Combined HLA-DR and -DQ disparity is associated with a stable course of ulcerative colitis after liver transplantation for primary sclerosing cholangitis.

Combined disparity of human leukocyte antigen (HLA)-DR and -DQ between mother and fetus is associated with less severe ulcerative colitis (UC) during pregnancy. We evaluated whether donor-recipient HLA disparity after liver transplantation (LT) affects UC in patients with primary sclerosing cholangitis (PSC). Sixty-nine consecutive patients with PSC underwent LT; all underwent colonoscopy before LT; 48 had UC before and 3 had de novo UC after LT. Clinical and laboratory data, activity and treatment of UC, post-LT cytomegalovirus infection, and disparity of HLA-A, -B, -DR, and -DQ for each donor-recipient pair were evaluated. Pre-LT quiescent UC was present in 26 patients. Post-LT UC activity was evaluated in 36 of 51 patients with UC who had not undergone pre-LT colectomy and who had >12 months' post-LT survival. Of these, 16 were stable, 17 had worsened, and 3 had de novo UC. Seven required colectomy (4 for dysplasia or cancer) after LT. Post-LT cytomegalovirus viremia was neither associated with worse UC activity (P = 0.58) nor de novo UC. Disparity with respect to HLA-A, -B, -DR, and -DQ was found in 58%, 27%, 44%, and 39% donor-recipient pairs, respectively. Post-LT UC course was similar with respect to single HLA disparity. However, disparity in none or only one HLA-DR or -DQ was significantly associated with worse activity compared with patients with disparity at both (65% vs. 0%, P = 0.009). Logistic regression found that the disparity for both -DR and -DQ was the only factor statistically significantly associated with post-LT UC activity. We conclude that disparity in both HLA-DR and -DQ between donor and recipient is associated with stable UC activity after LT.     

A systematic review of the performance of the model for end-stage liver disease (MELD) in the setting of liver transplantation.

The Model for End-Stage Liver Disease (MELD) score is now used for allocation in liver transplantation (LT) waiting lists, replacing the Child-Turcotte-Pugh (CTP) score. However, there is debate as whether it is superior to CTP score to predict mortality in patients with cirrhosis on the LT waiting list and after LT. We reviewed studies comparing the accuracy of MELD vs. CTP score in transplantation settings. We found that in studies of the LT waiting list (12,532 patients with cirrhosis), only 4 of 11 showed MELD to be superior to CTP in predicting short-term (3-month) mortality. In addition, 2 of 3 studies (n = 1,679) evaluating the changes in MELD score (DeltaMELD) showed that DeltaMELD had better prediction for mortality than the baseline MELD score. The impact of MELD on post-LT mortality was assessed in 15 studies (20,456 patients); only 6 (9,522 patients) evaluated the discriminative ability of MELD score using the concordance (c) statistic (the MELD score had always a c-statistic < 0.70). In 11 studies (19,311 patients), high MELD score indicated poor post-LT mortality for cutoff values of 24-40 points. In re-LT patients, 2 of 4 studies evaluated the discriminative ability of MELD score on post-LT mortality. Finally, several studies have shown that the predictive ability of MELD score increases by adding clinical variables (hepatic encephalopathy, ascites) or laboratory (sodium) parameters. On the basis of the current literature, MELD score does not perform better than the CTP score for patients with cirrhosis on the waiting list and cannot predict post-LT mortality.     

Long‐term follow‐up of immunosuppressive monotherapy in liver transplantation: tacrolimus and microemulsified cyclosporin

Cholongitas E, Shusang V, Germani G, Tsochatzis E, Raimondo ML, Marelli L, Senzolo M, Davidson BR, Patch D, Rolles K, Burroughs AK. Long‐term follow‐up of immunosuppressive monotherapy in liver transplantation: tacrolimus and microemulsified cyclosporin.
Clin Transplant 2011: 25: 614–624. © 2010 John Wiley & Sons A/S. Abstract: Background: Early withdrawal of steroids after liver transplantation has benefits, but rarely is total avoidance of steroids used. We evaluated long‐term results of patients with ab initio monotherapy with cyclosporin (CYA) vs. tacrolimus (TAC), in randomized and cohort studies. Methods: We evaluated long‐term outcomes in 66 adults randomized to TAC or CYA and 94 subsequent patients who received TAC. Protocol liver biopsies were performed. Rejection was treated with three 1 g/d methylprednisolone. Further rejection after two courses of methylprednisolone was defined as monotherapy failure. Results: Actuarial five‐yr survival was 68% in TAC and 70% CYA. Monotherapy failed in 8% TAC and 13% CYA patients; no rejection in 24% TAC and 19% CYA patients; 42% TAC and 33% CYA patients were not exposed to any steroids. Rejection episodes were less with TAC, compared to CYA: mean 1.8 vs. 2.5, p = 0.042. Chronic rejection occurred in only 4 (11%) CYA patients. During follow‐up of median 97 months (range: 0.06–145), there were 16 (44%) deaths in CYA and 48 (39%) in TAC patients (p > 0.05). Conclusions: TAC monotherapy ab initio is a viable immunosuppressive strategy in liver transplantation and was associated with lower rejection rates and renal complications, compared to CYA.     

Autoimmune hepatitis associated with Kikuchi-Fujimoto's disease

We describe a 20-year-old woman with autoimmune hepatitis (AIH) with cirrhosis who developed Kikuchi-Fujimoto's disease (KFD) and de novo minor features of systemic lupus erythematosus (SLE). This is the first report of a patient with histologically confirmed AIH developing KFD (histiocytic necrotizing lymphadenitis). One previous case described KFD after AIH (diagnosed clinically but without biopsy). KFD is a rare condition of unknown aetiology, first described in 1972, characterized by fever and cervical adenopathy and has a self-limiting course. KFD is associated with SLE, and SLE in turn can be associated with abnormal liver function tests, which in a minority of cases may be due to AIH. The association of AIH, KFD, and SLE in our patient suggests an autoimmune pathogenesis of KFD.     

Heparin‐like effect contributes to the coagulopathy in patients with acute liver failure undergoing liver transplantation

Introduction: Liver transplantation (LT) in cirrhotics is characterized by severe coagulopathy, associated with a well documented heparin‐like effect (HLE) seen by thromboelastography (TEG^?) after reperfusion. The amount of HLE present in patients with acute liver failure (ALF) and its role in their bleeding tendency before LT has not been investigated. Aim: To investigate the presence and extent of HLE in patients with ALF undergoing LT and to compare the extent of HLE in this group with a group of cirrhotics undergoing LT. Material and Methods: Ten consecutive ALF and 10 cirrhotic patients undergoing LT were included. TEG^? (with and without heparinase I), surrogate total thrombin generation (TTG) derived by TEG^? and haemodynamic variables were recorded for every stage of the LT. HLE was defined as a correction of r+k times on TEG^? of more than 50% by the addition of heparinase I. Results: Before incision, patients with ALF showed a significantly greater HLE compared with patients with cirrhosis (r+k time: 66 min corrected to 29 vs 45 min corrected to 32 min, P=0.001). After reperfusion, all the patients showed extensive HLE, without any difference between the two groups. Despite the greater HLE, patients with ALF showed similar TTG compared with the cirrhotic group. By the end of the operation, the extent of the HLE was greatly reduced in both the groups. Conclusions: Before transplantation, patients with ALF have a greater HLE than patients with liver cirrhosis. However, this did not affect the thrombin generation calculated by TEG^? and resolved after transplantation.     

A Comparison of Four- Versus Three-Pass Transjugular Biopsy Using a 19-G Tru-Cut Needle and a Randomized Study Using a Cassette to Prevent Biopsy Fragmentation

Recently, it has been shown that transjugular liver biopsy (TJLB) with three passes gives comparable specimens to percutaneous liver biopsy (PLB). The aim of this study was to evaluate the adequacy of TJLB using four passes in a consecutive series of patients, and whether using a supportive cassette can prevent fragmentation. One hundred consecutive TJLBs in 92 patients (48 transplanted), always using four passes (19-G Tru-Cut), were compared to three-pass TJLBs. The four-pass TJLB specimens were randomized at a 1:1 ratio of liver cores placed in a cassette versus not. The four-pass TJLBs, compared to three-pass TJLBs, resulted in better specimens for length (≥25 mm: 50% vs. 35%; p = 0.026) and number of complete portal tracts (CPTs) (≥11: 40% vs. 26%; p = 0.027), without a higher complication rate. The four-pass TJLB with ≥11 CPTs had a median length of 27 mm, and 57% of them longer than 28 mm contained ≥11 CPTs. Putting the liver biopsy cores into a cassette did not improve the fragmentation rate or adequacy of the specimen (length and number of CPTs) of TJLB. We conclude that at least four passes with TJLB should be performed when liver specimens are needed for grading and staging. Using a supportive cassette did not reduce fragmentation.     

Transjugular liver biopsy--indications, adequacy, quality of specimens, and complications--a systematic review

Transjugular liver biopsy (TJLB) is considered an inferior biopsy, used when percutaneous liver biopsy (PLB) is contraindicated. According to recent literature, specimens with 6 complete portal tracts (CPTs) are needed for histological diagnosis of chronic liver disease but 11 CPTs to reliably stage and grade. Mean CPT number in PLB series is 7.5; more passes increase complications. Sixty-four series reporting 7649 TJLBs were evaluated for quality of specimen and safety. Major indications were coagulation disorders and/or ascites. Success rate was 96.8%. Fragmentation rate was 34.3%, not correlating with length or diagnostic adequacy. With a mean of 2.7 passes, mean CPT number was 6.8. Histological diagnosis was achieved in 96.1% of TJLBs, correlating with length (p=0.007) and CPT number (p=0.04). Tru-Cut specimens had a mean CPT number of 7.5 and, compared to Menghini specimens, were longer (p<0.008), less fragmented (p<0.001) and more diagnostic (p<0.001). Thinner needles (>16-G) provided significantly longer and less fragmented specimens. Minor and major complication rates were 6.5% and 0.56%, respectively, and increased in children, but not with additional passes. In adults, mortality was 0.09% (haemorrhage 0.06%; ventricular arrhythmia 0.03%). TJLB is safe, providing specimens qualitatively comparable to PLB, and may improve further using > or = 18-G Tru-Cut needle and >3 passes.     

Ethnic variations in ulcerative colitis: Experience of an international hospital in Thailand

AIM: To investigate the clinical characteristics, treatment, medication use, and treatment response in patients with ulcerative colitis(UC) across ethnic groups.METHODS: This study retrospectively analyzed medical records of all 268465 patients who visited the Bumrungrad International Digestive Disease Center during 2005-2010. The demographics, clinical characteristics, medication use, results of investigations, and medical and surgical management for patients with UC were evaluated. Evaluation included sigmoidoscopy and colonoscopy performed in compliance with the American Society of Gastrointestinal Endoscopy practice guidelines. Patient ethnicities were categorized into seven groups: Thai, Oriental, South Asian(SA), Middle Eastern(ME), Caucasian, African, and Hispanic. UC pathological severity was classified into inactive, mild, moderate, and severe. Associations between categorical variables were analyzed using the χ2 or Fischer's exact test. Associations between categorical and interval variables were analyzed usingStudent's t-test and/or analysis of covariance.RESULTS: UC was diagnosed in 371 of the 268465 patients: male 56.33%; ME 42%, Caucasian 23%, and Thai 19%. Annual incidence of UC was 82 cases per 100000 with wide ethnic variation, ranging from 29 to 206 cases per 100000 in Oriental and ME patients, respectively. Of the patients with UC, 16.71% had severe UC with highest incidence among the patients from ME(20.39%) and lowest among the Caucasian population(11.90%). ME had highest proportion of pancolitis(52.90%), followed by Caucasian(45.35%) and Asian(34.40%). Only 20.93% of Caucasian patients received steroid, compared with 26.40% and 27.10% of Asian and Middle Eastern, respectively(P = 0.732). Overall, 13.72% of UC patients did not respond to steroid therapy, with non-significantly higher proportions of non-responders among Asian and Middle Eastern patients(15.22% and 15.04%, respectively)(P = 0.781). On average, 5.93% underwent surgical management with ethnic variation, ranging from 0% in African to 18% in SA. Cancer was found in three(Thai, ME, and African) cases(0.82 institution-specific incidence).CONCLUSION: Incidence, symptom duration, pathological severity, clinical manifestations, medication use, treatment response, need for surgical consultation, and cancer incidence of patients with UC potentially vary by ethnicity.