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)

Two hundred twelve Italian patients with genetic hemochromatosis (181 men, mean age 50 +/- 11 yr; and 31 women, mean age 49 +/- 10 yr) were followed for a median period of 44 mo (range = 3 to 218 mo). Alcohol abuse was present in 31 subjects (15%), and chronic HBV and HCV infection were seen in 19 (9%) and 35 (24%) of 145 cases tested, respectively. Twenty-four patients (11%) had concomitant beta-thalassemia trait. Liver biopsy revealed cirrhosis in 146 and a noncirrhotic pattern in the other 66. Perls' stain was degree III in 37 patients and IV in 171 patients. One hundred eighty-five patients underwent weekly venesection, and iron depletion was achieved in 122 cases after total iron removal of 3 to 41 gm. Death occurred in 44 patients after 3 to 198 mo and was due to hepatocellular carcinoma in 20 cases, liver failure in 10, extrahepatic cancer in six, heart failure in three and hemochromatosis unrelated causes in five. Cancer has developed in seven other patients still alive (hepatocellular in five and extrahepatic in two). No deaths were observed among noncirrhotic patients; cumulative survival rates in cirrhotic patients were 85%, 75%, 60% and 47% at 3, 5, 8 and 10 yr, respectively. Univariate analysis in the 146 cirrhotic patients showed that age greater than 60 yr, alcohol abuse, cardiomyopathy, skin pigmentation, portal hypertension, hypoalbuminemia, hypergammaglobulinemia and Child class B or C had significant negative prognostic value. At multivariate analysis, only alcohol abuse, gamma-globulins greater than 2.0 gm/dl and Child class B or C maintained their negative prognostic values (p less than 0.01, hazard ratio 2.7; p less than 0.001, hazard ratio 2.8; and p less than 0.001, hazard ratio 4.3, respectively).
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PMID:Survival and prognostic factors in 212 Italian patients with genetic hemochromatosis. 131 85

The prevalence of cholelithiasis and possible related factors was evaluated in 350 consecutive patients with alcoholic cirrhosis (218 cases, 174 male and 44 female, mean age 58 +/- 9 years) or genetic haemochromatotic cirrhosis (132 cases, 115 male and 17 female, mean age 53 +/- 10 years). At enrollment patients with alcoholic cirrhosis were significantly older than those with genetic haemochromatotic cirrhosis (P < 0.01), and their clinical status was more severe (Child's class B/C in 99 alcoholic cirrhosis cases versus 27 genetic haemochromatotic cirrhosis cases, P < 0.01). The overall frequency of cholelithiasis was 31% (67 cases) in the alcoholic cirrhosis group and 30% (40 cases) in the genetic haemochromatotic cirrhosis group, without differences according to gender, classes of age (< or = 49, 50-59, > or = 60 years), or HBsAg positivity in either group. In addition, in the genetic haemochromatotic cirrhosis group the presence of diabetes (45 cases), alcohol misuse (38 cases) and beta-thalassemia trait (13 cases) did not influence the prevalence of cholelithiasis. Body mass index, serum cholesterol and triglycerides, and the severity of the underlying liver disease (Child's class) did not distinguish patients with or without cholelithiasis. In conclusion, the frequency of cholelithiasis was high in both alcoholic cirrhosis and genetic haemochromatotic cirrhosis, and was three times higher than that reported in controls from the general population of the same area.
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PMID:Prevalence of cholelithiasis in alcoholic and genetic haemochromatotic cirrhosis. 827 82

Patients with homozygous beta-thalassemia show an abnormal lipoprotein profile. In asymptomatic heterozygotes the lipid pattern is less markedly affected but interestingly related to a diminished cardiovascular risk. The extent and significance of these findings are still a matter of debate and no data are available on lipoprotein(a) plasma levels. Seventy patients with homozygous beta-thalassemia (HT-P), 70 beta-thalassemia trait carriers (TT-C) and 70 sex and age-matched controls were investigated and their plasma lipoprotein profile and apo(a) phenotypes determined. In a subgroup of these same subjects (12 HT-P, 12 TT-C and 24 controls) and in 12 bone marrow-transplanted homozygous beta-thalassemic patients (BMT-P) plasma lipoprotein composition was assessed. HT-P disclosed significantly lower total-cholesterol, LDL-cholesterol, HDL-cholesterol, apo A-I, apo B plasma levels and higher triglyceride concentration than TT-C (-7, -11, -8, -8, -13 and +11%, respectively) or controls (-39, -50, -46, -32, -30 and + 35%, respectively). All lipoprotein subclasses were triglyceride-enriched, while LDLs were also protein-enriched and HDLs protein-depleted. TT-C disclosed a small but significant reduction in apo A-I and apo B plasma levels but only minor lipoprotein abnormalities with respect to the controls. BMT-P lipoprotein composition was intermediate between HT-P and normal subjects. Apo(a) plasma levels did not differ among the groups. A higher prevalence of 'small' apo(a) isoforms was present in HT-P. Within the same 'isoform group', apo(a) plasma levels were significantly lower in HT-P than in TT-C or controls. Since liver cirrhosis is almost always present in HT-P, it is conceivable that an altered hepatic apo(a) synthesis or catabolism due perhaps to diminished apolipoprotein glycation may be involved. In TT-C a partially improved cardiovascular risk profile was apparent (low hematocrit, low LDL-cholesterol and apo B), thus justifying the claim for a low prevalence of ischemic heart disease, but no Lp(a) plasma level modification could be detected.
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PMID:Plasma lipoprotein composition, apolipoprotein(a) concentration and isoforms in beta-thalassemia. 918 Feb 53

Juvenile hemochromatosis is a rare genetic disorder that causes iron overload. Clinical complications, which include liver cirrhosis, heart failure, hypogonadotropic hypogonadism and diabetes, appear earlier and are more severe than in HFE-related hemochromatosis. This disorder, therefore, requires an aggressive therapeutic approach to achieve iron depletion. We report here the case of a young Italian female with juvenile hemochromatosis who was unable to tolerate frequent phlebotomy because of coexistent ss-thalassemia trait. The patient was successfully iron-depleted by combining phlebotomy with recombinant human erythropoietin.
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PMID:Juvenile hemochromatosis associated with B-thalassemia treated by phlebotomy and recombinant human erythropoietin. 1094 34

Hereditary hemochromatosis is one of the most common autosomal recessive disorder among Caucasians since the genotype at risk for hemochromatosis accounts for 1:200-400 individuals of Northern European ancestry. The disease is characterized by an inappropriately increased intestinal iron absorption leading to early abnormalities of iron parameters followed by iron deposition in different organs. Excessive iron causes tissue damage and fibrosis, leading to organ failure. Clinical complications appear late in life and include liver cirrhosis, diabetes, cardiomyopathy, hypogonadism, arthropathy, skin pigmentation and susceptibility to liver cancer. Clinical symptoms develop only in homozygotes. Heterozy-gotes may show abnormalities of iron parameters, but are not clinically affected, unless carriers of other conditions which modify iron metabolism, such as chronic liver diseases, beta-thalassemia trait or other haemolytic anemias. The phenotypic expression of the disease is variable even within the same family, due to the effect of modifier genes or to environmental factors. Recent progress of genetics and molecular biology have shown that hemochromatosis is an heterogeneous disease, that may result from the inactivation of different genes. The identification of mutations of HFE and of other genes involved in the disease has allowed to develop molecular tests to support early diagnosis, allowing also to ameliorate the differential diagnosis with other iron loading disorders. In addition, the increased knowledge acquired from the study of hemochromatosis has contributed to clarify the pathophysiology of iron metabolism. For this reason hemochromatosis is considered a typical example of molecular medicine.
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PMID:Inherited hemochromatosis: from genetics to clinics. 1617 62

An African American male of West Indies descent was diagnosed to have elevated transferrin saturation, hyperferritinemia, severe iron deposition in hepatocytes, and hepatic cirrhosis at age 4. He was treated with serial phlebotomy to maintain a normal serum ferritin concentration thereafter. We evaluated him at age 23 and confirmed that he had normal serum ferritin levels, severe iron deposition in hepatocytes, hepatic cirrhosis, and portal hypertension. He did not have endocrinopathy, cardiomyopathy, or arthropathy. He was homozygous for the novel hemojuvelin (HJV) premature stop-codon mutation R54X (exon 3; c.160A-->T). He did not have either HFE C282Y, H63D, or S65C, or deleterious coding region mutations of SLC40A1, TFR2, or HAMP. His erythrocyte measures and hemoglobin electrophoresis were consistent with alpha-thalassemia trait. We conclude that homozygosity for HJV R54X accounts for his severe, early age-of-onset hemochromatosis; his phenotype was probably modified by serial phlebotomy therapy.
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PMID:Early age-of-onset iron overload and homozygosity for the novel hemojuvelin mutation HJV R54X (exon 3; c.160A-->T) in an African American male of West Indies descent. 1849 90