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Liver cirrhosis is a disease characterised by multiple complications and a poor prognosis. The prevalence is increasing worldwide. Chronic inflammation is ongoing in liver cirrhosis. No cure for the inflammation is available, and the current treatment of liver cirrhosis is only symptomatic. However, several different medical agents have been suggested as potential healing drugs. The majority are tested in rodents, but few human trials are effectuated. This review focuses on medical agents described in the literature with supposed alleviating and curing effects on liver cirrhosis. Twelve anti-inflammatory, five antioxidative, and three drugs with effects on gut microflora and the LPS pathway were found. Two drugs not categorised by the three former categories were found in addition. In total, 42 rodent studies and seven human trials were found. Promising effects of celecoxib, aspirin, curcumin, kahweol, pentoxifylline, diosmin, statins, emricasan, and silymarin were found in cirrhotic rodent models. Few indices of effects of etanercept, glycyrrhizin arginine salt, and mitoquinone were found. Faecal microbiota transplantation is in increasing searchlight with a supposed potential to alleviate cirrhosis. However, human trials are in demand to verify the findings in this review.

Background and objectives: Refractory ascites markedly worsens prognosis in cirrhosis. Large volume paracentesis (LVP) is standard treatment, but complications are common. In a randomized controlled case-series, we assessed a permanent tunneled peritoneal catheter versus LVP in patients with cirrhosis and ascites. Materials and Methods: Random allocation was computer-generated, and concealment used opaque envelopes. Patients were included from 01-2017 to 12-2018. Inclusion criteria were cirrhosis and recurrent ascites and expected survival of more than 3 months. Results: Thirteen patients were enrolled (PleurX =6 versus LVP =7). Seven were female, age range 51 to 80 years. No procedure-related complications occurred. Two patients died due to variceal bleeding (PleurX-group) and sepsis (LVP-group). One patient was withdrawn due to hyponatremia (PleurX-group). Two patients were withdrawn due to bacterial peritonitis and infection of unknown origin (Control-group). In the PleurX-group, all patients colonized the catheter, two developed bacterial peritonitis. The most common bacterial colonization was Staph. Epidermidis (n=4). Conclusions: In selected patients, the PleurX catheter mobilizes ascites and may be an alternative to LVP. The risk of infection should be considered in each case. The impact of colonization and risk of infections needs further investigation. Trial Registration: EudraCT: CIV-16-10-017324; clinicaltrials.gov: NCT 03027635; Scientific Ethics Committee journal no: H-1604179

Objective: To evaluate implementation of national guideline recommendations on treatment initiation for chronic hepatitis B (CHB) in Denmark. Methods: Using DANHEP, a nationwide cohort of chronic hepatitis B and C patients attending specialized hospital care in Denmark, we performed a descriptive cohort study from January 2002 through December 2017. We identified patients with CHB in 3 of 5 Danish regions, with at least two hospital/outpatient clinic visits during the study period. Results: We identified 990 CHB patients who remained untreated throughout the study period, and 265 who initiated treatment. At their last visit 952/990 (96%, 95% CI 95–97) untreated patients did not meet current national criteria for treatment initiation while 198/265 (75%, 95% CI 69–80) who initiated treatment met the national criteria. Overall, 198/236 (84%, 95% CI 79–88) who met national treatment criteria, initiated treatment. Conclusion: The majority of CHB patients received care in line with national guideline recommendations for treatment initiation. We found that only few patients eligible for treatment remained untreated. However, a fourth of patients who received treatment were not eligible according to national guidelines.

Background & aims Decompensated cirrhosis is characterized by disturbed haemodynamics, immune dysfunction, and high risk of infections. Translocation of viable bacteria and bacterial products from the gut to the blood is considered a key driver in this process. Intestinal decontamination with rifaximin may reduce bacterial translocation (BT) and decrease inflammation. In a randomized, placebo-controlled trial investigated the effects of rifaximin on inflammation and BT in decompensated cirrhosis. Methods Fifty-four out-patients with cirrhosis and ascites were randomized, mean age 56 years (±8.4), and MELD score 12 (±3.9). Patients received rifaximin 550 mg BD (n=36) or placebo BD (n=18). Blood and faecal (n=15) sampling were conducted at baseline and after four weeks. Bacterial DNA in blood was determined by real-time qPCR 16S rRNA gene quantification. Bacterial composition in faeces was analysed by 16S rRNA gene sequencing. Results Circulating markers of inflammation, including TNFα, interleukin-6, 10 and 18, Stromal cell-derived factor 1-α, transforming growth factor β-1 and high sensitivity CRP, were unaltered by rifaximin treatment. Rifaximin altered abundance of bacterial taxa in blood marginally, only a decrease in Pseudomonadales was observed. In faeces, rifaximin decreased bacterial richness, but effect on particular species was not observed. Subgroup analyses on patients with severely disturbed hemodynamics (n=34); or activated LBP (n=37) revealed no effect of rifaximin. Conclusion Four weeks of treatment with rifaximin had no impact on the inflammatory state and only minor effects on BT and intestinal bacterial composition in stable, decompensated cirrhosis (NCT01769040).

Decompensated cirrhosis is characterized by disturbed systemic and splanchnic hemodynamics. Bacterial translocation from the gut is considered the key driver in this process. Intestinal decontamination with rifaximin may improve hemodynamics. This double-blind, randomized, controlled trial (clinicaltrials.gov, NCT01769040) investigates the effects of rifaximin on hemodynamics, renal function, and vasoactive hormones. We randomized 54 stable outpatients with cirrhosis and ascites to rifaximin 550 mg twice a day (n = 36) or placebo twice a day (n = 18). Forty-five patients were male, mean age 56 years (±8.4), average Child score 8.3 (±1.3), and Model for End-Stage Liver Disease score 11.7 (±3.9). Measurements of hepatic venous pressure gradient, cardiac output, and systemic vascular resistance were made at baseline and after 4 weeks. The glomerular filtration rate and plasma renin, noradrenaline, lipopolysaccharide binding protein, troponin T, and brain natriuretic peptide levels were measured. Rifaximin had no effect on hepatic venous pressure gradient, mean 16.8 ± 3.8 mm Hg at baseline versus 16.6 ± 5.3 mm Hg at follow-up, compared to the placebo, mean 16.4 ± 4 mm Hg at baseline versus 16.3 ± 4.4 mm Hg at follow-up, P = 0.94. No effect was found on cardiac output, mean 6.9 ± 1.7 L/min at baseline versus 6.9 ± 2.3 L/min at follow-up, compared to placebo, mean 6.6 ± 1.9 L/min at baseline compared to 6.5 ±2.1 L/min at follow-up, P = 0.66. No effects on the glomerular filtration rate, P = 0.14, or vasoactive hormones were found. Subgroup analyses on patients with increased lipopolysaccharide binding protein and systemic vascular resistance below the mean (1,011 dynes × s/cm 5) revealed no effect of rifaximin. Conclusion: Four weeks of treatment with rifaximin did not reduce the hepatic venous pressure gradient or improve systemic hemodynamics in patients with cirrhosis and ascites; rifaximin did not affect glomerular filtration rate or levels of vasoactive hormones. (Hepatology 2017;65:592-603).

BACKGROUND: Non‐selective beta‐blockers are recommended for the prevention of bleeding in people with cirrhosis, portal hypertension and gastroesophageal varices. Carvedilol is a non‐selective beta‐blocker with additional intrinsic alpha(1)‐blocking effects, which may be superior to traditional, non‐selective beta‐blockers in reducing portal pressure and, therefore, in reducing the risk of upper gastrointestinal bleeding. OBJECTIVES: To assess the beneficial and harmful effects of carvedilol compared with traditional, non‐selective beta‐blockers for adults with cirrhosis and gastroesophageal varices. SEARCH METHODS: We combined searches in the Cochrane Hepato‐Biliary's Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and Science Citation Index with manual searches. The last search update was 08 May 2018. SELECTION CRITERIA: We included randomised clinical trials comparing carvedilol versus traditional, non‐selective beta‐blockers, irrespective of publication status, blinding, or language. We included trials evaluating both primary and secondary prevention of upper gastrointestinal bleeding in adults with cirrhosis and verified gastroesophageal varices. DATA COLLECTION AND ANALYSIS: Three review authors (AZ, RJ and LH), independently extracted data. The primary outcome measures were mortality, upper gastrointestinal bleeding and serious adverse events. We undertook meta‐analyses and presented results using risk ratios (RR) or mean differences (MD), both with 95% confidence intervals (CIs), and I(2) values as a marker of heterogeneity. We assessed bias control using the Cochrane Hepato‐Biliary domains and the quality of the evidence with GRADE. MAIN RESULTS: Eleven trials fulfilled our inclusion criteria. One trial did not report clinical outcomes. We included the remaining 10 randomised clinical trials, involving 810 participants with cirrhosis and oesophageal varices, in our analyses. The intervention comparisons were carvedilol versus propranolol (nine trials), or nadolol (one trial). Six trials were of short duration (mean 6 (range 1 to 12) weeks), while four were of longer duration (13.5 (6 to 30) months). Three trials evaluated primary prevention; three evaluated secondary prevention; while four evaluated both primary and secondary prevention. We classified all trials as at 'high risk of bias'. We gathered mortality data from seven trials involving 507 participants; no events occurred in four of these. Sixteen of 254 participants receiving carvedilol and 19 of 253 participants receiving propranolol or nadolol died (RR 0.86, 95% CI 0.48 to 1.53; I(2) = 0%, low‐quality evidence). There appeared to be no differences between carvedilol versus traditional, non‐selective beta‐blockers and the risks of upper gastrointestinal bleeding (RR 0.77, 95% CI 0.43 to 1.37; 810 participants; 10 trials; I(2) = 45%, very low‐quality evidence) and serious adverse events (RR 0.97, 95% CI 0.67 to 1.42; 810 participants; 10 trials; I(2) = 14%, low‐quality evidence). Significantly more deaths, episodes of upper gastrointestinal bleeding and serious adverse events occurred in the long‐term trials but there was not enough information to determine whether there were differences between carvedilol and traditional, non‐selective beta‐blockers, by trial duration. There was also insufficient information to detect differences in the effects of these interventions in trials evaluating primary or secondary prevention. There appeared to be no differences in the risk of non‐serious adverse events between carvedilol versus its comparators (RR 0.55, 95% CI 0.23 to 1.29; 596 participants; 6 trials; I(2) = 88%; very low‐quality evidence). Use of carvedilol was associated with a greater reduction in hepatic venous pressure gradient than traditional, non‐selective beta‐blockers both in absolute (MD ‐1.75 mmHg, 95% CI ‐2.60 to ‐0.89; 368 participants; 6 trials; I(2) = 0%; low‐quality evidence) and percentage terms (MD ‐8.02%, 95% CI ‐11.49% to ‐4.55%; 368 participants; 6 trials; I(2) = 0%; low‐quality evidence). However, we did not observe a concomitant reduction in the number of participants who failed to achieve a sufficient haemodynamic response (RR 0.76, 95% CI 0.57 to 1.02; 368 participants; 6 trials; I(2) = 42%; very low‐quality evidence) or in clinical outcomes. AUTHORS' CONCLUSIONS: We found no clear beneficial or harmful effects of carvedilol versus traditional, non‐selective beta‐blockers on mortality, upper gastrointestinal bleeding, serious or non‐serious adverse events despite the fact that carvedilol was more effective at reducing the hepatic venous pressure gradient. However, the evidence was of low or very low quality, and hence the findings are uncertain. Additional evidence is required from adequately powered, long‐term, double‐blind, randomised clinical trials, which evaluate both clinical and haemodynamic outcomes.

To evaluate the safety of PleurX in cirrhotic patients with refractory ascites.We prospectively registered patients who received a PleurX catheter cirrhosis-associated refractory ascites at our department from July 2015 to November 2016. Our control group consisted of matched cirrhotic patients with refractory ascites treated with large volume paracentesis (LVP) and patients with malignant ascites treated with PleurX during the same period.We included 25 patients with cirrhosis-related ascites (7 in PleurX group) and 17 with malignant ascites (14 in PleurX group). Of these, six patients had hepatocellular carcinoma and cirrhosis (5 in PleurX group). None were eligible for insertion of a TIPS or liver transplantation. The maximum duration of follow-up was (480 days) in the PleurX group and 366 days in the LVP group (median 84 and 173 days, respectively). There was no difference in mortality when comparing PleurX with LVP treatment (hazard ratios: 3.0 and 1.0, p = .23 and .96, respectively). Mortality was higher in patients with malignant ascites (p= .01). We found no significant differences in adverse events (incl. spontaneous bacterial peritonitis) or in P-albumin, P-creatinine and P-sodium between the groups.PleurX insertion for the treatment of refractory ascites in cirrhotic patients appears to be safe. Prospective randomized trials are necessary in order to confirm these findings.

Bacterial translocation (BT) may cause infections, in particular, spontaneous bacterial peritonitis (SBP). In the absence of overt infection, BT may further stimulate the immune system and contribute to haemodynamic alterations and complications. Bacterial DNA (bDNA) is claimed to be a promising surrogate marker for BT, although its clinical relevance has been questioned.In 38 cirrhotic patients with and without SBP, bDNA in blood and ascites were assessed by 16S rDNA quantitative PCR. Levels of lipopolysaccharide-binding protein in plasma and highly sensitive C-reactive protein, tumour necrosis factor-α, soluble urokinase plasminogen activating receptor, interleukin-6, interleukin 8, interferon-γ inducible protein-10 and vascular endothelial growth factor in plasma and ascites were measured by multiplex cytokine and ELISA assays.In patients without signs of SBP or positive cultures, we found a high frequency of bDNA but low concordance of bDNA between blood and ascites. Markers of inflammation were not significantly different between blood bDNA-positive (22%), ascites bDNA-positive (52%), and bDNA-negative patients. The 16S rDNA PCR failed to show bDNA in two out of six samples with SBP. Sequencing of positive samples did not determine the source of bDNA.bDNA as assessed by this PCR method was largely unrelated to markers of inflammation and does not seem to be of clinical value in the diagnosis of SBP. According to our results, bDNA is not a reliable marker of BT.

Circulating levels of IGF-I and IGFBP-3 are low in cirrhosis and are related to liver dysfunction. Metabolic disturbances include malnutrition with altered body composition and osteopenia. Since the effects of IGF-I may be associated to changes in body composition and bone mineral content (BMC) in cirrhotic patients, we investigated the relations between changes in the IGF-system and body composition and the effects of long-term alpha- and beta-blockade.The study was designed as a combined cross-sectional and prospective randomised controlled study of 62 patients with cirrhosis. Twenty-three of these patients were randomised to treatment with beta- or combined alpha/beta-blocker for 3 months. Haemodynamics, body composition, and systemic and hepatic IGF-I and IGFBP-3 levels were determined in all patients. In the subgroup changes in body composition and IGF-I/IGFBP-3 levels after 3 months of beta- or combined alpha/beta-blockade were additionally examined.Both the hepatic and the systemic IGF systems were suppressed and correlated with liver dysfunction and anthropometrics (p0.05-0.001). Multivariate analyses revealed that changes in the IGF-system were determined by metabolic liver dysfunction as well as anthropometrics. In the follow-up study, hepatic venous IGF-I (p=0.05) and IGFBP-3 (p=0.02) increased after 3 months only in the group who received beta-blocker. In both groups, fat body mass increased significantly after 3 months (p=0.05-0.001).In cirrhosis, the IGF-system is associated with both anthropometrics and synthetic capacity of the liver. Changes in IGF-I relate to changes in anthropometrics and there seems to be a differential effect depending on the type of adrenoreceptor blockade. Future longitudinal studies are needed to unravel these mechanisms in cirrhosis.

Patients with advanced cirrhosis often develop a hyperdynamic circulation with central hypovolaemia. The events that initiate the systemic haemodynamic abnormalities and the coupling of these factors to splanchnic haemodynamics are still unclear. Objective On the basis of a large population of patients with cirrhosis to identify splanchnic and clinical characteristics associated with the development of the hyperdynamic circulation and survival.We included 410 patients with cirrhosis. In all patients, a full haemodynamic investigation was performed. The data were analysed using regression analyses, principal components analyses, and Cox proportional hazards analyses.Multivariate regression analyses showed that higher cardiac output was independently associated with higher hepatic venous pressure gradient (HVPG) and higher hepatic blood flow (HBF) (p0.00001). Higher heart rate was independently associated with presence of ascites and higher HVPG (p0.0001). Central blood volume and circulation time were independently associated with higher HBF and lower postsinusoidal resistance, respectively (p0.0001). Systemic vascular resistance was independently associated with lower HVPG (p0.0001). The final Cox proportional hazards model showed that decreased survival was independently associated with higher age (p=0.003), lower blood haemoglobin concentration (p=0.0006), higher plasma creatinine (p=0.01), higher plasma alkaline phosphatase (p=0.007), lower right atrial pressure (p=0.004), and higher heart rate (p=0.002).The development of the hyperdynamic circulation and central hypovolaemia are mainly explained by changes in portal pressure and HBF. Together with indicators of liver dysfunction, central hypovolaemia is associated with poorer prognosis.

OBJECTIVES Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with β-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics and oxygenation are less studied. We therefore investigated systemic haemodynamics and oxygenation in patients with cirrhosis before and after 3 weeks of treatment with propranolol or spironolactone. MATERIALS AND METHODS Twenty-two patients with cirrhosis were allocated into three groups as follows: a β-blocker group (n=7), a spironolactone group (n=8) and a control group (n=7). At baseline, and after 3 weeks, we measured the arterial blood pressure (BP), heart rate, Q-T frequency-corrected interval, baroreflex sensitivity, cardiac output, peripheral arterial inflow (ABFin), transcutaneous oxygenation and hormonal status. We also assessed immediate effects of propranolol in the β-blocker group. RESULTS Short-term and long-term β-blockade significantly reduced BP (-7%) and heart rate (-15%) (P

The Finometer measures haemodynamic parameters including cardiac output (CO) using non-invasive volume-clamp techniques. The aim of this study was to determine the accuracy of the Finometer in hyperdynamic cirrhotic patients using an invasive indicator dilution technique as control. CO was measured in twenty-three patients referred for invasive measurements of the hepatic venous pressure gradient on suspicion of cirrhosis. Invasive measurements of CO were performed using indicator dilution technique (CO(I)) and simultaneous measurements of CO were recorded with the Finometer (CO(F)). In six patients, measurements of CO were performed with invasive technique and the Finometer both before and after beta-blockade using 80 mg of propranolol and the changes in CO (DeltaCO(I) and DeltaCO(F) respectively) were calculated to evaluate the Finometers ability to detect relative changes in CO. Mean CO(I) was 6.1 +/- 1.6 [3.9;9.7] l min(-1) (mean +/- SD [range]) compared to mean CO(F) of 7.2 +/- 2.3 [3.1;11.9] l min(-1). There was a mean difference between CO(F) and CO(I) of 1.0 +/- 1.8 [-2.1;4.0] l min(-1) and 95% confidence interval of [0.2;1.8], P

Background: Several new treatments of bleeding oesophageal varices (BOV) have been introduced during the last 25 years; among these are vasoactive drugs, improved endoscopic techniques and prophylactic antibiotics. Aims: The aim was to compare clinical outcomes based on Baveno IV criteria in two patient-cohorts (1983–1987, n=56 and 2000–2007, n=111) with respect to control of bleeding, rebleeding and mortality after a first episode of BOV. Further, we wanted to assess whether an eventual reduction in bleeding-related mortality occurred within the first 5 days or between Days 6 and 42 after the bleeding episode. Methods: Data from medical records were collected, according to the Baveno IV criteria, on key events: type of treatment, failure to control bleeding, failure to prevent rebleeding, 5-day and 6-week mortality. Results: Six-week mortality decreased from 30.4 to 17.1% [odds ratio (OR) 0.44; 0.21–0.95] with a reduction in 5-day mortality from 17.9 to 6.3% (OR 0.31; 0.11–0.86). A non-significant reduction was seen in the 5-day failure rate to control bleeding from 35.7 to 26.1%. Mortality and failure to prevent rebleeding Days 6–42 decreased from 15.2 to 11.5% (NS) and 22.2 to 10.7% (NS) respectively. Mean length of hospital stay decreased from 14.6 ± 12.5 to 9.1 ± 9.0 days (P

A 12-year-old Middle Eastern girl presented with abdominal pain, weight loss, and intermittent pain in both thighs. She was initially suspected of Crohn disease, but this diagnosis was excluded after extensive gastromedical evaluation. Plain x-rays of the femora were normal, whereas the initial Tc-99m methylene diphosphonate (MDP) bone scan showed several foci with increased activity in both femurs. MR scan showed excessive periostal inflammatory and mild intramedullary changes in both femurs. A percutaneous bone biopsy demonstrated changes consistent with chronic recurrent multifocal osteomyelitis (CRMO). The patient's symptoms disappeared spontaneously, but reappeared 1.5 years later, which led to a new MDP bone scan that showed normal findings.

Background and aims Newer studies suggest that carvedilol, a beta-blocker with a moderate anti-alpha-1 activity, is superior to propranolol in reducing the portal pressure and risk of variceal bleeding. The effect on arterial blood pressure is a matter of concern especially in decompensated patients. Aims to assess potential differential effects of beta-blockers and beta-blockers with moderate anti-alpha-1 activity on selected haemodynamic, humoral, and respiratory characteristics in cirrhosis. Methods Patients with cirrhosis and portal hypertension were randomised to receive carvedilol (n = 16) or propranolol (n = 13). Cardiac, systemic and splanchnic parameters along with oxygen saturation and plasma renin were measured at inclusion and after 3 months. Results Arterial blood pressure, heart rate, and cardiac output decreased equally, central circulation time and systemic vascular resistance increased significantly but similarly. Central blood volume, plasma volume and arterial compliance were unaltered. The QTc interval and renin levels decreased in the carvedilol group, however not significantly different from the propranolol group. Arterial oxygen saturation and alveolar arterial oxygen gradient remained constant in both groups. Hepatic venous pressure gradient decreased equally in the carvedilol and propranolol groups (−17% and −20%, non significant). Conclusions Systemic haemodynamics and pulmonary effects of carvedilol and propranolol are modest and this study could not demonstrate any significant difference between the two treatments.

Portal hypertension leads to development of serious complications such as esophageal varices, ascites, renal and cardiovascular dysfunction. The importance of the degree of portal hypertension has been substantiated within recent years. Measurement of the portal pressure is simple and safe and the hepatic venous pressure gradient (HVPG) independently predicts survival and development of complications such as ascites, HCC and bleeding from esophageal varices. Moreover, measurements of HVPG can be used to guide pharmacotherapy for primary and secondary prophylaxis for variceal bleeding. Assessment of HVPG should therefore be considered as a part of the general characterization of patients with portal hypertension in departments assessing and treating this condition.

Carvedilol is a non-selective β-blocker with intrinsic anti-α(1)-adrenergic activity, potentially more effective than propranolol in reducing hepatic venous pressure gradient (HVPG). We compared the long-term effect of carvedilol and propranolol on HVPG and assessed whether the acute response to oral propranolol predicted the long-term HVPG response on either drug.HVPG was measured in 38 patients with cirrhosis and HVPG ≥ 12 mm Hg at baseline and then again 90 min after an oral dose of 80 mg propranolol. Patients were double-blinded randomized to either carvedilol (21 patients) or propranolol (17 patients) and after 90 days of treatment HVPG measurements were repeated.HVPG decreased by 19.3 ± 16.1% (p0.01) and by 12.5 ± 16.7% (p0.01) in the carvedilol and propranolol groups, respectively, with no significant difference between treatment regimens (p = 0.21). Although insignificant, an acute decrease in HVPG of ≥12% was the best cut-off value to predict long-term HVPG response to propranolol when using ROC curve analysis.This randomized study showed that carvedilol is at least as effective as propranolol on HVPG after long-term administration. Furthermore, a predictive value of an acute propranolol test on HVPG could not be confirmed.

Randomized controlled trials have shown beneficial effects of vasoactive drugs, endoscopic treatment and prophylactic antibiotics on the outcome of bleeding oesophageal varices (BOV). However, translating guidelines based on randomized controlled trials into clinical practice is difficult. Our aims were to compare adherence to evidence-based guidelines in BOV between a specialized unit and a community hospital, and to investigate whether differences in adherence affected the outcome.Two cohorts hospitalized during 2000-2007 with a first episode of BOV were retrospectively enrolled, one in a community hospital comprising 66 patients and one in a specialized unit comprising 111 patients. Data on treatment, rebleeding and mortality were collected from medical records according to the Baveno III/IV Criteria.Treatments in the specialized unit versus the community hospital were: vasoactive drugs 79 vs. 66% (P = 0.06), prophylactic antibiotics 55 vs. 27% (P0.01), endoscopic treatment 86 vs. 74% (P= 0.04) and Sengstaken-Blakemore tube was used in 5 vs. 21% (P0.01). Secondary prophylaxis with pharmacological, endoscopic or transjugular intrahepatic portosystemic shunt therapy was initiated in 91 vs. 74% (P0.01) (specialized vs. community). Six-week mortality was 17 vs. 24% (P = 0.25) with 5-day mortality of 6 vs. 3% (P = 0.34) and mortality day 6-42, 12 vs. 22% (P = 0.07) (specialized vs. community). Failure to control bleeding and failure to prevent rebleeding were not statistically different.Our study shows that patients with BOV are more likely to receive therapy according to guidelines when hospitalized in a specialized unit compared with a community hospital. This however did not affect mortality.

We have read with interest the study by Lo et al 1 in a recent issue of Gut . Apart from the findings that short-term therapy with terlipressin in combination with ligation seems to improve outcome in bleeding oesophageal varices (BOVs) compared to longer treatment with terlipressin, a shorter treatment period with terlipressin most likely reduces the risk of severe side effects. Recently, a study observed that during a 5-day terlipressin treatment with 1 mg/4 h, the serum sodium decreased from 138±5 to 130±9 and in …

An episode of ischemia and reperfusion of the femoral head is thought to be the common pathway in the pathogenesis of femoral head necrosis. The influence of short-term high-dose steroid treatment on femoral head reperfusion after ischemia was investigated in a porcine model. Twenty-two pigs were randomized to receive methylprednisolone 20 mg/day/kg bodyweight intramuscularly for 3 days followed by methylprednisolone 10 mg/day/kg bodyweight for 11 days (n = 11), whereas the control group (n = 11) received no treatment. Femoral head ischemia was achieved by 6 hours of unilateral intraarticular hip pressure increase to 250 mm Hg. Femoral head blood flow was estimated using radiolabeled microspheres (15 microm in diameter) before ischemia, during hip tamponade, and 4 hours after tamponade release. Femoral head blood flow was lower in the corticosteroid treated pigs. Subtotal femoral head ischemia was documented in both groups during joint tamponade. Apart from two femoral head epiphyses in either group, reperfusion after tamponade release on the average occurred to a blood flow level similar to that before ischemia. Short-term high-dose methylprednisolone treatment depressed bone perfusion in general, but had no effect on reperfusion after femoral head ischemia in the porcine model.

The topographic reperfusion pattern of the femoral head after critical ischemia has not yet been investigated. We determined the blood flow of the porcine hip regions with the femoral head epiphysis divided into 24 subregions by the tracer microsphere technique. Blood flow was measured under steady-state conditions, at the end of a 6-hour increase in intracapsular hip joint pressure to 250 mm Hg, and 4 hours after release of the joint tamponade. Total femoral head epiphyseal blood flow decreased with ischemia and regained steady-state perfusion after tamponade. The reperfusion pattern of the femoral head epiphysis appeared identical with that of the steady state before ischemia. However, 2 of the 11 experimental epiphyses remained ischemic in the reperfusion phase. We conclude that hip joint tamponade above the arterial pressure level for 6 hours causes global ischemia in the femoral head epiphysis in the immature pig, without regional differences in reperfusion, and that reperfusion occurs at a level like that of the steady state before ischemia.