Case report: Cholecystoduodenostomy for cholestatic liver disease in a premature infant with cystic fibrosis and short gut syndrome.

BACKGROUND: Cholecystoduodenostomy is a surgical procedure that bypasses the extrahepatic biliary tree and connects the gallbladder directly to the duodenum. This case describes the successful use of this procedure in a novel situation. CASE PRESENTATION: A premature (34 weeks gestation) female infant with cystic fibrosis required a laparotomy on day 1 of life due to an intrauterine small bowel perforation. Resection of small bowel and ileostomy formation resulted in short gut syndrome, with 82 cm residual small bowel and intact ileocaecal valve. Post-ileostomy reversal at 2 months old, she developed conjugated hyperbilirubinaemia. Despite conservative management including increased enteral feeding, ursodeoxycholic acid, cholecystostomy drain insertion and flushes, her cholestatic jaundice persisted. A liver biopsy revealed an "obstructive/cholestatic" picture with fibrosis. To avoid further shortening her gut with an hepatoportoenterostomy, cholecystoduodenostomy was performed at 3 months of age with subsequent post-operative improvement and eventual normalisation of her clinical jaundice and liver biochemistry. CONCLUSIONS: This is the first reported case of a cholecystoduodenostomy being used successfully to treat an infant with persistent conjugated hyperbilirubinemia, cystic fibrosis and short gut syndrome. Cholecystoduodenostomy is a treatment option that with further study, may be considered for obstruction of the common bile duct in patients with short gut and/or where a shorter operating time with minimal intervention is preferred.

Jaundice in the emergency department: meeting the challenges of diagnosis and treatment [digest].

There are approximately 52,000 visits a year to emergency departments for patients presenting with jaundice. While many of these patients will not have immediately life-threatening pathology, it is essential that the emergency clinician understands the pathophysiology of jaundice, as this will guide the appropriate workup to detect critical diagnoses. Patients who present with jaundice could require intravenous antibiotics, emergent surgery, and, in severe cases, organ transplantation. This issue will focus on the challenge of evaluating and treating the jaundiced patient in the ED using the best available evidence from the literature. [Points & Pearls is a digest of Emergency Medicine Practice.].

Jaundice in the emergency department: meeting the challenges of diagnosis and treatment.

There are approximately 52,000 visits a year to emergency departments for patients presenting with jaundice. While many of these patients will not have immediately life-threatening pathology, it is essential that the emergency clinician understands the pathophysiology of jaundice, as this will guide the appropriate workup to detect critical diagnoses. Patients who present with jaundice could require intravenous antibiotics, emergent surgery, and, in severe cases, organ transplantation. This issue will focus on the challenge of evaluating and treating the jaundiced patient in the ED using the best available evidence from the literature.

α7-nAChR Knockout Mice Decreases Biliary Hyperplasia and Liver Fibrosis in Cholestatic Bile Duct-Ligated Mice.

α7-nAChR is a nicotinic acetylcholine receptor [specifically expressed on hepatic stellate cells (HSCs), Kupffer cells, and cholangiocytes] that regulates inflammation and apoptosis in the liver. Thus, targeting α7-nAChR may be therapeutic in biliary diseases. Bile duct ligation (BDL) was performed on wild-type (WT) and α7-nAChR-/- mice. We first evaluated the expression of α7-nAChR by immunohistochemistry (IHC) in liver sections. IHC was also performed to assess intrahepatic bile duct mass (IBDM), and Sirius Red staining was performed to quantify the amount of collagen deposition. Immunofluorescence was performed to assess colocalization of α7-nAChR with bile ducts (costained with CK-19) and HSCs (costained with desmin). The mRNA expression of α7-nAChR, Ki-67/PCNA (proliferation), fibrosis genes (TGF-ß1, fibronectin-1, Col1α1, and α-SMA), and inflammatory markers (IL-6, IL-1ß, and TNF-α) was measured by real-time PCR. Biliary TGF-ß1 and hepatic CD68 (Kupffer cell marker) expression was assessed using IHC. α7-nAChR immunoreactivity was observed in both bile ducts and HSCs and increased following BDL. α7-nAChR-/- BDL mice exhibited decreased (i) bile duct mass, liver fibrosis, and inflammation, and (ii) immunoreactivity of TGF-ß1 as well as expression of fibrosis genes compared to WT BDL mice. α7-nAChR activation triggers biliary proliferation and liver fibrosis and may be a therapeutic target in managing extrahepatic biliary obstruction.

Atorvastatin does not protect against ischemia-reperfusion damage in cholestatic rat livers.

BACKGROUND: Extrahepatic cholestasis sensitizes the liver to ischemia/reperfusion (I/R) injury during surgery for perihilar cholangiocarcinoma. It is associated with pre-existent sterile inflammation, microvascular perfusion defects, and impaired energy status. Statins have been shown to protect against I/R injury in normal and steatotic mouse livers. Therefore, the hepatoprotective properties of atorvastatin were evaluated in a rat model of cholestatic I/R injury. METHODS: Male Wistar rats were subjected to 70% hepatic ischemia (during 30 min) at 7 days after bile duct ligation. Rats were randomized to atorvastatin treatment or vehicle-control in three test arms: (1) oral treatment with 5 mg/kg during 7 days after bile duct ligation; (2) intravenous treatment with 2.5, 5, or 7.5 mg/kg at 24 h before ischemia; and (3) intravenous treatment with 5 mg/kg at 30 min before ischemia. Hepatocellular damage was assessed by plasma alanine aminotransferase (ALT) and histological necrosis. RESULTS: I/R induced severe hepatocellular injury in the cholestatic rat livers (~10-fold increase in ALT at 6 h after I/R and ~30% necrotic areas at 24 h after I/R). Both oral and intravenous atorvastatin treatment decreased ALT levels before ischemia. Intravenous atorvastatin treatment at 5 mg/kg at 24 h before ischemia was the only regimen that reduced ALT levels at 6 h after reperfusion, but not at 24 h after reperfusion. None of the tested regimens were able to reduce histological necrosis at 24 h after reperfusion. CONCLUSION: Pre-treatment with atorvastatin did not protect cholestatic livers from hepatocellular damage after I/R. Clinical studies investigating the role of statins in the protection against hepatic I/R injury should not include cholestatic patients with perihilar cholangiocarcinoma. These patients require (pharmacological) interventions that specifically target the cholestasis-associated hepatopathology.

Comparison of laparoscopic hepaticojejunostomy and open hepaticojejunostomy. Can stenosis of the hilar hepatic duct affect postoperative outcome?

INTRODUCTION: The aim of this study was to compare laparoscopic hepaticojejunostomy (LHJ) and open hepaticojejunostomy (OHJ) for choledochal cyst associated with hilar hepatic duct stenosis (HHDS). METHODS: Data collection was prospective for LHJ cases from 2009 and retrospective for OHJ cases from 2003 to 2008. Data were compared with respect to HHDS. HHDS was incised longitudinally as required during hilar hepatic ductoplasty. RESULTS: Fifty-eight subjects were studied (LHJ: n = 27, 4 boys, 23 girls; OHJ: n = 31; 6 boys, 25 girls). HHDS was present in 10 LHJ cases and 10 OHJ cases. Todani classification of choledochal cyst in LHJ patients was type 1A (n = 16) and type 4A (n = 11), and in OHJ patients, it was type 1A (n = 19) and type 4A (n = 12). There were significant differences between LHJ and OHJ with regard to mean operative time (386 vs 341 min), mean blood loss (5.9 vs 18.4 mL), recommencement of enteral feeding (3.9 vs 6.4 days), and hospital stay (11.7 vs 15.5 days) (all P < 0.05). Hepatic ductoplasty was performed in 23 LHJ patients and in 21 OHJ patients. There were no intraoperative complications and no conversions to OHJ. There were no significant differences between LHJ and OHJ, regardless of the presence of HHDS, for postoperative complications, which included minor bile leakage, anastomotic stricture, and intestinal obstruction. CONCLUSION: LHJ is as effective as OHJ for the treatment of choledochal cysts irrespective of the presence of HHDS and the need for hepatic ductoplasty.

Effects of Myrtus communis extract treatment in bile duct ligated rats.

BACKGROUND: The aim of our study was to investigate the antifibrotic and antioxidant effects of Myrtus communis subsp. communis (MC) extract against liver injury and fibrosis occurring in rats with biliary obstruction. MATERIALS AND METHODS: The rats were randomized into four groups (n = 8). Control group (C), MC-administrated group (MC), the bile duct ligation (BDL), and BDL + MC groups. MC was administered at a dose of 50 mg/kg a day orally for 28 days. In blood samples, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase levels, tumor necrosis factor-α, and interleukin-1ß measurement were measured. Oxidative injury was examined by measuring luminol and lucigenin chemiluminescence, malondialdehyde and glutathione levels, superoxide dismutase and myeloperoxidase activities. Transforming growth factor-beta and hydroxyproline levels were measured for analyzing fibrosis. The hepatic injury was also analyzed microscopically. RESULTS: Plasma total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, and interleukin-1ß levels were found significantly high in the BDL group, while these values significantly decreased in the BDL group treated with MC. On the other hand, the glutathione and superoxide dismutase values significantly decreased in the BDL group compared to the control group but increased markedly in BDL + MC group compared to the BDL group. Malondialdehyde levels, myeloperoxidase activity, tissue luminol, lucigenin, transforming growth factor-beta, and hydroxyproline levels when compared with the control group increased dramatically in the BDL group and reduced the MC + BDL group. CONCLUSIONS: Our results suggest that MC protects the liver tissues against oxidative damage following BDL via its radical scavenging and antioxidant activities, which appear to involve the inhibition of tissue neutrophil infiltration.

Protective Effects of Curcumin on Intestinal Damage in Cholestatic Rats.

BACKGROUND: The aim of this study was to evaluate the possible protective effects of curcumin on oxidative stress, cell proliferation, and apoptosis in the rat intestinal mucosa after bile duct ligation (BDL). METHODS: A total of 18 male Sprague Dawley rats were divided into three groups: sham control, BDL and BDL+curcumin; each group contain six animals. The rats in the curcumin-treated group were given curcumin (100 mg/kg) once a day orally for 14 days, starting 3 days prior to BDL operation. Following 14 days of treatment, all the animals were decapitated and intestinal tissues samples obtained for biochemical and histopathological investigation. RESULTS: Curcumin treatment was found to significantly lower elevated tissue malondialdehyde levels and myeloperoxidase activity, and to raise reduced glutathione levels in intestinal tissues samples. BDL caused severe histopathological injury, including shortening of the villi, loss of villous epithelium, multiple erosions, inflammatory cell infiltration, necrosis, and hemorrhage into the intestinal wall. Curcumin treatment significantly attenuated the severity of intestinal injury, with inhibition of BDL-induced apoptosis and cell proliferation. CONCLUSION: Curcumin treatment has a protective effect against intestinal damage induced by BDL. The ability of curcumin treatment is to inhibit BDL-induced oxidative stress, apoptosis, and cell proliferation.

Primary Sclerosing Cholangitis: Multiple Phenotypes, Multiple Approaches.

Primary sclerosing cholangitis (PSC) is a heterogeneous, idiopathic, inflammatory disorder frequently associated with inflammatory bowel diseases. PSC patients may be classified into several subphenotypes. Investigations of pediatric, nonwhite, and female PSC patients have revealed distinguishing features. The natural history of PSC is variable in progression with numerous possible clinical outcomes. PSC patients may suffer bacterial cholangitis, cholangiocarcinoma, or colorectal adenocarcinoma. Treatments focusing on bile acid therapy and immunosuppression have not proven beneficial. Interest in PSC and international collaboration has led to improved understanding of the heterogeneity and the genetic structure and introduced possible effective therapeutics.

Efficacy of diffusion-weighted magnetic resonance imaging in the evaluation of extrahepatic cholestasis-related hepatic fibrosis.

BACKGROUND/AIM: To investigate the efficacy of diffusion-weighted magnetic resonance imaging (DWI) in the diagnosis and staging of fibrosis induced by experimental bile duct ligation (BDL). MATERIALS AND METHODS: Twenty-four rats were divided randomly into four groups: control, BDL--3 days, BDL--2 weeks, and BDL--4 weeks. DWI was performed with b-values of 100 and 500 on the rats from control group at day zero, on the rats from the BDL--3 days group at the end of day 3, on the rats from the BDL--2 weeks group at the end of day 14, and on the rats from the BDL--4 weeks at the end of day 28. RESULTS: When fibrosis scores generated in all groups were evaluated together, a strong negative correlation was detected between fibrosis scores and apparent diffusion coefficient (ADC) values measured using b 100 and b 500. ADC values obtained using b 100 were found to be significantly higher compared to the fibrosis observed in both the BDL--2 weeks and BDL--4 weeks groups (P < 0.003 and P < 0.001, respectively). CONCLUSION: We think that DWI may be an alternative to liver biopsy for the diagnosis and staging of hepatic fibrosis with underlying extrahepatic cholestasis.

Vitamin A supplementation alleviates extrahepatic cholestasis liver injury through Nrf2 activation.

AIM: To investigate the role of vitamin A in liver damage induced by bile duct ligation (BDL) in rats. METHODS: Thirty male Wistar rats were randomly divided into three groups: SHAM group, BDL group, and BDL + VitA group . The concentrations of retinol and retinyl palmitate in the liver were analyzed using HPLC, and liver function was evaluated by the level of TBIL, ALT, AST, and ALP in serum. Hepatic oxidative status was estimated by measuring T-SOD, CAT, GSH, MDA, and AOPP. Nrf2 expression was assessed using immunohistochemistry and western blotting, and EMSA was performed to determine Nrf2 DNA-binding activity. The expression of the downstream factors such as Ho1 and Nqo1 was also examined using immunohistochemistry and western blotting assays. RESULTS: Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice. Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1. CONCLUSION: Vitamin A was here found to ameliorate cholestatic liver injury. This effect may be related to the activation of Nrf2/ARE pathway in bile duct ligation rats.

Síndrome DRESS secundario a ibuprofeno como causa de fallo hepático hiperagudo / DRESS syndrome secondary to ibuprofen as a cause of hyperacute liver failure

El fallo hepático agudo presenta alta mortalidad, siendo su primera etiología en España la viral. Presentamos un caso de fallo fulminante secundario a una reacción idiosincrásica a ibuprofeno, englobado en el síndrome de DRESS (Drug Rash with Eosinophilia and Systemic Symptoms). Dicho síndrome constituye un diagnóstico clave en el diagnóstico diferencial del fracaso hepático agudo, ya que su curso infausto obliga en muchas ocasiones a la realización de trasplante hepático como única terapéutica útil. Este caso es un buen ejemplo de la necesidad de la rapidez y la eficiencia en la coordinación a nivel intrahospitalario y entre centros sanitarios como factor clave en la mejoría del pronóstico (AU)

Acute liver failure has a high mortality and its most frequent cause in Spain is viral infection. In this article, we present a case of fulminant liver failure. The failure is secondary to an idiosyncratic reaction to ibuprofen, an entity included in the DRESS syndrome. This syndrome plays a key role in the differential diagnosis of acute liver failure, since its unfortunate course often requires liver transplantation as the only useful therapeutic weapon. This case illustrates the need for an efficient coordination between hospitals as a key factor for improving the prognosis (AU)

El íleo biliar como causa de abdomen agudo. Importancia del diagnóstico precoz para el tratamiento quirúrgico / Gallstone ileus as a cause of acute abdomen. Importance of early diagnosis for surgical treatment

El íleo biliar es una causa poco frecuente de obstrucción intestinal mecánica, causada por el paso del cálculo a través de la luz intestinal, de difícil diagnóstico preoperatorio en el Servicio de Urgencias. Presentamos un estudio retrospectivo de 5 casos de íleo biliar tratados entre 2000 y 2010. Se analizaron las características clínicas, las pruebas diagnósticas y el tratamiento quirúrgico realizado. Se incluyó a 5 pacientes, 2 empezaron con una obstrucción intestinal típica, otros 2 presentaron un íleo biliar recurrente previamente intervenido y el último presentó una peritonitis secundaria a la perforación de un divertículo ileal. En todos los casos, la TAC permitió el diagnóstico preoperatorio. En nuestra experiencia, el íleo biliar puede aparecer con clínica diferente a la obstrucción intestinal. En lo casos de sospecha, una TAC puede ser útil para disminuir el retraso diagnóstico relacionado con mayor número de complicaciones (AU)

Gallstone ileus is an uncommon type of mechanical intestinal obstruction caused by an intraluminal gallstone, and preoperative diagnosis is difficult in the Emergency department. This study is a retrospective analysis of the clinical presentation of 5 patients with gallstone ileus treated between 2000-2010. Clinical features, diagnostic testing, and surgical treatment were analyzed. Five patients were included: 2 cases showed bowel obstruction; 2 patients presented a recurrent gallstone ileus with prior surgical intervention; and one patient presented acute peritonitis due to perforation of an ileal diverticula. In all cases CT confirmed the preoperative diagnosis. In our experience, gallstone ileus may present with clinical features other than intestinal obstruction. In suspicious cases CT may be useful to decrease diagnostic delay, which is associated with more complications (AU)

[A quite usual pancreatitis?]. / Eine ganz normale Pankreatitis?

HISTORY AND CLINICAL FINDINGS: A 55-year-old man suffered from severe acute abdominal pain. 10 years previously he had been diagnosed with acute pancreatitis. On palpation, there was pronounced abdominal tenderness and guarding. INVESTIGATIONS: Emergency CT revealed signs of intra- and extrahepatic cholestasis and biliar sludge; serum-lipase was increased. TREATMENT AND COURSE: Acute biliary pancreatitis was diagnosed. After admission the patient's condition deteriorated; acute renal failure and respiratory insufficiency developed. After 4 weeks of intensive care he was discharged to a rehabilitation facility via normal ward. At that time pancreatic sonography showed a walled-off necrosis. 7 weeks later colicky abdominal pain occurred again. Altough there were no signs of infection, suction-irrigation drainage was administered. This led to a secondary infection of the necrotic cavity, and 20 sessions of endoscopic necrosectomy were performed for 3 month. Then the patient was discharged to follow-up treatment in a stable condition. CONCLUSION: Even in supposedly "usual" acute pancreatitis complications can lead to a prolonged course. Sterile necroses should be managed very cautiously.

Does an isolated benign choledochal stricture hide a PSC?

BACKGROUND: Strictures of the extra-hepatic biliary tree are rare in children and have a benign non-traumatic inflammatory origin or are related to idiopathic fibrosing pancreatitis. Primary sclerosing cholangitis (PSC) can manifest as multiple biliary strictures or as a single dominant stricture. We describe the presentation, treatment, and outcome of six cases of isolated benign choledochal stricture (IBCS). METHODS: All patients underwent magnetic resonance cholangiography (MRC). Five patients underwent diagnostic and therapeutic ERCP, and 4 patients underwent intra-choledochal mini-probe EUS and biopsy. Colonoscopy was performed in suspected ulcerative colitis (UC). RESULTS: We report 6 patients (mean age at diagnosis: four males, 12.1 years; two females, 14.2 years) with IBCS. Clinical onset included 3 cases of acute biliary pancreatitis and obstructive jaundice, one obstructive jaundice, one cholestasis, and one pancreatitis. At diagnosis, MRC confirmed IBCS in all patients. Biliary sphincterotomy, stricture dilation, and stenting were performed in 4 patients. One child underwent hepaticojejunostomy for a type I choledocal cyst. During follow-up (mean: 21 months; range: 1-3 years), all patients were asymptomatic. Four patients developed UC (three pancolitis, one descending colitis). One child developed PSC. CONCLUSION: IBCS can be successfully treated by therapeutic ERCP. The occurrence of UC could suggest that IBCS is a form of PSC.

[Vitamin K deficiency bleeding: a case secondary to transient neonatal cholestasis]. / Maladie hémorragique par déficit en vitamine K : à propos d'un cas secondaire à une cholestase néonatale transitoire.

We report the case of late vitamin K deficiency bleeding (VLDB), with appropriate but insufficient prophylaxis, secondary to extrahepatic cholestasis. Late VKDB is rare today but serious, with a risk of intracranial hemorrhage in more than half of the cases. The diagnosis, causes and prevention of this disease are discussed.

Superiority of ceftriaxon to cefazolin in a rat model of obstructive jaundice: an experimental study.

OBJECTIVE: The objective of this study was to evaluate the serum and bile concentrations of cefazolin and ceftriaxone at the third and sixth hours in an experimental obstructive jaundice model and to identify the rate of excretion of these antibiotics into the bile. MATERIAL AND METHODS: Thirty-two Wistar albino rats were used in this study. The bile and serum levels of cefazolin were measured at the third hour in the A1 group and at the sixth hour in the A2 group, with cefazolin administered as 5 mg/rat; while the bile and serum levels of ceftriaxone were studied at the third hour in the B1 group and at the sixth hour in the B2 group, with ceftriaxone administered as 5 mg/rat. RESULTS: After 3 hr of cefazolin administration, the serum concentration in the A1 group reached a mean of 1.8 µg/ml, while the bile concentration was 90% of the serum concentration, with a mean of 1.6 µg/ml; whereas in the B1 group, the third-hour serum concentration of ceftriaxone was 18.6 µg/ml, while the bile concentration was found to be as high as 330% of this level, i.e., 56 µg/ml. The serum value of cefazolin decreased to 1.4 µg/ml in the A2 group and ceftriaxone decreased to 3.7 µg/ml in the B2 group at the sixth hour. CONCLUSIONS: Although the excretory level of cefazolin and ceftriaxone into the bile reaches therapeutic doses, the duration for which these levels are above those required for bactericidal activity is short. Ceftriaxone is better concentrated in the serum and bile than cefazolin.

Loss of A(1) adenosine receptor attenuates alpha-naphthylisothiocyanate-induced cholestatic liver injury in mice.

Cholestasis has limited therapeutic options and is associated with high morbidity and mortality. The A(1) adenosine receptor (A(1)AR) was postulated to participate in the pathogenesis of hepatic fibrosis induced by experimental extrahepatic cholestasis; however, the contribution of A(1)AR to intrahepatic cholestatic liver injury remains unknown. Here, we found that mice lacking A(1)AR were resistant to alpha-naphthyl isothiocyanate (ANIT)-induced liver injury, as evidenced by lower serum liver enzyme levels and reduced extent of histological necrosis. Bile acid accumulation in liver and serum was markedly diminished in A(1)AR(-/-) mice compared with wild-type (WT) mice. However, biliary and urinary outputs of bile acids were significantly enhanced in A(1)AR(-/-) mice. In the liver, mRNA expression of genes related to bile acid transport (Bsep and Mdr2) and hydroxylation (Cyp3a11) was increased in A(1)AR(-/-) mice. In the kidney, A(1)AR deficiency prevented the decrease of glomerular filtration rate caused by ANIT. Treatment of WT mice with A(1)AR antagonist DPCPX also protected against ANIT hepatotoxicity. Our results indicated that lack of A(1)AR gene protects mice from ANIT-induced cholestasis by enhancing toxic biliary constituents efflux through biliary excretory route and renal elimination system and suggested a potential role of A(1)AR as therapeutic target for the treatment of intrahepatic cholestasis.

Calcium content of different compositions of gallstones and pathogenesis of calcium carbonate gallstones.

BACKGROUND/OBJECTIVES: Our aim was to investigate the calcium content of different gallstone compositions and the pathogenic mechanisms of calcium carbonate gallstones. METHODS: Between August 2001 and July 2007, gallstones from 481 patients, including 68 calcium carbonate gallstones, were analyzed for total calcium content. Gallbladder bile samples from 33 cases and six controls were analyzed for pH, carbonate anion level, free-ionized calcium concentration and saturation index for calcium carbonate. RESULTS: Total calcium content averaged 75.6 %, 11.8 %, and 4.2 % for calcium carbonate, calcium bilirubinate and cholesterol gallstones. In 29.4 % of patients, chronic and/or intermittent cystic duct obstructions were caused by polypoid lesions in the neck region and 70.6 % were caused by stones. A total of 82 % of patients had chronic low-grade inflammation of the gallbladder wall and 18.0 % had acute inflammatory exacerbations. In the bile, we found the mean pH, mean carbonate anion, free-ionized calcium concentrations, and mean saturation index for calcium carbonate to be elevated in comparison to controls. CONCLUSION: From our study, we found chronic and/or intermittent cystic duct obstructions and low-grade GB wall inflammation lead to GB epithelium hydrogen secretion dysfunction. Increased calcium ion efflux into the GB lumen combined with increased carbonate anion presence increases SI_CaCO(3) from 1 to 22.4. Thus, in an alkaline milieu with pH 7.8, calcium carbonate begins to aggregate and precipitate.

Extrahepatic complications of chronic cholestasis: current diagnosis and treatment.

Pruritus, fatigue and osteoporosis are the main symptoms of the extra hepatic manifestations of chronic cholestasis that affect patients' quality of life. Pruritus affects more often female patients, varies as intensity during a day and for longer period of time, typically can be localized on the palms of hands and soles of feet or can be generalized. Pruritus can be treated with anions resines exchange--cholestiramine, the pregnanne X receptor agonist Rifampicine, Naltrexone. Liver transplantation can be considered if severe pruritus remains refractory to all medical treatments. Fatigue is the most disabling complain in chronic colestasis. No specific therapies are available for fatigue and liver transplantation doesn't improve it. Osteoporosis and the risk of fractures are more severe with the duration and severity of hepatic disease. For treatment are recommended regular physical exercise, vitamin D and Ca supplimentation and bisphosphonates (Alendronate 70 mg/week) in severe cases. Only patients with atherosclerotic risk and hyperlipemia can be treated with statines. Fat soluble vitamin supplementation can be administrated only in symptomatic and proved vitamin deficiency.