Hepatobiliary and pancreatic manifestations in inflammatory bowel diseases: a referral center study.

BACKGROUND: Hepatobiliary and pancreatic manifestations have been reported in patients with Crohn's disease or ulcerative colitis. Our aim was to describe the prevalence of hepatobiliary and pancreatic manifestations in inflammatory bowel disease and their association with the disease itself and the medications used. METHODS: Data were retrospectively extracted from the clinical records of patients followed up at our tertiary IBD referral Center. RESULTS: Our study included 602 IBD patients, with liver function tests at regular intervals. The mean follow-up was 5.8 years (Std. Dev.: 6.72). Abdominal imaging examinations were present in 220 patients and revealed findings from the liver, biliary tract and pancreas in 55% of examined patients (120/220). The most frequent findings or manifestations from the liver, biliary tract and pancreas were fatty liver (20%, 44/220), cholelithiasis (14.5%, 32/220) and acute pancreatitis (0.6%, 4/602), respectively. There were 7 patients with primary sclerosing cholangitis. Regarding hepatitis viruses, one-third of the patients had been tested for hepatitis B and C. 5% (12/225) of them had positive hepatitis B surface antigen and 13.4% had past infection with hepatitis B virus (positive anti-HBcore). In addition, most of the patients were not immune against hepatitis B (negative anti-HBs), while 3% of patients were anti-HCV positive and only one patient had active hepatitis C. Furthermore, 24 patients had drug-related side effects from the liver and pancreas. The side effects included 21 cases of hepatotoxicity and 3 cases of acute pancreatitis. Moreover, there were two cases of HBV reactivation and one case of chronic hepatitis C, which were successfully treated. CONCLUSION: In our study, approximately one out of four patients had some kind by a hepatobiliary or pancreatic manifestation. Therefore, it is essential to monitor liver function at regular intervals and differential diagnosis should range from benign diseases and various drug related side effects to severe disorders, such as primary sclerosing cholangitis.

von Willebrand factor and procoagulant imbalance predict outcome in patients with cirrhosis and thrombocytopenia.

BACKGROUND & AIMS: Several lines of evidence suggest that the hemostatic disorders of cirrhosis may have a significant clinical impact. We investigated the independent predictive value of components of the hemostatic system on the occurrence of ascites, variceal bleeding (VB), and survival. METHODS: One hundred and two patients with thrombocytopenia (Child-Pugh class A/B/C: 34/34/34) were enrolled. Platelet counts, factors (F) II, V, VII, and VIII, antithrombin, protein C (PC), FVIII-to-PC ratio as an index of procoagulant imbalance, von Willebrand factor antigen (vWF-Ag), and model for end-stage liver disease (MELD) were evaluated. Two multivariate analyses were performed: one excluding (model 1) and one including MELD (model 2). RESULTS: Higher vWF-Ag levels and FVIII-to-PC ratios were the most prominent hemostatic disorders in patients with cirrhosis. Increased levels of vWF-Ag and FVIII, and higher FVIII-to-PC ratios independently predicted the presence of ascites and varices at baseline. Independent predictors of ascites and VB during follow-up were vWF-Ag (model 1/2: p=0.001/p=0.009 and p=0.008/p=0.01, respectively) and FVIII-to-PC ratio (model 1/2: p=0.003/p=0.02 and p=0.01/p=0.03, respectively). vWF-Ag (model 1/2: p=0.007/p=0.002), FVIII-to-PC ratio (model 1/2: p=0.001/p=0.01), and MELD (p=0.02) independently predicted mortality. Patient groups with significantly higher probability of new-onset ascites, VB, and mortality were identified by certain cut-offs of vWF-Ag (213%, 466%, and 321%, respectively) and FVIII-to-PC ratio (1.99, 3.29, and 2.36, respectively). vWF-Ag and FVIII-to-PC ratio equaled MELD in mortality prediction. CONCLUSIONS: Advanced cirrhosis is characterized by increased thrombotic potential. vWF-Ag and FVIII-to-PC ratio independently predict new-onset ascites, VB, and mortality. Targeting hypercoagulability could improve the outcome of patients with cirrhosis. LAY SUMMARY: Higher von Willebrand factor antigen (vWF-Ag) levels and factor VIII-to-protein C (FVIII-to-PC) ratio are the prominent hemostatic disorders in patients with cirrhosis. vWF-Ag and FVIII-to-PC ratio independently predict new-onset ascites, variceal bleeding, and mortality in these patients.

Thrombin generation measured as thrombin-antithrombin complexes predicts clinical outcomes in patients with cirrhosis.

AIM: Hypercoagulability has been detected in patients with cirrhosis yet its clinical significance remains unclear. We investigated the association of hypercoagulability with clinical outcomes in patients with cirrhosis. METHODS: Thrombin-antithrombin (TAT) complexes as thrombin generation (TG) marker, D-dimer, antithrombin (AT), protein C, protein S, international normalized ratio (INR), activated partial thromboplastin time, fibrinogen, Child-Pugh class and Model for End-Stage Liver Disease (MELD) were evaluated. Two different multivariate analyses were performed: one not including MELD (model 1) and one including MELD and excluding INR (model 2). RESULTS: Eighty-one patients (Child-Pugh class A/B/C: 27/27/27) and 40 healthy subjects were enrolled. Only ΤΑΤ and AT were independently associated with increasing liver disease severity. Increased TAT levels and MELD score were significantly associated with ascites and varices at baseline. Independent predictors of follow-up events were: TAT and MELD score for new-onset ascites; TAT and AT for variceal bleeding (VB); TAT and AT for portal vein thrombosis (PVT); and TAT and MELD for mortality. TAT equaled MELD in mortality prediction at 12 and 18 months. TAT cut-offs at 5.35, 14.6, 13.5 and 9.25 ng/mL identified patient groups with significantly higher probability of new-onset ascites, VB, PVT and mortality, respectively. CONCLUSION: Increased TG is strongly correlated with portal hypertension-related complications, PVT and mortality in patients with cirrhosis. Measuring TG by TAT could enable risk stratification and institution of preventive strategies to improve clinical outcomes.

Coexistence of Crohn's disease in a patient with systemic lupus erythematosus.

The concurrence of inflammatory bowel disease with systemic lupus erythematosus (SLE) is rare. The concomitant diagnosis of Crohn's disease and SLE is even more rare. The patient, a 40-year-old woman, was admitted to our hospital because of relapsing episodes of abdominal pain, diarrheas upper and lower extremities arthralgias, Raynaud's phenomenon with positive antinuclear antibodies, and fever for the last 2 years. The patient was diagnosed elsewhere with SLE and treated with hydroxychloroquine. Her medical history also included tonsillectomy and total hip replacement after a car accident. Family history was unremarkable. Physical examination was unremarkable except of very mild pain at lower left abdominal quadrant. Laboratory tests showed erythrocyte sedimentation rate at 32 mm/h, C-reactive protein at 36 mg/dl, positive rheumatoid factor, and increased C3, C4, positive antinuclear antibodies with the presence of anti-Sm and anti-RNP antibodies. Ileocolonoscopy revealed colonic inflammation with ulcers and pseudopolyps. Subsequent biopsies were diagnostic of Crohn's disease. Patient was diagnosed with Crohn's colitis concomitant to systemic lupus erythematosus and was started on therapy with azathioprine 2 mg/Kg, methylprednisolone 16 mg/d with slow tapering, mesalazine 1.5 g/day, and hydroxychloroquine. Patient is in excellent health status on the six-month follow-up.

Rifaximin improves systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites.

Circulating levels of endotoxin, interleukin (IL)-6, and tumor necrosis factor (TNF)-α increase with intestinal bacterial overgrowth and translocation, and are believed to be involved in the pathogenesis of hyperdynamic circulatory syndrome and functional renal failure in patients with advanced cirrhosis. We investigated the effects of the antibiotic rifaximin on systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites. We measured mean arterial pressure, cardiac output (CO) by Doppler ultrasound, systemic vascular resistance (as the ratio of mean arterial pressure:CO), plasma renin activity, levels of plasma aldosterone, the glomerular filtration rate by plasma clearance of technetium-99m-DTPA, natriuresis, levels of plasma endotoxin, and serum levels of IL-6 and TNF-α in 13 patients at baseline and after 4 weeks of treatment with rifaximin. Rifaximin treatment significantly reduced CO and significantly increased systemic vascular resistance, in association with a significant decrease in plasma rennin activity. The therapy also significantly increased the glomerular filtration rate and natriuresis while reducing levels of endotoxin, IL-6, and TNF-α. Intestinal decontamination with rifaximin improved systemic hemodynamics and renal function in patients with advanced cirrhosis.

Rifaximin improves thrombocytopenia in patients with alcoholic cirrhosis in association with reduction of endotoxaemia.

BACKGROUND: Thrombocytopenia is a major haematological disorder of cirrhosis with unclear pathogenesis. Endotoxaemia resulting from intestinal bacterial overgrowth could reduce platelet counts directly or through cytokine release. AIMS: To correlate endotoxaemia with platelet counts and study the effects of intestinal decontamination with rifaximin on thrombocytopenia in relation to changes in endotoxin and cytokine concentrations in patients with alcoholic cirrhosis. METHODS: Platelet counts, plasma endotoxin levels and serum interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels were measured in 23 thrombocytopenic cirrhotic patients (platelet count<150 000/µl) before and after 4-week treatment with rifaximin 1200 mg/d (n = 13) or no treatment (n = 10) and at baseline in 10 cirrhotic patients without thrombocytopenia; spleen size was measured at baseline in all patients. RESULTS: Endotoxin and IL-6 levels were significantly higher in patients with thrombocytopenia than in those without thrombocytopenia (2.76 ± 0.69 vs. 0.64 ± 0.09 EU/ml; P < 0.001 and 24.26 ± 3.38 vs. 2.66 ± 0.74 pg/ml; P = 0.001 respectively). Platelet counts were inversely correlated with endotoxin levels (r = -0.589; P = 0.003), Child-Pugh score (r = -0.625; P = 0.001), IL-6 levels (r = -0.464; P = 0.02) and spleen size (r = -0.455; P = 0.02) in patients with thrombocytopenia. Following rifaximin, platelet counts increased significantly (83 100 ± 9700 vs. 99 600 ± 11 200/µl; P = 0.006) in line with significant reductions in endotoxin (1.28 ± 0.41 vs. 2.54 ± 0.86 EU/ml; P = 0.005), IL-1 (3.1 ± 0.5 vs. 4.4 ± 1.2 pg/ml; P = 0.04), IL-6 (12.8 ± 2.5 vs. 21.1 ± 4.2 pg/ml; P = 0.01) and TNF-α (3.6 ± 1.3 vs. 5.8 ± 1.7; P = 0.02) levels. Platelet count changes were correlated with the changes in endotoxin (r = 0.573; P = 0.04), TNF-α (r = 0.554; P = 0.05) and IL-6 (r = 0.495; P = 0.07) levels. CONCLUSIONS: Rifaximin improves cirrhosis-related thrombocytopenia and this could be related with the reduction of endotoxaemia.

Terlipressin improves pulmonary pressures in cirrhotic patients with pulmonary hypertension and variceal bleeding or hepatorenal syndrome.

Terlipressin has been shown to improve both pulmonary and systemic hemodynamics in stable cirrhotic patients with pulmonary hypertension, whereas other vasoconstrictors may cause pulmonary pressures to deteriorate. We investigated the pulmonary and systemic hemodynamic effects of the first terlipressin dose (2 mg) in 7 cirrhotic patients with PH presenting with variceal bleeding (n=4) or hepatorenal syndrome (n=3). Terlipressin decreased pulmonary vascular resistance (158.8+/-8.9 vs 186.5+/-13.9 dynes · sec · cm-5; P=0.003) together with an increase in systemic vascular resistance (2143+/-126 vs 1643+/-126 dynes · sec · cm-5; P<0.001). Terlipressin should be the vasoconstrictor treatment of choice when patients present with variceal bleeding or HRS.

Effects of terlipressin and somatostatin on liver and thorax blood volumes in patients with cirrhosis.

BACKGROUND: Variceal bleeding in cirrhosis can cause liver ischaemia and deteriorate the hyperdynamic state; thus, the effects of vasoconstrictor therapy on liver blood volume (LBV) and thorax blood volume (ThBV) are important. AIM: To evaluate and compare the effects of terlipressin and somatostatin on LBV and ThBV in stable patients with cirrhosis and portal hypertension. METHODS: Twenty patients were studied (Child-Pugh class A/B/C: 5/8/7). The radioactivities in the liver region (LRR) and the thorax region (ThRR) by single-head gamma camera technique, as indicators of LBV and ThBV, respectively, and systemic haemodynamics were measured at baseline and after intravenous infusion of 2 mg of terlipressin (n=10) or somatostatin 250 mg/h after an initial bolus of 250 mg (n=10). RESULTS: LRR and ThRR decreased significantly with increasing severity of cirrhosis. Thirty minutes after terlipressin infusion, LRR and ThRR increased by 7.8 ± 4.4% (NS) and 14 ± 5.3% (P=0.01) compared with baseline values; the increase in ThRR was significantly related to the increase in LRR (r=0.682, P=0.03). In contrast, somatostatin reduced LRR and ThRR by 13.3 ± 6.5% (P=0.07) and 1 ± 4% (NS) respectively. LRR and ThRR increased significantly in the terlipressin group compared with the somatostatin group (P=0.01 and P=0.02 respectively). Terlipressin reduced cardiac output and heart rate (both P=0.01) and increased the mean arterial pressure (MAP) and systemic vascular resistance (P=0.009 and P=0.002 respectively); MAP decreased after somatostatin infusion (P=0.03). CONCLUSIONS: Terlipressin, but not somatostatin, maintains LBV, increases ThBV and improves the hyperdynamic state in cirrhosis. These effects can be beneficial in variceal bleeding, particularly in patients with advanced liver disease.

Effects of terlipressin on water excretion after oral water load test in nonazotemic cirrhotic patients with ascites without hyponatremia.

OBJECTIVE: Impaired water excretion is a major prognostic factor in decompensated cirrhotic patients. We investigated if terlipressin improves water excretion after a water load test in nonazotemic cirrhotic patients with ascites without hyponatremia. METHODS: Fifteen patients (Child-Pugh B/C: 6/9) were studied after an oral water intake of 20 ml/kg within 40 min and water excretion over 5 h was measured at baseline: day 1, and after a bolus infusion (2 mg) of terlipressin: day 3. Mean arterial pressure (MAP) before and after water loading on day 1, and MAP, cardiac output (CO), and systemic vascular resistance (SVR) before and 1 h after terlipressin infusion on day 3, were evaluated. The 5-h creatinine clearance (ClCre), diuresis, and sodium excretion were also evaluated in each study day. RESULTS: The water load excreted on day 1 was significantly correlated with Child-Pugh score, ClCre, sodium excretion, and SVR. The water load excreted and diuresis increased significantly after terlipressin infusion in the 12 patients that completed the study (48.3±3.3% vs. 39.5±4.9%; p=0.001 and 2.51±0.21 vs. 2.06±0.29 ml/min; p=0.001, respectively); significant increases in ClCre and sodium excretion, a significant decrease in CO and significant increases in MAP and SVR were also noted. The changes in the percentage of water load excreted were significantly correlated with the changes in SVR and ClCre. CONCLUSIONS: Terlipressin increases water excretion during a water load test in nonazotemic cirrhotic patients without hyponatremia, suggesting that the administration of arterial vasoconstrictors could influence the prognosis of these patients.

The role of colonoscopy in the management of intestinal obstruction: a 20-year retrospective study.

PURPOSE: The aim of the study was to assess the use colonoscopy over time in the assessment of large bowel obstruction in a tertiary university hospital. METHODS: Retrospective analysis of surgical and colonoscopy records for the years 1990-2009 in a university hospital. All patients diagnosed with non-conservatively managed bowel obstruction were included. RESULTS: We recorded 644 patients diagnosed with non-conservatively managed bowel obstruction. Four hundred forty-one (67.3%) were managed only by surgery, 157 (23.6%) were managed by colonoscopy, and 46 (6.9%) by combined colonoscopy and surgery. Patients over 77 years were more likely to receive colonoscopy as monotherapy or combined with surgery as compared to younger patients. Management by colonoscopy only and by combined colonoscopy and surgery increased over time. CONCLUSIONS: Colonoscopy in the management of non-conservatively treated bowel obstruction increased over time. However, therapeutic colonoscopy still has a limited role in bowel obstruction either as monotherapy or combined with surgery.

ATG16L1 T300A polymorphism is associated with Crohn's disease in a Northwest Greek cohort, but ECM1 T130M and G290S polymorphisms are not associated with ulcerative colitis.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are well-described disease entities with unknown etiopathogenesis. Environmental, genetic, gut microbiota, and host immune response correlations have been implicated. The role of susceptibility gene polymorphisms, such as ATG16L1 T300A and ECM1 T130M and G290S, is well-described, although controversial findings have been reported. METHODS: Two hundred five patients with inflammatory bowel disease (108 CD and 97 UC), and 223 healthy blood donors (control group) from the Northwest Greece region were genotyped for rs2241880 (T300A), rs3737240 (T130M) and rs13294 (G290S) single nucleotide polymorphisms. Genotyping was performed using the real-time polymerase chain reaction method. RESULTS: The frequency of G allele was significantly higher in CD patients compared to the control group (P=0.029; odds ratio [OR] 1.45, 95% confidence interval [CI] 1.04-2.03). Carriers of two G alleles (T300A), compared to those carrying only one, were 1.3 times more susceptible to CD (P=0.022; OR 2.45, 95%CI 1.14-5.27). In CD patients, the presence of the T300A polymorphism indicates a possible protective effect against developing a penetrating (B3) phenotype, while in UC patients, presence of the T300A polymorphism, indicates a possible protective effect against developing joint-involving extraintestinal manifestations. CONCLUSION: Our study found a significant association of the T300A polymorphism with CD susceptibility, suggesting that CD occurrence in our population has a strong genetic background, with the T300A G allele having an additive effect.

Presence of pseudopolyps in ulcerative colitis is associated with a higher risk for treatment escalation.

BACKGROUND: Pseudopolyps in ulcerative colitis (UC) are considered as indicators of previous episodes of severe inflammation and ulceration of the mucosa. The aim of the study was to investigate the long-term outcomes of patients treated for UC, with or without pseudopolyps. METHODS: This was a retrospective single-center study. Consecutive patients with UC and available endoscopic data from 2000 until 2016 were eligible for the study and were followed until June 2017. Patients with incomplete medical/endoscopic charts or interrupted follow up were excluded from the study. Primary outcomes included time to treatment escalation, treatment escalation to biological agents or surgery, and UC-related hospitalization. RESULTS: Eighty-three UC patients were included in the study, of whom 25 (30%) had pseudopolyps. The median duration of follow up was 2.8 years (interquartile range: 1.1-4.9). Multiple Cox regression analysis identified the presence of pseudopolyps as the only variable independently associated with treatment escalation (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.2-4.3; P=0.014) and escalation to biological agents or surgery (HR 6.3, 95%CI 1.9-20.7; P=0.002). CONCLUSION: This retrospective single-center study provides the first preliminary evidence that patients with UC and pseudopolyps may represent a subpopulation with a higher inflammatory burden and a greater need for treatment escalation, including to biological agents or surgery. Large, prospective multicenter studies are certainly warranted to confirm these findings.

Multiple myeloma presenting with pyomyositis caused by community-acquired methicillin-resistant Staphylococcus aureus: report of a case and literature review.

Pyomyositis is infrequently reported in patients with multiple myeloma. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is emerging as an important cause of soft tissue infections, including pyomyositis. Here, we report on the first case of CA-MRSA pyomyositis in a patient with multiple myeloma and review the relevant literature.

Clinical Use of Patency Capsule: A Comprehensive Review of the Literature.

The patency capsule is a radiopaque, dissolvable diagnostic tool, similar in shape and size to small bowel capsule endoscopes. It was developed to offer a simple, safe, efficient, and accurate evaluation of small bowel functional patency. Although unable to provide direct visual information regarding the presence and location of strictures, masses, or luminal narrowing of the small bowel, a successful patency test minimizes the risk of retention and allows the safe administration of a capsule endoscope. However, its use entails a low risk of potentially harmful adverse events, which in their majority are indolent and resolve spontaneously. Abdominal pain and symptomatic retention are accountable for the majority of reported adverse events, whereas a limited number of reports describe life-threatening complications, namely intestinal obstruction, perforation, and intestinal ischemia. Computed tomography is the modality of choice for the identification of the exact position of an impacted patency capsule, whilst the use of plain abdominal radiographs should be avoided for the evaluation of the patency capsule position, as they provide false information. Hereby, we present a comprehensive review of the available literature regarding the characteristics, indications, clinical use, effectiveness, and adverse events of the patency capsule.10.1093/ibd/izy152_video1izy152.video15777752348001.

Association of clinical and inflammatory markers with small bowel capsule endoscopy findings in Crohn's disease.

BACKGROUND: Mucosal healing is an established treatment endpoint in Crohn's disease (CD). Still, clinical indices and inflammatory markers are used widely in CD surveillance. AIM: The aim of this study was to investigate the diagnostic performance as well as the relationship of C-reactive protein (CRP) and Crohn's Disease Activity Index (CDAI) with small bowel capsule endoscopy's (SBCE) inflammation scoring index, the Lewis Score (LS). PATIENTS AND METHODS: CDAI, CRP, and SBCE findings of 30 CD patients with isolated small bowel disease were retrieved from our academic institution patient records and were analyzed statistically. RESULTS: SBCE showed significant mucosal inflammation [mean (SD) LS: 1599 (1380)], in nine (60.0%) of 15 patients who were in both clinical and biochemical remission. CDAI and CRP showed a weak and moderate correlation with LS (r=0.317, P=0.088 and r=0.516, P=0.004, respectively). The diagnostic performance of CDAI and CRP in predicting mucosal inflammation was as follows: sensitivity 23.8 and 52.4%; specificity 100 and 66.7%; positive predictive value 100 and 78.6%; and negative predictive value 36.0 and 37.5%. The area under the curve toward endoscopic activity prediction was 0.70 and 0.69, respectively. CONCLUSION: Both CDAI and CRP underestimated endoscopic activity as expressed by the LS in a significant proportion of patients with quiescent disease.

Hepatobiliary Manifestations and Complications in Inflammatory Bowel Disease: A Review.

Liver and biliary track diseases are common extraintestinal manifestations of inflammatory bowel disease (IBD), reported both in Crohn's disease and ulcerative colitis, and may occur at any time during the natural course of the disease. Their etiology is mainly related to pathophysiological changes induced by IBD, and secondary, due to drugs used in IBD. Fatty liver is considered as the most frequent hepatobiliary manifestation in IBD, while primary sclerosing cholangitis (PSC) is the most correlated hepatobiliary disorder and is more prevalent in patients with ulcerative colitis. PSC can cause serious complications from the liver, biliary tree, and gallbladder and can lead to liver failure. Less frequently, IBD-associated hepatobiliary manifestations include cholelithiasis, granulomatous hepatitis, portal vein thrombosis, IgG4-related cholangiopathy, pyogenic liver abscess, hepatic amyloidosis and primary biliary cirrhosis. Most of the drugs used for IBD treatment may cause liver toxicity. Methotrexate and thiopurines carry the higher risk for hepatotoxicity, and in many cases, dose adjustment may normalize the liver biochemical tests. Reactivation of hepatitis B and C virus during immunosuppressive use, especially during use of biological agents, is a major concern, and adequate screening, vaccination and prophylactic treatment is warranted.

Association of liver cirrhosis related IgA nephropathy with portal hypertension.

A high incidence of IgA nephropathy has been reported in patients with liver cirrhosis, though, clinically evident nephrotic syndrome is very uncommon. Impaired hepatic clearance of circulating IgA immune complexes and subsequent deposition in renal glomeruli has been considered principally in the pathogenesis of liver cirrhosis associated IgA nephropathy. Here we report on a patient with cryptogenic liver cirrhosis and splenic vein thrombosis, who presented with nephrotic syndrome. Renal biopsy showed findings consistent with IgA nephropathy. Lower endoscopy showed features of portal hypertensive colopathy. Following initiation of propranolol and anticoagulant treatment to reduce portal pressure, a gradual decrease of proteinuria and hematuria to normal range was noted. The potential pathogenetic role of portal hypertension in the development of IgA nephropathy in cirrhotic patients is discussed.