Fibrosis heterogeneity in nonalcoholic steatohepatitis and hepatitis C virus needle core biopsy specimens.

We examined 46 nonalcoholic steatohepatitis (NASH) and 52 hepatitis C virus (HCV) biopsy specimens to determine the magnitude of fibrosis heterogeneity and minimum length for accurate fibrosis staging. Three fibrosis scores were recorded: lowest regional, highest regional, and most common overall. Mean specimen lengths were 1.6 and 1.8 cm in NASH and HCV, respectively (P = .283). Mean (highest minus lowest) fibrosis heterogeneity scores (highest regional fibrosis - lowest regional fibrosis) were 3.7 and 2.0 in NASH and HCV, respectively (P < .001). Of 36 NASH specimens longer than 1.0 cm, 31 (86%) had the highest regional fibrosis in the deepest sampled parenchyma. Shorter specimens were associated significantly with greater fibrosis heterogeneity in NASH (coefficient, -1.3; P < .001) but not in HCV (P = .901). NASH specimens longer than 1.6 cm had significantly lower mean heterogeneity scores than specimens 1.6 cm or shorter (1.2 vs 3.4; P = .012). In NASH, fibrosis heterogeneity can be substantial and is greater than in HCV, and parenchymal injury, fibrosis, and healing might vary in different regions of the liver. The fibrosis stage in patients with NASH might not be assessed accurately in short specimens. Individual needle cores should be longer than 1.6 cm in NASH for accurate fibrosis staging.

Serum ferritin level predicts advanced hepatic fibrosis among U.S. patients with phenotypic hemochromatosis.

BACKGROUND: DNA-based HFE gene testing can confirm hereditary hemochromatosis in most people of Northern European descent. However, liver biopsy is important to detect cirrhosis. OBJECTIVE: To develop noninvasive criteria to predict the presence or absence of advanced hepatic fibrosis or cirrhosis in Americans with hemochromatosis. DESIGN: Cross-sectional study. SETTING: Six tertiary care referral clinics. PATIENTS: 182 patients with phenotypically defined hemochromatosis. MEASUREMENTS: Liver histopathology and serum ferritin, aspartate aminotransferase, and alanine aminotransferase levels. Multivariate logistic regression analysis was used to examine factors associated with cirrhosis (defined as bridging fibrosis or unequivocal cirrhosis on biopsy). RESULTS: Cirrhosis was present in 40 of 182 (22%) patients in the overall group and in 35 of 147 (24%) of C282Y homozygotes. Only 1 of 93 patients with a serum ferritin level less than 1000 microg/L had cirrhosis compared with 39 of 89 patients with serum ferritin levels greater than 1000 microg/L (P < 0.001). No C282Y homozygotes or C282Y/H63D compound heterozygotes with serum ferritin levels less than 1000 microg/L had cirrhosis. Elevated serum aminotransferase levels (P = 0.001) and serum ferritin levels greater than 1000 microg/L (P = 0.001), but not age older than 40 years (P = 0.2), were independently associated with cirrhosis. In a multivariate model, the probability of cirrhosis was 7.4% among patients with serum ferritin levels less than 1000 microg/L compared with 72% among patients with serum ferritin levels greater than 1000 microg/L after adjustment for age and elevated serum liver enzyme levels. CONCLUSIONS: Patients with hemochromatosis and serum ferritin levels less than 1000 microg/L are unlikely to have cirrhosis. Liver biopsy to screen for cirrhosis may be unnecessary in such patients, regardless of age or serum liver enzyme levels.

The burden of acute nonfulminant drug-induced hepatitis in a United States tertiary referral center [corrected].

BACKGROUND/GOALS: There are limited data regarding the frequency and proportionality of drug-induced hepatotoxicity in the United States. We sought to determine the scope of nonfulminant drug-induced hepatitis as seen in a community-based hepatology referral service. STUDY: From a population of 4,039 outpatients referred for evaluation of acute (n = 96) and chronic (n = 3,943) liver disease over a 10-year period, we reviewed the records of those patients diagnosed with acute bona fide drug-induced hepatitis. RESULTS: Thirty-two patients presented with self-limited acute drug-induced hepatitis, representing 0.8% of all hepatology patients and 33% of those patients presenting with acute liver injury. Antibiotics (amoxicillin/clavulanic acid, minocycline, nitrofurantoin, an investigational ketolide antibiotic, trimethoprim-sulfamethoxazole, and trovafloxacin) were the class of drugs most frequently implicated (14 of 32; 44%), while amiodarone was the single agent most commonly associated with liver injury (7 of 32; 22%). The mean age of affected patients was 52.2 years, and we found a male predominance (18 of 32; 56%). The mean time to biochemical resolution after discontinuation of the offending agent was 14.1 weeks. CONCLUSIONS: Drug-induced hepatitis is an uncommon entity in clinical hepatology but does represent a significant proportion of acute self-limited liver disease in the United States. Antibiotics and amiodarone were the most common drug culprits in our population. Time to resolution following the discontinuation of the offending agent may be protracted. Prospective studies are needed to further assess the burden of drug-induced liver injury.

Oral broccoli sprouts for the treatment of Helicobacter pylori infection: a preliminary report.

We sought to determine whether orally consumed broccoli sprouts could eradicate Helicobacter pylori infection in infected human volunteers. Helicobacter pylori-positive patients were identified by stool antigen testing or gastric biopsies. Patients consumed broccoli sprouts (14, 28, or 56 g) twice daily for 7 days. We performed stool antigen testing immediately following the completion of treatment (day 8) and at day 35. Urea breath testing was performed on those patients who remained negative at day 35. Patients completed pre- and posttreatment questionnaires regarding symptoms (abdominal discomfort--pain, nausea, bloating), recent medications, and palatability. Nine patients completed the course of treatment and began follow-up testing. Seven of nine (78%) patients were stool antigen negative immediately after the completion of therapy and six remained negative at day 35. Urea breath testing was completed on six patients. Two patients were negative, two positive, and two indeterminate. Endoscopic gastric biopsies were obtained from one patient with an indeterminate breath test and the tissue was negative for H. pylori by immunohistochemical staining. Of the five patients who provided information on pre- and posttreatment symptoms, two reported improvement, one no change, and one reported worsening. Six patients rated the taste of broccoli sprouts from okay to very good; one patient stated they were "not good." Consumption of oral broccoli sprouts was temporally associated with eradication of H. pylori infection in three of nine patients. Most patients found broccoli sprouts palatable. Further studies are needed to determine the optimal dose of broccoli sprouts and whether concomitant proton pump inhibitors or antibiotics might augment the effectiveness.