The role of Helicobacter spp. in the pathogenesis of primary biliary cirrhosis and primary sclerosing cholangitis.

Helicobacter species DNA has been detected in liver tissue of patients affected by primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). To investigate a potential causative relation between Helicobacter species and PBC/PSC, we compared the presence of Helicobacter species-specific DNA in liver tissue of patients with PBC/PSC (n=18/n=13) with those of a control group of patients with various liver diseases with known cause (n=29). A PCR with Helicobacter genus-specific 16S rRNA primers was performed on DNA isolated from paraffin embedded liver tissue. Control patients had hepatitis-B (n=9), alcoholic cirrhosis (n=14), or non-cirrhotic metabolic liver disease (n=6). There was no significant difference between the incidence of Helicobacter spp.-specific DNA in PBC/PSC (9/31; 29%) and the control group (10/29; 34%). Sequence analysis confirmed Helicobacter spp. DNA. Because Helicobacter spp. DNA can be found in approximately one-third of all samples tested, it is unlikely that PSC and PBC are caused by Helicobacter infection.

Heterotopic vs. orthotopic liver transplantation for chronic liver disease: a case-control comparison of short-term and long-term outcomes.

Between 1986 and 1990 we performed heterotopic liver transplantation (HLT) in 17 patients with chronic liver disease. In spite of theoretical advantages and favorable short-term results, we abandoned HLT because of doubts about the long-term outcome and the improved results of standard orthotopic liver transplantation (OLT). There are, however, no studies comparing the long-term survival after HLT and OLT for chronic liver disease. We performed a case-control study of HLT vs. OLT, with long-term patient and graft survival as the main outcome measures. Known confounders and differences in baseline characteristics between HLT and OLT patients were corrected for. At 1 year, 5 of the 17 HLT patients had died, compared with 9 of the 34 OLT patients (relative risk [RR], 1.15; 95% confidence interval [CI], 0.33-4.02; P = 0.83). After correction for confounders, the long-term risk of graft failure (RR, 18.0; 95% CI, 1.5-223.5; P = 0.02) and of death (RR, 5.2; 95% CI, 0.8-34.8; P = 0.09) was higher after HLT than after OLT. The main causes of graft loss and death at more than 1 year after HLT were de novo malignancies and a variety of biliary complications. In conclusion, our data, from 1 of the largest single-center series of HLTs available, showed no significant difference between HLT and OLT in 1-year survival. However, the long-term outcome of HLT was inferior. HLT cannot be recommended as an alternative to OLT for any of the indications we studied, even though only 1 of the late deaths was definitely related to the heterotopic technique.

Focal nodular hyperplasia: findings at state-of-the-art MR imaging, US, CT, and pathologic analysis.

Focal nodular hyperplasia (FNH) is the second most common benign liver tumor after hemangioma. FNH is classified into two types: classic (80% of cases) and nonclassic (20%). Distinction between FNH and other hypervascular liver lesions such as hepatocellular adenoma, hepatocellular carcinoma, and hypervascular metastases is critical to ensure proper treatment. An asymptomatic patient with FNH does not require biopsy or surgery. Magnetic resonance (MR) imaging has higher sensitivity and specificity for FNH than does ultrasonography or computed tomography. Typically, FNH is iso- or hypointense on T1-weighted images, is slightly hyper- or isointense on T2-weighted images, and has a hyperintense central scar on T2-weighted images. FNH demonstrates intense homogeneous enhancement during the arterial phase of gadolinium-enhanced imaging and enhancement of the central scar during later phases. Familiarity with the proper MR imaging technique and the spectrum of MR imaging findings is essential for correct diagnosis of FNH.

Early differentiation between rejection and infection in liver transplant patients by serum and biliary cytokine patterns.

BACKGROUND: Differentiation between acute liver graft rejection and infection remains a clinical challenge during the early posttransplantation period. Although cytokines play a pivotal role in mediating allograft rejection, previous studies demonstrate that most cytokines are not specific for liver graft rejection or infections. However, other studies suggest that adhesion molecules and cytokines in bile reflect the immunologic activity within the liver more closely. Therefore, we postulated that by combining cytokine patterns in serum and bile, early recognition of acute liver graft rejection and differentiation from infectious complications can be improved. METHODS: We performed a prospective study in 45 patients who were monitored daily for clinical events and cytokine patterns in serum and bile during the first month after liver transplantation. RESULTS: Soluble intercellular adhesion molecule-1 (sICAM-1) in serum and interleukin-8 in bile were specifically increased at the onset of acute rejection (P<0.001), whereas serum soluble tumor necrosis factor-receptor II was also significantly increased in patients with infectious complications and serum interleukin-6 only in patients with rejection during infection. In 68% of patients with increased sICAM-1, acute rejection was diagnosed within 10 days, whereas rejection occurred in only 26% of patients with low serum levels of sICAM-1. In patients with increased sICAM-1, the relative risk for rejection was 4.8 (P=0.009). CONCLUSIONS: Cytokine patterns in bile do not provide rejection markers with higher specificity compared with serum cytokines. Daily monitoring of sICAM-1 in serum could identify patients at risk for rejection; therefore, acute liver graft rejection may be recognized earlier in those patients.

Cytokine gene polymorphisms and acute human liver graft rejection.

Interindividual differences exist in the capacity to produce cytokines. It has been reported that levels of in vitro cytokine production measured after stimulated cell culture are associated with polymorphisms in cytokine genes. Moreover, a correlation between heart, kidney, liver, and lung graft rejection or survival with cytokine gene polymorphisms has been described. In the present study, we analyzed the association of gene polymorphisms in T helper subtype 1 (T(H)1-), T(H)2-, and regulatory-type cytokines with human liver allograft rejection. Patients who received a primary liver graft from 1992 onward and were seen at the transplant outpatient clinic since then were included on this study (n = 89). Patients were HLA typed routinely. Biopsy-proven acute rejection occurred in 41 of 89 patients. After informed consent, blood was collected and DNA was obtained. Using amplification-refractory mutation system polymerase chain reaction, the following cytokine gene polymorphisms were determined: IL-2+166, IL-2-330, IL-15+13689, IL-15-80, TNF-A-308, TNFd3, IFN-G+874 (T(H)1-type cytokines), IL-4+33, IL-4-590, IL-6-174, IL-10-592, IL-10-819, IL-10-1082, IL-13+2043, IL-13-1055 (T(H)2 type cytokines), TGF-B1+869, and TGF-B1+915 (regulatory-type cytokines). Univariate analysis showed that polymorphisms of IL-10-1082, TGF-B1+869, and HLA-DR6 were significantly related to liver graft rejection. Multiple logistic regression analysis was used to assess which variables remained significantly predictive of acute rejection. Multivariate analysis showed that TGF-B1+869 and HLA-DR6 were independently associated with the occurrence of acute rejection. These findings suggest a role for the regulatory-type cytokine transforming growth factor-beta1 in human liver graft rejection.

The importance of orthotopic liver transplantation in acute hepatic failure.

Selection of patients with acute hepatic failure for liver transplantation remains difficult, and there is no definite proof of a survival effect. We therefore did a retrospective study in 75 consecutive patients referred over a 12-year period. In two-thirds we identified a cause, mostly viruses or drugs. Patients were grouped by the Clichy and King's College criteria. In 20 there was no indication for transplantation. Of the 5 with autoimmune hepatitis, 3 died, significantly differing from the other 15 ( P = 0.009). The remaining 55 met our criteria, except 1. All 9 patients with absolute contraindications died. Of the 46 enlisted, 7 died without transplantation. One-year survival after transplantation was 69%, compared with 58% by "intention to treat." For patients enlisted, transplantation reduced mortality by 78% ( P = 0.069). The Clichy and King's College criteria reliably predict survival without transplantation, except in autoimmune hepatitis. Our study strongly suggests that transplantation improves survival.