Effects of cytomegalovirus infection on the differential diagnosis between biliary atresia and intrahepatic cholestasis in a Chinese large cohort study.

INTRODUCTION AND OBJECTIVES: Differentiating biliary atresia from other causes of neonatal cholestasis is challenging, particularly when cytomegalovirus (CMV) and biliary atresia occur simultaneously. We aimed to elucidate whether CMV infection would affect the differential diagnosis of biliary atresia and intrahepatic cholestasis. PATIENTS AND METHODS: This retrospective study was conducted among patients with neonatal cholestasis admitted to three tertiary hospitals between January 2010 and August 2019. The clinical characteristics, laboratory, and imaging findings were recorded. On the basis of the CMV serology results, the infants were classified into CMV-IgM (+) and CMV-IgM (-) groups. The clinical differences and diagnostic performances of routine predictors between biliary atresia and intrahepatic cholestasis were analyzed in each group. Finally, we compared the diagnostic performances of various tests in the two groups. RESULTS: A total of 705 patients with neonatal cholestasis were enrolled: 215 (30.5%) patients were positive for CMV-IgM, among whom 97 had biliary atresia and 118 had CMV hepatitis; 490 infants were CMV-IgM (-), among whom 240 had biliary atresia and 250 had intrahepatic cholestasis. The diagnostic performances of stool color, direct bilirubin level, γ-glutamyl transpeptidase level, abnormal gallbladder, triangular cord sign, and hepatobiliary scintigraphy between CMV hepatitis and CMV-IgM (+) biliary atresia were similar to those between CMV-IgM (-) biliary atresia and CMV-IgM (-) intrahepatic cholestasis groups. CONCLUSIONS: Our large-scale study showed a high prevalence of CMV infection in patients with neonatal cholestasis in China. The presence of CMV infection did not affect the routine predictors to discriminate biliary atresia and intrahepatic cholestasis.

Ursodeoxycholic acid enriches intestinal bile salt hydrolase-expressing Bacteroidetes in cholestatic pregnancy.

Ursodeoxycholic acid (UDCA) treatment can reduce itch and lower endogenous serum bile acids in intrahepatic cholestasis of pregnancy (ICP). We sought to determine how it could influence the gut environment in ICP to alter enterohepatic signalling. The gut microbiota and bile acid content were determined in faeces from 35 pregnant women (14 with uncomplicated pregnancies and 21 with ICP, 17 receiving UDCA). Faecal bile salt hydrolase activity was measured using a precipitation assay. Serum fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) concentrations were measured following a standardised diet for 21 hours. Women with a high ratio of Bacteroidetes to Firmicutes were more likely to be treated with UDCA (Fisher's exact test p = 0.0178) than those with a lower ratio. Bile salt hydrolase activity was reduced in women with low Bacteroidetes:Firmicutes. Women taking UDCA had higher faecal lithocholic acid (p < 0.0001), with more unconjugated bile acids than women with untreated ICP or uncomplicated pregnancy. UDCA-treatment increased serum FGF19, and reduced C4 (reflecting lower bile acid synthesis). During ICP, UDCA treatment can be associated with enrichment of the gut microbiota with Bacteroidetes. These demonstrate high bile salt hydrolase activity, which deconjugates bile acids enabling secondary modification to FXR agonists, enhancing enterohepatic feedback via FGF19.

Small intestinal bacterial overgrowth in patients with progressive familial intrahepatic cholestasis.

BACKGROUND & AIMS: To date, no studies concerning the presence of small intestinal bacterial overgrowth in patients with progressive familial intrahepatic cholestasis were published. Based upon characteristic of progressive familial intrahepatic cholestasis one can expect the coexistence of small intestinal bacterial overgrowth. The aim of the study was to assess the incidence of small intestinal bacterial overgrowth in patients with progressive familial intrahepatic cholestasis. METHODS: 26 patients aged 8 to 25 years with progressive familial intrahepatic cholestasis were included in the study. Molecular analysis of ABCB11 gene was performed in the vast majority of patients. In all patients Z-score for body weight and height, biochemical tests (bilirubin, bile acid concentration, fecal fat excretion) were assessed. In all patients hydrogen-methane breath test was performed. RESULTS: On the basis of first hydrogen-methane breath test, diagnosis of small intestinal bacterial overgrowth was confirmed in 9 patients (35%), 5 patients (19%) had borderline results. The second breath test was performed in 10 patients: in 3 patients results were still positive and 2 patients had a borderline result. The third breath test was conducted in 2 patients and positive results were still observed. Statistical analysis did not reveal any significant correlations between clinical, biochemical and therapeutic parameters in patients with progressive familial intrahepatic cholestasis and coexistence of small intestinal bacterial overgrowth. CONCLUSIONS: Our results suggest that small intestinal bacterial overgrowth is frequent in patients with progressive familial intrahepatic cholestasis. Moreover, it seems that this condition has the tendency to persist or recur, despite the treatment.

Liver radiofrequency ablation compromises the biological gut barrier.

AIM: Liver radiofrequency ablation (RFA) has been shown to disrupt the mechanical component of the gut barrier. The aim of the present study was to investigate the consequences of liver RFA on the biological gut barrier in terms of the effects of bile production rate and bowel inflammatory state on intestinal microflora balance. METHOD: A total of 25 New Zealand rabbits were assigned to five groups (n = 5 per group): group CBD: subjected to common bile duct (CBD) extracorporeal bypass; group CBD-RFA: subjected to CBD bypass plus one session of open liver RFA; group RFA: subjected to liver RFA; group sham: subjected to sham operation; and group TBD: subjected to total bile deviation (TBD). In groups CBD and CBD-RFA, bile production rate was assessed for 48 h. In groups sham and RFA, measurement of biliary glycine conjugates of cholic and deoxycholic acid levels, histopathologic examination of the non-ablated liver tissue, morphometric analysis, and histopathologic examination of the terminal ileum and microbiological analysis of fecal and tissue samples collected from the jejunum and the cecum (and in group TBD) were performed at 48 h post-operation. RESULTS: One session of liver RFA resulted in ablation of 18.7 ± 2.7% of liver weight. Following liver RFA, bile production rate was reduced, while the levels of biliary bile salts were not affected. There was mild injury of the non-ablated liver parenchyma, mild intestinal wall inflammation, intestinal mucosa atrophy, and intestinal microbial population overgrowth. CONCLUSION: Reduced in bile production and mild bowel inflammation secondary to liver RFA impaired the biological gut barrier as manifested by intestinal microflora imbalance.

Acute intrahepatic cholestasis accompanied with Chlamydophila pneumoniae infection.

We report a case of Chlamydophila (C.) pneumoniae infection presenting with fever and rapid intrahepatic cholestasis. A 63-year-old man had a week-long history of intermittent high fever and rapidly progressive jaundice with atypical erythema. The results of liver function tests were recorded. The results of all serological tests were negative; the IgM, IgG, and IgA titers for C. pneumoniae had increased, which indicates a C. pneumoniae infection. The patient's fever and liver dysfunction improved upon administration of minocycline. Light microscopic findings showed the presence of enlarged liver cells with clear cytoplasm, a few mitotic figures, multinucleated cells, and bile cholestasis. The electron microscopic appearance of liver biopsy showed that bile canaliculi exhibited intrahepatic forms of cholestasis. From the results of light and electron microscopy, we inferred atypical intrahepatic cholestasis, probably resulting from the C. pneumoniae infection.

Hepatitis colestásica por Mycoplasma pneumoniae sin compromiso pulmonar: caso clínico y revisión de la literatura / Cholestatic hepatitis due to mycoplasma pneumoniae without lung involvement: case report and review

El compromiso hepático es una rara manifestación de la infección por Mycoplasma pneumoniae. Casos de hepatitis colestásica sin compromiso pulmonar han sido descritos en niños con infección por M. pneumoniae, pero en adultos sólo unos pocos casos han sido reportados. En este artículo, presentamos el caso de un hombre de 21 años que consultó por un cuadro de fiebre, ictericia y dolor epigástrico asociado con alteración de los exámenes de laboratorio hepático. Los estudios serológicos de M. penumoniae fueron positivos para IgM e IgG. Los síntomas y exámenes de laboratorio mejoraron completamente luego del tratamiento con claritromicina y ácido ursodeoxicólico.

Liver dysfunction is an unusual manifestation of Mycoplasma pneumoniae infection. Cases of cholestatic hepatitis without pulmonary involvement have been described in children with M. pneumoniae infection,but only a few cases have been reported in adults. In this article, we report the case of a 21-year-old man who presented fever, jaundice and epigastric pain associated with altered liver function tests. Serological tests for M. pneumoniae were positive for IgG and IgM. Clinical symptoms and laboratory tests resolved completely after treatment with clarithromycin and ursodeoxicolic acid. A review of reported cases of liver involvement in M. pneumoniae infection is presented.

Hepatitis colestática grave por fiebre Q: presentación de un caso / Severe cholestatic hepatitis due to Q fever: Report of a case

La hepatitis colestática grave por Coxiella burnetii es una forma rara de presentación clínica de la fiebre Q aguda, que se detecta muy ocasionalmente en relación con esta enfermedad infecciosa. Se presenta un caso de hepatitis colestática grave por fiebre Q aguda, con clínica de insuficiencia hepática, marcada colestasis e insuficiencia renal. El estudio serológico inicial por fijación de complemento fue negativo en 2 ocasiones, y se precisó de la ayuda de la biopsia transyugular y de la serología por inmunofluorescencia indirecta para el diagnóstico. A pesar del tratamiento con doxiciclina y ciprofloxacino empeoró progresivamente la colestasis y aparecieron insuficiencia hepática y renal, que desaparecieron rápidamente tras tratamiento esteroideo (AU)

Severe cholestatic hepatitis due to Coxiella burnetii is a rare form of clinical presentation of acute Q fever that is only occasionally detected in association with this infectious disease. We report a case of severe cholestatic hepatitis due to acute Q fever, with clinical signs of hepatic insufficiency, marked cholestasis, and renal insufficiency. The results of the initial serologic study using a complement fixation test were negative on two occasions, and transjugular biopsy and serological analysis with indirect immunofluorescence were required to establish the diagnosis. Despite treatment with doxycycline and ciprofloxacin, the cholestasis progressively worsened, with the development of hepatic and renal insufficiency, which rapidly disappeared after corticosteroid treatment (AU)

[Severe cholestatic hepatitis due to Q fever: report of a case]. / Hepatitis colestática grave por fiebre Q: presentación de un caso.

Severe cholestatic hepatitis due to Coxiella burnetii is a rare form of clinical presentation of acute Q fever that is only occasionally detected in association with this infectious disease. We report a case of severe cholestatic hepatitis due to acute Q fever, with clinical signs of hepatic insufficiency, marked cholestasis, and renal insufficiency. The results of the initial serologic study using a complement fixation test were negative on two occasions, and transjugular biopsy and serological analysis with indirect immunofluorescence were required to establish the diagnosis. Despite treatment with doxycycline and ciprofloxacin, the cholestasis progressively worsened, with the development of hepatic and renal insufficiency, which rapidly disappeared after corticosteroid treatment.

Acute cholestatic hepatitis revealing Mycoplasma pneumoniae infection without lung involvement in an adult patient.

Liver involvement is an unusual manifestation of Mycoplasma pneumoniae infection. Cases of cholestatic hepatitis without pulmonary involvement have been described in children with M. pneumoniae infection but only two cases of cytolytic hepatitis have been reported in adults. We report here the case of an 18-year-old woman who presented with febrile epigastric pain of short duration associated with an elevation of gamma-glutamyl transpeptidase and alkaline phosphatase levels and with a mononuclear syndrome. Serological tests for M. pneumoniae were positive for IgG and IgM. Clinical symptoms and blood test perturbations completely resolved after treatment with macrolide.

Bile infection contributes to intrahepatic calculi formation after excision of choledochal cysts.

Intrahepatic calculi complicate choledochal cysts in 7-8% of patients. Although congenital stenoses and dilatation of the intrahepatic bile ducts are considered responsible for calculi formation, intrahepatic calculi are usually formed after cyst excision. In this study, bile specimens from patients with choledochal cysts were cultured for bacteria. Results were retrospectively analyzed among the following groups: the primary excision group, consisting of 97 patients undergoing cyst excision as a primary treatment (mean age 5.0 years), the internal drainage group, consisting of 13 patients who had previous cyst-enterostomy at cyst excision (mean age 20.2 years); and the hepatolithiasis group, consisting of 12 patients with postoperative hepatolithiasis (mean age 24.2 years). Bacteria were present in the bile of 10 patients (76.9%) in the internal drainage group and in all patients (100%) in the hepatolithiasis group, but present in only 17 patients (17.5%) in the primary excision group (p<0.01). Polymicrobial infection with Gram-negative enterobacteria such as Escherichia coli and Klebsiella species was predominant in the internal drainage and hepatolithiasis groups, while nonenteric bacteria were found in the primary excision group. Bile infection through bilioenterostomy may play an important role in intrahepatic calculus formation after excision of a choledochal cyst.

Ascending cholangitis provokes IL-8 and MCP-1 expression and promotes inflammatory cell infiltration in the cholestatic rat liver.

BACKGROUND/PURPOSE: Postoperative cholangitis is one of the most common complications after bile duct reconstruction. The pathogenesis and early consequences of ascending cholangitis still are unidentified. METHODS: Male Sprague-Dawley rats were divided into 5 treatment groups: control (n = 4), blood sampling and liver biopsy only; group I, [BDL/Eschericha coli; n = 6], ligation of common bile duct (BDL) for a week, followed by Roux-en-Y choledochojejunostomy (RYCJ) and injection of E coli (ATCC 25922) into Roux limb after 24 hours; group II, [BDL/NS; n = 5], same procedures as in group I, with injection of normal saline (NS) into Roux limb; group III, [SBDL/E coli; n = 6], primary RYCJ was constructed 1 week after sham ligation of common bile duct (SBDL) followed by the same treatment as group I; Group IV, [SBDL/N.S; n = 6], same procedures as in group III, but injecting NS into Roux limb. All animals were killed after 24 hours of treatment. Blood was sampled for culture and serum cytokine levels. The liver was harvested for quantitative bacterial culture, as well as for MCP-1, interleukin (IL)-8 (CINC in the rat) and transforming growth factor beta1 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR) and for immunohistochemistry. The choledochojejunostomy was resected for culture. Serum cytokine levels were detected by ELISA kits. RESULTS: A significant increase of E coli ATCC 25922, occurred in the livers of group I rats, compared with group IV (P =.037). MCP-1 expression increased in all groups, compared with control (P =.000). The IL-8 mRNA expression was significantly higher in group I than in control (P =.021). The expression of TGF-beta1 mRNA was similar among the groups (P =.361), consistent with the immunohistochemistry results. The serum MCP-1 and IL-8 levels were higher in the 4 groups than in the control (P =.000) and were significantly higher in group I than in group IV (P =.001). CONCLUSIONS: This study found that a significant colonization of E coli of the same strain was present in the cholestatic rat liver injected into the Roux limb, which was associated with a higher expression of liver MCP-1 and IL-8 mRNA, a significant increase of serum MCP-1 and IL-8, and a more evident inflammatory cell infiltration into the porta hepatis.

[Hepatic disorders related to Lyme disease. Study of two cases and a review of the literature]. / L'atteinte hépatique dans la maladie de Lyme. Etude de deux cas et revue de la littérature.

We report two cases of Lyme disease, revealed by hepatic damage in a 71- and a 59-year old man. In the first case, the disease was revealed by febrile jaundice whereas, in the second case, results of liver tests showed cytolytic and cholestatic abnormalities with fever. Lyme disease is a zoonosis due to infection by Borrelia burdorferi transmitted by ticks. The multiple phases of the disease explain the polymorphism of the clinical manifestations. Usually, extrahepatic symptoms are first observed, including neurological tropisms of Borrelia burdorferi. On the contrary, hepatic impairment due to Lyme disease is rare, often asymptomatic and with biological manifestations only.

Clinical factors associated with positive bile cultures during primary percutaneous biliary drainage.

PURPOSE: To evaluate the utility of routine bile cultures and to determine the risk factors for bacterial colonization of the bile as well as the biliary flora in patients with biliary obstruction undergoing primary percutaneous biliary drainage. MATERIALS AND METHODS: Between October 1995 and January 1997, bile cultures were prospectively obtained in all patients undergoing percutaneous biliary drainage. Seventy-six patients underwent 86 procedures. Culture results were correlated with clinical, laboratory, and demographic variables. The antibiotic sensitivities of cultured organisms were examined. RESULTS: Fever, previous endoscopic or percutaneous biliary instrumentation, and bilioenteric anastomosis were significant predictors of a positive bile culture. In the absence of any of these indicators, bile cultures were unlikely to be positive. Enterococcus species was the organism isolated most commonly. Yeast, gram-negative aerobic bacilli, and Streptococcus viridans followed in frequency. CONCLUSION: Bile cultures provide valuable information that was useful for planning antibiotic prophylaxis and treatment. The likelihood of positive bile cultures can be predicted based on certain clinical variables. Continued investigation is needed to better predict bacterial flora in individual patients. Given the association between previous instrumentation and biliary colonization, noninvasive imaging modalities should be exhausted before invasive procedures are performed for solely diagnostic purposes in patients with biliary obstruction.

The role of 16,16-dimethyl prostaglandin E2 on the intrahepatic biliary branches in dogs.

We studied the effects of the oral administration of a stable prostaglandin E2 analog, 16,16-dimethyl prostaglandin E2, on the intrahepatic biliary branches in a canine model. Obstructive cholestasis with a bacterial infection was induced surgically in two liver lobes in healthy mongrel dogs, and 16,16-dimethyl prostaglandin E2 was administered orally. We examined the morphological changes in the intrahepatic biliary branches and quantitatively estimated density of mucus-producing glandular elements in the ductal wall by counting these glands per unit area. Dogs treated with 16,16-dimethyl prostaglandin E2 (group 1) demonstrated fibrous thickening of the ductal wall, moderate infiltration by inflammatory cells and severe adenomatous hyperplasia of the bile duct epithelium, including striking proliferation of the mucous glands. The mean number of these mucous glands per unit area (4 mm2) was 43.0 +/- 9.0 (mean +/- S.D.; range = 36 to 56). In contrast, in a control group whose members did not receive 16,16-dimethyl prostaglandin E2 (group 2), the mean number of mucous glands per unit area was 19.4 +/- 8.0 (range = 10 to 29), significantly lower than that in group 1, although histological examination revealed chronic inflammation in the region of the large bile duct similar to that in group 1. These findings suggest that the increase in the number of mucous glands that typically occur in the setting of bile stasis and biliary infection is enhanced by 16,16-dimethyl prostaglandin E2.

Impaired liver clearance of bacteria in rats with chronic biliary obstruction.

125I-labeled E. coli was injected into the biliary tree of normal rats and rats with 3 weeks' obstruction of the common bile duct to investigate the liver clearance capacity for bacteria. Bile was collected during 15 min, immediately, 1 h, 4 h, or 24 h after the injection. Tissue specimens from the liver, lungs, spleen and kidneys, and blood and urine specimens were collected simultaneously. In normal rats, 40% of the bacteria was recovered in the bile immediately after the injection, whereas 30% was already trapped in the liver. Incubation of the bacteria in the bile duct for 1h, 4h, and 24h resulted in liver retentions of 43%, 15%, and 4%, respectively. The recovery in the bile was 13% after 1-h incubation, and further prolongation of the incubation did not result in a significant decrease. In contrast to these findings, 70% of the injected bacteria was retained in the biliary tree in rats with chronic biliary obstruction (P less than 0.05) as compared to normal rats) and only 1% was trapped in the liver (P less than 0.005) 15 min after injection. One-hour incubation of bacteria in the bile duct decreased the retention in the bile to 30%, but the retention in the liver increased only slightly in these animals. Four and 24 h after injection less than 30% of the bacteria was retained in the hepato-biliary system. Most of these animals showed almost no radioactivity exceeding the background count in the blood, urine, spleen, lungs, and kidneys 15 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS)