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1.
Z Gastroenterol ; 57(5): 611-680, 2019 May.
Article in German | MEDLINE | ID: mdl-31060080

ABSTRACT

This guideline provides evidence-based key recommendations for diagnosis and therapy of complications of liver cirrhosis and upgrades the 2011 version. An interdisciplinary team of medical experts and patient support groups developed the guideline following the AWMF recommendations for evidence based consensus guidelines. New chapters concerning diagnosis and therapy of hepatic encephalopathy were added.


Subject(s)
Hepatic Encephalopathy , Liver Cirrhosis , Practice Guidelines as Topic , Consensus , Gastroenterology , Hepatic Encephalopathy/diagnosis , Hepatic Encephalopathy/therapy , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/therapy
2.
Dis Colon Rectum ; 61(5): 604-611, 2018 May.
Article in English | MEDLINE | ID: mdl-29533249

ABSTRACT

BACKGROUND: Colonic diverticulosis is one of the most common gastroenterological disorders. Although diverticulosis is typically benign, many individuals develop diverticulitis or other aspects of diverticular disease. Diverticulosis is thought to stem from a complex interaction of environmental, dietary, and genetic factors; however, the contributing genetic factors remain unknown. OBJECTIVE: The aim of our present study was to determine the role of genetic variants within genes encoding for collagens of the connective tissue in diverticulosis. DESIGN: This was a transsectional genetic association study. SETTINGS: This study was conducted at three tertiary referral centers in Germany and Lithuania. PATIENTS: Single-nucleotide polymorphisms in COL3A1 (rs3134646, rs1800255) and COL1A1 (rs1800012) were genotyped in 422 patients with diverticulosis and 285 controls of white descent by using TaqMan assays. MAIN OUTCOME MEASURES: The association of colonoscopy-proven diverticulosis with genetic polymorphisms with herniations was assessed in multivariate models. RESULTS: The rs3134646, rs1800255, and rs1800012 variants were significantly associated with the risk of developing diverticulosis in the univariate model; however, these associations were not significant in the multivariate logistic regression analysis including additional nongenetic variables. When selectively analyzing sexes, the genotype AA (AA) in rs3134646 remained significantly associated with diverticulosis in men (OR, 1.82; 95% CI, 1.04-3.20; p = 0.04). LIMITATIONS: Because a candidate approach was used, additional relevant variants could be missed. Within our cohort of patients with diverticulosis, only a small proportion had diverticular disease and thus, we could not examine the variants in these subgroups. Functional studies, including the analysis of the involved collagens, are also warranted. CONCLUSIONS: Our study shows that a variant of COL3A1 (rs3134646) is associated with the risk of developing colonic diverticulosis in white men, whereas rs1800255 (COL3A1) and rs1800012 (COL1A1) were not associated with this condition after adjusting for confounding factors. Our data provide novel valuable insights in the genetic susceptibility to diverticulosis. See Video Abstract at http://links.lww.com/DCR/A504.


Subject(s)
Collagen Type III/genetics , DNA/genetics , Diverticulitis, Colonic/genetics , Polymorphism, Genetic , White People/ethnology , Adult , Aged , Aged, 80 and over , Collagen Type III/metabolism , Colonoscopy , Diverticulitis, Colonic/ethnology , Diverticulitis, Colonic/metabolism , Female , Follow-Up Studies , Genetic Association Studies , Genotyping Techniques , Germany/epidemiology , Humans , Incidence , Lithuania/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors , Young Adult
3.
Int J Colorectal Dis ; 33(4): 423-430, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29411119

ABSTRACT

PURPOSE: The purpose of this study is to investigate the association of intake of nonsteroidal anti-inflammatory drugs (NSAIDs) and in particular nonaspirin NSAIDs and compare it with other risk factors for the progression of diverticulosis to diverticulitis in patients who underwent colonoscopy. METHODS: A total of 194 patients who underwent complete colonoscopy in our center between 2012 and 2016 were recruited: 144 with diverticulosis without prior diverticulitis (median age 71 years, 59.7% men) and 50 with diverticulitis (median age 64 years, 54.0% men). Data concerning current and previous medication as well as concomitant diseases were collected using a structured questionnaire and by revision of patients medical charts. RESULTS: Patients with diverticulitis were significantly (p < 0.001) younger as compared to individuals with plain diverticulosis (median age 64 versus 71 years, respectively). The intake of NSAIDs significantly (p = 0.002) increased the risk of prior diverticulitis (OR 3.2, 95% CI 1.5-6.9). In the multivariate model, both age (p < 0.001) and NSAIDs (p = 0.03) proved to be independent determinants of diverticulitis. When analyzing aspirin intake, it was not associated with diverticulitis. CONCLUSIONS: Our study demonstrates, in line with previous reports, that intake of NSAIDs is associated with diverticulitis. We show in particular that nonaspirin NSAIDs might be selectively associated with diverticulitis. These results point to divergent role of aspirin and nonaspirin NSAIDs in the development of diverticulitis.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Diverticulitis/chemically induced , Aged , Cohort Studies , Comorbidity , Diverticulum/chemically induced , Female , Humans , Male , Risk Factors
4.
Gastroenterology ; 149(3): 660-8.e1, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25989386

ABSTRACT

BACKGROUND & AIMS: Patients with cirrhosis and variceal hemorrhage have a high risk of rebleeding. We performed a prospective randomized trial to compare the prevention of rebleeding in patients given a small-diameter covered stent vs those given hepatic venous pressure gradient (HVPG)-based medical therapy prophylaxis. METHODS: We performed an open-label study of patients with cirrhosis (92% Child class A or B, 70% alcoholic) treated at 10 medical centers in Germany. Patients were assigned randomly more than 5 days after variceal hemorrhage to groups given a small covered transjugular intrahepatic portosystemic stent-shunt (TIPS) (8 mm; n = 90), or medical reduction of portal pressure (propranolol and isosorbide-5-mononitrate; n = 95). HVPG was determined at the time patients were assigned to groups (baseline) and 2 weeks later. In the medical group, patients with an adequate reduction in HVPG (responders) remained on the drugs whereas nonresponders underwent only variceal band ligation. The study was closed 10 months after the last patient was assigned to a group. The primary end point was variceal rebleeding. Survival, safety (adverse events), and quality of life (based on the Short Form-36 health survey) were secondary outcome measures. RESULTS: A significantly smaller proportion of patients in the TIPS group had rebleeding within 2 years (7%) than in the medical group (26%) (P = .002). A slightly higher proportion of patients in the TIPS group experienced adverse events, including encephalopathy (18% vs 8% for medical treatment; P = .05). Rebleeding occurred in 6 of 23 patients (26%) receiving medical treatment before hemodynamic control was possible. Per-protocol analysis showed that rebleeding occurred in a smaller proportion of the 32 responders (18%) than in nonresponders who received variceal band ligation (31%) (P = .06). Fifteen patients from the medical group (16%) underwent TIPS placement during follow-up evaluation, mainly for refractory ascites. Survival time and quality of life did not differ between both randomized groups. CONCLUSIONS: Placement of a small-diameter, covered TIPS was straightforward and prevented variceal rebleeding in patients with Child A or B cirrhosis more effectively than drugs, which often required step-by-step therapy. However, TIPS did not increase survival time or quality of life and produced slightly more adverse events. Clinical Trial no: ISRCTN 16334693.


Subject(s)
Esophageal and Gastric Varices/therapy , Gastrointestinal Hemorrhage/prevention & control , Liver Cirrhosis/complications , Portasystemic Shunt, Transjugular Intrahepatic/instrumentation , Stents , Vasodilator Agents/therapeutic use , Venous Pressure/drug effects , Adrenergic beta-Antagonists/therapeutic use , Drug Therapy, Combination , Esophageal and Gastric Varices/diagnosis , Esophageal and Gastric Varices/etiology , Esophageal and Gastric Varices/mortality , Esophageal and Gastric Varices/physiopathology , Female , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/mortality , Gastrointestinal Hemorrhage/physiopathology , Germany , Humans , Isosorbide Dinitrate/analogs & derivatives , Isosorbide Dinitrate/therapeutic use , Kaplan-Meier Estimate , Liver Cirrhosis/diagnosis , Liver Cirrhosis/mortality , Male , Middle Aged , Nitric Oxide Donors/therapeutic use , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Portasystemic Shunt, Transjugular Intrahepatic/mortality , Propranolol/therapeutic use , Prospective Studies , Prosthesis Design , Quality of Life , Recurrence , Time Factors , Treatment Outcome , Vasodilator Agents/adverse effects
5.
Liver Int ; 36(8): 1133-42, 2016 08.
Article in English | MEDLINE | ID: mdl-26901072

ABSTRACT

BACKGROUND & AIMS: Circulating and peritoneal fragments of microbial DNA (bactDNA) are evidence for bacterial translocation in decompensated cirrhosis and may serve as a rational approach for antibiotic therapy when infection is suspected. METHODS: Prospective multicenter study to investigate whether identification of bactDNA from blood or ascitic fluid (AF) by multiplex polymerase chain reaction (PCR) is associated with increased 90-day mortality in 218 patients with cirrhosis and signs of infection. RESULTS: BactDNA in either compartment was detected in 134 (61%) patients, comprising 54 with bactDNA in blood and AF, 48 with AF bactDNA only, and 32 with blood bactDNA only. BactDNA was associated with spontaneous bacterial peritonitis and blood stream infections (SBP/BSI), acute-on-chronic liver failure (ACLF), encephalopathy and markers of inflammation. The prevalence of bactDNA in patients with proven SBP/BSI (36/49; 73%) was similar to that in patients with sterile ACLF (37/52; 71%). Actuarial 90-day survival was 56 ± 5% in the absence of bactDNA in both compartments and did not differ if bactDNA was detected in blood only (63 ± 9%), AF only (63 ± 7%), or in blood and AF (52 ± 7%). Predictors of 90-day mortality were SBP (HR = 3.10; 95% CI: 1.90-5.06), BSI (HR = 4.94; 95% CI: 2.71-9.02), and ACLF (HR = 2.20; 95% CI: 1.44-3.35). The detection of resistance genes in blood or AF in the absence of SBP/BSI (n = 11) was associated with poor 1-year survival (HR = 2.35; 95% CI: 1.03-5.35). CONCLUSIONS: BactDNA in sterile body fluids did not indicate increased mortality in cirrhotic patients with suspected infection. Using multiplex PCR for risk stratification cannot be recommended in these patients.


Subject(s)
Bacterial Translocation , DNA, Bacterial/blood , Liver Cirrhosis/complications , Peritonitis/complications , Acute-On-Chronic Liver Failure/microbiology , Aged , Ascites/microbiology , Ascitic Fluid/microbiology , Biomarkers , Drug Resistance, Multiple, Bacterial/genetics , Female , Germany/epidemiology , Humans , Liver Cirrhosis/microbiology , Male , Middle Aged , Multivariate Analysis , Peritonitis/microbiology , Prognosis , Prospective Studies , Survival Analysis , Tertiary Care Centers
7.
J Hepatol ; 58(1): 45-50, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22940408

ABSTRACT

BACKGROUND & AIMS: In a recent randomized international clinical trial (RCT) in high-risk cirrhotic patients with acute variceal bleeding, the early use of transjugular intrahepatic portosystemic shunt (TIPS) was associated with marked and significant reductions in both treatment failure and mortality. The aim of this study was to confirm these results in clinical practice in the same centers of the RCT study. METHODS: We retrospectively reviewed patients admitted for acute variceal bleeding and high risk of treatment failure (Child C <14 or Child B plus active bleeding), treated with early-TIPS (n=45) or drugs+endoscopic therapy (ET) (n=30). RESULTS: Patients treated with early-TIPS had a much lower incidence of failure to control bleeding or rebleeding than patients receiving drug+ET (3 vs. 15; p <0.001). The 1-year actuarial probability of remaining free of this composite end point was 93% vs. 53% (p <0.001). The same was observed in mortality (1-year actuarial survival was 86% vs. 70% respectively; p=0.056). Actuarial curves of failure to control bleeding+rebleeding and of survival were well within the confidence intervals of those observed in the RCT. CONCLUSIONS: This study supports the early use of TIPS in patients with cirrhosis and a high-risk variceal bleeding.


Subject(s)
Esophageal and Gastric Varices/mortality , Gastrointestinal Hemorrhage/mortality , Hypertension, Portal/mortality , Liver Cirrhosis/mortality , Portasystemic Shunt, Transjugular Intrahepatic/mortality , Adult , Aged , Female , Follow-Up Studies , Humans , Hypertension, Portal/surgery , Incidence , Liver Cirrhosis/surgery , Male , Middle Aged , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Postoperative Complications/mortality , Prognosis , Retrospective Studies , Risk Factors , Treatment Outcome
8.
J Hepatol ; 58(5): 922-7, 2013 May.
Article in English | MEDLINE | ID: mdl-23318604

ABSTRACT

BACKGROUND & AIMS: Refractory ascites (RA) affects 10% of patients with advanced cirrhosis and ascites. Usual therapy includes large volume paracentesis, and in selected patients, a transjugular portosystemic shunt (TIPS). These therapies may be associated with increased morbidity: paracentesis may induce circulatory dysfunction and impair quality of life and TIPS may induce encephalopathy and is associated with increased mortality in patients with severe liver dysfunction. We present the results of a multicenter, non-randomized trial to assess the safety and efficacy of a new automated pump system for treatment of RA. METHODS: Forty patients at 9 centers (February 2010-June 2011) received an implanted pump for the automated removal of ascites from the peritoneal cavity into the bladder, from where it was eliminated through normal urination. Patients were followed-up for 6months. The primary study outcome was safety. Secondary outcomes included recurrence of tense ascites and pump performance. RESULTS: Surgical complications occurred early in the study and became less frequent. The pump system removed 90% of the ascites and significantly reduced the median number of large volume paracentesis per month [3.4 (range 1-6) vs. 0.2 (range 0-4); p <0.01]. Cirrhosis-related adverse events decreased along follow-up. CONCLUSIONS: The automated pump seems an efficacious tool to move out ascites from the peritoneal cavity to the bladder. Its safety is still moderate, but a broad use in different countries will improve the surgical technique as well as the medical surveillance. A prospective randomized clinical trial vs. large volume paracentesis is underway to confirm these preliminary results.


Subject(s)
Ascites/epidemiology , Ascites/therapy , Membrane Transport Proteins/adverse effects , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hemodynamics/physiology , Humans , Kidney/blood supply , Liver/blood supply , Male , Middle Aged , Recurrence , Treatment Outcome
9.
N Engl J Med ; 362(25): 2370-9, 2010 Jun 24.
Article in English | MEDLINE | ID: mdl-20573925

ABSTRACT

BACKGROUND: Patients with cirrhosis in Child-Pugh class C or those in class B who have persistent bleeding at endoscopy are at high risk for treatment failure and a poor prognosis, even if they have undergone rescue treatment with a transjugular intrahepatic portosystemic shunt (TIPS). This study evaluated the earlier use of TIPS in such patients. METHODS: We randomly assigned, within 24 hours after admission, a total of 63 patients with cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy to treatment with a polytetrafluoroethylene-covered stent within 72 hours after randomization (early-TIPS group, 32 patients) or continuation of vasoactive-drug therapy, followed after 3 to 5 days by treatment with propranolol or nadolol and long-term endoscopic band ligation (EBL), with insertion of a TIPS if needed as rescue therapy (pharmacotherapy-EBL group, 31 patients). RESULTS: During a median follow-up of 16 months, rebleeding or failure to control bleeding occurred in 14 patients in the pharmacotherapy-EBL group as compared with 1 patient in the early-TIPS group (P=0.001). The 1-year actuarial probability of remaining free of this composite end point was 50% in the pharmacotherapy-EBL group versus 97% in the early-TIPS group (P<0.001). Sixteen patients died (12 in the pharmacotherapy-EBL group and 4 in the early-TIPS group, P=0.01). The 1-year actuarial survival was 61% in the pharmacotherapy-EBL group versus 86% in the early-TIPS group (P<0.001). Seven patients in the pharmacotherapy-EBL group received TIPS as rescue therapy, but four died. The number of days in the intensive care unit and the percentage of time in the hospital during follow-up were significantly higher in the pharmacotherapy-EBL group than in the early-TIPS group. No significant differences were observed between the two treatment groups with respect to serious adverse events. CONCLUSIONS: In these patients with cirrhosis who were hospitalized for acute variceal bleeding and at high risk for treatment failure, the early use of TIPS was associated with significant reductions in treatment failure and in mortality. (Current Controlled Trials number, ISRCTN58150114.)


Subject(s)
Esophageal and Gastric Varices/surgery , Gastrointestinal Hemorrhage/surgery , Liver Cirrhosis/surgery , Portasystemic Shunt, Transjugular Intrahepatic , Acute Disease , Adrenergic beta-Antagonists/therapeutic use , Adult , Esophageal and Gastric Varices/complications , Esophageal and Gastric Varices/mortality , Esophageal and Gastric Varices/therapy , Female , Gastrointestinal Hemorrhage/complications , Gastrointestinal Hemorrhage/mortality , Gastrointestinal Hemorrhage/therapy , Hepatic Encephalopathy/complications , Humans , Hypertension, Portal/complications , Liver Cirrhosis/complications , Liver Cirrhosis/mortality , Liver Cirrhosis/therapy , Male , Middle Aged , Polytetrafluoroethylene , Survival Rate , Treatment Outcome , Vasoconstrictor Agents/therapeutic use
10.
Liver Transpl ; 17(11): 1328-32, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21837734

ABSTRACT

The development of hepatorenal syndrome type 1 (HRS1) is associated with a poor prognosis. Liver transplantation improves this prognosis, but the degree of the improvement is unclear. Most patients receive vasoconstrictors such as terlipressin before transplantation, and this may affect the posttransplant outcomes. We examined a cohort of patients with access to liver transplantation from our previously published study of terlipressin plus albumin versus albumin alone in the treatment of HRS1. The purpose of this analysis was the quantification of the survival benefits of liver transplantation for patients with HRS1. Ninety-nine patients were randomized to terlipressin or placebo. Thirty-five patients (35%) received a liver transplant. Among those receiving terlipressin plus albumin, the 180-day survival rates were 100% for transplant patients and 34% for nontransplant patients; among those receiving only albumin, the rates were 94% for transplant patients and 17% for nontransplant patients. The survival rate was significantly better for those achieving a reversal of hepatorenal syndrome (HRS) versus those not achieving a reversal (47% versus 4%, P < 0.001), but it was significantly lower for the responders versus those undergoing liver transplantation (97%). We conclude that the use of terlipressin plus albumin has no significant impact on posttransplant survival. Liver transplantation offers a clear survival benefit to HRS1 patients regardless of the therapy that they receive or the success or failure of HRS reversal. The most likely benefit of terlipressin in patients undergoing liver transplantation for HRS1 is improved pretransplant renal function, and this should make the posttransplant management of this difficult group of patients easier. For patients not undergoing transplantation, HRS reversal with terlipressin and/or albumin improves survival.


Subject(s)
Hepatorenal Syndrome/mortality , Hepatorenal Syndrome/surgery , Liver Failure/mortality , Liver Failure/surgery , Liver Transplantation/mortality , Albumins/therapeutic use , Cohort Studies , Hepatorenal Syndrome/drug therapy , Humans , Liver Failure/drug therapy , Lypressin/analogs & derivatives , Lypressin/therapeutic use , Prognosis , Survival Rate , Terlipressin , Vasoconstrictor Agents/therapeutic use
11.
Hepatology ; 51(4): 1327-33, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20087966

ABSTRACT

UNLABELLED: Spontaneous bacterial peritonitis (SBP), a severe complication in patients with advanced liver cirrhosis, has been attributed to bacterial translocation from the intestine. Variants of the NOD2 (nucleotide-binding oligomerization domain containing 2) gene have been associated with impaired mucosal barrier function in Crohn disease. We hypothesized that the risk of acquiring SBP is increased in patients with cirrhosis carrying NOD2 variants. We recruited 150 nonselected patients with liver cirrhosis and ascites admitted to our unit, monitored survival, and recorded the development of SBP prospectively and retrospectively. SBP was defined as the presence of polymorphonuclear neutrophil (PMN) cells >250 per microL of ascitic fluid. Patients were genotyped for the NOD2 variants p.R702W, p.G908R, and c.3020insC. During a median follow-up of 155 days, 54 patients (36%) died and SBP was diagnosed in 30 patients (20%). The occurrence of SBP was increased significantly (P = 0.008) in carriers of NOD2 variants (odds ratio [OR] = 3.06). Retrospectively, SBP was observed in 22 additional patients, and the combined prospective and retrospective analysis substantiated the association between NOD2 and SBP (P = 0.004; OR = 2.98). Of note, carriers of NOD2 risk alleles showed a significantly (P = 0.007) reduced mean survival time (274 days) in comparison to patients with wildtype genotypes (395 days). CONCLUSION: Common NOD2 variants linked previously to impaired mucosal barrier function may be genetic risk factors for death and SBP. These findings might serve to identify patients with cirrhotic ascites eligible for preemptive antibiotic treatment.


Subject(s)
Bacterial Infections/genetics , Liver Cirrhosis/complications , Nod2 Signaling Adaptor Protein/genetics , Peritonitis/genetics , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Liver Cirrhosis/mortality , Middle Aged , Prospective Studies , Risk Factors
13.
Sci Rep ; 10(1): 1658, 2020 02 03.
Article in English | MEDLINE | ID: mdl-32015353

ABSTRACT

Colonic diverticulosis is a very common condition. Many patients develop diverticulitis or other complications of diverticular disease. Recent genome-wide association studies (GWAS) consistently identified three major genetic susceptibility factors for both conditions, but did not discriminate diverticulititis and diverticulosis in particular due the limitations of registry-based approaches. Here, we aimed to confirm the role of the identified variants for diverticulosis and diverticulitis, respectively, within a well-phenotyped cohort of patients who underwent colonoscopy. Risk variants rs4662344 in Rho GTPase-activating protein 15 (ARHGAP15), rs7609897 in collagen-like tail subunit of asymmetric acetylcholinesterase (COLQ) and rs67153654 in family with sequence similarity 155 A (FAM155A) were genotyped in 1,332 patients. Diverticulosis was assessed by colonoscopy, and diverticulitis by imaging, clinical symptoms and inflammatory markers. Risk of diverticulosis and diverticulitis was analyzed in regression models adjusted for cofactors. Overall, the variant in FAM155A was associated with diverticulitis, but not diverticulosis, when controlling for age, BMI, alcohol consumption, and smoking status (ORadjusted 0.49 [95% CI 0.27-0.89], p = 0.002). Our results contribute to the assessment specific genetic variants identified in GWAS in the predisposition to the development of diverticulitis in patients with diverticulosis.


Subject(s)
Diverticulitis, Colonic/genetics , Diverticulosis, Colonic/genetics , Membrane Proteins/genetics , Acetylcholinesterase/genetics , Aged , Cohort Studies , Collagen/genetics , Female , GTPase-Activating Proteins/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Genome-Wide Association Study , Germany , Humans , Lithuania , Male , Middle Aged , Muscle Proteins/genetics , Polymorphism, Single Nucleotide , Risk Factors
14.
Aliment Pharmacol Ther ; 52(2): 329-339, 2020 07.
Article in English | MEDLINE | ID: mdl-32506456

ABSTRACT

BACKGROUND: To evaluate medical versus interventional treatment (transjugular thrombus fragmentation, local thrombolysis with or without stent implantation) in patients with acute non-cirrhotic, non-malignant portal vein thrombosis (PVT). METHODS: This prospective, observational study enrolled 65 patients with acute (<28 days since begin of symptoms, no cavernoma) PVT in nine centres. Thirty patients received medical treatment and 35 patients received interventional treatment. PVT was graded into grade 1: short thrombosis and incomplete occlusion of the vessel lumen and grade 2: extended thrombosis or complete occlusion. Treatment response was classified as partial or complete, if thrombosis was reduced by one grade or to <25% of the vessel diameter respectively. RESULTS: Partial and complete response rates were 7% and 30% in the medical compared to 17% and 54% (P < 0.001) in the interventional treatment group. In the multivariate analysis, interventional treatment showed a strong positive (OR 4.32, P < 0.016) and a myeloproliferative aetiology a negative (OR 0.09, P = 0.006) prediction of complete response. Complications were rare in the medical group and consisted of septicaemia and upper gastrointestinal bleeding of unknown origin in one patient each. Interventional treatment was accompanied by mild and self-limiting bleeding complications in nine patients, moderate intra-abdominal bleeding requiring transfusions (2 units) in one patient and peritoneal bleeding requiring surgical rescue in one patient. Four patients in each group developed intestinal gangrene requiring surgery. One patient died 52 days after unsuccessful interventional treatment. CONCLUSIONS: Compared to medical treatment alone, interventional treatment doubled response rates at the cost of increased bleeding complications.


Subject(s)
Portal Vein/pathology , Portasystemic Shunt, Transjugular Intrahepatic , Thrombolytic Therapy , Venous Thrombosis/therapy , Acute Disease , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Female , Gastrointestinal Hemorrhage/etiology , Humans , Liver Diseases , Male , Middle Aged , Phenprocoumon/therapeutic use , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Prospective Studies , Venous Thrombosis/pathology , Young Adult
15.
Gastroenterology ; 134(5): 1360-8, 2008 May.
Article in English | MEDLINE | ID: mdl-18471513

ABSTRACT

BACKGROUND & AIMS: Hepatorenal syndrome (HRS) type 1 is a progressive functional renal failure in subjects with advanced liver disease. The aim of this study was to evaluate the efficacy and safety of terlipressin, a systemic arterial vasoconstrictor, for cirrhosis type 1 HRS. METHODS: A prospective, randomized, double-blind, placebo-controlled clinical trial of terlipressin was performed. Subjects with type 1 HRS were randomized to terlipressin (1 mg intravenously every 6 hours) or placebo plus albumin in both groups. The dose was doubled on day 4 if the serum creatinine (SCr) level did not decrease by 30% of baseline. Treatment was continued to day 14 unless treatment success, death, dialysis, or transplantation occurred. Treatment success was defined by a decrease in SCr level to

Subject(s)
Hepatorenal Syndrome/drug therapy , Lypressin/analogs & derivatives , Vasoconstrictor Agents/administration & dosage , Dose-Response Relationship, Drug , Double-Blind Method , Female , Follow-Up Studies , Germany/epidemiology , Hepatorenal Syndrome/mortality , Hepatorenal Syndrome/physiopathology , Humans , Injections, Intravenous , Kidney Function Tests , Lypressin/administration & dosage , Male , Middle Aged , Prospective Studies , Russia/epidemiology , Severity of Illness Index , Shock, Septic , Survival Rate , Terlipressin , Treatment Outcome , United States/epidemiology
16.
Scand J Gastroenterol ; 44(1): 116-20, 2009.
Article in English | MEDLINE | ID: mdl-18759151

ABSTRACT

A 55-year-old woman with suspected hilar cholangiocarcinoma presented with jaundice and dilated intrahepatic bile ducts owing to high-grade hepatic duct confluence stenosis. The suspected tumour and the entire extrahepatic bile duct system were resected and Roux-en-Y hepaticojejunostomy was performed. Histological investigations showed perihepatic fibrosis but no signs of malignancy. One year later the patient developed bilateral hydronephrosis caused by ureteral obstruction. Since the patient had a gynaecological history of widespread inflammation, she was referred for transabdominal operative ureterolysis combined with hysterectomy and adnexectomy. Histological investigations as well as fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) findings were compatible with retroperitoneal fibrosis (Ormond's disease). Treatment with tamoxifen was initiated. To the best of our knowledge, only a few cases of intraperitoneal fibroses mimicking cholangiocarcinoma followed by the typical symptoms of retroperitoneal Ormond's disease have been reported.


Subject(s)
Bile Duct Diseases/diagnosis , Bile Duct Neoplasms/diagnosis , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/diagnosis , Retroperitoneal Fibrosis/diagnosis , Anastomosis, Roux-en-Y , Bile Duct Diseases/pathology , Bile Duct Diseases/surgery , Cholangiopancreatography, Endoscopic Retrograde , Constriction, Pathologic/diagnosis , Diagnosis, Differential , Female , Hepatic Duct, Common/pathology , Humans , Jejunostomy/methods , Klatskin Tumor/diagnosis , Liver/surgery , Middle Aged , Positron-Emission Tomography/methods , Retroperitoneal Fibrosis/pathology , Retroperitoneal Fibrosis/surgery , Tomography, X-Ray Computed , Treatment Outcome
17.
Digestion ; 80(3): 165-9, 2009.
Article in English | MEDLINE | ID: mdl-19776579

ABSTRACT

BACKGROUND/AIMS: Coexisting gastric varices at baseline or the risk of their formation during treatment could alter the approach for primary bleeding prophylaxis in patients with large esophageal varices. METHODS: Data analysis of 152 patients with cirrhosis and large esophageal varices included in the German multicenter trial on primary prevention of variceal bleeding. RESULTS: 20 patients (13.6%) had coexisting gastric varices at baseline (GOV+). 10 of those each received either band ligation or propranolol, respectively. During follow-up (34.4 +/- 18.9 months) new gastric varices occurred in 2/75 (2.7%, ligation) and 4/77 (5.2%, propranolol) patients, respectively. One patient with newly developed gastric varices bled (propranolol group). GOV+ patients had a better baseline liver function and overall survival. Bleeding incidence did not differ significantly between GOV+ and GOV- patients (3-year actuarial risk: 20.0 +/- 10.6% (GOV+), 38.1 +/- 4.4% (GOV-), p = 0.195). Among GOV+ patients, bleeding occurred in 3/10 patients of the propranolol group and in 0/10 in the ligation group (p = 0.038). CONCLUSION: Prophylactic band ligation of large esophageal varices is safe and effective also in patients with coexisting gastric varices. Band ligation did not increase the risk of secondary gastric varices compared to propranolol.


Subject(s)
Esophageal and Gastric Varices/surgery , Gastrointestinal Hemorrhage/prevention & control , Liver Cirrhosis/complications , Adolescent , Adult , Aged , Esophageal and Gastric Varices/complications , Esophageal and Gastric Varices/pathology , Female , Gastrointestinal Hemorrhage/etiology , Humans , Kaplan-Meier Estimate , Ligation , Male , Middle Aged , Young Adult
18.
Clin Transl Gastroenterol ; 10(1): e00002, 2019 01.
Article in English | MEDLINE | ID: mdl-30702490

ABSTRACT

OBJECTIVES: Common nucleotide-binding oligomerization domain containing 2 (NOD2) gene variants have been associated with bacterial infections (BIs) in cirrhosis, in particular, spontaneous bacterial peritonitis, and mortality. Our aim was to evaluate the independent association of NOD2 variants with BI according to the decompensation stage. METHODS: Consecutive patients with cirrhosis in 2 academic medical centers were included and genotyped for the NOD2 variants p.R702W, p.G908R, and c.3020insC. Electronic medical records were screened for BI (requiring antibiotic therapy) and past and present decompensation (as defined by variceal bleeding, encephalopathy, ascites, and/or jaundice). Clinically significant portal hypertension (CSPH) was assessed with liver stiffness and/or hepatic venous pressure gradient measurements. RESULTS: Overall, 735 patients were recruited (men 65%; interquartile age range 53-68 years). Alcoholic cirrhosis was the predominant etiology (n = 406, 55%), and most patients were in the decompensated stage (n = 531, 72%). In total, 158 patients (21%) carried at least one NOD2 variant. BIs were detected in 263 patients (36%), and NOD2 variants were associated with BI (odds ratio = 1.58; 95% confidence interval 1.11-2.27; P = 0.02). In compensated patients, the combination of NOD2 variants and presence of CSPH was the best independent predictors of BI, whereas other factors, such as spleen size and hemoglobin, and decompensations including hepatic encephalopathy or jaundice, gained relevance in decompensated patients. CONCLUSIONS: NOD2 risk variants are associated with BI in cirrhosis. The genetic effect on BI is strongest in compensated patients, whereas in decompensated patients their presence is less relevant. In this situation, CSPH becomes an independent factor associated with BI.


Subject(s)
Bacterial Infections/epidemiology , Genetic Predisposition to Disease , Hypertension, Portal/epidemiology , Liver Cirrhosis/complications , Nod2 Signaling Adaptor Protein/genetics , Aged , Alleles , Bacterial Infections/genetics , Disease Progression , Female , Germany/epidemiology , Humans , Hypertension, Portal/etiology , Liver Cirrhosis/diagnosis , Male , Middle Aged , Polymorphism, Single Nucleotide , Prospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index
19.
Liver Int ; 28(7): 1019-25, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18410283

ABSTRACT

BACKGROUND/AIMS: Large-volume paracentesis in patients with cirrhosis and ascites induces arterial vasodilatation and decreases effective arterial blood volume, termed paracentesis-induced circulatory dysfunction (PICD), which can be prevented by costly intravenous albumin. Vasoconstrictors, e.g. terlipressin, may also prevent PICD. The aim was to compare the less expensive vasoconstrictor midodrine, an alpha-adrenoceptor agonist, with albumin in preventing PICD. METHODS: Twenty-four patients with cirrhosis and ascites were randomly assigned to be treated with either midodrine (n=11) (12.5 mg three times per day; over 2 days) or albumin (n=13) (8 g/L of removed ascites) after large-volume paracentesis. Effective arterial blood volume was assessed indirectly by measuring plasma renin and aldosterone concentration on days 0 and 6 after paracentesis; renal function and haemodynamic changes were also measured. PICD was defined as an increase in plasma renin concentration on day 6 by more than 50% of the baseline value. RESULTS: PICD developed in six patients of the midodrine group (60%) and in only four patients (31%) of the albumin group. Six days after paracentesis, the aldosterone concentration increased significantly in the midodrine group, but not in the albumin group. CONCLUSIONS: This pilot study suggests that midodrine is not as effective as albumin in preventing circulatory dysfunction after large-volume paracentesis in patients with cirrhosis and ascites.


Subject(s)
Adrenergic alpha-Agonists/therapeutic use , Albumins/therapeutic use , Ascites/therapy , Hypovolemia/prevention & control , Liver Cirrhosis/therapy , Midodrine/therapeutic use , Paracentesis/adverse effects , Albumins/administration & dosage , Aldosterone/blood , Ascites/etiology , Ascites/physiopathology , Double-Blind Method , Female , Humans , Hypovolemia/etiology , Hypovolemia/physiopathology , Liver Cirrhosis/complications , Liver Cirrhosis/physiopathology , Male , Middle Aged , Pilot Projects , Renin/blood , Treatment Outcome
20.
Med Klin (Munich) ; 103(7): 482-90, 2008 Jul 15.
Article in German | MEDLINE | ID: mdl-18604483

ABSTRACT

Patients with liver cirrhosis bear a considerable risk of a variety of complications that involve virtually all organ systems. They can be addressed with a wide spectrum of drugs for acute interventions as well as for prophylactic purposes. At the same time, treatment of the underlying disease, the identification and treatment of triggering factors, and the possibility of liver transplantation should be kept in mind.


Subject(s)
Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Algorithms , Carcinoma, Hepatocellular/prevention & control , Carcinoma, Hepatocellular/therapy , Combined Modality Therapy , Disease Progression , Humans , Liver Function Tests , Liver Neoplasms/prevention & control , Liver Neoplasms/therapy , Portasystemic Shunt, Transjugular Intrahepatic
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