Hepatobiliary malignancies are frequently seen in primary sclerosing cholangitis (PSC) and they complicate the evaluation of patients and timing of liver transplantation.
Data from all Nordic PSC ...patients listed for liver transplantation during 1990–2001 were recorded prospectively. Predictors of hepatobiliary malignancy and patient survival rates have been analysed.
Hepatobiliary malignancy was found in 52/255 (20%) patients accepted to the waiting list. Recent diagnosis of PSC, no ursodeoxycholic acid (UDCA) treatment, clinical suspicion and previous colorectal-cancer were predictors of malignancy. Among 89 patients with a strong suspicion of malignancy prior to acceptance, 35 (39%) had confirmed malignancy. A clinical suspicion had been raised in 35/52 (67%) patients with malignancy. Malignancy was found in 31/223 patients who received a liver allograft. The 1-, 3- and 5-year patient survival rates following transplantation for patients with PSC and cholangiocarcinoma were 65, 35 and 35%, respectively.
Hepatobiliary malignancy is suspected in 1/3 of the PSC patients and found in 1/5. Although cholangiocarcinoma is regarded as a contraindication to liver transplantation (LTX), PSC patients with cholangiocarcinoma had a 35% 5-year survival following transplantation.
OBJECTIVE:To validate new mitochondrial myopathy serum biomarkers for diagnostic use.
METHODS:We analyzed serum FGF21 (S-FGF21) and GDF15 from patients with (1) mitochondrial diseases and (2) ...nonmitochondrial disorders partially overlapping with mitochondrial disorder phenotypes. We (3) did a meta-analysis of S-FGF21 in mitochondrial disease and (4) analyzed S-Fgf21 and skeletal muscle Fgf21 expression in 6 mouse models with different muscle-manifesting mitochondrial dysfunctions.
RESULTS:We report that S-FGF21 consistently increases in primary mitochondrial myopathy, especially in patients with mitochondrial translation defects or mitochondrial DNA (mtDNA) deletions (675 and 347 pg/mL, respectively; controls66 pg/mL, p < 0.0001 for both). This is corroborated in mice (mtDNA deletions 1,163 vs 379 pg/mL, p < 0.0001). However, patients and mice with structural respiratory chain subunit or assembly factor defects showed low induction (human 335 pg/mL, p < 0.05; mice 335 pg/mL, not significant). Overall specificities of FGF21 and GDF15 to find patients with mitochondrial myopathy were 89.3% vs 86.4%, and sensitivities 67.3% and 76.0%, respectively. However, GDF15 was increased also in a wide range of nonmitochondrial conditions.
CONCLUSIONS:S-FGF21 is a specific biomarker for muscle-manifesting defects of mitochondrial translation, including mitochondrial transfer-RNA mutations and primary and secondary mtDNA deletions, the most common causes of mitochondrial disease. However, normal S-FGF21 does not exclude structural respiratory chain complex or assembly factor defects, important to acknowledge in diagnostics.
CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that elevated S-FGF21 accurately distinguishes patients with mitochondrial myopathies from patients with other conditions, and FGF21 and GDF15 mitochondrial myopathy from other myopathies.
Summary
Serum cholesterol reflects poorly cholesterol metabolism. From serum noncholesterol sterols cholestanol, campesterol, and sitosterol are surrogate markers of cholesterol absorption, but ...reflect also cholestasis, while those of lathosterol reflect cholesterol synthesis and hepatic parenchymal function. We investigated these sterols at end‐stage of primary biliary cirrhosis (PBC) – prior to liver transplantation and shortly after transplantation in 67 patients to show their role as index of cholestasis and parenchymal liver function. Median preoperative values of cholestanol were increased 7.6 times, those of plant sterols 1.6–3.7 times above and the campesterol/sitosterol ratio was decreased twice below our control values, respective lathosterol levels being mainly subnormal. After transplantation, the proportions to cholesterol of the absorption markers decreased, and those of synthesis markers and the ratios of campesterol/sitosterol increased significantly. Thus, surrogate sterol markers of cholesterol absorption and synthesis in serum are also good clinical markers of chronic cholestasis and degree of hepatic parenchymal cell function in PBC. Postoperative improvement of serum sterol profile indicate clinically good function of the liver graft.
Laparoscopic cholecystectomy is associated with a higher rate of bile duct injuries than an open cholecystectomy. The annual incidence of bile duct injuries has remained almost constant and these ...injuries tend to be more serious, making demands on the method of repair. We wanted to report the management and outcome of major bile duct injuries after laparoscopic cholecystectomy in patients referred to a hepatobiliary and liver transplantation unit. Eighteen patients (14 women), with a median age of 53.5 years were referred to the liver surgery unit with a major bile duct injury after laparoscopic cholecystectomy. The injury was identified after a median of 3 days (range, 0 to 25 days) after operation and the median time interval to referral was 79 days (0 to 2270 days). Fourteen patients had undergone surgery before referral. By the time of referral, four patients had developed end-stage cirrhosis, necessitating liver transplantation. Three of them had undergone bilioenteric drainage operations at the referring institute. Of the remaining 14 patients, three were managed by therapeutic endoscopic procedures. Ten patients were managed with Roux-en-Y hepaticojejunostomy. One died of septic complications before the repair. A median time for hospitalization in our unit was 33 days (range, 10 to 164 days). At present, 16 patients are alive. One patient died of Kaposi's sarcoma 7 months after liver transplantation. A long interval between bile duct injury and referral was associated with the development of end-stage liver disease. Surgery of biliary lesions is demanding, and surgical experience with multidisciplinary approach, including therapeutic endoscopy and liver transplantation, is necessary for successful outcome. (Liver Transpl 2002;8:1036-1043.)
Mutations in PRKCSH, encoding the β-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum (ER), cause autosomal dominant polycystic liver disease. We found that ...mutations in SEC63, encoding a component of the protein translocation machinery in the ER, also cause this disease. These findings are suggestive of a role for cotranslational protein-processing pathways in maintaining epithelial luminal structure and implicate noncilial ER proteins in human polycystic disease.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
AbstractAim and background. The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to ...short waiting times, donor liver allocation has been made without considerations of the model of end-stage liver disease (MELD) score. We aimed to summarize key outcome measures and developments for the activity up to December 2013. Materials and methods. The registry is integrated with the operational waiting-list and liver allocation system of Scandiatransplant (www.scandiatransplant.org) and accounted at the end of 2013 for 6019 patients out of whom 5198 were transplanted. Data for recipient and donor characteristics and relevant end-points retransplantation and death are manually curated on an annual basis to allow for statistical analysis and the annual report. Results. Primary sclerosing cholangitis, acute hepatic failure, alcoholic liver disease, primary biliary cirrhosis and hepatocellular carcinoma are the five most frequent diagnoses (accounting for 15.3%, 10.8%, 10.6%, 9.3% and 9.0% of all transplants, respectively). Median waiting time for non-urgent liver transplantation during the last 10-year period was 39 days. Outcome has improved over time, and for patients transplanted during 2004-2013, overall one-, five- and 10-year survival rates were 91%, 80% and 71%, respectively. In an intention-to-treat analysis, corresponding numbers during the same time period were 87%, 75% and 66%, respectively. Conclusion. The liver transplant program in the Nordic countries provides comparable outcomes to programs with a MELD-based donor liver allocation system. Unique features comprise the diagnostic spectrum, waiting times and the availability of an integrated waiting list and transplant registry (NLTR).
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