Tilman M. Bauer

Small intestinal bacterial overgrowth in patients with cirrhosis: prevalence and relation with spontaneous bacterial peritonitis.

OBJECTIVES:The significance of small intestinal bacterial overgrowth in patients with cirrhosis is not fully understood and its diagnostic criteria are not uniform. We examined the association of small intestinal bacterial overgrowth with spontaneous bacterial peritonitis and compared various microbiological criteria.METHODS:Jejunal secretions from 70 patients with cirrhosis were cultivated quantitatively and classified according to various definitions. Clinical characteristics of patients were evaluated and the incidence of spontaneous bacterial peritonitis was monitored during a 1-yr follow-up.RESULTS:Small intestinal bacterial overgrowth, defined as ≥105 total colony-forming units/ml jejunal secretions, was present in 61% of patients. Small intestinal bacterial overgrowth was associated with acid-suppressive therapy (p = 0.01) and hypochlorhydria (p < 0.001). Twenty-nine patients with persistent ascites were observed. Six episodes of spontaneous bacterial peritonitis occurred after an average 12.8 wk. Occurence of spontaneous bacterial peritonitis correlated with ascitic fluid protein concentration (p = 0.01) and serum bilirubin (p = 0.04) but not with small intestinal bacterial overgrowth (p = 0.39). Its association with acid-suppressive therapy was of borderline significance (hazard ratio = 7.0, p = 0.08).CONCLUSIONS:Small intestinal bacterial overgrowth in cirrhotic patients is associated with acid-suppressive therapy and hypochlorhydria, but not with spontaneous bacterial peritonitis. The potential role of acid-suppressive therapy in the pathogenesis of spontaneous bacterial peritonitis merits further studies.

Small intestinal bacterial overgrowth in human cirrhosis is associated with Systemic endotoxemia

OBJECTIVES:Systemic endotoxemia has been implicated in various pathophysiological sequelae of chronic liver disease. One of its potential causes is increased intestinal absorption of endotoxin. We therefore examined the association of small intestinal bacterial overgrowth with systemic endotoxemia in patients with cirrhosis.METHODS:Fifty-three consecutive patients with cirrhosis (Child-Pugh group A, 23; group B, 18; group C, 12) were included. Jejunal secretions were cultivated quantitatively and systemic endotoxemia determined by the chromogenic Limulus amoebocyte assay. Patients were followed up for 1 yr.RESULTS:Small intestinal bacterial overgrowth, defined as ≥105 total colony forming units per milliliter of jejunal secretions, was present in 59% of patients and strongly associated with acid suppressive therapy. The mean plasma endotoxin level was 0.86 ± 0.48 endotoxin units/ml (range = 0.03–1.44) and was significantly associated with small intestinal bacterial overgrowth (0.99 vs 0.60 endotoxin units/ml, p = 0.03). During the 1-yr follow-up, seven patients were lost to follow up or underwent liver transplantation and 12 patients died. Multivariate Cox regression showed Child-Pugh group to be the only predictor for survival.CONCLUSIONS:Small intestinal bacterial overgrowth in cirrhotic patients is common and associated with systemic endotoxemia. The clinical relevance of this association remains to be defined.

Diagnosis of small intestinal bacterial overgrowth in patients with cirrhosis of the liver: poor performance of the glucose breath hydrogen test

BACKGROUND/AIMS Small intestinal bacterial overgrowth is known to occur in association with cirrhosis of the liver and studies are needed to assess its pathophysiological role. The glucose breath hydrogen test as an indirect test for small intestinal bacterial overgrowth has been applied to patients with cirrhosis but has not yet been validated against quantitative culture of jejunal secretion in this particular patient population. METHODS Forty patients with cirrhosis underwent glucose breath hydrogen test and jejunoscopy. Jejunal secretions were cultivated quantitatively for aerobe and anaerobe microorganisms. RESULTS Small intestinal bacterial overgrowth was detected by culture of jejunal aspirates in 73% of patients, being associated with age and the administration of acid-suppressive therapy. The glucose breath hydrogen test correlated poorly with culture results, sensitivity and specificity ranging from 27%-52% and 36%-80%, respectively. CONCLUSIONS In patients with cirrhosis, the glucose breath hydrogen test correlates poorly with the diagnostic gold standard for small intestinal bacterial overgrowth. Until other non-invasive tests have been validated, studies addressing the role of small intestinal bacterial overgrowth in patients with cirrhosis should resort to microbiological culture of jejunal secretions.

Regulation of interleukin-6 receptor expression in human monocytes and hepatocytes

Human blood monocytes normally express the interleukin‐6 receptor. Treatment of cultured monocytes with endotoxin, interleukin‐1β, or interleukin‐6 results in a decrease of interleukin‐6 receptor mRNA levels. Glucocorticoids also cause a drop in monocytic interleukin‐6 receptor mRNA levels. We also found interleukin‐6 receptor expression in cultured human hepatocytes, but in contrast to monocytes, where interleukin‐6 receptor mRNA is repressed by the ligand and by interleukin‐1, treatment of hepatocytes with interleukin‐6 or interleukin‐1 resulted in increased interleukin‐6 receptor mRNA levels. Induction of interleukin‐6 receptor mRNA in hepatocytes was less pronounced when glucocorticoids were omitted from the culture medium. We conclude that during noninflammatory homeostasis, blood monocytes are involved in binding of trace amounts of circulating interleukin‐6. During inflammatory events, the main tissue target of interleukin‐6 may be changed from the monocytic population not only to activated B‐cells, but also to the hepatocytes.

Interleukin-6 release by rat liver macrophages

Tissue macrophages of the liver (Kupffer cells) release interleukin-6 (IL-6) in vitro. Since Kupffer cells reside in close proximity to hepatocytes, which are major target cells of IL-6, the regulation of IL-6 release by hepatic macrophages has been investigated in this study. Using the hybridoma growth test to detect IL-6, we found that Kupffer cells already maximally release IL-6 at endotoxin concentrations as low as 1.0 ng/ml. The stimulated secretion of IL-6 was increased 4-8-fold by endotoxin when compared to the control macrophages incubated in serum-containing medium alone. The preincubation of macrophages with interferon-gamma enhanced the capacity of Kupffer cells to respond to endotoxin. The secretion of IL-6 could also be induced by interleukin (IL)-1 beta and tumor necrosis factor (TNF-alpha). The most potent inducers, however, were the paramyxoviruses Newcastle Disease Virus and Sendai Virus. The release of IL-6 by macrophages upon stimulation with endotoxin was almost completely inhibited by 1 microM dexamethasone. Whereas 100 nM of prostaglandin E2 (PGE2) inhibited the release of TNF-alpha in rat Kupffer cells, it did not affect the secretion of IL-6.

Drug-induced hepatocellular liver injury due to benzylpenicillin with evidence of lymphocyte sensitization

BACKGROUND/AIMS Reports on drug-induced liver injury due to benzylpenicillin are scarce and predominantly describe cases of intrahepatic cholestasis. To our knowledge, no immunologically documented case of hepatocellular liver injury due to benzylpenicillin has been reported so far. CASE REPORT A previously healthy man required long-term therapy with benzylpenicillin because of vertebral spondylitis. After 4 weeks of treatment, liver tests showed a marked increase in transaminases associated with high peripheral eosinophil counts. Discontinuation of benzylpenicillin resulted in gradual recovery. INVESTIGATIONS Levels of eosinophil cationic protein were elevated, indicating eosinophil activation and the presence of an immunoallergic reaction. Skin tests and assays for specific Ig E-antibodies to benzylpenicillin were negative, but lymphocyte transformation tests demonstrated T-cell sensitization to benzylpenicillin. CONCLUSIONS According to current causality assessment schemes, our report constitutes a probable case of drug-induced hepatocellular liver injury due to benzylpenicillin.

Blut im Stuhl

Eine 50-jahrige Frau wird wegen blutiger Diarrho akut in die Medizinische Klinik eines Universitatsklinikums aufgenommen. Sie leidet seit 30 Jahren an Colitis ulcerosa und hatte insgesamt 5 akute Schube, letztmals vor 3 Jahren. In der Folge eines Griechenland-Aufenthaltes 4 Monate vor Aufnahme kommt es zu einer akuten Diarrho mit 3–6, z. T. geformten Stuhlen pro Tag, welche sich auf Intensivierung der Therapie mit 5-Aminosalicylsaure und Prednison nicht bessert. Koloskopisch ist 4 Wochen vor Aufnahme eine floride Proktosigmoiditis gesehen worden. Eine Stuhlkultur ergibt zu dem Zeitpunkt keine enteropathogenen Keime. In der Folge nimmt die Stuhlfrequenz auf 10/Tag zu, der Stuhlgang enthalt reichlich Blut- und Schleimbeimengung Die Patientin wird deshalb unter der Verdachts diagnose eines akuten Schubes der Colitis ulcerosa zur Intensivierung der immunsuppressiven Therapie in stationare Behandlung aufgenommen.

ER Folgen des Alkohols

Ein 54-jahriger Bankangestellter stellt sich im Marz 2000 bei seinem Hausarzt vor. Er leidet seit 4 Wochen an Mudigkeit, Schwache, Gewichtsverlust und rezidivierendem Fieber bis 38°C ohne sonstige fokale Symptome. Auf Befragen berichtet er von regelmasigem Bierkonsum (ca. 1 l Bier/Tag) seit vielen Jahren. Der Hausarzt findet klinische und sonographische Zeichen einer Leberzirrhose und weist ihn aufgrund des unklaren Krankheitsbildes stationar ein.