Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 50-year-old woman suffered from a diffuse skin rash, high fever and jaundice immediately after a second injection of glutathion and Stronger Neo-minophagen C which contains glycyrrhizin. Liver biopsy performed 11 months after the onset showed mild spotty hepatocyte necrosis, marked cholestasis in parenchyma, and some lymphocyte infiltration in the portal area. Interlobular bile ducts had undergone vacuolar degeneration or were absent in some portal tracts. In her hospital course, unremitting jaundice persisted and biliary cirrhosis developed with signs of portal hypertension; she died from liver failure 26 months after the onset. A liver specimen at her death revealed that most of the interlobular bile ducts had vanished. Based on the clinical course and pathology, drug-induced ductopenia, possibly due to an adverse reaction to glycyrrhizin, is the most likely diagnosis. While drug-related biliary cirrhosis is rarely fatal, this case presented an unusually rapid course of fatal biliary cirrhosis.
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PMID:A case of drug-induced ductopenia resulting in fatal biliary cirrhosis. 837 99

In Japan, hepatitis C virus (HCV) is the single most frequent cause of hepatocellular carcinoma (HCC), resulting in yearly deaths of over 30,000. Although the mechanism of how HCV induces HCC is not clear, persistent HCV infection and necro-inflammatory changes in chronic hepatitis C accelerate the development of liver cirrhosis and can eventuate in HCC. Hence, means of eradicating HCV as well as suppressing inflammation in the liver, even if patients stay infected with HCV, would decrease the incidence of HCC with chronic hepatitis C. For more than 40 years, a preparation of glycyrrhizin [Stronger Neo-Minophagen C (SNMC)] has been used for the treatment of 'allergic' hepatitis in Japan. In 1977, intravenous injection with SNMC was started in patients with chronic hepatitis or liver cirrhosis, most of whom have turned out to be infected with hepatitis viruses. In a multicenter double-blind study, alanine aminotransferase (ALT) levels decreased in the patients who received 40 ml/day of SNMC for 4 weeks at a rate significantly higher (p < 0.001) than controls receiving placebo. Furthermore, SNMC 100 ml/day for 8 weeks improved liver histology in 40 patients with chronic hepatitis, in correlation with improved ALT levels in serum. Liver cirrhosis occurred less frequently in 178 patients on long-term SNMC than in 100 controls (28 vs. 40% at year 13, p < 0.002). Finally, HCC developed less frequently in the 84 patients on long-term SNMC than in the 109 controls (13 vs. 25% at year 15, p < 0.002). Combined, these results indicate that a long-term treatment with SNMC prevents the development of HCC in the patients with chronic hepatitis. SNMC is particularly helpful in the patients with chronic hepatitis C who fail to respond to interferon and in those who cannot be treated with it for various reasons.
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PMID:Long-term treatment of chronic hepatitis C with glycyrrhizin [stronger neo-minophagen C (SNMC)] for preventing liver cirrhosis and hepatocellular carcinoma. 1186 94

Hepatocellular carcinoma (HCC) is one of the most common cancers and is the leading cause of cancer death in Taiwan. Curative surgery is feasible for only about 30% of patients. Transarterial embolization or chemoembolization (TAE/TACE) has been demonstrated to provide a survival benefit compared with supportive care for HCC patients with adequate liver reserves, tumors confined to the liver, and no evidence of portal vein thrombosis. Percutaneous ethanol injection (PEI) may provide long-term disease control if the extent of liver tumors is limited (3 or less in number and less than 3 cm in diameter). The relative efficacy of TAE/TACE, PEI, and other locoregional treatment modalities, such as radiofrequency ablation or cryosurgery, remains unclear. Radiotherapy has been used mostly as a salvage therapy in combination with other locoregional modalities. Despite the incorporation of 3-dimensional conformal technology, radiation-induced liver injury remains an important problem, especially for patients with hepatitis B-related cirrhosis. Systemic therapy is difficult for HCC because of the underlying cirrhosis and accompanying hypersplenism and peripheral cytopenia. HCC is typically resistant to most cytotoxic agents. Biochemical modulation with high-dose tamoxifen may sensitize HCC cells to doxorubicin-induced apoptosis and improve the clinical response to doxorubicin in patients with advanced HCC. Thalidomide, which inhibits angiogenesis induced by vascular endothelial growth factor and basic fibroblast growth factor, can produce a response in some HCC patients. Future research on drug therapy for HCC will focus on identification of tumor-specific targets.
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PMID:Recent advances in non-surgical treatment for advanced hepatocellular carcinoma. 1531 70

In a previous study of patients with hepatitis C virus (HCV)-associated liver cirrhosis (HCV-LC), we showed that increased liver inflammation, as assessed by higher serum alanine aminotransferase (ALT), was associated with increased risk for the development of hepatocellular carcinoma (HCC). This suggested that suppression of inflammation might inhibit HCC development in HCV-LC. Several agents have been suggested to possess chemopreventive potential against the development of HCC in chronic HCV-associated liver disease, including herbal medicines, such as Stronger-Neo-Minophagen C (glycyrrhizin) and Sho-saiko-to (TJ-9). Ursodiol [ursodeoxycholic acid (UDCA)], a bile acid widely used to treat cholestatic liver diseases, also possesses anti-inflammatory properties in liver disease. We hypothesized that suppression of liver inflammation, as assessed by decreases in serum ALT, might inhibit HCC occurrence in patients with HCV-LC. In this study, the preventive effect of UDCA on HCC was examined in patients with early-stage HCV-LC. One hundred two patients with HCV-LC (Child stage A) were treated with anti-inflammatory drugs, Stronger-Neo-Minophagen C,Sho-saiko-to, or UDCA, with the goal of lowering the average serum ALT level to <80 IU. Iftheaverage ALT level did not remain <80 IU after treatment with one agent, multiagent therapy was initiated. The patients were followed up for >5 years and were retrospectively subdivided into two groups: 56 UDCA users (group A) and 46 UDCA nonusers (group B). The mean +/- SD dosage of UDCA administered in group A was 473.7 +/- 183.0 mg/d. The average duration of UDCA administration in group A was 37.3 +/- 15.9 months over the 5-year study period. The cumulative incidence of HCC was recorded. The 5-year incidence of HCC in group A was 17.9% (10 of 56) and was significantly lower than that in group B (39.1%, 18 of 46; P = 0.025). The risk for HCC incidence, calculated by a logistic regression model, showed that the administration of UDCA significantly decreased hepatocarcinogenesis (P = 0.036). The herbal medicines used were comparable in dosage and treatment duration in the UDCA and non-UDCA groups. In conclusion, UDCA might prevent HCC development in HCV-LC. Interestingly, because the serum ALT trends over time were nearly the same in both groups, the chemopreventive effectiveness of UDCA was not accompanied by greater reductions in ALT compared with the UDCA nonusers.
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PMID:Ursodiol use is possibly associated with lower incidence of hepatocellular carcinoma in hepatitis C virus-associated liver cirrhosis. 1566 91

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in cellular necrosis, apoptosis, organ failure, tissue damage, inflammation and fibrosis. These processes, occurring in liver injury, may lead to cirrhosis. Thalidomide, alpha-N-phthalidoglutarimide, (C(13)H(10)N(2))(4), has been shown to have immunomodulatory and anti-inflammatory properties, possibly mediated through its anti-TNF-alpha effect. In this study, we investigated the in vitro and in vivo effects of thalidomide on hepatic fibrosis. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with transforming growth factor-beta1 (TGF-beta1) or TNF-alpha. The inhibitory effects of thalidomide on the NFkappaB signaling cascade and fibrosis markers including alpha-smooth muscle actin (alpha-SMA) and collagen, were assessed. An in vivo therapeutic study was conducted in dimethylnitrosamine (DMN)-treated rats, which were randomly assigned to 1 of 4 groups: vehicle (0.7% carboxyl methyl cellulose, CMC), thalidomide (40 mg/kg), thalidomide (200 mg/kg), or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting after 1 week of DMN administration. Thalidomide (100-800 nM) concentration-dependently inhibited NFkappaB transcriptional activity induced by TNF-alpha, including IKKalpha expression and IkappaBalpha phosphorylation in HSC-T6 cells. In addition, thalidomide also suppressed TGF-beta1-induced alpha-SMA expression and collagen deposition in HSC-T6 cells. Fibrosis scores of livers from DMN-treated rats receiving high dose of thalidomide (0.89 +/- 0.20) were significantly reduced in comparison with those of DMN-treated rats receiving vehicle (1.56 +/- 0.18). Hepatic collagen contents of DMN rats were also significantly reduced by either thalidomide or silymarin treatment. Immunohistochemical double staining results showed that alpha-SMA- and NFkappaB-positive cells were decreased in the livers from DMN rats receiving either thalidomide or silymarin treatment. In addition, real-time PCR analysis indicated that hepatic mRNA expressions of TGF-beta1, alpha-SMA, collagen 1alpha2, TNF-alpha and iNOS genes were attenuated by thalidomide treatment. In conclusion, our results showed that thalidomide inhibited activation of HSC-T6 cells by TNF-alpha and ameliorated liver fibrosis in DMN-intoxicated rats.
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PMID:Anti-fibrotic effects of thalidomide on hepatic stellate cells and dimethylnitrosamine-intoxicated rats. 1660 21

It is known that there is a very high incidence of hepatocellular carcinoma (HCC) among patients with type C chronic hepatitis and cirrhosis, and alpha -fetoprotein (AFP) has been widely used as a diagnostic marker for HCC. However, there are some patients showing continuous high AFP values but no evidence of HCC, and some studies have defined such patients as a high-risk group for HCC. In vitro study has shown that interferon (IFN) inhibits cell proliferation and enhances apoptosis as well as specific cytotoxic T lymphocytes against HCC, resulting in direct anticancer actions. In this study, we investigated the effect of IFN on AFP changes in chronic hepatitis C patients. Of 40 patients with chronic hepatitis C in whom diagnostic imaging confirmed the absence of HCC, 24 patients showed high pretreatment AFP values (high AFP group: AFP level > 10 ng/dl; mean +/- SD, 46.3 +/- 41.5 ng/dl) and 16 showed low pretreatment AFP values (low AFP group: pretreatment AFP level < or = 10 ng/dl; mean +/- SD, 5.3 +/- 2.2 ng/dl). Pretreatment clinical parameters were statistically evaluated in relation to the AFP value. In the high AFP group, the platelet count, albumin level, and prothrombin (%) were significantly lower (P = 0.047, P = 0.0002, and P = 0.044, respectively), suggesting that AFP value increases with advancing liver disease. Subsequently 27 patients were administered IFN (IFN group), and the remaining 13 patients were administered Stronger Neo-minophagen C (SNMC), a glycyrrhizin preparation (SNMC group), as a control group receiving liver-protective therapy. Alanine aminotransferase was reduced in both the IFN and the SNMC group (mean, 132.56 to 60.07 mg/ml [P < 0001] and 147.85 to 56.23 mg/ml [P = 0.0240], respectively). AFP was significantly reduced in the IFN group (mean, 30.03 to 12.65 ng/ml; P = 0.0034), but there was no significant change in AFP in the SNMC group (mean, 29.70 to 39.17 ng/ml). AFP is useful for diagnosing HCC; however, some patients show a persistently high AFP level in the absence of HCC, and these patients have been described as a high-risk group for HCC. In this study, we found that IFN therapy but not SNMC universally reduced the AFP baseline. Since AFP is a significant predictor for HCC, therapeutic strategies for hepatitis C, e.g., long-term low-dose IFN treatment, may reduce hepatocarcinogenesis.
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PMID:A decrease in AFP level related to administration of interferon in patients with chronic hepatitis C and a high level of AFP. 1661 8

This study investigated the effect of thalidomide on oxidative stress in rat liver cirrhosis. The cirrhosis of rat was induced by intraperitoneal injection of carbon tetrachloride thrice weekly; meanwhile, thalidomide (10mg/kg or 100mg/kg) was given daily by intragastric administration for 8 weeks. The content of oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde, in the liver was detected by biochemical assay. Immunohistochemistry revealed alpha-smooth muscle actin (alpha-SMA), desmin, and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein in the liver. Nuclear factor kappa B p65 (NF-kappaBp65) protein in nucleus and transforming growth factor beta1 (TGF-beta1) protein in cytoplasm were detected by Western blot. NF-kappaBp65, TGF-beta1, and TIMP-1 mRNA levels in the liver were studied using reverse transcriptase polymerase chain reaction. Liver histopathology was significantly improved in rats given high doses of thalidomide. The content of oxidative stress parameters and the expressions of NF-kappaBp65, TGF-beta1 and TIMP-1 protein, and mRNA were significantly decreased in these animals. The expressions of alpha-SMA and Desmin protein were also significantly decreased in them. Thalidomide might exert an effect on the inhibition of oxidative stress via downregulation of NF-kappaB signaling pathway to prevent the progression of liver cirrhosis.
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PMID:Thalidomide prevents rat liver cirrhosis via inhibition of oxidative stress. 1703 Apr 52

Chronic cholestasis and cholangitis may lead to the last phase known as biliary cirrhosis, characterized by cellular necrosis, apoptosis, tissue damage, local regeneration, inflammation and fibrosis. Such events are mediated by cytokines. Thalidomide and its analogs have shown to be effective immunomodulatory and hepatoprotective agents. The aim of this work was to evaluate the hepatoprotective properties of a thalidomide analog, the 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid (PDA), on bile duct obstruction-induced cirrhosis. Vehicle or PDA (67 mg/kg) was orally administered twice a day to sham (Sham) or bile duct-ligated (BDL) male Wistar rats. The animals were sacrificed 28 days after treatments. Alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGTP) and alanine aminotransferase (ALT) enzyme activities as well as direct and total bilirubins concentration were determined in plasma. Lipid peroxidation (LP), glycogen and collagen were quantified in liver; in addition, histopathology was performed. PDA improved cholestasis, necrosis and fibrosis by significantly diminishing most of liver injury markers (P<0.05). Histopathology also showed remarkable liver damage amelioration. PDA effectiveness may be due to its water-solubility, stability, phosphodiesterase-4 inhibitory and immunomodulatory actions. Thalidomide and its analogs seem to be promising drugs for further treatment of biliary cirrhosis.
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PMID:The thalidomide analog 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid improves the biliary cirrhosis in the rat. 1909 29

Increased intrahepatic resistance (IHR) within cirrhotic liver is caused by increased endotoxemia, cytokines tumor necrosis factor-alpha (TNF-alpha), vasoconstrictor thromboxane A(2) (TXA(2)), and disrupted microvasculatures. We evaluated the effects of thalidomide-related inhibition of TNF-alpha upon the hepatic microcirculation of cirrhosis in rats. Portal venous pressure (PVP), hepatic TNF-alpha, expression of thromboxane synthase (TXS), and leukocyte common antigen (LCA) were measured in bile-duct-ligated (BDL) rats receiving 1 month of thalidomide (BDL-thalido rats). Portal perfusion pressure (PPP), IHR, and hepatic TXA(2) production were measured in the isolated liver perfusion system. Intravital microscopy was used to examine hepatic microvascular disruptions. In BDL-thalido rats, PVP, PPP, IHR, hepatic TXA(2) and TNF-alpha, hydroxyproline content, expression of TXS and LCA, and LPS-induced leukocyte recruitment were significantly decreased. Conversely, hepatic microvascular density and perfused sinusoids were significantly increased. Thalidomide decreased PVP and IHR by reducing hepatic TXA(2) and improving hepatic microvascular disruptions in rats with biliary cirrhosis.
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PMID:Thalidomide decreases intrahepatic resistance in cirrhotic rats. 1928 19

The results of treatment of 52 patients, suffering obturation jaundice (OJ), were analyzed. The causes of the OJ occurrence were studied up. A peculiar attention was drawn to the treatment of patients, suffering OJ on a hepatic cirrhosis background. On the first stage of surgical treatment various operative procedures were applied to eliminate OJ. The impact of the tactics proposed, consisting of detoxication and infusion therapy, on duration of postoperative rehabilitation of the patients was studied up. In postoperative period to all the patients Hepasol Neo was prescribed, what have promoted their general condition improvement, the bilirubin level normalization, as well as the cytolysis and cholestasis elimination.
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PMID:[Application of a hepasol neo preparation in the treatment of obturation jaundice patients]. 2398 26


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