Abstract: Acute cellular rejection remains an important source of morbidity after liver transplantation, particularly if rejection is moderate or severe, as this usually is treated. Currently liver biopsies are seldom performed, so diagnostic noninvasive markers would be useful. We evaluated 690 consecutive first liver transplant patients to assess whether peripheral eosinophilia could predict moderate-severe rejection and its course. A protocol biopsy was performed 6 ± 2.5 days after transplant. A second biopsy was taken 6.1 ± 2 days after the first in 487 patients to assess histological improvement. Liver function tests, peripheral eosinophil count and changes between first and second biopsy, were evaluated using logistic regression. Histological rejection was present in 532 patients (77.1%), with moderate (30.6%) and severe rejection (3.9%). Peripheral eosinophil count was strongly associated with moderate-severe rejection (OR = 2.15; P = 0.007), although the area under ROC curve (AUROC) was 0.58. On second biopsy, rejection improved in 119 (24.4%) patients. The delta in eosinophil count between the first and second biopsies was the only independent predictor of histological improvement (OR = 3.12; P = 0.001), irrespective of whether bolus steroids were used (OR = 2.77; P = 0.004); AUROC was 0.72. Peripheral eosinophilia is not sufficiently predictive of moderate-severe histological rejection. However the changes in eosinophil count over time can accurately predict the histological resolution of rejection.
Abstract: Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise.
Abstract: Relative adrenal insufficiency (AI) occurs in patients with cirrhosis with sepsis, but not with variceal bleeding. We evaluated adrenal function in cirrhotic patients with and without bleeding.
Abstract: Clinical outcomes of recurrent hepatitis C virus after liver transplantation are difficult to predict. We evaluated collagen proportionate area (CPA), a quantitative histological index, at 1 year with respect to the first episode of clinical decompensation. Patients with biopsies at 1 year after liver transplantation were evaluated by Ishak stage/grade, and biopsy samples stained with Sirius red for digital image analysis were evaluated for CPA. Cox regression was used to evaluate variables associated with first appearance of clinical decompensation. Receiver operating characteristic (ROC) curves were also used. A total of 135 patients with median follow-up of 76 months were evaluated. At 1 year, median CPA was 4.6% (0.2%-36%) and Ishak stage was 0-2 in 101 patients, 3-4 in 23 patients, and 5-6 in 11 patients. Decompensation occurred in 26 (19.3%) at a median of 61 months (15-138). Univariately, CPA, tacrolimus monotherapy, and Ishak stage/grade at 1 year were associated with decompensation; upon multivariate analysis, only CPA was associated with decompensation (P = 0.010; Exp(B) = 1.169; 95%CI, 1.037-1.317). Area under the ROC curve was 0.97 (95%CI, 0.94-0.99). A cutoff value of 6% of CPA had 82% sensitivity and 95% specificity for decompensation. In the 89 patients with hepatic venous pressure gradient (HVPG) measurement, similar results were obtained. When both cutoffs of CPA > 6% and HVPG ≥ 6 mm Hg were used, all patients decompensated. Thus, CPA at 1-year biopsy after liver transplantation was highly predictive of clinical outcome in patients infected with hepatitis C virus who underwent transplantation, better than Ishak stage or HVPG.
Abstract: Hepatopulmonary syndrome is characterised by hypoxaemia and intrapulmonary shunting in the presence of portal hypertension. It is uncommon in the obstetric population but may occur in patients with Budd-Chiari syndrome in the absence of severe liver dysfunction. We discuss the management of a primigravida with Budd-Chiari syndrome and persistent hepatopulmonary syndrome post liver transplantation. A literature review revealed only one report of a successful pregnancy in association with hepatopulmonary syndrome. We discuss its recognition in patients with liver disease and anaesthetic considerations in its presence.
Abstract: Bleeding from the upper gastrointestinal (GI) tract is a common medical emergency, with an incidence of between 50-150 cases per 100,000 per year.1 A recent audit by the British Society of Gastroenterology showed the mortality rate from upper GI bleeds has fallen from 14%2 in 1993 to 10% in 2007.3 However, despite the use of proton pump inhibitors (PPIs), admission rates for peptic ulcer haemorrhage have increased in older age groups,4 probably related to increased use of antiplatelet agents such as aspirin and clopidogrel and anticoagulants in acute coronary syndromes, stroke and atrial fibrillation. The rising age of the population may also have offset further reductions in mortality and morbidity that may have otherwise come about through improved supportive and endoscopic care.
Abstract: Hemophilia B, an X-linked disorder, is ideally suited for gene therapy. We investigated the use of a new gene therapy in patients with the disorder.
Abstract: Adrenal insufficiency (AI) is reported in critically ill patients with cirrhosis and is associated with increased mortality. It is unclear if AI is an underlying condition or triggered by critical events (e.g. sepsis). We investigated AI in cirrhosis without infection or hemodynamic instability.
Abstract: Glypican 3 (GPC-3) is an oncofoetal protein that is expressed in most hepatocellular carcinomas (HCC). Since it is a potential target for T cell immunotherapy, we investigated the generation of functional, GPC-3 specific T cells from peripheral blood mononuclear cells (PBMC).
Abstract: Patients with primary biliary cirrhosis (PBC), despite excellent outcomes after liver transplantation (LT), may develop recurrent primary biliary cirrhosis (rPBC). The impact of immunosuppression and HLA mismatches on rPBC is unclear. We evaluated 103 consecutive PBC patients who underwent transplantation (follow-up > or = 10 months) with serial protocol biopsies. Cox regression was used to evaluate factors associated with rPBC: the Model for End-Stage Liver Disease score pre-LT, year of transplantation, age and gender of the recipient and donor, cold and warm ischemic times, HLA mismatches, rejection, infections, and immunosuppression (initial/maintenance). The mean follow-up was 108 months (10-239 months), rPBC occurred in 36, and the mean was 44 months (10-200 months). Immunosuppression was cyclosporine-based in 38 (10 initially on monotherapy) and tacrolimus-based in 62 (19 initially on monotherapy). Steroids were discontinued in all but 7. Azathioprine was part of the initial immunosuppression in 70, 26 discontinued it, and 33 were never exposed to it. rPBC was associated independently with nonuse/discontinuation of azathioprine (P = 0.015, hazard ratio = 0.046, 95% confidence interval = 0.008-0.261). The mean time to rPBC was 74 months with azathioprine, 43 months when AZA was discontinued, and 31 months if no azathioprine was used. Cyclosporine or tacrolimus alone had no impact on rPBC, but cyclosporine with azathioprine was protective for rPBC in comparison with tacrolimus/azathioprine (0/18 versus 7/25, respectively; P < 0.001). rPBC was not affected by HLA mismatches. Azathioprine use in PBC patients who underwent transplantation was associated with less disease recurrence and a longer time to rPBC. Tacrolimus or cyclosporine individually had no effect, but cyclosporine and azathioprine in combination resulted in the least rPBC.
Abstract: Budd-Chiari syndrome (BCS) is the end result of a number of disease states resulting in hepatic venous outflow obstruction. We report a Janus kinase 2-homozygous patient with BCS who thrombosed a transjugular intrahepatic portosystemic shunt (TIPS) despite treatment with warfarin (international normalized ratio = 3.0), aspirin, and clopidogrel. PlateletMapping (Haemonetics Corp.) is a novel point-of-care assay of platelet function based on thromboelastography (TEG) that has the ability to detect platelet inhibition (%) by antiplatelet therapy. Initial PlateletMapping traces showed no platelet inhibition by aspirin or clopidogrel but demonstrated adequate suppression of plasmatic coagulation. On this basis, the aspirin dose was doubled, and this resulted in a significant increase in platelet inhibition (45%). To further suppress platelet activity, the patient was started on tirofiban, a glycoprotein IIb/IIIa inhibitor. Repeat PlateletMapping revealed 100% inhibition of platelets by both pathways, and this coincided with angiographic evidence of TIPS blood flow. Subsequently, the patient developed bleeding from the venous access sites. TEG demonstrated poor underlying plasmatic coagulation with a prolonged R time of 9.2 minutes (normal = 2-8 minutes), and the international normalized ratio was found to be supratherapeutic (>4). Treatment with fresh frozen plasma stopped the bleeding without compromising the platelet inhibition. This case demonstrates that increased platelet activation may contribute to the development of thromboses in BCS. Despite the standard dose of dual antiplatelet therapy, there was minimal inhibition in platelet function, and anticoagulation with warfarin alone was not adequate to prevent thrombotic events. PlateletMapping was used to assess and then optimize the antiplatelet treatment while facilitating the management of complications without an increased risk of thrombosis.
Abstract: BACKGROUND: Refractory variceal bleeding is associated with a high mortality. Existing salvage techniques such as transjugular intrahepatic portosystemic shunt (TIPS) and balloon tamponade (BT) have important limitations and may not be appropriate for all patients. OBJECTIVE: To evaluate the safety and efficacy of a novel removable self-expanding metal stent in the management of refractory variceal bleeding. DESIGN: Case series. SETTING: Tertiary referral liver center. PATIENTS: Ten patients with variceal hemorrhage with contraindications to TIPS insertion or BT. INTERVENTIONS: Insertion of a self-expanding metal stent (SX-Ella DANIS stent). MAIN OUTCOME MEASURES: Survival, failure to control bleeding, and complications. RESULTS: Stent insertion was successful in 9 of 10 patients. Failure to control bleeding was observed in 3 patients (2 with gastric varices), with control of bleeding in the remainder. Overall survival at 42 days was 50%. Six patients survived the acute bleeding episode and had stents removed endoscopically at a median of 9 days after insertion. One patient had a minor ulceration of the esophagus caused by stent insertion. CONCLUSIONS: Insertion of the SX-Ella DANIS stent in patients with refractory variceal bleeding or complications of previous therapy is effective for the control of bleeding. Stent insertion can be achieved in the majority of patients without fluoroscopic control and without major complications. In selected patients, SX-Ella DANIS stent insertion offers an alternative to other methods of salvage such as BT and TIPS and could be considered a substitute for BT after a prospective trial.
Abstract: Recurrent hepatitis C is a common cause of graft loss in patients undergoing liver transplantation, and serial protocol liver biopsies have been used to identify patients at risk of graft loss from rapid fibrosis progression. The aim of this study was to derive a simple noninvasive index to predict fibrosis in patients with recurrent hepatitis C post-transplant. A retrospective study was performed assessing serial liver biopsies for post-transplant chronic hepatitis C infection. One hundred eighty-five patients were included in the analysis; median age 53 years (interquartile range 48-59) and 140 (76%) were male. Liver histology showed 53 (29%) had Ishak fibrosis stages F0/F1, 31 (17%) had F2, 29 (16%) had F3, 19 (10%) had F4 and 53 (29%) had F5/F6. The London Transplant Centres' (LTC) score was derived combining aspartate aminotransferase (AST IU/L), time from liver transplant (TFLT months), international normalized ratio and platelets. Diagnostic accuracy of the LTC score was assessed using area under receiver-operating characteristic (ROC) curves. The area under the ROC curve for moderate fibrosis (F >or= 2) was 0.78 (95% CI, 0.70-0.86; P < 0.0001), for advanced fibrosis (F4-6) was 0.80 (95% CI, 0.72-0.87; P < 0.0001) and for cirrhosis was 0.80 (95% CI, 0.72-0.88; P < 0.0001). An optimal cut-off value of 6.3 distinguished patients with no or mild fibrosis (F <or= 1) odds ratio 10.8 (95% CI, 5.1-22.9); P < 0.0001), sensitivity 88%, specificity 60%, negative predictive value 67% and positive predictive value 84%. The LTC score can identify patients with Hepatitis C virus recurrence following liver transplant with a low risk of significant fibrosis, thus avoiding the need for protocol biopsy.
Abstract: Hepatitis C virus core (HCVcore) protein was expressed in myeloid dendritic cells (DC) from C57/B6 mice (H-2K(b)) by electroporation of HCVcore mRNA to investigate its effect on the ability of DC to prime CD8+ T cells displaying a T cell receptor specific for OVA(257-264) peptide (SIINFEKL)/H-2K(b) complex. Expression of full length HCVcore(191), which is directed to the endoplasmic reticulum (ER) membrane by a C-terminal signal sequence, but not a truncated variant HCVcore(152), which has a wider subcellular localization including the nucleus, significantly reduced surface levels of the H-2K(b)/SIINFEKL complex and impaired the ability of DC to prime naïve CD8+ T cells when they had to process endogenous antigen but not when MHC class I molecules were loaded directly with SIINFEKL peptide. Exploitation of the MHC class I antigen-processing pathway by HCVcore(191) impairs the ability of DC to stimulate CD8+ T cells and may contribute to the persistence of HCV infection.
Abstract: Histopathological scoring of disease stage uses descriptive categories without measuring the amount of fibrosis. Collagen, the major component of fibrous tissue, can be quantified by computer-assisted digital image analysis (DIA) using histological sections. We determined relationships between DIA, Ishak stage, and hepatic venous pressure gradient (HVPG) reflecting severity of fibrosis. One hundred fifteen patients with hepatitis C virus (HCV) who had undergone transplantation had 250 consecutive transjugular liver biopsies combined with HVPG (median length, 22 mm; median total portal tracts, 12), evaluated using the Ishak system and stained with Sirus red for DIA. Liver collagen was expressed as collagen proportionate area (CPA). Median CPA was 6% (0.2-45), correlating with Ishak stage (stage 6 range, 13%-45%), and with HVPG (r = 0.62; P < 0.001). Median CPA was 4.1% when HVPG was less than 6 mm Hg and 13.8% when HVPG was 6 mm Hg or more (P < 0.0001) and 6% when HVPG was less than 10 mm Hg and 17.3% when HVPG was 10 mm Hg or higher (P < 0.0001). Only CPA, not Ishak stage/grade, was independently associated by logistic regression, with HVPG of 6 mm Hg or more [odds ratio, 1.206; 95% confidence interval (CI), 1.094-1.331; P < 0.001], or HVPG of 10 mm Hg or more (odds ratio, 1.105; 95% CI, 1.026-1.191; P = 0.009). CPA increased by 50% (3.6%) compared with 20% in HVPG (1 mm Hg) in 38 patients with repeated biopsies. CONCLUSION: CPA assessed by DIA correlated with Ishak stage scores and HVPG measured contemporaneously. CPA was a better histological correlate with HVPG than Ishak stage, had a greater numerical change when HVPG was low, and resulted in further quantitation of fibrosis in cirrhosis.
Abstract: Less potent immunosuppression is considered to reduce the severity of hepatitis C virus (HCV) recurrence after liver transplantation. An optimal regimen is unknown. We evaluated tacrolimus monotherapy versus triple therapy in a randomized trial of 103 first transplants for HCV cirrhosis. One hundred three patients who underwent transplantation for HCV were randomized to tacrolimus monotherapy (n = 54) or triple therapy with tacrolimus, azathioprine, and steroids (n = 49), which were tapered to zero by 3 to 6 months. Both groups had serial transjugular biopsies with hepatic venous pressure gradient (HVPG) measurement. The time to reach Ishak stage 4 was the predetermined endpoint. All factors documented in the literature as being associated with HCV recurrence and the allocated treatment were evaluated for reaching stage 4 and HVPG >or= 10 mm Hg. No significant preoperative, perioperative, or postoperative differences, including the frequency of biopsies between groups, were found. During a mean follow-up of 53.5 months, 9 monotherapy patients and 6 triple therapy patients died, and 5 monotherapy patients and 4 triple therapy patients underwent retransplantation. Stage 4 fibrosis was reached in 17 monotherapy patients and 10 triple therapy patients (P = 0.04), with slower fibrosis progression in the triple therapy patients (P = 0.048). Allocated therapy and histological acute hepatitis were independently associated with stage 4 fibrosis. HVPG increased to >or=10 mm Hg more rapidly in monotherapy patients versus triple therapy patients (P = 0.038). In conclusion, long-term maintenance immunosuppression with azathioprine and shorter term prednisolone with tacrolimus in HCV cirrhosis recipients resulted in a slower onset of histologically proven severe fibrosis and portal hypertension in comparison with tacrolimus alone, and this was independent of known factors affecting fibrosis.
Abstract: BACKGROUND AND AIM: To evaluate the association of the Risk, Injury, Failure, Loss and End-stage renal failure (RIFLE) score on mortality in patients with decompensated cirrhosis admitted to intensive care unit (ICU). METHODS: A cohort of 412 patients with cirrhosis consecutively admitted to ICU was classified according to the RIFLE score. Multivariable logistic regression analysis was used to evaluate the factors associated with mortality. Liver-specific, Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA) and RIFLE scores on admission, were compared by receiver-operator characteristic curves. RESULTS: The overall mortality during ICU stay or within 6 weeks after discharge from ICU was 61.2%, but decreased over time (76% during first interval, 1989-1992 vs 50% during the last, 2005-2006, P < 0.001). Multivariate analysis showed that RIFLE score (odds ratio: 2.1, P < 0.001) was an independent factor significantly associated with mortality. Although SOFA had the best discrimination (area under receiver-operator characteristic curve = 0.84), and the APACHE II had the best calibration, the RIFLE score had the best sensitivity (90%) to predict death in patients during follow up. CONCLUSIONS: RIFLE score was significantly associated with mortality, confirming the importance of renal failure in this large cohort of patients with cirrhosis admitted to ICU, but it is less useful than other scores.
Abstract: Hepatitis C virus (HCV) allograft cirrhosis may progress rapidly requiring re-transplantation but its course is little studied. We evaluated serially biopsied patients who developed HCV-related allograft cirrhosis. We assessed outcome of graft cirrhosis in 55 out of 234 consecutive patients and predictors of decompensation and mortality, including hepatic venous pressure gradient (HVPG) in 38. Allograft cirrhosis (Ishak stage 6, 60%; stage 5, 40%) was diagnosed between 12 and 172 months (median, 52) from transplantation; subsequent follow up was 22 (1-78) months. Faster development (<or=48 months) was associated with tacrolimus and nonuse of azathioprine and prednisolone. Decompensation occurred in 22% with a probability of not developing decompensation reaching 60% at 5 years. Survival among compensated patients was 77% at 5 years, but fell rapidly after decompensation (12% at 1 year). Decompensation and mortality were independently associated with HVPG >or= 10 mmHg, Child-Pugh score >or= 7, and albumin levels <or= 32 g/dl but not with fibrosis stage 5 or 6, HCV genotype (1b, 34%) or immunosuppression used after diagnosis of cirrhosis. In conclusion, Ishak stage 5 and 6 HCV-related cirrhosis have similar prognosis after liver transplantation. An HVPG >or= 10 mmHg, in addition to liver dysfunction, gives independent prognostic information prior to decompensation, allowing early relisting before prognosis becomes extremely poor.
Abstract: Despite improvements over the past 20 years in patient survival following episodes of acute variceal hemorrhage (AVH) secondary to cirrhosis, AVH is still associated with a high rate of mortality. The ability to predict which patients are at high risk of death, or which are not likely to respond to standard therapy at admission to hospital is important, as it enables the immediate initiation of vasoactive drugs, early endoscopic intervention and prophylactic antibiotics. This commentary discusses a study that attempts to predict early rebleeding and mortality after AVH in patients with cirrhosis using the Model for End-stage Liver Disease. In this study, the model was a significant predictor of mortality; however, several defects in the study's design limit the conclusions that can be drawn from it. The model described in this study is neither more useful, nor more accurate, than those previously published for the prediction of rebleeding and mortality in patients with AVH.
Abstract: BACKGROUND: The exact role of renal dysfunction in critically ill cirrhotics admitted to an intensive care unit (ICU) has not been assessed extensively. AIM: To evaluate the impact of acute renal failure (ARF) on 6 weeks mortality in cirrhotics admitted to ICU. PATIENTS/METHODS: Three hundred and twelve cirrhotics (182 male, mean age 49.6+/-11.5 years) were consecutively admitted during the study period. The patients (n=128, 40%) (group 1) with ARF on admission and/or during ICU were compared with the patients whose ICU stay was not complicated with ARF (n=184, 60%) (group 2). At admission, 40 variables were available, whereas Child-Turcotte-Pugh, Model for End-stage Liver Disease, Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment and Failure Organ System scores on admission, were evaluated and compared by receiver operating characteristic curves. RESULTS: Group 1, compared with group 2 patients, had longer ICU stay (7 vs. 4 days, P=0.04) and required cardiovascular support more frequently with inotropes (90 vs. 75%), (P<0.001). Mortality was significantly higher in group 1, compared with group 2 (91 vs. 47%, P<0.001). At admission, group 1, compared with group 2, had significantly higher Child-Turcotte-Pugh (12 vs. 11), Acute Physiology and Chronic Health Evaluation II (22 vs. 17), Model for End-stage Liver Disease (31 vs. 21), Sequential Organ Failure Assessment (13 vs. 9) and Failure Organ System (3 vs. 2) scores (P<0.001). In group 1, factors independently associated with mortality were: higher FiO2 (P=0.044), bilirubin (P=0.021) and creatinine (P=0.002) on admission. Mortality was not significantly different between those with ARF on admission, and those who developed ARF during ICU stay. CONCLUSION: ARF at admission or during ICU stay is strongly predictive of mortality, which is high, despite supportive therapeutic interventions. Preventive measures are needed to prevent ARF, to improve prognosis.
Abstract: INTRODUCTION: Battle's sign is a classical clinical sign that has long been held to be synonymous with fracture of the basal skull. As such the presence of Battle's sign is a strong indicator that a basal skull fracture could be present in the head injured patient, as exemplified by its inclusion as a major risk factor in scoring systems designed to assess the likelihood of basal skull fracture. DISCUSSION: We present a case that describes the occurrence of this classic clinical sign in an unlikely setting and, for the first time since it was described more than 120 years ago, re-examine the pathologic basis for its appearance.
Abstract: BACKGROUND: Capsule endoscopy (CE) is considered a first-line investigation for obscure GI bleeding (OGIB) and small-bowel polyp or tumor detection. The reliability of a negative CE in excluding gross small-bowel pathology remains unclear. New imaging modalities, such as double-balloon enteroscopy (DBE), CT enterography (CTE) or magnetic resonance enterography (MRE) now provide complementary roles to CE for these indications. OBJECTIVE: We describe our experience of significant small-bowel pathology missed at CE in 5 patients. The lesions were subsequently detected by DBE, CTE, or MRE. DESIGN: A retrospective case series. SETTING: Single-center academic endoscopy unit in a tertiary-referral hospital. PATIENTS: Five patients were evaluated: 4 with a history of OGIB (transfusion dependent in 2) and 1 patient with Peutz-Jeghers syndrome (PJS) under small-bowel surveillance. INTERVENTIONS: CE was performed in all patients. Further evaluation via DBE, CTE, or MRE was performed. Definitive treatment was carried out by enteroscopic polypectomy (1 patient), surgical resection (2 patients), and transjugular intrahepatic portosystemic shunt procedure and embolization (1 patient). MAIN OUTCOME MEASUREMENTS: Detection of significant small-bowel pathology by using DBE, CT, or MRE after a negative capsule study. RESULTS: Significant small-bowel pathology was missed at CE but was detected by alternative modalities in 5 patients. In 4 patients, the lesions were in the proximal small bowel (adenocarcinoma, malignant melanoma, varices, and stromal tumor). The fifth patient had a large PJS polyp in the proximal ileum. LIMITATIONS: Retrospective case series with small numbers. CONCLUSIONS: Gross pathology may be missed at CE, especially in the proximal small bowel, and a negative CE study does not exclude significant disease. Alternative imaging modalities, such as DBE, CTE, or MRE, should be considered when clinical suspicion persists.
Abstract: Conventional cytotoxic chemotherapy has not provided clinical benefit or prolonged survival for patients with advanced HCC. This review summarizes the results of prospective clinical trials of several categories of systemic therapy, with emphasis on the more promising results from recent trials of biologically targeted therapeutic agents in HCC.
Abstract: BACKGROUND AND AIM: The accuracy of prognostic models in critically ill cirrhotics at admission to intensive care units (ICU) may be unreliable. Predictive accuracy could be improved by evaluating changes over time, but this has not been published. The aim of the present study was to assess the performance of prognostic models in cirrhotics at admission (baseline) and at 48 h to predict mortality in the ICU or within 6 weeks after discharge from the ICU. METHODS: One hundred and twenty-eight cirrhotics (77 males, mean age 49 +/- 11.3 years) were consecutively admitted and alive 48 h after admission with 89% on mechanical ventilation, 76% on inotrope support, and 42% with renal failure. Prognostic models used were Child-Turcotte-Pugh (CTP), Model for End-stage Liver Disease (MELD), Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA), failing organ systems (FOS) at baseline and at 48 h, Deltascore (difference between baseline and at 48 h) and the mean score (MN - score admission + 48 h/2) which were compared by area under the receiver operating characteristic curves (AUC). RESULTS: Mortality was 54.7% (n = 70) due to multiple organ failure in 55%. CTP, MELD, APACHE II, SOFA and FOS performed better at 48 h (AUC: 0.78, 0.86, 0.78, 0.88 and 0.85, respectively) than at baseline (AUC: 0.75, 0.78, 0.75, 0.81 and 0.79, respectively). The mean score had better discrimination than the baseline score; the Deltascore had poor predictive ability (AUC < 0.70). SOFA score (48 h: 0.88, mean: 0.88) and FOS (mean: 0.88) had the best accuracy, with a SOFA and MN-SOFA > or = 10 predicting mortality in 93% and 91%, respectively, and MN-FOS > or = 1.5 in 98%. CONCLUSIONS: In cirrhotics, prognostic scores in the ICU at 48 h had better discrimination than baseline scores for short-term mortality. SOFA and FOS models had the best performance.
Abstract: Recently, treatment with corticosteroids in the setting of septic shock and adrenal insufficiency has been shown to decrease mortality. In septic patients, a blunted response to adrenal stimulation identifies patients with a poorer prognosis who may benefit from corticosteroid supplementation. This condition has been termed relative adrenal insufficiency (RAI). Given the similarities between septic shock and liver failure, a number of groups have now studied the incidence of RAI in various forms of liver disease. Although different definitions of RAI exist, the current literature suggests that RAI is common, being seen in 33% of acute liver failure patients and up to 65% of patients with chronic liver disease and sepsis. The finding that RAI can exist in the absence of sepsis and may be as high as 92% of patients undergoing liver transplantation using a steroid free protocol has led one group to propose the term hepatoadrenal syndrome. The purpose of this review is to summarise the existing evidence for adrenal insufficiency in liver disease, to examine the possibility that adrenal dysfunction in liver disease may have a separate pathogenesis to that observed in sepsis and to provide insight into the potential areas for further research into this condition.
Abstract: Hepatorenal syndrome (HRS) is a serious complication of advanced liver disease. Historically, the development of HRS was considered a pre-terminal event due to a lack of efficacious therapy. Although liver transplantation remains the optimum therapy for HRS, many patients may be unsuitable for liver grafting. In addition, organ shortage may necessitate the institution of alternative pharmacological therapies to bridge patients to transplantation or to maintain renal function. This article reviews the definitions of Types-1 and -2 HRS, and addresses strategies for the prevention of the syndrome. It will also discuss management approaches to the cirrhotic patient with renal failure, specifically, assessment of novel vasoconstrictor therapies, such as vasopressin analogues, alpha-adrenoreceptor agonists, and the use of transjugular intra-hepatic shunts either alone or in combination with other therapeutic agents.
Abstract: Collagenous colitis is a condition usually characterized by watery diarrhoea, macroscopically normal colonic mucosa and a typically thickened subepithelial collagen band on histological examination. It is rare in children, and coexistence with other inflammatory bowel diseases has been reported only rarely. We describe a case of diarrhoea presenting in infancy subsequently proved to be collagenous colitis that progressed to the typical features of Crohn's disease.
Abstract: Hepatocellular carcinoma (HCC) is common, and current therapies may not be suitable for the majority of patients with advanced disease. Cases of spontaneous regression suggest that immune mechanisms are important in the control of HCC. Experiments in animal models have shown that tolerance to HCC associated antigens can be overcome and using a number of different techniques researchers have been able to prevent the growth of implanted tumours. The most promising of these techniques is based on the use of dendritic cells, which are able to process and present antigens to activate naive T cells and, when loaded with tumour antigens, can stimulate a specific and durable anti-tumour response. The success of animal studies has led to interest in the clinical applicability of HCC immunotherapy. Non-specific adoptive immunotherapy has been successful in preventing disease recurrence after resection and cellular vaccines based on dendritic cells are now entering clinical trials. The use of dendritic-cell vaccination raises exciting possibilities of preventing the formation of HCC in high-risk individuals such as those with cirrhosis.
Abstract: Alcoholic hepatitis is a common condition with a high mortality. Although treatment options for established alcoholic hepatitis are limited, many of the complications of this condition are preventable. This case report and discussion illustrate the important role of early diagnosis and intervention in this patient group. Important management points are stressed to aid physicians who may encounter this condition rarely.
Abstract: BACKGROUND: Cyclosporine is the most common maintenance immunosuppressant in liver transplants patients, but it is often associated with nephrotoxicity. METHODS: We evaluated the safety and efficacy of monotherapy with mycophenolate mofetil (1 g twice daily) in five stable liver transplant patients with cyclosporine-induced renal impairment despite reduction of cyclosporine to subtherapeutic levels. Follow-up was 8.4+/-2.4 (range: 6-12) months. RESULTS: No major side effects have been observed to date. Serum creatinine levels were significantly reduced from a median of 201 micromol/L before to 142 micromol/L at 3 months after mycophenolate (P=0.04) and remained low at 6 months. New onset cellular rejection occurred in only one patient after 3 months on mycophenolate monotherapy, and it responded completely to an intravenous course of methylprednisolone. CONCLUSIONS: Monotherapy with mycophenolate mofetil in a dose of 1 g twice daily seems to significantly improve cyclosporine-induced renal impairment in stable liver transplant patients without major side effects or significant risk of rejection.
