Xenon computed tomography can evaluate the improvement of hepatic hemodynamics before and after endoscopic injection sclerotherapy.

BACKGROUND: Xenon computed tomography (Xe-CT) provides quantitative information on tissue blood flow (TBF). In the present study, Xe-CT was performed in patients with esophagogastric varices (EGV) before and after endoscopic injection sclerotherapy (EIS) to evaluate hepatic blood flow (HBF), hepatic arterial TBF (HATBF) and portal venous TBF (PVTBF). METHODS: Subjects comprised of 88 patients with EGV (49 men, 39 women, average age 65.8 ± 11.5 years, median age 68 years, 30-86 years) and liver cirrhosis related to either hepatitis C virus (C) (n = 33), hepatitis B virus (B) (n = 3), alcohol (AL) (n = 22), AL + C (n = 7), AL + B (n = 1), B + C + AL (n = 1), nonalcoholic steatohepatitis (NASH) (n = 4), autoimmune hepatitis (AIH) (n = 5), primary biliary cirrhosis (PBC) (n = 2), or cryptogenic (n = 10) were enrolled. All patients, who were enrolled in this study, were performed EIS for prophylaxis. Xe-CT and measurement of the retention rate of indocyanine green 15 min after administration (ICG R15) were performed before and after EIS. Total hepatic TBF (THTBF) and PVTBF/HATBF ratio (P/A) were also calculated. RESULTS: PVTBF, HATBF, THTBF, P/A and ICG R15 before EIS were 28.3 ± 8.91, 22.5 ± 14.4 and 50.8 ± 17.6 ml/100 ml/min, 1.62 ± 0.71 and 28.8 ± 12.7 %, respectively and those after EIS were 31.9 ± 10.0, 19.3 ± 11.6, and 51.2 ± 17.0 ml/100 ml/min, 1.92 ± 0.84 and 23.6 ± 11.3 %, respectively. PVTBF and P/A after EIS were significantly higher than those before EIS (p = 0.00444, p = 0.0179, respectively), and HATBF and ICG R15 after EIS were significantly lower than those before EIS (p = 0.00129, p < 0.001, respectively). CONCLUSIONS: Xenon computed tomography showed that PVTBF increased after EIS for EGV and HATBF decreased in response to an increase in PVTBF.

Gastric wash-based molecular testing for antibiotic resistance in Helicobacter pylori.

BACKGROUND: A number of noninvasive tests have been developed to establish the presence of Helicobacter pylori infection. However, thus far these tests have only been capable of detecting its presence. An increasing number of antibiotic-resistant H. pylori infections have been reported and they are known to be correlated with 23S rRNA single nucleotide polymorphisms (SNPs). We hypothesized that genomic analysis of H. pylori recovered from gastric washes could not only be less invasive, but also useful as a screening test and for assessing the outcome of eradication therapy. METHODS: Biopsy specimens and gastric washes were collected from 100 patients during endoscopic examination. Then we analyzed 23S rRNA, ureA, and cagA genes using PCR and high-throughput pyrosequencing analysis. RESULTS: Forty-five percent (44/97) of patients tested positive for ureA and 42.3% (41/97) tested positive by a rapid urease test. One hundred percent (35/35) of patients who tested positive by both methods were observed to have the cagA gene. Among these 35 patients, 23S rRNA SNPs were present in 34.3% (12/35). CONCLUSIONS: Gastric wash-based PCR and a pyrosequencing assay were used to rapidly detect and estimate the number of 23S rRNA SNPs in clinical isolates of H. pylori. Not only is this a less invasive technique, but it can also diagnose drug resistance.

Effect of nucleoside analog-interferon sequential therapy on patients with acute exacerbation of chronic hepatitis B.

AIM: Nucleoside analog (NA)-interferon (IFN) sequential therapy may enable the long-term control of chronic hepatitis B (CHB) and the withdrawal of the nucleoside analog. We evaluated the efficacy of NA-IFN sequential therapy for acute exacerbation of CHB. METHODS: A total of 12 patients with acute exacerbation of CHB, nine of whom were positive for hepatitis B e antigen (HBeAg), were enrolled in this study. All the patients were treated with lamivudine 100 mg/day alone for 20 weeks, then with both IFN-alpha 6 megaunits three times per week and lamivudine for 4 weeks, and lastly, with IFN-alpha alone for 20 weeks. Patients whose serum alanine aminotransferase (ALT) level was normalized, whose serum hepatitis B virus (HBV) DNA level decreased to less than 5 log copies/mL, and HBeAg level was absent 24 weeks after the end of treatment were defined as having sustained virological response (SVR). The other patients were defined as having no response (NR). RESULTS: Four out of nine (44.4%) HBeAg-positive and all three HBeAg-negative patients achieved SVR. The levels of serum alanine aminotransferase (ALT), HBV DNA and HBV core-related antigen were similar between SVR and NR patients at baseline. Three of four patients (75.0%) whose serum HBeAg became negative at the end of treatment achieved SVR, while one of five (20.0%) whose serum HBeAg remained positive achieved SVR. CONCLUSION: NA-IFN sequential therapy for patients with acute exacerbation of CHB enables the withdrawal of treatment and is particularly effective for patients whose serum HBeAg has become undetectable by the end of the IFN treatment.

Short-term prolongation of pegylated interferon and ribavirin therapy for genotype 1b chronic hepatitis C patients with early viral response.

AIM: We tailored extended treatments using pegylated interferon (PEG IFN) and ribavirin (RBV) to viral responses after initiation of therapy and investigated the efficacy and safety of its therapy for chronic hepatitis C (CHC) patients. METHODS: Eighty-two genotype 1b CHC patients were enrolled in the present study. All patients received PEG IFN-alpha-2b and weight-based RBV therapy. We defined a viral response in which serum HCV-RNA is undetectable at week 4 as rapid viral response (RVR), detectable at week 4 and undetectable by week 12 as early viral response (EVR), and detectable at week 12 and undetectable by week 24 as late viral response (LVR). We set the treatment duration depending on viral response; 48 weeks for RVR patients and 72 weeks for LVR. Furthermore, EVR patients received a short-term extension of treatment duration to 52-60 weeks. We prospectively investigated sustained viral response (SVR) rates of these groups. RESULTS: Overall SVR rate for the total patient group was 57.3%. SVR rates of the RVR, EVR and LVR patients were 100%, 80.5% and 40.0%, respectively. Nine patients could not complete this treatment protocol. Baseline platelet count and mutation in the interferon sensitivity-determining region of NS5A were significant independent predictors of SVR, and amino acid substitution of the core region was a significant independent predictor of non-viral response by multivariate logistic regression analyses. CONCLUSION: The results indicate that short-treatment extension of PEG IFN plus RBV treatment protocols in EVR patients can improve overall SVR rates.

Effect of treatment with interferon alpha-2b and ribavirin in patients infected with genotype 2 hepatitis C virus.

AIM: Nearly 20% of chronic hepatitis C (CHC) patients with genotype 2 hepatitis C virus (HCV) infection are not curable, even by interferon (IFN)-ribavirin combination therapy. The aim of this study is to investigate the factors that determine the efficacy of combination therapy in patients with genotype 2 HCV infection. METHODS: Fifty patients with CHC who underwent a treatment of 6 MU IFN alpha-2b with ribavirin for 24 weeks were retrospectively analyzed. RESULTS: All the patients showed no serum HCV-RNA within 12 weeks after starting the therapy. Forty-one of the 50 patients (82%) achieved a sustained virological response (SVR). The age, sex, genotype (2a vs. 2b) and grade/stage of the liver by histopathology and pretreatment viral load werenot different between the sustained responders and relapsers. Univariate analysis showed that an earlier viral clearance from blood and a larger number of amino acid substitutions in the interferon sensitivity determining region (ISDR) were predictors of SVR. Multivariate analysis showed that a large number of amino acid substitutions in the ISDR was a predictor of SVR. CONCLUSION: The characterization of the amino acid sequences of ISDR may be helpful for predicting a relapse after combination therapy in patients with genotype 2 HCV infection.

Fatal liver failure caused by reactivation of lamivudine-resistant hepatitis B virus: a case report.

We present a case of fetal liver failure caused by the activation of lamivudine-resistant hepatitis B virus (HBV) nine months after lamivudine treatment. A 57-year old man visited our hospital for the treatment of decompensated chronic hepatitis B. Lamivudine was started in December 2001. Subsequently, serum HBV was negative for HBV DNA with seroconversion from HBeAg to anti-HBe and improvement of liver function. However, HBV DNA and HBeAg were again detected in September 2002. He was complicated by breakthrough hepatitis and admitted to our hospital in November for severely impaired liver function. Vidarabine treatment was started and serum HBV DNA and alanine aminotransferase (ALT) decreased transiently. However, after the start of alpha-interferon treatment, HBV DNA level increased and liver function deteriorated. He died 1 mo after admission. An analysis of amino acid sequences in the polymerase region revealed that rtM204I/V with rtL80I/V occurred at the time of viral breakthrough. After the start of antiviral treatment, rtL180M was detected in addition to rtM204I/V and rtL80I/V, and became predominant in the terminal stage of the disease. HBV clone with a high replication capacity may be produced by antiviral treatment leading to the worsening of liver function. Antiviral therapy for patients with breakthrough hepatitis in advanced liver disease should be carefully performed.

Risk factors for retinopathy associated with interferon alpha-2b and ribavirin combination therapy in patients with chronic hepatitis C.

AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy. METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy. RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%) despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension, or pretreatment arteriosclerotic changes in the optic fundi. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P = 0.004, OR = 245.918, 95% CI = 5.6-10786.2). CONCLUSION: Retinopathy associated with combination therapy of interferon alpha-2b and ribavirin tends to develop in patients with hypertension.