Liver[JOURNAL]
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200 papers
Inclusion body myositis associated with hepatitis C virus infection.
Kase S, Shiota G, Fujii Y … +8 more , Okamoto K, Oyama K, Nakano T, Nomura T, Suou T, Nakashima K, Ito H, Kawasaki H
Liver · 2001 Oct · PMID 11589773 · Publisher ↗
The case of a 77-year-old woman with hepatitis C virus infection with a 5-year history of muscle weakness and mild disturbance of gait is reported. Steroid therapy did not improve her symptoms. She developed HCV-related...
The case of a 77-year-old woman with hepatitis C virus infection with a 5-year history of muscle weakness and mild disturbance of gait is reported. Steroid therapy did not improve her symptoms. She developed HCV-related liver cirrhosis and hepatocellular carcinoma, and muscle biopsy revealed inclusion body myositis. Immunohistochemistry showed that the nonstructural region of HCV and 8-hydroxy-2'-deoxyguanosine, a marker of DNA damage by reactive oxygen species, were present in striated muscle cells of this patient.
The insulin-like growth factor binding protein 3 ternary complex is reduced in cirrhosis.
Ottesen LH, Bendtsen F, Flyvbjerg A
Liver · 2001 Oct · PMID 11589772 · Publisher ↗
BACKGROUND/AIMS: In healthy adults, serum insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3) and acid labile subunit (ALS) form a 150-kDa ternary complex under the control of growth hormone (GH). Appro...
BACKGROUND/AIMS: In healthy adults, serum insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3) and acid labile subunit (ALS) form a 150-kDa ternary complex under the control of growth hormone (GH). Approximately 80-90% of circulating IGF-I is bound to the ternary complex. In cirrhosis the GH/IGF axis is severely disturbed and the individual components of the ternary complex are reduced. However, the degree of ternary complex formation in cirrhosis has not previously been described. METHODS: Serum IGF-I, IGFBP-3, ALS, the 150-kDa ternary complex and IGFBP-3 proteolysis were all measured in six compensated and six decompensated cirrhotic patients and compared to six healthy controls. RESULTS: Patients with compensated cirrhosis had decreased levels of IGF-I (55%), IGFBP-3 (64%) and ALS (53%), and in the decompensated patients these levels were decreased even further: IGF-I (32%), IGFBP-3 (37%) and ALS (27%) compared to healthy controls. The levels of the ternary complex followed this pattern, with low levels seen in the compensated patients (66%) and a further reduction in the decompensated patients (27%). Ternary complex levels correlated negatively with the Child-Pugh score. No increase in IGFBP-3 proteolysis was found in cirrhotic patients compared to healthy controls. CONCLUSION: Cirrhosis is associated with reduced levels of the 150-kDa ternary IGFBP-3 complex correlating with the degree of liver disease.
Estrogen receptor levels and lipid peroxidation in hepatocellular carcinoma with hepatitis C virus infection.
Shimizu I, Inoue H, Yano M … +7 more , Shinomiya H, Wada S, Tsuji Y, Tsutsui A, Okamura S, Shibata H, Ito S
Liver · 2001 Oct · PMID 11589771 · Publisher ↗
AIMS/BACKGROUND: Our preliminary studies showed that estradiol suppresses hepatic carcinogenesis and fibrogenesis in animal models. Hepatic estrogen receptors (ERs) medicate estradiol action in the liver. This study was...
AIMS/BACKGROUND: Our preliminary studies showed that estradiol suppresses hepatic carcinogenesis and fibrogenesis in animal models. Hepatic estrogen receptors (ERs) medicate estradiol action in the liver. This study was performed to assess possible implications of menopause and hepatic ER levels for the development of cirrhosis with hepatocellular carcinoma (HCC). METHODS: One thousand, one hundred and ninety-nine consecutive HCC patients with hepatitis C virus (HCV)-related cirrhosis were divided into two groups, based on a menopausal age of 49 years. Liver tissues were obtained during surgical resection of HCC and metastatic liver tumor. RESULTS: The proportion of females among the HCC subjects < or =49 years of age was significantly lower (15.0%) than was the proportion of females among subjects >49 years of age (29.8%). Univariate analysis showed that HCV-related cirrhotic patients who developed HCC were more likely to have low hepatic levels of ER and copper-zinc superoxide dismutase (CuZn-SOD) protein and a high hepatic level of a lipid peroxidation product, malondialdehyde (MDA). Logistic regression identified age greater than 49 years (odds ratio [OR]: 7.9, 95% confidence interval [CI]: 2.8-21.3), male sex (OR: 3.5, 95% CI: 1.3-10.2), a decreased ER level (OR: 16.8, 95% CI: 7.3-34.6), and an increased MDA (OR: 8.3, 95% CI: 2.8-24.0) as the variables independently associated with the development of HCC in HCV-infected patients with cirrhosis. ER level was significantly correlated with CuZn-SOD level (r=0.583) and was inversely proportional to MDA level (r=-0.553). The study also showed that ER levels in the cirrhotic livers from premenopausal females were significantly higher than in male cirrhotic livers. CONCLUSIONS: These findings suggest that increased lipid peroxidation and impaired SOD function in the liver may be associated with decreased hepatic ER levels in HCV-infected patients with cirrhosis and HCC, and that HCV-related cirrhotic women before menopause might have the ability to protect against developing HCC via hepatic ER.
HCV and cancer: a case-control study in a high-endemic area.
Montella M, Crispo A, de Bellis G … +7 more , Izzo F, Frigeri F, Ronga D, Spada O, Mettivier V, Tamburini M, Cuomo O
Liver · 2001 Oct · PMID 11589770 · Publisher ↗
BACKGROUND/AIMS: HCV is a RNA virus that cannot be integrated with the host genome; it can, however, exert its oncogenic potential indirectly by contributing to the modulatory effects of the host immune system, probably...
BACKGROUND/AIMS: HCV is a RNA virus that cannot be integrated with the host genome; it can, however, exert its oncogenic potential indirectly by contributing to the modulatory effects of the host immune system, probably through a capacity to elude the immune system. We have carried out a case-controlled study on the different oncological pathologies which have, to date, been shown to have a relationship with HCV. METHODS: We screened 495 patients with different types of cancer: 114 cases of liver cancer, 41 of multiple myeloma, 111 non-Hodgkin's lymphomas, 130 thyroid cancers, 63 cases of Hodgkin's disease. The controls were 226 patients with no history of cancer. The relationship between each cancer and HCV infection was assessed by means of odds ratios (OR) and corresponding 95% confidence intervals. RESULTS: Risks were greater for liver cancer (OR=32.9 95% CI 16.5-65.4, p<0.0001), multiple myeloma (OR=4.5 95% CI 1.9-10.7, p=0.0004) and B-cell non-Hodgkin's lymphoma (OR=3.7 95% CI 1.9-7.4, p=0.0001). For Hodgkin's disease there was no significant association (p=0.3). An association between HCV and thyroid cancer was noted (OR=2.8 95% CI 1.2-6.3, p=0.01). CONCLUSION: Our study is particularly important for public health since the high prevalence of HCV in the South of Italy gives reason to expect increases in not only liver cancer, but also tumors associated with the immune system and thyroid cancer in years to come.
Histological patterns of rejection using oral microemulsified cyclosporine and tacrolimus (FK506) as monotherapy induction after orthotopic liver transplantation.
Chau TN, Quaglia A, Rolles K … +2 more , Burroughs AK, Dhillon AP
Liver · 2001 Oct · PMID 11589769 · Publisher ↗
BACKGROUND/AIMS: We describe the histological patterns of rejection in liver transplant recipients using induction therapies with cyclosporine and tacrolimus monotherapy compared with standard triple therapy as historica...
BACKGROUND/AIMS: We describe the histological patterns of rejection in liver transplant recipients using induction therapies with cyclosporine and tacrolimus monotherapy compared with standard triple therapy as historical control. METHODS: Patients formed part of the initial cohort in an open-labelled, randomised pilot study and were selected consecutively if they had histological rejection and no other confounding diagnoses. There were 13 patients in the cyclosporine monotherapy group (CsA), 11 in the tacrolimus monotherapy group and 13 in the triple therapy group (CAP). The histology of liver biopsies was reassessed blindly and the severity of rejection was recorded. RESULTS: The total Royal Free Hospital (RFH) rejection scores as well as other histological features (zone 3 haemorrhage, apoptosis in zones 1 and 3, steatosis, cholestasis, nuclear vacuolation, lymphoblasts and ballooning) were comparable in the three groups. There was no difference in individual components of the histological features comprising the diagnosis of rejection, except that the portal inflammation score was significantly lower in the tacrolimus group when compared with the CsA group (p=0.04). There was no significant difference in the number of patients with moderate/severe rejection between the three groups. Overall, there was no significant increase in histological severity of rejection in the monotherapy groups. CONCLUSIONS: The results suggest that the monotherapy may be as effective as the triple therapy in the initial post-transplant phase and that no particular graft histological changes were associated with the type of treatment.
Characteristics of the hepatic stellate cell-selective carrier mannose 6-phosphate modified albumin (M6P(28)-HSA).
Beljaars L, Olinga P, Molema G … +5 more , de Bleser P, Geerts A, Groothuis GM, Meijer DK, Poelstra K
Liver · 2001 Oct · PMID 11589768 · Publisher ↗
BACKGROUND/AIMS: Drug targeting to hepatic stellate cells (HSC) may improve the pharmacological effects of antifibrotic drugs. Recently, albumin substituted with 28 mannose 6-phosphate moieties (M6P(28)-HSA) was found to...
BACKGROUND/AIMS: Drug targeting to hepatic stellate cells (HSC) may improve the pharmacological effects of antifibrotic drugs. Recently, albumin substituted with 28 mannose 6-phosphate moieties (M6P(28)-HSA) was found to distribute selectively to HSC in fibrotic rat livers. To assess whether this albumin can be used as a carrier for intracellular drug delivery, we explored the cellular handling of M6P(28)-HSA in HSC. METHODS/RESULTS: Application of competitive substrates for the M6P/IGFII receptor or other receptors showed that the binding of M6P-HSA to the M6P/IGFII receptor is specific. Binding was strong to activated HSC, but not to quiescent HSC. Furthermore, M6P(28)-HSA was extensively internalized by these cells. Using monensin, a specific inhibitor of the lysosomal pathway, proof was obtained that M6P-HSA is endocytosed via this route. The experiments performed with tissue slices, prepared from rat and human livers, revealed a specific binding and uptake of M6P(28)-HSA in both normal and cirrhotic livers. In livers from cirrhotic patients, HSC contributed predominantly to the uptake of this neoglycoprotein. CONCLUSIONS: Based on our in vivo data demonstrating the HSC-selectivity and on our in vitro data demonstrating binding and rapid internalization in activated HSC, we conclude that M6P(28)-HSA is applicable as a stellate cell-selective carrier for antifibrotic drugs that act intracellularly. This may have implications for the design of new strategies for the treatment of liver fibrosis.
Caspase activation during hepatocyte apoptosis induced by tumor necrosis factor-alpha in galactosamine-sensitized mice.
Osawa Y, Banno Y, Nagaki M … +3 more , Nozawa Y, Moriwaki H, Nakashima S
Liver · 2001 Oct · PMID 11589767 · Publisher ↗
BACKGROUND/AIMS: To clarify the mechanism of hepatocyte apoptosis induced by tumor necrosis factor-alpha (TNF-alpha), caspase cascade and ceramide formation were investigated in the liver of D-galactosamine (GalN)-sensit...
BACKGROUND/AIMS: To clarify the mechanism of hepatocyte apoptosis induced by tumor necrosis factor-alpha (TNF-alpha), caspase cascade and ceramide formation were investigated in the liver of D-galactosamine (GalN)-sensitized mice treated with TNF-alpha. METHODS: Seven-week-old male BALB/c mice were intraperitoneally injected with 20 mg GalN 30 min prior to the intravenous injection of recombinant mouse TNF-alpha (0.5 microg/mouse). Cytochrome c release and processing of procaspases in the liver were analyzed by Western blotting. Activities of caspases were measured using chromogenic peptides as substrates. Ceramide content was determined using Escherichia coli diacylglycerol kinase. RESULTS: Apoptosis of hepatocytes was observed in mice treated with both GalN and TNF-alpha (GalN/TNF-alpha), but not GalN or TNF-alpha alone. Activation of caspases-9 and -3, and cytochrome c release were observed only in liver from mice treated with GalN/TNF-alpha. In a cell-free system, processing of procaspases-9 and -3, and cytochrome c release were observed in the postnuclear fraction of liver obtained from GalN/TNF-alpha-treated mice, but not in that from control mice. Processing of procaspase-3 was inhibited by a caspase-9 inhibitor, but not by inhibitor for caspase-8 or -2. In a reconstitution assay system, procaspase-9 processing occurred, when both cytosol and membrane fractions were obtained from the liver of mice treated with GalN/TNF-alpha. Ceramide accumulation was observed only in apoptotic liver and preceded cytochrome c release and caspase activation. CONCLUSION: Cytochrome c release and caspase-9 activation are required for the activation of executor caspase-3 in TNF-alpha-induced hepatocyte apoptosis, but caspases-8 and -2 play, if any, a minimal role. Ceramide may be implicated in this apoptotic process.
Immunohistochemical and electron microscopic study of extrinsic hepatic reinnervation following orthotopic liver transplantation in rats.
Takahashi T, Kakita A, Sakamoto I … +4 more , Takahashi Y, Hayashi K, Tadokoro F, Yamashina S
Liver · 2001 Oct · PMID 11589766 · Publisher ↗
BACKGROUND/AIMS: Because little has been known about the morphological and functional consequences of liver transplantation on hepatic autonomic nerves, we examined the time-course of extrinsic hepatic innervation at the...
BACKGROUND/AIMS: Because little has been known about the morphological and functional consequences of liver transplantation on hepatic autonomic nerves, we examined the time-course of extrinsic hepatic innervation at the level of the porta hepatis of liver allografts. METHODS: Orthotopic liver transplantation was performed using male Lewis rats. Crosscut tissue specimens were obtained postoperatively for up to 6 months from the porta hepatis of transplanted livers, and processed for immunohistochemical staining for protein gene product 9.5 (PGP 9.5) and growth-associated protein 43 (GAP-43), and for transmission electron microscopy (TEM). RESULTS: Extrinsic nerve fibers at the porta hepatis stained positively for PGP 9.5 throughout the entire study period. In contrast, the immunoreactivity of GAP-43 was negative at postoperative day (POD) 1 and 2. GAP-43-positive nerves were first observed to appear in the porta hepatis at POD 3. The immunoreactivity of GAP-43 remained positive thereafter until 3 months post-OLT, and became negative in all the specimens at 4 months post-OLT. Transmission electron microscopy demonstrated a small number of regenerating axons existing among many degenerating axons at POD 3. At 3 months post-OLT, most regenerating axons had been fully ensheathed by the cytoplasm of Schwann cells, although their density remained at a lower level compared with normal. CONCLUSION: The results of this study suggest that liver allografts become extrinsically reinnervated, with the regenerating axons reaching the hepatic hilus 3 days after transplantation. The process of extrinsic hepatic reinnervation is considered to almost terminate 4 months after transplantation in rats.
Serum thioredoxin elucidates the significance of serum ferritin as a marker of oxidative stress in chronic liver diseases.
Sumida Y, Nakashima T, Yoh T … +7 more , Kakisaka Y, Nakajima Y, Ishikawa H, Mitsuyoshi H, Okanoue T, Nakamura H, Yodoi J
Liver · 2001 Oct · PMID 11589765 · Publisher ↗
BACKGROUND/AIMS: Serum thioredoxin (TRX) levels have recently been established as an indicator of oxidative stress in various diseases. The aim of the present study was to clarify the clinical significance of serum ferri...
BACKGROUND/AIMS: Serum thioredoxin (TRX) levels have recently been established as an indicator of oxidative stress in various diseases. The aim of the present study was to clarify the clinical significance of serum ferritin in chronic liver diseases. METHODS: Levels of ferritin, transferrin saturation (TS), aspartate aminotransferase (AST), and TRX were measured in the sera of patients with chronic hepatitis C (CH-C, n=92), chronic hepatitis B (CH-B, n=28), nonalcoholic fatty liver (FL, n=31), or alcoholic liver diseases (ALD, n=17). Serum TRX levels were evaluated with a recently established sandwich enzyme-linked immunosorbent assay kit. RESULTS: Serum TRX levels were significantly higher in CH-C, FL, and ALD than in healthy volunteers. A larger proportion of patients with CH-C, FL, and ALD had elevated levels of serum ferritin than CH-B. Serum ferritin levels were positively correlated with levels of TS, AST, and TRX in CH-C, but were merely correlated with TS values in CH-B. Ferritin levels were also well correlated with AST and TRX, but not with TS in FL and ALD. CONCLUSION: Oxidative stress, which was evaluated by measuring serum TRX, in addition to storage iron and hepatocyte damage is a cause of increasing serum ferritin levels in chronic liver diseases. An elevated serum ferritin level, which was correlated with TS, indicates that iron-induced oxidative stress contributes to CH-C. Elevated ferritin levels in FL and ALD may be mostly due to iron-unrelated stresses.
Can hepatic stellate cells express alpha-smooth muscle actin in normal human liver?
Lepreux S, Dubuisson L, Le Bail B … +3 more , Desmoulière A, Balabaud C, Bioulac-Sage P
Liver · 2001 Aug · PMID 11454194 · Publisher ↗
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Acute liver failure as the initial manifestation of acute leukaemia.
Anderson SH, Richardson P, Wendon J … +2 more , Pagliuca A, Portmann B
Liver · 2001 Aug · PMID 11454193 · Publisher ↗
BACKGROUND/AIMS: Haematological malignancies seldom cause clinically significant liver disease. Acute liver failure as the initial manifestation of acute leukaemia is very rare and carries a very poor prognosis. METHODS/...
BACKGROUND/AIMS: Haematological malignancies seldom cause clinically significant liver disease. Acute liver failure as the initial manifestation of acute leukaemia is very rare and carries a very poor prognosis. METHODS/RESULTS: Three cases of acute liver failure secondary to acute leukaemia are described. Each case presented initially as acute liver failure of uncertain cause. Specific treatment for the leukaemia was instituted; however, all three patients died as a consequence of the liver failure. We describe the clinical course and relevant investigations of these patients and discuss possible mechanisms of acute liver failure in this setting. CONCLUSION: Acute leukaemia presenting as acute liver failure has a very poor prognosis. Although a rare cause of acute liver failure, it should be considered in any patient presenting with acute liver failure with prodromal symptoms and a raised peripheral white cell count, lactate dehydrogenase and uric acid.
Chinese medicinal herbs for chronic hepatitis B: a systematic review.
Liu J, McIntosh H, Lin H
Liver · 2001 Aug · PMID 11454192 · Publisher ↗
AIMS/BACKGROUND: Chronic hepatitis B is a serious health problem worldwide. Chinese medicinal herbs are widely used for treatment of chronic hepatitis B in China and many clinical trials have been conducted. This systema...
AIMS/BACKGROUND: Chronic hepatitis B is a serious health problem worldwide. Chinese medicinal herbs are widely used for treatment of chronic hepatitis B in China and many clinical trials have been conducted. This systematic review is to assess the efficacy and safety of Chinese medicinal herbs for chronic hepatitis B. METHODS: Randomised clinical trials comparing Chinese medicinal herbs versus placebo, no intervention, nonspecific treatment, or interferon treatment for chronic hepatitis B with > or = 3 months follow-up were included. No language and blinding limitations were applied. The electronic databases were searched, combined with handsearches on Chinese literature. Data were extracted independently by two reviewers. The methodological quality of trials was assessed by the Jadad-scale plus allocation concealment. RESULTS: Nine randomised trials (n=936) were included, with only one being of high quality. There was a funnel plot asymmetry (intercept 3.37, p=0.047). Compared to nonspecific treatment or placebo, the herbal compound Fuzheng Jiedu Tang showed an effect on clearance of serum HBsAg (relative risk 5.19, 95% CI 1.24-21.79), HBeAg (10.85, 3.56-33.06), and HBV DNA (8.50, 1.23-58.85). Polyporus umbellatus polysaccharide showed an effect on serum HBeAg (3.06, 1.13-8.29) and HBV DNA (4.14, 1.0-17.19); Phyllanthus amarus showed an effect on serum HBeAg (3.35, 1.49-7.56). Phyllanthus compound and kurorinone showed no significant difference on clearance of serum HBeAg and HBV DNA and on alanine aminotransferase normalisation compared to interferon. No serious adverse event was observed. CONCLUSIONS: Chinese medicinal herbs are not recommended for chronic hepatitis B because of the publication bias and low quality of the trials. Rigorously designed, randomised, double-blind, placebo-controlled trials are needed.
Apoptotic pathways in primary biliary cirrhosis and autoimmune hepatitis.
Fox CK, Furtwaengler A, Nepomuceno RR … +2 more , Martinez OM, Krams SM
Liver · 2001 Aug · PMID 11454191 · Publisher ↗
BACKGROUND/AIMS: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases with unknown etiologies that primarily target the liver. In both diseases, liver lesions are accompanied by larg...
BACKGROUND/AIMS: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases with unknown etiologies that primarily target the liver. In both diseases, liver lesions are accompanied by large infiltrates of mononuclear cells. The purpose of this study was to determine if either the Fas-mediated or the granule-exocytosis pathways contribute to apoptosis in these diseases. METHODS: To determine the involvement of apoptosis in tissue injury we examined liver tissue for DNA fragmentation and morphological characteristics of apoptosis. The major cytotoxic pathways of activated lymphocytes were compared by quantitating the levels of transcripts for FasL and granzyme B, and expression was confirmed by immunoprecipitation of these molecules. RESULTS: In both diseases, apoptosis was observed. However, the main cell types undergoing apoptosis were hepatocytes in AIH, and biliary epithelial cells in PBC. In AIH the levels of FasL and granzyme B mRNA were increased over the levels detected in normal liver, while in PBC only the levels of granzyme B were elevated. Additionally, in AIH, the ratio of FasL transcripts to granzyme B transcripts was elevated, reflecting a possible increase in the relative contribution of FasL to the progression of the disease. Immunoprecipitation studies further support an increase in FasL protein expression in AIH. CONCLUSIONS: These data suggest that both FasL and granzyme B contribute to the apoptosis observed in AIH and PBC. However, FasL appears to play a more prominent role in the induction of hepatocyte apoptosis and tissue destruction in AIH.
Chronic hepatitis C and superimposed nonalcoholic fatty liver disease.
Ong JP, Younossi ZM, Speer C … +3 more , Olano A, Gramlich T, Boparai N
Liver · 2001 Aug · PMID 11454190 · Publisher ↗
BACKGROUND/AIMS: Hepatitis C and nonalcoholic fatty liver disease (NAFL) are the two most common forms of liver disease in the United States. Recently, obesity and its associated risk factors have been suggested to enhan...
BACKGROUND/AIMS: Hepatitis C and nonalcoholic fatty liver disease (NAFL) are the two most common forms of liver disease in the United States. Recently, obesity and its associated risk factors have been suggested to enhance HCV-related fibrosis. The aim of this study was to assess the impact of hepatic steatosis, steatohepatitis, and its associated risk factors on HCV-related fibrosis. METHODS: Patients with untreated, biopsy-proven, chronic hepatitis C (6/97-3/99) were included. Clinical and demographic data at the time of liver biopsy were obtained from chart review and verified by telephone survey. One hepatopathologist reviewed all pathologic specimens, using the modified histological activity index score and the Ishak staging for fibrosis and a NAFL pathologic protocol. RESULTS: One hundred and seventy patients with hepatitis C were included [age: 48.7+/-9.33 (years), body mass index (BMI): 28.1+/-5.7 (kg/m2) and type 2 diabetes mellitus (DM): 14%]. Of these, 77 (45.3%) had no or mild fibrosis and 93 (54.7%) had advanced fibrosis. Hepatic steatosis was seen in 90 (52.9%) patients. The grade of steatosis was associated with markers of obesity only. Age (p=0.002), type 2 DM (p=0.04), and superimposed steatohepatitis (p=0.047) were independently associated with advanced fibrosis. Superimposed nonalcoholic steatohepatitis (NASH) was seen in 17 (10%) patients. Patients with superimposed NASH were mostly obese (76.5%), males (62%) with 16% having type 2 diabetes and a BMI 33.8+/-7.12. CONCLUSION: In patients with chronic hepatitis C, type 2 DM and superimposed steatohepatitis are independently associated with advanced fibrosis.
Quantitative testing of liver function in relation to fibrosis in patients with chronic hepatitis B and C.
Herold C, Heinz R, Niedobitek G … +3 more , Schneider T, Hahn EG, Schuppan D
Liver · 2001 Aug · PMID 11454189 · Publisher ↗
BACKGROUND/AIM: Quantitative tests of liver function may be superior to conventional tests to assess the prognosis of patients with liver diseases. There are insufficient data from quantitative testing of liver function...
BACKGROUND/AIM: Quantitative tests of liver function may be superior to conventional tests to assess the prognosis of patients with liver diseases. There are insufficient data from quantitative testing of liver function (QTLF) for patients with chronic hepatitis B and C, particularly with regard to fibrosis. Therefore, we applied a broad panel of QTLF to these patients. METHODS: Three hundred and sixty-seven consecutive patients with chronic hepatitis B or C underwent liver biopsy and QTLF, which included tests for hepatic metabolism (aminopyrine breath test, galactose elimination capacity) and for hepatic perfusion (sorbitol clearance, indocyanine green clearance). QTLF values were correlated with liver histology (grading and staging for inflammation and fibrosis) and Child-Pugh classification for liver cirrhosis. RESULTS: In patients with no and moderate fibrosis, metabolic liver function was significantly decreased, whereas hepatic perfusion remained normal. Severe fibrosis and cirrhosis showed a significant decline in all QTLFs. Hepatic inflammation only reduced metabolic liver function, irrespective of the inflammatory grade. Viral etiology and HCV genotypes did not change QTLF. CONCLUSIONS: In summary, viral damage compromises hepatic metabolism before perfusion. Therefore, tests of metabolic liver function (aminopyrine breath test, galactose elimination capacity) should be useful to search for drugs that restore liver function in viral hepatitis irrespective of the fibrosis stage.
Clearance of hepatitis B surface antigen in chronic carriers of hepatitis delta antibodies.
Niro GA, Gravinese E, Martini E … +6 more , Garrubba M, Facciorusso D, Conoscitore P, Di Giorgio G, Rizzetto M, Andriulli A
Liver · 2001 Aug · PMID 11454188 · Publisher ↗
BACKGROUND/AIMS: We evaluated the rate of seroclearance of the hepatitis B surface antigen (HBsAg) and its clinical significance in patients with chronic hepatitis delta virus (HDV). METHODS: Antibody to HDV was tested i...
BACKGROUND/AIMS: We evaluated the rate of seroclearance of the hepatitis B surface antigen (HBsAg) and its clinical significance in patients with chronic hepatitis delta virus (HDV). METHODS: Antibody to HDV was tested in HBsAg-positive subjects admitted to our Hospital from 1991 to 1995. In 1997, a biochemical and virologic study was performed in the surviving anti-HD-positive patients who had not undergone transplantation. As a control, a cohort of 106 HBsAg-positive, anti-HD-negative patients was studied. RESULTS: One hundred and forty-one subjects were originally positive for anti-HD. After 4 years of follow-up, six of the 60 patients who underwent re-evaluation (10%) had cleared the HBsAg: three of the six patients had minimal changes at the initial liver histology and normal ALT, whereas in the remaining three patients with chronic active hepatitis ALT normalized during the observation. Anti-HD persisted in five of the six patients. Only one patient had raised anti-HBs. In contrast, three of 106 HBsAg carriers without HDV infection (2.8%) cleared the HBsAg within the same time and seroconverted to anti-HBs (p=0.002). CONCLUSION: HBsAg clearance is increased over the years in HDV patients compared to ordinary HBsAg carriers, and is often associated with improvement of HDV disease without seroconversion to anti-HBs.
Expression of hepatic transporters OATP-C and MRP2 in primary sclerosing cholangitis.
Oswald M, Kullak-Ublick GA, Paumgartner G … +1 more , Beuers U
Liver · 2001 Aug · PMID 11454187 · Publisher ↗
BACKGROUND/AIMS: In chronic cholestatic liver diseases, biliary excretion of organic anions from blood into bile is impaired. The aim of this study was to identify the underlying mechanism. METHODS: Expression of the bas...
BACKGROUND/AIMS: In chronic cholestatic liver diseases, biliary excretion of organic anions from blood into bile is impaired. The aim of this study was to identify the underlying mechanism. METHODS: Expression of the basolateral organic anion transporting polypeptide OATP-C (SLC21A6) and the canalicular multidrug resistance protein 2 (MRP2) was studied in patients with primary sclerosing cholangitis (PSC) (n=4), a chronic cholestatic liver disease, and in non-cholestatic controls (n=4) (two with chronic hepatitis C, one with idiopathic liver cirrhosis and one with fatty liver). Total RNA was isolated from liver tissue, reverse transcribed and subjected to polymerase chain reaction (PCR) amplification using primers specific for OATP-C, MRP2 and beta-actin. PCR products were quantified densitometrically. RESULTS: When normalized for beta-actin expression, the level of OATP-C mRNA in liver tissue of patients with PSC was 49% of controls (OATP-C/beta-actin 1.60+/-0.25 vs. 3.24+/-0.69; p<0.05) and the level of MRP2 mRNA was 27% of controls (MRP2/beta-actin 0.70+/-0.36 vs. 2.54+/-0.56; p<0.01). CONCLUSIONS: Both OATP-C and MRP2 are decreased as measured by mRNA level in PSC. Downregulation of OATP-C might be the consequence of impaired canalicular secretion of organic anions and could serve to reduce the organic anion load of cholestatic hepatocytes.
Immunohistochemical analysis of atypical ductular reaction in the human liver, with special emphasis on the presence of growth factors and their receptors.
Kiss A, Schnur J, Szabó Z … +1 more , Nagy P
Liver · 2001 Aug · PMID 11454186 · Publisher ↗
AIMS/BACKGROUND: The objective of this study was to characterize the expression of transforming growth factor-alpha/epidermal growth factor receptor, hepatocyte growth factor/c-met, transforming growth factor-beta/Type I...
AIMS/BACKGROUND: The objective of this study was to characterize the expression of transforming growth factor-alpha/epidermal growth factor receptor, hepatocyte growth factor/c-met, transforming growth factor-beta/Type I-II transforming growth factor-beta receptors, stem cell factor, urokinase plasminogen activator, smooth muscle actin, CD34 and alpha-fetoprotein in human liver samples with (sub)massive necrosis of different etiology containing atypical ductular reaction. METHODS: Their presence was studied by immunohistochemistry on paraffin-embedded tissue sections. RESULTS: Transforming growth factor-alpha and -beta, hepatocyte growth factor and their receptors were demonstrated in the ductules; additionally stem cell factor and urokinase plasminogen activator were also expressed. The atypical ductules were surrounded by smooth muscle actin-positive activated stellate cells. CONCLUSION: These phenotypic similarities confirm that the atypical ductules in the human liver may be equivalent of oval cells in the rat liver, which are regarded as the progeny of stem cells. That is, the atypical ductular proliferation may correspond to a stem cell-fed regenerative process.
Analysis of haemochromatosis gene mutations in a population from the Mediterranean Basin.
Campo S, Restuccia T, Villari D … +5 more , Raffa G, Cucinotta D, Squadrito G, Pollicino T, Raimondo G
Liver · 2001 Aug · PMID 11454185 · Publisher ↗
BACKGROUND/AIMS: The C282Y mutation in the haemochromatosis gene (HFE) located on chromosome 6 has been identified as the main genetic basis of hereditary haemochromatosis (HH). Two more mutations of that gene, H63D and...
BACKGROUND/AIMS: The C282Y mutation in the haemochromatosis gene (HFE) located on chromosome 6 has been identified as the main genetic basis of hereditary haemochromatosis (HH). Two more mutations of that gene, H63D and S65C, appear to be associated with milder forms of HH. A high allele frequency for C282Y and H63D mutations was reported in populations from North Europe, while incomplete information is available for individuals from the Mediterranean Basin where C282Y homozygotes comprise a smaller percentage of HH cases. In this study we investigated the allele frequency of HFE mutations and the association between HFE mutations and cases of HH in a population from the South of Italy (Sicily and Calabria). In addition, we evaluated a possible association between HFE mutations and either chronic liver disease or type II diabetes. PATIENTS AND METHODS: Three hundred and twenty-seven individuals (654 chromosomes) were tested for C282Y, H63D and S65C mutations of the HFE gene by restriction fragment length polymorphism. Four had HH, 23 had hepatocellular carcinoma, 100 had chronic liver disease, 100 had type II diabetes, and 100 were healthy controls. RESULTS: Both C282Y and S65C mutations were each detected in one of the 654 chromosomes analysed (allele frequency=0.15%), while H63D change was found in 122 chromosomes (allele frequency=18.6%) and was equally distributed in all the categories examined. One healthy individual had compound heterozygosity for C282Y and H63D mutations. The frequency of C282Y in this Southern Italian sample was the lowest yet reported for a population of European origin. None of the four HH patients was either homozygous or heterozygous for C282Y. CONCLUSIONS: In Mediterranean populations from Southern Italy the C282Y mutation occurs sporadically and HFE polymorphisms seem to have little diagnostic relevance.
Molecular mimicry and autoimmune liver disease: virtuous intentions, malign consequences.
Bogdanos DP, Choudhuri K, Vergani D
Liver · 2001 Aug · PMID 11454184 · Publisher ↗
The pathogenesis of autoimmune liver disease and autoimmunity associated with chronic viral hepatitis remains poorly understood. One of the major hurdles to a deeper understanding of these pathological processes is the a...
The pathogenesis of autoimmune liver disease and autoimmunity associated with chronic viral hepatitis remains poorly understood. One of the major hurdles to a deeper understanding of these pathological processes is the absence of clearly defined inductive mechanisms, which, if identified and characterised, could guide clinical strategies for their prevention or allow therapeutic intervention. Molecular mimicry leading to crossreactive autoimmune responses has gained strong experimental support in the past decade. A fundamental premise of this hypothesis is the involvement of a mimicking environmental trigger. In view of the numerous viral and bacterial agents epidemiologically linked to autoimmune liver diseases, we and others have proposed molecular mimicry to be an important mechanism in these diseases. We also propose similar crossreactive mechanisms to operate in the generation of autoimmunity in viral hepatitis. This review focuses on molecular mimicry at the level of the B-cell, as few data on T-cell crossreactivity in liver disease are thus far available.
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