All of the 13 in the beta-induction group (group 3) and 21 of 25 patients in the standard combination group (group 4) who were negative HCV-RNA PCR at week 24 had IFN monotherapy to maintain a negative HCV-RNA result for 48 weeks. RESULTS: An HCV-RNA-negative status at week 24 was observed in 96% (25/26) of groups 1 and 3 versus in 79% (41/52) of groups 2 and 4 (p<0.01). The sustained virological response (SVR) was 38% (5/13) in group 1 and 11% (3/27) in group 2 (p<0.05). In the maintenance treatment, SVR was observed in 46% (6/13) of group 3 and 32% (8/25) of group 4 (NS). CONCLUSIONS: A sustained negative HCV-RNA status for 48 weeks might be associated with viral elimination in patients with genotype 1 and super-high viral load.

Radiofrequency ablation in the treatment of small hepatocellular carcinomas: comparison of the radiofrequency effect with and without chemoembolization.

OBJECTIVE: The purpose of this study was to determine whether a combination of transcatheter arterial chemoembolization using doxorubicin and radiofrequency ablation can increase tumor destruction compared with radiofrequency alone in the treatment for hepatocellular carcinoma. SUBJECTS AND METHODS. Twenty-one patients with 26 nodules smaller than 3 cm in diameter were treated with radiofrequency ablation. Of these, 10 nodules were treated with a combination of radiofrequency ablation and chemoembolization using doxorubicin. All nodules were evaluated for size of induced coagulation, local recurrence, and complication. RESULTS: The therapeutic areas averaged 27.6 x 22.3 mm using an electrode with a 2-cm tip and 37.2 x 29.1 mm using an electrode with a 3-cm tip. With respect to the results for 14 nodules treated using an electrode with a 3-cm tip with or without chemoembolization, the greatest dimension of the area coagulated by combined therapy was significantly larger (longest axis dimension, 39.9 +/- 4.4 mm; shortest axis dimension, 32.3 +/- 5.2 mm; n = 7 nodules) than areas without chemoembolization (longest axis dimension, 34.6 +/- 2.6 mm; shortest axis dimension, 26.0 +/- 3.3 mm; n = 7 nodules) (longest and shortest axis dimensions, p < 0.05). No recurrence occurred in the nodules smaller than 2 cm in diameter. Among the nodules larger than 2 cm in diameter, one local recurrence was observed in seven nodules treated by combined therapy, while two local recurrences were observed in seven nodules treated by radiofrequency alone. Minor complications developed in three patients, two with persistent high fever and one with biliary stenosis. CONCLUSION: The combination of radiofrequency ablation and transcatheter arterial chemoembolization using doxorubicin markedly increased the extent of induced coagulation compared with radiofrequency alone, despite a small number of patients and the preliminary nature of this study.