Randomized controlled study to examine the efficacy of hepatic arterial infusion chemotherapy with cisplatin before radiofrequency ablation for hepatocellular carcinoma.

AIM: Hepatic arterial infusion chemotherapy (HAIC) with cisplatin is beneficial to patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. This study aimed to examine the effect of HAIC with cisplatin before radiofrequency ablation (RFA) in patients with HCC. METHODS: This was a multicenter, single-blinded, randomized controlled study (UMIN000007267). Early-stage HCC patients were randomly assigned (1:1) to receive HAIC with cisplatin before RFA therapy (HAIC group) or RFA monotherapy (non-HAIC group). The primary end-point was recurrence-free survival. Efficacy analysis and safety analysis followed the intention-to-treat principle. RESULTS: Between August 2012 and July 2016, 74 patients were recruited. A total of 70 eligible patients were randomly assigned to the HAIC group (n = 35) and non-HAIC group (n = 35). Recurrence-free survival rates at 1 (3) year in the HAIC group and non-HAIC group were 82.9% (54.3%) and 74.3% (34.3%), respectively (hazard ratio [HR], 0.597; 95% confidence interval [CI], 0.320-1.091; p = 0.094]. Subgroup analysis showed that the beneficial effect of HAIC was observed in patients with a single nodule and Child-Pugh score 5. Intrahepatic distant recurrence-free survival rate in the HAIC group was significantly better than that in the non-HAIC group (HR, 0.468; 95% CI, 0.235-0.896; p = 0.022). Adverse events were observed in just two patients in the HAIC group (6%) - grade 2 cholecystitis and grade 2 hyperkalemia. CONCLUSIONS: HAIC with cisplatin before RFA did not significantly decrease recurrence in patients with early-stage HCC. However, it might be effective in preventing intrahepatic distant recurrence.

[A case of severe colitis caused by immune checkpoint inhibitor].

A 74-year-old male with lung squamous cell carcinoma who was treated with the anti PD-1 antibody nivolumab developed frequent diarrhea four months after initiating treatment. However, his condition did not improve despite prednisolone at 20mg. Endoscopic examination revealed loss of vascular pattern, erosions, and mucosal friability, resembling ulcerative colitis. Colonoscopy revealed punch-out ulcers in the affected mucosa. Therefore, he was definitively diagnosed with severe colitis caused by immune checkpoint inhibitor treatment and cytomegalovirus colitis. Nivolumab was discontinued, and he was treated with 60mg prednisolone and ganciclovir. Although his colitis improved, he developed pneumonia and died thereafter. This case highlights adverse events that are associated with immune checkpoint inhibitors which should be treated properly.

Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study.

OBJECTIVE: To determine the relationship between treatment outcomes and hand-foot syndrome (HFS), and the relationship between survival rate and post-progression treatment after sorafenib therapy. METHODS: The study assessed 314 patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib at 5 general hospitals in Kagawa Prefecture, Japan. RESULTS: At the start of sorafenib therapy, 23.6% of the patients had HCC of a Child-Pugh class other than A. The initial sorafenib dose was 800 mg in 9.2% of the patients and 400 mg in 64.3%. Time to progression was 129 days (95% CI: 87.3-170.7) and the median overall survival (OS) was 392 days (95% CI: 316.0-468.0). The OS of the patients with Child-Pugh class A HCC was significantly better than that of the patients with Child-Pugh class B HCC (p < 0.0001). The survival curves for Child-Pugh class A-5 points and class A-6 points were significantly different, with that for class A-5 points being better (p < 0.0001). A significant difference was observed between the patients who exhibited HFS and those who did not, with the former exhibiting a better survival rate (p < 0.001). In addition, the survival rate of the patients who received post-progression treatment after sorafenib therapy was significantly better than that of the patients who did not (p < 0.001). CONCLUSION: In sorafenib therapy, patients with HFS and those who received post-progression treatment exhibited good OS.

Risk of secondary osteoporosis due to lobular cholestasis in non-cirrhotic primary biliary cholangitis.

BACKGROUND AND AIM: It remains unclear whether primary biliary cholangitis (PBC) represents a risk factor for secondary osteoporosis. METHODS: A case-control study was conducted to examine bone mineral density and bone turnover markers in middle-aged postmenopausal PBC patients without liver cirrhosis. We compared the incidence of low bone mineral density between propensity-score matched subgroups of PBC patients and healthy controls and investigated the mechanisms underlying unbalanced bone turnover in terms of the associations between bone turnover markers and PBC-specific histological findings. RESULT: Our analysis included 128 consecutive PBC patients, all postmenopausal women aged in their 50s or 60s, without liver cirrhosis or fragility fracture at the time of PBC diagnosis. The prevalence of osteoporosis was significantly higher in the PBC group than in the control group (26% vs 10%, P = 0.015, the Fisher exact probability test). In most PBC patients (95%), the level of bone-specific alkaline phosphatase was above the normal range, indicating increased bone formation. On the other hand, the urine type I collagen-cross-linked N-telopeptide showed variable levels among our PBC patients, indicating unbalanced bone resorption. Advanced fibrosis was associated with low bone turnover. Lobular cholestasis, evaluated as aberrant keratin 7 expression in hepatocytes, showed significant negative correlations with bone formation and resorption, indicating low bone turnover. CONCLUSION: Our results show that, compared with healthy controls, even non-cirrhotic PBC patients have significantly higher risk of osteoporosis. Moreover, lobular cholestasis was associated with low bone turnover, suggesting this feature of PBC may itself cause secondary osteoporosis in PBC patients.

Roles of alcohol consumption in fatty liver: a longitudinal study.

BACKGROUND & AIMS: Roles of alcohol consumption in non-alcoholic fatty liver disease are still controversial, although several cross-sectional studies have suggested the beneficial effect of light to moderate drinking on fatty liver. We analyzed the longitudinal relationship between drinking pattern and fatty liver. METHODS: We included 5297 Japanese individuals (3773 men and 1524 women) who underwent a baseline study in 2003 and follow-up at least once from 2004 to 2006. Generalized estimating equation was used to estimate any association between drinking pattern and fatty liver assessed by ultrasonography. RESULTS: At baseline, 1179 men (31.2%) and 235 women (15.4%) had fatty liver; 2802 men (74.2%) and 436 women (28.6%) reported alcohol consumption. At the latest follow-up, 348 of 2594 men (13.4%) and 101 of 1289 women (7.8%) had newly developed fatty liver; 285 of 1179 men (24.2%) and 70 of 235 women (29.8%) demonstrated a remission of fatty liver. In men, drinking 0.1-69.9 g/week (odds ratio, 0.79 [95% confidence interval, 0.68-0.90]), drinking 70.0-139.9 g/week (0.73 [0.63-0.84]), drinking 140.0-279.9 g/week (0.69 [0.60-0.79]), and drinking ⩾280.0 g/week (0.68 [0.58-0.79]) were inversely associated with fatty liver after adjusting for obesity, exercise, and smoking. In women, drinking 0.1-69.9 g/week (0.71 [0.52-0.96]) and drinking 70.0-139.9 g/week (0.67 [0.45-0.98]) were inversely associated with fatty liver after the adjustment. CONCLUSIONS: Light to moderate alcohol consumption, or even somewhat excessive amounts especially in men, was likely to protect most individuals against fatty liver over time.

[A case of renal salt-wasting syndrome during chemotherapy for advanced gastric cancer].

A 66-year-old woman was admitted to our hospital with heartburn and liver dysfunction. She was diagnosed with advanced gastric cancer. After the initiation of chemotherapy with trastuzumab, capecitabine, and cisplatin, she developed hyponatremia and renal failure with renal salt-wasting syndrome (RSWS). She recovered from these conditions after infusion of hypertonic saline. A diagnosis of RSWS should be considered in patients with hyponatremia who receive cisplatin-based chemotherapy.

Prevalence and associated factors with esophageal varices in early primary biliary cirrhosis.

BACKGROUND AND AIMS: Recent routine testing for anti-mitochondrial antibodies has increased the number of patients with early primary biliary cirrhosis (PBC). The prevalence and clinical significance of esophageal varices in those patients remains obscure. METHODS: A systematic cohort analysis of 256 PBC patients was performed to clarify the prevalence, characteristics, and prognosis of the patients with early PBC and esophageal varices. RESULTS: Twenty-two patients had esophageal varices at the time of diagnosis: 5.5% (12/217) with early disease of histological stage 1 or 2, and 25.6% (10/39) with advanced disease of stage 3 or 4. Immediate treatments were required for two patients with early PBC: one for bleeding varices, and the other for large varices. The overall survival of the patients with early PBC and esophageal varices at diagnosis did not significantly differ from that of patients without esophageal varices (P = 0.66). High alkaline phosphatase (ALP) ratios (odds ratio = 2.3) and low platelet counts (odds ratio = 0.77) were significantly associated with the presence of esophageal varices in the patients with early PBC. Significant associations of these two factors with the development of esophageal varices during follow-up were also revealed (odds ratio = 1.4 and 0.88, respectively). The patients with early PBC and high ALP ratios ≥ 1.9 had significantly high risks of developing esophageal varices during follow-up (P = 0.022). CONCLUSIONS: High ALP ratios and low platelet counts at diagnosis and decreased platelet counts during follow-up are useful predictors of esophageal varices in patients with early PBC.

Peppermint oil solution is useful as an antispasmodic drug for esophagogastroduodenoscopy, especially for elderly patients.

BACKGROUND: Although hyoscine butyl bromide (HB) and glucagon (GL) are often used as antispasmodic drugs during esophagogastroduodenoscopy (EGD), these agents may cause adverse effects. Recently, it was reported that peppermint oil solution (PO) was very effective and had few side effects. AIM: We clarified the efficacy and usefulness of PO as an antispasmodic during upper endoscopy, especially for elderly patients. METHODS: This study was a non-randomized prospective study. The antispasmodic score (1-5, where 5 represents no spasm) was defined according to the degree of spasms of the antrum and difficulty of biopsy. We compared the antispasmodic scores between non-elderly patients (younger than 70) and elderly patients (70 years old or older) according to the antispasmodic agent. RESULTS: A total of 8,269 (Group PO: HB: GL: NO (no antispasmodic) = 1,893: 6,063: 157: 156) EGD procedures were performed. There was no significant difference in the antispasmodic score between Group PO (mean score ± standard deviation: 4.025 ± 0.925) and Group HB (4.063 ± 0.887). Among the non-elderly patients, those in Group PO (n = 599, 3.923 ± 0.935) had a worse antispasmodic score than those in Group HB (n = 4,583, 4.062 ± 0.876, P < 0.001). However, among the elderly patients, those in Group PO (n = 1,294, 4.073 ± 0.917) had similar scores to those in Group HB (n = 1,480, 4.064 ± 0.921, P = 0.83), and significantly better scores than those in Group GL (n = 69, 3.797 ± 0.933, P < 0.05). CONCLUSION: Peppermint oil was useful as an antispasmodic during EGD, especially for elderly patients.

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.

Effect of low-dose gemcitabine on unresectable pancreatic cancer in elderly patients.

BACKGROUND/AIMS: The efficacy of gemcitabine (GEM) on unresectable pancreatic cancer has been reported. However, in elderly patients, severe toxicities are frequently observed. In this study we aimed to assess the efficacy of low-dose GEM on unresectable pancreatic cancer in elderly patients. METHODS: We reviewed 68 elderly patients (≥65 years) with unresectable pancreatic cancer. Thirty-six patients were treated with low-dose GEM (600-800 mg/m(2); GEM group), and the other 32 received best supportive care (BSC group). RESULTS: Median survival was 7.6 and 2.3 months in the GEM and BSC groups, respectively. In the GEM group, the median survival period was longer in 24 patients showing partial response or stable disease than in 12 patients showing progressive disease (11.4 vs. 5.3 months). Furthermore, the patients showing progressive disease had better 6-month survival than patients in the BSC group. Thirteen patients (36%) developed severe toxicities (grade 3 or 4). Low-dose GEM, stage of disease and performance status were associated with the prognosis. CONCLUSIONS: Low-dose GEM may improve the prognosis of elderly patients with unresectable pancreatic cancer. Furthermore, frequencies of severe toxicity seem lower in patients treated with low-dose GEM compared with previous reports.

Investigation of upper gastrointestinal bleeding after implantation of drug-eluting stents; prospective cohort study.

OBJECTIVE: After implantation of drug-eluting stents (DES), two or more anti-thrombotic agents are required. The risk of upper gastrointestinal bleeding (UGIB) in cases of DES implantation is thought to be significant. However, the incidence of UGIB has not yet been investigated in DES-implanted patients. This study aimed to investigate the incidence of UGIB after DES implantation and the awareness among cardiologists about this complication. MATERIAL AND METHODS: Subjects were 397 consecutive patients implanted with DES from August 2004 to September 2007 at two institutions. Endoscopic examinations were performed on DES-implanted patients who presented with hematemesis and/or tarry stools. The concomitant use of acid-suppressing agents was left to the cardiologists. In addition, 37 cardiologists were administered a questionnaire regarding UGIB after DES implantation. RESULTS: Low-dose aspirin and ticlopidine were prescribed in all patients. Forty-six patients had a past history of peptic ulcer. Acid-suppressing agents were concomitantly prescribed to 224 patients (56%) including 32 patients (70%) with a past history of peptic ulcer. UGIB due to gastric ulcers developed in 5 cases (1.3%). One case had received a half dose of H2-RA. No bleeding occurred in patients who received proton pump inhibitors (PPI). The incidence of UGIB was 4.0 per 1000 patient-years. The cardiologists who were surveyed recognized the risk of UGIB after DES implantation and the necessity for its prevention. However, they indicated that adequate management for preventing this complication has not been established. CONCLUSIONS: This study reassuringly demonstrated a low incidence of UGIB after DES implantation. Further study regarding the prophylaxis for UGIB after DES implantation is necessary.

Eradication of Helicobacter pylori infection improved gastric mucosal atrophy and prevented progression of intestinal metaplasia, especially in the elderly population: a long-term prospective cohort study.

BACKGROUND AND AIMS: It still remains controversial whether gastric mucosal atrophy and intestinal metaplasia are reversible after eradication of Helicobacter pylori infection. The aims of this study were to evaluate the histological changes in gastric mucosa after H. pylori eradication during long-term follow-up periods, and to verify the propriety of H. pylori eradication for the elderly population. METHODS: Two hundred and forty-one patients with H. pylori infection and 84 cases more than 60 years old were classified as the elderly group. The mean follow-up period was 101 months. A series of endoscopic examinations with five-point biopsies were performed before and every year after H. pylori eradication. We evaluated the histological grades according to the Updated Sydney System. Statistical analysis was performed using the Wilcoxon signed rank test and the Mann-Whitney U-test, and P < 0.05 was considered to be statistically significant. RESULTS: The atrophic grades improved only at the angle in the 5th year and at all points, except for the antrum, in the 10th year after H. pylori eradication. In the elderly group, the atrophic score improved in both the 5th and 10th year. However, improvement in the younger group was achieved only in the 10th year. The metaplastic score did not change in either the 5th or 10th year after H. pylori eradication in all patients. CONCLUSION: Eradication of H. pylori infection improved gastric atrophy and prevented the progression of intestinal metaplasia in the elderly population during the long-term follow-up periods. H. pylori eradication for the elderly population is effective.

Large waist circumference is a risk factor for reflux esophagitis in Japanese males.

BACKGROUND/AIMS: The prevalence of reflux esophagitis, which might lead to development of Barrett's esophagus and esophageal adenocarcinoma, has been increasing. The aim of this study was to assess risk factors for reflux esophagitis. METHODS: We conducted a cross-sectional study of 1,495 Japanese subjects undergoing health checkups (822 males and 673 females; median age 50 years) at a tertiary care center. RESULTS: One hundred and twenty-seven subjects (8%) had reflux esophagitis and hiatal hernia was observed in 292 subjects (20%). Reflux esophagitis (13 vs. 3%) and hiatal hernia (28 vs. 9%) were more frequent in males than females. Significant differences in clinical backgrounds were observed between females and males. Multivariate logistic regression analyses revealed that hiatal hernia (OR 6.63, 95% CI 2.47-17.8; p = 0.0002) was associated with reflux esophagitis in females. In males, age (per 1-year increment: OR 0.96, 95% CI 0.94-0.99; p = 0.007), hiatal hernia (OR 3.16, 95% CI 2.05-4.87; p < 0.0001) and waist circumference (per 1-cm increase: OR 1.09, 95% CI 1.02-1.15; p = 0.006) were associated with reflux esophagitis. CONCLUSIONS: Abdominal obesity may be an important risk factor for reflux esophagitis in males compared with females.

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.

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

[Case of primary malignant lymphoma of the liver treated by R-CHOP therapy].

A 75-year-old man was admitted to our hospital because of right hypochondralgia. Computed tomography (CT) revealed a large tumor in the right lobe of the liver. Ultrasonography (US) showed vessels in the tumor. Needle biopsy specimens showed malignant lymphoma (Diffuse large B cell lymphoma). Ga scintigraphy and FDG-PET did not demonstrate other lesions and the definitive diagnosis was primary malignant lymphoma of the liver. CHOP with Rituximab therapy (R-CHOP therapy) was performed. After 8 courses of therapy the FDG-PET results were negative and we considered complete remission. We describe a case of primary malignant lymphoma of the liver treated successfully by R-CHOP therapy.

Partial splenic embolization prior to combination therapy of interferon and ribavirin in chronic hepatitis C patients with thrombocytopenia.

AIM: A low platelet count leads to dose reduction of interferon (IFN) and is associated with failure to achieve a sustained virological response (SVR) in chronic hepatitis C patients. However, partial splenic embolization (PSE) is effective for treating thrombocytopenia resulting from hypersplenism. METHODS: We compared the clinical features of 10 patients receiving PSE prior to the combination therapy of IFN and ribavirin (RBV) (PSE group) with those of 10 non-receiving PSE patients (non-PSE group). RESULTS: In all 10 patients, PSE was successfully performed without serious adverse events. After PSE, leukocyte, neutrophil, and platelet counts significantly increased. The period from PSE to the initiation of the combination therapy was 15 (7-21) days. In the PSE group, two of six patients (33%) infected with genotype 1, and all four patients infected with genotype 2, achieved SVR. In the non-PSE group, only three patients infected with genotype 2 achieved SVR. Two patients in the PSE group and one in the non-PSE group discontinued the combination therapy. Three patients of the PSE group and five of the non-PSE group reduced the dose of pegylated IFN-alpha-2b because of thrombocytopenia. In the PSE group, platelet counts during the combination therapy fell to baseline levels; however, they did not fall to lower levels than baseline levels. In the non-PSE group, platelet counts 1 month after the initiation of the therapy were lower than baseline levels. CONCLUSION: The increase of platelet counts after PSE may allow the safe use of IFN and RBV and improve the SVR rate in chronic hepatitis C patients with thrombocytopenia.

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.

[Case report of asymptomatic arteriovenous malformation (AVM) of the pancreas; diagnostic advantage of three-dimensional computed tomography].

A 72-year-old man with diabetes mellitus and hypertension was admitted for further examination and therapy of diabetes. In order to evaluate his pancreas, abdominal computed tomography (CT) was performed, showing a space-occupying lesion (SOL) in the pancreatic uncus. He did not show any symptoms related to the pancreas or gastro intestinal tract. Three-dimensional CT (3D-CT) indicated that the SOL was not a solid tumor but a vessel fistula, fed by the superior mesenteric artery and the gastro duodenal artery, drained by the superior mesenteric vein. Abdominal angiography also showed its peculiar vessel structure, confirming arterio-venous (A-V) malformation in the pancreas. Pancreatic A-V malformation is a rare condition but should not be forgotten in the differential diagnosis of pancreatic SOL. Our case showed the advantages of 3D-CT with its low invasiveness and convenience for the diagnosis of A-V malformation in the pancreas.