The effect of albumin dialysis on cytokine levels in acute liver failure and need for liver transplantation

In acute liver failure (ALF), detoxification capacity of liver cells is reduced and a variety of cytokines, immune modulators, and toxic substances are accumulating. Multiple organ failure in ALF has been associated with increased blood cytokine levels. We have used a blood purification system, molecular adsorbent recirculating system (MARS), which is based on removal of both protein bound and water-soluble substances and toxins in liver failure. In this study, we measured the effect of MARS therapy on plasma cytokine levels in 49 patients with ALF. Interleukin 6 (IL-6), IL-8, IL-10 and tumor necrosis factor (TNF)alfa were determined immediately before and after the first MARS therapy and after the last session using enzyme-linked immunosorbent assays. The overall survival of these ALF patients was 82% at 6 months; the native liver recovered in 26 cases, and 14 were successfully transplanted. All three interleukins were increased before the MARS treatment but only anti-inflammatory IL-10 was reduced significantly during therapy, which in this setting could be interpreted as a positive effect. We were not able to show constant decreases in proinflammatory cytokines, but only transient effects on IL-8 and IL-6. Surprisingly TNFalfa level was normal and did not change during therapy. In theory, MARS albumin dialysis may remove toxic substances from the blood circulation and thereby improve the possibilities of the liver to recover; however, of the measured cytokines only IL-10 decreased significantly.     

Equal overall rejection rate in pre-transplant flow-cytometric cross-match negative and positive adult recipients in liver transplantation

T cell IgG flow-cytometric cross-matches (FCXM) using 48 stored pre-transplant patient serum samples and 40 stored serum samples collected 3 wk after liver transplantation and frozen spleen cells of cadaveric donors in 48 consecutive liver transplantations were performed retrospectively. T cell IgG FCXM using pre-transplant serum samples was compared with 46 complement-dependent lymphocytotoxic cross-matches (CDCXM) performed at the time of transplantation. Clinical relevance of these tests was evaluated in relation to acute rejection, 1-, 3- and 5-yr graft and patient survival. The incidence of positive FCXM was 33% (16 of 48) and 13% (six of 46) by CDCXM. The median time of acute rejection was 29 d after transplantation in FCXM positive group (range 13-101 d) and 22 d in FCXM negative group (range 7-157 d, NS). Rejection rate was similar in 16 pre-transplant FCXM positive patients (eight of 16, 50%) compared with six pre-transplant CDCXM positive patients (three of six, 50%; NS). Recipients having graft rejection tended to be more often pre-transplant FCXM positive (eight of 21, 38%) than CDCXM positive (three of 21, 14%), but the difference was not significant (p > 0.1). No difference was found in the positive predictive value in relation to acute rejection between positive FCXM and CDCXM (69% vs. 50%; NS). Furthermore there was no correlation between post-transplant positive FCXM and acute rejection. No difference was found between pre-transplant T cell IgG FCXM positive and negative recipients in relation to graft or patient survival. Our findings are supportive for little risk associated with preformed donor-specific antibodies in liver transplantation.     

Liver tumour MRI: what do we need for lesion characterization?

BACKGROUND: Hepatic lesions constitute a daily challenge to radiology in clinical settings, and non-invasive methods are valuable in the characterization of these liver tumours. We undertook our investigation to assess the lesion characterization potential of MRI by evaluating several unenhanced MR sequences and the dynamic gadolinium (Gd)-enhanced technique. METHODS: A total of 116 focal liver lesions in 116 patients were included in our retrospective study, and histological verification was available for 107 lesions. Nine haemangiomas had a follow-up of 2 years. The 1.5-T MR system was used. T1- and T2-weighted sequences and dynamic Gd-enhanced studies were evaluated by two individual readers as separate sequences and also collectively. Lesions were classified into benign or malignant, and a specific diagnosis was proposed. The McNemar test was used in statistical analysis, and interobserver variation was measured using kappa statistics. RESULTS: Lesion classification into benign and malignant tumours (by evaluating all images in concert) was assessed in 83% and 89% of cases by readers 1 and 2, respectively. From single sequences, best lesion classification was achieved with Gd-enhanced T1 by both readers. The difference in classification was statistically significant when all sequences were evaluated in comparison with any single sequence alone (P = 0.02). Specific diagnosis was correctly determined using all sequences together in 60% and 71% of cases by readers 1 and 2, respectively. For individual sequences, correct diagnosis was most frequently proposed with a Gd-enhanced T1-weighted sequence by both readers (59% and 65% for readers 1 and 2, respectively). CONCLUSION: Multisequential MRI using Gd-enhanced imaging performs extremely well in liver lesion classification, and with moderate ability to determine a specific diagnosis.     

Albumin dialysis has no clear effect on cytokine levels in patients with life-threatening liver insufficiency

Cytokines play a important role in life-threatening liver insufficiency. They are released within the liver in response to hepatic injury and inflammation. To study cytokine clearance during albumin dialysis treatment (Molecular Adsorbent Recirculating System [MARS]), we monitored proinflammatory (tumor necrosis factor alpha [TNF-alpha] and interleukin-8 [IL-8]) and anti-inflammatory (IL-10 and IL-6) cytokines and the lymphocyte activation marker IL-2sRalpha in 81 consecutive ICU patients displaying serious hepatic decompensation. Cytokine levels were measured before treatment and after the last MARS treatment in 49 acute liver failure (ALF) and 32 acute decompensation of chronic liver disease (AcOChr) patients who were mainly considered for liver transplantation. No significant change in cytokines was observed before versus after the last MARS treatment in the AcOChr group, and only IL-10 decreased significantly in the ALF group. Baseline levels of IL-8 and IL-6 were significantly lower and IL-10 was higher in the ALF group compared with those in the AcOChr group. TNF-alpha and IL-2sRalpha levels did not differ between the groups. After treatment, IL-8 was also significantly lower in ALF patients compared with the levels in AcOChr patients. In this study, MARS therapy did not show a clearly identifiable efficacy at removing circulating cytokines. However, the results revealed that ALF and AcOChr patients displayed different profiles of circulating cytokines.     

Effect of the aetiology and severity of liver disease on oral health and dental treatment prior to transplantation

Elimination of dental infection foci has been recommended before liver transplantation (LT) because lifelong immunosuppression may predispose to infection spread. Association between pre‐LT oral health and the aetiology and severity of chronic liver disease (CLD) was investigated retrospectively. A total of 212 adult patients (median age 51.1) who had received LT during 2000–2006 in Finland were included. Their oral health had been pre‐operatively examined. Patients were divided into seven different CLD groups. Common indications for LT were primary sclerosing cholangitis (PSC 25.5%), alcohol cirrhosis (ALCI 17.5%) and primary biliary cirrhosis (PBC 14.6%). Patients were also categorized by the Model for End stage Liver Disease (MELD) scoring system. Medical, dental and panoramic jaw x‐ray data were analysed between groups. PBC patients had the lowest number of teeth with significant difference to PSC patients (19.7 vs. 25.6, P < 0.005, anova , t‐test). ALCI patients had the highest number of tooth extractions with significant difference in comparison to PSC patients (5.6 vs. 2.5, P < 0.005). Lower MELD score resulted in fewer tooth extractions but after adjusting for several confounding factors, age was the most important factor associated with extractions (P < 0.005). The aetiology of CLD associated with the oral health status and there was a tendency towards worse dental health with higher MELD scores.