Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantitative determination of Schistosoma mansoni infection was carried out on 1995 cane cutters of the Hippo Valley and Triangle Sugar Estates. A total of 315 cutters were chosen for the study on the basis of S. mansoni infection and lack of anti-schistosomal chemotherapy during the previous three years. Stool consistency and blood and mucus in stool were determined for all the infected cutters. Overt and occult blood in stool was detected in a significantly high number of infected people compared to the control subjects (chi 2 p less than 0.001). However, the blood loss was found to have no anaemia-producing effect as determined by haemoglobin and red blood cell counts. Watery stool was prevalent among people with egg output exceeding 500 eggs per gram of stool. Mucus in stool was found to be more prevalent among infected people compared to the control subjects but the difference was not significant (p greater than 0.05). Symmer's periportal fibrosis (PPF) of various degrees of severity was detected in 47% of the infected people and grade one liver fibrosis was found in 7.5% of the control subjects (p less than 0.0001). Some 54.5% of those infected complained of abdominal pains compared to 35% of uninfected controls (p less than 0.01). There was a significant difference in the rate of absenteeism from work due to abdominal pains and diarrhoea among the infected and uninfected cane cutters (p less than 0.02).
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PMID:Morbidity due to Schistosoma mansoni among sugar-cane cutters in Zimbabwe. 195 65

We report on two sibs with syndromal congenital iron storage disease. Prenatal symptoms were IUGR, hydramnios, and placental hyperplasia. Clinical anomalies included hypertelorism and sparse, thin, curly hair (trichomalacia). Clinical course was marked by intractable diarrhoea, with normal histological and enzymological studies, cholestatic jaundice, hepatomegaly appearing after 30 days, and progressive liver failure, leading to death after a few months. The only metabolic anomaly was progressive hypermethioninemia. Pathologic examination of both children showed a similar pattern of multivisceral iron deposit compatible with a diagnosis of neonatal hemochromatosis: extensive liver fibrosis or cirrhosis with nodular regeneration, cholestasis, ductular proliferation, and hepatic, pituitary, thyroidal, adrenal, and pancreatic iron deposition. The unusual course for neonatal hemochromatosis in both sibs combined with concordant extrahepatic anomalies suggest that they could have a specific iron storage syndrome with possible autosomal recessive inheritance, probably similar to the sibship reported by Stanckler et al. [Arch Dis Child, 57:212-216, 1982].
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PMID:Tricho-hepato-enteric syndrome: further delineation of a distinct syndrome with neonatal hemochromatosis phenotype, intractable diarrhea, and hair anomalies. 902 Oct 8

Parasitologic, clinicopathologic, and pathologic aspects of Schistosoma japonicum infections of varying durations and intensities were studied in growing pigs injected intramuscularly with a dose of either 0, 100, 500, or 2,000 cercariae and killed at 4, 11, 17, or 24 weeks postinfection (PI). The number of viable worm pairs decreased significantly in the high dose group after 11 weeks PI but not in the lower dose groups; however, a stable population of immature worms persisted throughout the study in all dose groups. Liver egg counts also tended to decrease in the high dose group after 11 weeks but not in the other groups. Fecal egg excretion began at six weeks PI, was highest at eight weeks PI with a pronounced peak occurring only in the high dose group, and then decreased to low levels by 14 weeks PI in all groups. Egg counts from the feces as well as the liver correlated strongly with worm pair numbers during the acute phase of infection. The only clinicopathologic abnormality observed was an increase in circulating eosinophils corresponding to cercarial dose in all infected pigs by week six with peak counts occurring between six and eight weeks PI. The pigs exhibited no clinical signs of disease aside from diarrhea at the onset of patency. However, lesions were present throughout the large intestine of all infected pigs from 11 weeks PI, gradually decreasing with time. Severe liver fibrosis occurred in the 500 and 2,000 dose groups mainly at 11 weeks PI and then decreased in severity. In the liver, but not in the intestine, the severity of lesions at all time points was proportional to the cercarial dose given. The results indicate that after several weeks of patency, pigs with high intensities of S. japonicum infection are able to effectively eliminate the majority of adult worms while maintaining a stable population of immature schistosomes.
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PMID:Schistosoma japonicum in the pig: the host-parasite relationship as influenced by the intensity and duration of experimental infection. 950 11

This study assesses the long-term results of jejunoileal bypass (JIB) in 43 prospectively followed patients whose surgical bypass remained intact. Follow-up was 12.6+/-0.25 years from JIB. Weight loss and improved lipid levels, glucose tolerance, cardiac function, and pulmonary function were maintained. Adverse effects such as hypokalemia, cholelithiasis, and B12 or folate deficiency decreased over time. The incidence of diarrhea remained constant (63% vs 64% at five years), while the occurrence of hypomagnesemia increased (67% vs 43% at five years, P < 0.05). Nephrolithiasis occurred in 33% of patients. Hepatic fibrosis developed in 38% of patients and was progressive. Overall, after more than 10 years, 35% of patients appeared to benefit from JIB as defined by alleviation of preoperative symptoms and the development of only mild complications (vs 47% at five years). On the other hand, irreversible complications appeared to outweigh any benefit derived from the JIB in 19% (vs no patients at five years; P < 0.01). In summary, patients with JIB remain at risk for complications, particularly hepatic fibrosis, even into the late postoperative period.
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PMID:Long-term consequences after jejunoileal bypass for morbid obesity. 982 41

SCHISTOSOMA INTERCALATUM: Endemic in central Africa, S. intercalatum is the causal agent of this intestinal bilharziasis, which is similar to Mansoni's disease but with a characteristic lower localization (rectum and sigmoid). The principal clinical signs are digestive disorders: abdominal pain, diarrhea or dysentery, straining, tenesmus, rectal bleeding. The moderately enlarged liver is smooth and hard but not painful, especially observed in adolescents. ORIENTAL BILHARZIASIS: Schistosoma japonicum (found in lakes in China, Thailand, Philippines, Indonesia) and Schistosoma mekongi (Melong valley) are the principal agents. Both lead to major liver fibrosis producing severe portal hypertension and growth retardation in children.
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PMID:[Other forms of schistosomiasis]. 1107 81

It has not been fully determined whether isolated small bowel transplantation (ISBTx) can reverse liver dysfunction caused by intestinal failure requiring long-term total parenteral nutrition (TPN). A boy with congenital microvillus inclusion disease presented with vomiting and severe diarrhea since the first day of life and had been managed by TPN since then. He suffered from catheter-related sepsis several times. At 14 yr of age he developed progressive hepatosplenomegaly with thrombocytopenia and coagulopathy. He underwent ISBTx with an ileal graft from his blood-identical grandmother at the age of 16 yr. Oral feeding was started on the 14th day after ISBTx and gradually increased. TPN was completely withdrawn after 5 months. Liver was palpated 5 cm below the costal margin before ISBTx, while it became non-palpable 5 months after ISBTx. Serum liver enzyme levels and prothrombin time normalized in the 5 months following ISBTx. Liver biopsy showed marked steatosis, slight cholestasis, and mild bridging fibrosis before ISBTx. Although histological examination of liver biopsy revealed complete disappearance of steatosis 7 and 11 months after ISBTx, liver fibrosis remained unchanged. This clinical experience has shown that although steatosis and cholestasis are reversible after successful ISBTx and withdrawal of TPN, liver fibrosis may remain unchanged.
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PMID:Effects of isolated small bowel transplantation on liver dysfunction caused by intestinal failure and long-term total parenteral nutrition. 1210 May 9

PFIC 1 is a genetic disorder characterized by hepatic and gastrointestinal disease, often requiring LT during childhood. Extrahepatic symptoms, such as diarrhea and malabsorption, do not improve or may be aggravated after LT, as graft steatosis or steatohepatitis as consequences of the interaction between transplanted liver and native bowel. We describe a patient with PFIC 1 who presented with cholestasis in infancy, who developed intractable pruritus and liver fibrosis. The child underwent living donor LT at 3.6 yr of age, and he early developed severe refractory diarrhea, secondary malabsorption with protein-losing enteropathy, and an early fatty liver disease trough graft steatohepatitis. As the response to cholestyramine was unsatisfactory, we decided to perform an EBD by using the jejunal loop used for the cholangiojejunostomy. Diarrhea resolved rapidly after surgery. He remained well after six months following biliary diversion, with normal stool output and no protein loss. We documented a dramatic improvement of graft steatosis at histology as well as normalization of liver function test. EBD can be considered a valuable treatment option to avoid organ disfunction and loss in PFIC 1 transplanted patients who develop graft steatohepatitis.
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PMID:Recovery of graft steatosis and protein-losing enteropathy after biliary diversion in a PFIC 1 liver transplanted child. 2167 3

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation.
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PMID:Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. 2234 19

Individuals with congenital disorders of glycosylation (CDG) have recessive mutations in genes required for protein N-glycosylation, resulting in multi-systemic disease. Despite the well-characterized biochemical consequences in these individuals, the underlying cellular defects that contribute to CDG are not well understood. Synthesis of the lipid-linked oligosaccharide (LLO), which serves as the sugar donor for the N-glycosylation of secretory proteins, requires conversion of fructose-6-phosphate to mannose-6-phosphate via the phosphomannose isomerase (MPI) enzyme. Individuals who are deficient in MPI present with bleeding, diarrhea, edema, gastrointestinal bleeding and liver fibrosis. MPI-CDG patients can be treated with oral mannose supplements, which is converted to mannose-6-phosphate through a minor complementary metabolic pathway, restoring protein glycosylation and ameliorating most symptoms, although liver disease continues to progress. Because Mpi deletion in mice causes early embryonic lethality and thus is difficult to study, we used zebrafish to establish a model of MPI-CDG. We used a morpholino to block mpi mRNA translation and established a concentration that consistently yielded 13% residual Mpi enzyme activity at 4 days post-fertilization (dpf), which is within the range of MPI activity detected in fibroblasts from MPI-CDG patients. Fluorophore-assisted carbohydrate electrophoresis detected decreased LLO and N-glycans in mpi morphants. These deficiencies resulted in 50% embryonic lethality by 4 dpf. Multi-systemic abnormalities, including small eyes, dysmorphic jaws, pericardial edema, a small liver and curled tails, occurred in 82% of the surviving larvae. Importantly, these phenotypes could be rescued with mannose supplementation. Thus, parallel processes in fish and humans contribute to the phenotypes caused by Mpi depletion. Interestingly, mannose was only effective if provided prior to 24 hpf. These data provide insight into treatment efficacy and the broader molecular and developmental abnormalities that contribute to disorders associated with defective protein glycosylation.
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PMID:A zebrafish model of congenital disorders of glycosylation with phosphomannose isomerase deficiency reveals an early opportunity for corrective mannose supplementation. 2289 57

An obese 55-year-old woman with nonalcoholic fatty liver disease presented 7 years after resection of a T3N1 ileal carcinoid tumor with an elevated chromogranin A, multifocal metastatic disease to the liver, and carcinoid syndrome. She underwent right hepatic artery yttrium-90 (Y90) radioembolization, followed a month later by selective Y90 treatment to segment IV. She then presented to our clinic 10 months later, remaining symptomatic with flushing, diarrhea, anxiety, myalgia, pain, and persistent night sweats despite Sandostatin administration. At least 11 tumors were identified in the right lobe of the liver and three in segment IV on liver-specific imaging. These lesions were stable over a year with no new lesions. At exploration, there was marked hypertrophy of the left lateral segment due to the yttrium-90 treatment of segments IV-VIII, corresponding with preoperative volumetrics predicting a functional liver remnant (FLR) of 40% after extended right hepatectomy. The right lobe and segment IV were fibrotic, hard, and visibly damaged. The gland had a thick, fibrotic capsule, and the parenchyma was dense, inflexible, and difficult to dissect, consistent with the previously reported morbidity of these operations. Extended right hepatectomy was performed. Final pathology demonstrated 15 foci of metastatic well-differentiated neuroendocrine carcinoma that were negative for necrosis, as was expected given her continued symptoms despite radioembolization. Numerous amorphous spheres, frequently in clusters, were present in segments IV-VIII in vessels and approximating tumors consistent with prior Y90 radioembolization. The patient had an uneventful post-operative recovery and remains symptom free on follow-up. Treatment options for metastatic tumors to the liver have increased in recent years and currently include radioembolization in selected patients. Surgical cytoreduction and complete metastasectomy continue to offer improvement in symptoms, quality of life, and survival in patients with neuroendocrine liver metastases; however, hepatectomy after radioembolization is unique and carries increased morbidity/mortality, likely due to Y90-induced liver fibrosis. We demonstrate images of fibrotic yttrium-90 radiation-affected liver and histological sections of radioembolic microbeads in blood vessels and distributed around resected tumors.
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PMID:Hepatectomy After Yttrium-90 (Y90) Radioembolization-Induced Liver Fibrosis. 2684 53


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