High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial.

UNLABELLED: In uncontrolled clinical studies, ursodeoxycholic acid (UDCA) had a beneficial effect on nonalcoholic steatohepatitis (NASH). However, a large controlled trial using UDCA (13-15 mg/kg/day) was unable to confirm these results. Accordingly, a randomized, placebo-controlled study was initiated with a high dose of UDCA (23-28 mg/kg/day). The allocation of patients and the evaluation of liver histology were performed according to a modified Brunt score and the nonalcoholic fatty liver disease activity score (NAS). With the modified Brunt score, 185 patients with histologically proven NASH were randomized [intention to treat (ITT)], and 147 were treated per protocol (PP). With the NAS, 137 patients were confirmed to have NASH, 48 had borderline NASH, and 1 did not have NASH. The treatment time was 18 months. At entry, the treatment groups were comparable. A second biopsy sample was obtained from 139 of 185 patients (NAS: 107/137). The primary criterion for evaluation was a change in the liver histology; the secondary criteria were single histological variables and liver biochemistry. Significant differences in the overall histology could not be detected between the two treatment groups with the modified Brunt score (P = 0.881) or NAS (P = 0.355). Only lobular inflammation improved significantly (P for the modified Brunt score = 0.011, P for NAS = 0.005). In subgroup analyses, significant improvements in lobular inflammation were also observed in males, younger patients up to 50 years of age, slightly overweight patients, and patients with hypertension and an increased histology score. The fibrosis score did not change (P for ITT = 0.133, P for PP = 0.140). With the exception of gamma-glutamyl transferase, UDCA did not improve laboratory data. CONCLUSION: High-dose UDCA failed to improve the overall histology in patients with NASH in comparison with placebo.

Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy.

OBJECTIVES: Preliminary uncontrolled studies of photodynamic therapy (PDT) of bile duct cancer (BDC) have shown astonishingly good results in the reduction of cholestasis, improvement of life quality, and potential improvement of survival time. Therefore, we investigated the influence of PDT on survival time in advanced BDC in a randomized controlled study. METHODS: Thirty-two patients with nonresectable BDC were randomized. In the PDT group 48 h after intravenous application of 2 mg/kg body weight of Photosan-3((R)), light activation was performed. In the control group, patients were treated with endoprostheses but no PDT. RESULTS: PDT group and the control group were comparable due to age, gender, performance status, bilirubin level, and BDC stage (Bismuth classification). The median survival time after randomization was 7 months for the control group and 21 months for the PDT group (p= 0.0109). In half of the initially percutaneously treated patients, we could change from percutaneous to transpapillary drainage after PDT. Four patients showed infectious complications after PDT versus one patient in the control group. DISCUSSION: PDT is minimally invasive but shows a considerable postinterventional cholangitis rate. PDT has the potential to result in a changeover of current palliative treatment of BDC.

Improved preoperative tumor staging by 5-aminolevulinic acid induced fluorescence laparoscopy.

BACKGROUND: We report our data in 35 patients who underwent preoperative conventional and fluorescence-based staging laparoscopy. We use the data to address the questions of whether fluorescence examination increases the yield of metastatic lesions and alters treatment intervention. METHODS: Fluorescence laparoscopy was successfully performed in 30 patients with GI malignancies. After sensitization with 5-aminolevulinic acid, conventional white-light mode and fluorescence-light laparoscopies were sequentially performed. A suspected malignancy was biopsied. OBSERVATIONS: In 5 patients, examinations were incomplete because of adhesions. In 9 of 10 patients, hepatic or peritoneal metastases were detected by white-light examination. In 4 of these 9, blue-light examination yielded more metastatic lesions. In one patient with no lesions by white- or blue-light examination, surgery revealed hepatic metastasis in a location not accessible to laparoscopic examination. In 18 patients, surgery confirmed the absence of metastatic lesions. CONCLUSIONS: A fluorescence, blue-light examination yielded more lesions than the conventional white-light examination but did not alter treatment intervention and did not enhance yield when metastatic lesion is in an inaccessible location. Continued research should focus on whether treatment intervention will be altered by the fluorescence examination.

Prospective, randomized, single-center trial comparing 3 different 10F plastic stents in malignant mid and distal bile duct strictures.

BACKGROUND: The aim of this study was to determine whether patency rates differ with respect to the material, design, and surface texture of 3 different plastic stents. METHODS: A total of 120 patients (median age 70.5 years; interquartile range 62-78 years) with malignant mid or distal bile duct strictures, seen between March 1996 and May 1999, were prospectively randomized to receive a 10F polyurethane stent, a Teflon Tannenbaum stent, or a hydrophilic hydromer-coated polyurethane stent. The primary study outcome measure was the interval between stent insertion and the first episode of clogging (or the presence of jaundice at death without stent exchange). All 3 types of stent were studied by scanning electron microscopy before insertion. RESULTS: A total of 19 patients were excluded from long-term follow-up. Median duration of stent patency was 76 days overall (interquartile range 29-150 days) and 76 (interquartile range 30-110) days for hydrophilic hydromer-coated polyurethane, 108 (interquartile range 33-186) days for 10F polyurethane, and 58 (interquartile range 21-188) days for Teflon Tannenbaum stents. There were no statistically significant differences among stent types. The hydrophilic hydromer-coated stent had the smoothest surface, as visualized by scanning electron microscopy. CONCLUSIONS: No significant differences in the patency of 3 types of stents were detected in this randomized trial. In particular, the hydrophilic hydromer-coated plastic stent did not provide clinical advantages despite its smooth surface.

Single nucleotide insertion in the 5'-untranslated region of hepatitis C virus with clearance of the viral RNA in a liver transplant recipient during acute hepatitis B virus superinfection.

Hepatitis C virus (HCV) infection is an important etiology in patients undergoing orthotopic liver transplantation (OLT) world-wide. Antiviral therapy-related clearance of HCV RNA may occur both in patients with chronic HCV infection and in transplanted patients for HCV-related liver cirrhosis, but the role of the 5'-untranslated region (UTR) of HCV containing the internal ribosome entry site (IRES), which directs the translation of the viral open reading frame has not hitherto been evaluated. We studied the 5'-UTR in an HCV-infected recipient of a liver graft that showed spontaneous clearance of HCV RNA during an acute hepatitis B virus (HBV) superinfection. Sequencing of the 5'-UTR of HCV showed a nucleotide A insertion at position 193 of the IRES.