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)

To clarify the physiologic response of splenic lymphocytes to liver damage and the role of this response in regeneration versus malignant transformation, we cultured rat spleen lymphocytes with portal sera from rats subjected either to partial (70%) hepatectomy or to long-term oral administration of the hepatic carcinogen 3'-methyl-4-dimethylaminoazobenzene. Sera taken within 24h after partial hepatectomy contained a previously described signal protein which serves as a marker of liver damage. The MW 5,000-10,000 serum fraction also contained a factor that promoted cell growth, DNA synthesis, glucose utilization, and the production of anti-sheep erythrocyte plaque-forming cells in cultures of rat splenic lymphocytes. In contrast, the sera of rats subjected to liver damage by the carcinogen had no more effect on the cultured lymphocytes than sera from sham-operated or untreated controls. The signal protein was present initially in portal sera from carcinogen-treated rats, but decreased as hepatitis gave way to cirrhosis. Subsequent malignant transformation was marked by the appearance of serum alpha-fetoprotein. Our results suggest that activation of splenic lymphocytes by serum factor(s) is involved in hepatic regeneration and that this process is deranged in carcinogenesis.
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PMID:In-vitro immune response of splenic lymphocytes to portal serum agents from rats undergoing hepatic regeneration or hepatic carcinogenesis. 139 18

In the period 1982 to 1984, 14 HBS-AG-positive patients with chronic active hepatitis B were treated monthly with a cell wall preparation (5 or 10 mg) of Propionibacterium granulosum KP-45 (PG), intravenously administered for a period of 6 to 10 months. All 14 patients were monitored by serological and biochemical tests as well as liver biopsy two, three and five years after completing immunotherapy with PG. During this period the patients received neither a specific antiviral, corticosteroid or interferon therapy, nor PG. Re-appearance of HBSAG or HBeAG was never seen in patients who were already free from the antigens one year after completing PG immunotherapy. During the 5-year follow-up, spontaneous improvement in serological and morphological (liver biopsy) parameters of chronic virus B hepatitis occurred in six patients. Five years after completion of PG immunotherapy, only four of the 14 patients showed trace amounts of serum HBSAG (carriers), and in two low levels of anti-HBeAG were present, while the whole group showed a decreasing tendency and serum anti-HBc was still detectable in six patients. HBeAG- and DNA-polymerase-positivity was absent in all patients. Microscopic examination of liver biopsies 5 years after PG immunotherapy showed mild symptoms of chronic hepatitis with inflammatory infiltration, non-active cirrhosis, but without massive periportal and/or multilobular necrosis and trace amounts of HBsAG and HBcAG in hepatocytes only in the four carriers. The remaining 10 patients were free of symptoms of active hepatitis and/or active cirrhosis, but all the patients had moderate to intensive fibrosis in their liver biopsies.
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PMID:Immunotherapy of chronic active viral hepatitis B with propionibacterium granulosum KP-45 (a 5-year follow-up report). 142 77

Interferon alpha is the only available therapy for patients with chronic hepatitis B. With interferon alpha 3-15 MU thrice weekly or 5 MU daily during 3-6 months one-third of the patients achieve seroconversion of HBeAg and HBV-DNA together with normalization of aminotransferases and slight improvement of histology. Loss of HBsAg is reported in a minority of responders during treatment, but increases during follow-up. Patients with baseline alanine aminotransferase of at least twice the upper limit of normal and low HBV-DNA concentration achieve the best response rates. HIV-positive patients with low CD4 counts and Asians are poor responders. As side-effects influenza-like symptoms are experienced by almost all patients. Mild leukopenia, thrombocytopenia and decreased hairgrowth are frequently reported. Severe depression, depersonalization and psychosis are reported in a small number of patients but tend to be poorly recognized in some studies. The decision whether dose reduction is indicated seems strongly related to the opinion of the investigator. Although long-term effects on the occurrence of cirrhosis and the development of hepatocellular carcinoma are not available yet, the achieved results are promising.
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PMID:Current status of interferon alpha in the treatment of chronic hepatitis B. 143 94

Hepatitis B virus carriers in Israel are mostly HBeAg negative, of whom 5% to 10% have circulating hepatitis B virus. Recently, a hepatitis B virus variant with a stop codon in the precore region was identified, and it was suggested that specific mutations are associated with fulminant or severe chronic active hepatitis. We have analyzed serum samples from HBeAg-positive and HBeAg-negative patients by polymerase chain reaction, using primers spanning the precore/core region. Nucleotide sequence analysis (by direct sequencing) from amplified hepatitis B virus DNA demonstrated that viral genomes from all HBeAg-negative patients contain G to A mutation (nucleotide 1896), leading to the formation of a stop codon. An additional G to A mutation was identified three nucleotides downstream (nucleotide 1899). These patients are of various ethnic origins, with no unique clinical characteristics and with normal liver histology, chronic hepatitis or cirrhosis. No mutation at the precore/core region was observed in the HBeAg-positive patients. In conclusion, the precore mutations identified in hepatitis B virus carriers in Israel are identical regardless of the carrier's ethnic origin and are associated with mild-to-severe liver disease.
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PMID:Hepatitis B virus precore mutants are identical in carriers from various ethnic origins and are associated with a range of liver disease severity. 144 89

There are conflicting data regarding the ability of the liver to regenerate after partial hepatectomy in animals and humans with cirrhosis. The purpose of this study was to document liver regeneration after partial hepatectomy in a carbon tetrachloride rat model of cirrhosis and to determine whether exogenous putrescine, a polyamine that has been reported to stimulate liver regeneration in animal models of acute liver failure, enhances regenerative activity in cirrhosis. Liver fibrosis and cirrhosis were produced by weekly intragastric gavage with carbon tetrachloride in 130 adult male rats. Vehicle-gavaged rats (n = 12) served as healthy controls. At surgery and at 4 and 8 hr after 70% hepatectomy, rats received normal saline solution or 1 or 10 mg/kg putrescine by intraperitoneal injection. Another group (n = 32) of carbon tetrachloride-treated rats was given putrescine (100 mg/kg) or normal saline solution twice daily for 10 days before partial hepatectomy and at 0, 4 and 8 hr after partial hepatectomy. Liver regeneration was documented 24 and 48 hr after partial hepatectomy on the basis of restitution of liver mass, ornithine decarboxylase activity and [3H]thymidine incorporation into liver DNA. Automated image analysis of the resected liver specimens separated carbon tetrachloride-treated rats into two subgroups: those with bridging fibrosis (fibrotic group) and those with micronodular cirrhosis (cirrhotic group). Restitution of liver mass and ornithine decarboxylase activity at 24 and 48 hr after partial hepatectomy were similar to carbon tetrachloride-treated rats (both fibrotic and cirrhotic) and vehicle-treated healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Liver regeneration and the effect of exogenous putrescine on regenerative activity after partial hepatectomy in cirrhotic rats. 144 97

This paper reviews the genetic variants of alpha-1-antitrypsin (AAT) which have been sequenced with special emphasis on the s.c. deficiency variants. These result in AAT low plasma levels via three main mechanisms: 1) intracellular storage; 2) intracellular degradation; 3) lack of synthesis. Intracellular storage occurs with the classical Z variant and with a few variants called M-like, because of their isoelectric focusing (IF) pattern. The storage phenomenon causes liver damage and can be demonstrated at both light and electron microscopic level with the help of immunohistochemistry. We report a new deficiency variant of AAT (M-Cagliari) characterized by very low plasma levels, massive storage of AAT and liver cirrhosis. By using immunohistochemical techniques and DNA analysis we could demonstrate that M-Cagliari has antigenic and genetic properties other than the Z AAT.
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PMID:Genetic variants of alpha-1-antitrypsin (AAT). 144 62

The therapeutic effects of interferon alpha-2b (Intron A; Scherag) in patients with chronic active hepatitis caused by hepatitis B virus (HBV) were assessed in a randomised, case-controlled clinical trial conducted between January 1988 and June 1990. Treatment involved a short course of prednisone followed by interferon alpha-2b, initially 10 million U by subcutaneous injection, 3 times a week for 16 weeks. All patients were symptomatic, were known to have had hepatitis B surface antigen and hepatitis B e antigen (HBeAg) in their blood for at least 6 months, and had elevated serum aminotransferase activities with histological evidence of chronic active hepatitis. Patients with carcinoma, renal or haematological abnormalities or decompensated cirrhosis were excluded. In 6 of 10 patients randomised to receive interferon and 1 of 10 controls, HBeAg and HBV DNA were cleared from the blood during the 12-month study period (P < 0.05). An indeterminate response with clearance of HBV DNA but persistence of HBeAg was noted in 1 patient receiving interferon. Serum aminotransferase levels decreased only in those patients who had responded to treatment, but this did not reach statistical significance for the group as a whole. Histological studies, where available, showed decreased hepatic periportal necrosis in patients who underwent treatment. Two patients relapsed to HBeAg-positive status 2 months after their initial seroconversion; 1 became clear again during a repeat course of interferon. Side-effects of treatment were common and included fever, malaise, myalgias and myelosuppression. One patient developed hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Safety and efficacy of interferon alpha-2b following prednisone withdrawal in the treatment of chronic viral hepatitis B. A case-controlled, randomised study. 144 11

DNA stemlines of hepatocellular carcinoma (HCC) model of adult Wistar rats established by diethylnitrosamine were quantitatively measured by flow cytometry. The cancer-inducing course was divided into four stages, eg, precirrhosis stage, cirrhosis stage, early cancer stage and cancer progression stage. The advantageous DNA stemline of hepatocytes of normal adult Wistar rats was tetraploid (4C). It was from the cirrhosis stage that atavistic proliferation of hepatocytes with diploid (2C) DNA stemline started and replaced 4C hepatocytes, resulting in a new advantageous population. The features of early cancer stage were formation of HCC with 2C DNA stemline, whereas during the cancer progression stage, HCC cells with aneuploid (AN) DNA stemline presented the advantageous growth. The study clearly shows the change pattern of DNA stemline during the course of hepatocarcinogenesis from 4C-2C-AN, which is believed to be the biokinetic mechanism of the development and progression of HCC.
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PMID:Characteristic changes of DNA stemlines during hepatocarcinogenesis in rats. 145 56

Hemodialyzed patients and kidney recipients are frequently multiply-transfused and infected by hepatitis B virus (HBV). Hepatitis delta virus (HDV) has a symbiotic association with HBV. The prevalence of HDV infection has, surprisingly, not been assessed in patients in hemodialysis or renal transplantation setting. We retrospectively studied the prevalence of serum delta antigen and antidelta antibodies by a microenzyme-linked immunosorbent assay in 77 of the 80 HBsAg-positive patients who underwent a kidney transplantation over a 10-year period. Of these patients, 73% had active HBV replication as assessed by the presence of serum HBV DNA and 65% had a biopsy-proved chronic active hepatitis, including cirrhosis. None of our patients had any marker of HDV infection at the end of the hemodialysis period or at the end of follow-up in transplantation. These results establish that HDV superinfection has indeed been extremely rare during end-stage renal failure and kidney transplantation in France, in contrast to HBV reactivation or hepatitis C virus infection.
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PMID:Absence of hepatitis delta virus infection in chronic hemodialysis and kidney transplant patients in france. 146 75

From a series of 100 patients hospitalized for chronic hepatitis B infections (HBV), 51 chronic carriers of the HBs antigen without elevated aminotransferases or circulating HBV DNA were studied retrospectively. They had no unusual epidemiological or clinical features compared to the other patients, but were distinguished by their normal liver function tests, except for 5 cases of isolated hypergammaglobulinemia. Hepatic biopsies performed on 28 patients showed minor lesions or normal tissue in 61% of the cases and persistent chronic hepatitis (PCH) in 39% of them. No clinical or biological abnormality was significantly associated with PCH, which was attributed to a delta hepatitis (HDV) superinfection in only one case. There were no cases of active chronic hepatitis or cirrhosis. The significance of the histological lesions in the absence of HBV replication or other symptoms of hepatocyte aggression was not elucidated; their longterm prognosis is not known even if no other difference, identifiable by usual methods, seems to exist between these "pseudo-healthy" carriers and real healthy carriers of HBV.
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PMID:[Healthy and pseudo-healthy carriers of hepatitis B virus. A comparative clinical, biological and pathological approach]. 152 50


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