Aging impairs fibrosis-4 index after sustained virologic response by direct-acting antivirals in chronic hepatitis C infection.

INTRODUCTION AND OBJECTIVES: Sustained virologic response (SVR) is achieved in most cases of C-type liver disease after direct-acting antiviral (DAA) therapy. Although liver fibrosis improves, the degree of improvement is different. This study aimed to analyze the factors involved in improving liver fibrosis using the fibrosis 4 (FIB-4) index. MATERIAL AND METHODS: Patients were monitored for >3 years after SVR. At the start of therapy (SOT), liver fibrosis was categorized as either mild (<1.45 n = 28), moderate (1.45-3.25 n = 139), or advanced (>3.25 n = 236) based on the FIB-4 index. The FIB-4 index in the advanced group decreased significantly compared to that of the other two, so we selected the advanced group as the analysis target. SOT and end of therapy (EOT) factors that contributed to the FIB-4 index ≤3.25 at 3 years after therapy were examined using a multivariate analysis. RESULTS: Among the SOT factors, age (<72 years old), absence of liver cirrhosis (LC), alanine transferase (ALT) (≥50 U/L), platelet (PLT) (≥10.2 × 104/mm3), and total bilirubin (T.Bil) (<0.8 mg/dl) were the significant factors contributing to the improvement of the FIB-4 index. Among the EOT factors, age (<72 years), PLT (≥12.0 × 104/mm3), and hemoglobin (Hb) (≥12.1 g/dl) were the significant factors contributing to the improvement of FIB-4 index. CONCLUSIONS: Factors involved in the improvement of liver fibrosis after SVR were young age, absence of LC, low T.Bil., high ALT, high PLT, and high Hb levels. The levels of T.Bil, PLT, and Hb were considered to be related to portal hypertension. Aging strongly impaired the improvement in liver fibrosis.

Efficacy of Switching from Kanamycin Sulfate to Rifaximin in Patients with Hepatic Cirrhosis.

Objective This study evaluated the efficacy associated with switching to rifaximin in patients with hepatic cirrhosis receiving kanamycin sulfate for the treatment of hepatic encephalopathy and hyperammonemia. Methods We included 37 patients who switched from kanamycin sulfate to rifaximin at our institution from January 2017 to December 2018. The onset of hepatic encephalopathy and changes in blood ammonia values during a six-month period were retrospectively evaluated. Results There were 4 (11%) patients with hepatic encephalopathy at the time of switching from kanamycin sulfate to rifaximin. The cumulative incidence of hepatic encephalopathy was 3% and 16% at 3 and 6 months later, respectively. The blood ammonia levels at the time of switching to rifaximin and at 3 and 6 months later were 94 (range, 20-243) µg/dL, 95 (range, 33-176) µg/dL, and 81 (range, 32-209) µg/dL, respectively, and no significant changes were observed. However, in the 11 patients receiving an oral dose of <1,500 mg/day of kanamycin sulfate, the blood ammonia levels at the time of switching and at 3 and 6 months later were 136 (range, 35-243) µg/dL, 95 (range, 33-150) µg/dL, and 63 (range, 43-124) µg/dL, respectively. Furthermore, the blood ammonia levels significantly decreased at the time of the switching to rifaximin and at three and six months later (p=0.043 and p=0.011, respectively). Conclusion Switching to rifaximin in hepatic cirrhosis patients receiving kanamycin sulfate to treat hepatic encephalopathy and hyperammonemia showed effects that were equivalent to or greater than the original therapy, thereby demonstrating the clinical efficacy.

The association between serum zinc levels and subjective symptoms in zinc deficiency patients with chronic liver disease.

This study aimed to analyze the association between serum zinc levels and major subjective symptoms in zinc deficiency patients with chronic liver disease. 578 patients with chronic liver disease were enrolled. The patients, whose serum zinc level of <80 µg/dl, completed a questionnaire to determine whether they had subjective symptoms of the five conditions (taste disorder, aphthous stomatitis, dermatitis, alopecia, and anorexia). Then, the association between these subjective symptoms and serum zinc levels was analyzed. In total, 193 patients (33.4%) experienced any subjective symptoms. The prevalence of each symptom was as follows: 36 patients with taste disorder (6.2%), 46 with aphthous stomatitis (8.0%), 77 with dermatitis (13.3%), 46 with alopecia (8.0%), and 53 with anorexia (9.2%). In total, 70.8%, 34.1%, and 26.1% patients with serum zinc levels of <40, ≥40 to <60, and ≥60 to <80 µg/dl, respectively, had these symptoms. When zinc deficiency was defined as a serum zinc level of <80 µg/dl, approximately one-third of patients displayed symptoms presumably originating from zinc deficiency. As serum zinc levels decreased, the prevalence of these symptoms increased. Dermatitis, especially, was relevant to zinc.

Predictors of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting antiviral treatment: relationship with serum zinc.

The recently approved direct-acting antivirals (DAA) agents are effective in terms of sustained virologic response (SVR) rates and are well tolerated in most hepatitis C virus (HCV) patients. This study aimed to analyze the association between serum zinc levels in patients who developed hepatocellular carcinoma (HCC) following HCV eradication after DAA treatment. The retrospective study included 769 HCV-infected patients who achieved SVR after DAA treatment. We calculated the annual incidence rate of HCC and identified risk factors associated with HCC development. We also assessed serum zinc and clinical factors at both baseline and end of treatment (EOT). During follow-up (median duration 35 months), HCC occurred in 18/769 (2.3%) patients. From the multivariate analysis, serum zinc <60 µg/dl [hazard ratio (HR) 5.936] and AFP ≥6.0 ng/dl (HR 5.862) at baseline, baseline-zinc <60 µg/dl (HR 6.283), EOT-serum zinc <63 µg/dl (HR 6.011), baseline-AFP ≥6.0 ng/dl (HR 8.163), and EOT-M2BPGi ≥2.5 (HR 12.194) at baseline and EOT were independently associated with increased HCC risk. In patients who achieved HCV eradication following DAA treatment, serum zinc levels before and at EOT could be a risk factor for developing HCC.

Bile duct adenoma: imaging features and radiologic-pathologic correlation.

PURPOSE: This study aimed to reveal characteristic imaging features of bile duct adenoma (BDA) by radiologic-pathologic correlation. MATERIALS AND METHODS: We retrospectively analyzed pathological and imaging findings of seven patients with BDA. RESULTS: The median maximum diameter of BDA was 5.5 mm. Six lesions had hemispheric morphology. Seven lesions were located in the liver subcapsular region, and proliferation of bile ductules without atypia and fibrous stroma was observed. Two lesions had different microscopic findings. In both lesions, proliferation of bile ductules without atypia was observed in the margin. In one lesion, the percentage of fibrosis and hyalinization was higher at the center than at the margin. In the other lesion, inflammatory cell infiltration was observed in the center. On contrast-enhanced imaging, BDAs showed hypervascularity in the early phase and prolonged enhancement in the delayed phase. On contrast-enhanced multidetector computed tomography during hepatic arteriography, two lesions showed ring-like enhancement in the first phase and prolonged enhancement in the second phase. These were the different histopathologic features of BDAs between the margin and center. CONCLUSION: Bile duct adenoma can be characterized as a small semicircular lesion located in the liver subcapsular region, which show hypervascularity in the early phase with prolonged enhancement.

Zinc deficiency in patients with chronic liver disease in Japan.

AIM: This study aimed to determine the distributions of serum zinc levels and the prevalence of zinc deficiency in patients with chronic liver disease (CLD) in actual clinical practice, and to analyze the association between serum zinc levels and clinical characteristics. METHODS: This study analyzed 1973 patients with CLD, including 749 with liver cirrhosis, who were admitted to Sapporo Kosei General Hospital in 2017. RESULTS: Zinc deficiency, defined as a serum zinc level of <60 µg/dL, was observed in 555 patients overall (28.1%), including 182 (14.9%) patients without liver cirrhosis and 373 (49.8%) with liver cirrhosis. When marginal zinc deficiency was included, zinc deficiency (serum zinc level <80 µg/dL) was observed in 1594 (80.8%) patients overall, including 924 (75.5%) patients without liver cirrhosis and 670 (89.5%) with liver cirrhosis. Serum zinc levels were most strongly correlated with serum albumin levels. Of the 257 CLD patients with an albumin level of <3.5 g/dL, 234 (91.1%) had a serum zinc level of <60 µg/dL. CONCLUSIONS: Zinc deficiency is common in patients with CLD. Serum zinc levels should be regularly measured, particularly in patients with liver cirrhosis.

Evaluation of treatment with zinc acetate hydrate in patients with liver cirrhosis complicated by zinc deficiency.

AIM: In Japan, no zinc preparation had been approved for therapeutic purposes before March 2017. Zinc acetate hydrate was recently approved for the treatment of hypozincemia. We evaluated the efficacy and safety of treatment with zinc acetate hydrate. METHODS: A total of 97 patients with cirrhosis complicated by hypozincemia were treated with zinc acetate hydrate, and their serum zinc normalization rates; factors contributing to normalization; changes in blood ammonia levels; branched-chain amino acids-to-tyrosine ratios; levels of albumin, hemoglobin, alkaline phosphatase, serum copper, and iron; incidence of adverse events; improvement in subjective symptoms; and serum zinc levels taken at 3 months post-treatment were determined. RESULTS: The cumulative serum zinc normalization rates, when normalization was defined as achievement of a serum zinc level ≥80 µg/dL, after 2, 4, and 6 months of treatment were 64.9%, 80.3%, and 82.5%, respectively. Multivariate analysis identified an albumin level of ≥3.3 g/dL and branched-chain amino acids to tyrosine ratio of ≥3.46 as factors contributing to zinc normalization within 3 months of treatment. Treatment resulted in a significant decrease in blood ammonia and serum copper levels, and significant increases in branched-chain amino acids-to-tyrosine ratios and alkaline phosphatase levels. Seven (7.2%) patients prematurely discontinued treatment due to hypocupremia. By the end of treatment, subjective symptoms had resolved in 46.2% of patients. By 3 months post-treatment, serum zinc levels had reverted to levels close to those at baseline. CONCLUSIONS: Treatment with zinc acetate hydrate resulted in normalization of serum zinc levels at a high rate. The main reasons for discontinuation of treatment included hypocupremia.

Analysis of hepatitis B surface antigen (HBsAg) using high-sensitivity HBsAg assays in hepatitis B virus carriers in whom HBsAg seroclearance was confirmed by conventional assays.

AIM: We investigated the utility of high-sensitivity hepatitis B surface antigen (HBsAg) assays compared with conventional HBsAg assays. METHODS: Using serum samples from 114 hepatitis B virus (HBV) carriers in whom HBsAg seroclearance was confirmed by conventional HBsAg assays (cut-off value, 0.05 IU/mL), the amount of HBsAg was re-examined by high-sensitivity HBsAg assays (cut-off value, 0.005 IU/mL). Cases negative for HBsAg in both assays were defined as consistent cases, and cases positive for HBsAg in the high-sensitivity HBsAg assay only were defined as discrepant cases. RESULTS: There were 55 (48.2%) discrepant cases, and the range of HBsAg titers determined by high-sensitivity HBsAg assays was 0.005-0.056 IU/mL. Multivariate analysis showed that the presence of nucleos(t)ide analog therapy, liver cirrhosis, and negative anti-HBs contributed to the discrepancies between the two assays. Cumulative anti-HBs positivity rates among discrepant cases were 12.7%, 17.2%, 38.8%, and 43.9% at baseline, 1 year, 3 years, and 5 years, respectively, whereas the corresponding rates among consistent cases were 50.8%, 56.0%, 61.7%, and 68.0%, respectively. Hepatitis B virus DNA negativity rates were 56.4% and 81.4% at baseline, 51.3% and 83.3% at 1 year, and 36.8% and 95.7% at 3 years, among discrepant and consistent cases, respectively. Hepatitis B surface antigen reversion was observed only in discrepant cases. CONCLUSIONS: Re-examination by high-sensitivity HBsAg assays revealed that HBsAg was positive in approximately 50% of cases. Cumulative anti-HBs seroconversion rates and HBV-DNA seroclearance rates were lower in these cases, suggesting a population at risk for HBsAg reversion.

Safety of Sofosbuvir and Ribavirin Combination Therapy in a Patient Who Developed Anemia due to Ribavirin.

Interferon (IFN) and ribavirin (RBV) combination therapy was previously the standard of care for treatment of hepatitis C virus (HCV) genotype 2 infection. But, it often induced hemolytic anemia. In 2014, sofosbuvir (SOF) was approved for the treatment of chronic HCV genotype 2 in Japan. SOF/RBV therapy is more effective against genotype 2 than IFN/RBV therapy. We report a case of a 74-year-old woman with chronic HCV genotype 2b infection. She received five treatments including RBV and IFN therapy before SOF was approved and all of them were ineffective. Therapies that included RBV induced severe anemia and led to discontinuation of treatment. With pegylated IFN/RBV therapy, the maximum change in hemoglobin (Hb) from baseline was -3.7 g/dL. However, SOF/RBV therapy was effective and she achieved sustained virologic response (SVR) with a maximum change in Hb from baseline of only -1.2 g/dL. We also found reticulocyte count was very low during treatment in this case and speculate it was one of the reasons that she developed hemolytic anemia with RBV. In conclusion, SOF/RBV therapy is effective and allowed the patient to achieve SVR. An SOF/RBV regimen is safe and effective for patients who have or are at risk of anemia induced by RBV.

Successful achievement of sustained virological response to triple combination therapy containing simeprevir in two patients with chronic hepatitis C who had failed asunaprevir:Daclatasvir combination therapy.

Patients 1 and 2 were treatment-naive women who had genotype 1b chronic hepatitis C. Both had IL-28B genotype TT, and amino acid substitutions of core 70 and 91 were both wild type. Search for the presence of resistance-associated variants (RAV) in non-structural (NS)3 and NS5A regions confirmed wild-type D168 and L31, along with Y93H, in both patients. These patients participated in a Japanese phase III clinical study of asunaprevir and daclatasvir at the age of 52 and 67 years, respectively, and were treated with the combination regimen for 24 weeks. However, both experienced post-treatment relapse, and then treated with triple combination therapy with simeprevir, pegylated interferon (IFN) and ribavirin at the age of 53 and 68 years, respectively, and achieved sustained virological response. A search for RAV prior to simeprevir treatment identified multiple resistance including D168E, Y93H and L31V in both patients. It has been demonstrated that, in many cases, a treatment failure with a combination of asunaprevir and daclatasvir results in acquisition of RAV in NS3 and NS5A regions and that drug-resistant mutants, particularly those in the NS5A region, survive for a long time. In these cases, direct-acting antivirals targeted towards the NS5A region may have a limited efficacy. The present case report is based on an idea that a regimen containing IFN with simeprevir could be a therapeutic option particularly for those who are likely to be highly sensitive and tolerable to IFN.

[Antiviral therapy for patients with chronic hepatitis B with multi-drug resistance to nucleoside analogues].

In 18 of 547 patients who had received nucleoside analogue preparations for 1 year or more, multi-drug resistance was detected, after a median follow-up of 53 months. No patient showed liver failure related to multi-drug resistance acquisition. Multi-drug resistance was associated with entecavir (ETV) therapy in 7 lamivudine (LAM) -resistant patients, combination therapy with adefovir dipivoxil (ADV) in 8 LAM-resistant patients, LAM switching to ETV in 2 patients, and initial ETV administration in 1. For treatment, combination therapy with LAM and ADV was performed. In non-responders, combination therapy with ADV and ETV was employed. In all LAM- and ADV-resistant patients, and the HBV DNA level decreased to 3.0LC/ml or less. However, a similar decrease was noted in 7 (58.3%) of 12 LAM- and ETV-resistant patients. Of the 18 patients, 1 did not respond to combination therapy with ADV and ETV. Therapy with tenofovir disoproxil fumarate (TDF) was required.

Antiviral effects of peginterferon alpha-2b and ribavirin following 24-week monotherapy of telaprevir in Japanese hepatitis C patients.

BACKGROUND/AIMS: Anemia is commonly observed as a side effect in a treatment with protease inhibitors combined with peginterferon alpha and ribavirin for hepatitis C virus infection. This study assessed the safety, tolerability, viral kinetics, and selection of variants in telaprevir monotherapy for 24 weeks, and outcomes of the off-study treatment with peginterferon alpha-2b and ribavirin among Japanese female patients at a median age of 54 years who were difficult to treat with the standard therapy (peginterferon alpha-2b and ribavirin) alone in Japan. METHODS: Four treatment-naïve patients with chronic hepatitis C virus subtype 1b infection received telaprevir (750 mg every 8 h) alone for 24 weeks. All patients then started the off-study treatment with peginterferon alpha-2b and ribavirin. Safety, tolerability, hepatitis C virus RNA levels, and emergence of telaprevir-resistant variants were monitored. RESULTS: During the 24 weeks of telaprevir monotherapy, there was no discontinuation due to adverse events, but 2 patients stopped the intake at weeks 6 and 15 because of viral breakthrough. Emergence of telaprevir-resistant variants was observed in 3 patients who showed viral breakthrough. These variants were eliminated by the off-study treatment, and sustained virological response was achieved in all patients. CONCLUSIONS: Anemia was manageable by carefully adjusting the ribavirin dosage in the standard therapy that followed telaprevir monotherapy. This sequential regimen seems to be safer and more tolerable than the triple combination of telaprevir, peginterferon alpha, and ribavirin, especially among elderly females with low baseline hemoglobin.

Efficacy of color Doppler ultrasonography for the diagnosis of duodenal varices successfully treated with percutaneous transhepatic obliteration.

We treated a 74-year-old woman who complained of tarry stool. Neither endoscopic examination of the upper gastrointestinal tract nor colonoscopy revealed any finding indicative of bleeding, and (99m)Tc-HSA-D pool scintigraphic imaging showed no accumulation of blood in the digestive tract. Small tortuous collateral veins were observed on computed tomography (CT) in the distal third portion of the duodenum. Color Doppler ultrasonography obtained color flow images of varices in the distal third portion of the duodenum indicating turbulent flow, and color flow imaging showed the outflow vessel from duodenal varices. Duodenoscopy revealed tortuous varices, with erosions and blue in appearance, in the same area. Percutaneous transhepatic portography was carried out 18 days after the treatment of ascites, and hepatofugal blood flow was confirmed in the pancreatic duodenal vein originating near the junction between the splenic and inferior mesenteric veins with the passage of contrast medium into the duodenal varices, which drained into the left ovarian vein. We performed selective catheterization into the afferent vein of the varices, and injected 8 ml of a 5% solution of ethanolamine oleate containing iopamidol. Microcoil embolization using steel coils was added because the therapeutic effect resulting after the relatively rapid washout of sclerosant was insufficient. CT and color Doppler ultrasonography showed absence of blood flow in the varices 1 week after the therapy. This patient has had no episodes of rebleeding in the 24 months after therapy. Color Doppler ultrasonography was useful in diagnosing this case of duodenal varices and in evaluating therapeutic effect.

Hemodynamic evaluation of rectal varices by color Doppler ultrasonography: a case report.

A 69-year-old man with liver cirrhosis was admitted to our hospital with general fatigue. Colonoscopy revealed risky red color sign-positive enlarged tortuous rectal varices. Endoscopic injection sclerotherapy (EIS) was performed three times weekly using 5% ethanolamine oleate with iopamidol; the total amount of sclerosant was 7 ml. Images of rectal varices and the outflowing vessel from rectal varices were obtained via color Doppler ultrasonography before EIS, and fast Fourier transform analysis showed a continuous flow with a frequency shift of 276.6 Hz. We successfully performed EIS for this patient, having effective varicealography. After EIS, colonoscopy revealed shrinkage of the varices in the rectum, and color Doppler indicated an extreme decrease of blood flow in the rectal varices. In conclusion, color Doppler is a useful noninvasive modality for detecting rectal varices and for evaluating the therapeutic effects of EIS.

Usefulness of electronic radial endoscopic color Doppler ultrasonography in esophageal varices: comparison with convex type.

BACKGROUND: Endoscopic color Doppler ultrasonography (ECDUS) is a method for detecting color flow images in blood vessels. We previously reported on the usefulness of ECDUS (convex-type scanning instruments with forward--oblique viewing) for evaluating the hemodynamics of esophageal varices. In the present study, we report the usefulness of new electronic radial ECDUS in cases of esophageal varices by comparison with convex-type ECDUS. METHODS: Twenty-six patients with esophageal varices were identified and studied. The underlying pathologies of portal hypertension included liver cirrhosis (15 patients) and cirrhosis associated with hepatocellular carcinoma (11 patients). Endoscopic findings of esophageal varices were as follows: Cb, F3, and Ls varices in four patients; Cb, F2, and Lm varices in 21 patients; and Cb, Lm, and F1 varices in one patient. RC1 was observed in the esophagus in 14 of the 26 patients. RC2 was noted in 11 cases, and RC0 was seen in one patient. ECDUS was performed using a Pentax EG-3630UR (forward view) with a distal tip diameter of 12 mm. The instrument (electronic radial array) has a curved array scanning transducer with variable frequency (5.0, 7.5, 10.0 MHz). A Hitachi EUB 6500,8500 was used for the display, providing 270 degrees images. We monitored the color flow images of esophageal varices, paraesophageal veins, palisade veins, perforating veins, and pulsatile waves using this technique. As a control, 110 patients were examined by convex-type ECDUS. RESULTS: (1) Color flow images of esophageal varices and paraesophageal veins were obtained in 26 of the 26 patients, whereas color flow images of perforating veins were obtained in 18 of the 26 patients (69.2%). Color flow images of palisade veins were obtained in 12 of the 26 patients (46.2%). (2) Color flow images of pulsatile waves were obtained in 10 of the 26 patients (38.5%). Color flow images of pulsatile waves were detected in zero (0%) of the 4 F3 varices, in nine (42.9%) of the 21 F2 varices, and in the 1 (100%) case of F1 varices. Also, color flow images of pulsatile waves were detected in seven (50.0%) of the 14 RC1 varices, in two (18.2%) of the 11 RC2 varices, and in the 1 (100%) case of RC0 varices. (3) As a control, 110 patients were examined by convex-type ECDUS. Color flow images of esophageal varices and paraesophageal veins were obtained in 110 of the 110 patients, whereas color flow images of perforating veins were obtained in 74 of 110 (67.3%) with convex-type ECDUS. The detection rate of palisade veins with electronic radial ECDUS (12 of the 26 patients, 46.2%) was significantly higher than with convex-type ECDUS (28 of the 110 patients, 25.5%) (P<0.05). The detection rate of pulsatile waves with electronic radial ECDUS (10 of the 26 cases, 38.5%) was significantly higher than with convex-type ECDUS (3 of the 110 cases, 2.7%) (P<0.0001). CONCLUSIONS: Electronic radial ECDUS provides clear color flow images of blood vessels in esophageal varices with the additional advantages of forward-view optics and extended 270 degrees views. Electronic radial ECDUS was superior to convex-type ECDUS in detecting palisade veins and pulsatile waves.

Clinical features of hepatocellular carcinoma with extrahepatic metastases.

BACKGROUND: There are few detailed clinical reports about extrahepatic metastases of hepatocellular carcinoma (HCC). The purpose of the present study was to elucidate the clinical features of extrahepatic metastases of HCC. METHODS: The clinical records of 482 patients who had been diagnosed as having HCC during the period from January 1995 to March 2001 were retrospectively reviewed. Extrahepatic metastases had been detected in 65 patients. Clinical features of those 65 patients were analyzed. RESULTS: Patients with extrahepatic metastases had more advanced intrahepatic tumors at the first diagnosis of HCC: 73.8% of the patients with extrahepatic metastases had tumors of intrahepatic tumor stage T3 or T4 according to the TNM classification, while only 28.5% of the patients without extrahepatic metastases had tumors of T3 or T4 (P < 0.001). Vessel invasion was also detected at the first diagnosis of HCC more frequently in the patients with extrahepatic metastasis (P < 0.001). The frequent metastatic sites were lung (53.8%), bone (38.5%), and lymph node (33.8%). Other metastatic sites were the adrenal gland, peritoneum, skin, brain and muscle. The median survival time and 1-year survival rate were 7 months (range: 1-59 months) and 24.9%, respectively. Patients with Child-Pugh grade B and C (P = 0.0018) and patients with positive serum alpha-fetoprotein (P = 0.011) had significantly poor prognosis. CONCLUSIONS: Extrahepatic metastases of HCC are not rare. The possibility of extrahepatic metastases and the clinical features of extrahepatic metastases should be considered when examining patients with HCC, particularly those with advanced intrahepatic tumors, to enable precise evaluation of the spread of HCC and determination of the appropriate treatment method.

Efficacy of argon plasma coagulation for gastric antral vascular ectasia associated with chronic liver disease.

Gastric antral vascular ectasia (GAVE) is a rare cause of chronic gastrointestinal bleeding. The aim of this study was to evaluate the relationship between GAVE with cirrhotic patients and liver dysfunction, portal hypertension and the safety and efficacy of argon plasma coagulation (APC) in treating GAVE with cirrhotic patients. Eight cirrhotic patients with the characteristic endoscopic findings of GAVE were registered. In this study, APC was performed for GAVE in all eight patients. The patients-liver function was classified by Child-Pugh classification and classifications were: two class A, five class B and one class C (mean score: 7.8). Five patients had previously received prophylactic endoscopic injection sclerotherapy for esophageal varices and one had esophageal varices. Balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices had been performed in other one patient. Portal hypertensive gastropathy (PHG) was recognized in only one case. APC was performed in all eight patients and one to three treatment sessions were needed (mean: 1.8 sessions). No complications were observed in the initial treatment. During follow-up, endoscopies revealed the recurrence of GAVE in two patients requiring further treatment by APC (recurrence rate: 25%). After APC treatment, the recurrence of GAVE was not observed with endoscopy in the other six patients. The results suggest that GAVE is related to severe liver damage and portal hypertension in cirrhotic patients. APC is a safe and effective treatment against GAVE.

Evaluation of arterial blood flow in esophageal varices via endoscopic color Doppler ultrasonography with a galactose-based contrast agent.

BACKGROUND: We examined the usefulness of endoscopic color Doppler ultrasonography, using Levovist in evaluating the arterial blood flow, in patients with esophageal varices. METHODS: The study involved 110 patients with esophageal varices who were examined using endoscopic color Doppler ultrasonography (ECDUS). We compared vessel images detected by pre-contrast ECDUS with those detected by enhanced ECDUS. We evaluated the detection rate of the pulsatile wave, and measured systolic velocity and end-diastolic velocity. We calculated the resistance index (RI), which demonstrates the resistance of peripheral vessels in arterial flow. RESULTS: Color flow images of the pulsatile wave were obtained by pre-contrast ECDUS in 3 (2.7%) of the 110 patients. Color flow images of the pulsatile waves were obtained in 40 (36.4%) of the 110 patients by enhanced ECDUS using Levovist. That is, by using Levovist, a pulsatile wave could be delineated in 37 patients in whom pulsatile waves were previously undiagnosed via pre-contrast ECDUS. Color flow images of the pulsatile waves were detected in 37 (37.7%) of the 98 F2 varices and in 3 (25.0%) of the 12 F3 varices. Color flow images of the pulsatile wave were detected in 35 (40.2%) of the 87 red color (RC)(+) varices, and in 5 (21.7%) of the 23 RC(++) or RC (+++) varices. Next, we calculated the RI of the pulsatile wave, obtained by enhanced ECDUS using Levovist, in 40 patients. The RI ranged from 0.49 to 0.83 (mean, 0.67 +/- 0.09); there were nine patients with RIs of less than 0.60, and all 9 of these patients had both F2 and RC(+) type varices (100%). CONCLUSIONS: Levovist contrast in ECDUS examinations suggests that arterial flow is involved in the formation of esophageal varices.

Perforating veins in recurrent esophageal varices evaluated by endoscopic color Doppler ultrasonography with a galactose-based contrast agent.

BACKGROUND: We evaluated the usefulness of endoscopic color Doppler ultrasonography (ECDUS) with Levovist, a galactose-based contrast agents, for detecting veins in the esophageal wall in patients with recurrent esophageal varices after endoscopic therapies. METHODS: We compared vessel images detected prior to the use of contrast with those detected by enhanced ECDUS in 29 patients with recurrent esophageal varices. After the pre-contrast ECDUS examination, all 29 patients received Levovist intravenously, at a concentration of 300 mg/ml. A 7.5-ml dose of the contrast agent was injected at a slow infusion rate, of 1 ml/min. The perforating veins detected by ECDUS were classified, according to flow direction, into three different types. Type 1 showed inflow from the paraesophageal veins to the esophageal varices. Type 2 showed outflow from the esophageal varices to the paraesophageal veins, while type 3 was a mixed type with both inflow and outflow. For comparison, 26 patients without recurrent esophageal varices were studied. RESULTS: Color flow images of perforating veins were obtained in 9 (31.0%) of the 29 patients with recurrent esophageal varices with pre-contrast ECDUS. The detection rate of perforating veins in the patients with recurrent esophageal varices (31.0%) was significantly higher than that in patients without recurrent esophageal varices (0 of 26; 0%) with pre-contrast ECDUS. Color flow images of perforating veins were detected in 22 (75.9%) of the 29 patients with recurrent esophageal varices after Levovist contrast. On the other hand, color flow images of perforating veins were not detected in any of the 26 patients without recurrent esophageal varices after Levovist contrast. Type 1 perforating veins were recognized in 6 (20.7%) of the 29 patients, type 2 in 2 (6.9%) of the 29, and type 3 in 1 (3.4%) of the 29 prior to the use of contrast. After the enhanced ECDUS, type 1 perforating veins were recognized in 13 (44.8%) of the 29 patients, type 2 in 6 (20.7%) of the 29, and type 3 in 3 (10.3%) of the 29. All color-flow images detected with pre-contrast ECDUS were enhanced after Levovist contrast. CONCLUSIONS: Perforating veins can be detected at a high rate by ECDUS with Levovist in patients with recurrent esophageal varices after endoscopic therapy.