Liver[JOURNAL]
Sun
200 papers
Immunohistochemical evidence for hepatic progenitor cells in liver diseases.
Tan J, Hytiroglou P, Wieczorek R … +4 more , Park YN, Thung SN, Arias B, Theise ND
Liver · 2002 Oct · PMID 12390471 · Publisher ↗
BACKGROUND/AIM: Proliferative bile ductular reactions occur in a variety of liver diseases in humans. It is a matter of debate whether such reactions result from progenitor cell proliferation with biliary and hepatocytic...
BACKGROUND/AIM: Proliferative bile ductular reactions occur in a variety of liver diseases in humans. It is a matter of debate whether such reactions result from progenitor cell proliferation with biliary and hepatocytic differentiation, versus biliary metaplasia of damaged hepatocytes. We investigated bile ductular reactions in liver diseases, paying particular attention to the presence of cells with intermediate (hepatocytic/biliary) features (oval-like cells). METHODS: Five specimens each were selected of submassive hepatic necrosis and cirrhosis due to hepatitis B, hepatitis C, autoimmune hepatitis, alcohol injury, primary biliary cirrhosis and primary sclerosing cholangitis. Immunohistochemical stains were performed for biliary markers (cytokeratins [CKs] 7 and 19), as well as hepatocytic markers (HepParl and alpha-fetoprotein[AFP]) in sequential sections. The degree of staining of each cell type (biliary, hepatocytic, intermediate) was graded semiquantitatively. RESULTS: Hepatocytes always stained diffusely for HepParl, occasionally for CK7, and rarely for CK19. Biliary cells were always diffusely positive for CK7 and CK19, and rarely for HepParl. Intermediate cells were identified in all cases and showed widespread staining for both HepParl and CK7, and less commonly for CK19. AFP was not expressed in any cell type. The morphologic and immunohistochemical features of bile ductular reactions were similar in the different diseases. CONCLUSIONS: Proliferating hepatic parenchymal cells with intermediate (hepatocytic/biliary) morphologic features and combined immunophenotype can be identified in a variety of acute and chronic liver diseases. The similarity of bile ductular reactions among chronic hepatitic, alcoholic and biliary diseases suggests that they result from proliferation of oval-like progenitor cells.
Oval cell hyperplasia in asparaginase--induced liver damage.
Zuckerman E, Misselevich I, Boss JH
Liver · 2002 Aug · PMID 12296971 · Publisher ↗
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Inhibition of glucose production and stimulation of bile flow by R (+)-alpha-lipoic acid enantiomer in rat liver.
Anderwald C, Koca G, Fürnsinn C … +2 more , Waldhäusl W, Roden M
Liver · 2002 Aug · PMID 12296970 · Publisher ↗
AIMS/BACKGROUND: R (+)-alpha-lipoic acid (RLA) has been suggested for the treatment of liver diseases, but has also been shown to improve glucose utilization in diabetic patients. Because detailed information of RLA acti...
AIMS/BACKGROUND: R (+)-alpha-lipoic acid (RLA) has been suggested for the treatment of liver diseases, but has also been shown to improve glucose utilization in diabetic patients. Because detailed information of RLA action on carbohydrate metabolism in intact liver is lacking, we examined concentration-dependent effects of RLA on hepatic glucose production. METHODS: RLA (10(-6-)10(-3) mol L(-1)) or buffer (control) was infused in isolated livers of fasted rats during recirculating perfusion for 90 min (n = 4-6/group). Hepatic glucose and lactate fluxes and bile secretion were continuously monitored. RESULTS: RLA reduced lactate (10 mmol L(-1))-dependent glucose production in concentration-dependent fashion (R = - 0.780, P < 0.001) by up to 67% compared with control (0.36 +/- 0.02 micromol min(-1) g(-1)). In parallel, RLA dose dependently decreased lactate uptake (R = - 0.592, P < 0.001) also by up to 67% (control: 0.58 +/- 0.08 micromol min(-1) g(-1)). RLA (10(-4) mol L(-1) and 10(-3) mol L(-1)) stimulated bile flow by approximately 20 and approximately 50%, respectively (P < 0.02 vs. control). After 10(-3) mol L(-1) RLA infusion, liver glycogen was approximately 3 fold higher (5.2 +/- 1.1 vs. control: 1.8 +/- 0.2 micromol g(-1), P < 0.002). Also at low lactate concentrations (1 mmol L(-1)), 10(-3) mol L(-1) RLA reduced glucose production by approximately 53% and lactate uptake by approximately 60%, but stimulated bile secretion by approximately 50% (P < 0.05). CONCLUSION: RLA reduces hepatic glucose release by inhibiting lactate-dependent glucose production in a concentration-dependent fashion.
Effect of TT virus co-infection on interferon response in chronic hepatitis C patients.
Kawanaka M, Niiyama G, Mahmood S … +6 more , Ifukube S, Yoshida N, Onishi H, Hanano S, Ito T, Yamada G
Liver · 2002 Aug · PMID 12296969 · Publisher ↗
AIM: TT virus (TTV) is a single stranded DNA virus found in serum of patients with post-transfusion non-A to -G hepatitis. TTV-DNA has been investigated in sera of patients with various liver diseases. This study aimed a...
AIM: TT virus (TTV) is a single stranded DNA virus found in serum of patients with post-transfusion non-A to -G hepatitis. TTV-DNA has been investigated in sera of patients with various liver diseases. This study aimed at finding whether co-infection with TTV in HCV patients, may influence the effect of interferon (IFN) in complete elimination of HCV, and analysed the correlation between HCV and TTV by semi-quantification of both HCV RNAs and TTV DNA. METHODS: In 28 chronic hepatitis C (CH-C) patients with TTV co-infection, the presence of TTV DNA was checked in sera six months before and after the end of IFN therapy. RESULT: Five out of 28 patients became negative for both HCV-RNA and TTV-DNA following IFN therapy. But 10 out of 28 patients persistently remained positive for both. Among the remaining 13 patients, 5 tested negative for HCV-RNA but positive for TTV-DNA. Post IFN therapy changes in serum alanine aminotransferase (ALT) levels did not appear to be influenced by the presence of TTV co-infection. HCV-RNA was found to be the most important predictor of IFN response in CH-C patients with TTV co-infection. TTV DNA level in sera had no correlation with IFN response. In addition, there was no relationship between HCV RNA and TTV DNA. CONCLUSION: Based on these results, it can be concluded that the effectiveness of IFN in eliminating HCV does not seem to be influenced by co-infection.
Long-chain fatty acid uptake and oxidation in the perfused liver of Walker-256 tumour-bearing rats.
Vicentino C, Constantin J, Bracht A … +1 more , Yamamoto NS
Liver · 2002 Aug · PMID 12296968 · Publisher ↗
AIMS/BACKGROUND: The effect of the Walker-256 tumour on uptake and oxidation of long-chain fatty acids was investigated in perfused livers of rats. METHODS: Isolated livers were perfused in a non-recirculating system. Fa...
AIMS/BACKGROUND: The effect of the Walker-256 tumour on uptake and oxidation of long-chain fatty acids was investigated in perfused livers of rats. METHODS: Isolated livers were perfused in a non-recirculating system. Fatty acid uptake, ketogenesis, oxygen uptake and 14CO2-production were measured as well as the activities of the acyl carnitine transferases I and II (CAT I and CAT II). RESULTS: Basal oxygen uptake of livers from tumour-bearing rats was lower. Ketone bodies production derived from the long-chain fatty acids in livers from starved tumour-bearing rats was lower relative to the controls, but 14CO2 production was similar in both groups. The oxygen uptake increment and the mitochondrial NADH/NAD+ redox ratio were also decreased in tumour-bearing rats. The extent of these differences was dependent on the chain length and structure of the fatty acid, the following decreasing sequence of differences between control and tumour-bearing animals being valid: palmitate > oleate > stearate. The CAT I activity of the enzyme isolated from livers of tumour-bearing rats was half that from normal rats when palmitoyl-CoA and oleoyl-CoA were the substrates. CONCLUSIONS: Ketogenesis from exogenous fatty acids is decreased in the livers of Walker-256 tumour-bearing rats in consequence of the diminished activity of the mitochondrial CAT I. The lower rates of oxygen uptake indicate a decreased ATP synthesis, which is consistent with the in vivo lower phosphorylation potential.
In vivo quantification of ageing changes in the rat liver from early juvenile to senescent life.
Vollmar B, Pradarutti S, Richter S … +1 more , Menger MD
Liver · 2002 Aug · PMID 12296967 · Publisher ↗
AIMS/METHOD: Using high resolution multifluorescence in vivo microscopy, the present study was undertaken to determine the changes in rat hepatic tissue architecture and microvasculature during the growth associated with...
AIMS/METHOD: Using high resolution multifluorescence in vivo microscopy, the present study was undertaken to determine the changes in rat hepatic tissue architecture and microvasculature during the growth associated with juvenile maturation and adult senescence, i.e. the age of 1, 3, 12 and 24 months. RESULTS: By 1 month of age the liver attained its full size and functional capacity, as assessed by relative organ weight and hepatic bile flow. Survey of liver architecture revealed a progressive growth of lobular area with postsinusoidal venules exhibiting a proportional increase in length, diameter and inter-vascular distance up to the age of 12-24 months. In regard to the 3.5-4-fold average increase of lobular units, a minor reduction of sinusoidal density to 87% over life strongly implies the recruitment or formation of new sinusoidal microvessels as contributing mechanism to meet oxygen demand due to overall tissue enlargement. The sinusoidal perfusion rate remained above 98% over the whole lifespan. Leukocytic interaction with the hepatic microvascular endothelium was found within the physiological range in all age groups. Moreover, kinetics of clearance of latex beads as well as lobular distribution of Kupffer cells did not differ between animals of different age. Hepatic stellate cell-associated area of ultraviolet vitamin A-autofluorescence increased with age and significantly correlated with increasing tissue concentrations of vitamin A metabolites. Biochemical parameters serving as measures of tissue integrity did not indicate age-associated tissue alterations. CONCLUSION: These age-associated physiological changes should be carefully taken into account as a relevant variable in experimental research.
Mechanism of superoxide anion production by hepatic sinusoidal endothelial cells and Kupffer cells during short-term ethanol perfusion in the rat.
Hasegawa T, Kikuyama M, Sakurai K … +5 more , Kambayashi Y, Adachi M, Saniabadi AR, Kuwano H, Nakano M
Liver · 2002 Aug · PMID 12296966 · Publisher ↗
BACKGROUND/AIMS: The aim of this study was to clarify the candidate cells for and the mechanism of superoxide anion (O2*-) release into the hepatic sinusoids during short-term exposure to ethanol. METHODS: The rat liver...
BACKGROUND/AIMS: The aim of this study was to clarify the candidate cells for and the mechanism of superoxide anion (O2*-) release into the hepatic sinusoids during short-term exposure to ethanol. METHODS: The rat liver was perfused continuously with ethanol (a substrate for alcohol dehydrogenase) or tert-buthanol (not a substrate for alcohol dehydrogenase) for 20 min at a final concentration of 40 mM. In order to detect O2*- production, MCLA (2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo[1,2-a]pyrazin-3-one), a Cypridina luciferin analogue, was simultaneously infused and MCLA-enhanced chemiluminescence was measured. The effects of gadolinium chloride (GdCL3) (a suppressor of Kupffer cells (KCs)), staurosporine (ST) (an inhibitor of serine-threonine kinases, including protein kinase C), diphenyleneiodonium chloride (DPI) (an inhibitor of NADPH oxidase), ibuprofen (IB) (an inhibitor of cyclooxygenase) and 4-methylpyrazole (4MP) (an inhibitor of ethanol metabolism) on the ethanol-induced chemiluminescence were also evaluated. Sites where O2*- could be released were determined by histochemical detection of nitro blue tetrazolium reduction. RESULTS: Both ethanol and tert-buthanol rapidly caused O2*- release. GdCL3 suppressed the ethanol-induced O2*- release by 61%. Staurosporine and DPI, but neither IB nor 4-MP, also significantly inhibited the ethanol-induced O2*- release. In the histochemical examination, ethanol-stimulated liver showed blue formazan precipitate on both sinusoidal endothelial cells (SECs) and Kupffer cells (KCs), whereas the GdCl3-pretreated liver had the precipitate only on SECs. CONCLUSIONS: This study shows that ethanol itself stimulates both SECs and KCs to release O2*- via activation of NADPH oxidase probably involving protein kinase C (PKC).
Improvement in cholestasis associated with total parenteral nutrition after treatment with an antibody against tumour necrosis factor alpha.
Forrest EH, Oien KA, Dickson S … +2 more , Galloway D, Mills PR
Liver · 2002 Aug · PMID 12296965 · Publisher ↗
BACKGROUND: Many patients receiving long-term total parenteral nutrition (TPN) develop liver disease; cholestasis is common and may be severe. Antitumour necrosis factor alpha (TNFalpha) antibodies have recently been use...
BACKGROUND: Many patients receiving long-term total parenteral nutrition (TPN) develop liver disease; cholestasis is common and may be severe. Antitumour necrosis factor alpha (TNFalpha) antibodies have recently been used in order to treat Crohn's disease, but their effect on cholestasis in humans has not been previously described. CASE REPORT: A 45-year-old woman had complicated Crohn's disease with multiple fistulae and only 1 m of residual small bowel. She had been receiving TPN for 2.5 years when she developed cholestasis which worsened despite adjustments to her TPN regimen. Infliximab, an anti-TNFalpha antibody, was given with the aim of treating an enterocutaneous fistula, but it also produced a marked biochemical and histological improvement in the TPN-related cholestasis. CONCLUSIONS: Anti-TNFalpha antibodies appeared in this case to improve TPN-related cholestasis. This implies that TNFalpha may play an important role in the development of this condition.
Pyruvate dehydrogenase specific T cells in primary biliary cirrhosis show restricted antigen recognition sites.
Pingel S, Arenz M, Meyer zum Büschenfelde KH … +1 more , Löhr HF
Liver · 2002 Aug · PMID 12296964 · Publisher ↗
BACKGROUND/AIMS: The aim was to characterise the antigen recognition sites of the variable T cell receptor alpha-chain (TCRAV) and beta-chain (TCRBV) of T cells specific to the pyruvate dehydrogenase (PDC) in primary bil...
BACKGROUND/AIMS: The aim was to characterise the antigen recognition sites of the variable T cell receptor alpha-chain (TCRAV) and beta-chain (TCRBV) of T cells specific to the pyruvate dehydrogenase (PDC) in primary biliary cirrhosis. METHODS: In 21 PDC-specific T cell clones isolated from five patients we analysed TCRAV and TCRBV usage by RT-PCR and sequenced the CDR3 regions. RESULTS: Preferential expression of the TCR elements BV6 (6 clones), BV12 (4 clones) and BV1 (3 clones), and frequent usage of the joining elements JB2.3 and JB2.1 were seen. Analysis of the alpha chain revealed rearrangement of AV2 in 7 clones (35%) and AV7 in 3 clones, however, distribution of the joining elements was heterogenous and no common sequence motifs were detected. Evaluation of the physicochemical properties of the beta-chain demonstrated a positive charge at position P4 in several clones of two patients and a hydrophobic residue at position P5 in two different patients. Further, a conserved glycine at position P7 and neutral residues at positions P6 and P8 were frequently detected. CONCLUSIONS: Our data define TCR variable region restriction and preferred CDR3 features of PDC-specific T cells and support the notion that few relevant epitopes on the PDC complex are recognised by selected T cells.
Reduction of monocrotaline-induced hepatic injury by deleted variant of hepatocyte growth factor (dHGF) in rats.
Yamashita Y, Fujise N, Imai E … +1 more , Masunaga H
Liver · 2002 Aug · PMID 12296963 · Publisher ↗
BACKGROUND: Monocrotaline is a hepatotoxic agent which exerts predominant toxicity to central veins and centrilobular sinusoids. In this study, we investigated the effects of deleted variant of hepatocyte growth factor (...
BACKGROUND: Monocrotaline is a hepatotoxic agent which exerts predominant toxicity to central veins and centrilobular sinusoids. In this study, we investigated the effects of deleted variant of hepatocyte growth factor (dHGF) on monocrotaline-induced hepatic injury in rats. METHODS: 100 mg/kg monocrotaline was gavaged to male rats twice with a 4-days' interval. Treatment of dHGF was started 4 days before the initial administration of monocrotaline and 500 microg/kg was intravenously injected twice daily for 11 days. RESULTS: Monocrotaline induced severe damage of central veins and destruction of central zone of hepatic lobules concurrent with derangement of blood levels of total protein, albumin, alanine-aminotransferase, total bilirubin, direct bilirubin, and hepaplastin time. dHGF reduced the structural and blood-chemical abnormalities induced by monocrotaline. CONCLUSIONS: These results suggest that dHGF prevented and repaired the monocrotaline-induced hepatic injury, and could have therapeutic potency in hepatic failure with sever centrilobular destruction.
Liver pathology in compound heterozygous patients for hemochromatosis mutations.
Schöniger-Hekele M, Müller C, Polli C … +3 more , Wrba F, Penner E, Ferenci P
Liver · 2002 Aug · PMID 12296962 · Publisher ↗
BACKGROUND: While hepatic pathology of homozygous carriers of the C282Y mutation of the HFE haemochromatosis gene is well defined, the impact of the C282Y/H63D compound heterozygous carrier state is unknown. AIMS: To eva...
BACKGROUND: While hepatic pathology of homozygous carriers of the C282Y mutation of the HFE haemochromatosis gene is well defined, the impact of the C282Y/H63D compound heterozygous carrier state is unknown. AIMS: To evaluate the range of hepatic pathology in C282Y/H63D compound heterozygous patients. PATIENTS: 25 C282Y/H63D compound heterozygous patients with and without known underlying liver disease underwent liver biopsies for evaluation or abnormal liver tests. Eleven cadaveric liver donors with HFE wild type served as controls. METHODS: Mutations in the HFE gene were detected by polyacrylamide gel electrophoresis (PAGE) separation of digested polymerase chain reaction (PCR)-amplificates. The extent of light microscopic changes of liver architecture were studied on haematoxylin, eosin (H. E.) stains. In addition, the extent and the distribution of iron deposition was graded on Prussian blue-stained sections and hepatic iron was quantified by atom absorption spectroscopy. Serum ferritin concentration and the transferrin saturation index were measured using routine laboratory methods. RESULTS: Patients without underlying liver disease (n = 15): Hepatic inflammation was seen in only 8% but fibrosis was found in 36% of compound heterozygous patients. Eighty six percent of those patients had stainable iron predominantly found in Rappaport's zone 1 and 2, but all had a liver iron-index < 1.9. Transferrin saturation was found elevated in 36% of compound heterozygous patients. Patients with liver fibrosis showed significantly higher ferritin levels than patients without liver fibrosis (1110 ng/mL versus 307 ng/mL, p < 0.05). Patients with underlying disease (n = 10): In compound heterozygous patients, 77% had hepatic inflammation and 88% fibrosis. Stainable iron (44%) was less frequently found than in patients without underlying liver disease. Hepatic iron-index in patients with underlying liver disease was always below 1.17; transferrin saturation was elevated in only 22% of the compound heterozygous patients. Histologic hepatic iron-index was significantly lower in patients with underlying disease (median 0.047) as compared to patients without underlying liver disease (median 0.274, P < 0.05). CONCLUSIONS: The underlying liver disease determines the extent of hepatic pathology seen in livers of compound heterozygous patients. However, considerable histologic fibrosis can also be found in compound heterozygous patients without underlying liver disease.
Mesenchymal cells in the liver--one cell type or two?
Ramadori G, Saile B
Liver · 2002 Aug · PMID 12296961 · Publisher ↗
The wall of the liver sinusoid is made of highly specialized cells, the hepatic stellate cells (HSC) which together with the sinusoidal endothelial cells represent a loose barrier to the corpusculate part of the blood fl...
The wall of the liver sinusoid is made of highly specialized cells, the hepatic stellate cells (HSC) which together with the sinusoidal endothelial cells represent a loose barrier to the corpusculate part of the blood flowing through the liver. Quiescent stellate cells (quiescent HSC) store Vitamin A; "activated" stellate cells become involved in the reaction to acute or chronic noxae damaging the liver parenchyma. Activated HSC show increased protein synthesis capacity, increased DNA-synthesis and acquire a myofibroblast-like phenotype. Under similar conditions liver myofibroblasts (MF) of the portal field and of the pericentral area may also become "activated" by increasing protein synthesis, DNA synthesis and cell division. They express the fibulin-2 gene and produce large amounts of IL-6. In contrast to "activated" HSC they do not undergo spontaneous apoptosis in vitro and do not express the CD95-ligand gene. So far no definite prove has been found for a "transdifferentiation" of HSC to myofibroblasts. On the contrary an increasing amount of data support the conviction that HSC and MF represent two similar but not identical cell populations the latter being comparable to those of other organs.
MARS: optimistic therapy method in fulminant hepatic failure secondary to cytotoxic mushroom poisoning--a case report.
Shi Y, He J, Chen S … +4 more , Zhang L, Yang X, Wang Z, Wang M
Liver · 2002 · PMID 12220312 · Publisher ↗
Poisoning by cytotoxic mushrooms (Amanita phalloides and related species) is associated with severe morbidity and a high mortality rate (lethality > 20% in adults and > 50% in children). The main causes of this intoxicat...
Poisoning by cytotoxic mushrooms (Amanita phalloides and related species) is associated with severe morbidity and a high mortality rate (lethality > 20% in adults and > 50% in children). The main causes of this intoxication are the amatoxines, which inhibit DNA-dependent RNA Polymerase II or B. This interaction leads to a tight complex, and the inhibition is of a non-competitive type (1); in addition to those tight binding inhibitors of adenosine kinase, papain, cathepsin L, cathepsin B, cysteine proteinase and bromelain (2), inhibit the synthesis of messenger RNA in the hepatocytes, decrease the formation of coagulation factors and of immunoglobulins and effect a vasoconstriction. They also have an influence on the transcription and lesions that are seen in cells with rapid protein synthesis, particularly in liver and renal cells, with the cellular changes causing the fragmentation and segregation of all nuclear components, even at low toxin concentrations (3). Phallotoxin, which is the other toxin isolated from death cap, binds with a high affinity to microfilamentous structures - in particular, to F-actin, which stimulates the polymerization of G-actin, stabilizes the F-actin filaments, irreversibly polymerizes actin filaments and causes cholestasis (4). Liver is recognized as the target organ for Amanita phalloides toxins; it is presented by fatty degeneration, acute toxic dystrophy and centrilobular necroses (5). Therapeutic options employed to treat mushroom intoxication, such as hemodiaperfusion on activated charcoal, high dosages of penicillin G, oral charcoal, etc., very often failed to act properly and liver transplantation (when a graft is available) appeared to be the only solution. The most polarized debate concerns the value of extracorporeal elimination. Plasmapheresis and peritoneal dialysis proved much less useful for this purpose; neither haemodialysis (HD) nor haemoperfusion (HP) contributed to the clearance of amatoxin (6, 7). Recently, Stange et al. (8). introduced a new detoxication method (referred to as MARS) for protein-bound substances in patients with liver failure and grade III and IV hepatic encephalopathy. MARS was performed with an albumin-containing dialysate, which is recycled in a closed loop that contains a charcoal cartridge, an anion exchanger resin adsorber and a conventional haemodialyser. With dialysis using an albumin-containing dialysate, protein-bound substances, which are usually not sufficiently dialysable, can be eliminated. The treatments increase the rate of toxin elimination to the extent that the toxic exposure of highly susceptible cells, such as hepatocytes, is minimized. This leads to the surprise recovery of the poisoning patient, despite her severe condition, even as late as up to a week after mushroom ingestion.
MARS procedure as a bridge to combined liver-kidney transplantation in severe chromium-copper acute intoxication: a paediatric case report.
Prokurat S, Grenda R, Lipowski D … +2 more , Kaliciński P, Migdal M
Liver · 2002 · PMID 12220311 · Publisher ↗
We describe a case of multi-organ failure (liver-kidney insufficiency and brain oedema) caused by accidental, acute intoxication with a chromium and copper-containing substance, as an example of the introduction of the n...
We describe a case of multi-organ failure (liver-kidney insufficiency and brain oedema) caused by accidental, acute intoxication with a chromium and copper-containing substance, as an example of the introduction of the new extracorporeal procedure MARS (molecular adsorbents recirculating system) in a girl 3.5 years old.
Extracorporal albumin dialysis (MARS) improves cholestasis and normalizes low apo A-I levels in a patient with benign recurrent intrahepatic cholestasis (BRIC).
Sturm E, Franssen CF, Gouw A … +6 more , Staels B, Boverhof R, De Knegt RJ, Stellaard F, Bijleveld CM, Kuipers F
Liver · 2002 · PMID 12220310 · Publisher ↗
The familial cholestatic diseases Benign Recurrent Intrahepatic Cholestasis (BRIC) and Progessive Familial Intrahepatic Cholestasis type 1 (PFIC1) are characterized by intermittent or permanently elevated plasma bile sal...
The familial cholestatic diseases Benign Recurrent Intrahepatic Cholestasis (BRIC) and Progessive Familial Intrahepatic Cholestasis type 1 (PFIC1) are characterized by intermittent or permanently elevated plasma bile salt levels, therapy-resistant extreme pruritus and peculiar biochemical abnormalities including low apolipoprotein apo A-I. Previously, symptomatic improvement has been demonstrated in BRIC patients after extracorporal albumin dialysis (MARS). We hypothesized that MARS improves cholestasis, induces changes in the bile salt profile and normalizes apo A-I serum levels in BRIC. A 17-year-old-female patient with BRIC experienced an episode of cholestasis lasting for more than 6 months with extreme pruritus and diarrhoea not responding to standard therapy. During a period of five days the patient was treated 3 x 8 h with MARS. The procedures were well tolerated and resulted in reduction of plasma bile salts by 58%. The plasma bile salt profile changed into a more hydrophilic composition after MARS. Diarrhoea discontinued and the pruritus improved significantly from 9 to 4 on a subjective scale. These effects lasted 4 months until a relapse occurred. Low plasma apo A-I levels (0.52 g/l) normalized after MARS (0.98 g/l). The procedures were well tolerated. Fatigue was noted as the only transient side-effect. In conclusion, MARS may induce a long-term symptomatic improvement and decrease of cholestatic markers in BRIC. Further studies evaluating efficacy and mechanism of MARS in patients with BRIC are needed.
Modular extracorporeal life support for multiorgan failure patients.
Peek GJ, Killer HM, Sosnowski MA … +1 more , Firmin RK
Liver · 2002 · PMID 12220309 · Publisher ↗
Adults receiving respiratory Extracorporeal Membrane Oxygenation (ECMO) have 66% survival. Nonsurvivors develop multisystem organ failure (MSOF). Once hepatic failure develops, death usually follows shortly. Serum biliru...
Adults receiving respiratory Extracorporeal Membrane Oxygenation (ECMO) have 66% survival. Nonsurvivors develop multisystem organ failure (MSOF). Once hepatic failure develops, death usually follows shortly. Serum bilirubin > 300 micromol/l predicted death with 87.8% sensitivity and 90.3% specificity in 41 adults who received ECMO in our institution during 1998 and 1999. No patients survive with a peak bilirubin > 400 micromol/l. The Molecular Adsorbent Recirculating System (MARS) is a cell-free extracorporeal liver support device; we hypothesized that using MARS in adult respiratory ECMO patients with a bilirubin >300 micromol/l could improve survival in MSOF. The MARS was used in five such patients aged 19-56 who developed liver failure secondary to a respiratory illness. Mean peak bilirubin was 529 micromol/l and the lowest peak bilirubin was 436 micromol/l. Patients received between 1 and 8 MARS treatments, mean reduction in serum bilirubin for each patient ranging between 30 and 162 micromol/l. Two of five patients survived (40%), survivors showing the greatest reduction in serum bilirubin in response to MARS. All patients would have been expected to die according to our previous experience. We believe that MARS may prove a useful therapy for patients with MSOF.
Emerging indications for MARS dialysis.
Schachschal G, Morgera S, Küpferling S … +3 more , Neumayer HH, Lochs H, Schmidt HH
Liver · 2002 · PMID 12220308 · Publisher ↗
MARS stands for Molecular Adsorbent Recirculating System and represents an interesting option in treating patients with liver disease. There is still little known about the best time point of initiating this treatment an...
MARS stands for Molecular Adsorbent Recirculating System and represents an interesting option in treating patients with liver disease. There is still little known about the best time point of initiating this treatment and the exact selection criteria for patients who may benefit from this therapy. The list of potential applications using this procedure is expanding. We report on the experience in seven patients being treated with MARS dialysis for chronic cholestatic liver disease and acute on chronic liver failure. From August 2000 to October 2001 seven patients received 27 MARS treatments in our clinic, ranging from 2 to 12 treatments per subject. Presented cases were diagnosed as steatohepatitis because of alcoholism (n = 3), vanishing bile duct disease (n = 1), metabolic liver disease (n = 1), primary biliary cirrhosis (n = 1) and drug-induced hepatitis (n = 1). Based on this experience, we discuss the ongoing questions of various indications and the decision to initiate MARS dialysis.
First clinical experience with Molecular Adsorbent Recirculating System (MARS) in six patients with severe acute on chronic liver failure.
Mullhaupt B, Kullak-Ublick GA, Ambühl P … +5 more , Maggiorini M, Stocker R, Kadry Z, Clavien PA, Renner EL
Liver · 2002 · PMID 12220307 · Publisher ↗
UNLABELLED: Despite recent advances in general supportive care, the mortality rate of patients with severe liver insufficiency remains high. Recently a new artificial liver support system MARS has been used for selective...
UNLABELLED: Despite recent advances in general supportive care, the mortality rate of patients with severe liver insufficiency remains high. Recently a new artificial liver support system MARS has been used for selective removal of albumin-bound toxins. AIM: To assess the safety and efficacy of MARS treatment in patients with acute on chronic liver disease (n = 5) or liver failure after extended hepatic resection (n = 1). DESIGN/PATIENTS: Six patients, aged 34-58 years, with severe liver insufficiency (mean MELD-score 31 (range 24-35)) were treated one to 16 times with the MARS system. At baseline three patients were intubated, three were encephalopathic (HE) and three had multifactorial kidney failure requiring kidney replacement therapy. RESULTS AND CONCLUSION: In all the patients MARS treatment significantly reduced the serum bilirubin levels. In three patients encephalopathy improved. In two patients the extracorporeal treatment precipitated a disseminated intravascular coagulation with clinically significant bleeding. Bridging to liver transplantation was possible in one patient, the other five patients died 30 days (2-74 days) after starting MARS therapy. Our case series shows that MARS treatment in general can be safely performed in patients with severe liver disease. However, in patients with an activated clotting system severe bleeding complication can be triggered and MARS treatment should be used very cautiously in these situations. MARS seems to be a promising new treatment option for patients with acute on chronic liver failure. However, carefully conducted randomized controlled trials are necessary to define its potential place in the treatment of patients with severe liver disease.
Application of Molecular Adsorbent Recirculating System in patients with severe liver failure after hepatic resection or transplantation: initial single-centre experiences.
Kellersmann R, Gassel HJ, Bühler C … +2 more , Thiede A, Timmermann W
Liver · 2002 · PMID 12220306 · Publisher ↗
Acute liver failure after hepatic surgery is still plaqued with high mortality rate. Recently, a liver dialysis system (MARS) that allows detoxification of albumin-bound substances and may hereby support liver regenerati...
Acute liver failure after hepatic surgery is still plaqued with high mortality rate. Recently, a liver dialysis system (MARS) that allows detoxification of albumin-bound substances and may hereby support liver regeneration and patient's recovery has been developed. In the present study, we report our experiences with MARS dialysis in patients with liver failure after hepatic resection or transplantation. Between September 1999 and January 2001, five patients were treated with MARS (2-5 courses). Though beneficial effects such as improvement of encephalopathy and renal function as well as reduced bilirubin levels were recorded during MARS therapy, only one patient survived. Neither significant technical problems nor adverse effects occurred by using MARS dialysis. We conclude that in surgical patients, acute liver failure is usually part of a complicated clinical course affecting multipleorgan systems. Thus, it is difficult to determine the specific influence of MARS on patient's outcome. However, beneficial effects observed in our patients justify its continuous use and may stimulate further evaluation in controlled studies with surgical patients.
The Molecular Adsorbent Recirculating System in patients with severe liver failure: clinical results at the K.U. Leuven.
Wilmer A, Nevens F, Evenepoel P … +2 more , Hermans G, Fevery J
Liver · 2002 · PMID 12220305 · Publisher ↗
BACKGROUND: The Molecular Adsorbent Recirculating System (MARS) is a novel extracorporeal technique for liver support. We report the clinical results in the first 13 patients with severe liver failure treated at our inst...
BACKGROUND: The Molecular Adsorbent Recirculating System (MARS) is a novel extracorporeal technique for liver support. We report the clinical results in the first 13 patients with severe liver failure treated at our institution. METHODS: Patients with acute or acute on chronic liver failure of various aetiologies were treated with varying numbers of MARS sessions of six hours duration. RESULTS: Mean APACHE II score was 18. In general, patients with multiple organ failure faired poorly even with MARS treatment. Five patients (38%) survived the hospitalisation. Eight patients (62%) fulfilled criteria for UNOS type I or 2 A status. Two of these patients survived. Five patients had a UNOS 2B status and three survived. In proportion, patients with severe itch, patients with primary non-function and those where MARS was used as a bridge to transplantation seemed to profit most from the treatment. The median reduction in bilirubin concentrations after the treatment period was -28.2%. In survivors, the median reduction was -37.7% and in patients who died was -15.9%. The median encephalopathy score improved from 1.7 to 0.5. CONCLUSION: The molecular adsorbent recycling system (MARS) might be lifesaving in patients with severe liver failure of different aetiologies.
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