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Sample records for acute hepatic porphyria

  1. Acute Hepatic Porphyria

    PubMed Central

    Bissell, D. Montgomery; Wang, Bruce

    2015-01-01

    The porphyrias comprise a set of diseases, each representing an individual defect in one of the eight enzymes mediating the pathway of heme synthesis. The diseases are genetically distinct but have in common the overproduction of heme precursors. In the case of the acute (neurologic) porphyrias, the cause of symptoms appears to be overproduction of a neurotoxic precursor. For the cutaneous porphyrias, it is photosensitizing porphyrins. Some types have both acute and cutaneous manifestations. The clinical presentation of acute porphyria consists of abdominal pain, nausea, and occasionally seizures. Only a small minority of those who carry a mutation for acute porphyria have pain attacks. The triggers for an acute attack encompass certain medications and severely decreased caloric intake. The propensity of females to acute attacks has been linked to internal changes in ovarian physiology. Symptoms are accompanied by large increases in delta-aminolevulinic acid and porphobilinogen in plasma and urine. Treatment of an acute attack centers initially on pain relief and elimination of inducing factors such as medications; glucose is administered to reverse the fasting state. The only specific treatment is administration of intravenous hemin. An important goal of treatment is preventing progression of the symptoms to a neurological crisis. Patients who progress despite hemin administration have undergone liver transplantation with complete resolution of symptoms. A current issue is the unavailability of a rapid test for urine porphobilinogen in the urgent-care setting. PMID:26357631

  2. The acute hepatic porphyrias: current status and future challenges.

    PubMed

    Siegesmund, Marko; van Tuyll van Serooskerken, Anne-Moniek; Poblete-Gutiérrez, Pamela; Frank, Jorge

    2010-10-01

    The porphyrias are predominantly inherited metabolic disorders, which result from a specific deficiency of one of the eight enzymes along the pathway of haem biosynthesis. Historically, they have been classified into hepatic and erythropoietic forms, based on the primary site of expression of the prevailing dysfunctional enzyme. From a clinical point of view, however, it is more convenient to subdivide them into acute and non-acute porphyrias, thereby primarily considering the potential occurrence of life-threatening acute neurovisceral attacks. Unrecognised or untreated, such an acute porphyric attack is associated with a significant mortality of up to 10%. The acute hepatic porphyrias comprise acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and δ-aminolevulinic acid dehydratase deficiency porphyria. Making a precise diagnosis may be difficult because the different types of porphyrias may show overlapping clinical and biochemical characteristics. To date, the therapeutic possibilities are limited and mainly symptomatic. In this overview we report on what is currently known about pathogenesis, clinic, diagnostics, and therapy of the acute hepatic porphyrias. We further point out actual and future challenges in the management of these diseases.

  3. [Hepatic porphyrias with cutaneous symptoms].

    PubMed

    Timonen, Kaisa; Nuutinen, Pauliina; Raili, Kauppinen

    2012-01-01

    Hepatic porphyrias with cutaneous symptoms Cutaneous symptoms of porphyrias are initiated from a phototoxic reaction caused by sunlight and circulating porphyrins in the vascular walls of the skin. This leads in fragility, blistering and scarring of the skin on light-exposed areas. There are approximately 200 patients having hepatic porphyrias with cutaneous symptoms in Finland. Cutaneous symptoms of variegate porphyria and porphyria cutanea tarda are indistinguishable, but an effective treatment is available only for the latter. Differential diagnosis is important due to acute episodes occurring in variegate porphyria.

  4. [Porphyrias].

    PubMed

    Stölzel, U; Stauch, T; Doss, M O

    2010-12-01

    Porphyrias are metabolic disorders of the heme biosynthesis. Clinically, they can be differentiated into acute and non-acute porphyrias. The symptomatic phase of acute hepatic porphyrias is characterized by overproduction of neurotoxic porphyrin precursors and porphyrins. Acute intermittent porphyria, Variegate porphyria, Hereditary coproporphyria and Doss porphyria belong to this group of metabolic disorders. The clinical presentation of the acute hepatic porphyria syndrome includes abdominal, psychiatric, neurological and cardiovascular symptoms. The diagnosis is based on a tenfold increased urinary excretion of porphobilinogen (apart from Doss porphyria). Besides symptomatic therapy with non-porphyrinogenic drugs, electrolyte compensation and intensive monitoring, intravenous administration of glucose and heme arginate is established for treatment. Among the non-acute types like Porphyria cutanea tarda, Erythropoietic protoporphyria and Congenital erythropoietic porphyria, the accumulated porphyrins cause photosensitivity of the skin up to severe liver damage. The location of the deficient enzyme within the heme biosynthesic pathway determines the pattern of the accumulated porphyrins. Besides light protection, there are different therapies depending on the type of non-acute porphyria. Ultimately, liver transplantation may be considered in therapy-resistant cases of acute hepatic porphyrias and bone marrow transplantation in severe cases of erythropoietic porphyrias.

  5. Hepatic alteration of tryptophan metabolism in an acute porphyria model Its relation with gluconeogenic blockage.

    PubMed

    Lelli, Sandra M; Mazzetti, Marta B; San Martín de Viale, Leonor C

    2008-02-01

    This study focuses on the alterations suffered by the serotoninergic and kinurenergic routes of tryptophan (TRP) metabolism in liver, and their relation with gluconeogenic phosphoenolpyruvate-carboxykinase (PEPCK) blockage in experimental acute porphyria. This porphyria was induced in rats by a combined treatment of 2-allyl-2-isopropylacetamide (100, 250, 500 mg/kg bw) and 3,5-dietoxicarbonil 1,4-dihydrocollidine (constant 50 mg/kg bw dose). Results showed a marked dose-dependent increase of all TRP pyrrolase (TRPp) forms, active (holo, total) and inactive (apo), and a decrease in the degree of enzyme saturation by heme. Increases for holo, total, and apo-TRPp were 90, 150, and 230%, respectively, at the highest dose assayed (H). The treatment also impaired the serotoninergic route of TRP metabolism in liver, causing a decrease in serotonin level (H, 38%), and a concomitant enhancement in TRP content (H, 23%). The porphyrinogenic treatment promoted a blockage in PEPCK activity (H, 30%). This occurred in correlation to the development of porphyria, to TRPp alterations and to the production of hepatic microsomal thiobarbituric acid reactive substances. Porphyria was estimated through increases in 5-aminolevulinic acid-synthase (ALA-S) activity, ALA and porphobilinogen contents, and a decrease in ferrochelatase activity. Thus, the TRP kynurenine route was augmented whereas the serotoninergic route was reduced. PEPCK blockage could be partly attributed to quinolinate generated from TRP by the increase of TRPp activity, which would be due to the effect of porphyrinogenic drugs on TRP. The contribution of ROS to PEPCK blockage is analyzed. Likewise, the implication of these results in the control of porphyrias by glucose is discussed.

  6. Porphyria

    MedlinePlus

    Acute intermittent porphyria; Hereditary coproporphyria; Congenital erythropoietic porphyria; Erythropoietic protoporphyria ... during several steps of this process. People with porphyria are lacking certain enzymes needed for this process. ...

  7. [Acute intermittent porphyria].

    PubMed

    Catania, A; Caimi, G

    1983-11-10

    Acute intermittent porphyria (AIP) is a congenital disease which as its name suggests, runs intermittently. Biochemically it is characterised by over-production of hepatic ALA synthetase (ALA-s), inducible mitochondrial enzyme and an increase in prophyrinic precursors (PBG, ac S-ALA). Clinically it is characterised by an abdominal nervous symptomatology. The primary metabolic error has been identified as a deficiency in enzyme activity which partially blocks haem biosynthesis. During the appearance of clinical manifestations, certain factors are present which have the capacity of inducing hepatic ALA-s production in vitro. Apart from some preventive measures treatment is mainly of symptomatology and complications. More recently the use of ALA-s inhibitors has been introduced. PMID:6657112

  8. Weight Loss & Acute Porphyria

    MedlinePlus

    ... Sale You are here Home Diet and Nutrition Weight loss & acute Porphyria Being overweight is a particular problem ... one of these diseases before they enter a weight-loss program. Also, they should not participate in a ...

  9. Intermittent hepatic porphyria in pregnancy with good perinatal outcome.

    PubMed

    Vidosavljević, Domagoj; Sijanović, Siniša; Rubin, Mirjana; Košuta Petrović, Maja; Abičić Žuljević, Kristina; Simić, Ivana

    2012-02-01

    Porphyrias are rare metabolic diseases caused by enzymatic defects of the haeme biosynthesis. Association of pregnancy and acute porphyria is rare, but mortality rate among pregnant women from acute attack has been reported up to 42%. This paper presents a patient with pregnancy complicated by intermittent hepatic porphyria with good perinatal outcome. The pattern of the attack in pregnancy varies individually and it makes porphyric pregnancies a challenge. Previously diagnosed porphyria patients should be closely monitored during pregnancy and diagnosis of acute porphyria must be also considered in all pregnant women with unexplained abdominal pain.

  10. The neurologic manifestations of the acute porphyrias.

    PubMed

    Simon, Neil G; Herkes, Geoffrey K

    2011-09-01

    The porphyrias are diseases characterised by accumulation of porphyrins and porphyrin precursors owing to enzymatic deficiencies of the haem synthetic pathway. In the acute hepatic porphyrias accumulation of porphyrin precursors, in particular delta-aminolaevulinic acid (ALA), cause dysfunction of the central, peripheral and autonomic nervous systems. This leads to the characteristic clinical findings of abdominal pain, neuropsychiatric symptoms and neuropathy. The exact pathogenic mechanism is not clear but evidence to date suggests both direct toxic effects of ALA and intracellular metabolic derangement contribute to the neurologic disorders. This review explores the mechanisms of neural dysfunction in the acute porphyrias and the resultant clinical features of an acute attack.

  11. RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice.

    PubMed

    Yasuda, Makiko; Gan, Lin; Chen, Brenden; Kadirvel, Senkottuvelan; Yu, Chunli; Phillips, John D; New, Maria I; Liebow, Abigail; Fitzgerald, Kevin; Querbes, William; Desnick, Robert J

    2014-05-27

    The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks. Factors that induce the expression of hepatic 5-aminolevulinic acid synthase 1 (ALAS1) result in the accumulation of the neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which recent studies indicate are primarily responsible for the acute attacks. Current treatment of these attacks involves i.v. administration of hemin, but a faster-acting, more effective, and safer therapy is needed. Here, we describe preclinical studies of liver-directed small interfering RNAs (siRNAs) targeting Alas1 (Alas1-siRNAs) in a mouse model of acute intermittent porphyria, the most common acute hepatic porphyria. A single i.v. dose of Alas1-siRNA prevented the phenobarbital-induced biochemical acute attacks for approximately 2 wk. Injection of Alas1-siRNA during an induced acute attack significantly decreased plasma ALA and PBG levels within 8 h, more rapidly and effectively than a single hemin infusion. Alas1-siRNA was well tolerated and a therapeutic dose did not cause hepatic heme deficiency. These studies provide proof-of-concept for the clinical development of RNA interference therapy for the prevention and treatment of the acute attacks of the acute hepatic porphyrias.

  12. Liver Transplantation for Acute Intermittent Porphyria is Complicated by a High Rate of Hepatic Artery Thrombosis

    PubMed Central

    Dowman, Joanna K; Gunson, Bridget K; Mirza, Darius F; Bramhall, Simon R; Badminton, Mike N; Newsome, Philip N

    2012-01-01

    Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the UK Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation. Liver Transpl 18:195–200, 2012. © 2011 AASLD. PMID:21618697

  13. Anxiety and depression in the acute porphyrias.

    PubMed

    Millward, L M; Kelly, P; King, A; Peters, T J

    2005-01-01

    A previous study of self-rated psychosocial aspects in patients with acute porphyria found that depression, and particularly anxiety, is more common in porphyria patients than in the general population or general medical outpatient attenders. Nearly half of the sample (46%) reported at least some problem with anxiety and/or depression: anxiety caseness was 26% and depression caseness was 13%. This paper extends our previous observations and investigates further the associations between porphyria and anxiety, depression and general mental health in 90 patients (58 acute intermittent porphyria, 32 variegate porphyria). The findings of this study confirm that anxiety is raised in patients with acute intermittent porphyria and with variegate porphyria, in both males and females, compared to the normative population and, using a series of questionnaires exploring the physical and psychosocial features of anxiety, that this anxiety is experienced as a 'relatively stable personality trait', rather than a 'transitory emotional state' (i.e. intrinsic rather than secondary to the porphyria).

  14. Porphyrias.

    PubMed

    Puy, Hervé; Gouya, Laurent; Deybach, Jean-Charles

    2010-03-13

    Hereditary porphyrias are a group of eight metabolic disorders of the haem biosynthesis pathway that are characterised by acute neurovisceral symptoms, skin lesions, or both. Every porphyria is caused by abnormal function of a separate enzymatic step, resulting in a specific accumulation of haem precursors. Seven porphyrias are the result of a partial enzyme deficiency, and a gain of function mechanism has been characterised in a new porphyria. Acute porphyrias present with acute attacks, typically consisting of severe abdominal pain, nausea, constipation, confusion, and seizure, and can be life-threatening. Cutaneous porphyrias present with either acute painful photosensitivity or skin fragility and blisters. Rare recessive porphyrias usually manifest in early childhood with either severe cutaneous photosensitivity and chronic haemolysis or chronic neurological symptoms with or without photosensitivity. Porphyrias are still underdiagnosed, but when they are suspected, and dependent on clinical presentation, simple first-line tests can be used to establish the diagnosis in all symptomatic patients. Diagnosis is essential to enable specific treatments to be started as soon as possible. Screening of families to identify presymptomatic carriers is crucial to decrease risk of overt disease of acute porphyrias through counselling about avoidance of potential precipitants.

  15. Acute Intermittent Porphyria in Argentina: An Update

    PubMed Central

    Cerbino, Gabriela Nora; Gerez, Esther Noemí; Varela, Laura Sabina; Melito, Viviana Alicia; Parera, Victoria Estela; Rossetti, María Victoria

    2015-01-01

    Porphyrias are a group of metabolic diseases that arise from deficiencies in the heme biosynthetic pathway. A partial deficiency in hydroxymethylbilane synthase (HMBS) produces a hepatic disorder named Acute Intermittent Porphyria (AIP); the acute porphyria is more frequent in Argentina. In this paper we review the results obtained for 101 Argentinean AIP families and 6 AIP families from foreign neighbour countries studied at molecular level at Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP). Thirty-five different mutations were found, of which 14 were described for the first time in our population. The most prevalent type of mutations was the missense mutations (43%) followed by splice defects (26%) and small deletions (20%). An odd case of a double heterozygous presentation of AIP in a foreign family from Paraguay is discussed. Moreover, it can be noted that 38 new families were found carrying the most frequent mutation in Argentina (p.G111R), increasing to 55.66% the prevalence of this genetic change in our population and adding further support to our previous hypothesis of a founder effect for this mutation in Argentina. Identification of patients with an overt AIP is important because treatment depends on an accurate diagnosis, but more critical is the identification of asymptomatic relatives to avoid acute attacks which may progress to death. PMID:26075277

  16. Acute intermittent porphyria in Argentina: an update.

    PubMed

    Cerbino, Gabriela Nora; Gerez, Esther Noemí; Varela, Laura Sabina; Melito, Viviana Alicia; Parera, Victoria Estela; Batlle, Alcira; Rossetti, María Victoria

    2015-01-01

    Porphyrias are a group of metabolic diseases that arise from deficiencies in the heme biosynthetic pathway. A partial deficiency in hydroxymethylbilane synthase (HMBS) produces a hepatic disorder named Acute Intermittent Porphyria (AIP); the acute porphyria is more frequent in Argentina. In this paper we review the results obtained for 101 Argentinean AIP families and 6 AIP families from foreign neighbour countries studied at molecular level at Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP). Thirty-five different mutations were found, of which 14 were described for the first time in our population. The most prevalent type of mutations was the missense mutations (43%) followed by splice defects (26%) and small deletions (20%). An odd case of a double heterozygous presentation of AIP in a foreign family from Paraguay is discussed. Moreover, it can be noted that 38 new families were found carrying the most frequent mutation in Argentina (p.G111R), increasing to 55.66% the prevalence of this genetic change in our population and adding further support to our previous hypothesis of a founder effect for this mutation in Argentina. Identification of patients with an overt AIP is important because treatment depends on an accurate diagnosis, but more critical is the identification of asymptomatic relatives to avoid acute attacks which may progress to death.

  17. Porphyrias.

    PubMed

    Kauppinen, Raili

    Seven different porphyrias form a group of inherited metabolic disorders, each resulting from a partial deficiency of a specific enzyme in the haem biosynthesis pathway. Clinically, the three most important entities are an acute porphyric attack and acute and chronic skin symptoms. Porphyrias are rare and sometimes misdiagnosed, because various symptoms and signs mimic other diseases. Once porphyria is suspected, biochemical analyses easily detect porphyrins and their precursors from blood, urine, or faeces. Mutation screening can be done at the quiescent phase of the disease. Pathogenetic mechanisms and clinical manifestations differ in individual porphyrias and most of them require a specific treatment. Early diagnosis and information about precipitating factors can diminish mortality and prevent subsequent attacks among patients with acute porphyrias, so mutation screening is recommended for family members.

  18. Glucose Effect in the Acute Porphyrias

    MedlinePlus

    ... You are here Home Diet and Nutrition The glucose effect in acute porphyrias The disorders Acute Intermittent ... are treated initially with the administration of carbohydrate/glucose. This therapy has its basis in the ability ...

  19. A family with acute intermittent porphyria.

    PubMed

    Billoo, Abdul Gaffar; Lone, Saira Waqar

    2008-05-01

    Porphyrias are inherited defects in heme metabolism that result in excessive secretion of porphyrins and porphyrin precursors. Porphyrias can be classified into acute, (neuropsychiatric), cutaneous and mixed forms. There are seven main types of porphyrias; acute intermittent porphyria and plumboporphyria are predominantly neuropsychiatric; congenital erythropoietic porphyria, porphyria cutanea tarda and erythropoietic protoporphyria have predominantly cutaneous manifestations and hereditary coproporphyria and variegate porphyria are classified as mixed as they both have neuropsychiatric and cutaneous features. They cause life-threatening attacks of neurovisceral symptoms that mimic many other acute medical and psychiatric conditions. Lack of clinical recognition often delays effective treatment, and inappropriate diagnostic tests may lead to misdiagnosis and inappropriate treatment. Although the specific enzyme and gene defect have been identified, diagnosis and treatment of these disorders present formidable challenges because their signs and symptoms mimic other common conditions. We present a case report of a 13 years old girl who suffers from acute intermittent porphyria and the family tree showing all members who suffer from it.

  20. Manifestation of psychiatric behaviors in a mouse model of griseofulvin-induced hepatic porphyria.

    PubMed

    Satoh, Yoko; Iwadate, Reiko; Watanabe, Yukino; Kawai, Hiroshi; Kudo, Naomi; Kawashima, Yoichi; Mitsumoto, Atsushi

    2008-12-01

    Most patients with hepatic porphyria exhibit neuropsychiatric symptoms, including abdominal pain, peripheral neuropathy, confusion, insomnia and mental disturbances such as anxiety and depression. Although heme deficiency and accumulation of heme precursors are thought to be responsible for neuropsychiatric manifestations in patients with acute porphyria, the pathogenetic mechanisms remain poorly understood. In the present study, we observed psychiatric behaviors in mice with hepatic porphyria induced by the ingestion of a griseofulvin (GF)-containing diet over a period of 12 weeks. GF ingestion by the mice caused an accumulation of porphyrins in the feces and a decrease in heme in the liver; these effects were observed throughout the entire duration of the experiment, with maximum levels observed after circa 1 week of ingestion of this diet. In addition, the mice developed enlargement of the liver, hepatocyte injury, and cholestasis. Mice with hepatic porphyria manifested an anxiety-like behavior by the long-term treatment (over 5 weeks) in a GF-dose and duration dependent manner. The hepatic porphyria mice also manifested depression-like behaviors by the short-term treatment (3 weeks) of GF2.0, which was reversed by administration of anti-depressant, imipramine. In conclusion, this study for the first time demonstrated psychiatric manifestations in GF-induced hepatic porphyria mice. The present results suggest that model animals could be useful for elucidating the mechanisms underlying psychiatric manifestations in syndromes such as hepatic porphyria and hepatic encephalopathy that are associated with the impairment of hepatic function.

  1. Markers for vulnerability in acute porphyria. A hypothesis paper.

    PubMed

    Thunell, S; Andersson, C; Carlmark, B; Floderus, Y; Grönqvist, S O; Harper, P; Henrichson, A; Lindh, U

    1995-04-01

    Previously symptomatic and permanently asymptomatic carriers of a gene mutation for acute intermittent porphyria as well as matched controls were screened with regard to a series of variables of possible relevance to the development of porphyric symptoms. The basis for the study was a concept of acute porphyria as a condition of a permanent system overload of oxidative stress, with long term effects on hepatic and renal tissue, and with instances of periodic overload of free radicals giving rise to acute neurologic involvement. Leukocyte concentrations of manganese, calcium, iron and zinc, as well as erythrocyte calcium differed between the groups, acute intermittent porphyria gene carriers, irrespective of previous porphyric illness, showing significantly higher levels than the controls. Manganese was found to be the most discriminative component of all the 78 variables investigated, accounting for about 98 per cent of the variance between the groups. An increment, by a factor of four, in cellular manganese is suggestive of an increase, in acute intermittent porphyria, of a manganese associated enzyme, e.g. glutamine synthetase, pyruvate carboxylase or mitochondrial superoxide dismutase. The best fit into the model considered is provided by a theory focused on superoxide dismutase, induced in response to superoxide anion radical produced from aminolaevulinic acid. In porphyria gene carriers seemingly resistant to porphyric manifestations, an increase in potentially prooxidant cellular iron is matched by a proportional increment in manganese, i.e. presumably by a corresponding mitochondrial superoxide dismutase induction. This mechanism is not operative in porphyric individuals prone to development of neuropsychiatric symptoms. In acute intermittent porphyria with a history of porphyric illness there is a positive correlation between erythrocyte manganese and serum folate and a negative correlation between leukocyte ferrochelatase activity and serum cobalamin

  2. Markers for vulnerability in acute porphyria. A hypothesis paper.

    PubMed

    Thunell, S; Andersson, C; Carlmark, B; Floderus, Y; Grönqvist, S O; Harper, P; Henrichson, A; Lindh, U

    1995-04-01

    Previously symptomatic and permanently asymptomatic carriers of a gene mutation for acute intermittent porphyria as well as matched controls were screened with regard to a series of variables of possible relevance to the development of porphyric symptoms. The basis for the study was a concept of acute porphyria as a condition of a permanent system overload of oxidative stress, with long term effects on hepatic and renal tissue, and with instances of periodic overload of free radicals giving rise to acute neurologic involvement. Leukocyte concentrations of manganese, calcium, iron and zinc, as well as erythrocyte calcium differed between the groups, acute intermittent porphyria gene carriers, irrespective of previous porphyric illness, showing significantly higher levels than the controls. Manganese was found to be the most discriminative component of all the 78 variables investigated, accounting for about 98 per cent of the variance between the groups. An increment, by a factor of four, in cellular manganese is suggestive of an increase, in acute intermittent porphyria, of a manganese associated enzyme, e.g. glutamine synthetase, pyruvate carboxylase or mitochondrial superoxide dismutase. The best fit into the model considered is provided by a theory focused on superoxide dismutase, induced in response to superoxide anion radical produced from aminolaevulinic acid. In porphyria gene carriers seemingly resistant to porphyric manifestations, an increase in potentially prooxidant cellular iron is matched by a proportional increment in manganese, i.e. presumably by a corresponding mitochondrial superoxide dismutase induction. This mechanism is not operative in porphyric individuals prone to development of neuropsychiatric symptoms. In acute intermittent porphyria with a history of porphyric illness there is a positive correlation between erythrocyte manganese and serum folate and a negative correlation between leukocyte ferrochelatase activity and serum cobalamin

  3. Liver transplantation as a cure for acute intermittent porphyria.

    PubMed

    Soonawalla, Zahir F; Orug, Taner; Badminton, Michael N; Elder, George H; Rhodes, Jonathan M; Bramhall, Simon R; Elias, Elwyn

    2004-02-28

    Acute intermittent porphyria occasionally causes frequent and crippling acute neurovisceral attacks associated with increased hepatic production of porphyrin precursors, resulting in long-term damage, poor quality of life, and shortened life expectancy. There has been no cure for this condition, but replacement of deficient hepatic enzymes might restore excretion of porphyrin precursors to normal and prevent acute attacks. We aimed to treat severe acute intermittent porphyria in a 19-year-old woman by liver transplantation. After the transplant, concentrations of haem precursors in the patient's urine returned to normal, and 1.5 years later her quality of life was good. Our report suggests some hope of cure for selected patients with severe forms of this disease. PMID:15001330

  4. Porphyria

    MedlinePlus

    ... it is exposed to sunlight. The nervous system type is called acute porphyria. Symptoms include pain in the chest, abdomen, limbs, or back; muscle numbness, tingling, paralysis, or cramping; vomiting; constipation; and personality changes or mental disorders. These symptoms come and ...

  5. Drugs and acute porphyrias: reasons for a hazardous relationship.

    PubMed

    Roveri, Giulia; Nascimbeni, Fabio; Rocchi, Emilio; Ventura, Paolo

    2014-11-01

    The porphyrias are a group of metabolic diseases caused by inherited or acquired enzymatic deficiency in the metabolic pathway of heme biosynthesis. Simplistically, they can be considered as storage diseases, because the partial enzymatic defect gives rise to a metabolic "bottleneck" in the biosynthetic pathway and hence to an accumulation of different metabolic intermediates, potentially toxic and responsible for the various (cutaneous or neurovisceral) clinical manifestations observed in these diseases. In the acute porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and the very rare delta-aminolevulinic acid dehydratase ALAD-d porphyria), the characteristic severe neurovisceral involvement is mainly ascribed to a tissue accumulation of delta-aminolevulinic acid, a neurotoxic nonporphyrin precursor. Many different factors, both endogenous and exogenous, may favor the accumulation of this precursor in patients who are carriers of an enzymatic defect consistent with an acute porphyria, thus contributing to trigger the serious (and potentially fatal) clinical manifestations of the disease (acute porphyric attacks). To date, many different drugs are known to be able to precipitate an acute porphyric attack, so that the acute porphyrias are also considered as pharmacogenetic or toxygenetic diseases. This article reviews the different biochemical mechanisms underlying the capacity of many drugs to precipitate a porphyric acute attack (drug porphyrogenicity) in carriers of genetic mutations responsible for acute porphyrias, and addresses the issue of prescribing drugs for patients affected by these rare, but extremely complex, diseases.

  6. [Acute intermittent porphyria and inappropriate ADH syndrome].

    PubMed

    Tébar, M T; Aguilera, L

    2010-05-01

    A 44-year-old woman complained of abdominal pain of 4 days' duration accompanied by vomiting and painful urination. The admitting physician noted neurologic signs consistent with axonal polyneuropathy and hyponatremia. In the absence of other explanations for the syndrome, SIADH was diagnosed. Because of the nonspecific nature of the observations, the patient was assessed by various specialists and admitted to the anesthetic recovery unit due to worsening of neurologic signs and suspicion of acute intermittent porphyria. The diagnosis was confirmed by laboratory findings of elevated d-aminolevulinic acid and porphobilinogen levels and normal stool porphyrins. The patient improved with intravenous hematin infused over 4 days.

  7. Acute Porphyria in a Patient with Arnold Chiari Malformation

    PubMed Central

    Shen, Jianbin; O’Keefe, Kevin; Webb, Lisa B.; DeGirolamo, Angela

    2015-01-01

    Patient: Female, 33 Final Diagnosis: Acute porphyria Symptoms: Abdominal pain • alternating bowel habits Medication: Metronidazole • bactrim • oxybutynin Clinical Procedure: EMG • porhyria workup Specialty: Neurology Objective: Rare disease Background: Acute porphyria and Arnold Chiari malformation are both uncommon genetic disorders without known association. The insidious onset, non-specific clinical manifestations, and precipitating factors often cause diagnosis of acute porphyria to be missed, particularly in patients with comorbidities. Case Report: A women with Arnold Chiari malformation type II who was treated with oxybutynin and antibiotics, including Bactrim for neurogenic bladder and recurrent urinary tract infection, presented with non-specific abdominal pain, constipation, and diarrhea. After receiving Flagyl for C. difficile colitis, the patient developed psychosis, ascending paralysis, and metabolic derangements. She underwent extensive neurological workup due to her congenital neurological abnormalities, most of which were unremarkable. As a differential diagnosis of Guillain Barré syndrome, acute porphyria was then considered and ultimately proved to be the diagnosis. After hematin administration and intense rehabilitation, the patient slowly recovered from the full-blown acute porphyria attack. Conclusions: This case report, for the first time, documents acute porphyria attack as a result of a sequential combination of 3 common medications. This is the first case report of the concomitant presence of both acute porphyria and Arnold Chiari malformation, 2 genetic disorders with unclear association. PMID:25697467

  8. Role of delta-Aminolevulinic Acid in the Symptoms of Acute Porphyria

    PubMed Central

    Bissell, D. Montgomery; Lai, Jennifer C.; Meister, Raymond K.; Blanc, Paul D.

    2015-01-01

    Background Attacks of neuropathic pain, usually abdominal, are characteristic of the acute porphyrias and are accompanied by overproduction of heme-precursor molecules, specifically delta-aminolevulinic acid and porphobilinogen. The basis for the acute symptoms in these diseases has been speculative. Methods We review genetic acute porphyria, hereditary tyrosinemia, and an acquired condition, lead poisoning. All perturb heme synthesis and present with a very similar pain syndrome. Results While each of these conditions has characteristic urine biochemistry, all exhibit excess delta-aminolevulinic acid. Moreover, in all, treatment with hemin reduces delta-aminolevulinic acid and relieves symptoms. In contrast, use of recombinant porphobilinogen deaminase to knock down porphobilinogen in acute porphyria was ineffective. Conclusion There is now convincing evidence that delta-aminolevulinic acid is the cause of pain in the acute porphyrias. The efficacy of hemin infusion is due mainly, if not entirely, to its inhibition of hepatic delta-aminolevulinic acid synthase-1, the enzyme that catalyzes delta-aminolevulinic acid formation. Delta-aminolevulinic acid synthase-1 is a rational target for additional therapies to control symptoms in acute porphyria. PMID:25446301

  9. Diagnosis of feline acute intermittent porphyria presenting with erythrodontia requires molecular analyses.

    PubMed

    Clavero, Sonia; Ahuja, Yuri; Bishop, David F; Kwait, Brittany; Haskins, Mark E; Giger, Urs; Desnick, Robert J

    2013-12-01

    Erythrodontia is the hallmark of human congenital erythropoietic porphyria (CEP), but is also a major phenotypic feature of acute intermittent porphyria (AIP) in cats. In this study, detailed biochemical and molecular analyses were performed on two unrelated cats with autosomal dominant AIP that presented with erythrodontia, yellow-brown urine and mild changes in erythrocytes. The cats had elevated concentrations of urinary 5-aminolevulinic acid and porphobilinogen, and half normal erythrocytic hydroxymethylbilane synthase (HMBS) activity. Two novel HMBS mutations were detected; one cat had a deletion (c.107_110delACAG) and one cat had a splicing alteration (c.826-1G>A), both leading to premature stop codons and truncated proteins (p.D36Vfs 6 and p.L276Efs 6, respectively). These studies highlight the importance of appropriate biochemical and molecular genetic analyses for the accurate diagnoses of porphyrias in cats and extend the molecular genetic heterogeneity of feline AIP. Thus, although erythrodontia is a classic sign of congenital erythropoietic porphyria in human beings, cats with erythrodontia may have acute intermittent porphyria, a hepatic porphyria.

  10. Porphyrias: A 2015 update.

    PubMed

    Karim, Zoubida; Lyoumi, Said; Nicolas, Gael; Deybach, Jean-Charles; Gouya, Laurent; Puy, Hervé

    2015-09-01

    The hereditary porphyrias comprise a group of eight metabolic disorders of the heme biosynthesis pathway. Each porphyria is caused by abnormal function at a separate enzymatic step resulting in a specific accumulation of heme precursors. Porphyrias are classified as hepatic or erythropoietic, based on the organ system in which heme precursors (δ-aminolevulinic acid [ALA], porphobilinogen and porphyrins) are overproduced. Clinically, porphyrias are characterized by acute neurovisceral symptoms, skin lesions or both. However, most if not all the porphyrias impair hepatic or gastrointestinal function. Acute hepatic porphyrias present with severe abdominal pain, nausea, constipation, confusion and seizure, which may be life threatening, and patients are at risk of hepatocellular carcinoma without cirrhosis. Porphyria Cutanea presents with skin fragility and blisters, and patients are at risk of hepatocellular carcinoma with liver iron overload. Erythropoietic protoporphyria and X-linked protoporphyria present with acute painful photosensitivity, and patients are at risk of acute liver failure. Altogether, porphyrias are still underdiagnosed, but once they are suspected, early diagnosis based on measurement of biochemical metabolites that accumulate in the blood, urine, or feces is essential so specific treatment can be started as soon as possible and long-term liver complications are prevented. Screening families to identify presymptomatic carriers is also crucial to prevent overt disease and chronic hepatic complications.

  11. [Significant laparoscopy and ultrasound findings in chronic hepatic porphyria].

    PubMed

    Fengler, J D; Binus, R; Hintsche-Kilger, B; Baumgarten, R

    1990-09-01

    In the years from 1983 to 1989 we diagnosed in altogether 69 patients a chronic hepatic porphyria. As a rule the light microscopic and sonographic findings in the liver use to be uncharacteristic. Yet, unexpectedly by sonography in eight patients findings, suspicious for metastases, were stated. Multiple coin lesions with a marginal edge mostly rich in echoes were impressing. The laparoscopy resulted in grey/blue-discoloured depressions in an otherwise even surface of the liver, thus suggesting mass necroses respectively rebuilding processes. Subclinical stages of a chronic hepatic porphyria could have been proved by the partial red-fluorescence of bioptates and a corresponding porphyrin secretion. The histological changes of the liver were--in contrary to the impressing laparoscopic picture--rather insignificant. In case of a successful intervention the pathological porphyrin secretion was done in about eight months. Mostly, more than a year used to pass away till the sonographic findings normalized. The seldom described phenomena use to conceal the danger of a false interpretation and an unnecessary stress for the patient. More over the causes and the development of these peculiar porphyria findings are unclear; they need in an discussion among medical special branches.

  12. Biallelic inactivation of protoporphyrinogen oxidase and hydroxymethylbilane synthase is associated with liver cancer in acute porphyrias.

    PubMed

    Schneider-Yin, Xiaoye; van Tuyll van Serooskerken, Anne-Moon; Siegesmund, Marko; Went, Philip; Barman-Aksözen, Jasmin; Bladergroen, Reno S; Komminoth, Paul; Cloots, Roy H E; Winnepenninckx, Véronique J; zur Hausen, Axel; Weber, Markus; Driessen, Ann; Poblete-Gutiérrez, Pamela; Bauer, Peter; Schroeder, Christopher; van Geel, Michel; Minder, Elisabeth I; Frank, Jorge

    2015-03-01

    Variegate porphyria (VP) and acute intermittent porphyria (AIP), the two most common types of acute porphyrias (AHPs), result from a partial deficiency of protoporphyrinogen oxidase (PPOX) and hydroxymethylbilane synthase (HMBS), respectively. A rare but serious complication in the AHPs is hepatocellular carcinoma (HCC). However, the underlying pathomechanisms are yet unknown. We performed DNA sequence analysis in cancerous and non-cancerous liver tissue of a VP and an AIP patient, both with HCC. In samples of both cancerous and non-cancerous liver tissues from the patients, we identified the underlying PPOX and HMBS germline mutations, c.1082dupC and p.G111R, respectively. Additionally, we detected a second somatic mutation, only in the cancer tissue i.e., p.L416X in the PPOX gene of the VP patient and p.L220X in the HMBS gene of the AIP patient, both located in trans to the respective germline mutations. Both somatic mutations were not detected in 10 non-porphyria-associated HCCs. Our data demonstrate that in the hepatic cancer tissue of AHP patients, somatic second-hit mutations result in nearly complete inactivation of the enzymes catalyzing major steps in the heme biosynthetic pathway. Both PPOX and HMBS, which might act as tumor suppressors, play a crucial role in the development of HCC in these individuals.

  13. Preclinical Development of a Subcutaneous ALAS1 RNAi Therapeutic for Treatment of Hepatic Porphyrias Using Circulating RNA Quantification

    PubMed Central

    Chan, Amy; Liebow, Abigail; Yasuda, Makiko; Gan, Lin; Racie, Tim; Maier, Martin; Kuchimanchi, Satya; Foster, Don; Milstein, Stuart; Charisse, Klaus; Sehgal, Alfica; Manoharan, Muthiah; Meyers, Rachel; Fitzgerald, Kevin; Simon, Amy; Desnick, Robert J; Querbes, William

    2015-01-01

    The acute hepatic porphyrias are caused by inherited enzymatic deficiencies in the heme biosynthesis pathway. Induction of the first enzyme 5-aminolevulinic acid synthase 1 (ALAS1) by triggers such as fasting or drug exposure can lead to accumulation of neurotoxic heme intermediates that cause disease symptoms. We have demonstrated that hepatic ALAS1 silencing using siRNA in a lipid nanoparticle effectively prevents and treats induced attacks in a mouse model of acute intermittent porphyria. Herein, we report the development of ALN-AS1, an investigational GalNAc-conjugated RNAi therapeutic targeting ALAS1. One challenge in advancing ALN-AS1 to patients is the inability to detect liver ALAS1 mRNA in the absence of liver biopsies. We here describe a less invasive circulating extracellular RNA detection assay to monitor RNAi drug activity in serum and urine. A striking correlation in ALAS1 mRNA was observed across liver, serum, and urine in both rodents and nonhuman primates (NHPs) following treatment with ALN-AS1. Moreover, in donor-matched human urine and serum, we demonstrate a notable correspondence in ALAS1 levels, minimal interday assay variability, low interpatient variability from serial sample collections, and the ability to distinguish between healthy volunteers and porphyria patients with induced ALAS1 levels. The collective data highlight the potential utility of this assay in the clinical development of ALN-AS1, and in broadening our understanding of acute hepatic porphyrias disease pathophysiology. PMID:26528940

  14. Preclinical Development of a Subcutaneous ALAS1 RNAi Therapeutic for Treatment of Hepatic Porphyrias Using Circulating RNA Quantification.

    PubMed

    Chan, Amy; Liebow, Abigail; Yasuda, Makiko; Gan, Lin; Racie, Tim; Maier, Martin; Kuchimanchi, Satya; Foster, Don; Milstein, Stuart; Charisse, Klaus; Sehgal, Alfica; Manoharan, Muthiah; Meyers, Rachel; Fitzgerald, Kevin; Simon, Amy; Desnick, Robert J; Querbes, William

    2015-01-01

    The acute hepatic porphyrias are caused by inherited enzymatic deficiencies in the heme biosynthesis pathway. Induction of the first enzyme 5-aminolevulinic acid synthase 1 (ALAS1) by triggers such as fasting or drug exposure can lead to accumulation of neurotoxic heme intermediates that cause disease symptoms. We have demonstrated that hepatic ALAS1 silencing using siRNA in a lipid nanoparticle effectively prevents and treats induced attacks in a mouse model of acute intermittent porphyria. Herein, we report the development of ALN-AS1, an investigational GalNAc-conjugated RNAi therapeutic targeting ALAS1. One challenge in advancing ALN-AS1 to patients is the inability to detect liver ALAS1 mRNA in the absence of liver biopsies. We here describe a less invasive circulating extracellular RNA detection assay to monitor RNAi drug activity in serum and urine. A striking correlation in ALAS1 mRNA was observed across liver, serum, and urine in both rodents and nonhuman primates (NHPs) following treatment with ALN-AS1. Moreover, in donor-matched human urine and serum, we demonstrate a notable correspondence in ALAS1 levels, minimal interday assay variability, low interpatient variability from serial sample collections, and the ability to distinguish between healthy volunteers and porphyria patients with induced ALAS1 levels. The collective data highlight the potential utility of this assay in the clinical development of ALN-AS1, and in broadening our understanding of acute hepatic porphyrias disease pathophysiology. PMID:26528940

  15. Acute intermittent porphyria with SIADH and fluctuating dysautonomia.

    PubMed

    Nabin, A; Thapa, L J; Paudel, R; Rana, P V S

    2012-01-01

    Three cases of acute intermittent porphyria are reported. While in first case severe pain in abdomen with intermittent exacerbation was the only presentation, the second patient presented as accelerated hypertension and acute abdominal crises in whom the clinical course was characterized by development of deep coma due to inappropriate secretion of antidiuretic hormone before she made complete recovery. The third patient, initially manifested as acute encephalitic syndrome. After initial improvement, she developed features of acute intermittent porphyria i.e. acute abdomen, neuropsychiatric symptoms, and rapidly progressing acute motor neuropathy leading to respiratory and bulbar paralysis. In addition, she developed severe and fluctuating dysautonomia leading to cardiac arrest and fatal termination. The importance of early diagnosis, recognition of autonomic disturbances, prompt treatment and counseling for avoidance of precipitating factors is stressed.

  16. Acute intermittent porphyria: Diagnostic dilemma and treatment options

    PubMed Central

    Kaur, Mohan Deep; Hazarika, Nita; Saraswat, Namita; Sood, Rajesh

    2015-01-01

    Acute intermittent porphyria (AIP) presents with diverse group of symptoms making its early diagnosis difficult. Delaying diagnosis and treatment of AIP can be fatal or can cause long term or permanent neurological damage. We present here a case report of AIP where the diagnosis was missed. The diversity of symptoms and details concerning the treatment options for AIP are discussed. PMID:26330726

  17. The porphyrias: advances in diagnosis and treatment.

    PubMed

    Balwani, Manisha; Desnick, Robert J

    2012-11-29

    The inborn errors of heme biosynthesis, the porphyrias, are 8 genetically distinct metabolic disorders that can be classified as "acute hepatic," "hepatic cutaneous," and "erythropoietic cutaneous" diseases. Recent advances in understanding their pathogenesis and molecular genetic heterogeneity have led to improved diagnosis and treatment. These advances include DNA-based diagnoses for all the porphyrias, new understanding of the pathogenesis of the acute hepatic porphyrias, identification of the iron overload-induced inhibitor of hepatic uroporphyrin decarboxylase activity that causes the most common porphyria, porphyria cutanea tarda, the identification of an X-linked form of erythropoietic protoporphyria due to gain-of-function mutations in erythroid-specific 5-aminolevulinate synthase (ALAS2), and new and experimental treatments for the erythropoietic porphyrias. Knowledge of these advances is relevant for hematologists because they administer the hematin infusions to treat the acute attacks in patients with the acute hepatic porphyrias, perform the chronic phlebotomies to reduce the iron overload and clear the dermatologic lesions in porphyria cutanea tarda, and diagnose and treat the erythropoietic porphyrias, including chronic erythrocyte transfusions, bone marrow or hematopoietic stem cell transplants, and experimental pharmacologic chaperone and stem cell gene therapies for congenital erythropoietic protoporphyria. These developments are reviewed to update hematologists on the latest advances in these diverse disorders.

  18. Tissue-specific splicing mutation in acute intermittent porphyria

    SciTech Connect

    Grandchamp, B.; Picat, C. ); Mignotte, V.; Romeo, P.H.; Goossens, M. ); Wilson, J.H.P.; Sandkuyl, L. ); Te Velde, K. ); Nordmann, Y. )

    1989-01-01

    An inherited deficiency of porphobilinogen deaminase in humans is responsible for the autosomal dominant disease acute intermittent porphyria. Different classes of mutations have been described at the protein level suggesting that this is a heterogeneous disease. It was previously demonstrated that porphobilinogen deaminase is encoded by two distinct mRNA species expressed in a tissue-specific manner. Analysis of the genomic sequences indicated that these two mRNAs are transcribed from two promoters and only differ in their first exon. The first mutation identified in the human porphobilinogen deaminase gene is a single-base substitution (G {yields} A) in the canonical 5{prime} splice donor site of intron 1. This mutation leads to a particular subtype of acute intermittent porphyria characterized by the restriction of the enzymatic defect to nonerythropoietic tissues. Hybridization analysis using olignonucleotide probes after in vitro amplification of genomic DNA offers another possibility of detecting asymptomatic carriers of the mutation in affected families.

  19. Clinically important features of porphyrin and heme metabolism and the porphyrias.

    PubMed

    Besur, Siddesh; Hou, Wehong; Schmeltzer, Paul; Bonkovsky, Herbert L

    2014-11-03

    Heme, like chlorophyll, is a primordial molecule and is one of the fundamental pigments of life. Disorders of normal heme synthesis may cause human diseases, including certain anemias (X-linked sideroblastic anemias) and porphyrias. Porphyrias are classified as hepatic and erythropoietic porphyrias based on the organ system in which heme precursors (5-aminolevulinic acid (ALA), porphobilinogen and porphyrins) are chiefly overproduced. The hepatic porphyrias are further subdivided into acute porphyrias and chronic hepatic porphyrias. The acute porphyrias include acute intermittent, hereditary copro-, variegate and ALA dehydratase deficiency porphyria. Chronic hepatic porphyrias include porphyria cutanea tarda and hepatoerythropoietic porphyria. The erythropoietic porphyrias include congenital erythropoietic porphyria (Gűnther's disease) and erythropoietic protoporphyria. In this review, we summarize the key features of normal heme synthesis and its differing regulation in liver versus bone marrow. In both organs, principal regulation is exerted at the level of the first and rate-controlling enzyme, but by different molecules (heme in the liver and iron in the bone marrow). We also describe salient clinical, laboratory and genetic features of the eight types of porphyria.

  20. Clinically Important Features of Porphyrin and Heme Metabolism and the Porphyrias

    PubMed Central

    Besur, Siddesh; Hou, Weihong; Schmeltzer, Paul; Bonkovsky, Herbert L.

    2014-01-01

    Heme, like chlorophyll, is a primordial molecule and is one of the fundamental pigments of life. Disorders of normal heme synthesis may cause human diseases, including certain anemias (X-linked sideroblastic anemias) and porphyrias. Porphyrias are classified as hepatic and erythropoietic porphyrias based on the organ system in which heme precursors (5-aminolevulinic acid (ALA), porphobilinogen and porphyrins) are chiefly overproduced. The hepatic porphyrias are further subdivided into acute porphyrias and chronic hepatic porphyrias. The acute porphyrias include acute intermittent, hereditary copro-, variegate and ALA dehydratase deficiency porphyria. Chronic hepatic porphyrias include porphyria cutanea tarda and hepatoerythropoietic porphyria. The erythropoietic porphyrias include congenital erythropoietic porphyria (Gűnther’s disease) and erythropoietic protoporphyria. In this review, we summarize the key features of normal heme synthesis and its differing regulation in liver versus bone marrow. In both organs, principal regulation is exerted at the level of the first and rate-controlling enzyme, but by different molecules (heme in the liver and iron in the bone marrow). We also describe salient clinical, laboratory and genetic features of the eight types of porphyria. PMID:25372274

  1. The porphyrias: advances in diagnosis and treatment.

    PubMed

    Balwani, Manisha; Desnick, Robert J

    2012-01-01

    The inborn errors of heme biosynthesis, the porphyrias, are 8 genetically distinct metabolic disorders that can be classified as "acute hepatic," "hepatic cutaneous," and "erythropoietic cutaneous" diseases. Recent advances in understanding their pathogenesis and molecular genetic heterogeneity have led to improved diagnosis and treatment. These advances include DNA-based diagnoses for all the porphyrias, new understanding of the pathogenesis of the acute hepatic porphyrias, identification of the iron overload-induced inhibitor of hepatic uroporphyrin decarboxylase activity that causes the most common porphyria, porphyria cutanea tarda, the identification of an X-linked form of erythropoietic protoporphyria due to gain-of-function mutations in erythroid-specific 5-aminolevulinate synthase (ALAS2), and new and experimental treatments for the erythropoietic prophyrias. Knowledge of these advances is relevant for hematologists because they administer the hematin infusions to treat the acute attacks in patients with the acute hepatic porphyrias, perform the chronic phlebotomies to reduce the iron overload and clear the dermatologic lesions in porphyria cutanea tarda, and diagnose and treat the erythropoietic porphyrias, including chronic erythrocyte transfusions, bone marrow or hematopoietic stem cell transplants, and experimental pharmacologic chaperone and stem cell gene therapies for congenital erythropoietic protoporphyria. These developments are reviewed to update hematologists on the latest advances in these diverse disorders.

  2. An update of clinical management of acute intermittent porphyria

    PubMed Central

    Pischik, Elena; Kauppinen, Raili

    2015-01-01

    Acute intermittent porphyria (AIP) is due to a deficiency of the third enzyme, the hydroxymethylbilane synthase, in heme biosynthesis. It manifests with occasional neuropsychiatric crises associated with overproduction of porphyrin precursors, aminolevulinic acid and porphobilinogen. The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are the key symptoms indicating possible acute porphyria. More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start a treatment. Currently, the prognosis of the patients with AIP is good, but physicians should be aware of a potentially fatal outcome of the disease. Mutation screening and identification of type of acute porphyria can be done at the quiescent phase of the disease. The management of patients with AIP include following strategies: A, during an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, polyneuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy. B, during remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members. C, management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in patients with severe recurrent attacks. D, follow-up of the AIP

  3. Acute intermittent porphyria in pregnancy: a case report and review of literature.

    PubMed

    Pandey, Uma; Dixit, V K

    2013-12-01

    The porphyrias are a group of rare metabolic disorders, each arising from a predominantly hereditary catalytic dysfunction of one of the eight enzymes in the porphyrin-haem biosynthetic pathway. Acute intermittent porphyria is the commonest type of porphyria worldwide. The disease is more common in women than men. It is therefore important for the obstetricians to know about this entity as many women present with abdominal pain during pregnancy. This case shows that if acute intermittent porphyria is properly treated in a mother there is normal maternal and foetal outcome. A case of acute intermittent porphyria known before pregnancy has been reported in a patient who had three spontaneous abortions in the past, she was delivered by elective caesarean section. The pathogenesis of the disease, its' symptoms, diagnosis, therapeutic approach both during and out of pregnancy have been also discussed.

  4. [Treatment of acute porphyrias. The importance of follow-up of patients and carriers].

    PubMed

    Tasnádi, Gyöngyi; Bor, Márta; Pusztai, Agnes

    2003-05-11

    Acute porphyrias are caused by the inherited decreased activity of the enzymes of the heme biosynthesis pathway. Depending on the affected enzyme there are 4 types of them: acute intermittent porphyria, porphyria variegata, coproporphyria and delta-aminolevulinic acid dehydratase deficient porphyria, listed in order of their frequency. Basically the clinical picture is the same in the four types of acute porphyria. The most frequent complaints and symptoms are: cramping abdominal pain, nausea, vomiting, muscle weakness of the limbs then, in the advanced phase, there is a red-colored urine, hyponatremia, subileus, acute psychosis and Landry-type paralysis. Without proper treatment death is caused by respiratory paralysis or serious arrhythmia. In case of suspicion of acute porphyria it is mandatory to identify the type of the acute porphyria and the actual status of the patient. The later indicates what kind of treatment should be used. In the acute phase the early therapy with heme arginate is the treatment of choice. Since the clinical symptoms are precipitated by endogenous or exogenous inducing factors--most often by drugs-, the drugs negatively affecting the heme biosynthesis should be omitted at once even in the suspicion of acute porphyria. The role of the inducing factors in the manifestation of the clinical symptoms makes possible the prevention. It is possible to avoid the inducing factors and this way to prevent the acute attack if the acute porphyrias are recognized in time and the patients and the carriers are under regular control. The patients receive special identification card and the up-to-date list of safe drugs. They can use only these drugs in any kind of illness. Other drugs should be considered as porphyrinogenic since it is impossible to predict based on their chemical structure if they negatively affect the heme biosynthesis.

  5. Acute intermittent porphyria: A critical diagnosis for favorable outcome.

    PubMed

    Divecha, Chhaya; Tullu, Milind S; Gandhi, Akanksha; Deshmukh, Chandrahas T

    2016-07-01

    Acute intermittent porphyria (AIP) is an inherited metabolic disorder characterized by the accumulation of toxic metabolites of the heme pathway. It rarely presents in the prepubertal age group. AIP often presents with nonspecific and nonlocalizing symptoms. Moreover, several commonly used medications and stress states are known to precipitate an attack. We present the case of a previously healthy 5 years female who was diagnosed as acute central nervous system infection/inflammation at admission. It was the presence of red flags that led to a correct diagnosis. Besides supportive management, a dedicated search for intravenous hemin (chemically heme arginate, aminolevulinic acid synthase inhibitor, and drug of choice) was attempted. Unexpected help was rendered by doctors from a medical college in Gujarat, and two ampoules could be obtained. The patient received three doses of intravenous hemin; however, she succumbed later. This case is presented for the diagnostic and therapeutic challenges faced in developing countries. PMID:27555700

  6. Acute intermittent porphyria: A critical diagnosis for favorable outcome

    PubMed Central

    Divecha, Chhaya; Tullu, Milind S.; Gandhi, Akanksha; Deshmukh, Chandrahas T.

    2016-01-01

    Acute intermittent porphyria (AIP) is an inherited metabolic disorder characterized by the accumulation of toxic metabolites of the heme pathway. It rarely presents in the prepubertal age group. AIP often presents with nonspecific and nonlocalizing symptoms. Moreover, several commonly used medications and stress states are known to precipitate an attack. We present the case of a previously healthy 5 years female who was diagnosed as acute central nervous system infection/inflammation at admission. It was the presence of red flags that led to a correct diagnosis. Besides supportive management, a dedicated search for intravenous hemin (chemically heme arginate, aminolevulinic acid synthase inhibitor, and drug of choice) was attempted. Unexpected help was rendered by doctors from a medical college in Gujarat, and two ampoules could be obtained. The patient received three doses of intravenous hemin; however, she succumbed later. This case is presented for the diagnostic and therapeutic challenges faced in developing countries. PMID:27555700

  7. Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria.

    PubMed Central

    Puy, H; Deybach, J C; Lamoril, J; Robreau, A M; Da Silva, V; Gouya, L; Grandchamp, B; Nordmann, Y

    1997-01-01

    Acute intermittent porphyria (AIP) is the major autosomal dominant form of acute hepatic porphyrias. The disease is due to mutations in the gene encoding for porphobilinogen (PBG) deaminase and is characterized by life-threatening neurovisceral attacks, often precipitated by drugs, fasting, cyclical hormonal changes, or infectious diseases. This report describes a prospective study on the molecular epidemiology of PBG deaminase gene defects in AIP. It uses a sensitive, reliable, and easy-to-handle method for routine AIP molecular diagnosis and family study based on an exon-by-exon denaturing gradient gel electrophoresis (DGGE) strategy followed by direct sequencing. Fifteen genomic DNA fragments, including all the coding sequence and covering 3.35 kb of the PBG deaminase gene, were investigated in 405 subjects from 121 unrelated French Caucasian AIP families who had not been screened previously at the DNA level. PBG deaminase gene mutations were identified in 109 families, but only 78 were of different type, and each of them had a prevalence rate < 5%. Among these mutations, 33 had not been published previously. Sixty percent of these 78 mutations were located in only three exons (exons 10, 12, and 14), 44% were missense, 18% were splice defect, 19% were frameshift, and 16% were nonsense. In addition, two de novo mutational events were characterized. The evaluation of the efficiency of the standard PBG deaminase enzymatic screening method for gene-carrier detection indicated 95% of concordancy with the molecular-based diagnosis. Images Figure 1 Figure 2 PMID:9199558

  8. Non-viral delivery of the porphobilinogen deaminase cDNA into a mouse model of acute intermittent porphyria.

    PubMed

    Johansson, Annika; Nowak, Grzegorz; Möller, Christer; Harper, Pauline

    2004-05-01

    Acute intermittent porphyria (AIP), an inborn error of metabolism, results from the deficient activity of the third enzyme in the heme biosynthetic pathway, porphobilinogen deaminase (PBGD). Clinical symptoms of this autosomal dominant hepatic porphyria include episodic acute attacks of abdominal pain, neuropathy, and psychiatric disturbances. Current therapy based on intravenous heme administration is palliative and there is no way to prevent the attacks. Thus, efforts are focused on methods to replace the deficient activity in the liver to prevent the acute attacks of this hepatic porphyria. Here we explore the efficiency of a non-viral gene delivery to obtain PBGD expression in the liver of AIP transgenic mice. Four vectors were evaluated: naked DNA and DNA complexed to liposomes, polyethylenimine (PEI), and PEI-galactose, using a luciferase construct as reporter gene. The vectors were administered intravenously or directly into the portal vein with transient blood flow blockage. After tail vein injection of the DNA complexes, the liposome vector had the highest luciferase expression in lung and less in liver. When injected into the portal vein, the naked DNA had considerably higher hepatic reporter gene expression; 100 microg of naked DNA had the highest hepatic luciferase expression 24h after portal vein injection. When these vectors were used to deliver the PBGD gene into the AIP mouse model no enhancement of the endogenous PBGD activity in liver was detectable, despite the presence of the PBGD-plasmids as verified by PCR. Thus, more efficient non-viral vectors are needed to express sufficient PBGD activity over the endogenous hepatic level (approximately 30% of normal) in this murine system.

  9. Severe neurologic manifestations in acute intermittent porphyria developed after spine surgery under general anesthesia: a case report

    PubMed Central

    Park, Eun Young; Kim, Yi Seul; Lim, Kyung-Jee; Lee, Hye Kyoung; Lee, Soo Kyung; Choi, Hyun

    2014-01-01

    Porphyrias are inherited metabolic disorders resulting from a specific enzyme defect in the heme biosynthetic pathway. Porphyrias are induced by various precipitants. Clinical features include abdominal pain, neurologic manifestations, autonomic neuropathy, and mental disturbance. Diagnosis may be delayed because of variable symptoms that mimic other diseases and because of the rarity of of porphyrias. Although most patients with known porphyria can complete anesthesia and surgery safely, undiagnosed porphyric patients are in danger of porphyric crisis due to inadvertent exposure to precipitating drugs and environment. We report a case of a patient who experienced delayed emergence with neurological disturbance after general anesthesia, ultimately diagnosed as acute intermittent porphyria. PMID:25302100

  10. Porphyria variegata.

    PubMed

    Dean, G

    1982-01-01

    A form of porphyria inherited as a Mendelian dominant characteristic can cause both cutaneous lesions on the exposed skin and attacks of acute porphyria following certain drugs, for instance barbiturates. Because it presents in a variety of forms it has been named porphyria variegata. This form of porphyria is very common among the White and Coloured South Africans because of 'founder effect'. A high proportion of the present population are descendants of a small number of early settlers, one of whom introduced the gene for this condition. The disease has been traced over 17 generations to Gerrit Jansz who came from Deventer in Holland and who married Ariaantje, an orphan from Rotterdam, in 1688. In the quiescent state porphyria variegata is best diagnosed by the examination of a solution of the stool in ultraviolet light which shows the pink fluorescence of porphyrin. In the acute attack porphobilinogen and porphyrin are greatly increased in the urine. Porphyria variegata also occurs outside of South Africa but in these countries it is less common than acute intermittent porphyria. The diagnosis and treatment is described and the story that the insanity of King George III of England was due to porphyria variegata is refuted.

  11. Acute variegate porphyria following a Scarsdale Gourmet Diet.

    PubMed

    Quiroz-Kendall, E; Wilson, F A; King, L E

    1983-01-01

    Symptoms of porphyria developed in a 34-year-old woman following 3 weeks of a low carbohydrate diet. Reversal of a comatose state was obtained following multiple infusions of hematin. The diagnosis of variegate porphyria was made from the pattern of quantitative urine and stool porphyrins and a plasma fluorescence that was maximal at 626 nm. This fluorescence wavelength maxima also was found in the plasma of two family members screened for latent porphyria.

  12. The incidence of inherited porphyrias in Europe.

    PubMed

    Elder, George; Harper, Pauline; Badminton, Michael; Sandberg, Sverre; Deybach, Jean-Charles

    2013-09-01

    Retrospective estimates of the prevalence of porphyrias have been reported but there has been no large scale prospective study of their incidence. The European Porphyria Network collected information prospectively over a 3 year period about the number of newly diagnosed symptomatic patients with an inherited porphyria (335 patients from 11 countries). Prevalence was calculated from the incidence and mean disease duration. The incidence of hepato-cellular carcinoma (HCC) in acute hepatic porphyria and the prevalence of patients with recurrent acute attacks of porphyria were also investigated. The incidence of symptomatic acute intermittent porphyria (AIP) was similar in all countries (0.13 per million per year; 95 % CI: 0.10 - 0.14) except Sweden (0.51; 95 % CI: 0.28-0.86). The incidence ratio for symptomatic AIP: variegate porphyria: hereditary coproporphyria was 1.00:0.62: 0.15. The prevalence of AIP (5.4 per million; 95 % CI: 4.5-6.3) was about half that previously reported. The prevalence of erythropoietic protoporphyria (EPP) was less uniform between countries and, in some countries, exceeded previous estimates. Fourteen new cases of HCC (11 from Sweden) were reported in patients with acute porphyria. Sixty seven patients (3 VP; 64 AIP: 53 females, 11 males) with recurrent attacks of acute porphyria were identified. The estimated percentage of patients with AIP that will develop recurrent acute attacks was 3-5 %. In conclusion, the prevalence of symptomatic acute porphyria may be decreasing, possibly due to improved management, whereas the prevalence of EPP may be increasing due to improved diagnosis and its greater recognition as a cause of photosensitivity.

  13. Porphyrias in Japan: compilation of all cases reported through 2002.

    PubMed

    Kondo, Masao; Yano, Yuzo; Shirataka, Masuo; Urata, Gumpei; Sassa, Shigeru

    2004-06-01

    The first case of porphyria on record in Japan was a patient with congenital erythropoietic porphyria (CEP) reported by Sato and Takahashi in 1920. Since then until the end of December 2002, 827 cases of porphyrias have been diagnosed from characteristic clinical and/or laboratory findings (463 males, 358 females, and 6 of unknown sex). Essentially all inherited porphyrias have been found in Japan, with the incidences and clinical symptoms generally being similar to those reported for other countries. The male-female ratio was approximately 1:1 for CEP, whereas it was higher for erythropoietic protoporphyria. In contrast, preponderances of female patients exist with acute hepatic porphyrias, such as acute intermittent porphyria (AIP), variegate porphyria (VP), and hereditary coproporphyria (HCP), and with undefined acute porphyria. Although porphyria cutanea tarda (PCT) is believed to be increasing recently in women in other countries because of smoking and the use of contraceptives, it is still by far more prominent in males in Japan than in females. The recent increasing contribution of hepatitis C virus infection to PCT in Japan has also been recognized. but there have been no PCT cases in Japan with HFE gene mutations. Familial occurrence and consanguinity were high for CEP, as expected; however, significant consanguinity was also noted in families where CEP, AIP, HCP, VP, or PCT occurred as a single isolated case without a family history of disease. This survey also revealed that as many as 71% of acute hepatic porphyria cases were initially diagnosed as nonporphyria and later revised or corrected to porphyria, indicating the difficulty of diagnosing porphyria in the absence of specific laboratory testing for porphyrins and their precursors in urine, stool, plasma, and erythrocyte samples.

  14. [Cortical amaurosis and status epilepticus with acute porphyria].

    PubMed

    Wessels, T; Blaes, F; Röttger, C; Hügens, M; Hüge, S; Jauss, M

    2005-08-01

    The most common neurologic manifestations of acute intermittent porphyria (AIP) are autonomic visceral neuropathy, peripheral motor neuropathy, and CNS dysfunctions including seizures and neuropsychiatric disturbances. In rare instances, however, AIP patients have presented with acute cortical blindness. We present a 20-year-old woman who suffered her first attack of AIP. Following 1 week of abdominal pain, she was transferred from a surgical department because of sudden visual loss and deterioration of consciousness. On admission, she developed several generalized seizures. Magnetic resonance imaging showed bilateral DWI lesions occipitally and in the left anterior circulation. Cerebrospinal fluid, MR angiography, and duplex ultrasound were normal. On the following day, sedation and intubation became necessary because of a generalized status epilepticus. Analysis of porphyrinogens in blood, urine and stool showed significantly elevated values. Intravenous therapy with häm-arginate was initiated and antiepileptic therapy was changed to gagabentine. Under this therapeutical regime she remained stable and extubation was possible 48 h later. PMID:15791420

  15. Porphyrins and Porphyria Diagnosis

    MedlinePlus

    ... Contact Us About Porphyria AIP VP HCP ADP PCT EPP CEP HEP Diet and Nutrition History of ... Alliance Healthcare Professionals AIP, HCP, VP & ADP EPP PCT Drug Safety in Acute Porphyrias Emergency Room Guidelines ...

  16. Femoral and sciatic nerve block for knee arthroscopy in a patient with acute intermittent porphyria.

    PubMed

    Bosch, L; Villar, T; Latorre, M Y; Pacreu, S

    2016-01-01

    Acute intermittent porphyria is an autosomal dominant disorder that results from a partial deficiency of porphobilinogen deaminase and that causes very severe symptoms. Attacks may be triggered by a series of drugs and by other factors that the anesthesiologist should be aware of in order to reduce morbidity and mortality. Our objective is to review anesthetic considerations in acute intermittent porphyria. We present the case of a patient diagnosed with acute intermittent porphyria who was scheduled for knee arthroscopy. The anesthetic technique used was a femoral and sciatic nerve block under sedation with an infusion of remifentanil. The surgery proceeded without incident and the patient was discharged home after 24h. We consider the use of a peripheral plexus block of the lower limb to have been the safest anesthetic technique for this patient. PMID:27220836

  17. Challenges in the successful management of a case of acute intermittent porphyria in India.

    PubMed

    Patell, Rushad; Dosi, Rupal; Joshi, Harsh; Shah, Purav; Tripathi, Rishi

    2016-07-01

    Acute intermittent porphyria (AIP) is a rare metabolic disease involving a defect in haem biosynthesis resulting in the accumulation and excessive secretion of porphyrins and its precursors. Acute attacks present with episodes of severe abdominal pain, nausea, confusion and severe life-threatening seizures. A high index of suspicion is required for the initial diagnosis of AIP.

  18. The cutaneous porphyrias.

    PubMed

    Schulenburg-Brand, Danja; Katugampola, Ruwani; Anstey, Alexander V; Badminton, Michael N

    2014-07-01

    The porphyrias are a group of mainly inherited disorders of heme biosynthesis where accumulation of porphyrins and/or porphyrin precursors gives rise to 2 types of clinical presentation: cutaneous photosensitivity and/or acute neurovisceral attacks. The cutaneous porphyrias present with either bullous skin fragility or nonbullous acute photosensitivity. This review discusses the epidemiology, pathogenesis, clinical presentation, laboratory diagnosis, complications, and current approach to porphyria management. Although focusing mainly on their dermatological aspects, the article also covers the management of acute porphyria, which by virtue of its association with variegate porphyria and hereditary coproporphyria, may become the responsibility of the clinical dermatologist.

  19. The cutaneous porphyrias.

    PubMed

    Schulenburg-Brand, Danja; Katugampola, Ruwani; Anstey, Alexander V; Badminton, Michael N

    2014-07-01

    The porphyrias are a group of mainly inherited disorders of heme biosynthesis where accumulation of porphyrins and/or porphyrin precursors gives rise to 2 types of clinical presentation: cutaneous photosensitivity and/or acute neurovisceral attacks. The cutaneous porphyrias present with either bullous skin fragility or nonbullous acute photosensitivity. This review discusses the epidemiology, pathogenesis, clinical presentation, laboratory diagnosis, complications, and current approach to porphyria management. Although focusing mainly on their dermatological aspects, the article also covers the management of acute porphyria, which by virtue of its association with variegate porphyria and hereditary coproporphyria, may become the responsibility of the clinical dermatologist. PMID:24891059

  20. (Far) Outside the box: genomic approach to acute porphyria.

    PubMed

    Thunell, S

    2006-01-01

    If I were living in Caucasus I would be writing fairy tales there Chekov, 1888 The question of the reasons for the extreme variation in morbidity among the gene carriers of acute porphyria and the great diversity of the precipitating factors are approached by the aid of a model of interacting genomic circuits. It is based on the current paradigm of the acute porphyric attack as a result of a toxic proximal overload of the enzyme-deficient heme-biosynthetic patway. Porphyrogenic influx of precursors is seen as a consequence of uncontrolled induction of its gate-keeping enzyme, ubiquitous 5-aminolevulinate synthase (ALAS1), due to attenuated post-translational control of the enzyme combined with activated gene transcription. Focus is directed on the genomic control of the master-regulator of ALAS1-transcription, the nuclear receptor pair constitutively active receptor (CAR) and pregnane xenobiotic receptor (PXR). On activation by their ligands, i.e. lipophilic drugs, solvents, alcohols, hormonal steroids and biocides, these DNA-binding proteins transform xenobiotic or steroid stimuli to coordinated activations of gene transcription-programs for ALAS1 and apo-cytochromes P450 (apo-CYPs), thus effecting the formation of xenobiotic-metabolizing cytochrome P450 enzymes. The potency of the CAR/PXR-transduction axis is enhanced by co-activators generated in at least four other genomic circuits, each triggered by different external and internal stimuli clinically experienced to be porphyrogenic, and each controlled by co-activating and co-repressing modulators. The expressions of the genes for CAR and PXR are thus augmented by binding glucocorticoid receptor (GR) activated by a steroid hormone, e.g, cortisol generated in fasting, infection or different forms of stress. The promotor regions of ALAS1 and apoCYPs contain binding sites for at least three co-activating transcription factors enhancing CAR/PXR transduction: i.e. the ligand-independent growth hormone (GH

  1. Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias.

    PubMed

    Stubenhaus, Bradford M; Dustin, John P; Neverett, Emily R; Beaudry, Megan S; Nadeau, Leanna E; Burk-McCoy, Ethan; He, Xinwen; Pearson, Bret J; Pellettieri, Jason

    2016-05-31

    Porphyrias are disorders of heme metabolism frequently characterized by extreme photosensitivity. This symptom results from accumulation of porphyrins, tetrapyrrole intermediates in heme biosynthesis that generate reactive oxygen species when exposed to light, in the skin of affected individuals. Here we report that in addition to producing an ommochrome body pigment, the planarian flatworm Schmidtea mediterranea generates porphyrins in its subepithelial pigment cells under physiological conditions, and that this leads to pigment cell loss when animals are exposed to intense visible light. Remarkably, porphyrin biosynthesis and light-induced depigmentation are enhanced by starvation, recapitulating a common feature of some porphyrias - decreased nutrient intake precipitates an acute manifestation of the disease. Our results establish planarians as an experimentally tractable animal model for research into the pathophysiology of acute porphyrias, and potentially for the identification of novel pharmacological interventions capable of alleviating porphyrin-mediated photosensitivity or decoupling dieting and fasting from disease pathogenesis.

  2. Abdominal pain and syndrome of inappropriate antidiuretic hormone secretion as clinical presentation of acute intermittent porphyria.

    PubMed

    Valle Feijóo, M L; Bermúdez Sanjurjo, J R; González Vázquez, L; Rey Martínez, M; de la Fuente Aguado, J

    2015-01-01

    Acute intermittent porphyria (AIP) is a rare condition characterized by abdominal pain and a wide range of nonspecific symptoms. We report the case of a woman with abdominal pain and syndrome of inappropriate antidiuretic hormone secretion (SIADH) as clinical presentation of AIP. The diagnosis was achieved through the etiologic study of the SIADH.

  3. Characterization of the Porphobilinogen Deaminase Deficiency in Acute Intermittent Porphyria

    PubMed Central

    Anderson, Peter M.; Reddy, Raman M.; Anderson, Karl E.; Desnick, Robert J.

    1981-01-01

    The molecular pathology of the porphobilinogen (PBG)-deaminase deficiency in heterozygotes for acute intermittent porphyria (AIP) was investigated by means of biochemical and immunologic techniques. The stable enzyme-substrate intermediates (A, B, C, D, and E) of PBG-deaminase were separated by anion-exchange chromatography of erythrocyte lysates from heterozygotes for AIP and normal individuals. In normal lysates, the intermediates eluted in a characteristic pattern with decreasing amounts of activity (A > B > C > D > E), the combined A and B intermediates representing >75% of total recovered activity. In contrast, two different profiles were observed in lysates from heterozygotes for AIP. In most heterozygotes, the elution profile was similar to that of normal individuals, but each intermediate was reduced ∼50%. A second profile in which the C intermediate had disproportionately higher activity than the A or B intermediates was observed in asymptomatic heterozygotes with high urinary levels of PBG (>5 μg/ml) as well as in heterozygotes during acute attacks. These findings suggested that the C intermediate (the dipyrrole-enzyme intermediate) may be rate limiting in the stepwise conversion of the monopyrrole, PBG, to the linear tetrapyrrole, hydroxymethylbilane. To investigate further the nature of the enzymatic defect in AIP, sensitive immunotitration and immunoelectrophoretic assays were developed with the aid of a rabbit anti-human PBG-deaminase IgG preparation produced against the homogeneous enzyme. Equal amounts of erythrocyte lysate activity from 32 heterozygotes for AIP from 22 unrelated families and 35 normal individuals were immunoelectrophoresed. There were no detectable differences in the amounts of cross-reactive immunologic material (CRIM) in lysates from the normal individuals and 25 heterozygotes from 21 of the 22 unrelated families with AIP. In contrast, when equal enzymatic activities were coimmunoelectrophoresed, all seven heterozygotes from

  4. Hepatocellular carcinoma in variegate porphyria: a case report and literature review.

    PubMed

    Luvai, Ahai; Mbagaya, Wycliffe; Narayanan, Deepa; Degg, Tim; Toogood, Giles; Wyatt, Judith I; Swinson, Daniel; Hall, Claire J; Barth, Julian H

    2015-05-01

    Variegate porphyria is an autosomal dominant acute hepatic porphyria characterized by photosensitivity and acute neurovisceral attacks. Hepatocellular carcinoma has been described as a potential complication of variegate porphyria in case reports. We report a case of a 48-year-old woman who was diagnosed with hepatocellular carcinoma following a brief history of right upper quadrant pain which was preceded by a few months of blistering lesions in sun-exposed areas. She was biochemically diagnosed with variegate porphyria, and mutational analysis confirmed the presence of a heterozygous mutation in the protoporphyrinogen oxidase gene. Despite two hepatic resections, she developed pulmonary metastases. She responded remarkably well to Sorafenib and remains in remission 16 months after treatment. A review of the literature revealed that hepatocellular carcinoma in variegate porphyria has been described in at least eight cases. Retrospective and prospective cohort studies have suggested a plausible association between hepatocellular carcinoma and acute hepatic porphyrias. Hepatic porphyrias should be considered in the differential diagnoses of hepatocellular carcinoma of uncertain aetiology. Patients with known hepatic porphyrias may benefit from periodic monitoring for this complication.

  5. Molecular mechanisms of dominant expression in porphyria.

    PubMed

    Badminton, M N; Elder, G H

    2005-01-01

    Partial deficiency of enzymes in the haem synthetic pathway gives rise to a group of seven inherited metabolic disorders, the porphyrias. Each deficiency is associated with a characteristic increase in haem precursors that correlates with the symptoms associated with individual porphyrias and allows accurate diagnosis. Two types of clinical presentation occur separately or in combination; acute life-threatening neurovisceral attacks and/or cutaneous symptoms. Five of the porphyrias are low-penetrance autosomal dominant conditions in which clinical expression results from additional factors that act by increasing demand for haem or by causing an additional decrease in enzyme activity or by a combination of these effects. These include both genetic and environmental factors. In familial porphyria cutanea tarda (PCTF), environmental factors that include alcohol, exogenous oestrogens and hepatotropic viruses result in inhibition of hepatic enzyme activity via a mechanism that involves excess iron accumulation. In erythropoietic protoporphyria (EPP), co-inheritance of a functional polymorphism in trans to a null ferrochelatase allele accounts for most clinically overt cases. In the autosomal dominant acute hepatic porphyrias (acute intermittent porphyria, variegate porphyria, hereditary coproporphyria), acute neurovisceral attacks occur in a minority of those who inherit one of these disorders. Although various exogenous (e.g. drugs, alcohol) and endogenous factors (e.g. hormones) have been identified as provoking acute attacks, these do not provide a full explanation for the low penetrance of these disorders. It seems probable that genetic background influences susceptibility to acute attacks, but the genes that are involved have not yet been identified.

  6. The acute porphyrias: a diagnostic and therapeutic challenge in internal and emergency medicine.

    PubMed

    Ventura, Paolo; Cappellini, Maria Domenica; Rocchi, Emilio

    2009-08-01

    The porphyrias are a heterogeneous group of metabolic diseases resulting from a variable catalytic defect of one of the eight enzymes involved in the heme biosynthesis pathway; they are mostly inherited diseases, but in some circumstances the metabolic disturbance may be acquired. The specific patterns of tissue overproduction (and hence accumulation and excretion) of toxic heme precursors, associated with each enzymatic deficiency, are responsible for the characteristic biochemical and clinical features of each of these diseases. Moreover, even in the presence of a specific inherited enzymatic defect, many different environmental factors (such as drugs, calorie restriction, hormones, sunlight exposition, infections, etc.) often play a key role in triggering the clinical expression of the various forms of porphyrias. The porphyrias are often misdiagnosed diseases, due their multiform clinical manifestations, able to mimic many other more common diseases. For this reason, many different specialists, such as surgeons, psychiatrists, gastroenterologists, neurologists, emergency physicians and dermatologists may be variably involved in the diagnostic process, especially for the forms presenting with acute and life-threatening clinical features. According to the clinical features, the porphyrias can be classified into neuropsychiatric (characterized by neurovisceral crises involving autonomic and central nervous system but also the liver and the kidney with possible consequences in terms of neurological, psychic, cardiac, respiratory, liver and kidney functions), dermatological (mostly presenting with cutaneous lesions due to photosensitivity), and mixed forms. From a strictly clinical point of view, porphyrias presenting with neurovisceral attacks are also referred as acute porphyrias: they are the object of the present review. An accurate diagnosis of acute porphyria requires knowledge and the use of correct diagnostic tools, and it is mandatory to provide a more

  7. A challenging diagnosis for potential fatal diseases: recommendations for diagnosing acute porphyrias.

    PubMed

    Ventura, Paolo; Cappellini, Maria Domenica; Biolcati, Gianfranco; Guida, Claudio Carmine; Rocchi, Emilio

    2014-07-01

    Acute porphyrias are a heterogeneous group of metabolic disorders resulting from a variable catalytic defect of four enzymes out of the eight involved in the haem biosynthesis pathway; they are rare and mostly inherited diseases, but in some circumstances, the metabolic disturbance may be acquired. Many different environmental factors or pathological conditions (such as drugs, calorie restriction, hormones, infections, or alcohol abuse) often play a key role in triggering the clinical exacerbation (acute porphyric attack) of these diseases that may often mimic many other more common acute medical and neuropsychiatric conditions and whose delayed diagnosis and treatment may be fatal. In order to obtain an accurate diagnosis of acute porphyria, the knowledge and the use of appropriate diagnostic tools are mandatory, even in order to provide as soon as possible the more effective treatment and to prevent the use of potentially unsafe drugs, which can severely precipitate these diseases, especially in the presence of life-threatening symptoms. In this paper, we provide some recommendations for the diagnostic steps of acute porphyrias by reviewing literature and referring to clinical experience of the board members of the Gruppo Italiano Porfiria (GrIP).

  8. How porphyrinogenic drugs modeling acute porphyria impair the hormonal status that regulates glucose metabolism. Their relevance in the onset of this disease.

    PubMed

    Matkovic, Laura B; D'Andrea, Florencia; Fornes, Daiana; San Martín de Viale, Leonor C; Mazzetti, Marta B

    2011-11-28

    This work deals with the study of how porphyrinogenic drugs modeling acute porphyrias interfere with the status of carbohydrate-regulating hormones in relation to key glucose enzymes and to porphyria, considering that glucose modulates the development of the disease. Female Wistar rats were treated with 2-allyl-2-isopropylacetamide (AIA) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) using different doses of AIA (100, 250 and 500mg/kg body weight) and a single dose of DDC (50mg DDC/kg body weight). Rats were sacrificed 16h after AIA/DDC administration. In the group treated with the highest dose of AIA (group H), hepatic 5-aminolevulinic acid synthase (ALA-S) increased more than 300%, phosphoenolpyruvate carboxykinase (PEPCK) and glycogen phosphorylase (GP) activities were 43% and 46% lower than the controls, respectively, plasmatic insulin levels exceeded normal values by 617%, and plasmatic glucocorticoids (GC) decreased 20%. GC results are related to a decrease in corticosterone (CORT) adrenal production (33%) and a significant reduction in its metabolization by UDP-glucuronosyltransferase (UGT) (62%). Adrenocorticotropic hormone (ACTH) stimulated adrenal production 3-fold and drugs did not alter this process. Thus, porphyria-inducing drugs AIA and DDC dramatically altered the status of hormones that regulate carbohydrate metabolism increasing insulin levels and reducing GC production, metabolization and plasmatic levels. In this acute porphyria model, gluconeogenic and glycogenolytic blockages caused by PEPCK and GP depressed activities, respectively, would be mainly a consequence of the negative regulatory action of insulin on these enzymes. GC could also contribute to PEPCK blockage both because they were depressed by the treatment and because they are positive effectors on PEPCK. These disturbances in carbohydrates and their regulation, through ALA-S de-repression, would enhance the porphyria state promoted by the drugs on heme synthesis and destruction

  9. Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias

    PubMed Central

    Stubenhaus, Bradford M; Dustin, John P; Neverett, Emily R; Beaudry, Megan S; Nadeau, Leanna E; Burk-McCoy, Ethan; He, Xinwen; Pearson, Bret J; Pellettieri, Jason

    2016-01-01

    Porphyrias are disorders of heme metabolism frequently characterized by extreme photosensitivity. This symptom results from accumulation of porphyrins, tetrapyrrole intermediates in heme biosynthesis that generate reactive oxygen species when exposed to light, in the skin of affected individuals. Here we report that in addition to producing an ommochrome body pigment, the planarian flatworm Schmidtea mediterranea generates porphyrins in its subepithelial pigment cells under physiological conditions, and that this leads to pigment cell loss when animals are exposed to intense visible light. Remarkably, porphyrin biosynthesis and light-induced depigmentation are enhanced by starvation, recapitulating a common feature of some porphyrias – decreased nutrient intake precipitates an acute manifestation of the disease. Our results establish planarians as an experimentally tractable animal model for research into the pathophysiology of acute porphyrias, and potentially for the identification of novel pharmacological interventions capable of alleviating porphyrin-mediated photosensitivity or decoupling dieting and fasting from disease pathogenesis. DOI: http://dx.doi.org/10.7554/eLife.14175.001 PMID:27240733

  10. European porphyria initiative (EPI): a platform to develop a common approach to the management of porphyrias and to promote research in the field.

    PubMed

    Deybach, J-Ch; Badminton, M; Puy, H; Sandberg, S; Frank, J; Harper, P; Martasek, P; Minder, E; Parker, S; Thunell, S; Elder, G

    2006-01-01

    Porphyrias are uncommon inherited diseases of haem biosynthesis for which the diagnosis and treatment varies in individual countries. Despite the existence of guidelines recommended by porphyria experts concerning the diagnosis and management of the acute porphyrias, and of specialist centres in most European countries, many clinicians still do not apply these guidelines. The European Porphyia Initiative (EPI) network was formed in 2001 in order to compare experience among countries to attempt to develop a common approach to the management of the porphyrias, particularly concerning recommendation of safe and unsafe drugs, and to facilitate international collaborative clinical and biological research. The main achievements of EPI during this period have been: * Drafting and agreeing to consensus protocols for the diagnosis and management of acute hepatic porphyrias. * Creation of a multilingual website, particularly focusing on guidelines for common prescribing problems in acute porphyria and on providing information for patients that is now available in 10 languages: (www.porphyria-europe.org). EPI's current objectives are to develop the EPI platform, expand to new countries, extend to non-acute porphyrias and design European research and clinical trials in porphyria. The project will focus on: 1. Setting up a European laboratory external quality assurance scheme (EQAS) for biochemical and molecular investigations and their interpretation 2. Establishing a consensus drug list in collaboration with the Nordic porphyria network 3. Improving patient counseling 4. Developing large multi-centre, multi-national research projects. Due to the rarity of the porphyrias, it would be very difficult for any one country to provide this data with a sufficient number of patients and within a reasonable timescale. The progress achieved will facilitate improvements in the treatment and development of new therapeutic strategies. It will set a pattern for establishing, and

  11. Rapid screening test for porphyria diagnosis using fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Lang, A.; Stepp, H.; Homann, C.; Hennig, G.; Brittenham, G. M.; Vogeser, M.

    2015-07-01

    Porphyrias are rare genetic metabolic disorders, which result from deficiencies of enzymes in the heme biosynthesis pathway. Depending on the enzyme defect, different types of porphyrins and heme precursors accumulate for the different porphyria diseases in erythrocytes, liver, blood plasma, urine and stool. Patients with acute hepatic porphyrias can suffer from acute neuropathic attacks, which can lead to death when undiagnosed, but show only unspecific clinical symptoms such as abdominal pain. Therefore, in addition to chromatographic methods, a rapid screening test is required to allow for immediate identification and treatment of these patients. In this study, fluorescence spectroscopic measurements were conducted on blood plasma and phantom material, mimicking the composition of blood plasma of porphyria patients. Hydrochloric acid was used to differentiate the occurring porphyrins (uroporphyrin-III and coproporphyrin-III) spectroscopically despite their initially overlapping excitation spectra. Plasma phantom mixtures were measured using dual wavelength excitation and the corresponding concentrations of uroporphyrin-III and coproporphyrin-III were determined. Additionally, three plasma samples of porphyria patients were examined and traces of coproporphyrin-III and uroporphyrin-III were identified. This study may therefore help to establish a rapid screening test method with spectroscopic differentiation of the occurring porphyrins, which consequently allows for the distinction of different porphyrias. This may be a valuable tool for clinical porphyria diagnosis and rapid or immediate treatment.

  12. Neurovisceral porphyrias: what a hematologist needs to know.

    PubMed

    Bonkovsky, Herbert L

    2005-01-01

    The acute or inducible hepatic porphyrias comprise four inherited disorders of heme biosynthesis. They usually remain asymptomatic for most of the lifespan of individuals who inherit the specific enzyme deficiencies but may cause life-threatening attacks of neurovisceral symptoms. Failure to consider the diagnosis frequently delays effective treatment, and inappropriate diagnostic tests and/or mistaken interpretation of results may lead to misdiagnosis and inappropriate treatment. The four disorders are ALA dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. Other conditions that clinically and biochemically may mimic acute porphyria include lead poisoning and hereditary tyrosinemia type I. The diagnosis of one of these acute porphyric syndromes should be considered in many patients with otherwise unexplained abdominal pain, severe constipation, systemic arterial hypertension, or other characteristic symptoms. Critical to the rapid diagnosis of the three most common of these disorders is demonstration of markedly increased urinary porphobilinogen (PBG) in a single-void urine specimen. The treatment of choice for all but mild attacks of the acute porphyrias is intravenous hemin therapy, which should be started as soon as possible. Intravenous glucose alone is recommended only for mild attacks (no weakness or hyponatremia) or until hemin is available.

  13. Anesthetic implication of tricuspid valve replacement in a patient with acute intermittent porphyria

    PubMed Central

    Saberi, Kianoush; Salehi, Mehrdad; Rahmanian, Mehrzad; Bakhshandeh, Ali Reza; Mahlabani, Mohammad Amin Gorji

    2016-01-01

    Facing a patient with acute intermittent porphyria (AIP), there is narrow safety margin which circumscribe all the therapeutic actions including choice of drugs. This would become even more complicated when it comes to a stressful and drug-dependent process like a cardiopulmonary bypass. According to author's researches, no specific AIP case of tricuspid valve (TV) replacement is reported recently. Furthermore, fast-track anesthesia was safely used in this 37-year-old male known the case of AIP, who was a candidate for TV replacement and removing the port catheter. The patient was extubated subsequently, only 3 h after entering the Intensive Care Unit. PMID:27052088

  14. Porphyria in Sweden.

    PubMed

    Thunell, S; Floderus, Y; Henrichson, A; Harper, P

    2006-01-01

    In a brief survey the work of Swedish porphyrinologists through time is presented, from the organic chemist Jakob Berzelius 1840 to the molecular biologists of today. The building up in Stockholm of a Swedish national competence centre for porphyria is touched upon and the emergence of a computerized national register on the porphyria gene carriers in the country described. Figures for the prevalences of the seven different forms of porphyria diagnosed in Sweden are given. The geographical distribution of gene mutation spectra is shown for the most frequent form, acute intermittent porphyria. The organisation at Porphyria Centre Sweden of its diagnostic and consultative services is described, as is the decentralized model for porphyria care applied in the form of a clinical network covering the long and sparsely populated country. The ideas and activities of the Swedish Porphyria Patients' Association are presented. Its focus on protection-by-information of the porphyria gene carrier against maltreatment in health service contacts, and against other exposures to environmental threats to his or her health, is discussed. The combined efforts of the national porphyria centre and the patients' association have resulted in early and accurate diagnosis of most of the porphyria gene carriers in the country. The information to the carriers and to the health service regarding the mechanisms of the diseases and the importance of avoiding exposure to disease triggering environmental factors have greatly reduced porphyric morbidity. In the case of the acute porphyrias, by this programme and after the introduction of heme arginate in the therapy, mortality in the acute phase has become extremely rare in Sweden. In contrast, probably due to greater awareness of the high risk for liver cancer in acute porphyrias the number of hepatoma cases diagnosed has increased. The current research activities at the Porphyria Centre which aim at finding ways to substitute the mutated gene in

  15. [Hereditary porphyrias and heme related disorders].

    PubMed

    Puy, Hervé; Gouya, Laurent; Deybach, Jean-charles

    2014-06-01

    Hereditary porphyrias comprise a group of eight metabolic disorders of the haem biosynthesis pathway, characterised by acute neurovisceral symptoms and/or skin lesions. Each porphyria is caused by abnormal functioning of a particular enzymatic step, resulting in specific accumulation of heme precursors. Seven porphyrias are due to a partial enzyme deficiency, while a gain-of-function mechanism has recently been identify in a novel porphyria. Acute porphyrias present with severe abdominal pain, nausea, constipation and confusion, and are sometimes complicated by seizures and severe neurological disorders, which may be life-threatening. Cutaneous porphyrias can also be present, with either acute painful photosensitivity or skin fragility and blisters. Rare recessive porphyrias usually manifest in early childhood with either severe chronic neurological symptoms or chronic haemolysis and severe cutaneous photosensitivity. Porphyrias are still under-diagnosed, but recent advances in the pathogenesis and genetics of human porphyrias are leading to better care of these patients and their families.

  16. Review of hepatocellular cancer, hypertension and renal impairment as late complications of acute porphyria and recommendations for patient follow-up.

    PubMed

    Stewart, Mary Felicity

    2012-11-01

    This review critically appraises the data emerging from small retrospective and prospective cohort studies suggesting that patients with the autosomal dominant acute porphyrias may be at increased risk of hepatocellular cancer (HCC), hypertension (HT) and renal impairment. The most striking finding is a marked excess risk of HCC in Swedish patients with acute intermittent porphyria (AIP). As Sweden has a relatively high prevalence of AIP due to a founder effect, it is uncertain to what extent the finding is generalisable to other populations or other acute porphyrias and whether early intervention through screening can improve outcomes. As yet there is no evidence for the cost-effectiveness of systematic surveillance for HCC in acute porphyria outside Sweden. Data from several populations also suggest a high prevalence of chronic sustained HT and renal impairment in AIP, but it is uncertain if this represents a true excess risk, in particular for asymptomatic patients. As these long-term complications are important and potentially treatable, a pragmatic recommendation is that symptomatic patients with acute porphyria should be offered specialist long-term follow-up and, for those aged >50 years, annual liver ultrasound may be considered following discussion of the likely risks and benefits. Opportunistic cardiovascular risk assessment can readily be incorporated into a structured annual review so that appropriate drugs safe for use in acute porphyria are prescribed promptly. As these diseases are rare, collaborative international epidemiological studies such as those being coordinated through the European Porphyria Network are essential to inform best clinical practice.

  17. Haem Biosynthesis and Antioxidant Enzymes in Circulating Cells of Acute Intermittent Porphyria Patients

    PubMed Central

    Ferrer, Miguel D.; Mestre-Alfaro, Antonia; Martínez-Tomé, Magdalena; Carrera-Quintanar, Lucrecia; Capó, Xavier; Jiménez-Monreal, Antonia M.; García-Diz, Luis; Roche, Enrique; Murcia, María A.; Tur, Josep A.

    2016-01-01

    The aims of the present study were to explore the expression pattern of haem biosynthesis enzymes in circulating cells of patients affected by two types of porphyria (acute intermittent, AIP, and variegate porphyria, VP), together with the antioxidant enzyme pattern in AIP in order to identify a possible situation of oxidative stress. Sixteen and twelve patients affected by AIP and VP, respectively, were analysed with the same numbers of healthy matched controls. Erythrocytes, neutrophils and peripheral blood mononuclear cells (PBMCs) were purified from blood, and RNA and proteins were extracted for quantitative real time PCR (qRT-PCR) and Western-blot analysis, respectively. Porhobilinogen deaminase (PBGD) and protoporphyrinogen oxidase (PPOX) gene and protein expression was analysed. Antioxidant enzyme activity and gene expression were additionally determined in blood cells, together with protein carbonyl content in plasma. PBMCs isolated from AIP patients presented low mRNA levels of PBGD when compared to controls, while PBMCs isolated from VP patients presented a decrease in PPOX mRNA. PPOX protein content was higher in AIP patients and lower in VP patients, compared to healthy controls. Regarding antioxidant enzymes, PBMCs and erythrocyte superoxide dismutase (SOD) presented statistically significant higher activity in AIP patients compared to controls, while catalase activity tended to be lower in these patients. No differences were observed regarding antioxidant gene expression in white blood cells. Circulating cells in AIP and VP patients present altered expression of haem biosynthetic enzymes, which could be useful for the differential diagnosis of these two types of porphyria in certain difficult cases. AIP patients present a condition of potential oxidative stress similar to VP patients, evidenced by the post-transcriptional activation of SOD and possible catalase impairment. PMID:27788171

  18. Feline porphyria associated with anemia, severe hepatic disease, and renal calculi.

    PubMed

    Schnier, Jonathan J; Hanna, Paul

    2010-10-01

    A 13-year-old, neutered male domestic cat presented with signs of weight loss, anemia, and hepatomegaly. Pathognomonic signs of porphyria were identified. Charcoal-like renal calculi and severe liver changes were observed, neither of which has been previously reported in association with feline porphyria.

  19. Guillain Barré Syndrome, Systemic Lupus Erythematosus and Acute Intermittent Porphyria - A Deadly Trio.

    PubMed

    Patil, Ankita D; Karnik, Niteen D; Nadkar, Milind Y; Gupta, Vishal A; Muralidhara, Krithika; Passidhi, Suresh

    2015-11-01

    Peripheral nervous system involvement occurs in 3-18% patients of systemic lupus erythematosus (SLE) cases. American College of Rheumatology (ACR) includes 19 neuropsychiatric syndromes for diagnosis of SLE divided into neurological syndromes of central, peripheral and autonomic nervous systems along with the psychiatric syndromes. Sensorimotor quadriparesis in a suspected case of SLE could be due to a Guillain Barré (GBS)-like illness, mononeuritis multiplex presenting as plexopathies, an anterior spinal artery syndrome or it can present like an acute transverse myelitis or hypokalemic periodic paralysis related to Sjogren's syndrome with renal tubular acidosis. We here report a case of a fulminant quadriparesis due to a SLE flare which subsequently was also found to be a case of Acute Intermittent Porphyria. PMID:27608785

  20. High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria.

    PubMed

    Pallet, Nicolas; Mami, Iadh; Schmitt, Caroline; Karim, Zoubida; François, Arnaud; Rabant, Marion; Nochy, Dominique; Gouya, Laurent; Deybach, Jean-Charles; Xu-Dubois, Yichum; Thervet, Eric; Puy, Hervé; Karras, Alexandre

    2015-08-01

    Acute intermittent porphyria (AIP) is a genetic disorder of the synthesis of heme caused by a deficiency in hydroxymethylbilane synthase (HMBS), leading to the overproduction of the porphyrin precursors δ-aminolevulinic acid and porphobilinogen. The aim of this study is to describe the clinical and biological characteristics, the renal pathology, and the cellular mechanisms of chronic kidney disease associated with AIP. A total of 415 patients with HMBS deficiency followed up in the French Porphyria Center were enrolled in 2003 in a population-based study. A follow-up study was conducted in 2013, assessing patients for clinical, biological, and histological parameters. In vitro models were used to determine whether porphyrin precursors promote tubular and endothelial cytotoxicity. Chronic kidney disease occurred in up to 59% of the symptomatic AIP patients, with a decline in the glomerular filtration rate of ~1 ml/min per 1.73 m(2) annually. Proteinuria was absent in the vast majority of the cases. The renal pathology was a chronic tubulointerstitial nephropathy, associated with a fibrous intimal hyperplasia and focal cortical atrophy. Our experimental data provide evidence that porphyrin precursors promote endoplasmic reticulum stress, apoptosis, and epithelial phenotypic changes in proximal tubular cells. In conclusion, the diagnosis of chronic kidney disease associated with AIP should be considered in cases of chronic tubulointerstitial nephropathy and/or focal cortical atrophy with severe proliferative arteriosclerosis. PMID:25830761

  1. High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria.

    PubMed

    Pallet, Nicolas; Mami, Iadh; Schmitt, Caroline; Karim, Zoubida; François, Arnaud; Rabant, Marion; Nochy, Dominique; Gouya, Laurent; Deybach, Jean-Charles; Xu-Dubois, Yichum; Thervet, Eric; Puy, Hervé; Karras, Alexandre

    2015-08-01

    Acute intermittent porphyria (AIP) is a genetic disorder of the synthesis of heme caused by a deficiency in hydroxymethylbilane synthase (HMBS), leading to the overproduction of the porphyrin precursors δ-aminolevulinic acid and porphobilinogen. The aim of this study is to describe the clinical and biological characteristics, the renal pathology, and the cellular mechanisms of chronic kidney disease associated with AIP. A total of 415 patients with HMBS deficiency followed up in the French Porphyria Center were enrolled in 2003 in a population-based study. A follow-up study was conducted in 2013, assessing patients for clinical, biological, and histological parameters. In vitro models were used to determine whether porphyrin precursors promote tubular and endothelial cytotoxicity. Chronic kidney disease occurred in up to 59% of the symptomatic AIP patients, with a decline in the glomerular filtration rate of ~1 ml/min per 1.73 m(2) annually. Proteinuria was absent in the vast majority of the cases. The renal pathology was a chronic tubulointerstitial nephropathy, associated with a fibrous intimal hyperplasia and focal cortical atrophy. Our experimental data provide evidence that porphyrin precursors promote endoplasmic reticulum stress, apoptosis, and epithelial phenotypic changes in proximal tubular cells. In conclusion, the diagnosis of chronic kidney disease associated with AIP should be considered in cases of chronic tubulointerstitial nephropathy and/or focal cortical atrophy with severe proliferative arteriosclerosis.

  2. Audit of the Use of Regular Haem Arginate Infusions in Patients with Acute Porphyria to Prevent Recurrent Symptoms.

    PubMed

    Marsden, Joanne T; Guppy, Simon; Stein, Penelope; Cox, Timothy M; Badminton, Michael; Gardiner, Tricia; Barth, Julian H; Stewart, M Felicity; Rees, David C

    2015-01-01

    The National Acute Porphyria Service (NAPS) provides acute care support and clinical advice for patients in England with active acute porphyria requiring haem arginate treatment and patients with recurrent acute attacks.This audit examined the benefits and complications of regular haem arginate treatment started with prophylactic intent to reduce the frequency of recurrent acute attacks in a group of patients managed through NAPS. We included 22 patients (21 female and 1 male) and returned information on diagnosis, indications for prophylactic infusions, frequency and dose, analgesia, activity and employment and complications including thromboembolic disease and iron overload.The median age at presentation with porphyria was 21 years (range 9-44), with acute abdominal pain as the predominant symptom. Patients had a median of 12 (1-400) attacks before starting prophylaxis and had received a median of 52 (0-1,350) doses of haem arginate. The median age at starting prophylaxis was 28 years (13-58) with a median delay of 4 years (0.5-37) between presentation and prophylaxis. The frequency of prophylactic haem arginate varied from 1 to 8 per month, and 67% patients were documented as having a reduction in pain frequency on prophylaxis. Only one patient developed clinically significant iron overload and required iron chelation, but the number of venous access devices required varied from 1 to 15, with each device lasting a median of 1.2 years before requiring replacement. Six patients stopped haem arginate and in three this was because their symptoms had improved. Prophylactic haem arginate appears to be beneficial in patients with recurrent acute porphyria symptoms, but maintaining central venous access may prove challenging. PMID:25762493

  3. Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome and lateralized periodic discharges plus fast activity on EEG.

    PubMed

    Silveira, Diosely C; Bashir, Mahrukh; Daniel, Joshua; Lucena, Michelle H; Bonpietro, Frank

    2016-01-01

    We report on a 20-year-old patient with a 6-month history of recurrent abdominal pain and a 3-day history of vomiting, hypertension, seizures, and encephalopathy. The brain MRI showed posterior reversible encephalopathy syndrome, and continuous EEG (cEEG) monitoring showed lateralized periodic discharges plus fast activity. Comprehensive CSF studies were negative. Because of severe abdominal pain without a definite etiology, we requested urine porphobilinogen and serum and fecal porphyrins, which suggested acute intermittent porphyria (AIP). The patient had a complete resolution of her symptoms with carbohydrate loading and high caloric diet. Acute intermittent porphyria is potentially life-threatening without proper management and prevention of triggers if it is not recognized.

  4. Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome and lateralized periodic discharges plus fast activity on EEG.

    PubMed

    Silveira, Diosely C; Bashir, Mahrukh; Daniel, Joshua; Lucena, Michelle H; Bonpietro, Frank

    2016-01-01

    We report on a 20-year-old patient with a 6-month history of recurrent abdominal pain and a 3-day history of vomiting, hypertension, seizures, and encephalopathy. The brain MRI showed posterior reversible encephalopathy syndrome, and continuous EEG (cEEG) monitoring showed lateralized periodic discharges plus fast activity. Comprehensive CSF studies were negative. Because of severe abdominal pain without a definite etiology, we requested urine porphobilinogen and serum and fecal porphyrins, which suggested acute intermittent porphyria (AIP). The patient had a complete resolution of her symptoms with carbohydrate loading and high caloric diet. Acute intermittent porphyria is potentially life-threatening without proper management and prevention of triggers if it is not recognized. PMID:27660746

  5. Anthropometric and Quality-of-Life Parameters in Acute Intermittent Porphyria Patients.

    PubMed

    Jiménez-Monreal, Antonia M; Murcia, M Antonia; Gómez-Murcia, Victoria; Bibiloni, Maria Del Mar; Pons, Antoni; Tur, Josep A; Martínez-Tomé, Magdalena

    2015-07-01

    The porphyrias are a group of rare metabolic disorders. The incidence and prevalence are low because the acute intermittent porphyria (AIP) is rare. Our aim was to assess the use of anthropometric and quality-of-life parameters in porphyric patients in order to identify predictor factors that might help in characterizing AIP patients.Sixteen AIP patients from Murcia (Spain) were recruited from local health centers in 2008 and 2009. A control group of 16 healthy people was established. Body composition was assessed by bioelectrical impedance analysis (BIA) and anthropometric measurements: body weight; height; knee-heel height; waist, hip, upper arm and calf circumferences (CCs); biacromion and biiliac diameters; bicondylar and biepicondylar width; and triceps, subscapular, supraspinale, and calf skinfold thickness. Anthropometric indicators were obtained from anthropometric measurements. A quality-of-life evaluation was carried out using the EuroQol-5D (EQ-5D) questionnaire and Barthel and Katz indexes. Significant differences in means were tested by unpaired Student t test. Group differences in anthropometric measurements were tested with a 2-way analysis of variance (group × condition: age group, overweight, and adiposity degree). Relative frequencies were obtained for noncontinuous variables. Significant differences in prevalence were calculated by means of χ.AIP patients showed statistically significant differences in terms of knee-heel height, biiliac diameter, CC, triceps skinfold thickness, BIA, ponderal index, endomorphy, and ectomorphy. Only 1 quality-of-life indicator, visual analog scale, in the EQ-5D questionnaire showed significant differences between porphyric and control groups.Some anthropometric parameters and the EQ-5D questionnaire could be used to appreciate the presence or follow the evolution of the disease in AIP patients.

  6. Anthropometric and Quality-of-Life Parameters in Acute Intermittent Porphyria Patients

    PubMed Central

    Jiménez-Monreal, Antonia M; Murcia, MAntonia; Gómez-Murcia, Victoria; Bibiloni, Maria del Mar; Pons, Antoni; Tur, Josep A.; Martínez-Tomé, Magdalena

    2015-01-01

    Abstract The porphyrias are a group of rare metabolic disorders. The incidence and prevalence are low because the acute intermittent porphyria (AIP) is rare. Our aim was to assess the use of anthropometric and quality-of-life parameters in porphyric patients in order to identify predictor factors that might help in characterizing AIP patients. Sixteen AIP patients from Murcia (Spain) were recruited from local health centers in 2008 and 2009. A control group of 16 healthy people was established. Body composition was assessed by bioelectrical impedance analysis (BIA) and anthropometric measurements: body weight; height; knee-heel height; waist, hip, upper arm and calf circumferences (CCs); biacromion and biiliac diameters; bicondylar and biepicondylar width; and triceps, subscapular, supraspinale, and calf skinfold thickness. Anthropometric indicators were obtained from anthropometric measurements. A quality-of-life evaluation was carried out using the EuroQol-5D (EQ-5D) questionnaire and Barthel and Katz indexes. Significant differences in means were tested by unpaired Student t test. Group differences in anthropometric measurements were tested with a 2-way analysis of variance (group × condition: age group, overweight, and adiposity degree). Relative frequencies were obtained for noncontinuous variables. Significant differences in prevalence were calculated by means of χ2. AIP patients showed statistically significant differences in terms of knee-heel height, biiliac diameter, CC, triceps skinfold thickness, BIA, ponderal index, endomorphy, and ectomorphy. Only 1 quality-of-life indicator, visual analog scale, in the EQ-5D questionnaire showed significant differences between porphyric and control groups. Some anthropometric parameters and the EQ-5D questionnaire could be used to appreciate the presence or follow the evolution of the disease in AIP patients. PMID:26222840

  7. Variegate porphyria and heavy metal poisoning from ingestion of "moonshine".

    PubMed

    Hughes, G S; Davis, L

    1983-08-01

    A patient with cavitary tuberculosis, hepatic cirrhosis, bullous skin lesions over sun-exposed surfaces, disorientation, and a chronic, as well as recent, history of illicit alcohol consumption was found to have acute variegate porphyria by characteristic fecal and urinary porphyrin studies. Elevated levels of lead and arsenic were found in serum and urine without evidence of heavy metal storage in hair and liver. We suspect that the variegate porphyria was precipitated by the ingestion of heavy metals contained in illicit alcohol. In a patient with disorientation, bullous skin lesions, and a history of illicit alcohol ingestion, one must consider heavy metal intoxication and secondary porphyrin abnormalities.

  8. Urinary metabolic fingerprint of acute intermittent porphyria analyzed by (1)H NMR spectroscopy.

    PubMed

    Carichon, Mickael; Pallet, Nicolas; Schmitt, Caroline; Lefebvre, Thibaud; Gouya, Laurent; Talbi, Neila; Deybach, Jean Charles; Beaune, Philippe; Vasos, Paul; Puy, Hervé; Bertho, Gildas

    2014-02-18

    (1)H NMR is a nonbiased technique for the quantification of small molecules that could result in the identification and characterization of potential biomarkers with prognostic value and contribute to better understand pathophysiology of diseases. In this study, we used (1)H NMR spectroscopy to analyze the urinary metabolome of patients with acute intermittent porphyria (AIP), an inherited metabolic disorder of heme biosynthesis in which an accumulation of the heme precursors 5-aminolaevulinic acid (ALA) and porphobilinogen (PBG) promotes sudden neurovisceral attacks, which can be life-threatening. Our objectives were (1) to demonstrate the usefulness of (1)H NMR to identify and quantify ALA and PBG in urines from AIP patients and (2) to identify metabolites that would predict the response to AIP crisis treatment and reflect differential metabolic reprogramming. Our results indicate that (1)H NMR can help to diagnose AIP attacks based on the identification of ALA and PBG. We also show that glycin concentration increases in urines from patients with frequent recurrences at the end of the treatment, after an initial decrease, whereas PBG concentration remains low. Although the reasons for this altered are elusive, these findings indicate that a glycin metabolic reprogramming occurs in AIPr patients and is associated with recurrence. Our results validate the proof of concept of the usefulness of (1)H NMR spectroscopy in clinical chemistry for the diagnosis of acute attack of AIP and identify urinary glycin as a potential marker of recurrence of AIP acute attacks. PMID:24437734

  9. [Porphyrias and haem related disorders].

    PubMed

    Peoc'h, K; Martin-Schmitt, C; Talbi, N; Deybach, J-C; Gouya, L; Puy, H

    2016-03-01

    The hereditary porphyrias comprise a group of eight metabolic disorders of the haem biosynthesis pathway characterised by acute neurovisceral symptoms, skin lesions or both. Each porphyria is caused by abnormal function of a separate enzymatic step resulting in a specific accumulation of haem precursors. Seven porphyrias are the consequence of a partial enzyme deficiency while a gain of function mechanism has been recently characterised in a novel porphyria. Acute porphyrias present with severe abdominal pain, nausea, constipation, confusion and seizure, which may be life threatening. Cutaneous porphyrias can be present with either acute painful photosensitivity or skin fragility and blisters. Rare recessive porphyrias usually manifest in early childhood with either severe chronic neurological symptoms or chronic haemolysis and severe cutaneous photosensitivity. Porphyrias are still underdiagnosed, but once they are suspected, and depending on the clinical presentation, a specific and simple front line test allows the diagnosis in all symptomatic patients. Diagnosis is essential to institute as soon as possible a specific treatment. Screening families to identify presymptomatic carriers is crucial to prevent chronic complications and overt disease by counselling on avoiding potential precipitants. PMID:26774916

  10. [Porphyrias and haem related disorders].

    PubMed

    Peoc'h, K; Martin-Schmitt, C; Talbi, N; Deybach, J-C; Gouya, L; Puy, H

    2016-03-01

    The hereditary porphyrias comprise a group of eight metabolic disorders of the haem biosynthesis pathway characterised by acute neurovisceral symptoms, skin lesions or both. Each porphyria is caused by abnormal function of a separate enzymatic step resulting in a specific accumulation of haem precursors. Seven porphyrias are the consequence of a partial enzyme deficiency while a gain of function mechanism has been recently characterised in a novel porphyria. Acute porphyrias present with severe abdominal pain, nausea, constipation, confusion and seizure, which may be life threatening. Cutaneous porphyrias can be present with either acute painful photosensitivity or skin fragility and blisters. Rare recessive porphyrias usually manifest in early childhood with either severe chronic neurological symptoms or chronic haemolysis and severe cutaneous photosensitivity. Porphyrias are still underdiagnosed, but once they are suspected, and depending on the clinical presentation, a specific and simple front line test allows the diagnosis in all symptomatic patients. Diagnosis is essential to institute as soon as possible a specific treatment. Screening families to identify presymptomatic carriers is crucial to prevent chronic complications and overt disease by counselling on avoiding potential precipitants.

  11. Porphyria Diagnostics – Part 1: A brief overview of the porphyrias

    PubMed Central

    Ramanujam, Vaithamanithi-Mudumbai Sadagopa; Anderson, Karl Elmo

    2015-01-01

    The porphyria diseases are a group of metabolic disorders caused by abnormal functioning of heme biosynthesis enzymes and characterized by the excessive accumulation and excretion of porphyrins and their precursors. Precisely which of these chemicals builds up depends on the type of porphyria. Porphyria is not a single disease but a group of nine disorders: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), delta-aminolevelunic acid dehyratase deficiency porphyria (ADP), porphyria cutanea tarda (PCT), hepatoerythropoetic porphyria (HEP), congenital erythropoetic porphyria (CEP), erythropoetic protoporphyria (EPP), and X-linked protoporphyria (XLP). Each porphyria results from overproduction of heme precursors secondary to partial deficiency or, in XLP, increased activity of one of the enzymes of heme biosynthesis. Taken together, all forms of porphyria afflict fewer than 200,000 people in the United States. Based on European studies, the prevalence of the most common porphyria, PCT, is 1 in 10,000, the most common acute porphyria, AlP, is about 1 in 20,000, and the most common erythropoietic porphyria, EPP, is estimated at 1 in 50,000 to 75,000. CEP is extremely rare with prevalence estimates of 1 in 1,000,000 or less. Only 6 cases of ADP are documented. The current porphyria literature is very exhaustive and a brief overview of porphyria diseases is essential in order for the reader to better appreciate the relevance of this area of research prior to undertaking biochemical diagnostics procedures. This unit summarizes the current knowledge on the classification, clinical features, etiology, pathogenesis, and genetics of these porphyria diseases. PMID:26132003

  12. Porphyria Diagnostics-Part 1: A Brief Overview of the Porphyrias.

    PubMed

    Ramanujam, Vaithamanithi-Mudumbai Sadagopa; Anderson, Karl Elmo

    2015-07-01

    Porphyria diseases are a group of metabolic disorders caused by abnormal functioning of heme biosynthesis enzymes and characterized by excessive accumulation and excretion of porphyrins and their precursors. Precisely which of these chemicals builds up depends on the type of porphyria. Porphyria is not a single disease but a group of nine disorders: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), δ-aminolevulinic acid dehydratase deficiency porphyria (ADP), porphyria cutanea tarda (PCT), hepatoerythropoietic porphyria (HEP), congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP), and X-linked protoporphyria (XLP). Each porphyria results from overproduction of heme precursors secondary to partial deficiency or, in XLP, increased activity of one of the enzymes of heme biosynthesis. Taken together, all forms of porphyria afflict fewer than 200,000 people in the United States. Based on European studies, the most common porphyria, PCT, has a prevalence of 1 in 10,000, the most common acute porphyria, AlP, has a prevalence of ∼1 in 20,000, and the most common erythropoietic porphyria, EPP, is estimated at 1 in 50,000 to 75,000. CEP is extremely rare, with prevalence estimates of 1 in 1,000,000 or less. Only six cases of ADP are documented. The current porphyria literature is very exhaustive and a brief overview of porphyria diseases is essential in order for the reader to better appreciate the relevance of this area of research prior to undertaking biochemical diagnostics procedures. This unit summarizes the current knowledge on the classification, clinical features, etiology, pathogenesis, and genetics of porphyria diseases.

  13. THINK PORPHYRIA: CASE REPORT AND REVIEW OF LITERATURE.

    PubMed

    Straume, Zane; Skuja, Vita; Proskurina, Anna; Māliņa, Justīne; Hasnere, Sigita; Krupnova, Inga; Lejnieks, Aivars; Derovs, Aleksejs

    2015-01-01

    Porphyrias are a group of rare disorders caused by enzyme defects in haem biosynthesis pathway. Acute intermittent porphyria is the most common hepatic porphyria. The disorder presents with severe neuropathic abdominal pain that can be accompanied by a wide range of gastrointestinal, psychiatric and neurological symptoms, making the diagnosis clarification very challenging. We report a case of a 27-year-old female patient who presented with acute abdominal pain, vomiting and marked hyponatremia, developed seizures and disorientation, and eventually required intensive care unit treatment to maintain breathing. Her symptoms were initially misinterpreted as a functional gastrointestinal disorder, thus delaying the needed specific treatment. She was diagnosed a week after the initial hospital admission, and her condition improved after receiving treatment with intravenous glucose and haemin. For patients with acute neurovisceral attacks, early clinical recognition is essential. Severe hyponatremia, urine that develops orange colour on exposure to light and gastrointestinal symptom combination with neurologic symptoms are three valuable clues that may lead to the right diagnosis faster. Pathophysiology of hyponatremia in case of acute intermittent porphyria in only partly understood and can be associated with syndrome of inappropriate antidiuretic hormone secretion, gastrointestinal or renal sodium loss.

  14. Ultrasound-guided regional anesthesia in a pediatric patient with acute intermittent porphyria: literature review and case report.

    PubMed

    Olutunmbi, Yetunde; Gurnaney, Harshad G; Galvez, Jorge A; Simpao, Allan F

    2014-06-01

    Ultrasound-guided regional anesthesia techniques placed under general anesthesia have not been reported in pediatric patients with acute intermittent porphyria (AIP). A 9-year-old male with AIP presented for right inguinal herniorraphy. Family history included one relative's death after anesthesia. Preoperative preparation included reviewing medications safe for AIP patients, minimizing known AIP triggers (fasting, stress) and ensuring access to rescue medications. Intraoperative management included a propofol induction with the patient's mother present in the operating room. We performed an ultrasound-guided ilioinguinal-iliohypogastric nerve block under general anesthesia. The surgery proceeded without complications and the patient did not demonstrate signs of an AIP crisis. PMID:25137868

  15. Studies in porphyria. IV. Expression of the gene defect of acute intermittent porphyria in cultured human skin fibroblasts and amniotic cells: prenatal diagnosis of the porphyric trait

    PubMed Central

    1975-01-01

    The gene lesion of the porphyrin-heme synthetic pathway in acute intermittent porphyria (AIP) is reflected in a deficient level of activity of the cytosol enzyme uroporphyrinogen I synthetase (URO-S). A marked URO-S deficiency has been demonstrated in the liver and in circulating erythrocytes of individuals with both active and latent AIP. This enzymic abnormality accounts for the excessive production and excretion into urine of the porphyrin precursors, lamda-aminolevulinic acid (ALA) and porphobilinogen (PBG) in AIP subjects. In this study, utilizing cell culture techniques, a marked URO-S deficiency has also been demonstrated in skin fibroblasts from AIP patients and in cells derived through aminocentesis from an approximately 17-wk old fetus. The prenatal diagnosis of the AIP trait in this fetus was confirmed postnatally by the demonstration in the child of a deficient level of erythrocyte URO-S activity which was comparable to those found in her AIP mother and affected sibling and which was approximately one-half the levels characterizing her normal father and aunt and a second unaffected sibling. The identification of the URO-S deficiency in cultured human fibroblasts from AIP patients was facilitated by a newly developed, sensitive assay for the enzyme activity. In this assay, the ability of such cells to convert ALA to protoporphyrin was quantitated; in the sequence of reactions involved in this transformation, URO-S is limiting so that the gene defect of AIP could be simply and precisely determined by appropriate spectrofluorometry of cell extracts. The technique described has distinct advantages over the direct enzymatic assay for URO-S activity in cultured human skin fibroblasts and permits clear differentiation of AIP carrier from normal individuals. PMID:1165472

  16. Studies in porphyria. IV. Expression of the gene defect of acute intermittent porphyria in cultured human skin fibroblasts and amniotic cells: prenatal diagnosis of the porphyric trait.

    PubMed

    Sassa, S; Solish, G; Levere, R D; Kappas, A

    1975-09-01

    The gene lesion of the porphyrin-heme synthetic pathway in acute intermittent porphyria (AIP) is reflected in a deficient level of activity of the cytosol enzyme uroporphyrinogen I synthetase (URO-S). A marked URO-S deficiency has been demonstrated in the liver and in circulating erythrocytes of individuals with both active and latent AIP. This enzymic abnormality accounts for the excessive production and excretion into urine of the porphyrin precursors, lamda-aminolevulinic acid (ALA) and porphobilinogen (PBG) in AIP subjects. In this study, utilizing cell culture techniques, a marked URO-S deficiency has also been demonstrated in skin fibroblasts from AIP patients and in cells derived through aminocentesis from an approximately 17-wk old fetus. The prenatal diagnosis of the AIP trait in this fetus was confirmed postnatally by the demonstration in the child of a deficient level of erythrocyte URO-S activity which was comparable to those found in her AIP mother and affected sibling and which was approximately one-half the levels characterizing her normal father and aunt and a second unaffected sibling. The identification of the URO-S deficiency in cultured human fibroblasts from AIP patients was facilitated by a newly developed, sensitive assay for the enzyme activity. In this assay, the ability of such cells to convert ALA to protoporphyrin was quantitated; in the sequence of reactions involved in this transformation, URO-S is limiting so that the gene defect of AIP could be simply and precisely determined by appropriate spectrofluorometry of cell extracts. The technique described has distinct advantages over the direct enzymatic assay for URO-S activity in cultured human skin fibroblasts and permits clear differentiation of AIP carrier from normal individuals.

  17. Porphyria and its neurologic manifestations.

    PubMed

    Tracy, Jennifer A; Dyck, P James B

    2014-01-01

    Porphyrias are rare disorders resulting from a defect in the heme biosynthetic pathway. They can produce significant disease of both the peripheral and central nervous systems, in addition to other organ systems, with acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria as the subtypes associated with neurologic manifestations. The presence of a motor-predominant peripheral neuropathy (axonal predominant), accompanied by gastrointestinal distress and neuropsychiatric manifestations, should be a strong clue to the diagnosis of porphyria. Clinical confirmation can be made through evaluation of urine porphyrins during an exacerbation of disease. While hematin is helpful for acute treatment, long-term effective management requires avoidance of overstimulation of the cytochrome P450 pathway, as well as other risk factor control.

  18. Acute hepatic failure in children.

    PubMed Central

    Riely, C. A.

    1984-01-01

    Many diseases may present as acute hepatic failure in the pediatric age group, including viral hepatitis A and B, adverse drug reactions, both toxic and "hepatitic," and inherited metabolic disorders such as tyrosinemia, alpha 1 antitrypsin deficiency, and Wilson's disease. Management is primarily supportive, with care taken to anticipate the known complications of hepatic failure. Few "curative" therapies are known, although attempts at stimulating hepatic regeneration may be helpful. Images FIG. 1 FIG. 3 FIG. 4 PMID:6433587

  19. Porphyrin and heme metabolism and the porphyrias.

    PubMed

    Bonkovsky, Herbert L; Guo, Jun-Tao; Hou, Weihong; Li, Ting; Narang, Tarun; Thapar, Manish

    2013-01-01

    Porphyrins and metalloporphyrins are the key pigments of life on earth as we know it, because they include chlorophyll (a magnesium-containing metalloporphyrin) and heme (iron protoporphyrin). In eukaryotes, porphyrins and heme are synthesized by a multistep pathway that involves eight enzymes. The first and rate-controlling step is the formation of delta-aminolevulinic acid (ALA) from glycine plus succinyl CoA, catalyzed by ALA synthase. Intermediate steps occur in the cytoplasm, with formation of the monopyrrole porphobilinogen and the tetrapyrroles hydroxymethylbilane and a series of porphyrinogens, which are serially decarboxylated. Heme is utilized chiefly for the formation of hemoglobin in erythrocytes, myoglobin in muscle cells, cytochromes P-450 and mitochondrial cytochromes, and other hemoproteins in hepatocytes. The rate-controlling step of heme breakdown is catalyzed by heme oxygenase (HMOX), of which there are two isoforms, called HMOX1 and HMOX2. HMOX breaks down heme to form biliverdin, carbon monoxide, and iron. The porphyrias are a group of disorders, mainly inherited, in which there are defects in normal porphyrin and heme synthesis. The cardinal clinical features are cutaneous (due to the skin-damaging effects of excess deposited porphyrins) or neurovisceral attacks of pain, sometimes with weakness, delirium, seizures, and the like (probably due mainly to neurotoxic effects of ALA). The treatment of choice for the acute hepatic porphyrias is intravenous heme therapy, which repletes a critical regulatory heme pool in hepatocytes and leads to downregulation of hepatic ALA synthase, which is a biochemical hallmark of all forms of acute porphyria in relapse.

  20. [Porphyria cutanea tara].

    PubMed

    Merk, H F

    2016-03-01

    Porphyria cutanea tara (PCT) has a prevelance of about 40 new diagnoses per 1 million people per year and is the most frequently occurring type of porphyria worldwide. Inhibition of the uroporphyrinogen decarboxylase (UROD) is the main cause of the disease, which can be the result of a heterozygous or homozygous mutation of the UROD gene; however, xenobiotics or other diseases may play an important role for the precipitation of the disease. Risk factors include alcohol, estrogen, iron overload, and hemochromatosis, hepatitis C or poisoning, e.g., with polyhalogenated aromatic compounds such as hexachlorobenzene. Signs and symptoms are blisters, skin fragility, erosions hyperpigmentation, sclerodermoid plaques. Therapy includes sun protection, prevention of risk factors, phlebotomy, and chloroquine. PMID:26743054

  1. Porphyria Treatment Options

    MedlinePlus

    ... only. For treatment options for Porphyria Cutanea Tarda (PCT) , Congenital Erythropoietic Protoporphyria (CEP) and Hepatoerythropoietic Porphyria (HEP) ... Contact Us About Porphyria AIP VP HCP ADP PCT EPP CEP HEP Diet and Nutrition History of ...

  2. Severe porphyric neuropathy--importance of screening for porphyria in Guillain-Barré syndrome.

    PubMed

    Schutte, Clara-Maria; van der Meyden, Cornelius H; van Niekerk, Linette; Kakaza, Mandisa; van Coller, Riaan; Ueckermann, Veronica; Oosthuizen, Nicky M

    2015-11-20

    The hepatic porphyrias are a group of rare metabolic disorders, each of which is associated with a specific enzymatic alteration in the haem biosynthesis pathway. In South Africa (SA), a high incidence of variegate porphyria (VP) is seen as a result of a founder effect, but acute intermittent porphyria (AIP) is also encountered. The development of acute neurovisceral attacks is related to environmental factors, including medications, hormones and diet. A possible manifestation of a severe attack is rapidly progressing quadriparesis, which may mimic Guillain-Barré syndrome. We present four such cases, highlighting that acute porphyria should be considered in the differential diagnosis of Guillain-Barré syndrome. Three patients presented to Steve Biko Academic Hospital, Pretoria, SA, with progressive quadriparesis, and one to a private hospital with acute abdominal pain followed by rapidly progressive quadriparesis. Two patients had started antiretroviral therapy before the development of symptoms, and one had started antituberculosis therapy. All patients had marked weakness with depressed reflexes, and showed varying degrees of confusion. An initial diagnosis of Guillain-Barré syndrome led to administration of intravenous immunoglobulins in two patients. On testing for porphyria, it was found that two patients had AIP and two VP. Electrophysiological investigations revealed severe mainly motor axonal neuropathy in all. Two patients deteriorated to the point of requiring mechanical ventilation, and one of them died due to complications of critical illness. Haemin was administered to three patients, but the process of obtaining this medication was slow, which delayed the recommended early administration. The surviving patients showed minimal recovery and remained severely disabled. Porphyric neuropathy should always be considered as a differential diagnosis in a patient with an acute neuropathy, especially in SA. Absence of abdominal pain does not exclude the

  3. Porphyrias at a glance: diagnosis and treatment.

    PubMed

    Cappellini, Maria Domenica; Brancaleoni, Valentina; Graziadei, Giovanna; Tavazzi, Dario; Di Pierro, Elena

    2010-10-01

    Porphyrias are a group of eight rare inherited metabolic disorders of heme biosynthesis pathway. Porphyrias are still underdiagnosed, although examinations of urine and plasma are first-line tests for detecting excess of porphyrins or heme precursors in suspected patients. Diagnosis, particularly for the acute forms, is essential to avoid precipitating factors and the use of triggering drugs. Mutation screening of family members is recommended to identify presymptomatic carriers and to prevent acute attacks. The therapeutic approach should be appropriate regarding specific forms of porphyria and treatment should be started promptly.

  4. [Laboratory tests and therapeutic strategies for the porphyrias].

    PubMed

    Poblete-Gutiérrez, P; Wiederholt, T; Merk, H F; Frank, J

    2006-06-01

    The porphyrias are a heterogeneous group of predominantly hereditary metabolic diseases resulting from a dysfunction of heme biosynthesis. Most of the porphyrias can manifest with a broad range of cutaneous symptoms on the sun-exposed areas of the body, whereas other variants reveal life-threatening acute neurological attacks. Further, mixed types of porphyrias exist. Besides the skin, other organs can be affected, such as the liver and the central nervous system. Therefore, interdisciplinary supervision of these patients is mandatory. In this review we will first present the clinical picture and diagnosis of the porphyrias, including the specific biochemical laboratory tests and a diagnostic algorithm. Thereafter, the current therapeutic concepts will be briefly addressed. Finally, we introduce the European Porphyria Initiative (EPI), an association of various European porphyria centers that is aiming at gathering the broad experience of internationally renowned porphyria experts for the development of European consensus guidelines for diagnosis and treatment of these metabolic disorders.

  5. The effect of therapeutic drugs and other pharmacologic agents on activity of porphobilinogen deaminase, the enzyme that is deficient in intermittent acute porphyria.

    PubMed

    Tishler, P V

    1999-01-01

    Drugs and toxins precipitate life-threatening acute attacks in patients with intermittent acute porphyria. These materials may act by directly inhibiting enzyme activity, thus further reducing porphobilinogen (PBG) deaminase activity below the ca. 50% level that results from the gene defect. To test this, we studied the effects of drugs that precipitate acute attacks (lead, phenobarbital, griseofulvin, phenytoin, sulfanilamide, sulfisoxazole, 17alpha-ethinyl estradiol, 5beta-pregnan-3alpha-ol-20-one), drugs that are safe (lithium, magnesium, chlorpromazine, promethazine), and those with uncertain effects (ethyl alcohol, imipramine, diazepam, haloperidol) on activity of PBG deaminase in vitro and in vivo. In the in vitro studies, of PBG deaminase from human erythrocytes from normals and individuals with IAP, only lead (> or = .01 mM) inhibited enzyme activity. Chlorpromazine (> or = .01 mM), promethazine (> or = .01 mM) and imipramine (1 mM) seemed to increase enzyme activity. In most in vivo experiments, male rats were injected intraperitoneally with test material twice daily for 3 days and once on day four; and erythrocyte and hepatic PBG deaminase activity was assayed thereafter. Effects on enzyme activity were observed only with 17alpha-ethinyl estradiol (0.05 microg/kg/day; reduction of 11% in erythrocyte enzyme [NS], and of 20% in liver enzyme [P=.02]), and imipramine (12.5 mg/kg/day; reduction in erythrocyte enzyme activity of 13% [P<.001]). Rats given lead acetate in their drinking water (10 mg/ml) for the first 60 days of life, resulting in high blood and liver lead levels, had increased erythrocyte PBG deaminase (167% of control; P=.004). Thus, enzyme inhibition by lead in vitro was not reflected in a similar in vivo inhibition. The only inhibitory effects in vivo, with ethinyl estradiol and imipramine, appear to be mild and biologically inconsequential. We conclude that inhibition of PBG deaminase activity by materials that precipitate acute attacks is an

  6. The little imitator--porphyria: a neuropsychiatric disorder.

    PubMed Central

    Crimlisk, H L

    1997-01-01

    Three common subtypes of porphyria give rise to neuropsychiatric disorders; acute intermittent porphyria, variegate porphyria, and coproporphyria. The second two also give rise to cutaneous symptoms. Neurological or psychiatric symptoms occur in most acute attacks, and may mimic many other disorders. The diagnosis may be missed because it is not even considered or because of technical problems, such as sample collection and storage, and interpretation of results. A negative screening test does not exclude the diagnosis. Porphyria may be overrepresented in psychiatric populations, but the lack of control groups makes this uncertain. The management of patients with porphyria and psychiatric symptoms causes considerable problems. Three cases are described to illustrate some of these issues. Advances in molecular biology permit identification of patients and latent carriers in the family. Care to avoid relapses and improved treatments have reduced the mortality. PMID:9120442

  7. Chronic urticaria following acute hepatitis A.

    PubMed

    Griffin, Paul M; Kevat, Dev A S; McCarthy, James S; Woods, Marion L

    2012-09-18

    Urticaria has a documented association with the prodromal phases of hepatitis A, B and, although still contentious, likely hepatitis C. Despite the documented association there are few actual reported cases of urticaria occurring with hepatitis A infection and in all of the cases reported so far the urticaria preceded the diagnosis of hepatitis A and was acute rather than chronic. We describe a case of urticaria occurring following acute infection with hepatitis A, which persisted beyond 6 weeks and therefore was by definition chronic. Although chronic urticaria has been reported to be associated with other forms of viral hepatitis, to the best of our knowledge this has not been reported previously with hepatitis A.

  8. Dual porphyrias revisited.

    PubMed

    Poblete-Gutiérrez, Pamela; Badeloe, Sadhanna; Wiederholt, Tonio; Merk, Hans F; Frank, Jorge

    2006-09-01

    The porphyrias are clinically and genetically heterogeneous metabolic diseases, which predominantly result from a hereditary dysfunction in the pathway of haeme biosynthesis. Currently, at least eight different forms of porphyrias can be differentiated, all of them characterized by a specific enzyme deficiency that is either inherited in an autosomal-dominant fashion, autosomal recessively or, in the case of porphyria cutanea tarda, might also be acquired. All genes encoding these enzymes have been cloned and several mutations underlying the different types of porphyrias have been reported. Traditionally, the diagnosis of porphyria is made on the basis of clinical symptoms, characteristic biochemical findings and enzyme assays. In some porphyria patients and families, however, these diagnostic tools can reveal simultaneous findings compatible with two different forms of porphyria, a phenomenon referred to as dual porphyria. Here, we give an overview on what is currently known about these peculiar variants of porphyria and suggest that, whenever feasible, molecular genetic analysis should complement the analytical techniques used to characterize patients and families in which a double enzymatic deficiency within the haeme biosynthetic pathway is assumed.

  9. Fulminant hepatic failure (FHF) due to acute hepatitis C.

    PubMed

    Younis, Bilal Bin; Arshad, Rozina; Khurhsid, Saima; Masood, Junaid; Nazir, Farhan; Tahira, Maham

    2015-01-01

    Acute hepatitis C (HCV) infection has been identified as an important cause of fulminant hepatic failure (FHF), characterized by rapid deterioration of liver function from massive hepatic necrosis leading to encephalopathy and multi-organ failure. We admitted a female patient at Shalamar Hospital with jaundice, fever, encephalopathy and coagulopathy of short duration with no history of any comorbidity. Her hepatitis viral screen revealed positive anti HCV. Her viral loads were also high. A diagnosis of FHF due to acute HCV infection was made. Patient was treated conservatively and improved gradually. In summary, acute HCV can cause FHF and should be ruled out in patients with FHF of unknown cause in an endemic country for HCV like Pakistan.

  10. N-alkylprotoporphyrin formation and hepatic porphyria in dogs after administration of a new antiepileptic drug candidate: mechanism and species specificity.

    PubMed

    Nicolas, Jean-Marie; Chanteux, Hugues; Mancel, Valérie; Dubin, Guy-Marie; Gerin, Brigitte; Staelens, Ludovicus; Depelchin, Olympe; Kervyn, Sophie

    2014-10-01

    A new antiepileptic synaptic vesicle 2a (SV2a) ligand drug candidate was tested in 4-week oral toxicity studies in rat and dog. Brown pigment inclusions were found in the liver of high-dose dogs. The morphology of the deposits and the accompanying liver changes (increased plasma liver enzymes, increased total hepatic porphyrin level, decreased liver ferrochelatase activity, combined induction, and inactivation of cytochrome P-450 CYP2B11) suggested disruption of the heme biosynthetic cascade. None of these changes was seen in rat although this species was exposed to higher parent drug levels. Toxicokinetic analysis and in vitro metabolism assays in hepatocytes showed that dog is more prone to oxidize the drug candidate than rat. Mass spectrometry analysis of liver samples from treated dogs revealed an N-alkylprotoporphyrin adduct. The elucidation of its chemical structure suggested that the drug transforms into a reactive metabolite which is structurally related to a known reference porphyrogenic agent allylisopropylacetamide. That particular metabolite, primarily produced in dog but neither in rat nor in human, has the potential to alkylate the prosthetic heme of CYP. Overall, the data suggested that the drug candidate should not be porphyrogenic in human. This case study further exemplifies the species variability in the susceptibility to drug-induced porphyria.

  11. Acute viral E hepatitis with chronic liver disease (autoimmune hepatitis).

    PubMed

    Desai, H G; Naik, A S

    2005-03-01

    A 36 years old male presented with anorexia, jaundice and ascites. He was suffering from acute viral E hepatitis. In view of ascites, he was investigated for associated asymptomatic chronic liver disease (CLD). The CLD was diagnosed as cirrhosis with autoimmune hepatitis and was treated with steroid with good response. He is maintaining good health with low dose steroid, on follow up for 1 year.

  12. Acute Intermittent Porphyria (AIP)

    MedlinePlus

    ... Panhematin ® is irritation of the vein used for infusion (phlebitis). This is avoided by slow infusion through a large caliber vein or central line. ... ensuring proper caloric intake, which can include intravenous infusion of sufficient nutrients (glucose and salt). Carbohydrate loading ...

  13. Acute intermittent porphyria: A single-base deletion and a nonsense mutation in the human hydroxymethylbilane synthase gene, predicting truncations of the enzyme polypeptide

    SciTech Connect

    Lee, G.L.; Astrin, K.H.; Desnick, R.J.

    1995-08-28

    Acute intermittent porphyria (AIP) is an autosomal-dominant inborn error of metabolism that results from the half-normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase (HMB-synthase). AIP is an ecogenetic condition, since the life-threatening acute attacks are precipitated by various factors, including drugs, alcohol, fasting, and certain hormones. Biochemical diagnosis is problematic, and the identification of mutations in the HMB-synthase gene provides accurate detection of presymptomatic heterozygotes, permitting avoidance of the acute precipitating factors. By direct solid-phase sequencing, two mutations causing AIP were identified, an adenine deletion at position 629 in exon 11(629delA), which alters the reading frame and predicts premature truncation of the enzyme protein after amino acid 255, and a nonsense mutation in exon 12 (R225X). These mutations were confirmed by either restriction enzyme analysis or family studies of symptomatic patients, permitting accurate presymptomatic diagnosis of affected relatives. 29 refs., 2 figs.

  14. Acute abdomen caused by brucellar hepatic abscess.

    PubMed

    Ibis, Cem; Sezer, Atakan; Batman, Ali K; Baydar, Serkan; Eker, Alper; Unlu, Ercument; Kuloglu, Figen; Cakir, Bilge; Coskun, Irfan

    2007-10-01

    Brucellosis is a zoonotic infection that is transmitted from animals to humans by ingestion of infected food products, direct contact with an infected animal, or aerosol inhalation. The disease is endemic in many countries, including the Mediterranean basin, the Middle East, India, Mexico, Central and South America and, central and southwest Asia. Human brucellosis is a systemic infection with a wide clinical spectrum. Although hepatic involvement is very common during the course of chronic brucellosis, hepatic abscess is a very rare complication of Brucella infection. We present a case of hepatic abscess caused by Brucella, which resembled the clinical presentation of surgical acute abdomen.

  15. Did Ulysses have porphyria?

    PubMed

    Pierach, Claus A

    2004-07-01

    Although the biosynthetic pathway to heme has been well elucidated and errors along that route have been identified and firmly connected to specific diseases, the porphyrias, slight but nonspecific abnormalities, are occasionally invoked as proof of porphyria or in support of other diagnoses. An errant patient with a conundrum of symptoms but without an explanation for them might have to take iatrogenic detours only to learn after what are at times ulyssean vagaries that the initial diagnosis of porphyria is in the end untenable. Thus the porphyrias are superb examples of the interface between laboratory and clinical medicine, in which the occurrence of the Ulysses syndrome can be curtailed through the careful ordering of tests and cogent interpretation of their results.

  16. Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

    PubMed

    Shin, Su Rin; Moh, In Ho; Jung, Sung Won; Kim, Jin Bae; Park, Sang Hoon; Kim, Hyoung Su; Jang, Myung Kuk; Lee, Myung Seok

    2013-01-01

    The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n  = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications.

  17. Acute viral hepatitis in California sea lions.

    PubMed

    Britt, J O; Nagy, A Z; Howard, E B

    1979-11-01

    Acute viral hepatitis was diagnosed in five California sea lions (Zalophus californianus) stranded along the Los Angeles coast. Light microscopy revealed large nuclear inclusion bodies in hepatocytes. Electron microscopy provided evidence that these inclusion bodies were composed of adenovirus-like virions. Attempts to grow the virus in cell culture systems were unsuccessful. PMID:521373

  18. Ischaemic Markers in Acute Hepatic Injury

    PubMed Central

    Jena, Sushanta Kumar; Nanda, Rachita; Mangaraj, Manaswini; Nayak, Parsuram

    2016-01-01

    Introduction Hepatic injury of varied aetiology may progress to Acute Liver Failure (ALF). Compromised microcirculation is thought to be a deciding factor of hepatic hypoxia may be involved in disease progression that needs early detection. Ischaemia markers like serum Ischaemia- modified albumin (IMA), ALT-LDH ratio and ALT-LDH index have been suggested for its detection at early stage. Aim To find out the association of Ischaemia markers like serum IMA, ALT-LDH ratio and ALT-LDH index in acute hepatic injury cases. Materials and Methods Forty one diagnosed acute liver injury cases of varied aetiology admitted in Department of Medicine, and Gastroenterology of SCB Medical College, Cuttack were enrolled in the study along with 30 age and sex matched healthy controls. Blood collected at time of admission and at time of discharge (1st day and 7th day) were evaluated for FPG, RFT, LFT, Serum Albumin along with serum LDH, IMA, PT-INR and platelet count. Result Serum bilirubin, hepatic enzymes, IMA, PT-INR was more markedly raised in cases than controls on the 1st day of admission. ALT-LDH ratio and index were significantly low in complicated cases. However, on responding to treatment the ALT-LDH index on 7th day registered a rise in comparison to the 1st day, while serum IMA revealed an insignificant decline showing improvement in hepatic hypoxia. ALT-LDH ratio remains more or less same on response to treatment. Conclusion Serum IMA and ALT-LDH Index reveals association with disease process in Acute Hepatic Injury cases both clinically and biochemically and can be used as supportive parameters for the diagnosis of disease process. PMID:27190791

  19. High frequency of mutations in exon 10 of the porphobilinogen deaminase gene in patients with a CRIM-positive subtype of acute intermittent porphyria

    SciTech Connect

    Gu, X.F.; Rooij, F. de; Voortman, G.; Velde, K.T.; Nordmann, Y.; Grandchamp, B.

    1992-09-01

    Acute intermittent porphyria (AIP) is an autosomal dominant disease characterized by a partial deficiency of porphobilinogen (PBG) deaminase. Different subtypes of the disease have been defined, and more than 10 different mutations have been described. The authors focused their study on exon 10, since they previously found that three different mutations were located in this exon and that two of them seemed to be relatively common. They used denaturing gradient gel electrophoresis (DGGE) after in vitro amplification to detect all possible mutations in exon 10 in 41 unrelated AIP patients. In about one-fourth of these patients they could distinguish three abnormal migration patterns, indicating the presence of various mutations. Additional sequencing demonstrated the presence of three different single-base substitutions. Two of these mutations had already been described. A third one consisted of a C-to-T transition located at position 499 of the PBG deaminase mRNA and resulted in an Arg-to-Trp substitution. All three mutations were found in patients with crossreacting immunological material (CRIM)-positive forms of AlP. The high frequency of these mutations make DGGE analysis of exon 10 a useful approach allowing the direct detection of the DNA abnormality in most of the families with the CRIM-positive subtype of AlP. 23 refs., 3 figs., 1 tab.

  20. Safety and liver transduction efficacy of rAAV5-cohPBGD in nonhuman primates: a potential therapy for acute intermittent porphyria.

    PubMed

    Pañeda, Astrid; Lopez-Franco, Esperanza; Kaeppel, Christine; Unzu, Carmen; Gil-Royo, Ana Gloria; D'Avola, Delia; Beattie, Stuart G; Olagüe, Cristina; Ferrero, Roberto; Sampedro, Ana; Mauleon, Itsaso; Hermening, Stephan; Salmon, Florence; Benito, Alberto; Gavira, Juan Jose; Cornet, María Eugenia; del Mar Municio, María; von Kalle, Christof; Petry, Harald; Prieto, Jesus; Schmidt, Manfred; Fontanellas, Antonio; González-Aseguinolaza, Gloria

    2013-12-01

    Acute intermittent porphyria (AIP) results from haplo-insufficient activity of porphobilinogen deaminase (PBGD) and is characterized clinically by life-threatening, acute neurovisceral attacks. To date, liver transplantation is the only curative option for AIP. The aim of the present preclinical nonhuman primate study was to determine the safety and transduction efficacy of an adeno-associated viral vector encoding PBGD (recombinant AAV serotype 5-codon-optimized human porphobilinogen deaminase, rAAV5-cohPBGD) administered intravenously as part of a safety program to start a clinical study in patients with AIP. Macaques injected with either 1 × 10(13) or 5 × 10(13) vector genomes/kg of clinical-grade rAAV5-cohPBGD were monitored by standardized clinical parameters, and vector shedding was analyzed. Liver transduction efficacy, biodistribution, vector integration, and histopathology at day 30 postvector administration were determined. There was no evidence of acute toxicity, and no adverse effects were observed. The vector achieved efficient and homogenous hepatocellular transduction, reaching transgenic PBGD expression levels equivalent to 50% of the naturally expressed PBGD mRNA. No cellular immune response was detected against the human PBGD or AAV capsid proteins. Integration site analysis in transduced liver cells revealed an almost random integration pattern supporting the good safety profile of rAAV5-cohPBGD. Together, data obtained in nonhuman primates indicate that rAAV5-cohPBGD represents a safe therapy to correct the metabolic defect present in AIP patients. PMID:24070415

  1. Zafirlukast-induced acute hepatitis.

    PubMed

    Su, Chien-Wei; Wu, Jaw-Ching; Huang, Yi-Hsiang; Huang, Yi-Shin; Chang, Full-Young; Lee, Shou-Dong

    2002-11-01

    Zafirlukast, a competitive cysteinyl leukotriene receptor antagonist, is a new class of asthma medications. It has shown an adverse event profile similar to that of placebo. Herein, we present a 69-year-old female patient who suffered from general malaise, poor appetite, nausea and jaundice after 3 months of zafirlukast therapy for asthma. She had no past history of liver disease, nor history of alcoholism, herb medication, blood transfusion, acupuncture, tattoo or recent traveling history. Liver biochemistries revealed elevated serum alanine aminotransferase and aspartase aminotransferase levels up to 481 U/L and 212 U/L, respectively. Moreover, peak serum total bilirubin level was elevated to 34.8 mg/dL during admission. Serum viral hepatitis marker, antinuclear antibody, anti-mitochondrial antibody and anti-smooth muscle antibody were all negative. Her general condition and liver biochemistries improved gradually after zafirlukast was discontinued. Roussel Uclaf causality assessment for adverse drug reaction confirmed the diagnosis of drug-induced liver injury. This case reminds us that zafirlukast is a potentially hepato-toxic drug. If clinical manifestations of hepatitis develop, patients should be managed cautiously and closely monitored for liver biochemistries. If drug-induced hepatitis is suspected, medication should be discontinued immediately to prevent further liver injury. PMID:12583521

  2. Studies in Porphyria

    PubMed Central

    Sassa, Shigeru; Zalar, Gregory L.; Kappas, Attallah

    1978-01-01

    A 50% reduction in the activity of uroporphyrinogen-I (URO) synthase in liver, erythrocytes, and cultured skin fibroblasts characterizes all patients with clinically active acute intermittent porphyria (AIP). The same enzyme defect has also been demonstrated in the erythrocytes and skin fibroblasts of completely latent gene carriers of this disorder and presumably exists in the liver as well. In this study, we examined whether or not the formation of URO-synthase is impaired in AIP cells using lymphocytes treated with mitogens or infected with Epstein-Barr virus. Both mitogens (phytohemagglutinin and pokeweed mitogen) and Epstein-Barr virus induced the synthesis of URO-synthase in lymphocytes, but the induction of URO-synthase in AIP lymphocytes was only 50% as compared with that in normal lymphocytes. The impaired induction of URO-synthase in AIP lymphocytes reflects a specific gene defect because AIP lymphocytes showed normal [3H] thymidine uptake into DNA, [3H] uridine uptake into RNA, and normal δ-aminolevulinic acid (ALA) synthase, ALA-dehydratase, catalase activities, and heme content. Utilizing the same methodology, the ferrochelatase deficiency of hereditary erythropoietic protoporphyria could also be identified. The Km of the induced URO-synthase in AIP cells was identical to that of the enzyme in normal cells. The induced URO-synthase of mitogen-treated AIP lymphocytes was not accompanied by a concurrent enhanced level of ALA-synthase. Moreover, the URO-synthase deficiency in lymphocytes from actively ill AIP patients was not different from the level of enzyme activity when they were in clinical remission, or when compared with the enzyme activity of cells from completely latent AIP gene carriers. The results of this study indicate that the URO-synthase deficiency in AIP may be the result of a gene mutation regulating the rate of synthesis of a normal enzyme rather than a mutation causing a structural abnormality of this enzyme protein. PMID:621286

  3. Acute hepatitis after ingestion of herbs.

    PubMed

    Shad, J A; Chinn, C G; Brann, O S

    1999-11-01

    Herbal preparations are marketed as natural and safe alternatives to conventional medicines for the prevention and treatment of a variety of ailments. However, consumers may not be fully aware of their potential side effects. We report two cases of acute hepatitis after the ingestion of herbal preparations. One of the mixtures included chaparral and bee pollen; the other was pure bee pollen. Chaparral has been reported to have similar effects in other patients, but we found no reports of acute hepatitis from bee pollen. We discuss chaparral and several other hepatotoxic herbs and review the literature. Our case reports remind primary care physicians to ask their patients about herbal use and discuss their potential toxicities.

  4. Alverine citrate induced acute hepatitis.

    PubMed

    Arhan, Mehmet; Koklu, Seyfettin; Koksal, Aydln-S; Yolcu, Omer-F; Koruk, Senem; Koruk, Irfan; Kayacetin, Ertugrul

    2004-08-01

    Alverine citrate is a commonly used smooth muscle relaxant agent. A MEDLINE search on January 2004 revealed only 1 report implicating the hepatotoxicity of this agent. A 34-year-old woman was investigated because of the finding of elevated liver function tests on biochemical screening. Other etiologies of hepatitis were appropriately ruled out and elevated enzymes were ascribed to alverine citrate treatment. Although alverine citrate hepatotoxicity was related to an immune mechanism in the first case, several features such as absence of predictable dose-dependent toxicity of alverine citrate in a previous study and absence of hypersensitivity manifestations in our patient are suggestive of a metabolic type of idiosyncratic toxicity. PMID:15259090

  5. Alverine citrate induced acute hepatitis

    PubMed Central

    Arhan, Mehmet; Köklü, Seyfettin; Köksal, Aydln S; Yolcu, Ömer F; Koruk, Senem; Koruk, Irfan; Kayacetin, Ertugrul

    2004-01-01

    Alverine citrate is a commonly used smooth muscle relaxant agent. A MEDLINE search on January 2004 revealed only 1 report implicating the hepatotoxicity of this agent. A 34-year-old woman was investigated because of the finding of elevated liver function tests on biochemical screening. Other etiologies of hepatitis were appropriately ruled out and elevated enzymes were ascribed to alverine citrate treatment. Although alverine citrate hepatotoxicity was related to an immune mechanism in the first case, several features such as absence of predictable dose-dependent toxicity of alverine citrate in a previous study and absence of hypersensitivity manifestations in our patient are suggestive of a metabolic type of idiosyncratic toxicity. PMID:15259090

  6. Acute hepatitis associated with autochthonous hepatitis E virus infection--San Antonio, Texas, 2009.

    PubMed

    Tohme, Rania A; Drobeniuc, Jan; Sanchez, Roger; Heseltine, Gary; Alsip, Bryan; Kamili, Saleem; Hu, Dale J; Guerra, Fernando; Teshale, Eyasu H

    2011-10-01

    Locally acquired hepatitis E infection is increasingly being observed in industrialized countries. We report 2 cases of autochthonous acute hepatitis E in the United States. Hepatitis E virus genotype 3a related to US-2 and swine hepatitis E virus strains was isolated from one of the patients, indicating potential food-borne or zoonotic transmission. PMID:21896699

  7. Congenital Erythropoietic Porphyria with Undescended Testis

    PubMed Central

    Arora, Sandeep; Harith, Arun Kumar; Sodhi, Neha

    2016-01-01

    Hereditary porphyrias are a group of metabolic disorders of heme biosynthesis pathway that are characterized by acute neurovisceral symptoms, skin lesions, or both. Congenital erythropoietic porphyria (CEP) is an extremely rare disease with a mutation in the gene that codes for uroporphyrinogen III synthase leading to accumulation of porphyrin in different tissues and marked cutaneous photosensitivity. We report a case of CEP with infancy onset blistering, photosensitivity, red colored urine, and teeth along with scarring. Examination revealed an undescended testis of the left side. Mutation analysis revealed mutation in the uroporphyrinogen III synthase gene (UROS) resulting in c. 56 A > G (Tyr19Cys). The presence of undescended testis with a rare mutation in a case of CEP which itself is an extremely rare condition make the case interesting. PMID:27512208

  8. Modern diagnosis and management of the porphyrias.

    PubMed

    Sassa, Shigeru

    2006-11-01

    Recent advances in the molecular understanding of the porphyrias now offer specific diagnosis and precise definition of the types of genetic mutations involved in the disease. Molecular diagnostic testing is powerful and very useful in kindred evaluation and genetic counselling when a disease-responsible mutation has been identified in the family. It is also the only way to properly screen asymptomatic gene carriers, facilitating correct treatment and appropriate genetic counselling of family members at risk. However, it should be noted that DNA-based testing is for the diagnosis of the gene carrier status, but not for the diagnosis of clinical syndrome or severity of the disease, e.g. an acute attack. For the diagnosis of clinically expressed porphyrias, a logical stepwise approach including the analysis of porphyrins and their precursors should not be underestimated, as it is still very useful, and is often the best from the cost-effective point of view.

  9. The genetic basis of "Scarsdale Gourmet Diet" variegate porphyria: a missense mutation in the protoporphyrinogen oxidase gene.

    PubMed

    Frank, J; Poh-Fitzpatrick, M B; King, L E; Christiano, A M

    1998-08-01

    The porphyrias are disorders of porphyrin or porphyrin-precursor metabolism that result from inherited or acquired aberrations in the control of the porphyrin-heme biosynthetic pathway. Variegate porphyria (VP), one of the acute hepatic porphyrias, is characterized by a partial reduction in the activity of protoporphyrinogen oxidase (PPO), and recently, mutations in the PPO gene on chromosome 1q22-23 have been described. Our purpose was to identify the underlying genetic lesion in a severely affected patient with VP and to detect the silent mutation carriers in her family. The disease in this patient was precipitated by carbohydrate restriction as outlined in the "Scarsdale Gourmet Diet". Our mutation detection and confirmation strategy included PCR, automated sequencing, and restriction enzyme digestion. We identified a missense mutation in the patient and five family members. The mutation consisted of a previously unreported C-to-T transition in exon 5 of the PPO gene, resulting in the substitution of arginine by cysteine, designated R152C. This arginine residue is evolutionarily highly conserved in humans, mice, bacteria, yeast, and plants, indicating the importance of this residue in PPO. Our study established that a missense mutation in the PPO gene was the underlying mutation in this patient with VP and explained the occurrence of the phenotype in this family.

  10. Acute hepatic failure among hospitalized Thai children.

    PubMed

    Poovorawan, Yong; Chongsrisawat, Voranush; Shafi, Fakrudeen; Boudville, Irving; Liu, Yanfang; Hutagalung, Yanee; Bock, Hans L

    2013-01-01

    We conducted a hospital-based study from June 2002 to December 2006 of Thai children aged 1-15 years with acute hepatic failure (AHF) to determine the causes and outcomes. Eleven children were included in the study. Hepatitis B virus was the cause of AHF in one child, infection-associated hemophagocytic syndrome was the cause in 1 child, Wilson's disease was the cause in 1 child and dengue fever was suspected to be the cause in 2 children. In 6 children the cause of AHF was unknown. Jaundice was reported in 9 of 11 children. Ten of 11 children had mild to moderate encephalopathy on admission. Five of 11 children died due to AHF. No liver transplantations were performed among the children in this study. Further studies into the relationship between dengue infection and AHF are needed.

  11. Erythropoietic porphyrias: animal models and update in gene-based therapies.

    PubMed

    Richard, Emmanuel; Robert-Richard, Elodie; Ged, Cécile; Moreau-Gaudry, François; de Verneuil, Hubert

    2008-06-01

    The inherited porphyrias are inborn errors of haem biosynthesis, each resulting from the deficient activity of a specific enzyme of the haem biosynthetic pathway. Porphyrias are divided into erythropoietic and hepatic according to the predominant porphyrin-accumulating tissue. Three different erythropoietic porphyrias (EP) have been described: erythropoietic protoporphyria (EPP, MIM 177000) the most frequent, congenital erythropoietic porphyria (CEP, MIM 263700), and the very rare hepatoerythropoietic porphyria (HEP, MIM 176100). Bone marrow transplantation is considered as the only curative treatment for severe cases of erythropoietic porphyria (especially CEP), if donors are available. Some EPP patients who undergo liver failure may require hepatic transplantation. Murine models of EPP and CEP have been developed and mimic most of the human disease features. These models allow a better understanding of the pathophysiological mechanisms involved in EP as well as the development of new therapeutic strategies. The restoration of deficient enzymatic activity in the bone marrow compartment following gene therapy has been extensively studied. Murine oncoretroviral, and recently, lentiviral vectors have been successfully used to transduce hematopoietic stem cells, allowing full metabolic and phenotypic correction of both EPP and CEP mice. In CEP, a selective survival advantage of corrected cells was demonstrated in mice, reinforcing the arguments for a gene therapy approach in the human disease. These successful results form the basis for gene therapy clinical trials in severe forms of erythropoietic porphyrias.

  12. Acute Hepatitis and Pancytopenia in Healthy Infant with Adenovirus.

    PubMed

    Matoq, Amr; Salahuddin, Asma

    2016-01-01

    Adenoviruses are a common cause of respiratory infection, pharyngitis, and conjunctivitis in infants and young children. They are known to cause hepatitis and liver failure in immunocompromised patients; they are a rare cause of hepatitis in immunocompetent patients and have been known to cause fulminant hepatic failure. We present a 23-month-old immunocompetent infant who presented with acute noncholestatic hepatitis, hypoalbuminemia, generalized anasarca, and pancytopenia secondary to adenovirus infection. PMID:27340581

  13. montalcino, a Zebrafish Model for Variegate Porphyria

    PubMed Central

    Dooley, Kimberly A.; Fraenkel, Paula G.; Langer, Nathaniel B.; Schmid, Bettina; Davidson, Alan J.; Weber, Gerhard; Chiang, Ken; Foott, Helen; Dwyer, Caitlin; Wingert, Rebecca A.; Zhou, Yi; Paw, Barry H.; Zon, Leonard I.

    2008-01-01

    Objective Inherited or acquired mutations in the heme biosynthetic pathway lead to a debilitating class of diseases collectively known as porphyrias, with symptoms that can include anemia, cutaneous photosensitivity, and neurovisceral dysfunction. In a genetic screen for hematopoietic mutants, we isolated a zebrafish mutant, montalcino (mno), which displays hypochromic anemia and porphyria. The objective of this study was to identify the defective gene and characterize the phenotype of the zebrafish mutant. Methods Genetic linkage analysis was utilized to identify the region harboring the mno mutation. Candidate gene analysis together with RT-PCR was utilized to identify the genetic mutation, which was confirmed via allele specific oligo hybridizations. Whole mount in situ hybridizations and 0-dianisidine staining were used to characterize the phenotype of the mno mutant. mRNA and morpholino microinjections were performed to phenocopy and/or rescue the mutant phenotype. Results Homozygous mno mutant embryos have a defect in the protoporphyrinogen oxidase (ppox) gene, which encodes the enzyme that catalyzes the oxidation of protoporphyrinogen. Homozygous mutant embryos are deficient in hemoglobin, and by 36 hpf are visibly anemic and porphyric. The hypochromic anemia of mno embryos was partially rescued by human ppox, providing evidence for the conservation of function between human and zebrafish ppox. Conclusion In humans, mutations in ppox result in variegate porphyria. At present, effective treatment for acute attacks requires the administration intravenous hemin and/or glucose. Thus, mno represents a powerful model for investigation, and a tool for future screens aimed at identifying chemical modifiers of variegate porphyria. PMID:18550261

  14. Hepatitis E virus is the leading cause of acute viral hepatitis in Lothian, Scotland

    PubMed Central

    Kokki, I.; Smith, D.; Simmonds, P.; Ramalingam, S.; Wellington, L.; Willocks, L.; Johannessen, I.; Harvala, H.

    2015-01-01

    Acute viral hepatitis affects all ages worldwide. Hepatitis E virus (HEV) is increasingly recognized as a major cause of acute hepatitis in Europe. Because knowledge of its characteristics is limited, we conducted a retrospective study to outline demographic and clinical features of acute HEV in comparison to hepatitis A, B and C in Lothian over 28 months (January 2012 to April 2014). A total of 3204 blood samples from patients with suspected acute hepatitis were screened for hepatitis A, B and C virus; 913 of these samples were also screened for HEV. Demographic and clinical information on patients with positive samples was gathered from electronic patient records. Confirmed HEV samples were genotyped. Of 82 patients with confirmed viral hepatitis, 48 (59%) had acute HEV. These patients were older than those infected by hepatitis A, B or C viruses, were more often male and typically presented with jaundice, nausea, vomiting and/or malaise. Most HEV cases (70%) had eaten pork or game meat in the few months before infection, and 14 HEV patients (29%) had a recent history of foreign travel. The majority of samples were HEV genotype 3 (27/30, 90%); three were genotype 1. Acute HEV infection is currently the predominant cause of acute viral hepatitis in Lothian and presents clinically in older men. Most of these infections are autochthonous, and further studies confirming the sources of infection (i.e. food or blood transfusion) are required. PMID:26904201

  15. Immune dysfunction in acute alcoholic hepatitis

    PubMed Central

    Dhanda, Ashwin D; Collins, Peter L

    2015-01-01

    Acute alcoholic hepatitis (AAH) is a serious complication of alcohol misuse and has high short term mortality. It is a clinical syndrome characterised by jaundice and coagulopathy in a patient with a history of recent heavy alcohol use and is associated with profound immune dysfunction with a primed but ineffective immune response against pathogens. Here, we review the current knowledge of the pathogenesis and immune defects of AAH and identify areas requiring further study. Alcohol activates the immune system primarily through the disruption of gut tight junction integrity allowing the escape of pathogen-associated molecular particles (PAMPs) into the portal venous system. PAMPs stimulate cells expressing toll-like receptors (mainly myeloid derived cells) and initiate a network of intercellular signalling by secretion of many soluble mediators including cytokines and chemokines. The latter coordinates the infiltration of neutrophils, monocytes and T cells and results in hepatic stellate cell activation, cellular damage and hepatocyte death by necrosis or apoptosis. On the converse of this immune activation is the growing evidence of impaired microbial defence. Neutrophils have reduced phagocytic capacity and oxidative burst and there is recent evidence that T cell exhaustion plays a role in this. PMID:26576079

  16. A case of acute hepatitis following mad honey ingestion.

    PubMed

    Sari Dogan, Fatma; Ozaydin, Vehbi; Incealtin, Onur; Guneysel, Ozlem; Demireller, Merve

    2015-12-01

    Acute hepatitis is characterized by liver inflammation and liver cell necrosis. The most frequently observed underlying cause thereof is viruses, but various other causes, such as alcohol, medication, or toxins may also lead thereto. In this paper, a case of acute hepatitis presenting with bradycardia, hypotension, and a prominent increase in liver enzymes following mad honey ingestion is discussed. Since there are only few cases of acute hepatitis following mad honey ingestion in the literature, we want to present this subject matter. PMID:27239626

  17. [Acute myelitis related to hepatitis A after travel to Senegal].

    PubMed

    Ficko, C; Imbert, P; Mechaï, F; Barruet, R; Nicand, E; Rapp, C

    2010-02-01

    Neurological complications are rare following hepatitis A. Acute myelitis is even more uncommon. The purpose of this report is to describe a case of acute myelitis related to hepatitis A virus (HAV) in a 43-year-old-woman returning from Senegal. Diagnosis of myelitis was confirmed by spinal MRI and detection of anti-HAV Ig M antibodies in serum. The patient made a spontaneous clinical recovery in one month. Spinal MRI findings were normal at three months. Hepatitis A should be considered in the diagnostic approach to acute myelitis in returning travelers and patients living in highly endemic countries where prophylactic vaccination is unavailable.

  18. Excess risk of adverse pregnancy outcomes in women with porphyria: a population-based cohort study.

    PubMed

    Tollånes, Mette Christophersen; Aarsand, Aasne Karine; Sandberg, Sverre

    2011-02-01

    The porphyrias comprise a heterogeneous group of rare, primarily hereditary, metabolic diseases caused by a partial deficiency in one of the eight enzymes involved in the heme biosynthesis. Our aim was to assess whether acute or cutaneous porphyria has been associated with excess risks of adverse pregnancy outcomes. A population-based cohort study was designed by record linkage between the Norwegian Porphyria Register, covering 70% of all known porphyria patients in Norway, and the Medical Birth Registry of Norway, based on all births in Norway during 1967-2006. The risks of the adverse pregnancy outcomes preeclampsia, delivery by caesarean section, low birth weight, premature delivery, small for gestational age (SGA), perinatal death, and congenital malformations were compared between porphyric mothers and the rest of the population. The 200 mothers with porphyria had 398 singletons during the study period, whereas the 1,100,391 mothers without porphyria had 2,275,317 singletons. First-time mothers with active acute porphyria had an excess risk of perinatal death [adjusted odds ratio (OR) 4.9, 95% confidence interval (CI) 1.5-16.0], as did mothers with the hereditable form of porphyria cutanea tarda (PCT) (3.0, 1.2-7.7). Sporadic PCT was associated with an excess risk of SGA [adjusted relative risk (RR) 2.0, 1.2-3.4], and for first-time mothers, low birth weight (adjusted OR 3.4, 1.2-10.0) and premature delivery (3.5, 1.2-10.5) in addition. The findings suggest women with porphyria should be monitored closely during pregnancy.

  19. Role of genetic testing in the management of patients with inherited porphyria and their families.

    PubMed

    Whatley, S D; Badminton, M N

    2013-05-01

    The porphyrias are a group of mainly inherited metabolic conditions that result from partial deficiency of individual enzymes in the haem biosynthesis pathway. Clinical presentation is either with acute neurovisceral attacks, skin photosensitivity or both, and is due to overproduction of pathway intermediates. The primary diagnosis in the proband is based on biochemical testing of appropriate samples, preferably during or soon after onset of symptoms. The role of genetic testing in the autosomal dominant acute porphyrias (acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) is to identify presymptomatic carriers of the family specific pathogenic mutation so that they can be counselled on how to minimize their risk of suffering an acute attack. At present the additional genetic factors that influence penetrance are not known, and all patients are treated as equally at risk. Genetic testing in the erythropoietic porphyrias (erythropoietic protoporphyria, congenital erythropoietic porphyria and X-linked dominant protoporphyria) is focused on predictive and preconceptual counselling, prenatal testing and genotype-phenotype correlation. Recent advances in analytical technology have resulted in increased sensitivity of mutation detection with success rates of greater than 90% for most of the genes. The ethical and consent issues are discussed. Current research into genetic factors that affect penetrance is likely to lead to a more refined approach to counselling for presymptomatic gene carriers.

  20. New developments in erythropoietic porphyrias.

    PubMed

    Darwich, E; Herrero, C

    2013-04-01

    In recent years, important advances have been made in our understanding of the genetics of porphyrias, particularly with respect to erythropoietic protoporphyria (EPP) and congenital erythropoietic porphyria (CEP), 2 forms of erythropoietic porphyria no longer considered to be monogenic. The identification of mutations in genes not previously associated with these disorders as causative factors or modulators of severity has helped to explain the presence of genotypic and phenotypic differences between patients carrying the same mutations. These advances have also led to the identification of causative genetic defects in patients who, based on molecular studies, had no mutations in the uroporphyrinogen III synthase gene UROS (in CEP) or in the ferrochelatase gene FECH (in EPP). Better understanding and characterization of the genetics of porphyrias will allow us to determine genotypic and phenotypic correlations and improve the molecular classification of these diseases, which will have both practical and prognostic implications.

  1. Diet and Nutrition in Porphyria

    MedlinePlus

    ... Art Sale You are here Home Diet and Nutrition A proper diet is important to all individuals, ... alter food intake. Therefore, attention to diet and nutrition is important in almost any disease. Porphyrias are ...

  2. Porphyria: Pathophysiology, diagnosis, and treatment.

    PubMed

    Gasson, Tracy; Klein, Kathleen

    2015-08-15

    Porphyrias are inherited metabolic disorders that involve alterations in enzymes utilized in the heme biosynthetic pathway. Most of these conditions are inherited; however, some are believed to be acquired through environmental exposures. Patients with porhyrias often present with a wide range of clinical symptoms, making it difficult to diagnose. Treatments vary depending on clinical presentation. A thorough and detailed history is essential and key to discovering a porphyria diagnosis.

  3. A review of the clinical presentation, natural history and inheritance of variegate porphyria: its implausibility as the source of the 'Royal Malady'.

    PubMed

    Hift, Richard J; Peters, Timothy J; Meissner, Peter N

    2012-03-01

    It has been suggested that King George III of Great Britain suffered from the haem biosynthetic disorder, variegate porphyria. This diagnosis is pervasive throughout the scientific and popular literature, and is often referred to as the 'Royal Malady.' The authors believe it inappropriate to view the case for porphyria purely in terms of symptoms, as has generally been the case in his presumptive acute porphyria diagnosis. Accordingly, this review provides a current description of the natural history and clinical presentation of the porphyrias, against which we measure the case for porphyria in George III and his relatives. The authors have critically assessed the prevalence of porphyria in a population, the expected patterns and frequency of inheritance, its penetrance and its expected natural history in affected individuals, and conclude that neither George nor his relatives had porphyria, based on four principal reasons. First, the rarity of the disease mandates a very low prior probability, and therefore implies a vanishingly low positive predictive value for any diagnostic indicator of low specificity, such as a historical reading of the symptoms. Second, penetrance of this autosomal dominant disorder is approximately 40%, and one may expect to have identified characteristic clinical features of porphyria in a large number of descendants without difficulty. Third, the symptoms of both George III and his relatives are highly atypical for porphyria and are more appropriately explained by other much commoner conditions. Finally, the natural history of the illnesses reported in this family is as atypical for variegate porphyria as are their symptoms.

  4. A case of acute hepatitis B in a chronic hepatitis C patient after daclatasvir and asunaprevir combination therapy: hepatitis B virus reactivation or acute self-limited hepatitis?

    PubMed

    Hayashi, Kazuhiko; Ishigami, Masatoshi; Ishizu, Yoji; Kuzuya, Teiji; Honda, Takashi; Nishimura, Daisaku; Goto, Hidemi; Hirooka, Yoshiki

    2016-08-01

    Reactivation of hepatitis B virus (HBV) in HBV surface antigen (HBsAg)-positive patients treated with cytotoxic chemotherapy is well known. HBV reactivation in patients with HBV and hepatitis C virus (HCV) coinfection caused by direct-acting antiviral (DAA) therapy has also recently been reported. We report a case of acute hepatitis B in a patient with HCV infection after DAA therapy. An 83-year-old woman was referred for chronic hepatitis C. She was infected with HCV genotype 1b and negative for HBsAg at baseline. She received daclatasvir and asunaprevir therapy, and HCV became negative at 4 weeks and remained negative until 6 months after the end of DAA therapy. Acute hepatitis B developed 5 months after ending DAA therapy. Genome sequencing revealed the subgenotype as B1, and the serological subtype as adr. T118 K mutation at the S region as an immune escape mutant was identified. These virologic features led to HBV reactivation. The presence of hepatitis B core antibody or HBs antibody was not determined before DAA therapy, so prior HBV infection status was unclear. This case is speculated to represent HBV reactivation in a patient with previously resolved HBV induced by DAA therapy, based on virologic analysis and clinical status. The risk might be very low, but DAA therapy can cause HBV reactivation in chronic hepatitis C patients with prior HBV infection. When acute hepatitis emerges in patients who have received DAA therapy for HCV, HBV reactivation should be considered to allow early initiation of anti-HBV therapy. PMID:27329484

  5. Congenital erythropoietic porphyria.

    PubMed

    Fritsch, C; Lang, K; Bolsen, K; Lehmann, P; Ruzicka, T

    1998-01-01

    Congenital erythropoietic porphyria (CEP) is one of the rarest autosomal-recessive disorders of the porphyrin metabolism caused by the homozygous defect of uroporphyrinogen III cosynthase. High amounts of uroporphyrin I accumulate in all cells and tissues, reflected by an increased erythrocyte porphyrin concentration and excretion of high porphyrin amounts in urine and feces. Dermal deposits of uroporphyrin frequently induce a dramatic phototoxic oxygen-dependent skin damage with extensive ulcerations and mutilations. Splenomegaly and hemolytic anemia are typical internal symptoms. Skeletal changes such as osteolysis and calcifications are frequent. Up to date 130 cases of CEP have been published. Splenectomy and erythrocyte transfusions showed some beneficial effect. Bone marrow transplantation was performed in 3 patients and stem cell transplantation in 1. The best therapy is the avoidance of sunlight. We give a report on our latest cases of CEP. PMID:10343205

  6. [Friedrich Wilhelm I and porphyria].

    PubMed

    Pierach, C A; Jennewein, E

    1999-01-01

    Historical evidence has been collected attempting to diagnose members of royal houses, perhaps most publicized by Macalpine and Hunter (1969) for George III and his assumed porphyria, claiming that his insanity was a classic case of thereof. This rare metabolic disease presents with a variety of signs and symptoms: skin disease, abdominal pain, tachycardia, and neuro-psychiatric findings. The porphyrias are hereditary and since George III and Frederick William I share ancestors it seemed reasonable to investigate if the latter may also have suffered from porphyria. The pathography of both kings is meticulous, showing for both that abdominal pain, erratic behavior, restlessness, and discolored urine were frequently observed and complete recovery interictally was common. Intercurrent illnesses, fasting, alcohol and even tobacco smoking have been shown to be inducers of attacks and these risk factors are well documented in royal history.--The diagnosis of porphyria was not recognized then and other names were used, such as Cachexia hypochondriaca, Asthma spasmodico flatulentum, dolores arthritici.--We propose that Frederick William I suffered from an inducible porphyria.

  7. Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients*

    PubMed Central

    Vieira, Fatima Mendonça Jorge; Nakhle, Maria Cristina; Abrantes-Lemos, Clarice Pires; Cançado, Eduardo Luiz Rachid; dos Reis, Vitor Manoel Silva

    2013-01-01

    BACKGROUND Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil. OBJECTIVES Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors (hepatitis C, HIV, alcoholism and estrogen) and their link with HFE mutations. METHODS An ambispective study of 60 patients with PCT was conducted during the period from 2003 to 2012. Serological tests for hepatitis C and HIV were performed and histories of alcohol abuse and estrogen intake were investigated. HFE mutations were identified with real-time PCR. RESULTS Porphyria cutanea tarda predominated in males and alcohol abuse was the main precipitating factor. Estrogen intake was the sole precipitating factor present in 25% of female patients. Hepatitis C was present in 41.7%. All HIV-positive patients (15.3%) had a history of alcohol abuse. Allele frequency for HFE mutations, i.e., C282Y (p = 0.0001) and H63D (p = 0.0004), were significantly higher in porphyria cutanea tarda patients, compared to control group. HFE mutations had no association with the other precipitating factors. CONCLUSIONS Alcohol abuse, hepatitis C and estrogen intake are prevalent precipitating factors in our porphyria cutanea tarda population; however, hemochromatosis in itself can also contribute to the outbreak of porphyria cutanea tarda, which makes the research for HFE mutations necessary in these patients PMID:24068123

  8. Studies on immunoregulatory mechanisms in acute and chronic hepatitis B.

    PubMed Central

    Lemm, G; Salzer, K; Warnatz, H

    1983-01-01

    Patients with acute hepatitis B and HBV-induced chronic hepatitis as well as normal control persons participated in the study. Hepatitis patients of both groups have decreased OKT4+/OKT8+T cell ratios due to an percental increase of OKT8+T cells in peripheral blood compared to the data of controls. Lymphocyte cultures of chronic hepatitis patients show reduced DNA synthesis after stimulation by allogeneic non-T cells, PHA, Con A and PWM. PWM-induced immunoglobulin secretion by B cells, determined by means of a reverse haemolytic plaque assay (RHPA) and a solid phase ELISA, showed comparable results in hepatitis B patients and controls. The AMLR, which is thought to reflect an autologous immunoregulatory phenomenon, is slightly impaired in cultures of hepatitis B patients in comparison to controls. Con A-induced suppressor cell activity on T cell reactions is decreased in hepatitis, whereas suppressor cell activity on B cell activation is within the same range as in cultures of controls. It is concluded from these data, that suppressor cell activity on T cell function is impaired in hepatitis B, whereas B cell functions and suppressor cell activity on B cell function are in the normal range. The results with the functional assays and the finding of increased proportions of OKT8+T cells in hepatitis B are considered to reflect properties of different T cell subpopulations, responsible for different immunoregulatory functions. PMID:6222854

  9. Indium-111 WBC scan in acute toxic centrilobular hepatic necrosis

    SciTech Connect

    Davidson, R.M.; Dhekne, R.D.; Moore, W.H. )

    1989-12-01

    In this case of prolonged fever and abnormal liver functions, dual tracer scintigraphy with In-111 WBCs and Tc-99m SC led to a biopsy-proven diagnosis of severe acute toxic hepatitis (hepatocellular necrosis). Correlation of the Tc-99m SC scan findings with those previously reported for pseudotumors of the liver is discussed. A pseudonormal scan pattern is described for the In-111 WBC scintigraphy. Discordance between In-111 WBC and Tc-99m SC scintigraphy in this clinical setting should raise the possibility of hepatic necrosis as a diagnostic alternative to hepatic abscess.

  10. Transient sinus node dysfunction with acute hepatitis of unknown etiology.

    PubMed

    Al-Fagih, Ahmed R; Al-Ghamdi, Saleh A; Dagriri, Khaled G; Al-Malki, Ahmed S

    2010-05-01

    We reported a case of a 72-year-old male, known diabetic on insulin, referred because of complete atrioventricular block. He was found to have acute hepatitis during which he developed transient atrial arrhythmia, and sinus node dysfunction. His cardiac symptoms disappeared completely after hepatitis improvement. All of his cardiac investigations were normal including electrocardiogram, echocardiography and thalium stress test. At 3 and 6 months follow up, his Holter monitoring did not show any further arrhythmia, and he denied any further episodes of palpitation or pre-syncope. We reviewed the literature regarding the relationship between hepatitis and atrial arrhythmia. PMID:20464052

  11. Acute Liver Failure and Hepatic Encephalopathy After Cleft Palate Repair.

    PubMed

    Kocaaslan, Nihal Durmuş; Tuncer, Fatma Betul; Tutar, Engin; Celebiler, Ozhan

    2015-09-01

    Paracetamol is the most commonly used analgesic after cleft palate repair. It has rarely caused acute hepatic failure at therapeutic or supratherapeutic doses. Only one case of therapeutic paracetamol toxicity after cleft palate repair had been reported previously. Here, we present a similar patient who developed acute liver failure and hepatic encephalopathy after an uncomplicated cleft palate surgery. Lack of large prospective trials in young children due to ethical concerns increases the value of the case reports of acetaminophen toxicity at therapeutic doses. The dosing recommendations of paracetamol may need to be reconsidered after cleft palate surgery.

  12. Acute pancreatitis associated with acute viral hepatitis A (HAV) - a case report.

    PubMed

    Arafat, S M; Azad, A K; Basher, A; Ananna, M A; Islam, M S; Abdullah, S; Abdullah, A M; Islam, M A

    2013-01-01

    In this case report, a young woman had acute viral hepatitis (HAV) and acute pancreatitis together. She was admitted to our hospital with fever, jaundice and abdominal pain. Hepatic and pancreatic enzymes were elevated. Her serum alanine aminotransferase (ALT) level was high. An initial abdominal ultrasound was per-formed at hospital and revealed features of acute viral hepatitis. Spiral computed imaging revealed imaging features of an acute stage of pancreatitis and gallbladder wall thickness. HAV infection was diagnosed by the detection of immunoglobulin M (IgM) against HAV in the serum. She was closely monitored and treated conservatively. On 10th day of hospital admission she was discharge after an uneventful recovery. In the current literature HAV infections have rarely been reported as a cause of acute pancreatitis.

  13. A Case of Variegate Porphyria in Association With Coeliac Disease and Bisphosphonate Associated Dental Osteonecrosis

    PubMed Central

    Ogundipe, Olayinka A.

    2009-01-01

    This case describes an older patient with a rare diagnosis of variegate porphyria presenting with acute abdominal pains and bloating, intermittent loose stools and jaw pains following surgical repair of an osteoporotic hip fracture. She was noted to have acute hyponatraemia. All the abdominal symptoms and the hyponatraemia were initially attributed to an acute episode of variegate porphyria with an accompanying syndrome of inappropriate antidiuretic hormone secretion. However, following further evaluations necessitated by the incomplete resolution of the abdominal symptoms, it became apparent that some of the persisting symptoms were due to a concurrent and new presentation of serology positive coeliac disease. The jaw pains were established to be due to dental osteonecrosis in association with the use of bisphosphonate therapy for treatment of osteoporosis. The various symptoms and signs subsequently settled uneventfully following institution of appropriate management options for the various coexisting diagnoses. Keywords Abdominal pain; Abdominal bloating; Loose stools; Hyponatraemia; Variegate porphyria; Coeliac disease; Osteoporosis; Bisphosphonates; Osteonecrosis PMID:22481993

  14. The Association of Viral Hepatitis and Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.; Olsen, Harvey; Swanson, Virginia; Rinderknecht, Heinrich

    1972-01-01

    The histological features of 24 pancreases obtained from patients who died of causes other than hepatitis, pancreatitis or pancreatic tumors, included a variable degree of autolysis, rare foci of inflammatory reaction but no hemorrhagic fat necrosis or destruction of elastic tissue in vessel walls (elastolysis). Assays of elastase in extracts of these pancreases showed no free enzyme, but varying amounts of proelastase. A review of autopsy findings in 33 patients with fatal liver necrosis attributed to halothane anesthesia, demonstrated changes of acute pancreatitis only in two. On the other hand, a review of 16 cases of fulminant viral hepatitis revealed changes characteristic of acute pancreatitis in seven – interstitial edema, hemorrhagic fat necrosis, inflammatory reaction and frequently elastolysis in vessel walls. Determination of elastase in extracts of one pancreas showed the bulk of the enzyme in free form. Furthermore, assays of urinary amylase in 44 patients with viral hepatitis showed increased levels of this enzyme (2583 ± 398 mean value ± standard error, Somogyi units per 100 ml in 13, or 29.5 percent). The evidence suggests that acute pancreatitis may at times complicate viral hepatitis. Although direct proof of viral pancreatic involvement is not feasible at present, a rational hypothesis is advanced which underlines similar mechanisms of tissue involvement in both liver and pancreas that may be brought about by the hepatitis viruses. PMID:5070694

  15. Toxic acute hepatitis and hepatic fibrosis after consumption of chaparral tablets.

    PubMed

    Kauma, H; Koskela, R; Mäkisalo, H; Autio-Harmainen, H; Lehtola, J; Höckerstedt, K

    2004-11-01

    In this report we describe a young, previously healthy woman who developed severe acute hepatitis after consumption of chaparral tablets, a commonly used herbal product. In this case, the elimination-rechallenge event and the exclusion of other possible aetiologic factors strongly supported true causality between the herbal product and the liver damage. Primary liver biopsy showed severe toxic hepatitis consistent with previous reports of chaparral-induced liver damage. Later, 6 months after the liver function tests had normalized, permanent hepatic fibrosis could still be seen.

  16. Hepatitis E as a cause of acute jaundice syndrome in northern Uganda, 2010-2012.

    PubMed

    Gerbi, Gemechu B; Williams, Roxanne; Bakamutumaho, Barnabas; Liu, Stephen; Downing, Robert; Drobeniuc, Jan; Kamili, Saleem; Xu, Fujie; Holmberg, Scott D; Teshale, Eyasu H

    2015-02-01

    Hepatitis E virus (HEV) is a common cause of acute viral hepatitis in developing countries; however, its contribution to acute jaundice syndrome is not well-described. A large outbreak of hepatitis E occurred in northern Uganda from 2007 to 2009. In response to this outbreak, acute jaundice syndrome surveillance was established in 10 district healthcare facilities to determine the proportion of cases attributable to hepatitis E. Of 347 acute jaundice syndrome cases reported, the majority (42%) had hepatitis E followed by hepatitis B (14%), malaria (10%), hepatitis C (5%), and other/unknown (29%). Of hepatitis E cases, 72% occurred in Kaboong district, and 68% of these cases occurred between May and August of 2011. Residence in Kaabong district was independently associated with hepatitis E (adjusted odds ratio = 13; 95% confidence interval = 7-24). The findings from this surveillance show that an outbreak and sporadic transmission of hepatitis E occur in northern Uganda.

  17. Hepatitis E as a cause of acute jaundice syndrome in northern Uganda, 2010-2012.

    PubMed

    Gerbi, Gemechu B; Williams, Roxanne; Bakamutumaho, Barnabas; Liu, Stephen; Downing, Robert; Drobeniuc, Jan; Kamili, Saleem; Xu, Fujie; Holmberg, Scott D; Teshale, Eyasu H

    2015-02-01

    Hepatitis E virus (HEV) is a common cause of acute viral hepatitis in developing countries; however, its contribution to acute jaundice syndrome is not well-described. A large outbreak of hepatitis E occurred in northern Uganda from 2007 to 2009. In response to this outbreak, acute jaundice syndrome surveillance was established in 10 district healthcare facilities to determine the proportion of cases attributable to hepatitis E. Of 347 acute jaundice syndrome cases reported, the majority (42%) had hepatitis E followed by hepatitis B (14%), malaria (10%), hepatitis C (5%), and other/unknown (29%). Of hepatitis E cases, 72% occurred in Kaboong district, and 68% of these cases occurred between May and August of 2011. Residence in Kaabong district was independently associated with hepatitis E (adjusted odds ratio = 13; 95% confidence interval = 7-24). The findings from this surveillance show that an outbreak and sporadic transmission of hepatitis E occur in northern Uganda. PMID:25448237

  18. Past and future: porphyria and porphyrins.

    PubMed

    Norman, Robert A

    2005-01-01

    Porphyria is a compelling disease--disrupted enzyme pathways, heightened sensitivities, and a fascinating history tied in with tales of Dracula. This review discusses the history, pathophysiology, classification, and treatment of porphyria. It further discusses the way in which research on the etiologies of the various porphyrias has led to the development of porphyrin-based photodynamic therapy, which shows great promise in targeted therapy for a variety of serious pathologies.

  19. Genetics Home Reference: porphyria

    MedlinePlus

    ... of iron in the liver, alcohol consumption, smoking, hepatitis C or HIV infection, or certain hormones. Mutations in ... Diagnostic Tests Drug Therapy Surgery and Rehabilitation Genetic Counseling Palliative Care Related Information How are genetic conditions ...

  20. Acute Hepatic Failure in a Dog after Xylitol Ingestion.

    PubMed

    Schmid, Renee D; Hovda, Lynn R

    2016-06-01

    Xylitol is a five-carbon sugar alcohol produced from natural resources frequently used as a sugar substitute for humans. We report the development and successful treatment of acute hepatic failure and coagulopathy in a dog after xylitol ingestion. A 9-year-old 4.95 kg (10.9 lb) neutered male Chihuahua was evaluated at a veterinary clinic for vomiting after ingesting 224 g (45 g/kg, 20.5 g/lb) of granulated xylitol. Hypoglycemia developed within 1-2 h, elevated liver values, suggesting the development of acute hepatic failure, within 12 h and coagulopathy less than 24 h after ingestion. Treatment included maropitant, intravenous dextrose, phytonadione, metronidazole, and fresh frozen plasma. N-acetylcysteine (NAC) and S-adensoyl-L-methionine (SAMe) provided hepatic detoxification and support. The dog survived and liver values returned to normal within 1 month post ingestion. No adverse effects to hepatic function have been identified 2 years after acute xylitol toxicity. This paper is one of the few reports of successful management of a dog with hypoglycemia, hepatic failure, and coagulopathy caused by xylitol toxicity. To date, this is the highest published xylitol dose survived by a dog, as well as the only reported case that documents laboratory changes throughout the course of toxicity and includes normal hepatic indices for 7 months following xylitol toxicity. The rapidly expanding use of xylitol in a variety of products intended for human consumption has led to a rise in xylitol toxicity cases reported in dogs, and clinicians should be aware that more dogs may potentially be exposed and develop similar manifestations.

  1. Butachlor-induced acute toxic hepatitis.

    PubMed

    Daryani, Nasser Ebrahimi; Hosseini, Parviz; Bashashati, Mohammad; Haidarali, Mona; Sayyah, Alireza

    2007-01-01

    Butachlor is a highly effective herbicidal substance widely used by farmers. We report a 60-year-old man with exfoliative dermatitis, jaundice, increase in liver enzymes and eosinophilia one day after accidental dermal exposure to butachlor toxin. The diagnostic workup showed no other cause and liver histology was consistent with substance-induced toxic hepatitis. Within two weeks of conservative therapy, his liver function tests returned to normal.

  2. Clinical, Biochemical and Molecular Characteristics of the Main Types of Porphyria.

    PubMed

    Szlendak, Urszula; Bykowska, Ksenia; Lipniacka, Agnieszka

    2016-01-01

    Porphyrias are diverse disorders that arise from various inherited enzyme defects in the heme biosynthesis pathway, except for porphyria cutanea tarda (PCT), in which the enzyme deficiency in most cases is acquired. The biosynthetic blocks resulting from the defective enzymes are largely expressed either in the liver or bone marrow, the sites where the majority of heme is produced. Although the pathophysiologic mechanisms of the clinical manifestations of the porphyrias are not fully understood, two cardinal features prevail: skin photosensitivity and neurologic symptoms of intermittent autonomic neuropathy, acute neurovisceral attacks, and disorders of the nervous system. The primary diagnosis of the proband is based on biochemical testing, which is not always able to identify acute porphyrias, especially in asymptomatic family carriers when heme precursors and porphyrins excretion is normal, low-normal and high-reduced values of enzyme activity overlap, and hematological diseases responsible for abnormal blood cells distribution coexist. Molecular analysis of gene mutations responsible for each type of porphyria is the best diagnostic approach for symptomatic as well as presymptomatic gene carriers.

  3. Clinical, Biochemical and Molecular Characteristics of the Main Types of Porphyria.

    PubMed

    Szlendak, Urszula; Bykowska, Ksenia; Lipniacka, Agnieszka

    2016-01-01

    Porphyrias are diverse disorders that arise from various inherited enzyme defects in the heme biosynthesis pathway, except for porphyria cutanea tarda (PCT), in which the enzyme deficiency in most cases is acquired. The biosynthetic blocks resulting from the defective enzymes are largely expressed either in the liver or bone marrow, the sites where the majority of heme is produced. Although the pathophysiologic mechanisms of the clinical manifestations of the porphyrias are not fully understood, two cardinal features prevail: skin photosensitivity and neurologic symptoms of intermittent autonomic neuropathy, acute neurovisceral attacks, and disorders of the nervous system. The primary diagnosis of the proband is based on biochemical testing, which is not always able to identify acute porphyrias, especially in asymptomatic family carriers when heme precursors and porphyrins excretion is normal, low-normal and high-reduced values of enzyme activity overlap, and hematological diseases responsible for abnormal blood cells distribution coexist. Molecular analysis of gene mutations responsible for each type of porphyria is the best diagnostic approach for symptomatic as well as presymptomatic gene carriers. PMID:27627571

  4. Hepatitis E virus as a Cause of Acute Hepatitis in The Netherlands

    PubMed Central

    Tholen, Aletta T. R.; Schinkel, Janke; Molenkamp, Richard; Ang, C. Wim

    2016-01-01

    Background Recent studies indicate that 27% of Dutch blood donors have evidence of past infection with HEV. However, the low number of diagnosed HEV infections indicates either an asymptomatic course or under diagnosis. Objectives We investigated whether HEV is a cause of acute hepatitis in Dutch patients and which diagnostic modality (serology or PCR) should be used for optimal detection. Study design Serum samples were retrospectively selected from non-severely immuno-compromised patients from a university hospital population, suspected of having an infectious hepatitis. Criteria were: elevated alanine aminotransferase (ALT> 34 U/l) and request for antibody testing for CMV, EBV or Hepatitis A (HAV). Results All samples were tested for HEV using ELISA and PCR. Ninety patients/sera were tested, of which 22% were HEV IgG positive. Only one serum was IgM positive. HEV PCR was positive in two patients: one patient was both HEV IgM and IgG positive, the other patient was only IgG positive. Both HEV RNA positive samples belonged to genotype 3. Evidence of recent infection with CMV, EBV and HAV was found in 13%, 10% and 3% respectively. Conclusions Although our study is limited by small numbers, we conclude that HEV is a cause of acute hepatitis in hospital associated patients in The Netherlands. Moreover, in our study population the prevalence of acute HAV (3%) was almost similar to acute HEV (2%). We propose to incorporate HEV testing in panels for acute infectious hepatitis. Negative results obtained for HEV IgM in a HEV PCR positive patient, indicates that antibody testing alone may not be sufficient and argues for PCR as a primary diagnostic tool in hospital associated patients. The high percentage of HEV IgG seropositivity confirms earlier epidemiological studies. PMID:26840767

  5. Symptoms and signs of acute alcoholic hepatitis

    PubMed Central

    Basra, Gurjot; Basra, Sarpreet; Parupudi, Sreeram

    2011-01-01

    Although there is not one specific sign or symptom related to alcoholic hepatitis (AH), a constellation of symptoms and signs can help make the diagnosis of AH with reasonable accuracy. Documentation of chronic and active alcohol abuse is paramount in making a diagnosis of AH. Clinical presentation after abstinence for more than 3 m should raise doubts about the diagnosis of AH and dictate the need for considering other causes of liver disease, decompensation of alcoholic cirrhosis, sepsis and malignancy as the cause of patient’s clinical profile. PMID:21731904

  6. Neurologic Disorders in Immunocompetent Patients with Autochthonous Acute Hepatitis E

    PubMed Central

    Perrin, H. Blasco; Cintas, P.; Abravanel, F.; Gérolami, R.; d'Alteroche, L.; Raynal, J.-N.; Alric, L.; Dupuis, E.; Prudhomme, L.; Vaucher, E.; Couzigou, P.; Liversain, J.-M.; Bureau, C.; Vinel, J.-P.; Kamar, N.; Izopet, J.

    2015-01-01

    Neurologic disorders, mainly Guillain-Barré syndrome and Parsonage–Turner syndrome (PTS), have been described in patients with hepatitis E virus (HEV) infection in industrialized and developing countries. We report a wider range of neurologic disorders in nonimmunocompromised patients with acute HEV infection. Data from 15 French immunocompetent patients with acute HEV infection and neurologic disorders were retrospectively recorded from January 2006 through June 2013. The disorders could be divided into 4 main entities: mononeuritis multiplex, PTS, meningoradiculitis, and acute demyelinating neuropathy. HEV infection was treated with ribavirin in 3 patients (for PTS or mononeuritis multiplex). One patient was treated with corticosteroids (for mononeuropathy multiplex), and 5 others received intravenous immunoglobulin (for PTS, meningoradiculitis, Guillain-Barré syndrome, or Miller Fisher syndrome). We conclude that pleiotropic neurologic disorders are seen in HEV-infected immunocompetent patients. Patients with acute neurologic manifestations and aminotransferase abnormalities should be screened for HEV infection. PMID:26490255

  7. Severe fever with thrombocytopenia syndrome presenting as acute hepatic failure

    PubMed Central

    Park, Jung Gil

    2015-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is characterized by fever, thrombocytopenia, leukopenia, and altered consciousness, which may also involve multi-organ failure. Initially SFTS mortality was as high as 30%, when diagnosis remained unclear. We present a case of a 53-year- old man with SFTS presenting with acute hepatic failure. On admission, he presented with confusion, elevated serum liver enzyme and ammonia levels, whose serum markers were negative for acute viral hepatitis. He was diagnosed with SFTS based on reverse transcription-polymerase chain reaction identification of the SFTS virus M segment. Percutaneous liver biopsy was performed to identify the degree and extent of necroinflammation and patient prognosis. After recovery, he was followed-up for 12 months with no SFTS-related sequelae. A discordance in severity between biopsy findings and clinical course could explain the rapid clinical improvement. Atypical presentations with multi-organ failure can delay timely diagnosis and management of infected patients. PMID:27752587

  8. Hepatic encephalopathy in acute-on-chronic liver failure.

    PubMed

    Lee, Guan-Huei

    2015-10-01

    The presence of hepatic encephalopathy (HE) within 4 weeks is part of the criteria for defining acute-on-chronic liver failure (ACLF). The pathophysiology of HE is complex, and hyperammonemia and cerebral hemodynamic dysfunction appear to be central in the pathogenesis of encephalopathy. Recent data also suggest that inflammatory mediators may have a significant role in modulating the cerebral effect of ammonia. Multiple prospective and retrospective studies have shown that hepatic encephalopathy in ACLF patients is associated with higher mortality, especially in those with grade III-IV encephalopathy, similar to that of acute liver failure (ALF). Although significant cerebral edema detected by CT in ACLF patients appeared to be less common, specialized MRI imaging was able to detect cerebral edema even in low grade HE. Ammonia-focused therapy constitutes the basis of current therapy, as in the treatment of ALF. Emerging treatment strategies focusing on modulating the gut-liver-circulation-brain axis are discussed.

  9. Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents: A Case Report.

    PubMed

    Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro

    2016-01-01

    The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians should rule

  10. Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents

    PubMed Central

    Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro

    2016-01-01

    Abstract The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians

  11. Hepatitis A related acute liver failure by consumption of contaminated food.

    PubMed

    Chi, Heng; Haagsma, Elizabeth B; Riezebos-Brilman, Annelies; van den Berg, Arie P; Metselaar, Herold J; de Knegt, Robert J

    2014-11-01

    We present a patient with no medical history admitted for jaundice and dark coloured urine. Further investigations revealed hepatitis A related acute liver failure while the patient had no travel history, nor contact with infected individuals. After admission, the patient deteriorated fulfilling the King's College criteria for acute liver failure. Two days after admission, he underwent liver transplantation and recovered. Careful investigation identified imported semi-dried tomatoes as the source of the hepatitis A infection. This patient was part of a foodborne hepatitis A outbreak in the Netherlands in 2010 affecting 13 patients. Virus sequence analysis of our patient's virus showed a strain commonly found in Turkey. Hepatitis A related acute liver failure is rare, but is associated with a poor prognosis. In developed countries, the incidence of hepatitis A is low, but foodborne outbreaks are emerging. Further, we review the literature on recent foodborne hepatitis A outbreaks in developed countries, hepatitis A related acute liver failure, and hepatitis A vaccine.

  12. Acute Pancreatitis, Hepatitis and Bone Erosion in Acute Yellow Phosphorous Compound Poisoning – A Rare Complication

    PubMed Central

    Kamarthi, Prabhakar; Gopu, Arun Vardharaju; Prasad, Reddy; Srinivasa, Chandrakala

    2016-01-01

    We report a case of acute pancreatitis and hepatitis following ingestion of yellow phosphorous. The condition of the patient progressed to encephalopathy and bony erosion of the nasal septum. Fungal mass was observed in both the nasal cavities by endoscopy. Microbiological investigation revealed the identity of the fungus as Aspergillus flavus and Candida tropicalis. Patient improved with fluconazole treatment. PMID:27504287

  13. Acute Pancreatitis, Hepatitis and Bone Erosion in Acute Yellow Phosphorous Compound Poisoning - A Rare Complication.

    PubMed

    Kamarthi, Prabhakar; Subramani, Parimala; Gopu, Arun Vardharaju; Prasad, Reddy; Srinivasa, Chandrakala

    2016-06-01

    We report a case of acute pancreatitis and hepatitis following ingestion of yellow phosphorous. The condition of the patient progressed to encephalopathy and bony erosion of the nasal septum. Fungal mass was observed in both the nasal cavities by endoscopy. Microbiological investigation revealed the identity of the fungus as Aspergillus flavus and Candida tropicalis. Patient improved with fluconazole treatment. PMID:27504287

  14. Relation of porphyria to atrial fibrillation.

    PubMed

    Dhoble, Abhijeet; Patel, Mehul B; Abdelmoneim, Sahar S; Puttarajappa, Chethan; Abela, George S; Bhatt, Deepak L; Thakur, Ranjan K

    2009-08-01

    Porphyrias are a group of inherited disorders affecting enzymes in the heme biosynthesis pathway, leading to overproduction and/or accumulation of porphyrin or its precursors. Porphyrias have been associated with autonomic dysfunction, which in turn can develop atrial fibrillation (AF). The purpose of this study was to characterize the prevalence of AF and atrial flutter (AFl) in patients with porphyrias. A single-center retrospective cohort study was designed using data from chart reviews of patients who were admitted to the hospital from January 2000 to June 2008. Fifty-six distinct cases were found with a discharge diagnosis of porphyria including all its subtypes. From the same database, age- and gender-matched controls were identified using computer-generated random numbers. We selected 1 age- and gender-matched control for each case. Electrocardiograms and echocardiograms were reviewed by 2 independent reviewers. Only patients with available 12-lead electrocardiograms that showed AF/AFl were labeled with that diagnosis. All patients with a diagnosis of porphyria were included in the study irrespective of their age. Seven of 56 patients with porphyria met inclusion criteria, yielding a prevalence of AF/AFl of 12.5%. This association was significant (p = 0.028, relative risk 7.45, 95% confidence interval 1.01 to 66.14) compared with the age- and gender-matched control group (2%). In conclusion, our observations suggest that porphyria may be significantly associated with AF/AFl.

  15. High titre of antibody to hepatitis B core antigen detected by immune adherence haemagglutination in HBsAg-positive acute hepatitis.

    PubMed

    Ikegami, F; Takasu, S; Jo, K; Miyakawa, Y; Tsuda, F; Mayumi, M

    1982-08-01

    Nine patients with HBsAg-positive acute hepatitis were tested for antibody to hepatitis B core antigen (anti-HBc) by the immune adherence haemagglutination method. A high anti-HBc titre (2(15) or more) was found in three, while anti-HBc was not detectable in the remaining six. All of them recovered from hepatitis with the return of hepatic function tests to normal, but HBsAg persisted in the three patients whose acute-phase serum had revealed high anti-HBc titres. On the basis of these observations, the three patients were thought to be persistent HBsAg carriers who had contracted opportunistic acute hepatitis of non-B aetiology. Titration of anti-HBc may be indicated in patients with HBsAg-positive acute hepatitis, because it helps distinguish persistent HBsAg carriers with non-B hepatitis from patients with hepatitis B at the outset, during the episode of acute hepatitis.

  16. Drug-induced acute autoimmune hepatitis during combination therapy with atorvastatin and ezetimibe.

    PubMed

    van Heyningen, Charles

    2005-09-01

    A case is presented of a patient who developed acute hepatitis during cholesterol-lowering treatment with atorvastatin and ezetimibe. Further investigations reveal a probable drug-induced autoimmune hepatitis, and ezetimibe is considered to be the most likely causal agent. This case is the first report of an autoimmune hepatitis associated with ezetimibe therapy.

  17. Unexpectedly high incidence of indigenous acute hepatitis E within South Hampshire: time for routine testing?

    PubMed

    De Silva, Aminda N; Muddu, Ajay K; Iredale, John P; Sheron, Nick; Khakoo, Salim I; Pelosi, Emanuela

    2008-02-01

    Hepatitis E indigenous to developed countries (hepatitis EIDC) is a form of hepatitis E in persons with no travel history to highly endemic areas. It has been recognized recently as an emerging clinical entity in a significant number of economically developed countries including UK. However, it is still perceived as a rare disease and routine laboratory testing for hepatitis E is not performed. A series of 13 cases of hepatitis EIDC, diagnosed in a 13-month period from June 2005 within a single center in South Hampshire, UK, is presented. These patients were identified after implementing a novel-screening algorithm that introduced routine hepatitis E serological investigations. Patients were middle aged or elderly and males were affected more commonly. Four patients (31%) required hospital admission. All reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed cases carried hepatitis E virus (HEV) genotype-3, which bore close sequence homology to HEV circulating in UK pigs. None of these patients recalled eating undercooked pork products or close contact with pigs during the 2 months preceding the onset of acute hepatitis. In comparison, during the same period, only two cases of hepatitis A and five cases of acute hepatitis B were diagnosed. These data illustrate the importance of introducing routine hepatitis E testing in all patients with unexplained acute liver disease and absence of relevant travel history. Routine testing can clarify hepatitis E epidemiology whilst improving the clinical management of patients with acute liver disease. PMID:18098134

  18. Porphyria: A Suitable Case for Teaching.

    ERIC Educational Resources Information Center

    Hawkey, Roy

    1990-01-01

    The porphyrias are a family of genetic disorders whose genetics and biochemistry are largely identified. Background information on these diseases are discussed including porphyrins, gene expression, population genetics, and historical significance. (CW)

  19. Porphyria Cutanea Tarda and Agent Orange

    MedlinePlus

    ... survivors' benefits . Research on porphyria cutanea tarda and herbicides The Health and Medicine Division (HMD) (formally known ... on " Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam " that there was sufficient evidence ...

  20. Reversible myopathy during successful treatment with pegylated interferon and ribavirin for acute hepatitis C.

    PubMed

    Golstein, P E; Delforge, M L; Deviere, J; Marcellin, P

    2004-03-01

    There is no standard approved treatment for acute hepatitis C and the combination of pegylated interferon-alpha and ribavirin, currently recognized as the standard of care for chronic hepatitis C, has not been evaluated for acute hepatitis C. Adverse events induced by interferon therapy are numerous but myopathy is rare and has not been described with the use of pegylated interferon-alpha. We report the case of a 33-year-old Caucasian man who was successfully treated for acute hepatitis C with the combination of pegylated interferon-alpha2b and ribavirin, and who during treatment developed myopathy which proved reversible.

  1. ACUTE HEPATIC NECROSIS INDUCED BY BRUCELLA INFECTION IN HYPERTHYROID MICE

    PubMed Central

    Bradley, G. Mary; Spink, Wesley W.

    1959-01-01

    When small numbers of Brucella melitensis were inoculated into ABC mice, occasional hepatic granulomas without necrosis were demonstrated. The greatest multiplication of brucellae was detected in the spleens. Because it had been previously observed that ACTH or cortisone markedly accelerated the multiplication of brucellae in the livers of infected mice with destruction of liver cells, it was considered that triiodothyronine might likewise exaggerate a brucella infection by stimulating endogenous adrenal secretion. Although adrenal hypertrophy was produced, infection of mice treated with triiodothyronine resulted in severe hepatic necrosis or infarcts without the multiplication of brucellae in either the livers or spleens. The lesions were not encountered in untreated infected mice or in control mice treated with triiodothyronine. The necrosis was associated with minimal inflammatory reaction. The necrosis was not induced in mice treated with triiodothyronine and given brucella endotoxin. The precise genesis of the acute hepatic necrosis cited in these experiments remains undefined. Triiodothyronine did not cause deaths in mice infected with Br. melitensis. The infection was neither enhanced nor suppressed. PMID:13803714

  2. Brief report: acute viral hepatitis and poor maternal and perinatal outcomes in pregnant Sudanese women.

    PubMed

    Ahmed, Rihab E; Karsany, Mubarak S; Adam, Ishag

    2008-10-01

    Sixteen pregnant women presented at the three main hospitals in Khartoum province, Sudan during the period of March-September 2007 with features of acute viral hepatitis. Their mean (SD) gestational age was 28.0(6.7) weeks. The etiology of acute viral hepatitis was hepatitis B virus in five women (31.3%), hepatitis C virus in one woman (6.3%), hepatitis E virus in eight women (50%), and hepatitis non-A-to-E virus in two women (12.5%). There were four (25%) maternal deaths and three (18.7%) intrauterine fetal deaths. Three of these maternal deaths were due to hepatitis E virus and the fourth was due to hepatitis B virus.

  3. Polyphyletic Strains of Hepatitis E Virus Are Responsible for Sporadic Cases of Acute Hepatitis in Japan

    PubMed Central

    Mizuo, Hitoshi; Suzuki, Kazuyuki; Takikawa, Yasuhiro; Sugai, Yoshiki; Tokita, Hajime; Akahane, Yoshihiro; Itoh, Keiichi; Gotanda, Yuhko; Takahashi, Masaharu; Nishizawa, Tsutomu; Okamoto, Hiroaki

    2002-01-01

    Among 87 patients who were previously treated for acute hepatitis of unknown etiology between 1992 and 2001 at five hospitals in Japan, 11 (13%) patients were positive for immunoglobulin M-class antibodies to hepatitis E virus (HEV) by enzyme immunoassay and had detectable HEV RNA by reverse transcription-PCR with two independent sets of primers derived from well-conserved genomic areas in open reading frames 1 and 2. Clinical HEV infection was significantly associated with male sex (9 of 11 versus 29 of 76 patients [P < 0.01]) and older age (52 ± 11 [mean ± standard deviation] versus 41 ± 17 years [P < 0.05]), and its prevalence differed by geographic region (6 to 25%), with a higher rate in the northern part of Japan. At admission, the 11 patients with HEV-associated hepatitis had elevated alanine aminotransferase levels of 914 to 4,850 IU/liter, and all but 1 had elevated bilirubin levels of 1.5 to 24.0 mg/dl. The 11 HEV isolates were of genotype III or IV and were segregated into three groups with intergroup nucleotide differences of 9.5 to 22.0%. Phylogenetic analysis revealed that four isolates of genotype III were closely related to a Japanese isolate, while the other four isolates of the same genotype were nearest those from the United States. The remaining three isolates were close to known isolates of genotype IV in China and Taiwan but shared less than 88% identity with them. These results indicate that multiple genotypes of HEV cocirculate in Japan and contribute to the development of sporadic acute hepatitis, with the prevalence differing by age, sex, and geographic region. PMID:12202555

  4. Studies on the role of the Ah receptor in hexachloro-benzene-induced porphyria

    SciTech Connect

    Hahn, M.E.

    1987-01-01

    Many of the effects of hexachlorobenzene (HCB) resemble those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), whose effects are initiated by its binding to the AH receptor, the regulatory gene product of the Ah locus. I investigated the ability of HCB to interact with the AH receptor and the involvement of this protein in HCB-induced porphyria. The induction of two cytochrome P450 isozymes regulated by the Ah locus was also examined in light of their possible role in the pathogenesis of HCB- and TCDD-induced porphyria. HCB competitively inhibited the in vitro specific binding of ({sup 3}H)-TCDD to the rat hepatic Ah receptor (K{sub I} = 2.1 {mu}M) without affecting the solubility of ({sup 3}H)TCDD. Following the administration of HCB to rats, the number of ({sup 3}H)TCDD specific binding sites was reduced by up to 40%. HCB induced cytochromes P450b, P450e, P450c, and P450d, confirming that it is a mixed-type P450 inducer. The presence of porphyria in mice was assessed by measuring urinary and hepatic porphyrins and hepatic uroporphyrinogen decarboxylase activity.

  5. ALAD porphyria is a conformational disease.

    PubMed

    Jaffe, Eileen K; Stith, Linda

    2007-02-01

    ALAD porphyria is a rare porphyric disorder, with five documented compound heterozygous patients, and it is caused by a profound lack of porphobilinogen synthase (PBGS) activity. PBGS, also called "delta-aminolevulinate dehydratase," is encoded by the ALAD gene and catalyzes the second step in the biosynthesis of heme. ALAD porphyria is a recessive disorder; there are two common variant ALAD alleles, which encode K59 and N59, and eight known porphyria-associated ALAD mutations, which encode F12L, E89K, C132R, G133R, V153M, R240W, A274T, and V275M. Human PBGS exists as an equilibrium of functionally distinct quaternary structure assemblies, known as "morpheeins," in which one functional homo-oligomer can dissociate, change conformation, and reassociate into a different oligomer. In the case of human PBGS, the two assemblies are a high-activity octamer and a low-activity hexamer. The current study quantifies the morpheein forms of human PBGS for the common and porphyria-associated variants. Heterologous expression in Escherichia coli, followed by separation of the octameric and hexameric assemblies on an ion-exchange column, showed that the percentage of hexamer for F12L (100%), R240W (80%), G133R (48%), C132R (36%), E89K (31%), and A274T (14%) was appreciably larger than for the wild-type proteins K59 and N59 (0% and 3%, respectively). All eight porphyria-associated variants, including V153M and V275M, showed an increased propensity to form the hexamer, according to a kinetic analysis. Thus, all porphyria-associated human PBGS variants are found to shift the morpheein equilibrium for PBGS toward the less active hexamer. We propose that the disequilibrium of morpheein assemblies broadens the definition of conformational diseases beyond the prion disorders and that ALAD porphyria is the first example of a morpheein-based conformational disease.

  6. Clinically important immunological processes in acute and fulminant hepatitis, mainly due to hepatitis B virus.

    PubMed Central

    Mackenjee, M K; Kiepiela, P; Cooper, R; Coovadia, H M

    1982-01-01

    Clinically useful criteria were found by studying immunological functions on admission in 15 African children with acute hepatitis (AH) (11 of whom were HBsAg positive) and in 11 children with fulminant hepatic failure (FHF) (8 of whom were HBsAg positive), and by comparing these results with normal controls. Nine of the FHF patients died. All the AH patients survived despite the development of transient liver failure in seven. There was significant diminution of components of the classical and alternative pathways of complement and total haemolytic complement in FHF compared with AH, and in both groups in comparison with controls. Cellular immunity tested by phytohaemagglutinin and HBsAg transformation of lymphocytes and leucocyte migration inhibition with HBsAg, were more impaired in FHF than AH. These indices were reduced in both groups of patients compared with controls. The most important index correlating with severity of clinical disease was C3. It was lowest in FHF, but within this group was highest in 2 patients who survived, and in AH the C3 on admission was significantly lower in patients who subsequently showed signs of transient liver failure than in those who did not. The prothrombin index was less sensitive in differentiating serious from mild illness. It is suggested that C3 levels can be helpful in monitoring patients with acute liver disease. PMID:7082040

  7. HEV infection as an aetiologic factor for acute hepatitis: experience from a tertiary hospital in Bangladesh.

    PubMed

    Mamun-Al-Mahtab; Rahman, Salimur; Khan, Mobin; Karim, Fazal

    2009-02-01

    Acute hepatitis is seen sporadically round the year in Bangladesh. The incidence of acute viral hepatitis E increases after floods as this allows sewerage contamination of piped and groundwater. The aim of this retrospective study was to assess the burden of hepatitis E virus (HEV infection) in Bangladesh. Patients attending the Hepatology Unit III of the Bangabandhu Sheikh Mujib Medical University, during June 2004-December 2006, were included in the study. All viral markers were tested by enzyme-linked immunosorbent assay. The study population was divided in four groups. Group 1 included 144 patients with acute viral hepatitis. The inclusion criteria were: nausea and/or vomiting, loss of appetite, serum bilirubin >200 micromol/L, raised serum transaminases, and prothrombin time >3 seconds prolonged beyond control value. In Group 2, there were 31 pregnant women with acute viral hepatitis. All the patients had prodrome, icterus, raised serum bilirubin and raised serum transaminase levels. Group 3 included 23 patients presenting with fulminant hepatic failure. In Group 4, 69 patients with cirrhosis of liver were included. They presented with features of decompensation for the first time. The inclusion criteria were: patients with established cirrhosis with jaundice and/or ascites and/or hepatic encephalopathy. In Group 1, 58.33% of the 144 patients had acute viral hepatitis E. In Group 2, 45.16% of the pregnant women also had acute viral hepatitis E. HEV was responsible for 56.52% cases of fulminant hepatic failure in Group 3. In 21.7% cases in Group 4, decompensation of cirrhosis was due to HEV. Acute viral hepatitis E in the third trimester of pregnancy and HEV-induced fulminant hepatic failure were associated with 80% of mortality despite the best possible care. In this clinical context, acute viral hepatitis E is the leading cause of wide spectrum of liver disease ranging from severe acute viral hepatitis, fulminant hepatic failure, to decompensation of liver in

  8. Pharmacotherapy of acute alcoholic hepatitis in clinical practice

    PubMed Central

    Abenavoli, Ludovico; Milic, Natasa; Rouabhia, Samir; Addolorato, Giovanni

    2014-01-01

    Severe alcoholic hepatitis (AH) is an acute form of alcohol induced liver disease with a poor prognosis that is seen in the patients who consume large quantities of alcohol. The diagnosis of AH is based on the appropriate alcohol intake history and is supported with clinical and histological features, and several scoring systems. Glucocorticoids are the mainstay for treating severe AH with pentoxifylline used as an alternative to steroids in addition to total alcohol abstinence. Liver transplantation is a possible therapeutic option for severe AH. Among the anti-craving medications able to improve abstinence rate, baclofen seems to be effective and safe in the alcoholic patients affected by severe liver damage. PMID:24605014

  9. Fifty years of porphyria at the University of Cape Town.

    PubMed

    Meissner, Peter N; Corrigall, Anne V; Hift, Richard J

    2012-03-02

    The porphyrias are a group of disorders resulting from defective haem biosynthesis. One form, variegate porphyria, is common in South Africa as a result of a founder effect. Over the past 50 years, the University of Cape Town Faculty of Health Sciences has built and maintained an international reputation for excellence in the field of porphyria. The porphyria group is respected for its research and for its accumulated experience in the management of these disorders. Equally important has been the comprehensive and holistic care offered to patients with porphyria, and to their families.

  10. Porphyria

    MedlinePlus

    ... Griffin Rodgers, Director of the NIDDK Clinical Trials Current research studies and how you can volunteer Community Outreach and Health Fairs Science-based information and tips for planning an outreach effort or community event For Health Care Professionals Patient and provider resources ...

  11. Porphyria

    MedlinePlus

    ... Fax: 713–840–9552 Email: porphyrus@aol.com Internet: www.porphyriafoundation.com Iron Disorders Institute P.O. ... or 864–292–1175 Email: cgarrison@irondisorders.org Internet: www.irondisorders.org National Institutes of Health Office ...

  12. Hepatitis e and acute liver failure in pregnancy.

    PubMed

    Shalimar; Acharya, Subrat K

    2013-09-01

    Hepatitis E virus is a positive strand RNA virus with three open reading frames which is transmitted predominantly through the fecal contamination of water and food. It is the most common cause of acute liver failure in endemic areas. Pregnant women especially from the Indian subcontinent and Africa are at increased risk of contracting acute HEV infection as well as developing severe complications including ALF. Transmission of HEV occurs from mother to unborn child. Both maternal and fetal complications may occur, including abortion, fetal demise, preterm labor and maternal or neonatal death. The precise reasons for increased susceptibility to HEV infection during pregnancy and associated severe disease are still an enigma. Management is supportive and termination of pregnancy is not recommended as a general rule. Prevention of infection is of vital importance, as availability of clean drinking water can reduce the burden of this disease in the community. There is a need for future research to focus on prevention of ALF in pregnancy and to study the disease pathogenesis, which is not explicitly understood at present. The availability of a vaccine may alter the natural course of the disease in this select population which is at risk. PMID:25755503

  13. Cutaneous porphyrias part II: treatment strategies.

    PubMed

    Tintle, Suzanne; Alikhan, Ali; Horner, Mary E; Hand, Jennifer L; Davis, Dawn Marie R

    2014-01-01

    The porphyrias are diverse in pathophysiology, clinical presentation, severity, and prognosis, presenting a diagnostic and therapeutic challenge. Although not easily curable, the dermatological manifestations of these diseases, photosensitivity and associated cutaneous pathology, can be effectively prevented and managed. Sun avoidance is essential, and patient education regarding the irreversibility of photocutaneous damage is a necessary corollary. Beyond preventative measures, the care of fragile, vulnerable skin, and pain management, each of the porphyrias has a limited number of unique additional therapeutic options. Many of the treatments have been published only in small case series or anecdotal reports and do not have well-understood nor proven mechanisms of action. This article presents a comprehensive review of available therapeutic options and long-term management recommendations for the cutaneous porphyrias.

  14. Coincidence of acute brucella hepatitis and dengue fever or serologic cross-reactivity?

    PubMed

    Bzeizi, Khalid I; Benmousa, Ali; Sanai, Faisal M

    2010-01-01

    Hepatic involvement in brucellosis is not uncommon since 10-20% of patient infected with brucella species can have abnormal liver function tests. The usual presentation of brucella hepatitis is in the form of chronic granulomatous hepatitis with mild to moderate elevation of liver enzymes, while acute hepatitis is rare. We report a young patient who presented with acute brucella-induced hepatitis and co-infection with dengue hemorrhagic virus resulting in severe elevation of liver enzymes and absence of granuloma on histology. His mother also simultaneously tested positive for both infections. The patient responded well to anti-brucella therapy with normalization of his liver profile. We discuss, herein, the hepatic involvement of these two infections and discuss the possible serological cross-reactivity between brucella and dengue fever virus.

  15. Injections given in healthcare settings as a major source of acute hepatitis B in Moldova.

    PubMed

    Hutin, Y J; Harpaz, R; Drobeniuc, J; Melnic, A; Ray, C; Favorov, M; Iarovoi, P; Shapiro, C N; Woodruff, B A

    1999-08-01

    Two case-control studies were conducted between January 1994 and August 1995 to determine the relative importance of injections and other exposures as a source of acute hepatitis B in Moldova among adults (aged 15 years) and children (aged 2-15 years). Results showed that injections in various health care settings were associated with acute hepatitis B and showed a higher proportion among adults compared with children. Contact with an HBsAg-positive person was also associated with illnesses; however, there was no statistically significant association between acute hepatitis B and other exposures. The risk of HBV transmission following percutaneous exposure is high (at least 30%). Calculation of the population attributable to risk suggests that injections associated with acute hepatitis B cases occurred in adults (52%) and children (21%). Adverse effects of injections may not be apparent in causing chronic infections. Transmission of blood-borne pathogens through unsafe injection practices is a problem increasingly identified worldwide.

  16. Acute Hepatitis E in the US Today Occurs in Diverse Patient Populations: Case Reports

    PubMed Central

    Aderinto-Adike, Abimbola; Schwartz, Mary R.; Monsour, Howard P.

    2014-01-01

    Hepatitis E has long been thought of as an infection confined to the developing world. However, there has been an increased incidence of locally acquired cases in developed countries especially in transplant patients. Our first case is a 56-year-old Caucasian female post-heart transplant patient who presented with diarrhea and abdominal pain. She was found to be acutely infected with hepatitis E and progressed to stage 3 liver fibrosis. Our second patient was an otherwise healthy 76-year-old Vietnamese female who presented with abdominal pain, jaundice and fatigue. She was diagnosed with acute hepatitis E complicated by acute renal failure. There have only been a few reported cases of acute hepatitis E complicated by renal failure.

  17. Acute hepatitis due to hepatitis A virus subgenotype IA as an imported infectious disease from Indonesia.

    PubMed

    Utsumi, Takako; Yano, Yoshihiko; Amin, Mochamad; Lusida, Maria I; Soetjipto; Hotta, Hak; Hayashi, Yoshitake

    2014-10-01

    A 25-year-old Japanese man was admitted with general malaise and fever, which had developed 12 days after coming back to Japan from Indonesia. Blood examination revealed elevated transaminase levels and positivity for the IgM anti-HAV antibody; therefore, he was diagnosed with acute hepatitis A. HAV-RNA was detected in his serum and phylogenetically classified as subgenotype IA. The partial genome in the VP1/P2A region was consistent with the strain recently isolated from Surabaya, which indicated that he had been infected during his stay in Indonesia. Thus, HAV vaccination is recommended before visiting HAV-endemic countries for a long period of time.

  18. Hepatitis E Virus Genotype 3 in Sewage and Genotype 1 in Acute Hepatitis Cases, Israel.

    PubMed

    Ram, Daniela; Manor, Yossi; Gozlan, Yael; Schwartz, Eli; Ben-Ari, Ziv; Mendelson, Ella; Mor, Orna

    2016-07-01

    Hepatitis E virus (HEV) is an emerging infectious agent in developed countries. HEV genotypes 1 (G1) and 3 (G3) have been identified in environmental and clinical samples in Europe. In Israel, the overall prevalence of anti-HEV IgG antibodies was found to be 10.6%; however, reports of HEV infection are scarce. In this study, the presence of HEV in Israel was investigated using 169 sewage samples from 32 treatment facilities and 49 samples from acute hepatitis patients, all collected between 2013 and 2015. Fourteen sewage samples, from Haifa (11/18 samples), Tel Aviv (2/29 samples), and Beer Sheva (1/17 samples), regions with good sanitary conditions and middle-high socioeconomic populations, were HEV positive. Among the patient samples, 6.1% (3/49) were HEV positive, all returning travelers from India. Genotype analysis revealed G1 HEV in patients and G3 HEV sequences in sewage. Evidence that HEV could be establishing itself in our region may justify more active surveillance to monitor its spread. PMID:27246446

  19. Prevalence of leptospira in acute hepatitis syndrome and assessment of IL-8 and TNF-alpha level in leptospiral hepatitis.

    PubMed

    Rizvi, M; Azam, M; Ajmal, M R; Shukla, I; Malik, A

    2011-10-01

    To study the prevalence of leptospira in acute hepatitis syndrome and to assess interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha levels in the pathogenesis of hepatitis due to leptospiral infection. Two hundred and forty-seven consecutive cases with symptoms of acute hepatitis and 30 healthy controls were enrolled in the study and detailed clinical history was elicited from them. Enzyme-linked immunosorbent assays (ELISAs) for HAV, HBV, HCV and HEV were performed to rule out common viral aetiology of hepatitis. IgM antibodies to leptospira were detected by ELISA. IL-8 and TNF-alpha levels were estimated in leptospira-positive cases and healthy controls by ELISA. Out of 247 cases of acute hepatitis, 46 (18.62%) were observed to be positive for IgM antibodies for leptospira. The mean age of these patients was 31.99 ± 0.28 years (25 males and 21 females; M/F ratio: 1.19:1). The mean ALT, AST and ASP were raised in the majority of patients. IL-8 was found to be elevated (130.81 pg/ml) in a large majority of cases 41/46, 89.1% (P < 0.001). Patients with more severe symptoms were associated with higher levels of IL-8. One mortality was observed due to leptospira. Unpredictably, TNF-alpha level was largely suppressed (45.63 pg/ml) in most of the leptospira-positive patients in comparison with healthy controls. Leptospira-induced hepatitis should be actively looked for in patients negative for A-E viral hepatitis. IL-8 appears to play an important role in the pathogenesis of leptospiral hepatitis. High TNF-alpha should alert clinicians for aggressive in hospital management of patients. PMID:22185944

  20. Effects of acute ethanol exposure on hepatic metallothionein, zinc and glutathione in male and female rats

    SciTech Connect

    Harris, J.; Harrell, B. )

    1991-03-15

    The purpose of this study was to determine the simultaneous responses of hepatic metallothionein (MT), zinc (Zn) and glutathione (GSH) in male and female rats to an acute ethanol dose. In male rats, hepatic MT has been shown to be induced by an acute ethanol dose. The Sprague-Dawley rats were fed the Lieber-DeCarli control diet for a five day period and then divided into 6 groups: baseline females and males, ethanol-treated females and males, pair-fed females and males. At t=0, baseline rats were killed, ethanol-treated rats were given ethanol by intragastric tube, and pair-fed rats were given ethanol by intragastric tube, and pair-fed rats were given an isocaloric sucrose solution by intragastric tube. At t=24 h, the ethanol-treated and pair-fed rats were killed. Livers were assayed for MT. Zn and GSH. Concentrations of blood ethanol (BEC) were significantly greater for male than female rats. A two way ANOVA with the independent variables being time and sex was performed to analyze differences for hepatic MT, Zn and GSH. For rats dosed with ethanol and killed 24 h later compared with rats at baseline, hepatic MT was significantly greater and hepatic Zn and GSH were not significantly different. Hepatic MT, Zn and GSH were not significantly different by sex. A significant correlation existed between hepatic Zn/g and MT/g. In conclusion, 24 h after an acute dose of ethanol, female as well as male rats responded with the induction of hepatic MT; and enough cysteine was available for the induction of hepatic MT and the maintenance of hepatic GSH levels. The measurement of Zn bound to hepatic MT rather than total hepatic Zn would be desirable to discern if changes in Zn distribution occur.

  1. Clinical characteristics and outcomes of acute hepatitis a in Korea: a nationwide multicenter study.

    PubMed

    Kwon, So Young; Park, Sang Hoon; Yeon, Jong Eun; Jeong, Sook Hyang; Kwon, Oh Sang; Lee, Jin Woo; Kim, Hong Soo; Seo, Yeon Seok; Kim, Young Seok; Sohn, Joo Hyun; Yim, Hyung Joon; Choi, Jong Young; Lee, Myung Seok; Kweon, Young Oh; Cheong, Jae Youn; Kim, Haak Cheoul; Lee, Heon Ju; Baik, Soon Koo; An, Hyonggin; Byun, Kwan Soo

    2014-02-01

    The aim of this study was to investigate the clinical characteristics of acute hepatitis A during a recent outbreak in Korea. Data of patients diagnosed with acute hepatitis A from 2007 to 2009 were collected from 21 tertiary hospitals retrospectively. Their demographic, clinical, and serological characteristics and their clinical outcomes were analyzed. A total of 4,218 patients (mean age 33.3 yr) were included. The median duration of admission was 9 days. The mean of the highest ALT level was 2,963 IU/L, total bilirubin was 7.3 mg/dL, prothrombin time INR was 1.3. HBsAg was positive in 3.7%, and anti-HCV positive in 0.7%. Renal insufficiency occurred in 2.7%, hepatic failure in 0.9%, relapsing hepatitis in 0.7%, and cholestatic hepatitis in 1.9% of the patients. Nineteen patients (0.45%) died or were transplanted. Complications of renal failure or prolonged cholestasis were more frequent in patients older than 30 yr. In conclusion, most patients with acute hepatitis A recover uneventfully, however, complication rates are higher in patients older than 30 yr than younger patients. Preventive strategies including universal vaccination in infants and active immunization of hepatitis A to adult population should be considered for prevention of community-wide outbreaks of hepatitis A in Korea.

  2. An outbreak of refrigerant-induced acute hepatitis in Hong Kong.

    PubMed

    Kan, Y M; Lau, C F; Chan, W C; Chan, W S; Tung, Y M; Loo, C K

    2014-12-01

    We report a cluster of acute hepatitis in five air-conditioning maintenance workers following accidental exposure to 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123). They presented to us with complaints of feverishness, generalised malaise, and epigastric discomfort. Their blood biochemistry tests were compatible with acute hepatitis. Viral hepatitis serology, tests for autoimmune hepatitis, and analyses for drugs and alcohol consumption were all negative. No focal hepatic lesion was detected by ultrasound imaging. Percutaneous liver biopsy samples were taken from two of them. The patients were managed with supportive treatment. All had spontaneous, but slow, recovery. Their liver function tests returned to normal after 4 months and their outcomes were favourable. Physicians should be aware of this occupational disease entity. PMID:25488036

  3. [Social determinants and risk of acute viral hepatitis].

    PubMed

    Malvasio, P; Russo, R; Zotti, C; Vigna, I; Ruggenini Moiraghi, A

    1998-01-01

    The authors examined the relationship between viral hepatitis risk and social determinants in Piedmont region population surveyed by SEIEVA (sistema epidemiologico integrato dell'epatite virale acuta). The education and the working position showed different correlation with incidence rates of different types of viral hepatitis A, B, non-A non-B. The hepatitis A risk is proportional to education and the probability of hepatitis B and non-A non-B is higher in low social classes. This situation is only apparently a balanced risk: the clinical seriousness and the strong probability of complications of hepatitis B and non-A non-B make the risks deeply unequal.

  4. Hepatitis C core antigen testing: a reliable, quick, and potentially cost-effective alternative to hepatitis C polymerase chain reaction in diagnosing acute hepatitis C virus infection.

    PubMed

    Cresswell, Fiona V; Fisher, Martin; Hughes, Daniel J; Shaw, Simon G; Homer, Gary; Hassan-Ibrahim, Mohammed O

    2015-01-15

    Hepatitis C virus (HCV) is increasingly common among human immunodeficiency virus (HIV)-infected men who have sex with men. We evaluated the efficacy of HCV core antigen in diagnosing acute HCV in an HIV-infected cohort. Compared with HCV polymerase chain reaction, core antigen proved sensitive (100%) and specific (97.9%). As a quick, simple, and cost-effective test, it has considerable utility in screening for acute HCV.

  5. Shifting hepatitis B virus genotypes of acute hepatitis B patients in northeast Japan.

    PubMed

    Inoue, Jun; Kondo, Yasuteru; Umetsu, Teruyuki; Yamamoto, Takeshi; Miura, Masahito; Mano, Yutaka; Kobayashi, Tomoo; Obara, Noriyuki; Niitsuma, Hirofumi; Kogure, Takayuki; Nakagome, Yu; Kimura, Osamu; Iwata, Tomoaki; Morosawa, Tatsuki; Fujisaka, Yasuyuki; Shimosegawa, Tooru

    2016-01-01

    It has been reported that acute hepatitis B (AHB) patients with genotype A HBV (HBV/A) have been increasing since the 1990s in metropolitan areas in Japan. However, little is known about the trends of HBV genotypes in AHB patients in northeast Japan where genotype B HBV (HBV/B) prevails more than in other areas. In this study, we aimed to clarify the changes in the HBV genotypes and clinical characteristics of AHB patients in this area. HBV genotypes were determined by direct sequencing (n = 125) or enzyme immunoassay (n = 9) using serum samples from AHB patients including fulminant hepatitis in 1987-2014. Among 134 patients, 26 (19%), 33 (25%), and 75 (56%) patients were infected with HBV of genotypes A, B, and C, respectively. HBV/A emerged from 2001 and the percentage was increased gradually up to 48% in 2010-2014, whereas HBV/B was reduced from 40% in 1987-1994 to 10% in 2010-2014. Phylogenetic analysis showed that three major subgenotype A2 strains had come into this area serially. The levels of HBV DNA and prothrombin time were higher in HBV/A patients than other genotypes. This study could not show significant difference in the HBsAg-positive period among genotypes nor the effect of nucleoside analogues to shorten the HBsAg-positive period. A higher level of initial HBV DNA was associated with late disappearance of HBsAg. In conclusion, the percentage of HBV/A in AHB patients has been increasing in northeast Japan since 2001, which is later than metropolitan areas, whereas that of HBV/B is decreasing.

  6. Porphyria cutanea tarda in a HIV- positive patient.

    PubMed

    Franzon, Valéria Aparecida Zanela; Mikilita, Emanuella Stella; Camelo, Fernanda Henriques; Camargo, Rosana

    2016-01-01

    This is a case report about Porphyria cutanea tarda (PCT) and its relationship with the infection caused by the human immunodeficiency virus (HIV). Cutaneous porphyria is an illness caused by enzymatic modification that results in partial deficiency of uroporphyrinogen decarboxylase (Urod), which may be hereditary or acquired. Several studies suggest that HIV infection associated with cofactors might trigger the development of porphyria cutanea tarda. In this case report, we present a patient infected with HIV, who after the introduction of antiretroviral therapy (ART) enjoyed clinical improvement of porphyria cutanea tarda symptoms. PMID:27579753

  7. Porphyria cutanea tarda in a HIV- positive patient*

    PubMed Central

    Franzon, Valéria Aparecida Zanela; Mikilita, Emanuella Stella; Camelo, Fernanda Henriques; Camargo, Rosana

    2016-01-01

    This is a case report about Porphyria cutanea tarda (PCT) and its relationship with the infection caused by the human immunodeficiency virus (HIV). Cutaneous porphyria is an illness caused by enzymatic modification that results in partial deficiency of uroporphyrinogen decarboxylase (Urod), which may be hereditary or acquired. Several studies suggest that HIV infection associated with cofactors might trigger the development of porphyria cutanea tarda. In this case report, we present a patient infected with HIV, who after the introduction of antiretroviral therapy (ART) enjoyed clinical improvement of porphyria cutanea tarda symptoms. PMID:27579753

  8. Acute acalculous cholecystitis caused by Hepatitis C: A rare case report

    PubMed Central

    Omar, Ahmed; Osman, Medhet; Bonnet, Gerard; Ghamri, Nafiz

    2015-01-01

    Introduction Acute acalculous cholecystitis (AAC) is rarely encountered in clinical practice and has a high morbidity and mortality. AAC caused by viral hepatitis, with hepatitis A, B and EBV infections are rare, but well documented in the literature. Hepatitis C virus has not been reported as cause of AAC. This case report documents the first case of AAC associated with Acute Hepatitis C. Presenting concerns We present a 40 years old female with abdominal pain. She has a history of previous HCV infection. Her liver function tests were markedly deranged with elevated inflammatory markers. USS scan showed rather a very unusual appearance of an inflamed gallbladder with no gallstones and associated acute hepatitis, confirmed by an abdominal CT scan. HCV RNA PCR confirms flair up of the virus. The patient was managed conservatively in the hospital with follow up USS scan and Liver function tests showed complete recovery. Follow up HCV RNA PCR also returned to an undetectable level. The patient recovered completely with no adverse outcomes. Conclusion This case report is to the first to document the association between acute HCV and AAC. Despite being uncommon in western countries, viral hepatitis should be suspected as a causative agent of AAC, particularly when there is abnormal liver function test and no biliary obstruction. PMID:26722714

  9. Prevalence and types of drug-resistant variants in Chinese patients with acute hepatitis B.

    PubMed

    Su, Feifei; Dai, Jianyi; Yang, Shoufeng; Jiang, Xiangao; Cui, Xiaoya; Ning, Hongye; Li, Junhua; Huang, Mohe

    2015-09-01

    The presence of therapy-associated hepatitis B virus (HBV) variants is the main drawback of antiviral therapy for HBV infection. Moreover, drug-resistant variants are more insensitive to a second agent and more therapy-associated mutations will be present. To apply better nucleos(t)ide analogues (NA) and reduce the occurrence of resistance, the prevalence and types of drug-resistant mutations in acute hepatitis B patients were investigated in this study. One hundred three HBV DNA-positive patients with symptomatic acute hepatitis B that were observed from 2011 to 2013 were enrolled. Direct polymerase chain reaction sequencing was used firstly to screen HBV reverse-transcriptase domain to detect HBV mutants. Five lamivudine-resistant variants were identified. Clonal sequencing was performed for 5 resistance-positive samples and 10 other random samples. Interestingly, all detected samples harbored drug-resistant mutations, although with different percentage. Thirteen harbored lamivudine-related alone (five) or together with other NA related mutations (five with adefovir, one with entecavir, and one with telbivudine), and two of them harbored adefovir-related mutations. Also, mutations associated with four currently used NA were all detected, and the frequency is in accordance with the popularity of NA used in clinical practice. These data suggest that drug-resistant variants are present in patients with acute hepatitis B and NA should be applied more carefully for chronic hepatitis B patients developed from acute hepatitis B.

  10. Peripheral blood mononuclear cells and regulatory T cells in acute viral hepatitis.

    PubMed Central

    Barnaba, V; Tamburrini, E; Laghi, V; Cauda, R; Levrero, M; Ruocco, G; Ortona, L; Balsano, F

    1985-01-01

    During acute viral hepatitis, we observed a significant decrease in OKT4/OKT8 ratio with a significant increase in the OKT8 positive subset in acute type B and non-A-non-B hepatitis. This altered ratio persisted in type B for a long time until HBsAg antibody became detectable, while it soon returned to normal in type A and non-A-non-B hepatitis. In the majority of acute hepatitis the altered ratio is because of an increase and not to a decrease in the whole T cell population, as described in chronic HBV infection. The number of HNK-1 positive cells remained raised during the recovery phase of type B and non-A-non-B hepatitis, a finding consistent with the hypothesis that NK cells play a role in the host defence against B and non-A-non-B virus infections. Serum beta 2-microglobulin concentrations were increased only in acute hepatitis B and non-A-non-B where immunological mechanisms are suspected to be involved, and showed a good correlation with the population of activated OKIa positive cells. PMID:2862096

  11. Hepatic metabolism of ibuprofen in rats under acute hypobaric hypoxia.

    PubMed

    Gola, Shefali; Keshri, Gaurav Km; Gupta, Asheesh

    2013-09-01

    Hypobaric hypoxia induced at high altitude causes a subnormal oxygen concentration in cells which affects the drug metabolic and pharmacokinetic (PK) capacity of the body. The metabolism and PK of drugs like ibuprofen may be impaired under hypoxia and may require a different than usual therapeutic dose regimen to ensure safe therapy. The present investigation was undertaken to evaluate the effect of acute hypobaric hypoxia (AHH) on hepatic metabolism and PK of ibuprofen in rats. Animals were exposed to simulated altitude of 7620 m (∼25,000 ft) for AHH exposure (6 and 24 h) in a decompression chamber and were administrated with single dose of ibuprofen (80 mg/kg body weight, p.o.). The results showed that GST activity was significantly reduced at 6 h (15%) and 24 h (23%) (p<0.05) in hypoxic group as compared to normoxic. A significant increase by 20-24% (p<0.05) in AST level was observed after AHH exposure. LDH activity also exhibited significant increase (p<0.05) after 24h of AHH. A significant down-regulated CYP2C9 level and mild histopathological changes were observed after 24h of AHH. Furthermore, PK variables viz. elimination half-life (T½) and mean residence time (MRT) of ibuprofen exhibited significant increase by 42% and 51% (p<0.05) respectively after 24h of AHH. Thus, results suggest that AHH exposure of 24h significantly affects phase II conjugation pathway, CYP2C9 level, AST level, liver histology and PK parameters. This asserts that AHH can impair disposition of ibuprofen however, it requires further investigation under chronic hypobaric hypoxic conditions.

  12. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.

    PubMed

    Romero-Gómez, Manuel; Montagnese, Sara; Jalan, Rajiv

    2015-02-01

    Hepatic encephalopathy in a hospitalized cirrhotic patient is associated with a high mortality rate and its presence adds further to the mortality of patients with acute-on-chronic liver failure (ACLF). The exact pathophysiological mechanisms of HE in this group of patients are unclear but hyperammonemia, systemic inflammation (including sepsis, bacterial translocation, and insulin resistance) and oxidative stress, modulated by glutaminase gene alteration, remain as key factors. Moreover, alcohol misuse, hyponatremia, renal insufficiency, and microbiota are actively explored. HE diagnosis requires exclusion of other causes of neurological, metabolic and psychiatric dysfunction. Hospitalization in the ICU should be considered in every patient with overt HE, but particularly if this is associated with ACLF. Precipitating factors should be identified and treated as required. Evidence-based specific management options are limited to bowel cleansing and non-absorbable antibiotics. Ammonia lowering drugs, such as glycerol phenylbutyrate and ornithine phenylacetate show promise but are still in clinical trials. Albumin dialysis may be useful in refractory cases. Antibiotics, prebiotics, and treatment of diabetes reduce systemic inflammation. Where possible and not contraindicated, large portal-systemic shunts may be embolized but liver transplantation is the most definitive step in the management of HE in this setting. HE in patients with ACLF appears to be clinically and pathophysiologically distinct from that of acute decompensation and requires further studies and characterization.

  13. Chinese green tea and acute hepatitis: a rare yet recurring theme.

    PubMed

    Lugg, Sebastian Thomas; Braganza Menezes, Darryl; Gompertz, Simon

    2015-09-23

    A previously healthy 16-year-old girl presented with signs of acute hepatitis. On initial enquiry, she had not taken any prescribed or 'over-the-counter' medications, and there was no recent travel history. Further investigations revealed no viral, autoimmune or metabolic cause of hepatitis. Only following specific questioning did she reveal that she had, in the preceding 3 months, regularly consumed internet ordered Chinese green tea, which contained Camellia sinensis. After ceasing green tea consumption, there was a rapid and sustained recovery of her hepatitis. The authors discuss the probable cause of herbal tea in this case of acute hepatitis, and the importance of awareness of this rare yet recurring theme for patients and clinicians alike.

  14. Acute hepatitis in an opossum (Didelphis virginiana) infected with Salmonella turnidorp.

    PubMed

    Lu, Y S; Rehg, J; Lawton, G

    1982-04-01

    Salmonella turnidorp was isolated in pure culture from the liver of an opossum that died of acute hepatitis. Microscopically, there were random foci of hepatic coagulation necrosis and gram negative bacteria within hepatocytes. The Salmonella turnidorp isolate was aberrant in that it did not utilize citrate and did not agglutinate by a commercial Salmonella polyvalent antiserum. Additional Salmonella serotypes, including Salmonella mbandaka, Salmonella rubislaw, and Salmonella anatum were isolated from three of five healthy opossums caught in Texas.

  15. Acute Lymphoblastic Leukemia in a Young Adult Presenting as Hepatitis and Acute Kidney Injury

    PubMed Central

    Heincelman, Marc; Karakala, Nithin; Rockey, Don C.

    2016-01-01

    Acute lymphoblastic leukemia (ALL) in adults is a relatively rare malignancy. The typical presentation includes signs and symptoms associated with bone marrow failure, including fevers, infections, fatigue, and excessive bruising. In this article, we report an unusual systemic presentation of ALL in a previously healthy 18-year-old man. He initially presented with several-day history of nausea and vomiting, 10-pound weight loss, and right upper quadrant abdominal pain with evidence of acute hepatocellular liver injury (elevations in aspartate aminotransferase/alanine aminotransferase) and elevation in serum creatinine. Further history revealed that he just joined the Marine Corp; in preparation, he had been lifting weights and taking protein and creatine supplements. A complete serological evaluation for liver disease was negative and creatine phosphokinase was normal. His aspartate aminotransferase and alanine aminotransferase declined, and he was discharged with expected improvement. However, he returned one week later with continued symptoms and greater elevation of aminotransferases. Liver biopsy was nondiagnostic, revealing scattered portal and lobular inflammatory cells (primarily lymphocytes) felt to be consistent with drug-induced liver injury or viral hepatitis. Given his elevated creatinine, unresponsive to aggressive volume expansion, a kidney biopsy was performed, revealing normal histology. He subsequently developed an extensive left lower extremity deep venous thrombosis. Given his deep venous thrombosis, his peripheral blood was sent for flow cytometry, which revealed lymphoblasts. Bone marrow biopsy revealed 78% blasts with markers consistent with acute B-cell lymphoblastic leukemia. This report emphasizes that right upper quadrant abdominal pain with liver test abnormalities may be the initial presentation of a systemic illness such as ALL. PMID:27722178

  16. Desferrioxamine treatment of porphyria cutanea tarda in a patient with HIV and chronic renal failure.

    PubMed

    Vasconcelos, Pedro; Luz-Rodrigues, H; Santos, Carla; Filipe, Paulo

    2014-01-01

    Porphyria cutanea tarda (PCT) can occur in HIV patients. Current evidence suggests that HIV infection may interfere with the hepatic cytochrome oxidase system, leading to porphyrin metabolism impairment. Moreover, chronic hemodialysis in renal failure may be a risk factor for PCT. In addition to the contributory factors for PCT associated to HIV infection, it is possible that porphyrin accumulation secondary to renal failure may play a role in the expression of this disease. We report a case of PCT in an HIV-1 infected patient under blood dialysis, refractory to antimalarials and controlled with desferrioxamine.

  17. Human Immunodeficiency Virus Associated Sporadic Nonfamilial Porphyria Cutanea Tarda.

    PubMed

    Guha, Sibashish Kamal; Bandyopadhyay, Debabrata; Saha, Abanti; Lal, Niharika Ranjan

    2016-01-01

    Porphyria cutanea tarda (PCT), a relatively uncommon metabolic disease, is the most common cutaneous porphyria. Here, we present the case of a patient diagnosed with sporadic, nonfamilial PCT that presented with classical cutaneous findings and multiple risk factors, including alcohol abuse, human immunodeficiency virus/AIDS, that have been strongly associated with the sporadic form of PCT. PMID:27293254

  18. Porphyria and porphyrinology--the past fifteen years.

    PubMed

    McDonagh, A F; Bissell, D M

    1998-01-01

    The porphyrias are diseases caused by defective biosynthesis of heme. Leavened by digressions on porphyria trivia, this article presents selected highlights from the last 15 years of research on the chemistry, diagnosis, and treatment of the porphyrias. Thanks largely to genetic analysis and new light shed on the magical chemistry of heme biosynthesis, this period has seen great advances in the understanding of porphyria. Sequence analyses of the genes for all of the enzymes required for heme biosynthesis have revealed the porphyrias as highly heterogeneous, with multiple mutations underlying each type. As a result of technical advances, clinical porphyrin analyses are easier and more detailed, but their misapplication to "multiple chemical sensitivity syndrome" or "intoxication porphyria" is unfortunate. The prospect of gene therapy shines ever brighter but is neither safe nor effective enough to be considered for porphyria. As practical spin-offs, porphyrins are in use increasingly for diagnosis and treatment of cancer and as herbicides and pesticides. Accounts of alleged porphyria in "Prominent People" in the popular press continue to appear, generating fanciful misconceptions, often at the expense of patients with these fascinating diseases.

  19. Human Immunodeficiency Virus Associated Sporadic Nonfamilial Porphyria Cutanea Tarda

    PubMed Central

    Guha, Sibashish Kamal; Bandyopadhyay, Debabrata; Saha, Abanti; Lal, Niharika Ranjan

    2016-01-01

    Porphyria cutanea tarda (PCT), a relatively uncommon metabolic disease, is the most common cutaneous porphyria. Here, we present the case of a patient diagnosed with sporadic, nonfamilial PCT that presented with classical cutaneous findings and multiple risk factors, including alcohol abuse, human immunodeficiency virus/AIDS, that have been strongly associated with the sporadic form of PCT. PMID:27293254

  20. [Strategies for diagnosis and biochemical control of porphyrias].

    PubMed

    Brock, Axel; Rasmussen, Lars Melholt; Hertz, Jens Michael

    2014-02-17

    Porphyrias are rare, distinct and well characterized diseases due to impairment of one of the eight steps in the biosynthesis of haem, which is the functional group of haemoglobin, myoglobin and cytochromes, including the cytochrome P-450 family. The actual strategies for diagnosis and biochemical control of the five most common porphyrias are described.

  1. Acute and chronic effect of ethanol on hepatic albumin synthesis in rat liver in vitro

    SciTech Connect

    Ohtake, H.; Kato, S.; Murawaki, Y.; Kishimoto, Y.; Wakushima, T.; Hirayama, C.

    1986-08-01

    To study the effects of ethanol and its metabolite on albumin metabolism, we examined the hepatic albumin synthesis and secretion in male Wistar rats in vitro, following acute and chronic ethanol administration. After acute ethanol administration, proalbumin synthesis in rat liver in vitro, declined to 47% of the control level at 4 hrs, the lowest level, and increased thereafter to slightly higher than the control level at 16 hrs. On the other hand, chronic ethanol administration for 4 weeks, increased proalbumin synthesis to 1.5 times that of the control level. In the acute ethanol group, a significant negative correlation was observed between proalbumin radioactivity and the concentration of hepatic ethanol and acetaldehyde. The variation between proalbumin radioactivity and hepatic ethanol concentration was wider than the variation between proalbumin and hepatic acetaldehyde. In the chronic ethanol group, ethanol was not detected in the liver. No significant differences from the proalbumin/albumin ratio were seen at any time point after acute or chronic ethanol administration. These findings suggest that the effects of ethanol on hepatic albumin synthesis differ with the method of ethanol administration, and acetaldehyde and/or ethanol is involved in the reduction in albumin synthesis, however, proalbumin-albumin conversion is not disturbed.

  2. Pathologic and ultrastructural changes of acute and chronic delta hepatitis in an experimentally infected chimpanzee.

    PubMed Central

    Govindarajan, S.; Fields, H. A.; Humphrey, C. D.; Margolis, H. S.

    1986-01-01

    A hepatitis B surface antigen (HBsAg) chronic carrier chimpanzee experimentally superinfected with delta virus (DV) developed chronic DV infection. Over a period of 12 months, serologic and biochemical changes were correlated with morphologic abnormalities of the liver. Severe hepatic necrosis and inflammation accompanied the initial acute episode of hepatitis on Day 35 after inoculation, followed by complete resolution of these lesions over the next 3 months. A second episode of hepatitis occurred on Day 145, and severe necrosis and inflammation recurred along with the reappearance of delta antigen in the hepatocytes. Delta antigen persisted in the liver following the second episode of hepatitis and has remained positive throughout the observation period of 1 year. During the initial acute episode, the hepatocytes exhibited foamy cytoplasmic changes resembling microvesicular fat. However, ultrastructural studies of the same cells revealed only vacuolization of the cytoplasm without evidence of fat droplets. The inflammatory infiltrate during both episodes of hepatitis demonstrated a striking predominance of macrophages over lymphocytes. Hepatocyte abnormalities observed by electron microscopy included vacuoles, proliferated endoplasmic reticulum, and tubules similar to those seen in posttransfusion non-A, non-B hepatitis. However, the tubular and reticular abnormalities coincided with delta antigen expression in liver biopsies detected by direct immunoperoxidase staining and abnormal alanine aminotransferase levels in the serum, which suggests a possible causal relationship. Nuclear abnormalities were not seen. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:3511726

  3. Acute enteral manganese intoxication with hepatic failure due to ingestion of a joint supplement overdose.

    PubMed

    Borchers, Angela; Epstein, Steven E; Gindiciosi, Blaz; Cartoceti, Andrew; Puschner, Birgit

    2014-09-01

    Manganese is a ubiquitous, essential trace element and a common ingredient of joint supplement tablets. Little information is known about the inherent toxic potential if ingested at higher doses. A 5-year-old female spayed Pug dog presented for evaluation of vomiting and ataxia after accidental ingestion of approximately 100 joint supplement tablets. The dog developed acute hepatic failure and was euthanized 6 days after presentation due to progression of the disease. Necropsy showed severe acute hepatic necrosis. Liver and kidney samples were submitted for toxicology analysis, results of which showed severely elevated manganese concentrations in the liver and kidneys.

  4. Risk factors and prognosis of hepatic acute GvHD after allogeneic hematopoietic cell transplantation.

    PubMed

    Arai, Y; Kanda, J; Nakasone, H; Kondo, T; Uchida, N; Fukuda, T; Ohashi, K; Kaida, K; Iwato, K; Eto, T; Kanda, Y; Nakamae, H; Nagamura-Inoue, T; Morishima, Y; Hirokawa, M; Atsuta, Y; Murata, M

    2016-01-01

    Hepatic acute GvHD (aGvHD) is associated with high mortality owing to poor response to immunosuppressive therapy. The pathogenesis of hepatic aGvHD differs from that of other lesions, and specific risk factors related to pre-transplant liver conditions should be determined. We conducted a cohort study by using a Japanese transplant registry database (N=8378). Of these subjects, 1.5% had hepatitis C virus Ab (HCV-Ab) and 9.4% had liver dysfunction (elevated transaminase or bilirubin levels) before hematopoietic cell transplantation (HCT). After HCT, the cumulative incidence of hepatic aGvHD was 6.7%. On multivariate analyses, HCV-Ab positivity (hazard ratio (HR), 1.93; P=0.02) and pre-transplant liver dysfunction (HR, 1.85; P<0.01), as well as advanced HCT risk, unrelated donors, HLA mismatch and cyclosporine as GvHD prophylaxis, were significant risk factors for hepatic aGvHD, whereas hepatitis B virus surface Ag was not. Hepatic aGvHD was a significant risk factor for low overall survival and high transplant-related mortality in all aGvHD grades (P<0.01). This study is the first to show the relationship between pre-transplant liver conditions and hepatic aGvHD. A prospective study is awaited to validate the results of this study and establish a new strategy especially for high-risk patients. PMID:26367230

  5. Acute sterol o-acyltransferase 2 (SOAT2) knockdown rapidly mobilizes hepatic cholesterol for fecal excretion.

    PubMed

    Marshall, Stephanie M; Gromovsky, Anthony D; Kelley, Kathryn L; Davis, Matthew A; Wilson, Martha D; Lee, Richard G; Crooke, Rosanne M; Graham, Mark J; Rudel, Lawrence L; Brown, J Mark; Temel, Ryan E

    2014-01-01

    The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE). We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2) increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD), the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ∼ 2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion.

  6. Acute Sterol O-Acyltransferase 2 (SOAT2) Knockdown Rapidly Mobilizes Hepatic Cholesterol for Fecal Excretion

    PubMed Central

    Marshall, Stephanie M.; Gromovsky, Anthony D.; Kelley, Kathryn L.; Davis, Matthew A.; Wilson, Martha D.; Lee, Richard G.; Crooke, Rosanne M.; Graham, Mark J.; Rudel, Lawrence L.

    2014-01-01

    The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE). We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2) increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD), the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ∼2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion. PMID:24901470

  7. Use of iron colloid-enhanced MRI for study of acute radiation-induced hepatic injury

    SciTech Connect

    Suto, Yuji; Ametani, Masaki; Kato, Takashi; Hashimoto, Masayuki; Kamba, Masayuki; Sugihara, Syuji; Ohta, Yoshio

    1996-03-01

    We present a case with acute radiation-induced hepatic injury using chondroitin sulfate iron colloid (CSIC)-enhanced MRI. Uptake of CSIC was decreased in the irradiated portion of the liver. CSIC-enhanced MRI is useful for obtaining information on the function of the reticuloendothelial system and demarcates between irradiated and nonirradiated zones. 18 refs., 3 figs

  8. Acute hepatitis C virus infections attributed to unsafe injection practices at an endoscopy clinic--Nevada, 2007.

    PubMed

    2008-05-16

    On January 2, 2008, the Nevada State Health Division (NSHD) contacted CDC concerning surveillance reports received by the Southern Nevada Health District (SNHD) regarding two persons recently diagnosed with acute hepatitis C. A third person with acute hepatitis C was reported the following day. This raised concerns about an outbreak because SNHD typically confirms four or fewer cases of acute hepatitis C per year. Initial inquiries found that all three persons with acute hepatitis C underwent procedures at the same endoscopy clinic (clinic A) within 35-90 days of illness onset. A joint investigation by SNHD, NSHD, and CDC was initiated on January 9, 2008. The epidemiologic and laboratory investigation revealed that hepatitis C virus (HCV) transmission likely resulted from reuse of syringes on individual patients and use of single-use medication vials on multiple patients at the clinic. Health officials advised clinic A to stop unsafe injection practices immediately, and approximately 40,000 patients of the clinic were notified about their potential risk for exposure to HCV and other bloodborne pathogens. This report focuses on the six cases of acute hepatitis C identified during the initial investigation, which is ongoing; additional cases of acute hepatitis C associated with exposures at clinic A might be identified. Comprehensive measures involving viral hepatitis surveillance, health-care provider education, public awareness, professional oversight, licensing, and improvements in medical devices can help detect and prevent transmission of HCV and other bloodborne pathogens in health-care settings.

  9. Hepatitis

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...

  10. Severe acute hepatitis in the DRESS syndrome: Report of two cases.

    PubMed

    Lens, Sabela; Crespo, Gonzalo; Carrión, Jose A; Miquel, Rosa; Navasa, Miquel

    2010-01-01

    The DRESS (drug rash, eosinophilia and systemic symptoms) syndrome, also known as DIHS (drug-induced hypersensitivity syndrome), is a severe idiosyncratic reaction to several drugs, mainly antiepileptics and antibiotics, which can occasionally produce acute liver failure. In this article we present two cases of the DRESS syndrome presenting with severe acute hepatitis, including the first case of DRESS associated with levetiracetam. Although both cases finally resolved with good outcomes, DRESS can lead to acute liver failure and has a bad prognosis when liver damage is present. Rapid diagnosis is crucial since withdrawal of the offending drug is the key of treatment, while the potential role of corticosteroids is discussed. PMID:20526017

  11. Acute toxic hepatitis caused by an aloe vera preparation in a young patient: a case report with a literature review.

    PubMed

    Lee, Jeonghun; Lee, Mi Sun; Nam, Kwan Woo

    2014-07-01

    Aloe is one of the leading products used in phytomedicine. Several cases of aloe-induced toxic hepatitis have been reported in recent years. However, its toxicology has not yet been systematically described in the literature. A 21-year-old female patient was admitted to our hospital with acute hepatitis after taking an aloe vera preparation for four weeks. Her history, clinical manifestation, laboratory findings, and histological findings all led to the diagnosis of aloe vera-induced toxic hepatitis. We report herein on a case of acute toxic hepatitis induced by aloe vera.

  12. Quantitative Proteomics Identifies Host Factors Modulated during Acute Hepatitis E Virus Infection in the Swine Model

    PubMed Central

    Rogée, Sophie; Le Gall, Morgane; Chafey, Philippe; Bouquet, Jérôme; Cordonnier, Nathalie; Frederici, Christian

    2014-01-01

    ABSTRACT Hepatitis E virus (HEV) causes acute enterically transmitted hepatitis. In industrialized countries, it is a zoonotic disease, with swine being the major reservoir of human HEV contamination. The occurrence and severity of the disease are variable, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In the absence of a robust cell culture system or small-animal models, the HEV life cycle and pathological process remain unclear. To characterize HEV pathogenesis and virulence mechanisms, a quantitative proteomic analysis was carried out to identify cellular factors and pathways modulated during acute infection of swine. Three groups of pigs were inoculated with three different strains of swine HEV to evaluate the possible role of viral determinants in pathogenesis. Liver samples were analyzed by a differential proteomic approach, two-dimensional difference in gel electrophoresis, and 61 modulated proteins were identified by mass spectroscopy. The results obtained show that the three HEV strains replicate similarly in swine and that they modulate several cellular pathways, suggesting that HEV impairs several cellular processes, which can account for the various types of disease expression. Several proteins, such as heterogeneous nuclear ribonucleoprotein K, apolipoprotein E, and prohibitin, known to be involved in other viral life cycles, were upregulated in HEV-infected livers. Some differences were observed between the three strains, suggesting that HEV's genetic variability may induce variations in pathogenesis. This comparative analysis of the liver proteome modulated during infection with three different strains of HEV genotype 3 provides an important basis for further investigations on the factors involved in HEV replication and the mechanism of HEV pathogenesis. IMPORTANCE Hepatitis E virus (HEV) is responsible for acute hepatitis, with clinical symptoms ranging from asymptomatic

  13. Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology.

    PubMed

    Horner, Mary E; Alikhan, Ali; Tintle, Suzanne; Tortorelli, Silvia; Davis, Dawn Marie R; Hand, Jennifer L

    2013-12-01

    The porphyrias are a group of disorders characterized by defects in the heme biosynthesis pathway. Many present with skin findings including photosensitivity, bullae, hypertrichosis, and scarring. Systemic symptoms may include abdominal pain, neuropsychiatric changes, anemia, and liver disease. With advances in DNA analysis, researchers are discovering the underlying genetic causes of the porphyrias, enabling family members to be tested for genetic mutations. Here we present a comprehensive review of porphyria focusing on those with cutaneous manifestations. In Part I, we have included the epidemiology, pathogenesis, presentation, diagnosis, and histopathology. Treatment and management options will be discussed in Part II.

  14. [Humoral and cellular immune phenomena in an acute viral hepatitis (author's transl)].

    PubMed

    Sodomann, C P

    1975-08-01

    During the course of acute viral hepatitis A and B, several humoral and cellular immune phenomena have been observed, part of which is predominantly or even exclusively associated with hepatitis B: 1. Relative and absolute counts for T-lymphocytes depressed and for "null" -cells elevated; 2. mild elevation of serum globulin levels; 3. IgM augmentation occurring fastly, pronounced, and long lasting in typical cases; 4. IgG augmentation occurring later, less pronounced, and for a shorter period in typical cases; 5. autoantibodies to smooth muscles and mitochondria in low titers in some patients; 6. specific antibodies to "e" -antigen (early) and HB-Ag (later in the course) in part of the cases with hepatitis B; 7. immune complexes including HB-Ag, IgG and probably IgM (and IgA) as well as complement in some cases; 8. depressed levels of the fourth component of complement and - in cases complicated by "allergic" symptoms - of C3, C4, and total complement; 9. occurrence of activated lymphocytes ("virocytes") in peripheral blood; 10. enhanced spontaneous lymphocytic DNA-synthesis; 11. enchanced phytohaemagglutinin stimulation of lymphocytes; 12. mild lymphocyte proliferation to HB-Ag in part of the acute and convalescent cases of hepatitis B; 13. production of migration inhibition factor to liver specific protein (and HB-Ag) or lymphocytes in different percentages of patients with hepatitis B. Origin, diagnostic and prognostic importance, as well as pathogenetic revelance of the described immune phenomena are discussed.

  15. Contribution of Hepatitis B to Long-Term Outcome Among Patients With Acute Myocardial Infarction

    PubMed Central

    Kuo, Pei-Lun; Lin, Kun-Chang; Tang, Pei-Ling; Cheng, Chin-Chang; Huang, Wei-Chun; Chiang, Cheng-Hung; Lin, Hsiao-Chin; Chuang, Tzu-Jung; Wann, Shue-Ren; Mar, Guang-Yuan; Cheng, Jin-Shiung; Liu, Chun-Peng

    2016-01-01

    Abstract Although a possible association between hepatitis B and cardiovascular disease has been identified, the impact of viral hepatitis B on long-term prognosis after an acute myocardial infarction (AMI) is uncertain. Therefore, the aim of our study was to evaluate the specific impact of viral hepatitis B on survival after a first AMI through a retrospective analysis of data from the Taiwan National Health Insurance Research Database. This was a nationwide, propensity score-matched case–control study of patients admitted to hospitals between January 2000 and December 2012 with a primary diagnosis of a first AMI. Among the 7671 prospective patients, 244 patients with a confirmed diagnosis of viral hepatitis B infection were identified. A propensity score, one-to-one matching technique was used to match 244 controls to the AMI group for analysis. Controls were matched on the following variables: sex, age, hypertension, dyslipidemia, diabetes, peripheral vascular disease, heart failure, cerebrovascular accidents, end-stage renal disease, chronic obstructive pulmonary disease, and percutaneous coronary intervention (PCI). Overall, viral hepatitis B infection did not influence the 12-year survival rate (P = 0.98). However, survival was lower in female patients with viral hepatitis B infection compared to those without (P = 0.03; hazard ratio, 1.79; 95% confidence interval, 1.08–2.94). Inclusion of percutaneous coronary management improved survival, independent of sex, age, or hepatitis B status. Hepatitis B infection might increase the mortality risk of female patients after a first AMI. PCI may improve the long-term survival of patients after a first AMI, regardless of sex, age, and hepatitis B status. PMID:26844504

  16. A cluster of acute hepatitis E infection in United Nations Bangladeshi peacekeepers in Haiti.

    PubMed

    Drabick, J J; Gambel, J M; Gouvea, V S; Caudill, J D; Sun, W; Hoke, C H; Innis, B L

    1997-10-01

    In the fall of 1995, within a month of deployment to Haiti for peacekeeping duty, four Bangladeshi soldiers developed acute icteric hepatitis in rapid succession. Hepatitis E virus (HEV) was found to be the etiology by demonstrating HEV genomic sequences in serum samples by the polymerase chain reaction (PCR) and serologically by the detection of elevated IgM titers to HEV. No case had serologic evidence of acute hepatitis A or C infection. The soldiers had probably acquired their infection while living in a cantonment area outside Dhaka, Bangladesh for one month prior to deployment. Cloning and sequencing of amplified PCR products demonstrated a single strain suggestive of a common source of infection. Furthermore, high genomic identity with Asian strains of HEV and dissimilarity with the Mexican strain was demonstrated, verifying that the strain had indeed been imported. Human waste management from the Bangladesh camp in Haiti was strictly controlled and no secondary cases were observed. A convenience sample of 105 (12%) soldiers from the Bangladesh battalion (850 men) revealed anicteric or asymptomatic HEV infection in seven (7%) of 105. This report contains the first demonstration of acute hepatitis E in natives of Bangladesh and demonstrates the power of the PCR in the rapid diagnosis and epidemiologic analysis of HEV infection. More importantly, this cluster demonstrates the importation of an important infectious disease by multinational peacekeepers to a potentially susceptible host country.

  17. Euforia-induced acute hepatitis in a patient with scleroderma.

    PubMed

    Jiménez-Encarnación, Esther; Ríos, Grissel; Muñoz-Mirabal, Angel; Vilá, Luis M

    2012-12-19

    Euforia, a supplement containing a variety of natural ingredients, is widely used as an antioxidant and anti-inflammatory formula. It is not approved by the US Food and Drug Administration and its side effects are unknown. We report a 45-year-old woman with limited systemic sclerosis who presented with jaundice and marked elevation of serum transaminases. One month before, she started taking Euforia juice. A liver biopsy disclosed submassive hepatocellular necrosis with histopathological changes consistent with toxic hepatitis. The patient's symptoms resolved with cessation of Euforia. Six months later, she persisted with abnormal liver function tests, but these resolved 18 months after discontinuation of Euforia. The mechanism by which Euforia causes liver injury is unknown. Some ingredients contained in this supplement (green tea, Aloe vera, noni and goji) are linked to hepatic injury. To our knowledge, this is the first report of hepatotoxicity associated with Euforia.

  18. Transverse Myelitis in Acute Hepatitis A Infection: The Rare Co-Occurrence of Hepatology and Neurology

    PubMed Central

    Chonmaitree, Piyanant; Methawasin, Kulthida

    2016-01-01

    Transverse myelitis refers to the inflammatory process involving the spinal cord. Clinical features can be either acute or subacute onset that results in neurological deficits such as weakness and/or numbness of extremities as well as autonomic dysfunctions. While there are some etiologies related, a viral infection is common. However, the hepatitis A virus rarely causes myelitis. This report provides details of a hepatitis A infectious patient who developed myelitis as comorbidity. Although, the disability was initially severe, the patient successfully recovered with corticosteroid treatment. PMID:27403101

  19. Transverse Myelitis in Acute Hepatitis A Infection: The Rare Co-Occurrence of Hepatology and Neurology.

    PubMed

    Chonmaitree, Piyanant; Methawasin, Kulthida

    2016-01-01

    Transverse myelitis refers to the inflammatory process involving the spinal cord. Clinical features can be either acute or subacute onset that results in neurological deficits such as weakness and/or numbness of extremities as well as autonomic dysfunctions. While there are some etiologies related, a viral infection is common. However, the hepatitis A virus rarely causes myelitis. This report provides details of a hepatitis A infectious patient who developed myelitis as comorbidity. Although, the disability was initially severe, the patient successfully recovered with corticosteroid treatment. PMID:27403101

  20. Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

    PubMed Central

    Vilela, Luciano Rezende; Gomides, Lindisley Ferreira; David, Bruna Araújo; Antunes, Maísa Mota; Diniz, Ariane Barros; Moreira, Fabrício de Araújo; Menezes, Gustavo Batista

    2015-01-01

    Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD), protects against cocaine toxicity. URB597 (1.0 mg/kg) abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg) reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen) increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse. PMID:25999668

  1. [A case report of alverine-citrate-induced acute hepatitis].

    PubMed

    Han, Jee Young; Lee, Jin Woo; Kim, Joon Mee; Joo, Kowoon; Chon, Ung; Lee, Jung Il; Jeong, Seok; Lee, Don Haeng; Kim, Young Soo; Min, Kyung Sun

    2010-03-01

    Alverine citrate is one of the most commonly used antispasmodic drugs for patients with irritable bowel syndrome. Alverine-citrate-induced hepatotoxicity is extremely rare, with only a few cases having been reported worldwide. We present a case of a 75-year-old female patient who experienced complicated jaundice and abdominal discomfort after taking alverine citrate. Other causes of hepatitis were ruled out and the results of the liver function test returned to normal after ceasing the drug. This is the first case report in Korea of alverine-citrate-induced hepatotoxicity. PMID:20375645

  2. Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury.

    PubMed

    Zhang, Xi-ping; Wang, Lei; Zhang, Jie

    2007-04-01

    Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death. Its complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR (oxygen free radical), endotoxin, etc. may play important roles in its progression.

  3. Acute cholestatic hepatitis caused by amoxicillin/clavulanate

    PubMed Central

    Beraldo, Daniel Oliveira; Melo, Joanderson Fernandes; Bonfim, Alexandre Vidal; Teixeira, Andrei Alkmim; Teixeira, Ricardo Alkmim; Duarte, André Loyola

    2013-01-01

    Amoxicillin/clavulanate is a synthetic penicillin that is currently commonly used, especially for the treatment of respiratory and cutaneous infections. In general, it is a well-tolerated oral antibiotic. However, amoxicillin/clavulanate can cause adverse effects, mainly cutaneous, gastrointestinal, hepatic and hematologic, in some cases. Presented here is a case report of a 63-year-old male patient who developed cholestatic hepatitis after recent use of amoxicillin/clavulanate. After 6 wk of prolonged use of the drug, he began to show signs of cholestatic icterus and developed severe hyperbilirubinemia (total bilirubin > 300 mg/L). Diagnostic investigation was conducted by ultrasonography of the upper abdomen, serum tests for infection history, laboratory screening of autoimmune diseases, nuclear magnetic resonance (NMR) of the abdomen with bile duct-NMR and transcutaneous liver biopsy guided by ultrasound. The duration of disease was approximately 4 mo, with complete resolution of symptoms and laboratory changes at the end of that time period. Specific treatment was not instituted, only a combination of anti-emetic (metoclopramide) and cholestyramine for pruritus. PMID:24379601

  4. The Clinical Course of Cirrhosis Patients Hospitalized for Acute Hepatic Deterioration: A Prospective Bicentric Study.

    PubMed

    Shi, Yu; Yan, Huadong; Zhou, Zhibo; Fang, Hong; Li, Jiawei; Ye, Honghua; Sun, Wenjie; Zhou, Wenhong; Ye, Jingfen; Yang, Qiao; Yang, Ying; Hu, Yaoren; Chen, Zhi; Sheng, Jifang

    2015-11-01

    Patients with cirrhosis are vulnerable to acute hepatic insults and are more likely to develop rapid hepatic deterioration. The aim of this study is to describe the clinical course of patients with cirrhosis and hospitalized for acute hepatic deterioration (AHD).This is a prospective study involving 163 patients with cirrhosis and AHD. The occurrence of organ failures, systemic inflammatory response syndrome (SIRS), and infections during hospital stay were recorded and the relationship between organ failure and death or SIRS/infection was subsequently analyzed.Of 163 patients, 35 did not develop any organ failure during in-hospital follow-ups (90-day mortality: 0%); 84 had intrahepatic organ failures (IH-OFs, defined by liver and/or coagulation failure) (90-day mortality: 22.0%); and 44 patients developed extra-hepatic organ failures (EH-OFs, defined by kidney, cerebral, circulation, and respiratory failure) on the basis of IH-OF with a 90-day mortality of 90.9%. On multivariable analysis by a Cox proportion hazard model, age, WBC, presence of IH-OF, and EH-OF all predicted 90-day death. A logistic regression analysis identified SIRS being associated with the development of EH-OF. Furthermore, IH-OF at admission and infections occurred during the hospital stay were shown to be another 2 potential risk factors.The clinical course of cirrhosis patients with acute hepatic injury was characterized by 3 consecutive stages (AHD, IH-OF, and EH-OF), which provided a clear risk stratification. The PIRO criteria provided an accurate frame for prognostication of those patients. The systemic inflammatory response syndrome may be a target for blocking the progression to the EH-OF stage.

  5. The Clinical Course of Cirrhosis Patients Hospitalized for Acute Hepatic Deterioration

    PubMed Central

    Shi, Yu; Yan, Huadong; Zhou, Zhibo; Fang, Hong; Li, Jiawei; Ye, Honghua; Sun, Wenjie; Zhou, Wenhong; Ye, Jingfen; Yang, Qiao; Yang, Ying; Hu, Yaoren; Chen, Zhi; Sheng, Jifang

    2015-01-01

    Abstract Patients with cirrhosis are vulnerable to acute hepatic insults and are more likely to develop rapid hepatic deterioration. The aim of this study is to describe the clinical course of patients with cirrhosis and hospitalized for acute hepatic deterioration (AHD). This is a prospective study involving 163 patients with cirrhosis and AHD. The occurrence of organ failures, systemic inflammatory response syndrome (SIRS), and infections during hospital stay were recorded and the relationship between organ failure and death or SIRS/infection was subsequently analyzed. Of 163 patients, 35 did not develop any organ failure during in-hospital follow-ups (90-day mortality: 0%); 84 had intrahepatic organ failures (IH-OFs, defined by liver and/or coagulation failure) (90-day mortality: 22.0%); and 44 patients developed extra-hepatic organ failures (EH-OFs, defined by kidney, cerebral, circulation, and respiratory failure) on the basis of IH-OF with a 90-day mortality of 90.9%. On multivariable analysis by a Cox proportion hazard model, age, WBC, presence of IH-OF, and EH-OF all predicted 90-day death. A logistic regression analysis identified SIRS being associated with the development of EH-OF. Furthermore, IH-OF at admission and infections occurred during the hospital stay were shown to be another 2 potential risk factors. The clinical course of cirrhosis patients with acute hepatic injury was characterized by 3 consecutive stages (AHD, IH-OF, and EH-OF), which provided a clear risk stratification. The PIRO criteria provided an accurate frame for prognostication of those patients. The systemic inflammatory response syndrome may be a target for blocking the progression to the EH-OF stage. PMID:26632701

  6. Acute hepatitis A in Italy: incidence, risk factors and preventive measures.

    PubMed

    Tosti, M E; Spada, E; Romanò, L; Zanetti, A; Mele, A

    2008-10-01

    The incidence of, and risk factors for, acute hepatitis A (AHA) were assessed by using data collected from the Italian surveillance system of acute viral hepatitis (SEIEVA). To this end, a case-control study within a population-based surveillance for acute viral hepatitis was performed. AHA incidence has been estimated since 1991; the association with considered risk factors was analysed from 2001 to 2006 employing cases of acute hepatitis B (AHB) as controls. The incidence of AHA declined from 4 / 100 000 in 1991 to 1.4/100 000 in 2006, with a peak during 1996-1998 due to an outbreak in southern Italy. The incidence of AHA was highest among persons aged 15-24 years. The case-fatality rate was 2.9 / 10 000. Contact with individuals with AHA [adjusted OR (OR(adj)) = 3.8, 95% CI 2.7-5.5; population-attributable risk (PAR) = 7.5%], travelling to endemic areas (OR(adj) = 3.1, 95% CI = 2.6-3.8; PAR = 19.5%), ingestion of raw shellfish (OR(adj) = 1.8, 95% CI = 1.6-2.1; PAR = 26.6%), and cohabitation with day care children (OR(adj) = 1.3, 95% CI = 1.01-1.7; PAR = 2.3%) were the main important risk factors. In 2003, an outbreak, with high case-fatality rate occurred among intravenous drug users, in a central Italian town. A weak association was found for male homosexuality when acute hepatitis C cases were employed as controls (OR(adj) = 1.4 CI, 95% CI = 1.1-1.9). Hepatitis A virus infections are currently occurring more frequently in adults, in whom the disease is most severe. In conclusion, looking at the attributable risks, at present most of the AHA infections are due to shellfish consumption, travel to endemic areas and contact with patients with AHA. Vaccination of individuals at increased risk of infection, as well as persons with underling liver disease and those at increased risk of complications, combined with surveillance of shellfish retail outlets are efficient control measures. PMID:18837830

  7. Acute Thrombocytopenia: An Unusual Complication Occurring After Drug-Eluting Microspheres Transcatheter Hepatic Chemoembolization

    SciTech Connect

    Poggi, Guido; Quaretti, Pietro; Montagna, Benedetta Sottotetti, Federico Tagliaferri, Barbara Pozzi, Emma Amatu, Alessio Pagella, Chiara; Bernardo, Giovanni

    2011-02-15

    Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.

  8. Liver receptor homolog 1 is a negative regulator of the hepatic acute-phase response.

    PubMed

    Venteclef, Nicolas; Smith, Jason C; Goodwin, Bryan; Delerive, Philippe

    2006-09-01

    The orphan nuclear receptor liver receptor homolog 1 (LRH-1) has been reported to play an important role in bile acid biosynthesis and reverse cholesterol transport. Here, we show that LRH-1 is a key player in the control of the hepatic acute-phase response. Ectopic expression of LRH-1 with adenovirus resulted in strong inhibition of both interleukin-6 (IL-6)- and IL-1beta-stimulated haptoglobin, serum amyloid A, and fibrinogen beta gene expression in hepatocytes. Furthermore, induction of the hepatic inflammatory response was significantly exacerbated in HepG2 cells expressing short hairpin RNA targeting LRH-1 expression. Moreover, transient-transfection experiments and electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that LRH-1 regulates this cytokine-elicited inflammatory response by, at least in part, antagonizing the CCAAT/enhancer binding protein beta signaling pathway. Finally, we show, by using LRH-1 heterozygous mice, that LRH-1 is involved in the control of the inflammatory response at the hepatic level in vivo. Taken together, our results outline an unexpected role for LRH-1 in the modulation of the hepatic acute-phase response.

  9. [The frequency of the e-antigen in acute and chronic hepatitis (author's transl)].

    PubMed

    Fay, O H; Tanno, H; Roncoroni, M; Findor, J; Igartua, E B; Domecq, R

    1975-08-01

    Five groups of patients were studied: (a) 88 HBsAg-positive cases of acute viral hepatitis (AVH) who completely cured within 90 days; (b) 75 cases of acute HBsAg-negative hepatitis with early resolution; (c) 15 AVH patients who became chronic; (d) 94 HBsAg-positive cases of chronic hepatitis (CH) and liver cirrhosis; (e) HBsAg-negative cases with CH. The e-antigen was investigated in every patient and was found in 9 of the AVH cases with favorable evolution, and in 8 of the AVH patients evolving to chronicity. Amont the CH and cirrhosis group, 48 of the HBsAg carriers were positive while e-antigen could not be detected in any of the HBsAg-negative ones. The high incidence of e-antigen carriers among patients with chronic hepatitis and liver cirrhosis as well as among those with AVH who later entered the chronic stage of the disease, deserves especial consideration. A possible role of e-antigen in the evolution to chronicity and a prognostic significance is suggested.

  10. Acute Hepatitis after Ingestion of a Preparation of Chinese Skullcap and Black Catechu for Joint Pain.

    PubMed

    Papafragkakis, Charilaos; Ona, Mel A; Reddy, Madhavi; Anand, Sury

    2016-01-01

    Many herbal preparations are routinely used and have been occasionally associated with a wide range of side effects, from mild to severe. Chinese skullcap and black catechu are herbal medications commonly used for their hepatoprotective and other properties. We report a case of acute toxic hepatitis associated with ingestion of Chinese skullcap and black catechu in one preparation for the alleviation of joint pain. PMID:27144042

  11. Acute Hepatitis after Ingestion of a Preparation of Chinese Skullcap and Black Catechu for Joint Pain

    PubMed Central

    Papafragkakis, Charilaos; Ona, Mel A.; Reddy, Madhavi; Anand, Sury

    2016-01-01

    Many herbal preparations are routinely used and have been occasionally associated with a wide range of side effects, from mild to severe. Chinese skullcap and black catechu are herbal medications commonly used for their hepatoprotective and other properties. We report a case of acute toxic hepatitis associated with ingestion of Chinese skullcap and black catechu in one preparation for the alleviation of joint pain. PMID:27144042

  12. Terpene-induced porphyria and the illness of Vincent van Gogh

    SciTech Connect

    Lambrecht, R.; Cable, E.; Cable, J.; Clements, E.; Donohue, S.; Greene, Y.; Srivastava, K.; Arnold, W.; Bonkovsky, H. Univ. of Kansas Medical Center, Kansas City )

    1992-01-01

    Vincent van Gogh suffered from recurrent bouts of an illness that may have been acute porphyria and abused camphor and alcohol, the latter particularly in the form of absinthe, a liqueur distilled from wormwood that was popular in 19th C France. To learn whether camphor or terpenes found in absinthe are porphyrogenic, the authors studied them in cultures of chick embryo liver cells. All were found to be porphyrogenic, especially in the presence of deferoxamine. The terpenes also induced the activity and protein amount of 5-aminolevulinate synthase and heme oxygenase, and induced activities of benzphetamine demethylase. The degree of porphyrin and enzyme induction produced by 1mM camphor was similar to that produced by 50uM glutethimide, a potent porphyrogen. Potency of pinene and thujone were lower. Camphor and glutethimide both produced accumulations of 8- and 7-COOH porphyrins, whereas pinene and thujone produced 4- and 2-COOH porphyrin accumulation. The authors conclude that camphor, pinen and thujone are porphyrogenic, cable of exacerbating acute porphyria, and may have done so in van Gogh.

  13. The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis

    PubMed Central

    1995-01-01

    Cytotoxic T lymphocytes (CTL) are thought to contribute to viral clearance and liver cell injury during hepatitis B virus (HBV) infection. Using a strategy involving the in vitro stimulation of peripheral blood mononuclear cells (PBMC) with HBV-derived synthetic peptides containing HLA-A2.1, -A31, and -Aw68 binding motifs, we have previously described CTL responses to several epitopes within the HBV nucleocapsid and envelope antigens in patients with acute hepatitis. In this study we define six HLA-A2-restricted CTL epitopes located in the highly conserved reverse transcriptase and RNase H domains of the viral polymerase protein, and we show that the CTL response to polymerase is polyclonal, multispecific, and mediated by CD8+ T cells in patients with acute viral hepatitis, but that it is not detectable in patients with chronic HBV infection or uninfected healthy blood donors. Importantly, the peptide-activated CTL recognize target cells that express endogenously synthesized polymerase protein, suggesting that these peptides represent naturally processed viral epitopes. DNA sequence analysis of the viruses in patients who did not respond to peptide stimulation indicated that CTL nonresponsiveness was not due to infection by viral variants that differed in sequences from the synthetic peptides. CTL specific for one of the epitopes were unable to recognize several naturally occurring viral variants, except at high peptide concentration, underlining the HBV subtype specificity of this response. Furthermore, CTL responses against polymerase, core, and envelope epitopes were detectable for more than a year after complete clinical recovery and seroconversion, reflecting either the persistence of trace amounts of virus or the presence of long lived memory CTL in the absence of viral antigen. Finally, we demonstrated that wild type viral DNA and RNA can persist indefinitely, in trace quantities, in the serum and PBMC after complete clinical and serological recovery

  14. [Acute liver failure due to T cell lymphoma without hepatic infiltration].

    PubMed

    Ortega López Juan, J; López Espinosa, J; Roqueta Mas, J; Sabado Alvarez, C; Ruiz Marcellan, C; Iglesias Berengué, J

    2003-01-01

    Hepatomegaly and alterations in hepatic function are common to all patients with sickle-cell disease. In these patients, hepatic sickling is a manifestation of severe intrahepatic vaso-oclusive crises, even at levels of 25 % HbS and hematocrits of more than 45-50 %, which in 10 % of cases can lead to acute hepatic failure (AHF). AHF can be due to a variety of causes, including hematologic malignancies, but T cell lymphoma, which is usually secondary to diffuse hepatic infiltration and ischemia, is an exceptional cause, although other mechanisms can be involved. Cytokines released by lymphomas have recently been implicated as a cause of AHF.We describe a black girl with sickle cell disease, who developed AHF due to T cell lymphoma without lymphomatous infiltration of the liver. The only mechanism found to explain the clinical findings was release of cytokines by lymphoma. In patients with AHF of unknown etiology we propose early liver biopsy, because prognosis depends on the presence or absence of hepatic tumour infiltration. If AHF develops in a patient with diagnosed malignant disease, cytokine release may be the cause of AHF. Consequently, early diagnosis of the underlying disease and provision of liver support, as well as direct removal of inflammatory mediators from the circulation by exchange transfusion or other methods, should be the main priorities. PMID:12628121

  15. Hepatic Steatosis in Response to Acute Alcohol Exposure in Zebrafish requires Srebp Activation

    PubMed Central

    Passeri, Michael J.; Cinaroglu, Ayca; Gao, Chuan; Sadler, Kirsten C.

    2008-01-01

    Steatosis is the most common consequence of acute alcohol abuse and may predispose to more severe hepatic disease. Increased lipogenesis driven by the sterol response element binding protein (SREBP) transcription factors is essential for steatosis associated with chronic alcohol ingestion, but the mechanisms underlying steatosis following acute alcohol exposure are unknown. Zebrafish larvae represent an attractive vertebrate model for studying alcoholic liver disease (ALD), because they possess the pathways to metabolize alcohol, the liver is mature by 4 days post-fertilization (dpf), and alcohol can be simply added to their water. Exposing 4 dpf zebrafish larvae to 2% ethanol (EtOH) for 32 hours achieves ∼80 mM intracellular EtOH and upregulation of hepatic cyp2e1, sod and bip, indicating that EtOH is metabolized and provokes oxidant stress. EtOH-treated larvae develop hepatomegaly and steatosis accompanied by changes in the expression of genes required for hepatic lipid metabolism. Based on the importance of SREPBs in chronic ALD, we explored the role of Srebps in this model of acute ALD. Srebp activation was prevented in gonzo larvae, which harbor a mutation in the membrane bound transcription factor protease 1 (mbtps1) gene, and in embryos injected with a morpholino to knock-down Srebp cleavage activating protein (scap). Both gonzo mutants and scap morphants were resistant to steatosis in response to 2% EtOH, and the expression of many Srebp target genes are down regulated in gonzo mutant livers. Conclusion Zebrafish larvae develop signs of acute ALD, including steatosis. Srebp activation is required for steatosis in this model. The tractability of zebrafish genetics provides a valuable tool for dissecting the molecular pathogenesis of acute ALD. PMID:19127516

  16. Acute viral hepatitis E presenting with haemolytic anaemia and acute renal failure in a patient with glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    Tomar, Laxmikant Ramkumarsingh; Aggarwal, Amitesh; Jain, Piyush; Rajpal, Surender; Agarwal, Mukul P

    2015-10-01

    The association of acute hepatitis E viral (HEV) infection with glucose-6-phosphate dehydrogenase (G6PD) deficiency leading to extensive intravascular haemolysis is a very rare clinical entity. Here we discuss such a patient, who presented with acute HEV illness, developed severe intravascular haemolysis and unusually high levels of bilirubin, complicated by acute renal failure (ARF), and was later on found to have a deficiency of G6PD. The patient recovered completely with haemodialysis and supportive management. PMID:25500531

  17. [Early cirrhosis, an early modality of the evolution of acute hepatitis. The clinico-biological, immunological and morphological aspects].

    PubMed

    Banciu, T; Tudose, N; Arcan, P

    1990-01-01

    A group of 12 patients with recent acute hepatitis (8/86 with HVB and 4/22 with alcoholic hepatitis) had a rapid evolution (under 2 years) towards hepatic cirrhosis (early H.C.). The clinical-biological, immunological and morphological study made evident several characteristics, which became predictive markers of the early cirrhotic evolution of acute hepatitis. Clinically, a persistence of dyspeptic disorders and appearance of several systemic manifestations is noticed. Biologically, the maintenance of some increased transmainases, variable bilirubinemia and decrease of serinemia. Immunologically, the transfer of IgM towards increased IgM, the decrease of the total T lymphocyte and of T1 substrate, the increase of the active B and T lymphocyte. The morphologic exploration is decisive for specification of the diagnosis in the early hepatic cirrhosis. PMID:1982190

  18. The Impact of Acute Matriptase Inhibition in Hepatic Inflammatory Models.

    PubMed

    Pomothy, Judit; Szombath, Gergely; Rokonál, Patrik; Mátis, Gábor; Neogrády, Zsuzsanna; Steinmetzer, Torsten; Pászti-Gere, Erzsébet

    2016-01-01

    Purpose. Dysfunction of matriptase-2 can be involved in iron regulatory disorder via downregulation of hepcidin expression. In the present study, we investigated the effects of 3-amidinophenylalanine-derived matriptase inhibitors on porcine hepatic inflammatory cell models. Methods. Hepatocyte-Kupffer cell cocultures (ratio of 2 : 1 and 6 : 1) were treated with four structurally related matriptase inhibitors at 50 μM. Cell cytotoxicity and relative expressions of IL-6 and IL-8 and the levels of hepcidin were determined by MTS and porcine-specific ELISA. The extracellular H2O2 contents were analyzed by Amplex Red method. Results. Matriptase inhibitors at 50 µM for 24 h did not increase cell death rate. The elevated ROS production observed after short-term application of inhibitor MI-441 could be correlated with lowered hepcidin expression. MI-460 could significantly enhance hepcidin levels in the supernatants of cocultures (by 62.21 ± 26.8% in hepatocyte-Kupffer cell, 2 : 1, and by 42.6 ± 14.3% in hepatocyte-Kupffer cell, 6 : 1, cocultures, resp.). No significant changes were found in IL-6 and IL-8 levels in cocultures exposed to matriptase inhibitors. Conclusions. Based on in vitro findings, administration of MI-460 via modulation of hepcidin expression without cytotoxic and oxidative stress inducing properties might be a reliable alternative to treat iron overload in human and veterinary clinical practice. PMID:27642598

  19. The Impact of Acute Matriptase Inhibition in Hepatic Inflammatory Models

    PubMed Central

    Szombath, Gergely; Rokonál, Patrik; Mátis, Gábor; Neogrády, Zsuzsanna

    2016-01-01

    Purpose. Dysfunction of matriptase-2 can be involved in iron regulatory disorder via downregulation of hepcidin expression. In the present study, we investigated the effects of 3-amidinophenylalanine-derived matriptase inhibitors on porcine hepatic inflammatory cell models. Methods. Hepatocyte-Kupffer cell cocultures (ratio of 2 : 1 and 6 : 1) were treated with four structurally related matriptase inhibitors at 50 μM. Cell cytotoxicity and relative expressions of IL-6 and IL-8 and the levels of hepcidin were determined by MTS and porcine-specific ELISA. The extracellular H2O2 contents were analyzed by Amplex Red method. Results. Matriptase inhibitors at 50 µM for 24 h did not increase cell death rate. The elevated ROS production observed after short-term application of inhibitor MI-441 could be correlated with lowered hepcidin expression. MI-460 could significantly enhance hepcidin levels in the supernatants of cocultures (by 62.21 ± 26.8% in hepatocyte-Kupffer cell, 2 : 1, and by 42.6 ± 14.3% in hepatocyte-Kupffer cell, 6 : 1, cocultures, resp.). No significant changes were found in IL-6 and IL-8 levels in cocultures exposed to matriptase inhibitors. Conclusions. Based on in vitro findings, administration of MI-460 via modulation of hepcidin expression without cytotoxic and oxidative stress inducing properties might be a reliable alternative to treat iron overload in human and veterinary clinical practice.

  20. The Impact of Acute Matriptase Inhibition in Hepatic Inflammatory Models

    PubMed Central

    Szombath, Gergely; Rokonál, Patrik; Mátis, Gábor; Neogrády, Zsuzsanna

    2016-01-01

    Purpose. Dysfunction of matriptase-2 can be involved in iron regulatory disorder via downregulation of hepcidin expression. In the present study, we investigated the effects of 3-amidinophenylalanine-derived matriptase inhibitors on porcine hepatic inflammatory cell models. Methods. Hepatocyte-Kupffer cell cocultures (ratio of 2 : 1 and 6 : 1) were treated with four structurally related matriptase inhibitors at 50 μM. Cell cytotoxicity and relative expressions of IL-6 and IL-8 and the levels of hepcidin were determined by MTS and porcine-specific ELISA. The extracellular H2O2 contents were analyzed by Amplex Red method. Results. Matriptase inhibitors at 50 µM for 24 h did not increase cell death rate. The elevated ROS production observed after short-term application of inhibitor MI-441 could be correlated with lowered hepcidin expression. MI-460 could significantly enhance hepcidin levels in the supernatants of cocultures (by 62.21 ± 26.8% in hepatocyte-Kupffer cell, 2 : 1, and by 42.6 ± 14.3% in hepatocyte-Kupffer cell, 6 : 1, cocultures, resp.). No significant changes were found in IL-6 and IL-8 levels in cocultures exposed to matriptase inhibitors. Conclusions. Based on in vitro findings, administration of MI-460 via modulation of hepcidin expression without cytotoxic and oxidative stress inducing properties might be a reliable alternative to treat iron overload in human and veterinary clinical practice. PMID:27642598

  1. Hepatic Dysfunction in Hospitalized Patients with Acute Thyrotoxicosis: A Decade of Experience

    PubMed Central

    Elias, Richard M.; Dean, Diana S.; Barsness, Gregory W.

    2012-01-01

    Thyroid disease is a common condition, and thyroid hormone excess or deficiency is known to have wide-ranging effects on a variety of organ systems. Our objective is to describe the magnitude, biochemical features, and clinical characteristics of hepatic abnormalities in patients with acute thyrotoxicosis. We performed a retrospective review of all patients admitted to our institution between January 1, 1998 and December 31, 2008 with a discharge diagnosis of acute thyrotoxicosis excluding iatrogenic causes. The records of these patients were reviewed and data extracted regarding demographic, biochemical, and clinical data particularly relevant to liver function. Fourteen patients were identified of which eleven had liver studies performed. The majority (90.9%) had Graves disease. Nine of eleven patients (81.8%) had some degree of hepatic abnormality. Seven patients (63.6%) had an elevation in one or both transaminases, and two (18.2%) had isolated synthetic dysfunction as manifested as an elevated INR and/or decreased albumin without transaminitis. The mean magnitude of deviation from the normal range was greater in the transaminases as compared to bilirubin, INR, or albumin. Definitive treatment was radioiodine ablation in six cases (54.5%) and surgical thyroidectomy in two cases (18.2%). Noniatrogenic acute thyrotoxicosis requiring hospitalization is a rare condition which is most frequently caused by Graves disease. The majority of patients have disordered liver tests of a highly variable nature, making the recognition of this association important in the care of patients presenting with acute thyrotoxicosis. PMID:23251814

  2. Hepatic steatosis depresses alpha-1-antitrypsin levels in human and rat acute pancreatitis

    PubMed Central

    Wang, Qian; Du, Jianjun; Yu, Pengfei; Bai, Bin; Zhao, Zhanwei; Wang, Shiqi; Zhu, Junjie; Feng, Quanxin; Gao, Yun; Zhao, Qingchuan; Liu, Chaoxu

    2015-01-01

    Hepatic steatosis (HS) can exacerbate acute pancreatitis (AP). This study aimed to investigate the relation between α1-antitrypsin (AAT) and acute pancreatitis when patients have HS. Using proteomic profiling, we identified 18 differently expressed proteins pots in the serum of rats with or without HS after surgical establishment of AP. AAT was found to be one of the significantly down-regulated proteins. AAT levels were significantly lower in hepatic steatosis acute pancreatitis (HSAP) than in non-HSAP (NHSAP) (P < 0.001). To explore the clinical significance of these observations, we measured the levels of AAT in the serum of 240 patients with HSAP, NHSAP, fatty liver disease (FLD), or no disease. Compared with healthy controls, serum AAT levels in patients with NHSAP were significantly higher (P < 0.01), while in patients with HSAP serum AAT levels were significantly lower (P < 0.01). Further studies showed that acute physiology and chronic health evaluation (APACHE-II) scores were negatively correlated with serum AAT levels (r = −0.85, P < 0.01). In conclusion, low serum levels of AAT in patients with HSAP are correlated with disease severity and AAT may represent a potential target for therapies aiming to improve pancreatitis. PMID:26634430

  3. Porphyria cutanea tarda associated with HFE C282Y homozygosity, iron overload, and use of a contraceptive vaginal ring

    PubMed Central

    Barton, James C.; Edwards, Corwin Q.

    2016-01-01

    Porphyria cutanea tarda (PCT) is characterized by decreased uroporphyrinogen decarboxylase activity in hepatocytes, uroporphyrin I and heptacarboxyl porphyrin III accumulation, photosensitivity dermatitis, and increased storage iron. In women, estrogen therapy, including oral contraceptives, postmenopausal hormone replacement, and tamoxifen for breast cancer treatment, is a risk factor for PCT. We report the case of a woman who presented with PCT, HFE C282Y homozygosity, and hepatic iron overload and was using a contraceptive vaginal ring containing ethinyl estradiol, an estrogen. We discuss this case in the context of characteristics of other persons with PCT, including common HFE mutations, iron overload, and estrogen exposure. PMID:26908385

  4. Acute Overactive Endocannabinoid Signaling Induces Glucose Intolerance, Hepatic Steatosis, and Novel Cannabinoid Receptor 1 Responsive Genes

    PubMed Central

    Ruby, Maxwell A.; Nomura, Daniel K.; Hudak, Carolyn S. S.; Barber, Anne; Casida, John E.; Krauss, Ronald M.

    2011-01-01

    Endocannabinoids regulate energy balance and lipid metabolism by stimulating the cannabinoid receptor type 1 (CB1). Genetic deletion and pharmacological antagonism have shown that CB1 signaling is necessary for the development of obesity and related metabolic disturbances. However, the sufficiency of endogenously produced endocannabinoids to cause hepatic lipid accumulation and insulin resistance, independent of food intake, has not been demonstrated. Here, we show that a single administration of isopropyl dodecylfluorophosphonate (IDFP), perhaps the most potent pharmacological inhibitor of endocannabinoid degradation, increases hepatic triglycerides (TG) and induces insulin resistance in mice. These effects involve increased CB1 signaling, as they are mitigated by pre-administration of a CB1 antagonist (AM251) and in CB1 knockout mice. Despite the strong physiological effects of CB1 on hepatic lipid and glucose metabolism, little is known about the downstream targets responsible for these effects. To elucidate transcriptional targets of CB1 signaling, we performed microarrays on hepatic RNA isolated from DMSO (control), IDFP and AM251/IDFP-treated mice. The gene for the secreted glycoprotein lipocalin 2 (lcn2), which has been implicated in obesity and insulin resistance, was among those most responsive to alterations in CB1 signaling. The expression pattern of IDFP mice segregated from DMSO mice in hierarchal cluster analysis and AM251 pre-administration reduced (>50%) the majority (303 of 533) of the IDFP induced alterations. Pathway analysis revealed that IDFP altered expression of genes involved in lipid, fatty acid and steroid metabolism, the acute phase response, and amino acid metabolism in a CB1-dependent manner. PCR confirmed array results of key target genes in multiple independent experiments. Overall, we show that acute IDFP treatment induces hepatic TG accumulation and insulin resistance, at least in part through the CB1 receptor, and identify novel

  5. Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors.

    PubMed

    Rodrigues, Robim M; Sachinidis, Agapios; De Boe, Veerle; Rogiers, Vera; Vanhaecke, Tamara; De Kock, Joery

    2015-09-01

    Besides their role in the elucidation of pathogenic processes of medical and pharmacological nature, biomarkers can also be used to document specific toxicological events. Hepatic cells generated from human skin-derived precursors (hSKP-HPC) were previously shown to be a promising in vitro tool for the evaluation of drug-induced hepatotoxicity. In this study, their capacity to identify potential liver-specific biomarkers at the gene expression level was investigated with particular emphasis on acute liver failure (ALF). To this end, a set of potential ALF-specific biomarkers was established using clinically relevant liver samples obtained from patients suffering from hepatitis B-associated ALF. Subsequently, this data was compared to data obtained from primary human hepatocyte cultures and hSKP-HPC, both exposed to the ALF-inducing reference compound acetaminophen. It was found that both in vitro systems revealed a set of molecules that was previously identified in the ALF liver samples. Yet, only a limited number of molecules was common between both in vitro systems and the ALF liver samples. Each of the in vitro systems could be used independently to identify potential toxicity biomarkers related to ALF. It seems therefore more appropriate to combine primary human hepatocyte cultures with complementary in vitro models to efficiently screen out potential hepatotoxic compounds.

  6. Molecular analysis of hepatitis A virus strains obtained from patients with acute hepatitis A in Mongolia, 2004-2013.

    PubMed

    Tsatsralt-Od, Bira; Baasanjav, Nachin; Nyamkhuu, Dulmaa; Ohnishi, Hiroshi; Takahashi, Masaharu; Kobayashi, Tominari; Nagashima, Shigeo; Nishizawa, Tsutomu; Okamoto, Hiroaki

    2016-04-01

    Despite the high endemicity of hepatitis A virus (HAV) in Mongolia, the genetic information on those HAV strains is limited. Serum samples obtained from 935 patients with acute hepatitis in Ulaanbaatar, Mongolia during 2004-2013 were tested for the presence of HAV RNA using reverse transcription-PCR with primers targeting the VP1-2B region (481 nucleotides, primer sequences at both ends excluded). Overall, 180 patients (19.3%) had detectable HAV RNA. These 180 isolates shared 94.6-100% identity and formed four phylogenetic clusters within subgenotype IA. One or three representative HAV isolates from each cluster exhibited 2.6-3.9% difference between clusters over the entire genome. Cluster 1 accounted for 65.0% of the total, followed by Cluster 2 (30.6%), Cluster 3 (3.3%), and Cluster 4 (1.1%). Clusters 1 and 2 were predominant throughout the observation period, whereas Cluster 3 was undetectable in 2009 and 2013 and Cluster 4 became undetectable after 2009. The Mongolian HAV isolates were closest to those of Chinese or Japanese origin (97.7-98.5% identities over the entire genome), suggesting the evolution from a common ancestor with those circulating in China and Japan. Further molecular epidemiological analyses of HAV infection are necessary to investigate the factors underlying the spread of HAV and to implement appropriate prevention measures in Mongolia.

  7. Virological Characteristics of Acute Hepatitis B in Eastern India: Critical Differences with Chronic Infection

    PubMed Central

    Sarkar, Neelakshi; Pal, Ananya; Das, Dipanwita; Saha, Debraj; Biswas, Avik; Bandopadhayay, Bhaswati; Chakraborti, Mandira; Ghosh, Mrinmoy; Chakravarty, Runu

    2015-01-01

    Hepatitis B Virus (HBV) manifests high genetic variability and is classifiable into ten genotypes (A-J). HBV infection can lead to variable clinical outcomes, ranging from self-limiting acute hepatitis to active chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study characterizes HBV strains circulating among patients with acute (AHB) and chronic HBV infection (CHB). Among a total of 653 HBsAg positive cases, 40 manifested acute infection. After sequencing the surface(S), basal core promoter/pre-core(BCP/PC) and the X gene regions, phylogenetic tree was constructed using MEGA4 by neighbor-joining method. Statistical robustness was established with bootstrap analysis. Nucleotide diversity was determined by Shannon entropy per site using the Entropy program of the Los Alamos National Laboratories. Analyses of acute patients revealed that HBV/D2 is the major circulating sub-genotype and commonly associated with sexual promiscuity and the age group between15-30 years. Comparison of AHB and CHB patients revealed that HBeAg positivity, ALT levels and genotype D were significantly high in AHB, whereas CHB patients were predominantly male, had a high viral load, and were commonly associated with genotype C. The frequencies of mutations in the S, BCP/PC, and X gene were low in AHB as compared to CHB. Drug resistant mutations were not detectable in the polymerase gene of AHB. Average nucleotide diversity in AHB was considerably low as compared to CHB. Further, the highest average ΔH (average difference in entropy between chronic and acute infection) was observed in the BCP/PC region implying that this region was most vulnerable to mutations upon HBV persistence, especially in case of genotype C. Additionally, among all substitutions, the A1762T and G1764A BCP mutations were the strongest indicators of chronicity. In conclusion, the study exhibits a general portrait of HBV strains circulating among acute hepatitis B patients in Eastern India and their

  8. Hepatitis A complicated with acute renal failure and high hepatocyte growth factor: A case report.

    PubMed

    Oe, Shinji; Shibata, Michihiko; Miyagawa, Koichiro; Honma, Yuichi; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru

    2015-08-28

    A 58-year-old man was admitted to our hospital. Laboratory data showed severe liver injury and that the patient was positive for immunoglobulin M anti-hepatitis A virus (HAV) antibodies. He was also complicated with severe renal dysfunction and had an extremely high level of serum hepatocyte growth factor (HGF). Therefore, he was diagnosed with severe acute liver failure with acute renal failure (ARF) caused by HAV infection. Prognosis was expected to be poor because of complications by ARF and high serum HGF. However, liver and renal functions both improved rapidly without intensive treatment, and he was subsequently discharged from our hospital on the 21(st) hospital day. Although complication with ARF and high levels of serum HGF are both important factors predicting poor prognosis in acute liver failure patients, the present case achieved a favorable outcome. Endogenous HGF might play an important role as a regenerative effector in injured livers and kidneys.

  9. Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure.

    PubMed

    Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling

    2015-01-01

    Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called "second pathway of liver regeneration." The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin.

  10. Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure

    PubMed Central

    Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling

    2015-01-01

    Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called “second pathway of liver regeneration.” The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin. PMID:26136687

  11. A Korean patient with Guillain-Barré syndrome following acute hepatitis E whose cholestasis resolved with steroid therapy

    PubMed Central

    Ji, Sung Bok; Lee, Sang Soo; Jung, Hee cheul; Kim, Hong Jun; Kim, Hyun Jin; Kim, Tae Hyo; Jung, Woon Tae; Lee, Ok Jae; Song, Dae Hyun

    2016-01-01

    Autochthonous hepatitis E virus (HEV) is an emerging pathogen in developed countries, and several cases of acute HEV infection have been reported in South Korea. However, there have been no reports on HEV-associated Guillain-Barré syndrome (GBS) in Korea. We recently experienced the case of a 58-year-old Korean male with acute HEV infection after ingesting raw deer meat. Persistent cholestasis was resolved by the administration of prednisolone. At 2.5 months after the clinical presentation of HEV infection, the patient developed weakness of the lower limbs, and was diagnosed with GBS associated with acute hepatitis E. To our knowledge, this is the second report on supportive steroid therapy for persistent cholestasis due to hepatitis E, and the first report of GBS in a Korean patient with acute HEV infection. PMID:27572076

  12. Increased loss and decreased synthesis of hepatic glutathione after acute ethanol administration. Turnover studies.

    PubMed Central

    Speisky, H; MacDonald, A; Giles, G; Orrego, H; Israel, Y

    1985-01-01

    The effect of acute ethanol administration on rates of synthesis and utilization of hepatic glutathione (GSH) was studied in rats after a pulse of [35S]cysteine. A 35% decrease in hepatic GSH content 5h after administration of 4 g of ethanol/kg body wt. was accompanied by a 33% increase in the rate of GSH utilization. The decrease occurred without increases in hepatic oxidized glutathione (GSSG) or in the GSH/GSSG ratio. The rate of non-enzymic condensation of GSH with acetaldehyde could account for only 6% of the rate of hepatic GSH disappearance. The increased loss of [35S]GSH induced by ethanol was not accompanied by an increased turnover; rather, a 30% inhibition of GSH synthesis balanced the increased rate of loss, leaving the turnover rate unchanged. The rate of acetaldehyde condensation with cysteine in vitro occurred at about one-third of the rate of GSH loss in ethanol-treated animals. However, ethanol induced only a minor decrease in liver cysteine content, which did not precede, but followed, the decrease in GSH. The characteristics of 2-methylthiazolidine-4-carboxylic acid, the condensation product between acetaldehyde and cysteine, were studied and methodologies were developed to determine its presence in tissues. It was not found in the liver of ethanol-treated animals. Ethanol administration led to a marked increase (47%) in plasma GSH in the post-hepatic inferior vena cava, but not in its pre-hepatic segment. Data suggest that an increased loss of GSH from the liver constitutes an important mechanism for the decrease in GSH induced by ethanol. In addition, an inhibition of GSH synthesis is observed. PMID:3977847

  13. Characterization of Acute and Chronic Hepatitis B Virus Genotypes in Canada

    PubMed Central

    Osiowy, Carla; Giles, Elizabeth; Trubnikov, Max; Choudhri, Yogesh; Andonov, Anton

    2015-01-01

    Objective The prevalence and distribution of hepatitis B virus (HBV) genotypes in Canada is not known. Genotypic analysis may contribute to a better understanding of HBV strain distribution and transmission risk. Methods HBV surface antigen (HBsAg) positive samples of acute (n = 152) and chronic (n = 1533) HBV submitted for strain analysis or reference genotype testing between 2006 and 2012 were analyzed. The HBsAg coding region was amplified to determine the HBV genotype by INNO-LiPA assay or sequence analysis. Single and multivariate analyses were used to describe genotypes’ associations with known demographic and behavioral risk factors for 126 linked cases of acute HBV. Results Nine genotypes were detected (A to I), including mixed infections. Genotype C (HBV/C) dominated within chronic infections while HBV/D and A prevailed among acute HBV cases. History of incarceration and residing with a chronic HBV carrier or injection drug user were the most frequently reported risks for acute HBV infection. Over time, HBV/A increased among both acute and chronic infections, and HBV/C and HBV/D decreased among chronic infections. Conclusion Chronic and acute HBV genotypes in Canada differ in the relative distribution and their associations with known risk factors, suggesting different routes of transmission and clinical progression of infection. PMID:26406309

  14. Clinical course and management of acute and chronic viral hepatitis during pregnancy.

    PubMed

    Licata, A; Ingrassia, D; Serruto, A; Soresi, M; Giannitrapani, L; Montalto, G; Craxì, A; Almasio, P L

    2015-06-01

    Pregnancy is a para-physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually terminates the progression of these disorders. All chronic liver diseases, such as chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, and cirrhosis of different aetiologies may cause liver damage, independently from pregnancy. In this review we will also comment the clinical implications of pregnancies occurring in women who received a orthotopic liver transplantation (OLT) Therefore, the management of immunosuppressive therapy before and after the delivery in women who received liver transplant is becoming a relevant clinical issue. Finally, we will focus on acute and chronic viral hepatitis occurring during pregnancy, on management of advanced liver disease and we will review the literature on the challenging issue regarding pregnancy and OLT.

  15. Inhibition of Hepatitis C Virus-Like Particle Binding to Target Cells by Antiviral Antibodies in Acute and Chronic Hepatitis C

    PubMed Central

    Steinmann, Daniel; Barth, Heidi; Gissler, Bettina; Schürmann, Peter; Adah, Mohammed I.; Gerlach, J. Tilman; Pape, Gerd R.; Depla, Erik; Jacobs, Dirk; Maertens, Geert; Patel, Arvind H.; Inchauspé, Geneviève; Liang, T. Jake; Blum, Hubert E.; Baumert, Thomas F.

    2004-01-01

    Hepatitis C virus (HCV) is a leading cause of chronic viral hepatitis worldwide. The study of antibody-mediated virus neutralization has been hampered by the lack of an efficient and high-throughput cell culture system for the study of virus neutralization. The HCV structural proteins have been shown to assemble into noninfectious HCV-like particles (HCV-LPs). Similar to serum-derived virions, HCV-LPs bind and enter human hepatocytes and hepatoma cell lines. In this study, we developed an HCV-LP-based model system for a systematic functional analysis of antiviral antibodies from patients with acute or chronic hepatitis C. We demonstrate that cellular HCV-LP binding was specifically inhibited by antiviral antibodies from patients with acute or chronic hepatitis C in a dose-dependent manner. Using a library of homologous overlapping envelope peptides covering the entire HCV envelope, we identified an epitope in the N-terminal E2 region (SQKIQLVNTNGSWHI; amino acid positions 408 to 422) as one target of human antiviral antibodies inhibiting cellular particle binding. Using a large panel of serum samples from patients with acute and chronic hepatitis C, we demonstrated that the presence of antibodies with inhibition of binding activity was not associated with viral clearance. In conclusion, antibody-mediated inhibition of cellular HCV-LP binding represents a convenient system for the functional characterization of human anti-HCV antibodies, allowing the mapping of envelope neutralization epitopes targeted by naturally occurring antiviral antibodies. PMID:15308699

  16. The relationship between visfatin, liver inflammation, and acute phase reactants in chronic viral hepatitis B.

    PubMed

    Yüksel, Enver; Akbal, Erdem; Koçak, Erdem; Akyürek, Ömer; Köklü, Seyfettin; Ekiz, Fuat; Yılmaz, Barış

    2016-09-01

    Chronic viral hepatitis B (CHB) is an important cause of morbidity and mortality. Adipokine stimulation might play an important role in the pathogenesis of chronic inflammation. The aim of this study was to evaluate serum visfatin concentrations and the relationship between visfatin, fibrosis, liver inflammation, and acute phase reactants in CHB patients.The sampling universe of the study consisted of 41 CHB patients and 25 healthy controls. All patients had positive hepatitis B surface antigen (Hepatitis e antigen (HBeAg) positive n: 7, n: 34 HBeAg negative) for at least 6 months and detectable serum HBV DNA. Serum visfatin concentrations were significantly higher in the CHB patients [18.0 ± 10.9 ng dL(-1)] than in the healthy controls [9.4 ± 1.6 ng dL(-1)] [P < 0.001]. On the other hand, fibrinogen and haptoglobin concentrations were significantly lower in CHB patients. A strong negative correlation was observed between serum visfatin concentration, haptoglobin, and fibrinogen levels; however, there was no significant correlation between visfatin, glucose, alanine aminotransferase, aspartate aminotransferase, BMI, Knodell score, fibrosis score, hepatitis B virus DNA, sedimentation, and C-reactive protein. Visfatin concentrations were elevated and visfatin was negatively correlated with haptoglobin and fibrinogen levels in CHB patients.

  17. Hepatitis

    MedlinePlus

    ... has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool to ... risk for severe disease. Others A variety of viruses can affect the liver Signs and Symptoms Hepatitis ...

  18. Dose-Reduced Trastuzumab Emtansine: Active and Safe in Acute Hepatic Dysfunction

    PubMed Central

    Sharp, Adam; Johnston, Stephen R.D.

    2015-01-01

    Breast cancer is the most common cancer in women worldwide. The majority of deaths attributed to breast cancer are a result of metastatic disease, and 30% of early breast cancers (EBC) will develop distant disease. The 5-year survival of patients with metastatic disease is estimated at 23%. Breast cancer subtypes continue to be stratified histologically on oestrogen, progesterone and human epidermal growth factor-2 (HER2) receptor expression. HER2-positive breast cancers represent 25% of all breast cancer diagnoses. The therapies available for metastatic breast cancer (MBC) are expanding, in particular within the field of HER2-positive disease, with the approval of trastuzumab, pertuzumab, lapatinib and trastuzumab emtansine (TDM-1). Recently, TDM-1 has been shown to improve progression-free survival in HER2 MBC when compared to capecitabine and lapatinib in clinical studies. Its main toxicities are deranged liver function tests and thrombocytopenia. There have also been cases of acute liver failure. Therefore, its use in acute hepatic dysfunction, to our knowledge, has been neither studied nor reported. We report a patient with progressive HER2-positive MBC who had previously responded to multiple HER2-targeted therapies that presented with acute hepatic dysfunction. She was treated with dose-reduced TDM-1 safely, with clear evidence of rapid biochemical, clinical and radiological response. This allowed dose escalation of TDM-1, and the patient maintains an ongoing response. PMID:25873876

  19. [Bleeding gastric ulcers and acute hepatitis: 2 simultaneous adverse reactions due to nimesulide in a case].

    PubMed

    Tejos, S; Torrejón, N; Reyes, H; Meneses, M

    2000-12-01

    A 66 year-old obese woman with arthrosis, self-medicated with oral nimesulide, 200 mg daily. After 6 weeks she developed nausea, jaundice and dark urine. Two weeks later she had recurrent hematemesis and was hospitalized. Besides obesity and anemia her physical examination was unremarkable. An upper GI endoscopy revealed 3 acute gastric ulcers and a 4th one in the pyloric channel. Abdominal ultrasonogram showed a slightly enlarged liver with diffuse reduction in ecogenicity; the gallbladder and biliary tract were normal. Blood tests demonstrated a conjugated hyperbilirubinemia (maximal total value: 18.4 mg/dl), ALAT 960 U/l, ASAT 850 U/l, GGT 420 U/l, alkaline phosphatases mildly elevated, pro-time 49% and albumin 2.7 mg/dl. Serum markers for hepatitis A, B and C viruses were negative. ANA, AMA, anti-SmA, were negative. Ceruloplasmin was normal. A liver biopsy showed bridging necrosis and other signs of acute toxic liver damage. Gastric ulcers healed after conventional treatment and hepatitis subsided after 2 months leaving no signs of chronic liver damage. The diagnosis of toxic hepatitis due to nimesulide was supported by the time-course of drug usage, sex, age, absence of other causes of liver disease, a compatible liver biopsy and the improvement after drug withdrawal. Peptic ulcers or toxic hepatitis have been previously described as independent adverse reactions in patients taking nimesulide or other NSAIDs but their simultaneous occurrence in a single patient is a unique event that deserves to be reported.

  20. A case of thyroid storm complicated by acute hepatitis due to propylthiouracil treatment

    PubMed Central

    Hashim, Nazhri; Sze, Candy; Waterhouse, Mona

    2015-01-01

    Summary A 57-year-old female presented 17 days after treatment with radioactive iodine (RAI) for difficult-to-control hyperthyroidism. She was febrile, had a sinus tachycardia, and was clinically thyrotoxic. Her thyroid function tests showed a suppressed TSH <0.02 mU/l, with free thyroxine (FT4) >75 pmol/l and total triiodothyronine (TT3) 6.0 nmol/l. She was diagnosed with thyroid storm and was managed with i.v. fluids, propylthiouracil (PTU) 200 mg four times a day, prednisolone 30 mg once daily and propanolol 10 mg three times a day. She gradually improved over 2 weeks and was discharged home on PTU with β blockade. On clinic review 10 days later, it was noted that, although she was starting to feel better, she had grossly abnormal liver function (alanine transaminase (ALT) 852 U/l, bilirubin 46 μmol/l, alkaline phosphatase (ALP) 303 U/l, international normalized ratio (INR) 0.9, platelets 195×109/l). She was still mildly thyrotoxic (TSH <0.02 mU/l, FT4 31 pmol/l, TT3 1.3 nmol/l). She was diagnosed with acute hepatitis secondary to treatment with PTU. Ultrasound showed mild hepatic steatosis. PTU was stopped and she was managed with fluids and prednisolone 60 mg once daily and continued β blockade. Her liver function gradually improved over 10 days (bilirubin 9 μmol/l, ALT 164 U/l, ALP 195 U/l, INR 0.9, platelets 323×109/l) with conservative management and had normalised by clinic review 3 weeks later. This case highlights the potentially fatal, but rare, complications associated with both RAI and PTU, namely, thyroid storm and acute hepatitis respectively. Learning points Thyroid storm is an important, albeit rare, endocrinological emergency.Thyroid storm following RAI treatment is extremely rare.Management is with i.v. fluids, β blockade, anti-thyroid drugs and steroids.High dose glucocorticoid steroids can block the peripheral conversion of T4 to active T3.Liver dysfunction, acute hepatitis and potential hepatic failure

  1. Novel Management of Acute or Secondary Biliary Liver Conditions Using Hepatically Differentiated Human Dental Pulp Cells

    PubMed Central

    Ishkitiev, Nikolay; Imai, Toshio; Tanaka, Tomoko; Fushimi, Naho; Mitev, Vanyo; Okada, Mio; Tominaga, Noriko; Ono, Sachie; Ishikawa, Hiroshi

    2015-01-01

    The current definitive treatment for acute or chronic liver condition, that is, cirrhosis, is liver transplantation from a limited number of donors, which might cause complications after donation. Hence, bone marrow stem cell transplantation has been developed, but the risk of carcinogenesis remains. We have recently developed a protocol for hepatic differentiation of CD117+ stem cells from human exfoliated deciduous teeth (SHED). In the present study, we examine whether SHED hepatically differentiated (hd) in vitro could be used to treat acute liver injury (ALI) and secondary biliary cirrhosis. The CD117+ cell fraction was magnetically separated from SHED and then differentiated into hepatocyte-like cells in vitro. The cells were transplanted into rats with either ALI or induced secondary biliary cirrhosis. Engraftment of human liver cells was determined immunohistochemically and by in situ hybridization. Recovery of liver function was examined by means of histochemical and serological tests. Livers of transplanted animals were strongly positive for human immunohistochemical factors, and in situ hybridization confirmed engraftment of human hepatocytes. The tests for recovery of liver function confirmed the presence of human hepatic markers in the animals' blood serum and lack of fibrosis and functional integration of transplanted human cells into livers. No evidence of malignancy was found. We show that in vitro hdSHED engraft morphologically and functionally into the livers of rats having acute injury or secondary biliary cirrhosis. SHED are readily accessible adult stem cells, capable of proliferating in large numbers before differentiating in vitro. This makes SHED an appropriate and safe stem cell source for regenerative medicine. PMID:25234861

  2. Acute hepatitis C virus infection related to capillary blood glucose meter

    PubMed Central

    Inayat, Faisal; Rai, Aitzaz BinSultan

    2016-01-01

    Hepatitis C virus (HCV) infects an estimated 130-150 million people worldwide, becoming the major cause of chronic liver disease, cirrhosis, hepatocellular carcinoma, and liver transplantation. There are various preventable modes of transmission of HCV infection, including needlestick and sharps injuries. However, HCV infection secondary to needlestick injury by a capillary blood glucose meter (CBGM) lancet has not been previously well reported. We describe an unusual case of a 25-year-old male medical student, acquiring acute HCV infection with a lancing device of CBGM. The source patient was a 54-year-old diabetic male with positive anti-HCV test results. In our patient, after 3 months of initial exposure, a standard set of investigations confirmed the diagnosis of acute HCV infection with the same genotype (3a) as the source. The CBGM, as in our case, may have a role in the transmission of HCV infection warranting radical advancements in diabetes screening and monitoring technology. PMID:26739982

  3. Delayed type hypersensitivity (DTH) skin reaction to hepatitis B surface antigen (HBsAg) in patients with type B acute and chronic hepatitis.

    PubMed Central

    Nagafuchi, S; Kashiwagi, S; Hayashi, S; Inoue, T; Imayama, S; Takeshita, M; Kikuchi, M

    1985-01-01

    Skin reactivity to HBsAg was studied in patients with type B acute and chronic hepatitis and in healthy controls. HBsAg preparations containing 50 micrograms/ml of antigen both with and without alum elicited positive skin reactions in all seven anti-HBs+ persons. Histological examination of skin tissue from the reactive area using monoclonal antibodies to the cell surface of lymphocytes revealed accumulation of Leu-3a positive lymphocytes, showing that the inflammation was a typical delayed type hypersensitivity (DTH) reaction. Irrespective of the presence of HBeAg and anti-HBe, patients with chronic type B hepatitis responded clearly to PPD and SK/SD antigens, whereas they did not exhibit DTH skin reactivity to HBsAg. In contrast, although patients with acute type B hepatitis did not exhibit specific DTH a reaction to HBsAg in the acute period, they began to develop DTH skin reactivity to HBsAg in the convalescent phase of the disease preceding the appearance of anti-HBs antibody. It is suggested that DTH reaction to HBsAg might play an important role in the pathogenesis of type B viral hepatitis. Images Fig. 2 PMID:4075587

  4. The interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) and 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) in TCDD-induced porphyria

    SciTech Connect

    Yao, Cheng Catsby.

    1989-01-01

    Halogenated aryl hydrocarbon(HAH)-induced porphyria is caused by alteration of porphyrin metabolism and results in the accumulation of hepatic and urinary porphyrins. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (75 {mu}/kg) caused significant increases of hepatic porphyrin levels in C57BL/6 male, female and ovariectomized female, and C57BL/10 male mice 3 weeks after treatment. In contrast, 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) was inactive at a dose of 750 {mu}mol/kg. Cotreatment with MCDF (750 {mu}mol/kg) and 2,3,7,8-TCDD (75 {mu}g/kg) resulted in partial antagonism of 2,3,7,8-TCDD-induced porphyrin accumulation in female but not in male mice. In female C57BL/6 mice, 2,3,7,8-TCDD-induced porphyria was accompanied by the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities and the inhibition of uroporphyrinogen decarboxylase (UROD) activity. MCDF (750 {mu}mol/kg) did not significantly affect these enzyme activities. In coadministration studies, MCDF partially antagonized 2,3,7,8-TCDD-induced hepatic porphyrin accumulation but did not affect the activities of hepatic AHH, EROD or UROD. These results demonstrate that the induction of the monooxygenase enzyme activities and the inhibition of UROD activity by 2,3,7,8-TCDD and the development of porphyria are not coordinately regulated in C57BL/6 female mice. In cultured chick embryo hepatocytes, 2,3,7,8-TCDD caused a significant increase in porphyrin levels and induced AHH and EROD activities. MCDF and Aroclor 1254 partially antagonized the 2,3,7,8-TCDD induced AHH and EROD activities but not the porphyrin accumulation.

  5. Assessing candidacy for acute hepatitis C treatment among active young injection drug users: a case-series report.

    PubMed

    Asher, Alice; Lum, Paula J; Page, Kimberly

    2012-01-01

    Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All five acutely-infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. Establishing treatment candidacy for young IDU in the acute phase involves various health domains. An acute infection's short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care. PMID:21497111

  6. Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting MAPKs and Apoptosis

    PubMed Central

    Omar, Hany A.; Mohamed, Wafaa R.; Arab, Hany H.; Arafa, El-Shaimaa A.

    2016-01-01

    Despite its broad applications, cisplatin affords considerable nephro- and hepatotoxicity through triggering inflammatory and oxidative stress cascades. The aim of the current investigation was to study the possible protective effects of tangeretin on cisplatin-induced hepatotoxicity. The impact of tangeretin on cisplatin-evoked hepatic dysfunction and histopathologic changes along with oxidative stress, inflammatory and apoptotic biomarkers were investigated compared to silymarin. Tangeretin pre-treatment significantly improved liver function tests (ALT and AST), inhibited cisplatin-induced lipid profile aberrations (total cholesterol and triglycerides) and diminished histopathologic structural damage in liver tissues. Tangeretin also attenuated cisplatin-induced hepatic inflammatory events as indicated by suppression of tumor necrosis factor-α (TNF-α) and enhancement of interleukin-10 (IL-10). Meanwhile, it lowered malondialdehyde (MDA), nitric oxide (NO) and nuclear factor erythroid 2-related factor 2 (NRF-2) levels with restoration of glutathione (GSH), and glutathione peroxidase (GPx). Regarding mitogen-activated protein kinase (MAPK) pathway, tangeretin attenuated cisplatin-induced increase in phospho-p38, phospho-c-Jun N-terminal kinase (p-JNK) and phospho-extracellular signal-regulated kinase (p-ERK1/2) in liver tissues. In addition, tangeretin downregulated Bax expression with augmentation of Bcl-2 promoting liver cell survival. Our results highlight the protective effects of tangeretin against cisplatin-induced acute hepatic injury via the concerted modulation of inflammation, oxidative stress, MAPKs and apoptotic pathways. PMID:27031695

  7. Positive selection of cytotoxic T lymphocyte escape variants during acute hepatitis C virus infection.

    PubMed

    Guglietta, Silvia; Garbuglia, Anna Rosa; Pacciani, Valentina; Scottà, Cristiano; Perrone, Maria Paola; Laurenti, Luca; Spada, Enea; Mele, Alfonso; Capobianchi, Maria Rosaria; Taliani, Gloria; Folgori, Antonella; Vitelli, Alessandra; Ruggeri, Lionello; Nicosia, Alfredo; Piccolella, Enza; Del Porto, Paola

    2005-09-01

    Cellular immune responses are induced during hepatitis C virus (HCV) infection and acute-phase CD8+ T cells are supposed to play an important role in controlling viral replication. In chimpanzees, failure of CD8+ T cells to control HCV replication has been associated with acquisition of mutations in MHC class I-restricted epitopes. In humans, although selection of escape mutations in an immunodominant CTL epitope has been recently described, the overall impact of immune escape during acute HCV infection is unclear. Here, by performing an in depth analysis of the relationship between early cellular immune responses and viral evolution in a chronically evolving HCV acutely infected individual, we demonstrate: (i) the presence of a potent and focused CD8(+ T cell response against a novel epitope in the NS3 protein, (ii) the elimination of the quasi-species harboring the original amino acid sequence within this epitope, and (iii) the selection for a virus population bearing amino acid changes at a single residue within the cytotoxic T cell epitope that strongly diminished T cell recognition. These results support the view that acute-phase CD8+ T cell responses exert a biologically relevant pressure on HCV replication and that viruses escaping this host response could have a significant survival advantage. PMID:16114108

  8. Heterotopic Auxiliary Rat Liver Transplantation With Flow-regulated Portal Vein Arterialization in Acute Hepatic Failure

    PubMed Central

    Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria

    2014-01-01

    In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.1-3 The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.4 In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.5-6 We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.  The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor’s portal vein was carried out via the recipient’s right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient’s aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. 7 In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft’s weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure

  9. Heterotopic auxiliary rat liver transplantation with flow-regulated portal vein arterialization in acute hepatic failure.

    PubMed

    Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria

    2014-01-01

    In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.(1-3) The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.(4) In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.(5-6) We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.  The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor's portal vein was carried out via the recipient's right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient's aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. (7) In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft's weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure

  10. Early warning and clinical outcome prediction of acute-on-chronic hepatitis B liver failure

    PubMed Central

    Chen, En-Qiang; Zeng, Fan; Zhou, Ling-Yun; Tang, Hong

    2015-01-01

    Hepatitis B virus (HBV) associated acute-on-chronic liver failure (ACLF) is an increasingly recognized fatal liver disease encompassing a severe acute exacerbation of liver function in patients with chronic hepatitis B (CHB). Despite the introduction of an artificial liver support system and antiviral therapy, the short-term prognosis of HBV-ACLF is still extremely poor unless emergency liver transplantation is performed. In such a situation, stopping or slowing the progression of CHB to ACLF at an early stage is the most effective way of reducing the morbidity and mortality of HBV-ACLF. It is well-known that the occurrence and progression of HBV-ACLF is associated with many factors, and the outcomes of HBV-ACLF patients can be significantly improved if timely and appropriate interventions are provided. In this review, we highlight recent developments in early warning and clinical outcome prediction in patients with HBV-ACLF and provide an outlook for future research in this field. PMID:26576085

  11. Atg7 Knockdown Augments Concanavalin A-Induced Acute Hepatitis through an ROS-Mediated p38/MAPK Pathway.

    PubMed

    Zhuang, Yan; Li, Yi; Li, Xuefeng; Xie, Qing; Wu, Min

    2016-01-01

    Concanavalin A (ConA), a T-cell mitogen that induces acute autoimmune hepatitis, is widely used to model pathophysiological processes of human acute autoimmune liver disease. Although autophagy has been extensively studied in the past decade, little is known about its molecular mechanism underlying the regulation of ConA-induced acute hepatitis. In this study, we used a Cre-conditional atg7 KO mouse to investigate the effects of Atg7-associated autophagy on ConA-induced murine hepatitis. Our results demonstrated that atg7 deficiency in mice enhanced macrophage activation and increased pro-inflammatory cytokines upon ConA stimulation. Atg7 silencing resulted in accumulation of dysfunctional mitochondria, disruption of reactive oxygen species (ROS) degradation, and increase in pro-inflammatory cytokines in Raw264.7 cells. p38/MAPK and NF-κB levels were increased upon ConA induction due to Atg7 deficiency. Blocking ROS production inhibited ConA-induced p38/IκB phosphorylation and subsequent intracellular inflammatory responses. Hence, this study demonstrated that atg7 knockout in mice or Atg7 knockdown in cell culture augmented ConA-induced acute hepatitis and related cellular malfunction, indicating protective effects of Atg7 on regulating mitochondrial ROS via a p38/MAPK-mediated pathway. Collectively, our findings reveal that autophagy may attenuate macrophage-mediated inflammatory response to ConA and may be the potential therapeutic targets for acute liver injury. PMID:26939081

  12. Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status.

    PubMed

    Ajith, T A; Hema, U; Aswathy, M S

    2007-11-01

    A large number of xenobiotics are reported to be potentially hepatotoxic. Free radicals generated from the xenobiotic metabolism can induce lesions of the liver and react with the basic cellular constituents - proteins, lipids, RNA and DNA. Hepatoprotective activity of aqueous ethanol extract of Zingiber officinale was evaluated against single dose of acetaminophen-induced (3g/kg, p.o.) acute hepatotoxicity in rat. Aqueous extract of Z. officinale significantly protected the hepatotoxicity as evident from the activities of serum transaminase and alkaline phosphatase (ALP). Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and ALP activities were significantly (p<0.01) elevated in the acetaminophen alone treated animals. Antioxidant status in liver such as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase and glutathione-S-transferase (GST), a phase II enzyme, and levels of reduced glutathione (GSH) were declined significantly (p<0.01) in the acetaminophen alone treated animals (control group). Hepatic lipid peroxidation was enhanced significantly (p<0.01) in the control group. Administration of single dose of aqueous extract of Z. officinale (200 and 400mg/kg, p.o.) prior to acetaminophen significantly declines the activities of serum transaminases and ALP. Further the hepatic antioxidant status was enhanced in the Z. officinale plus acetaminophen treated group than the control group. The results of the present study concluded that the hepatoprotective effect of aqueous ethanol extract of Z. officinale against acetaminophen-induced acute toxicity is mediated either by preventing the decline of hepatic antioxidant status or due to its direct radical scavenging capacity. PMID:17637489

  13. Acute Ethanol Causes Hepatic Mitochondrial Depolarization in Mice: Role of Ethanol Metabolism

    PubMed Central

    Zhong, Zhi; Ramshesh, Venkat K.; Rehman, Hasibur; Liu, Qinlong; Theruvath, Tom P.; Krishnasamy, Yasodha; Lemasters, John J.

    2014-01-01

    Background/Aims An increase of ethanol metabolism and hepatic mitochondrial respiration occurs in vivo after a single binge of alcohol. Here, our aim was to determine how ethanol intake affects hepatic mitochondrial polarization status in vivo in relation to ethanol metabolism and steatosis. Methods Hepatic mitochondrial polarization, permeability transition (MPT), and reduce pyridine nucleotides, and steatosis in mice were monitored by intravital confocal/multiphoton microscopy of the fluorescence of rhodamine 123 (Rh123), calcein, NAD(P)H, and BODIPY493/503, respectively, after gavage with ethanol (1–6 g/kg). Results Mitochondria depolarized in an all-or-nothing fashion in individual hepatocytes as early as 1 h after alcohol. Depolarization was dose- and time-dependent, peaked after 6 to 12 h and maximally affected 94% of hepatocytes. This mitochondrial depolarization was not due to onset of the MPT. After 24 h, mitochondria of most hepatocytes recovered normal polarization and were indistinguishable from untreated after 7 days. Cell death monitored by propidium iodide staining, histology and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was low throughout. After alcohol, mitochondrial NAD(P)H autofluorescence increased and decreased, respectively, in hepatocytes with polarized and depolarized mitochondria. Ethanol also caused steatosis mainly in hepatocytes with depolarized mitochondria. Depolarization was linked to ethanol metabolism, since deficiency of alcohol dehydrogenase and cytochrome-P450 2E1 (CYP2E1), the major ethanol-metabolizing enzymes, decreased mitochondrial depolarization by ∼70% and ∼20%, respectively. Activation of aldehyde dehydrogenase decreased depolarization, whereas inhibition of aldehyde dehydrogenase enhanced depolarization. Activation of aldehyde dehydrogenase also markedly decreased steatosis. Conclusions Acute ethanol causes reversible hepatic mitochondrial depolarization in vivo that may contribute to

  14. Autoimmune hepatitis

    MedlinePlus

    Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...

  15. Feature Hepatitis: The Dangers of Hepatitis: What you should know from A to E

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Feature Hepatitis The Dangers of Hepatitis: What you should know from A to E ... drugs. In some cases, hepatitis lasts a lifetime. Hepatitis: Acute or Chronic? Acute hepatitis is the initial ...

  16. Molecular Evolution and Phylodynamics of Acute Hepatitis B Virus in Japan

    PubMed Central

    Lin, Serena Y. C.; Toyoda, Hidenori; Kumada, Takashi; Liu, Hsin-Fu

    2016-01-01

    Hepatitis B virus (HBV) is prevalent worldwide and causes liver diseases, including acute and chronic hepatitis. Ten HBV genotypes (A–J) with distinct geographic distributions have been reported. Cases of acute HBV infection with genotype A have increased in Japan nationwide since the 1990s, mainly through sexual transmission. To investigate the molecular evolution and phylodynamics of HBV genotypes, we collected acute HBV isolates acquired in Japan from 1992–2002. Full genomes were obtained for comprehensive phylogenetic and phylodynamic analysis, with other Japanese HBV sequences from GenBank that were isolated during 1991–2010. HBV genotypes were classified using the maximum-likelihood and Bayesian methods. The GMRF Bayesian Skyride was used to estimate the evolution and population dynamics of HBV. Four HBV genotypes (A, B, C, and H) were identified, of which C was the major genotype. The phylodynamic results indicated an exponential growth between the 1960s and early 1990s; this was followed by a population bottleneck after 1995, possibly linked with successful implementation of a nationwide vaccination program. However, HBV/A increased from 1990 to 2003–2004, and then started to decrease. The prevalence of genotype A has increased over the past 10 years. Phylodynamic inference clearly demonstrates a steady population growth compatible with an ongoing subepidemic; this might be due to the loss of immunity to HBV in adolescents and people being born before the vaccination program. This is the first phylodynamic study of HBV infection in Japan and will facilitate understanding the molecular epidemiology and long-term evolutionary dynamics of this virus in Japan. PMID:27280441

  17. Rac1 modulates acute and subacute genotoxin-induced hepatic stress responses, fibrosis and liver aging

    PubMed Central

    Bopp, A; Wartlick, F; Henninger, C; Kaina, B; Fritz, G

    2013-01-01

    To investigate the importance of the Ras-homologous GTPase Rac1 for the hepatic response to genotoxic insults and liver aging, rac1 was deleted in liver of mice by Mx1-Cre-based recombination. Knockout of rac1 caused complex changes in basal as well as doxorubicin and ionizing radiation-induced mRNA expression of various genotoxic stress response-related genes, including hspa1b, rad51, wrn and xpc. Rac1 deletion protected the liver from acute toxicity following doxorubicin treatment. Moreover, the level of S139 phosphorylated histone H2AX (γH2AX), which is indicative of DNA damage, and mRNA expression of pro-inflammatory (IL-6) and pro-fibrotic (CTGF, TGFβ, αSMA) factors were mitigated in rac1 knockout animals. By contrast, lack of rac1 promoted subacute hepatotoxicity, which was determined 3 weeks after injection of multiple low doses of doxorubicin by assaying the γH2AX level, mitotic index and pro-fibrotic gene expression. Regarding ionizing radiation, rac1 deficiency had no major effects on DNA damage induction or acute pro-inflammatory and pro-fibrotic stress responses. Mice lacking hepatic rac1 for extended period of time (15 months) revealed increased mRNA expression of fibrosis-related factors (CTGF, TGFβ, collagen, MMP1) and fibrotic tissue remodeling. In addition, protein expression of the senescence marker p16 was enhanced in the absence of rac1. Taken together, the data provide evidence that Rac1 is required for doxorubicin-induced DNA damage induction. It is also involved in both the acute and delayed inflammatory and fibrotic stress response in the liver following doxorubicin, but not ionizing radiation, treatment and, furthermore, protects against endogenous liver aging. PMID:23519127

  18. Investigation of intestine function during acute viral hepatitis using combined sugar oral loads.

    PubMed Central

    Parrilli, G; Cuomo, R; Nardone, G; Maio, G; Izzo, C M; Budillon, G

    1987-01-01

    One fifth of all cases of A virus hepatitis (AVH) have symptoms of gastroenteritis at the onset. This study investigated the mediated intestinal absorption of D-xylose (D-xyl) and 3-o-methyl-D-glucose (3-omG) and the non-mediated permeation of lactulose (Lacl, mol wt 342) and L-rhamnose (L-rh, mol wt 164) during acute and remission phases of AVH. Ten patients with AVH were given an oral load containing these sugars (5 g D-xyl: 2.5 g 3-omG, 1 g L-rh, 5 g lacl in 250 ml water) once during the acute phase and again during remission. The same load was given once to a group of 22 healthy controls. The mean concentration of D-xyl in urine and the ratio of D-xyl to 3-omG in plasma and urine were normal in both the AVH phases, ruling out intestinal malabsorption even in the acute phase. This study showed a significant increase in non-mediated permeation to Lacl, but not to L-rh, during the acute phase. These data indicate that the barrier function of the intestine is compromised in AVH infection while the absorptive function is not. An abnormally low concentration of D-xyl and 3-omG in plasma at one hour was found in all patients during the acute phase. This finding cannot be explained by alterations in intestinal absorption, but could be accounted for by increased space distribution of the sugars because of increased diffusion into tissue cells and/or expansion of the extracellular space by fluid retention. PMID:3428669

  19. Establishing a network of specialist Porphyria centres - effects on diagnostic activities and services

    PubMed Central

    2012-01-01

    Background The porphyrias are a heterogeneous group of rare metabolic diseases. The full spectrum of porphyria diagnostics is usually performed by specialized porphyria laboratories or centres. The European Porphyria Initiative (EPI), a collaborative network of porphyria centres formed in 2001, evolved in 2007 into the European Porphyria Network (EPNET), where participating centres are required to adhere to agreed quality criteria. The aim of this study was to examine the state and distribution of porphyria diagnostic services in 2009 and to explore potential effects of increased international collaboration in the field of these rare diseases in the period 2006–2009. Methods Data on laboratory, diagnostic and clinical activities and services reported to EPI/EPNET in yearly activity reports during 2006 through 2009 were compared between reporting centres, and possible time trends explored. Results Thirty-five porphyria centres from 22 countries, five of which were non-European associate EPNET members, filed one or more activity reports to EPI/EPNET during the study period. Large variations between centres were observed in the analytical repertoire offered, numbers of analyses performed and type and number of staff engaged. The proportion of centres fulfilling the minimum criteria set by EPNET to be classified as a specialist porphyria centre increased from 80% to 94% during the study period. Conclusions Porphyria services are unevenly distributed, and some areas are probably still lacking in specialized porphyria services altogether. However, improvements in the quality of diagnostic services provided by porphyria centres participating in EPI/EPNET were observed during 2006 through 2009. PMID:23227998

  20. Clinical outcome of acute and chronic hepatitis delta over time: a long-term follow-up study.

    PubMed

    Buti, M; Homs, M; Rodriguez-Frias, F; Funalleras, G; Jardí, R; Sauleda, S; Tabernero, D; Schaper, M; Esteban, R

    2011-06-01

    Long-term changes in the frequency and outcome of hepatitis delta virus (HDV) infection have seldom been analysed. This retrospective, longitudinal study includes 398 consecutive hepatitis B surface antigen (HBsAg)-positive patients with anti-HDV antibodies who attended our institution between 1983 and 2008. At enrolment, 182 patients had acute and 216 chronic hepatitis. Patients were grouped into two periods. Those who attended between 1983 and 1995 and those between 1996 and 2008. The former group was significantly younger, mainly intravenous drugs users, and had a greater incidence of acute HDV and HIV and HCV coinfection. Patients with acute HBV/HDV coinfection cleared both infections in 90% of cases, while all patients with HDV superinfection evolved to chronic disease. One hundred and fifty-eight patients with chronic HDV were followed for a median period of 158months. Seventy-two per cent of the patients remained stable, 18% had hepatic decompensation, 3% developed hepatocellular carcinoma, and 8% cleared HBsAg. Liver-related death was observed in 13% of patients and mainly occurred in patients from the first period (P=0.012). These results indicate an outbreak of HDV at the end of the 1980s and the beginning of the 1990s, with a large number of acute HDV cases affecting predominately young, male intravenous drug users. Currently, patients with chronic HDV disease are older, and factors associated with worse prognosis include the presence of cirrhosis and age at the time of diagnosis.

  1. Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection

    PubMed Central

    McElroy, Kerensa; Gaudieri, Silvana; Pham, Son T.; Chopra, Abha; Cameron, Barbara; Maher, Lisa; Dore, Gregory J.; White, Peter A.; Lloyd, Andrew R.

    2011-01-01

    Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection. PMID:21912520

  2. Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1/Fas) mediated apoptosis.

    PubMed

    Strand, S; Hofmann, W J; Grambihler, A; Hug, H; Volkmann, M; Otto, G; Wesch, H; Mariani, S M; Hack, V; Stremmel, W; Krammer, P H; Galle, P R

    1998-05-01

    Wilson's disease can result in fulminant liver failure due to hepatic copper overload. The CD95 system mediates apoptosis and has been demonstrated to be involved in liver disease. In this study CD95 mediated apoptosis was investigated in patients with fulminant hepatic failure in the course of Wilson's disease and in an in vitro model of copper treated human hepatoma cells. In patients, hepatic expression of CD95 and CD95L mRNA and apoptosis were detected. Copper overload in vitro resulted in hepatocytic apoptosis which could be reduced with a neutralizing anti-CD95L antibody. Copper treatment of hepatocytes results in activation of the CD95 system and induction of apoptosis which is operative during the course of hepatic failure in acute Wilson's disease.

  3. The effects of acute ethanol exposure on inhibitors of hepatic regenerative activity in the rat.

    PubMed

    Zhang, M N; Gong, Y; Minuk, G Y

    2000-04-01

    The purpose of this study was to identify the mechanism(s) whereby acute ethanol exposure inhibits hepatic regenerative activity in the rat. Adult, male, Sprague-Dawley rats (200-250 g) were randomized to receive either ethanol (1 g/kg i.p. q 4 h) or an equal volume of saline (controls) for 24 h beginning 1 h prior to a 70% partial hepatectomy (PHx). At 0, 3, 6, 12 and 24 h post-PHx, rats were sacrificed (N = 4-6/group), and the expression of the following genes associated with inhibition of hepatocyte proliferation were documented; p53, p21, transforming growth factor-beta1 (TGF-beta1) and gamma aminobutyric acid transport protein (GABA-TP). Inhibition of hepatic regenerative activity was confirmed by 3H-thymidine incorporation into hepatic DNA at 24 h post-PHx. The results of the study revealed that in ethanol-treated rats, DNA synthesis was inhibited by 37% when compared to saline-treated controls (p < 0.01). Regarding suppressor gene expression, both p21 and TGF-beta1 mRNA expression in ethanol-treated rats were similar to those obtained in saline-treated controls. Although p53 mRNA expression differed in the two groups, in the ethanol-treated group, p53 mRNA expression was decreased rather than increased (relative to controls) at 24 h post-PHx, a finding not in keeping with inhibition of DNA synthesis. GABA-TP mRNA was strongly expressed prior to PHx in both ethanol- and saline-treated rats. Following PHx, GABA-TP mRNA expression decreased in both groups but remained low in the saline-treated group while returning to pre-PHx values in ethanol-treated rats. In summary, the results of this study indicate that the inhibitory effects of ethanol on hepatic regeneration are not associated with significant or the appropriate changes in mRNA expression of the p53, p21 or TGF-beta1 suppressor genes. On the other hand, transcriptional changes in GABA-TP gene expression post-PHx are in keeping with an inhibitory effect of GABA on hepatic regeneration.

  4. Patterns of Hepatitis C Virus RNA Levels during Acute Infection: The InC3 Study

    PubMed Central

    Hajarizadeh, Behzad; Grady, Bart; Page, Kimberly; Kim, Arthur Y.; McGovern, Barbara H.; Cox, Andrea L.; Rice, Thomas M.; Sacks-Davis, Rachel; Bruneau, Julie; Morris, Meghan; Amin, Janaki; Schinkel, Janke; Applegate, Tanya; Maher, Lisa; Hellard, Margaret; Lloyd, Andrew R.; Prins, Maria; Dore, Gregory J.; Grebely, Jason

    2015-01-01

    Background Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV) infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection. Methods Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study). Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels≤120 days) were categorised by a priori-defined patterns of HCV RNA levels: i) spontaneous clearance, ii) partial viral control with persistence (≥1 log IU/mL decline in HCV RNA levels following peak) and iii) viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak). Factors associated with HCV RNA patterns were assessed using multinomial logistic regression. Results Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%), partial viral control with persistence (27%), and viral plateau with persistence (41%). HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P=0.018). In the two groups with persistence, Interferon lambda 3 (IFNL3) CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02). In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83). Conclusions Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female sex

  5. Pure red-cell aplasia and autoimmune hemolytic anemia in a patient with acute hepatitis A.

    PubMed

    Chang, Hyo Jeong; Sinn, Dong Hyun; Cho, Sung Gyun; Oh, Tae Hoon; Jeon, Tae Joo; Shin, Won Chang; Choi, Won Choong

    2014-06-01

    Pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) have rarely been reported as an extrahepatic manifestation of acute hepatitis A (AHA). We report herein a case of AHA complicated by both PRCA and AIHA. A 49-year-old female with a diagnosis of AHA presented with severe anemia (hemoglobin level, 6.9 g/dL) during her clinical course. A diagnostic workup revealed AIHA and PRCA as the cause of the anemia. The patient was treated with an initial transfusion and corticosteroid therapy. Her anemia and liver function test were completely recovered by 9 months after the initial presentation. We review the clinical features and therapeutic strategies for this rare case of extrahepatic manifestation of AHA.

  6. Acute Liver Injury Induces Nucleocytoplasmic Redistribution of Hepatic Methionine Metabolism Enzymes

    PubMed Central

    Delgado, Miguel; Garrido, Francisco; Pérez-Miguelsanz, Juliana; Pacheco, María; Partearroyo, Teresa; Pérez-Sala, Dolores

    2014-01-01

    Abstract Aims: The discovery of methionine metabolism enzymes in the cell nucleus, together with their association with key nuclear processes, suggested a putative relationship between alterations in their subcellular distribution and disease. Results: Using the rat model of d-galactosamine intoxication, severe changes in hepatic steady-state mRNA levels were found; the largest decreases corresponded to enzymes exhibiting the highest expression in normal tissue. Cytoplasmic protein levels, activities, and metabolite concentrations suffered more moderate changes following a similar trend. Interestingly, galactosamine treatment induced hepatic nuclear accumulation of methionine adenosyltransferase (MAT) α1 and S-adenosylhomocysteine hydrolase tetramers, their active assemblies. In fact, galactosamine-treated livers showed enhanced nuclear MAT activity. Acetaminophen (APAP) intoxication mimicked most galactosamine effects on hepatic MATα1, including accumulation of nuclear tetramers. H35 cells that overexpress tagged-MATα1 reproduced the subcellular distribution observed in liver, and the changes induced by galactosamine and APAP that were also observed upon glutathione depletion by buthionine sulfoximine. The H35 nuclear accumulation of tagged-MATα1 induced by these agents correlated with decreased glutathione reduced form/glutathione oxidized form ratios and was prevented by N-acetylcysteine (NAC) and glutathione ethyl ester. However, the changes in epigenetic modifications associated with tagged-MATα1 nuclear accumulation were only prevented by NAC in galactosamine-treated cells. Innovation: Cytoplasmic and nuclear changes in proteins that regulate the methylation index follow opposite trends in acute liver injury, their nuclear accumulation showing potential as disease marker. Conclusion: Altogether these results demonstrate galactosamine- and APAP-induced nuclear accumulation of methionine metabolism enzymes as active oligomers and unveil the implication of

  7. Telaprevir in the Treatment of Acute Hepatitis C Virus Infection in HIV-Infected Men

    PubMed Central

    Fierer, Daniel S.; Dieterich, Douglas T.; Mullen, Michael P.; Branch, Andrea D.; Uriel, Alison J.; Carriero, Damaris C.; van Seggelen, Wouter O.; Hijdra, Rosanne M.; Cassagnol, David G.; Akil, Bisher; Bailey, Juan; Bellman, Paul; Bowers, Daniel; Bungay, Krisczar; Burger, Susanne; Carpenter, Ward; Chavez, Robert; Chow, Rita; Cohen, Robert; Dalton, Patrick; Dellosso, John; Demidont, Adrian; Dillon, Stephen; Donlon, Eileen; Farrow, Terry; Gardenier, Donald; Guadron, Rodolfo; Haber, Stuart; Higgins, Lawrence; Hitzeman, Lawrence; Hsu, Ricky; Huprikar, Shirish; Inada, Victor; Jacob, Sneha; Johnson, Livette; Johnston, Barbara; Kaminsky, Donald; Klein, Oscar; Kwong, Jeffrey; Lares-Guia, Jose; Leach, Eric; Levine, Randy; Linetskaya, Irina; Litvinova, Larisa; Malhotra, Amisha; Mandell, William; Markowitz, Martin; Mayer, Gal; Meraz, Eddie; Mortensen, Erik; Ng, Michel; Olivieri, Joseph; Paolino, Charles; Photangtham, Punyadech; Psevdos, George; Radix, Anita; Rapaport, Steven; Rodriguez-Caprio, Gabriela; Shay, William; Somasundaram, Nirupama; Sorra, Lembitu; Stivala, Alicia; Tran, Richie; Urbina, Antonio; Vail, Rona; Wallach, Francis; Wang, Wen; Weiss, Susan; Wiener, Melissa

    2014-01-01

    Background. There is an international epidemic of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)–infected men who have sex with men. Sustained virologic response (SVR) rates with pegylated interferon and ribavirin treatment are higher in these men during acute HCV than during chronic HCV, but treatment is still lengthy and SVR rates are suboptimal. Methods. We performed a pilot study of combination therapy with telaprevir, pegylated interferon, and ribavirin in acute genotype 1 HCV infection in HIV-infected men. Men who were treated prior to the availability of, or ineligible for, telaprevir were the comparator group. The primary endpoint was SVR12, defined as an HCV viral load <5 IU/mL at least 12 weeks after completing treatment. Results. In the telaprevir group, 84% (16/19) of men achieved SVR12 vs 63% (30/48) in the comparator group. Among men with SVR, median time to undetectable viral load was week 2 in the telaprevir group vs week 4 in the comparator group, and 94% vs 53% had undetectable viral loads at week 4. Most patients (81%) who achieved SVR in the telaprevir group received ≤12 weeks of treatment and there were no relapses after treatment. The overall safety profile was similar to that known for telaprevir-based regimens. Conclusions. Incorporating telaprevir into treatment of acute genotype 1 HCV in HIV-infected men halved the treatment duration and increased the SVR rate. Larger studies should be done to confirm these findings. Clinicians should be alert to detect acute HCV infection of HIV-infected men to take advantage of this effective therapy and decrease further transmission in this epidemic. PMID:24336914

  8. Regulation of TREM expression in hepatic macrophages and endothelial cells during acute endotoxemia.

    PubMed

    Chen, Li C; Laskin, Jeffrey D; Gordon, Marion K; Laskin, Debra L

    2008-04-01

    Triggering receptor expressed on myeloid cells (TREM) regulates inflammatory responses to lipopolysaccharide (LPS). In these studies, we analyzed the expression of TREM in hepatic macrophages and endothelial cells which play a central role in LPS clearance. LPS administration to C3H/HeOuJ mice resulted in a rapid induction of TREM-1 and TREM-3, but a decrease in TREM-2 in liver macrophages and endothelial cells. The observation that TREM family members are detectable in endothelial cells is novel and demonstrates that their expression is not limited to myeloid cells. LPS-induced alterations in TREM expression were not evident in cells from C3H/HeJ TLR-4 mutant mice, indicating that the response is dependent on TLR-4. IL-1beta and TNFalpha upregulated TREM-1 and TREM-3 expression and suppressed TREM-2 expression in macrophages and endothelial cells. This activity involved PI3-kinase and p38 MAP kinase signaling. Interestingly, no significant differences were noted in TREM expression between wild-type and TNFR1-/- mice treated with LPS. Treatment of macrophages and endothelial cells with LPS upregulated expression of nitric oxide synthase-2 (NOS-2). This was blocked by TREM-1 Fc/fusion protein, indicating that TREM-1 mediates LPS-induced NOS-2 expression. These results suggest that TREM proteins are important in the inflammatory response of hepatic macrophages and endothelial cells to acute endotoxemia. PMID:18222421

  9. Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) presenting with acute fulminant hepatic failure.

    PubMed

    Mhanni, A A; Chan, A; Collison, M; Seifert, B; Lehotay, D C; Sokoro, Ah; Huynh, H Q; Greenberg, C R

    2008-03-01

    We report on two Aboriginal patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Both presented with acute hepatic failure with severe hypertransaminasemia and coagulopathy, prompting evaluation for emergent liver transplantation. The diagnosis of HHH syndrome was based on the presence of typical metabolic abnormalities. A protein-restricted diet and L-arginine or L-citrulline supplementation were immediately started, with rapid normalization of liver function test results and other biochemical abnormalities. Molecular analysis of the SLC25A15 gene showed that the two patients were homozygous for the common French Canadian mutation (F188Delta). The diagnosis of HHH syndrome should be considered in patients with unexplained fulminant hepatic failure. There does not appear to be a genotype-phenotype correlation for this presentation, inasmuch as the only other reported patient presenting with this picture had two different point mutations. Early identification and prompt treatment of these patients is crucial to avoid liver transplantation and can be life saving. PMID:18376250

  10. Acute acetaminophen intoxication leads to hepatic iron loading by decreased hepcidin synthesis.

    PubMed

    van Swelm, Rachel P L; Laarakkers, Coby M M; Blous, Linda; Peters, Janny G P; Blaney Davidson, Esmeralda N; van der Kraan, Peter M; Swinkels, Dorine W; Masereeuw, Rosalinde; Russel, Frans G M

    2012-09-01

    Acetaminophen (APAP), a major cause of acute liver injury in the Western world, is mediated by metabolism and oxidative stress. Recent studies have suggested a role for iron in potentiating APAP-induced liver injury although its regulatory mechanism is not completely understood. The current study was designed to unravel the iron-regulating pathways in mice after APAP-induced hepatotoxicity. Mice with severe injury showed a significant increase in liver iron concentration and oxidative stress. Concurrently, the plasma concentration of hepcidin, the key regulator in iron metabolism, and hepatic hepcidin antimicrobial peptide (Hamp) mRNA expression levels were significantly reduced. We showed that hepcidin transcription was inhibited via several hepcidin-regulating factors, including the bone morphogenetic protein/small mother against decapentaplegic (BMP/SMAD) pathway, CCAAT/enhancer-binding protein α (C/EBPα), and possibly also via erythropoietin (EPO). Downregulation of the BMP/SMAD signaling pathway was most likely caused by hypoxia-inducible factor 1α (HIF-1α), which was increased in mice with severe APAP-induced liver injury. HIF-1α stimulates cleaving of hemojuvelin, the cofactor of the BMP receptor, thereby blocking BMP-induced signaling. In addition, gene expression levels of C/ebpα were significantly reduced, and Epo mRNA expression levels were significantly increased after APAP intoxication. These factors are regulated through HIF-1α during oxidative stress and suggest that HIF-1α is a key modulator in reduced hepcidin transcription after APAP-induced hepatotoxicity. In conclusion, acute APAP-induced liver injury leads to activation of HIF-1α, which results in a downregulation in hepcidin expression through a BMP/SMAD signaling pathway and through C/EBPα inhibition. Eventually, this leads to hepatic iron loading associated with APAP cytotoxicity. PMID:22610607

  11. 38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... porphyria cutanea tarda. (a) Disability benefits. Except as provided in paragraph (c) of this section, a... Vietnam era, and who suffers from chloracne or porphyria cutanea tarda which became manifest within...

  12. 38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... porphyria cutanea tarda. (a) Disability benefits. Except as provided in paragraph (c) of this section, a... Vietnam era, and who suffers from chloracne or porphyria cutanea tarda which became manifest within...

  13. 38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... porphyria cutanea tarda. (a) Disability benefits. Except as provided in paragraph (c) of this section, a... Vietnam era, and who suffers from chloracne or porphyria cutanea tarda which became manifest within...

  14. 38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... porphyria cutanea tarda. (a) Disability benefits. Except as provided in paragraph (c) of this section, a... Vietnam era, and who suffers from chloracne or porphyria cutanea tarda which became manifest within...

  15. 38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... porphyria cutanea tarda. (a) Disability benefits. Except as provided in paragraph (c) of this section, a... Vietnam era, and who suffers from chloracne or porphyria cutanea tarda which became manifest within...

  16. Reduced hepatic mitochondrial respiration following acute high-fat diet is prevented by PGC-1α overexpression.

    PubMed

    Morris, E Matthew; Jackman, Matthew R; Meers, Grace M E; Johnson, Ginger C; Lopez, Jordan L; MacLean, Paul S; Thyfault, John P

    2013-12-01

    Changes in substrate utilization and reduced mitochondrial respiratory capacity following exposure to energy-dense, high-fat diets (HFD) are putatively key components in the development of obesity-related metabolic disease. We examined the effect of a 3-day HFD on isolated liver mitochondrial respiration and whole body energy utilization in obesity-prone (OP) rats. We also examined if hepatic overexpression of peroxisomal proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial respiratory capacity and biogenesis, would modify liver and whole body responses to the HFD. Acute, 3-day HFD (45% kcal) in OP rats resulted in increased daily energy intake, energy balance, weight gain, and adiposity, without an increase in liver triglyceride (triacylglycerol) accumulation. HFD-fed OP rats also displayed decreased whole body substrate switching from the dark to the light cycle, which was paired with reductions in hepatic mitochondrial respiration of multiple substrates in multiple respiratory states. Hepatic PGC-1α overexpression was observed to protect whole body substrate switching, as well as maintain mitochondrial respiration, following the acute HFD. Additionally, liver PGC-1α overexpression did not alter whole body dietary fatty acid oxidation but resulted in greater storage of dietary free fatty acids in liver lipid, primarily as triacylglycerol. Together, these data demonstrate that a short-term HFD can result in a decrease in metabolic flexibility and hepatic mitochondrial respiratory capacity in OP rats that is completely prevented by hepatic overexpression of PGC-1α.

  17. Reduced hepatic mitochondrial respiration following acute high-fat diet is prevented by PGC-1α overexpression

    PubMed Central

    Morris, E. Matthew; Jackman, Matthew R.; Meers, Grace M. E.; Johnson, Ginger C.; Lopez, Jordan L.; MacLean, Paul S.

    2013-01-01

    Changes in substrate utilization and reduced mitochondrial respiratory capacity following exposure to energy-dense, high-fat diets (HFD) are putatively key components in the development of obesity-related metabolic disease. We examined the effect of a 3-day HFD on isolated liver mitochondrial respiration and whole body energy utilization in obesity-prone (OP) rats. We also examined if hepatic overexpression of peroxisomal proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial respiratory capacity and biogenesis, would modify liver and whole body responses to the HFD. Acute, 3-day HFD (45% kcal) in OP rats resulted in increased daily energy intake, energy balance, weight gain, and adiposity, without an increase in liver triglyceride (triacylglycerol) accumulation. HFD-fed OP rats also displayed decreased whole body substrate switching from the dark to the light cycle, which was paired with reductions in hepatic mitochondrial respiration of multiple substrates in multiple respiratory states. Hepatic PGC-1α overexpression was observed to protect whole body substrate switching, as well as maintain mitochondrial respiration, following the acute HFD. Additionally, liver PGC-1α overexpression did not alter whole body dietary fatty acid oxidation but resulted in greater storage of dietary free fatty acids in liver lipid, primarily as triacylglycerol. Together, these data demonstrate that a short-term HFD can result in a decrease in metabolic flexibility and hepatic mitochondrial respiratory capacity in OP rats that is completely prevented by hepatic overexpression of PGC-1α. PMID:24091599

  18. Tlr4-mutant mice are resistant to acute alcohol-induced sterol-regulatory element binding protein activation and hepatic lipid accumulation.

    PubMed

    Zhang, Zhi-Hui; Liu, Xiao-Qian; Zhang, Cheng; He, Wei; Wang, Hua; Chen, Yuan-Hua; Liu, Xiao-Jing; Chen, Xi; Xu, De-Xiang

    2016-01-01

    Previous studies demonstrated that acute alcohol intoxication caused hepatic lipid accumulation. The present study showed that acute alcohol intoxication caused hepatic lipid accumulation in Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic sterol-regulatory element binding protein (SREBP)-1, a transcription factor regulating fatty acid and triglyceride (TG) synthesis, was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic Fas, Acc, Scd-1 and Dgat-2, the key genes for fatty acid and TG synthesis, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Additional experiment showed that hepatic MyD88 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic NF-κB was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Moreover, hepatic GSH content was reduced and hepatic MDA level was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic CYP2E1 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic p67phox and gp91phox, two NADPH oxidase subunits, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin-trapping agent, protected against alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. In conclusion, Tlr4-mutant mice are resistant to acute alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. PMID:27627966

  19. Tlr4-mutant mice are resistant to acute alcohol-induced sterol-regulatory element binding protein activation and hepatic lipid accumulation

    PubMed Central

    Zhang, Zhi-Hui; Liu, Xiao-Qian; Zhang, Cheng; He, Wei; Wang, Hua; Chen, Yuan-Hua; Liu, Xiao-Jing; Chen, Xi; Xu, De-Xiang

    2016-01-01

    Previous studies demonstrated that acute alcohol intoxication caused hepatic lipid accumulation. The present study showed that acute alcohol intoxication caused hepatic lipid accumulation in Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic sterol-regulatory element binding protein (SREBP)-1, a transcription factor regulating fatty acid and triglyceride (TG) synthesis, was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic Fas, Acc, Scd-1 and Dgat-2, the key genes for fatty acid and TG synthesis, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Additional experiment showed that hepatic MyD88 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic NF-κB was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Moreover, hepatic GSH content was reduced and hepatic MDA level was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic CYP2E1 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic p67phox and gp91phox, two NADPH oxidase subunits, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin-trapping agent, protected against alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. In conclusion, Tlr4-mutant mice are resistant to acute alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. PMID:27627966

  20. Scoring systems predict the prognosis of acute-on-chronic hepatitis B liver failure: an evidence-based review.

    PubMed

    Wu, Fa-Ling; Shi, Ke-Qing; Chen, Yong-Ping; Braddock, Martin; Zou, Hai; Zheng, Ming-Hua

    2014-08-01

    Acute-on-chronic hepatitis B liver failure is a devastating condition that is associated with mortality rates of over 50% and is consequent to acute exacerbation of chronic hepatitis B in patients with previously diagnosed or undiagnosed chronic liver disease. Liver transplantation is the definitive treatment to lower mortality rate, but there is a great imbalance between donation and potential recipients. An early and accurate prognostic system based on the integration of laboratory indicators, clinical events and some mathematic logistic equations is needed to optimize treatment for patients. As parts of the scoring systems, the MELD was the most common and the donor-MELD was the most innovative for patients on the waiting list for liver transplantation. This review aims to highlight the various features and prognostic capabilities of these scoring systems. PMID:24762209

  1. Hepatitis

    MedlinePlus

    ... fever, fatigue, lack of appetite, nausea, jaundice and dark urine.These symptoms can last up to five ... fever, fatigue, lack of appetite, nausea, jaundice and dark urine. Acute symptoms can last several months, during ...

  2. [Acute hemolytic crisis followed by fulminant hepatic failure with fatal outcome, as a first clinical manifestation of Wilson's disease].

    PubMed

    de Andrade Júnior, D R; Fujita Neto, F G; Vieira, G S; Tibério, I F; Warth, M P; Calich, I

    1994-01-01

    We describe in this work a clinical case of a female patient aged 21 years, bearer of Wilson's disease, a first clinical manifestation of the disease occurred as an acute hemolytic crisis followed by fulminant hepatic failure evolving to death after 26 days' internment. The definitive diagnosis was obtained only as a quantitative measurement of hepatic copper from the necropsy material. The search for Kayser-Fleischer ring was negative and the serum ceruloplasmin level was 9 mg/dl (15 to 60). No involvement of the central nervous system was noted from the pathologic analysis. The patient presented two Coombs negative hemolytic crises during the internment; the first on being admitted to hospital and the second after a transjugular hepatic biopsy carried out on the 16th day after internment. The last hemolytic crisis was accompanied by an increase of serum and urinary copper levels. On this occasion the patient evolved to a progressive hepatic failure with severe jaundice and hepatic encephalopathy. We are presenting the clinical-biochemical evolution of the patient and we shall discuss the existent hypotheses to the pathophysiology of this rare form for manifestation of the Wilson's disease as well the diagnostic difficulties.

  3. Occult infection with HBV intergenotypic A2/G recombinant following acute hepatitis B caused by an HBV/A2 isolate.

    PubMed

    de Barros, José Júnior França; Peres, Luciana Rego; de Sousa, Paulo Sérgio Fonseca; do Amaral Mello, Francisco Campello; de Araujo, Natalia Motta; de Andrade Gomes, Selma; Niel, Christian; Lewis-Ximenez, Lia Laura

    2015-06-01

    Viral and host factors leading to occult hepatitis B virus (HBV) infection (OBI) are not fully understood. Whether HBV genotype may influence the occurrence and course of OBIs is unknown. Here, we describe the case of a patient infected with HBV genotype A2 who developed symptomatic acute hepatitis and did not seroconvert after loss of HBsAg and HBeAg. The acute phase of hepatitis B was followed by a period of more than 2 years during which the DNA of an intergenotypic HBV/A2/G recombinant was intermittently detected in serum.

  4. Analysis of the Molecular Evolution of Hepatitis B Virus Genotypes in Symptomatic Acute Infections in Argentina

    PubMed Central

    Rodrigo, María Belén; Mojsiejczuk, Laura Noelia; Torres, Carolina; Sevic, Ina; González López Ledesma, María Mora; Perez, Paula Soledad; Bouzas, María Belén; Galdame, Omar; Marciano, Sebastián; Fainboim, Hugo; Flichman, Diego Martín; Campos, Rodolfo Héctor

    2016-01-01

    Hepatitis B virus (HBV) is a globally distributed human pathogen that leads to both self-limited and chronic infections. At least eight genotypes (A-H) with distinct geographical allocations and phylodynamic behaviors have been described. They differ substantially in many virological and probably some clinical parameters. The aim of this study was to analyze full-length HBV genome sequences from individuals with symptomatic acute HBV infections using phylogenetic and coalescent methods. The phylogenetic analysis resulted in the following subgenotype distribution: F1b (52.7%), A2 (18.2%), F4 (18.2%) and A1, B2, D3 and F2a 1.8% each. These results contrast with those previously reported from chronic infections, where subgenotypes F1b, F4, A2 and genotype D were evenly distributed. This differential distribution might be related to recent internal migrations and/or intrinsic biological features of each viral genotype that could impact on the probability of transmission. The coalescence analysis showed that after a diversification process started in the 80s, the current sequences of subgenotype F1b were grouped in at least four highly supported lineages, whereas subgenotype F4 revealed a more limited diversification pattern with most lineages without offspring in the present. In addition, the genetic characterization of the studied sequences showed that only two of them presented mutations of clinical relevance at S codifyng region and none at the polymerase catalytic domains. Finally, since the acute infections could be an expression of the genotypes currently being transmitted to new hosts, the predominance of subgenotype F1b might have epidemiological, as well as, clinical relevance due to its potential adverse disease outcome among the chronic cases. PMID:27433800

  5. Serial measurement of Doppler hepatic hemodynamic parameters for the diagnosis of acute rejection after live donor liver transplantation.

    PubMed

    Sugimoto, Hiroyuki; Kato, Koichi; Hirota, Masashi; Takeda, Shin; Kamei, Hideya; Nakamura, Taro; Kiuchi, Tetsuya; Nakao, Akimasa

    2009-09-01

    To elucidate the role of Doppler hepatic hemodynamic parameters as surrogate markers of acute rejection (AR) after live donor liver transplantation (LDLT), serial Doppler measurements were prospectively performed during the first 2 weeks after LDLT to compare the longitudinal hepatic hemodynamic changes between patients with histologically proven AR and patients without histologically proven AR. Forty-six patients that had undergone adult-to-adult LDLT using a right lobe graft were enrolled in this study. The portal venous maximum velocity (PVV; cm/second), portal venous flow volume, hepatic arterial peak systolic velocity, hepatic arterial pulsatility index, hepatic venous maximum velocity, hepatic venous pulsatility index, and splenic arterial pulsatility index were measured. Fourteen patients were diagnosed by biopsy to have clinically relevant AR. Markedly increased PVV was seen soon after surgery and gradually decreased in both patients with clinically relevant AR and patients without clinically relevant AR. This serial change of decreasing PVV was significantly greater in patients with clinically relevant AR (P < 0.0001). After postoperative day 6, the PVV in patients with clinically relevant AR was significantly lower than that in patients without clinically relevant AR (PVV on postoperative day 6: 35.6 +/- 21.3 versus 58.3 +/- 27.1 cm/second, respectively, P = 0.0080). A PVV cutoff value of 20.2 cm/second demonstrated the best accuracy for predicting clinically relevant AR. The sensitivity and specificity for predicting clinically relevant AR were 92.9% and 87.1%, respectively. The area under the curve was 0.94. In conclusion, serial Doppler measurement of hepatic parameters in LDLT is useful for the diagnosis of clinically relevant AR. Clinically relevant AR should therefore be suspected when a marked unexpected decrease in the PVV is observed.

  6. Immunosuppression status of liver transplant recipients with hepatitis C affects biopsy-proven acute rejection

    PubMed Central

    Kim, Jong Man; Lee, Kwang-Woong; Song, Gi-Won; Jung, Bo-Hyun; Lee, Hae Won; Yi, Nam-Joon; Kwon, ChoonHyuck David; Hwang, Shin; Suh, Kyung-Suk; Joh, Jae-Won; Lee, Suk-Koo; Lee, Sung-Gyu

    2016-01-01

    Background/Aims The relationship between patient survival and biopsy-proven acute rejection (BPAR) in liver transplant recipients with hepatitis C remains unclear. The aims of this study were to compare the characteristics of patients with and without BPAR and to identify risk factors for BPAR. Methods We retrospectively reviewed the records of 169 HCV-RNA-positive patients who underwent LT at three centers. Results BPAR occurred in 39 (23.1%) of the HCV-RNA-positive recipients after LT. The 1-, 3-, and 5-year survival rates were 92.1%, 90.3%, and 88.5%, respectively, in patients without BPAR, and 75.7%, 63.4%, and 58.9% in patients with BPAR (P<0.001). Multivariate analyses showed that BPAR was associated with the non-use of basiliximab and tacrolimus and the use of cyclosporin in LT recipients with HCV RNA-positive. Conclusion The results of the present study suggest that the immunosuppression status of HCV-RNA-positive LT recipients should be carefully determined in order to prevent BPAR and to improve patient survival. PMID:27729628

  7. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

    PubMed

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-10-28

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.

  8. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: An Italian position statement

    PubMed Central

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-01-01

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  9. Giant Inflammatory Fibroid Polyp of the Hepatic Flexure of Colon Presenting with an Acute Abdomen

    PubMed Central

    Shrestha, Pradita

    2016-01-01

    Background. Inflammatory Fibroid Polyp (IFP) of the colon is an exceedingly rare condition. Since 1952 till now only 32 cases have been reported worldwide of which only 5 were giant (>4 cm) polyps mostly found in the caecum (15 cases) with only 3 in the descending colon. Case Presentation. A 36-year-old female with no previous illness presented to the emergency unit with an acute onset pain over the right hypochondrium for 3 days associated with intermittent fever and anorexia. As she had evidence of localized peritonitis she underwent a diagnostic laparoscopy and subsequently an exploratory laparotomy. A mass measuring 8 × 7 × 5 cm arising from the hepatic flexure of colon was noted. Right hemicolectomy with ileotransverse anastomosis was performed. The mass was subsequently reported to be IFP. Conclusion. IFP is a very rare condition with clinical presentation depending upon its size and location. Definitive diagnosis is possible with histopathological examination of tissue aided by immunohistochemical studies. Surgical resection has been the most common method of treatment especially for large and giant colonic IFPs owing to challenges in terms of diagnosis and technical difficulties associated with endoscopic methods. PMID:27781129

  10. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

    PubMed

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-10-28

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  11. Incorporation of haemoglobin haem into the rat hepatic haemoproteins tryptophan pyrrolase and cytochrome P-450

    SciTech Connect

    Wyman, J.F.; Gollan, J.L.; Settle, W.; Farrell, G.C.; Correia, M.A.

    1986-01-01

    After its administration to intact rats, haemoglobin haem was incorporated into hepatic tryptophan pyrrolase as shown by the marked increase in functional constitution of this enzyme. Incorporation of haemoglobin haem into cytochrome P-450 was demonstrated in intact rats and in the isolated rat liver perfused with haemoglogin-free medium. In both systems, haemoglobin haem restored cytochrome P-450 content and its dependent mixed-function-oxidase activity after substrate-induced destruction of the cytochrome P-450 haem moiety. Further confirmation that heamoglobin haem could be incorporated prosthetically into cytochrome P-450 was achieved by administration of (tritium) haemoglobin to rats and subsequent isolation and characterization of radiolabelled substrate-alkylated products of cytochrome P-450 haem. Findings indicate that, although hepatic uptake of parenteral haemoglobin is slower than that of haem, it appears to serve as an effective haem donor to the intrahepatic free haem pool. Thus parenteral haemoglobin may warrant consideration as a therapeutic alternative to haem in the acute hepatic porphyrias.

  12. Moderate (2%, v/v) Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice

    PubMed Central

    Deshpande, Krutika T.; Liu, Shinlan; McCracken, Jennifer M.; Jiang, Lu; Gaw, Ta Ehpaw; Kaydo, Lindsey N.; Richard, Zachary C.; O’Neil, Maura F.; Pritchard, Michele T.

    2016-01-01

    Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl4-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl4 exposure. Mice were fed moderate ethanol (2% v/v) for two days and then were exposed to CCl4 and euthanized 24–96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl4-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl4 exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl4-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl4. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure. PMID:26751492

  13. Moderate (2%, v/v) Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice.

    PubMed

    Deshpande, Krutika T; Liu, Shinlan; McCracken, Jennifer M; Jiang, Lu; Gaw, Ta Ehpaw; Kaydo, Lindsey N; Richard, Zachary C; O'Neil, Maura F; Pritchard, Michele T

    2016-01-06

    Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl₄-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl₄ exposure. Mice were fed moderate ethanol (2% v/v) for two days and then were exposed to CCl₄ and euthanized 24-96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl₄-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl₄ exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl₄-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl₄. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure.

  14. Cerebral Venous Thrombosis as an Extrahepatic Manifestation of Acute Anicteric Hepatitis A Infection

    PubMed Central

    Zis, Panagiotis; Kontogeorgi, Elli; Karakalos, Dimitrios; Pavlopoulou, Despoina; Sevastianos, Vassilios A.

    2012-01-01

    Among the many infective causes of cerebral venous thrombosis (CVT), viral hepatitis has been regarded as a rare associated condition. We report the case of a 31-year-old woman presenting with CVT associated with hepatitis A virus (HAV) infection, outlining probable pathogenic mechanisms. We suggest that hepatitis A serological markers should be routinely included in the investigation of cerebral venous thrombosis of unknown etiology, in nonvaccinated patients with risk factors of a recent HAV exposure. PMID:22934203

  15. Serum Metabolomic Profiling in Acute Alcoholic Hepatitis Identifies Multiple Dysregulated Pathways

    PubMed Central

    Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N.; Cooper, Sara; Malik, Shahid; Behari, Jaideep

    2014-01-01

    Background and Objectives While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. Methods This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Results Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Conclusion Severe AAH is

  16. Acute Hepatitis C Virus Infection Induces Consistent Changes in Circulating MicroRNAs That Are Associated with Nonlytic Hepatocyte Release

    PubMed Central

    El-Diwany, Ramy; Wasilewski, Lisa N.; Witwer, Kenneth W.; Bailey, Justin R.; Page, Kimberly; Ray, Stuart C.; Cox, Andrea L.; Thomas, David L.

    2015-01-01

    ABSTRACT Plasma microRNAs (miRNAs) change in abundance in response to disease and have been associated with liver fibrosis severity in chronic hepatitis C virus (HCV) infection. However, the early dynamics of miRNA release during acute HCV infection are poorly understood. In addition, circulating miRNA signatures have been difficult to reproduce among separate populations. We studied plasma miRNA abundance during acute HCV infection to identify an miRNA signature of early infection. We measured 754 plasma miRNAs by quantitative PCR array in a discovery cohort of 22 individuals before and during acute HCV infection and after spontaneous resolution (n = 11) or persistence (n = 11) to identify a plasma miRNA signature. The discovery cohort derived from the Baltimore Before and After Acute Study of Hepatitis. During acute HCV infection, increases in miR-122 (P < 0.01) and miR-885-5p (Pcorrected < 0.05) and a decrease in miR-494 (Pcorrected < 0.05) were observed at the earliest time points after virus detection. Changes in miR-122 and miR-885-5p were sustained in persistent (P < 0.001) but not resolved HCV infection. The circulating miRNA signature of acute HCV infection was confirmed in a separate validation cohort that was derived from the San Francisco-based You Find Out (UFO) Study (n = 28). As further confirmation, cellular changes of signature miRNAs were examined in a tissue culture model of HCV in hepatoma cells: HCV infection induced extracellular release of miR-122 and miR-885-5p despite unperturbed intracellular levels. In contrast, miR-494 accumulated intracellularly (P < 0.05). Collectively, these data are inconsistent with necrolytic release of hepatocyte miRNAs into the plasma during acute HCV infection of humans. IMPORTANCE MicroRNAs are small noncoding RNA molecules that emerging research shows can transmit regulatory signals between cells in health and disease. HCV infects 2% of humans worldwide, and chronic HCV infection is a major cause of severe

  17. Pre-acute hepadnaviral infection is associated with activation-induced apoptotic death of lymphocytes in the woodchuck (Marmota monax) model of hepatitis B.

    PubMed

    Gujar, Shashi A; Jenkins, Adam K M; Macparland, Sonya A; Michalak, Tomasz I

    2010-09-01

    Woodchucks (Marmota monax) infected with woodchuck hepatitis virus (WHV) represent a highly valuable immunopathogenic model of hepatitis B virus (HBV) infection. Both WHV and HBV are noncytopathic hepadnaviruses which induce a strong but delayed virus-specific cellular immune response believed to be a cause of hepatitis. The reason behind this postponement is not well understood and its dissection in the woodchuck model has been hampered by the lack of appropriate research tools. In this study, we applied an assay for the simultaneous detection of cell apoptosis and proliferation to determine the fate of T lymphocytes after WHV infection leading to acute hepatitis. The results revealed that pre-acute WHV infection is associated with the significantly heightened susceptibility of T lymphocytes to activation-induced apoptotic death. This suggests that T lymphocyte function is compromised very early in the course of hepadnaviral infection and this may directly contribute to the postponement of virus-specific T cell response.

  18. Acute, fatal Sarcocystis calchasi-associated hepatitis in Roller pigeons (Columba livia f. dom.) at Philadelphia Zoo.

    PubMed

    Trupkiewicz, J G; Calero-Bernal, R; Verma, S K; Mowery, J; Davison, S; Habecker, P; Georoff, T A; Ialeggio, D M; Dubey, J P

    2016-01-30

    Four Roller pigeons (Columba livia f. dom.) at the Philadelphia Zoo died suddenly. Necropsy examination revealed macroscopic hepatitis. Microscopically, the predominant lesions were in liver, characterized with necrosis and mixed cell inflammatory response. Sarcocystis calchasi-like schizonts and free merozoites were identified in liver. Transmission electron microscopy confirmed that schizonts were in hepatocytes. A few schizonts were in spleen. PCR using S. calchasi-specific primers confirmed the diagnosis. Neither lesions nor protozoa were found in brain and muscles. This is the first report of acute visceral S. calchasi-associated sarcocystosis in naturally infected avian hosts.

  19. Capacity of a natural strain of woodchuck hepatitis virus, WHVNY, to induce acute infection in naive adult woodchucks.

    PubMed

    Freitas, Natalia; Lukash, Tetyana; Dudek, Megan; Litwin, Sam; Menne, Stephan; Gudima, Severin O

    2015-07-01

    Woodchuck hepatitis virus (WHV) is often used as surrogate to study mechanism of HBV infection. Currently, most infections are conducted using strains WHV7 or WHV8 that have very high sequence identity. This study focused on natural strain WHVNY that is more genetically distant from WHV7. Three naive adult woodchucks inoculated with WHVNY developed productive acute infection with long lasting viremia. However, only one of two woodchucks infected with WHV7 at the same multiplicity demonstrated productive liver infection. Quantification of intracellular WHV RNA and DNA replication intermediates; percentages of core antigen-positive hepatocytes; and serum relaxed circular DNA showed that strains WHVNY and WHV7 displayed comparable replication levels and capacities to induce acute infection in naive adult woodchucks. Strain WHVNY was therefore validated as valuable reagent to analyze the mechanism of hepadnavirus infection, especially in co- and super-infection settings, which required discrimination between two related virus genomes replicating in the same liver. PMID:25979221

  20. Circulating plasmacytoid dendritic cells in acutely infected patients with hepatitis C virus genotype 4 are normal in number and phenotype.

    PubMed

    Mansour, Hala; Laird, Melissa E; Saleh, Rasha; Casrouge, Armanda; Eldin, Noha Sharaf; El Kafrawy, Sherif; Hamdy, Maha; Decalf, Jérémie; Rosenberg, Brad R; Fontanet, Arnaud; Abdel-Hamid, Mohammed; Mohamed, Mostafa K; Albert, Matthew L; Rafik, Mona

    2010-12-01

    The incidence of hepatitis C virus (HCV) genotype 4 infection in Egypt provides a unique opportunity to study the innate immune response to symptomatic acute HCV infection. We investigated whether plasmacytoid dendritic cells (pDCs) are activated as a result of HCV infection. We demonstrate that, even during symptomatic acute infection, circulating pDCs maintained a similar precursor frequency and resting phenotype, compared with pDCs in healthy individuals. Moreover, stimulation with a Toll-like receptor 9 agonist resulted in an intact inflammatory response. These data support the growing consensus that pDCs are not directly activated by HCV and therefore are viable targets for immunotherapy throughout HCV infection.

  1. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient

    PubMed Central

    Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine

    2016-01-01

    Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units. PMID:27800206

  2. Hepatic and Nephric NRF2 Pathway Up-Regulation, an Early Antioxidant Response, in Acute Arsenic-Exposed Mice

    PubMed Central

    Li, Jinlong; Duan, Xiaoxu; Dong, Dandan; Zhang, Yang; Li, Wei; Zhao, Lu; Nie, Huifang; Sun, Guifan; Li, Bing

    2015-01-01

    Inorganic arsenic (iAs), a proven human carcinogen, damages biological systems through multiple mechanisms, one of them being reactive oxygen species (ROS) production. NRF2 is a redox-sensitive transcription factor that positively regulates the genes of encoding antioxidant and detoxification enzymes to neutralize ROS. Although NRF2 pathway activation by iAs has been reported in various cell types, however, the experimental data in vivo are very limited and not fully elucidated in humans. The present investigation aimed to explore the hepatic and nephric NRF2 pathway upregulation in acute arsenic-exposed mice in vivo. Our results showed 10 mg/kg NaAsO2 elevated the NRF2 protein and increased the transcription of Nrf2 mRNA, as well as up-regulated NRF2 downstream targets HO-1, GST and GCLC time- and dose-dependently both in the liver and kidney. Acute NaAsO2 exposure also resulted in obvious imbalance of oxidative redox status represented by the increase of GSH and MDA, and the decrease of T-AOC. The present investigation reveals that hepatic and nephric NRF2 pathway expression is an early antioxidant defensive response upon iAs exposure. A better knowledge about the NRF2 pathway involvment in the cellular response against arsenic could help improve the strategies for reducing the cellular toxicity related to this metalloid. PMID:26473898

  3. Protective Effect of Baccharis trimera Extract on Acute Hepatic Injury in a Model of Inflammation Induced by Acetaminophen

    PubMed Central

    Pádua, Bruno da Cruz; Rossoni Júnior, Joamyr Victor; de Brito Magalhães, Cíntia Lopes; Chaves, Míriam Martins; Silva, Marcelo Eustáquio; Pedrosa, Maria Lucia; de Souza, Gustavo Henrique Bianco; Brandão, Geraldo Célio; Rodrigues, Ivanildes Vasconcelos; Lima, Wanderson Geraldo; Costa, Daniela Caldeira

    2014-01-01

    Background. Acetaminophen (APAP) is a commonly used analgesic and antipyretic. When administered in high doses, APAP is a clinical problem in the US and Europe, often resulting in severe liver injury and potentially acute liver failure. Studies have demonstrated that antioxidants and anti-inflammatory agents effectively protect against the acute hepatotoxicity induced by APAP overdose. Methods. The present study attempted to investigate the protective effect of B. trimera against APAP-induced hepatic damage in rats. The liver-function markers ALT and AST, biomarkers of oxidative stress, antioxidant parameters, and histopathological changes were examined. Results. The pretreatment with B. trimera attenuated serum activities of ALT and AST that were enhanced by administration of APAP. Furthermore, pretreatment with the extract decreases the activity of the enzyme SOD and increases the activity of catalase and the concentration of total glutathione. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by APAP. Conclusions. The hepatoprotective action of B. trimera extract may rely on its effect on reducing the oxidative stress caused by APAP-induced hepatic damage in a rat model. General Significance. These results make the extract of B. trimera a potential candidate drug capable of protecting the liver against damage caused by APAP overdose. PMID:25435714

  4. Late onset post-transfusion hepatitis E developing during chemotherapy for acute promyelocytic leukemia.

    PubMed

    Fuse, Kyoko; Matsuyama, Yuichi; Moriyama, Masato; Miyakoshi, Shukuko; Shibasaki, Yasuhiko; Takizawa, Jun; Furukawa, Tatsuo; Fuse, Ichiro; Matsumura, Hiro; Uchida, Shigeharu; Takahashi, Yoshifumi; Kamimura, Kenya; Abe, Hiroyuki; Suda, Takeshi; Aoyagi, Yutaka; Sone, Hirohito; Masuko, Masayoshi

    2015-01-01

    We herein report the case of a leukemia patient who developed hepatitis E seven months after undergoing a transfusion with contaminated blood products. The latency period in this case was significantly longer than that of typical hepatitis E. Recently, chronic infection with hepatitis E virus (HEV) genotype 3 has been reported in immunocompromised patients. There is a possibility that our patient was unable to eliminate the virus due to immunosuppression following chemotherapy and the administration of steroids. The prevalence of HEV in healthy Japanese individuals is relatively high and constitutes a critical source of infection via transfusion. Hepatitis E is an important post-transfusion infection, and immunocompromised patients may exhibit a long latency period before developing the disease.

  5. Protective Effects of Dracocephalum heterophyllum in ConA-Induced Acute Hepatitis

    PubMed Central

    Wang, Qilan; Lu, Xiaohua; Shi, Qiangqiang; Zou, Junhui

    2016-01-01

    Dracocephalum heterophyllum (DH) is a Chinese herbal medicine used in treating hepatitis. However, the protective effects and pharmacological mechanisms of DH in hepatitis are unknown. In this study, we found that pretreatment with DH extract significantly ameliorated liver injury and suppressed the production of inflammatory cytokines, including tumor necrosis factor (TNF-α) and interferon-γ (IFN-γ) in Concanavalin A- (ConA-) induced hepatitis (CIH). DH recruited more CD11b+ Gr1+ myeloid-derived suppressor cells (MDSCs) to the liver and suppressed infiltration of macrophages (Kupffer cells) in the liver. The present work explores DH as an effective hepatoprotective medicine to inhibit inflammation and liver injury caused by hepatitis. PMID:27524863

  6. CHARACTERISTICS AND TREATMENT OUTCOMES AMONGST HIV POSITIVE INDIVIDUALS WITHIN THE AUSTRALIAN TRIAL IN ACUTE HEPATITIS C (ATAHC)

    PubMed Central

    Matthews, G; Hellard, M; Haber, P; Yeung, B; Marks, P; Baker, D; McCaughan, G; Sasadeusz, J; White, P; Rawlinson, W; Lloyd, A; Kaldor, J; Dore, GJ

    2010-01-01

    Background The Australian Trial in Acute Hepatitis C (ATAHC) is an NIH funded prospective cohort study of natural history and treatment efficacy in individuals with recently acquired hepatitis C. Enrolment is open to both HIV positive and HIV negative individuals. The aim of this paper was to evaluate characteristics and virological outcomes within HIV positive individuals enrolled in ATAHC Methods Eligibility criteria include first anti-HCV antibody positive within 6 months and either clinical hepatitis C within the past 12 months or documented anti-HCV seroconversion within the past 24 months. Results Of the initial 103 subjects enrolled 27 (26%) were HIV positive. HIV positive subjects were more likely to be older, have genotype 1 infection and high HCV RNA at baseline than HCV monoinfected subjects. Sexual acquisition accounted for the majority (56%) of HCV infections in HIV positive subjects compared to only 8% of HCV monoinfected subjects. Median duration from estimated HCV infection to treatment was 30 weeks. Treatment with 24 weeks of Pegylated interferon and ribavirin resulted in rates of HCV RNA undetectability of 95%, 90% and 80% at weeks 12, 24 and 48 respectively. Week 4 undetectability was achieved in 44% of subjects and gave positive and negative predictive values for SVR of 100% and 33% respectively. Conclusions Significant differences are demonstrated between HIV positive and HIV negative individuals enrolled into ATAHC. Treatment responses in HIV positive individuals with both acute and early chronic infection are encouraging and support regular HCV screening of high risk individuals and early treatment for recently acquired HCV infection. PMID:19191653

  7. Treatment of severe, nonfulminant acute hepatitis B with lamivudine vs placebo: a prospective randomized double-blinded multicentre trial.

    PubMed

    Wiegand, J; Wedemeyer, H; Franke, A; Rößler, S; Zeuzem, S; Teuber, G; Wächtler, M; Römmele, U; Ruf, B; Spengler, U; Trautwein, C; Bock, C T; Fiedler, G M; Thiery, J; Manns, M P; Brosteanu, O; Tillmann, H L

    2014-10-01

    Acute hepatitis B virus (aHBV) infection can lead to fulminant liver failure, which likely is prevented by early lamivudine therapy. Even nonfulminant but severe acute hepatitis B can lead to significant morbidity and impaired quality of life. Therefore, lamivudine was evaluated in patients with severe aHBV in a placebo-controlled trial. Patients with severe aHBV infection (ALT >10× ULN, bilirubin >85 μm, prothrombin time >50%) were prospectively treated with lamivudine 100 mg/day or with placebo within 8 days after the diagnosis. The primary end point was time to bilirubin <34.2 μm. Secondary end points were time to clear HBsAg and HBV-DNA, development of anti-HBs and normalization of ALT. Eighteen cases were randomized to lamivudine, 17 to placebo. 94% of patients were hospitalized. No individual progressed to hepatic failure; all but one patient achieved the primary end point. Due to smaller than expected patient numbers, all study end points did not become statistically significant between treatment arms. Median time end points [in days] were bilirubin <34.2 μm (26.5 vs 32), ALT normalization (35 vs 48) and HBsAg clearance (48 vs 67) referring to earlier recovery under lamivudine, in contrast to loss of HBV-DNA (62 vs 54) and development of anti-HBs (119 vs 109). In all but two patients (one in every group), HBsAg clearance was reached in the study. Adverse events occurred more frequently during lamivudine therapy, but did not reach statistical significance. Lamivudine may ameliorate severe aHBV infection, but limited patient numbers prevented definite conclusions.

  8. Endothelial cells are damaged by autophagic induction before hepatocytes in Con A-induced acute hepatitis.

    PubMed

    Yang, Ming-Chen; Chang, Chih-Peng; Lei, Huan-Yao

    2010-08-01

    We have reported both T-cell-dependent and -independent hepatitis in immunocompetent and immunodeficiency mice, respectively, after intravenous injection of Con A in mice. The mode of hepatocyte cell death is different: autophagy for T-cell-independent hepatitis in contrast to apoptosis for T-cell-dependent one. In this study, we further demonstrate that liver blood vessels are the first target in both modes. The infused Con A bond to the hepatic vascular endothelial cells and cause its damage with autophagy. Before the elevation of the serum alanine aminotransferase at 6 h post-injection, the plasma leakage and hemorrhage occur at 1-3 h without inflammation. Con A induces autophagy of endothelial cells and hemorrhage that is enhanced by IFN-gamma. Using the endothelial cell line HMEC-1, a dose- and time-dependent cell death with autophagic LC3-II (microtubule-associated protein light chain 3) conversion was induced by Con A and was enhanced by IFN-gamma. In conclusion, Con A induced autophagy on hepatic endothelial cells; the damage of liver blood vessel occurs before the induction of T-cell-dependent hepatitis via apoptosis or T-cell-independent hepatitis via autophagy.

  9. Protect Yourself from Hepatitis

    MedlinePlus

    ... develop yellowish eyes and skin. All the hepatitis viruses can cause acute, or short-term, hepatitis. Some can also cause chronic hepatitis, in which the infection lasts a long time, sometimes for your whole life. Chronic hepatitis can eventually lead to scarring of ...

  10. Association of Proton Pump Inhibitor Therapy with Hepatic Encephalopathy in Hepatitis B Virus-related Acute-on-Chronic Liver Failure

    PubMed Central

    Lin, Zhao-Ni; Zuo, Yong-Qing; Hu, Peng

    2014-01-01

    Background: Hepatic encephalopathy (HE) is an important neuropsychiatry complication of acute-on-chronic liver failure (ACLF). PPI therapy may increase the intestinal bacterial overgrowth and infections. Objectives: The aim of this study was to assess whether PPI use in ACLF is associated with HE. Patients and Methods: A retrospective case-control study was performed. Fifty five admitted patients with hepatitis B virus (HBV)-related ACLF complicated by Stage II-IV HE developed after admission between January 2008 and December 2012 were matched (by sex, age, and MELD score) with comparable HBV-related ACLF patients (n = 110) who did not develop this complication during hospitalization. We excluded combined HE upon admission and other neurological disorders in patients with ACLF. Univariate and multivariate analyses of 30 variables (laboratory examination, predisposition, treatment, etc.) before the occurrence of HE were carried out to identify the factors predictive of HE. Results: In univariate analysis, patients with HE in ACLF had a significantly higher rate of PPI use (89.1%) compared with non-HE (63.6%, P = 0.001). In addition, clinical and standard laboratory variables were significantly different between the two groups regarding the infection rate, hyponatremia, alpha-fetoprotein (AFP), Arginine Hydrochloride use and Lactulose use. Logistic regression analysis was used to examine the combined effects of the variables with HE as the outcome. HE in ACLF was associated with hyponatremia (odds ratio (OR) = 6. 318, 95% confidence interval (CI) = 2. 803-14.241; P = 0. 000), PPI use was independently associated with HE (OR = 4. 392, CI = 1. 604-12.031; P = 0. 004), and lactulose use was protective (OR = 0. 294, CI = 0. 136-0.675; P = 0. 003). Conclusions: The occurrence of HE is associated with hyponatremia and PPI use in patients with ACLF. PMID:24748895

  11. Injecting risk behaviours following treatment for hepatitis C virus infection among people who inject drugs: the Australian Trial in Acute Hepatitis C

    PubMed Central

    Alavi, Maryam; Spelman, Tim; Matthews, Gail V.; Haber, Paul S.; Day, Carolyn; van Beek, Ingrid; Walsh, Nick; Yeung, Barbara; Bruneau, Julie; Petoumenos, Kathy; Dolan, Kate; Kaldor, John M.; Dore, Gregory J; Hellard, Margaret; Grebely, Jason

    2015-01-01

    Background A barrier to hepatitis C virus (HCV) treatment among people who inject drugs (PWID) has been a concern that interferon-based HCV treatment may increase injecting risk behaviours. This study evaluated recent (past month) injecting risk behaviours during follow-up among PWID that did and did not receive HCV treatment. Methods The Australian Trial in Acute Hepatitis C (ATAHC) was a prospective study of natural history and treatment of recent HCV infection. Analyses were performed using generalized estimating equations. Results Among 124 participants with a history of injecting drug use (median age 32 years), 69% were male, and 68% were treated for HCV infection. HCV treatment was not associated with an increase in recent injecting drug use [adjusted odds ratio (aOR) 1.06, 95% CI 0.93, 1.21] or recent used needle and syringe borrowing during follow-up (aOR 0.99, 95% CI 0.89, 1.08). HCV treatment was associated with a decrease in recent ancillary injecting equipment sharing during follow-up (aOR 0.85, 95% CI 0.74, 0.99). Further, among treated participants who remained in follow-up (n=24), ancillary injecting equipment sharing significantly decreased from 54% at enrolment to 17% during follow-up (P=0.012). Conclusions HCV treatment was not associated with drug use or used needle and syringe borrowing during follow-up, but was associated with decreased ancillary injecting equipment sharing during follow-up. Programs to enhance HCV assessment and treatment among PWID should be expanded, given that HCV treatment does not lead to increases in injecting risk behaviours and has previously been demonstrated to be safe and effective among PWID. PMID:26115881

  12. Gut microbiota are linked to increased susceptibility to hepatic steatosis in low aerobic capacity rats fed an acute high fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Poor aerobic fitness is linked to nonalcoholic fatty liver disease and increased all-cause mortality. We previously found that low capacity running (LCR) rats fed acute high fat diet (HFD; 45% kcal from fat) for 3 days resulted in positive energy balance and increased hepatic steatosis compared with...

  13. A unique presentation of acute liver failure from herpes simplex virus hepatitis.

    PubMed

    Gutierrez, C; Kebriaei, P; Turner, K A; Yemelyanova, A; Ariza-Heredia, E J; Foo, W C

    2016-08-01

    We present the case of a patient, with history of myelodysplastic syndrome and recent bone marrow transplant, who developed fulminant liver failure secondary to herpes simplex virus (HSV) hepatitis. His presentation was unique, as findings of liver microabscesses on computed tomography scan have not been described previously in this patient population. Despite initial treatment with acyclovir, he continued to deteriorate, and later sensitivities found the HSV strain to be resistant to acyclovir. HSV hepatitis with secondary liver failure is rare and, without appropriate treatment, its mortality is >80%. Early suspicion and immediate therapy are the keys to improve patient survival. PMID:27222930

  14. Analysis of HBV genotype, drug resistant mutations, and pre-core/basal core promoter mutations in Korean patients with acute hepatitis B.

    PubMed

    Lee, Jong Ho; Hong, Sun Pyo; Jang, Eun Sun; Park, Sang Jong; Hwang, Seong Gyu; Kang, Sook-Kyoung; Jeong, Sook-Hyang

    2015-06-01

    Acute hepatitis B, caused by hepatitis B virus (HBV) strains with drug resistant mutations or pre-core/basal core promoter (PC/BCP) mutations, is a public health concern, because this infection is often associated with poor disease outcome or difficulty in therapeutic choice. The HBV genotype, the prevalence of drug resistant mutations, and PC/BCP mutations in Korean patients with acute hepatitis B were studied. From 2006 to 2008, 36 patients with acute hepatitis B were enrolled prospectively in four general hospitals. Among them, 20 showed detectable HBV DNA (median value was 4.8 log copies/mL). HBV genotyping and analysis of HBV mutations that conferred resistance against lamivudine, adefovir, or entecavir and of PC/BCP mutations were performed using highly sensitive restriction fragment mass polymorphism (RFMP) analysis. All 20 patients were infected with HBV genotype C, which causes almost all cases of chronic hepatitis B in Korea. No patient showed mutations that conferred resistance against lamivudine (L180M, M204V/I), adefovir (A181T, N236S), or entecavir (I169M, A184T/V, S202I/G, M250V/I/L). However, four patients had BCP mutations, and two had PC mutations. Platelet counts were significantly lower in the four patients with PC/BCP mutations compared to those with wild type. In this study, all acute hepatitis B patients had genotype C HBV strains with no drug resistant mutations. However, 20% showed PC/BCP mutations. This highlights the need for further study on the significance of PC/BCP mutations.

  15. The severity of hereditary porphyria is modulated by the porphyrin exporter and Lan antigen ABCB6

    PubMed Central

    Fukuda, Yu; Cheong, Pak Leng; Lynch, John; Brighton, Cheryl; Frase, Sharon; Kargas, Vasileios; Rampersaud, Evadnie; Wang, Yao; Sankaran, Vijay G.; Yu, Bing; Ney, Paul A.; Weiss, Mitchell J.; Vogel, Peter; Bond, Peter J.; Ford, Robert C.; Trent, Ronald J.; Schuetz, John D.

    2016-01-01

    Hereditary porphyrias are caused by mutations in genes that encode haem biosynthetic enzymes with resultant buildup of cytotoxic metabolic porphyrin intermediates. A long-standing open question is why the same causal porphyria mutations exhibit widely variable penetrance and expressivity in different individuals. Here we show that severely affected porphyria patients harbour variant alleles in the ABCB6 gene, also known as Lan, which encodes an ATP-binding cassette (ABC) transporter. Plasma membrane ABCB6 exports a variety of disease-related porphyrins. Functional studies show that most of these ABCB6 variants are expressed poorly and/or have impaired function. Accordingly, homozygous disruption of the Abcb6 gene in mice exacerbates porphyria phenotypes in the Fechm1Pas mouse model, as evidenced by increased porphyrin accumulation, and marked liver injury. Collectively, these studies support ABCB6 role as a genetic modifier of porphyria and suggest that porphyrin-inducing drugs may produce excessive toxicities in individuals with the rare Lan(−) blood type. PMID:27507172

  16. The severity of hereditary porphyria is modulated by the porphyrin exporter and Lan antigen ABCB6.

    PubMed

    Fukuda, Yu; Cheong, Pak Leng; Lynch, John; Brighton, Cheryl; Frase, Sharon; Kargas, Vasileios; Rampersaud, Evadnie; Wang, Yao; Sankaran, Vijay G; Yu, Bing; Ney, Paul A; Weiss, Mitchell J; Vogel, Peter; Bond, Peter J; Ford, Robert C; Trent, Ronald J; Schuetz, John D

    2016-08-10

    Hereditary porphyrias are caused by mutations in genes that encode haem biosynthetic enzymes with resultant buildup of cytotoxic metabolic porphyrin intermediates. A long-standing open question is why the same causal porphyria mutations exhibit widely variable penetrance and expressivity in different individuals. Here we show that severely affected porphyria patients harbour variant alleles in the ABCB6 gene, also known as Lan, which encodes an ATP-binding cassette (ABC) transporter. Plasma membrane ABCB6 exports a variety of disease-related porphyrins. Functional studies show that most of these ABCB6 variants are expressed poorly and/or have impaired function. Accordingly, homozygous disruption of the Abcb6 gene in mice exacerbates porphyria phenotypes in the Fech(m1Pas) mouse model, as evidenced by increased porphyrin accumulation, and marked liver injury. Collectively, these studies support ABCB6 role as a genetic modifier of porphyria and suggest that porphyrin-inducing drugs may produce excessive toxicities in individuals with the rare Lan(-) blood type.

  17. Intrinsic aerobic capacity impacts susceptibility to acute high-fat diet-induced hepatic steatosis

    PubMed Central

    Matthew Morris, E.; Jackman, Matthew R.; Johnson, Ginger C.; Liu, Tzu-Wen; Lopez, Jordan L.; Kearney, Monica L.; Fletcher, Justin A.; Meers, Grace M. E.; Koch, Lauren G.; Britton, Stephen L.; Scott Rector, R.; Ibdah, Jamal A.; MacLean, Paul S.

    2014-01-01

    Aerobic capacity/fitness significantly impacts susceptibility for fatty liver and diabetes, but the mechanisms remain unknown. Herein, we utilized rats selectively bred for high (HCR) and low (LCR) intrinsic aerobic capacity to examine the mechanisms by which aerobic capacity impacts metabolic vulnerability for fatty liver following a 3-day high-fat diet (HFD). Indirect calorimetry assessment of energy metabolism combined with radiolabeled dietary food was employed to examine systemic metabolism in combination with ex vivo measurements of hepatic lipid oxidation. The LCR, but not HCR, displayed increased hepatic lipid accumulation in response to the HFD despite both groups increasing energy intake. However, LCR rats had a greater increase in energy intake and demonstrated greater daily weight gain and percent body fat due to HFD compared with HCR. Additionally, total energy expenditure was higher in the larger LCR. However, controlling for the difference in body weight, the LCR has lower resting energy expenditure compared with HCR. Importantly, respiratory quotient was significantly higher during the HFD in the LCR compared with HCR, suggesting reduced whole body lipid utilization in the LCR. This was confirmed by the observed lower whole body dietary fatty acid oxidation in LCR compared with HCR. Furthermore, LCR liver homogenate and isolated mitochondria showed lower complete fatty acid oxidation compared with HCR. We conclude that rats bred for low intrinsic aerobic capacity show greater susceptibility for dietary-induced hepatic steatosis, which is associated with a lower energy expenditure and reduced whole body and hepatic mitochondrial lipid oxidation. PMID:24961240

  18. Acute hepatitis A in an elderly patient after care worker travel to high endemicity country.

    PubMed

    Aasheim, Erlend T; Seymour, Martin; Balogun, Koye; Ngui, Siew-Lin; Williams, Chris J; Shankar, Ananda Giri

    2013-11-01

    Hepatitis A virus (HAV) is considered one of the most important vaccine-preventable diseases in travelers. HAV spreads from person to person via the fecal-oral route and gives rise to an estimated 1.4 million cases worldwide each year. In developing countries with poor sanitary conditions people tend to be infected during childhood and have few symptoms, whereas in developed countries with good sanitary conditions fewer people develop immunity during childhood. This leads to susceptible populations of adults, who are also more prone to severe complications. Here we describe two confirmed cases of hepatitis A associated with a nursing home. The index case was a care worker who had recently traveled to a high-endemicity country, and the second case was a resident at the nursing home where the index case worked. Both cases had an identical genotype IIIA strain, consistent with a transmission event. Current policy does not include a requirement for hepatitis A vaccine in care workers who travel to high endemicity countries despite the fact that infected care workers can potentially spread the disease to elderly patients and other groups at risk of severe complications from HAV infection. We suggest that employers should consider hepatitis A vaccine upon employment; particularly in care workers who plan to visit areas where HAV is known to be endemic.

  19. Autoimmune hepatitis.

    PubMed

    Roberts, E A

    1995-01-01

    Autoimmune hepatitis can present as either acute or chronic disease in children. Clinical and laboratory features, including association with extrahepatic autoimmune syndromes and prompt response to immunosuppressive treatment, circulating autoantibodies and hypergammaglobulinemia, suggest an immune etiology. However, the disease mechanism remains uncertain. Different types of autoimmune hepatitis are defined on the basis of which autoantibodies are present: anti-smooth muscle (type 1), anti-liver/kidney microsomal (type 2), or anti-soluble liver antigen (type 3). Diseases which may be clinically similar to autoimmune hepatitis must be excluded before the diagnosis of autoimmune hepatitis is established: Wilson's disease, primary sclerosing cholangitis, chronic hepatitis B or C, and drug-induced liver disease are among the most important entities. Corticosteroids alone or with azathioprine constitute the usual treatment for autoimmune hepatitis. Although some children achieve a complete remission, or even recovery, and can stop immunosuppressive treatment, others required low-dose prednisone treatment indefinitely.

  20. Lack of variant specific CD8+ T-cell response against mutant and pre-existing variants leads to outgrowth of particular clones in acute hepatitis C

    PubMed Central

    2013-01-01

    Background CTL escape mutations have been described during acute hepatitis C in patients who developed chronic disease later on. Our aim was to investigate the mutual relationship between HCV specific CD8+ T cells and evolution of the viral sequence during early acute HCV infection. Results We sequenced multiple clones of NS3 1406 epitope in 4 HLA-A*02 patients with acute hepatitis C genotype 1b infection. Pentamers specific for the variants were used to monitor the corresponding CD8+ T cell response. We observed outgrowth of mutations, which induced only a weak and thus potentially insufficient CD8+ T cell response. In one patient we observed outgrowth of variant epitopes with similarities to a different genotype rather than de novo mutations most probably due to a lack of responsiveness to these likely pre-existing variants. We could show that in acute hepatitis C CTL escape mutations occur much earlier than demonstrated in previous studies. Conclusions The adaption of the virus to a new host is characterized by a high and rapid variability in epitopes under CD8+ T cell immune pressure. This adaption takes place during the very early phase of acute infection and strikingly some sequences were reduced below the limit of detection at some time points but were detected at high frequency again at later time points. Independent of the observed variability, HCV-specific CD8+ T cell responses decline and no adaption to different or new antigens during the course of infection could be detected. PMID:24073713

  1. FitzPatrick Lecture: King George III and the porphyria myth - causes, consequences and re-evaluation of his mental illness with computer diagnostics.

    PubMed

    Peters, Timothy

    2015-04-01

    Recent studies have shown that the claim that King George III suffered from acute porphyria is seriously at fault. This article explores some of the causes of this misdiagnosis and the consequences of the misleading claims, also reporting on the nature of the king's recurrent mental illness according to computer diagnostics. In addition, techniques of cognitive archaeology are used to investigate the nature of the king's final decade of mental illness, which resulted in the appointment of the Prince of Wales as Prince Regent. The results of this analysis confirm that the king suffered from bipolar disorder type I, with a final decade of dementia, due, in part, to the neurotoxicity of his recurrent episodes of acute mania.

  2. FitzPatrick Lecture: King George III and the porphyria myth - causes, consequences and re-evaluation of his mental illness with computer diagnostics.

    PubMed

    Peters, Timothy

    2015-04-01

    Recent studies have shown that the claim that King George III suffered from acute porphyria is seriously at fault. This article explores some of the causes of this misdiagnosis and the consequences of the misleading claims, also reporting on the nature of the king's recurrent mental illness according to computer diagnostics. In addition, techniques of cognitive archaeology are used to investigate the nature of the king's final decade of mental illness, which resulted in the appointment of the Prince of Wales as Prince Regent. The results of this analysis confirm that the king suffered from bipolar disorder type I, with a final decade of dementia, due, in part, to the neurotoxicity of his recurrent episodes of acute mania. PMID:25824070

  3. Acute hepatitis B caused by a vaccine-escape HBV strain in vaccinated subject: sequence analysis and therapeutic strategy.

    PubMed

    Luongo, Monica; Critelli, Rosina; Grottola, Antonella; Gitto, Stefano; Bernabucci, Veronica; Bevini, Mirco; Vecchi, Chiara; Montagnani, Giuliano; Villa, Erica

    2015-01-01

    HBV vaccine contains the 'a' determinant region, the major immune-target of antibodies (anti-HBs). Failure of immunization may be caused by vaccine-induced or spontaneous 'a' determinant surface gene mutants. Here, we evaluate the possible lack of protection by HBV vaccine, describing the case of an acute hepatitis B diagnosed in a 55-year-old Caucasian male unpaid blood donor, vaccinated against HBV. Sequencing data for preS-S region revealed multiple point mutations. Of all the substitutions found, Q129H, located in the "a" determinant region of HBsAg, can alter antigenicity, leading to mutants. This mutant may cause vaccine failure especially when associated with high viremia of infecting source.

  4. Acute Disseminated Encephalomyelitis following Vaccination against Hepatitis B in a Child: A Case Report and Literature Review.

    PubMed

    Yuan, Jun-Liang; Wang, Shuang-Kun; Guo, Xiao-Juan; Hu, Wen-Li

    2016-01-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system, which has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, and the Hog vaccine. Here, we presented a case of 12-year-old child who suffered from ADEM three weeks after hepatitis B vaccination. He was admitted to our hospital with symptoms of weakness of limbs, high fever, and alteration of consciousness. Some abnormalities were also found in CSF. Treatment with high-dose corticosteroids and intravenous immunoglobulin had significant effect, with marked improvement of the clinical symptoms and the results of CSF. The findings of MRI also detected some abnormal lesions located in both brain and spinal cord. The clinical features, the findings of CSF and MRI, and therapeutic effect may contribute to such diagnosis of ADEM. PMID:27478662

  5. Acute Disseminated Encephalomyelitis following Vaccination against Hepatitis B in a Child: A Case Report and Literature Review

    PubMed Central

    Yuan, Jun-liang; Wang, Shuang-kun; Guo, Xiao-juan

    2016-01-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system, which has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, and the Hog vaccine. Here, we presented a case of 12-year-old child who suffered from ADEM three weeks after hepatitis B vaccination. He was admitted to our hospital with symptoms of weakness of limbs, high fever, and alteration of consciousness. Some abnormalities were also found in CSF. Treatment with high-dose corticosteroids and intravenous immunoglobulin had significant effect, with marked improvement of the clinical symptoms and the results of CSF. The findings of MRI also detected some abnormal lesions located in both brain and spinal cord. The clinical features, the findings of CSF and MRI, and therapeutic effect may contribute to such diagnosis of ADEM. PMID:27478662

  6. Interferon lambda 3 genotype predicts hepatitis C virus RNA levels in early acute infection among people who inject drugs: The InC3 Study

    PubMed Central

    Hajarizadeh, Behzad; Grady, Bart; Page, Kimberly; Kim, Arthur Y.; McGovern, Barbara H.; Cox, Andrea L.; Rice, Thomas M.; Sacks-Davis, Rachel; Bruneau, Julie; Morris, Meghan; Amin, Janaki; Schinkel, Janke; Applegate, Tanya; Maher, Lisa; Hellard, Margaret; Lloyd, Andrew R.; Prins, Maria; Geskus, Ronald B; Dore, Gregory J.; Grebely, Jason

    2014-01-01

    Background and Objectives Hepatitis C virus (HCV) RNA level in acute HCV infection is predictive of spontaneous clearance. This study assessed factors associated with HCV RNA levels during early acute infection among people who inject drugs with well-defined acute HCV infection. Study design Data were from International Collaboration of Incident HIV and Hepatitis C in Injecting Cohorts (InC3) Study, an international collaboration of nine prospective cohorts studying acute HCV infection. Individuals with available HCV RNA levels during early acute infection (first two months following infection) were included. The distribution of HCV RNA levels during early acute infection were compared by selected host and virological factors. Results A total of 195 individuals were included. Median HCV RNA levels were significantly higher among individuals with interferon lambda 3 (IFNL3, formerly called IL28B) CC genotype compared to those with TT/CT genotype (6.28 vs. 5.39 log IU/mL, respectively; P=0.01). IFNL3 CC genotype was also associated with top tertile HCV RNA levels (≥6.3 IU/mL; vs. TT/CT genotype; adjusted Odds Ratio: 4.28; 95%CI: 2.01, 9.10; P<0.01). Conclusions This study indicates that IFNL3 CC genotype predicts higher HCV RNA levels in early acute HCV infection. PMID:25256151

  7. Toxic myopathy and acute hepatic necrosis in cattle caused by ingestion of Senna obtusifolia (sicklepod; coffee senna) in Brazil.

    PubMed

    Furlan, Fernando Henrique; Zanata, Carina; Damasceno, Everson Dos Santos; de Oliveira, Leonardo Pintar; da Silva, Leilane Aparecida; Colodel, Edson Moleta; Riet-Correa, Franklin

    2014-12-15

    The epidemiological, clinical and pathological findings of field and experimental Senna obtusifolia (sicklepod; coffee senna) poisoning in cattle are described. The low availability of good quality forage and high rate of infestation of pastures by S. obtusifolia were the factors that led to poisonous plant ingestion. In this study, the morbidity ranged between 2% and 27.9%, and the lethality was 100%. For the experimental study, six cattle were fed with the aerial parts of S. obtusifolia collected in three different seasons at 9%-38% of the animal's body weight. The experimental and field diseases were similar. The main clinical signs were diarrhea, reluctance to move, muscular weakness and recumbency. The gross findings included pale discoloration of the skeletal muscle. Microscopically, the affected cattle showed degeneration and necrosis of the skeletal muscles and occasionally of the cardiac muscles. Additionally, two cattle showed centrilobular hepatic necrosis. In this study, S. obtusifolia collected from the same farm showed seasonal variation in toxicity. Poisoning by S. obtusifolia is an important cause of death of cattle in the Central Western region of Brazil. The toxicosis caused by this plant is similar to S. occidentalis poisoning; however, in S. obtusifolia poisoning, acute hepatic necrosis is sometimes present. PMID:25255730

  8. Protective effect of danhong injection on acute hepatic failure induced by lipopolysaccharide and d-galactosamine in mice.

    PubMed

    Wang, Ying; Gao, Li-Na; Cui, Yuan-Lu; Jiang, Heng-Li

    2014-01-01

    Acute hepatic failure (AHF), which leads to an extremely high mortality rate, has become the focus of attention in clinic. In this study, Danhong injection (DHI) was investigated to evaluate the preventive and protective effect on AHF induced by lipopolysaccharide (LPS) and D-galactosamine (GalN) in mice. For AHF induction, ICR mice were intraperitoneally injected with D-GalN (700 mg/kg) and LPS (20  μ g/kg). DHI was administrated twice, at 12 and 1 h, respectively, before D-GalN/LPS injection. After stimulation with D-GalN/LPS for 1 and 6 h, serum and livers were collected for analysis. We found that mice administrated with DHI displayed a higher survival rate, lower serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), glutathione S-transferase (GST), and tumor necrosis factor (TNF)- α . DHI inhibited the elevations of hepatic lipid peroxidation (malondialdehyde), caspase-8 activity, and mRNA expression levels of inflammatory cytokines (interleukin-1 β and interleukin-6) increased by D-GalN/LPS in the liver. Furthermore, liver histopathological analysis indicated that the DHI group showed markedly fewer apoptotic (TUNEL positive) cells and less pathological changes than those in the AHF model group. These results provide a novel insight into the pharmacological actions of DHI as a potential candidate for treating AHF.

  9. Toxic myopathy and acute hepatic necrosis in cattle caused by ingestion of Senna obtusifolia (sicklepod; coffee senna) in Brazil.

    PubMed

    Furlan, Fernando Henrique; Zanata, Carina; Damasceno, Everson Dos Santos; de Oliveira, Leonardo Pintar; da Silva, Leilane Aparecida; Colodel, Edson Moleta; Riet-Correa, Franklin

    2014-12-15

    The epidemiological, clinical and pathological findings of field and experimental Senna obtusifolia (sicklepod; coffee senna) poisoning in cattle are described. The low availability of good quality forage and high rate of infestation of pastures by S. obtusifolia were the factors that led to poisonous plant ingestion. In this study, the morbidity ranged between 2% and 27.9%, and the lethality was 100%. For the experimental study, six cattle were fed with the aerial parts of S. obtusifolia collected in three different seasons at 9%-38% of the animal's body weight. The experimental and field diseases were similar. The main clinical signs were diarrhea, reluctance to move, muscular weakness and recumbency. The gross findings included pale discoloration of the skeletal muscle. Microscopically, the affected cattle showed degeneration and necrosis of the skeletal muscles and occasionally of the cardiac muscles. Additionally, two cattle showed centrilobular hepatic necrosis. In this study, S. obtusifolia collected from the same farm showed seasonal variation in toxicity. Poisoning by S. obtusifolia is an important cause of death of cattle in the Central Western region of Brazil. The toxicosis caused by this plant is similar to S. occidentalis poisoning; however, in S. obtusifolia poisoning, acute hepatic necrosis is sometimes present.

  10. Risk factors for acute hepatitis A infection in Korea in 2007 and 2009: a case-control study.

    PubMed

    Seo, Joo Youn; Choi, Bo Youl; Ki, Moran; Jang, Hye Lim; Park, Hee Suk; Son, Hyun Jin; Bae, Si Hyun; Kang, Jin Han; Jun, Dae Won; Lee, Jin-Woo; Hong, Young Jin; Kim, Young Seok; Kim, Chang-Hwi; Chang, U Im; Kim, Jong-Hyun; Yang, Hyeon Woong; Kim, Hong Soo; Park, Kyeong Bae; Hwang, Jae Seok; Heo, Jeong; Kim, In Hee; Kim, Jung Soo; Cheon, Gab Jin

    2013-06-01

    This study aimed to identify the risk factors associated with acute hepatitis A virus (HAV) infection in the Korean population. Participants were recruited from five referral hospitals across the country in 2007 and from 11 hospitals in 2009. Patients with positive anti-HAV IgM antibody tests became the case group, while patients treated for non-contagious diseases at the same hospitals were recruited as controls. A total of 222 and 548 case-control pairs were studied in the 2007 and 2009 surveys, respectively. Data from the surveys were analyzed jointly. In a multivariate analysis, sharing the household with HAV-infected family members (OR, 6.32; 95% CI, 1.4-29.6), contact with other HAV-infected individuals (OR, 4.73; 95% CI, 2.4-9.4), overseas travel in 2007 (OR, 19.93; 95% CI, 2.3-174.4), consumption of raw shellfish (OR, 2.51; 95% CI, 1.8-3.5), drinking bottled water (OR, 1.64; 95% CI, 1.3-8.4), and occupation that involve handling food (OR, 3.30; 95% CI, 1.3-8.4) increased the risk of HAV infection. Avoiding contact with HAV-infected individuals and avoiding raw foods eating could help minimize the risk of hepatitis A infection. Immunization must be beneficial to individuals who handle food ingredients occupationally or travel overseas to HAV-endemic areas.

  11. Low rate of sustained virological response in an outbreak of acute hepatitis C in HIV-infected patients.

    PubMed

    Laguno, Montserrat; Martínez-Rebollar, Maria; Perez, Iñaki; Costa, Josep; Larrousse, Maria; Calvo, Marta; Loncá, Montse; Muñoz, Ana; González-Cordón, Ana; Blanco, José Luís; Martínez, Esteban; Gatell, Josep Maria; Mallolas, Josep

    2012-10-01

    Recent reports have suggested an increased risk of acute hepatitis C (AHC) infection in homosexual HIV-infected men and that early treatment with interferon-alfa, alone or associated with ribavirin, significantly reduces the risk of chronic evolution. A retrospective analysis of 38 HIV-infected patients who were consecutively diagnosed as developing AHC, defined by both seroconversion of anti-hepatitis C virus (HCV) antibodies and detection of serum HCV-RNA in those with previous negative results. Thirty-six patients were men with history of unprotected sexual intercourse with men and two were women with sexual and nosocomial risk factors. AHC infection was asymptomatic in 26 patients; asthenia and jaundice were the most frequent symptoms. HCV genotype 1 was present in 19 patients and genotype 4 in 14 patients. Thirty-five patients received early antiviral treatment with pegylated interferon-alfa associated with ribavirin; 15 of the 32 patients who completed the follow-up (47%) achieved a sustained virological response, as defined by undetectable HCV-RNA 6 months after the end of therapy. There is a risk of sexual transmission of HCV in HIV-infected men who have sex with men. In our experience, early treatment of AHC with pegylated interferon-alfa plus ribavirin in HIV patients achieves poor results. PMID:22428909

  12. Hepatic fatty acid biosynthesis is more responsive to protein than carbohydrate in rainbow trout during acute stimulations.

    PubMed

    Dai, Weiwei; Panserat, Stéphane; Kaushik, Sadasivam; Terrier, Frédéric; Plagnes-Juan, Elisabeth; Seiliez, Iban; Skiba-Cassy, Sandrine

    2016-01-01

    The link between dietary carbohydrate/protein and de novo lipogenesis (DNL) remains debatable in carnivorous fish. We aimed to evaluate and compare the response of hepatic lipogenic gene expression to dietary carbohydrate intake/glucose and dietary protein intake/amino acids (AAs) during acute stimulations using both in vivo and in vitro approaches. For the in vivo trial, three different diets and a controlled-feeding method were employed to supply fixed amount of dietary protein or carbohydrate in a single meal; for the in vitro trial, primary hepatocytes were stimulated with a low or high level of glucose (3 mM or 20 mM) and a low or high level of AAs (one-fold or four-fold concentrated AAs). In vitro data showed that a high level of AAs upregulated the expression of enzymes involved in DNL [fatty acid synthase (FAS) and ATP citrate lyase (ACLY)], lipid bioconversion [elongation of very long chain fatty acids like-5 (Elovl5), Elovl2, Δ6 fatty acyl desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD1)], NADPH production [glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme (ME)], and transcriptional factor sterol regulatory element binding protein 1-like, while a high level of glucose only elevated the expression of ME. Data in trout liver also showed that high dietary protein intake induced higher lipogenic gene expression (FAS, ACLY, and Elovl2) regardless of dietary carbohydrate intake, while high carbohydrate intake markedly suppressed the expression of acetyl-CoA carboxylase (ACC) and Elovl5. Overall, we conclude that, unlike rodents or humans, hepatic fatty acid biosynthetic gene expression in rainbow trout is more responsive to dietary protein intake/AAs than dietary carbohydrate intake/glucose during acute stimulations. This discrepancy probably represents one important physiological and metabolic difference between carnivores and omnivores. PMID:26491101

  13. Hepatic fatty acid biosynthesis is more responsive to protein than carbohydrate in rainbow trout during acute stimulations.

    PubMed

    Dai, Weiwei; Panserat, Stéphane; Kaushik, Sadasivam; Terrier, Frédéric; Plagnes-Juan, Elisabeth; Seiliez, Iban; Skiba-Cassy, Sandrine

    2016-01-01

    The link between dietary carbohydrate/protein and de novo lipogenesis (DNL) remains debatable in carnivorous fish. We aimed to evaluate and compare the response of hepatic lipogenic gene expression to dietary carbohydrate intake/glucose and dietary protein intake/amino acids (AAs) during acute stimulations using both in vivo and in vitro approaches. For the in vivo trial, three different diets and a controlled-feeding method were employed to supply fixed amount of dietary protein or carbohydrate in a single meal; for the in vitro trial, primary hepatocytes were stimulated with a low or high level of glucose (3 mM or 20 mM) and a low or high level of AAs (one-fold or four-fold concentrated AAs). In vitro data showed that a high level of AAs upregulated the expression of enzymes involved in DNL [fatty acid synthase (FAS) and ATP citrate lyase (ACLY)], lipid bioconversion [elongation of very long chain fatty acids like-5 (Elovl5), Elovl2, Δ6 fatty acyl desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD1)], NADPH production [glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme (ME)], and transcriptional factor sterol regulatory element binding protein 1-like, while a high level of glucose only elevated the expression of ME. Data in trout liver also showed that high dietary protein intake induced higher lipogenic gene expression (FAS, ACLY, and Elovl2) regardless of dietary carbohydrate intake, while high carbohydrate intake markedly suppressed the expression of acetyl-CoA carboxylase (ACC) and Elovl5. Overall, we conclude that, unlike rodents or humans, hepatic fatty acid biosynthetic gene expression in rainbow trout is more responsive to dietary protein intake/AAs than dietary carbohydrate intake/glucose during acute stimulations. This discrepancy probably represents one important physiological and metabolic difference between carnivores and omnivores.

  14. Studies in porphyria: functional evidence for a partial deficiency of ferrochelatase activity in mitogen-stimulated lymphocytes from patients with erythropoietic protoporphyria.

    PubMed Central

    Sassa, S; Zalar, G L; Poh-Fitzpatrick, M B; Anderson, K E; Kappas, A

    1982-01-01

    In this paper we show that the ferrochelatase defect in erythropoietic protoporphyria (EPP) can readily be identified in mitogen-stimulated lymphocytes since such cells from patients with EPP accumulate approximately twice as much protoporphyrin IX as cells from normal subjects when incubated with a porphyrin precursor, gamma-aminolevulinic acid (ALA). Treatment of cultures with ALA and with the iron chelator, CaMgEDTA significantly increased the level of protoporphyrin IX in mitogen-stimulated lymphocytes from normal subjects, while the same treatment failed to produce an increase in protoporphyrin IX in cell preparations from EPP patients. In contrast to the results with the chelator treatment, supplementation of the cultures with iron and ALA reduced the level of protoporphyrin IX in normal cells, but not in EPP cells. These findings are compatible with a partial deficiency of ferrochelatase in EPP lymphocytes. The gene defects of acute intermittent porphyria and hereditary coproporphyria have previously been identified using lymphocyte preparations from the gene carriers of these diseases. The present study demonstrates that EPP represents another form of human porphyria in which the gene defect of the disease can now be identified in lymphocyte preparations. PMID:6804493

  15. Uroporphyrinogen III Synthase Knock-In Mice Have the Human Congenital Erythropoietic Porphyria Phenotype, Including the Characteristic Light-Induced Cutaneous Lesions

    PubMed Central

    Bishop, David F.; Johansson, Annika; Phelps, Robert; Shady, Amr A.; Ramirez, Maria C. M.; Yasuda, Makiko; Caro, Andres; Desnick, Robert J.

    2006-01-01

    Congenital erythropoietic porphyria (CEP), an autosomal recessive inborn error, results from the deficient but not absent activity of uroporphyrinogen III synthase (URO-synthase), the fourth enzyme in the heme biosynthetic pathway. The major clinical manifestations include severe anemia, erythrodontia, and disfiguring cutaneous involvement due to the accumulation of phototoxic porphyrin I isomers. Murine models of CEP could facilitate studies of disease pathogenesis and the evaluation of therapeutic endeavors. However, URO-synthase null mice were early embryonic lethals. Therefore, knock-in mice were generated with three missense mutations, C73R, V99A, and V99L, which had in vitro–expressed activities of 0.24%, 5.9%, and 14.8% of expressed wild-type activity, respectively. Homozygous mice for all three mutations were fetal lethals, except for mice homozygous for a spontaneous recombinant allele, V99AT/V99AT, a head-to-tail concatemer of three V99A targeting constructs. Although V99AT/V99AT and C73R/V99AT mice had ∼2% hepatic URO-synthase activity and normal hepatic microsomal heme and hemoprotein levels, they had 20% and 13% of wild-type activity in erythrocytes, respectively, which indicates that sufficient erythroid URO-synthase was present for fetal development and survival. Both murine genotypes showed marked porphyrin I isomer accumulation in erythrocytes, bone, tissues, and excreta and had fluorescent erythrodontia, hemolytic anemia with reticulocytosis and extramedullary erythropoiesis, and, notably, the characteristic light-induced cutaneous involvement. These mice provide insight into why CEP is an erythroid porphyria, and they should facilitate studies of the disease pathogenesis and therapeutic endeavors for CEP. PMID:16532394

  16. Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have an acute-phase response

    PubMed Central

    Rivory, L P; Slaviero, K A; Clarke, S J

    2002-01-01

    Inflammatory disease states (infection, arthritis) are associated with reduced drug oxidation by the cytochrome P450 3A system. Many chemotherapy agents are metabolised through this pathway, and disease may therefore influence inter-individual differences in drug pharmacokinetics. The purpose of this study was to assess cytochrome P450 3A function in patients with advanced cancer, and its relation to the acute-phase response. We evaluated hepatic cytochrome P450 3A function in 40 patients with advanced cancer using the erythromycin breath test. Both the traditional C20min measure and the recently proposed 1/TMAX values were estimated. The marker of acute-phase response, C-reactive protein and the pro-inflammatory cytokines IL-6, IL-1β, TNFα and IL-8 were measured in serum or plasma at baseline. Cancer patients with an acute phase response (C-reactive protein >10 mg l−1, n=26) had reduced metabolism as measured with the erythromycin breath test 1/TMAX (Kruskal–Wallis Anova, P=0.0062) as compared to controls (C-reactive protein ⩽10 mg l−1, n=14). Indeed, metabolism was significantly associated with C-reactive protein over the whole concentration range of this acute-phase marker (r=−0.64, Spearman Rank Correlation, P<0.00001). C-reactive protein serum levels were significantly correlated with those of IL-6 (Spearman coefficient=0.58, P<0.0003). The reduction in cytochrome P450 3A function with acute-phase reaction was independent of the tumour type and C-reactive protein elevation was associated with poor performance status. This indicates that the sub-group of cancer patients with significant acute-phase response have compromised drug metabolism, which may have implications for the safety of chemotherapy in this population. British Journal of Cancer (2002) 87, 277–280. doi:10.1038/sj.bjc.6600448 www.bjcancer.com © 2002 Cancer Research UK PMID:12177794

  17. Acute Increase in Hepatic Arterial Flow During TIPS Identified by Intravascular Flow Measurements

    SciTech Connect

    Radeleff, Boris Sommer, Christof-Matthias; Heye, Tobias; Lopez-Benitez, Ruben; Sauer, Peter; Schmidt, Jan; Kauczor, Haus-Ulrich; Richter, Goetz Martin

    2009-01-15

    The purpose of this study was to investigate alterations of hepatic arterial flow during transjugular intrahepatic portosystemic stent shunt (TIPS) applying intravascular Doppler sonography. This prospective monocenter study included 25 patients with liver cirrhosis (alcohol induced [n = 19], chronic hepatitis associated [n = 3], primary biliary cirrhosis associated [n = 1], and cryptogenic [n = 2]) successfully treated with TIPS. All patients underwent intravascular hepatic arterial flow measurements during TIPS using an endoluminal flow sensor. The average arterial peak velocity (APV) and the maximum arterial peak velocity (MPV) were registered. Twenty-two patients (88%) showed increased APV, one patient (4%) showed unaffected APV, and two patients (8%) showed decreased APV after TIPS. The average portosystemic pressure gradient decreased significantly, from 22.0 {+-} 5.1 mmHg before TIPS to 11.0 {+-} 4.1 mmHg after TIPS (-50.0%; p < 0.0001). The average APV increased significantly, from 41.9 {+-} 17.8 cm/s before TIPS to 60.7 {+-} 19.0 cm/s after TIPS (+44.9%; p < 0.0001). The average MPV increased significantly, from 90.8 {+-} 31.7 cm/s before TIPS to 112.6 {+-} 34.9 cm/s after TIPS (+24.0%; p = 0.0002). These changes in perfusion set in within seconds after TIPS tract formation in all the patients with increased APV. We conclude that TIPS-induced portosystemic decompression leads to a significant increase in hepatic arterial flow. The changes occurred within seconds, suggesting a reflex-like mechanism.

  18. Acute Hepatitis and Pneumonitis Caused by Disseminated Bacillus Calmette-Guérin Infection

    PubMed Central

    Shehadeh, Ihab; Abu Atta, Osama

    2016-01-01

    Intravesical instillation of Bacillus Calmette-Guérin (BCG) is the treatment of choice for superficial bladder carcinoma. We report a case of disseminated BCG infection in an early stage bladder cancer patient that initially presented with hepatitis followed by pneumonitis and sepsis. A complete clinical response was achieved in 14 days with anti-mycobacterial therapy and prednisolone. Disseminated BCG is a rare treatment complication and is likely a combination of direct infection and hypersensitivity. PMID:26958569

  19. Acute hepatitis after starting pinaverium bromide in a patient taking mirtazapine.

    PubMed

    Tak, Sandeep; Tak, Shubhanjali

    2014-01-01

    A 56-year-old man presented with chronic abdominal pain. He had been evaluated extensively in the recent past undergoing upper gastrointestinal endoscopy, colonoscopy and CT scan of the abdomen with normal results. The provisional diagnosis of irritable bowel syndrome was performed and pinaverium bromide was started. The patient had pre-existing hypertension, a major depressive disorder and gastro-oesophageal reflux disease. He had been taking nebivolol and pantoprazole for several years and mirtazapine for the last 1 year. The patient developed nausea, vomiting and anorexia after 5 days of starting pinaverium bromide. Investigations revealed marked elevation of liver enzymes and bilirubin. He was negative for HIV, HBSAg, anti-hepatitis C virus, IgM for hepatitis A virus, hepatitis E virus, antinuclear antibody and antimitochondrial antibody. An ultrasound showed mild hepatomegaly with hypoechoic echo texture; the rest of scan was normal. Pinaverium and mirtazapine were stopped immediately. The patient was treated symptomatically and his liver profile returned to normal after 4 weeks. PMID:25015163

  20. Acute hepatitis after starting pinaverium bromide in a patient taking mirtazapine

    PubMed Central

    Tak, Sandeep; Tak, Shubhanjali

    2014-01-01

    A 56-year-old man presented with chronic abdominal pain. He had been evaluated extensively in the recent past undergoing upper gastrointestinal endoscopy, colonoscopy and CT scan of the abdomen with normal results. The provisional diagnosis of irritable bowel syndrome was performed and pinaverium bromide was started. The patient had pre-existing hypertension, a major depressive disorder and gastro-oesophageal reflux disease. He had been taking nebivolol and pantoprazole for several years and mirtazapine for the last 1 year. The patient developed nausea, vomiting and anorexia after 5 days of starting pinaverium bromide. Investigations revealed marked elevation of liver enzymes and bilirubin. He was negative for HIV, HBSAg, anti-hepatitis C virus, IgM for hepatitis A virus, hepatitis E virus, antinuclear antibody and antimitochondrial antibody. An ultrasound showed mild hepatomegaly with hypoechoic echo texture; the rest of scan was normal. Pinaverium and mirtazapine were stopped immediately. The patient was treated symptomatically and his liver profile returned to normal after 4 weeks. PMID:25015163

  1. Report of a novel C1483W mutation in the hepatitis E virus polymerase in patients with acute liver failure.

    PubMed

    Borkakoti, Jayanta; Ahmed, Giasuddin; Kar, Premashis

    2016-10-01

    Here, we report the molecular alterations in the HEV genome from patients with acute liver failure (ALF) and acute viral hepatitis (AVH) from North India, including pregnant women and its association with the poor outcome of the disease. We partially sequenced the RNA Dependent RNA polymerase (RdRp) region of the ORF 1 protein in the HEV genome from representative samples from patients with ALF and AVH and identified two novel mutations Cysteine 1483 Tryptophan and Asparagine 1530 Threonine in 100% (25/25) of the patients with ALF compared to none (0/30) of the patients with AVH (P<0.0001). Disease severity parameters along with viral load corresponding to the samples with C1483W and N1530T mutations were significantly higher compared to those lacking the mutation showing significant association with the outcome in ALF patients. The nucleotide substitutions in the RdRp region may play a crucial role in enhancing HEV replication thus leading to disease severity. PMID:27320795

  2. Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B.

    PubMed Central

    Li, Hai; Chen, Liu-Ying; Zhang, Nan-nan; Li, Shu-Ting; Zeng, Bo; Pavesi, Marco; Amorós, Àlex; Mookerjee, Rajeshwar P; Xia, Qian; Xue, Feng; Ma, Xiong; Hua, Jing; Sheng, Li; Qiu, De-kai; Xie, Qing; Foster, Graham R; Dusheiko, Geoffrey; Moreau, Richard; Gines, Pere; Arroyo, Vicente; Jalan, Rajiv

    2016-01-01

    The diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were ‘hepatic’ and ‘coagulation’. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p < 0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles. PMID:27146801

  3. The porphyrias: clinic, diagnostics, novel investigative tools and evolving molecular therapeutic strategies.

    PubMed

    van Serooskerken, A-M van Tuyll; Poblete-Gutiérrez, P; Frank, J

    2010-01-01

    The porphyrias are clinically and genetically heterogeneous metabolic disorders resulting from a predominantly hereditary dysfunction of specific enzymes involved in heme biosynthesis. Today, the clinical, biochemical, and genetic characteristics of this fascinating group of diseases are well established. Recently, different in vitro and animal models have facilitated the investigation of etiopathologic mechanisms in the different types of porphyria and the development of causal treatment strategies such as pathway interference, enzyme replacement, and gene therapy. The continuous progress in basic science has made an invaluable contribution to the rapid translation of discoveries made in the laboratory into new diagnostics and therapeutics in the near future.

  4. New Point Mutations in Surface and Core Genes of Hepatitis B Virus Associated with Acute on Chronic Liver Failure Identified by Complete Genomic Sequencing

    PubMed Central

    Lou, Guohua; Zheng, Min; Cao, Qingyi; Chen, Zhi

    2015-01-01

    The objective of this study was to identify new viral biomarkers associated with acute on chronic liver failure (ACLF) by complete genomic sequencing of HBV. Hepatitis B virus mutations associated with ACLF were screened by Illumina high-throughput sequencing in twelve ACLF cases and twelve age-matched mild chronic hepatitis B patients, which were validated in 438 chronic hepatitis B patients (80 asymptomatic carriers, 152 mild chronic hepatitis B patients, 102 severe chronic hepatitis B patients and 104 ACLF patients) by direct sequencing. The results of Illumina sequencing showed that the mutations at 7 sites (T216C, G285A, A1846T, G1896A, C1913A/G, A2159G, and A2189C) of 12 ACLF patients were significantly higher than those of 12 controls. In the validation cohorts, a significantly higher ratio of genotype B to C was found in patients with ACLF than in patients with non-ACLF. Multivariate analysis showed that T216C, G1896A, C1913A/G and A2159G/C were independent risk factors for ACLF. C216 in any combination, A/G1913 in any combination, and G/C2159 in any combination had high specificity for ACLF. In summary, T216C and A2159G/C mutations were novel factors independently associated with ACLF. Combined mutations in hepatitis B cases could play important roles in ACLF development. PMID:25849554

  5. Iron Regulatory Protein-1 Protects against Mitoferrin-1-deficient Porphyria*

    PubMed Central

    Chung, Jacky; Anderson, Sheila A.; Gwynn, Babette; Deck, Kathryn M.; Chen, Michael J.; Langer, Nathaniel B.; Shaw, George C.; Huston, Nicholas C.; Boyer, Leah F.; Datta, Sumon; Paradkar, Prasad N.; Li, Liangtao; Wei, Zong; Lambert, Amy J.; Sahr, Kenneth; Wittig, Johannes G.; Chen, Wen; Lu, Wange; Galy, Bruno; Schlaeger, Thorsten M.; Hentze, Matthias W.; Ward, Diane M.; Kaplan, Jerry; Eisenstein, Richard S.; Peters, Luanne L.; Paw, Barry H.

    2014-01-01

    Mitochondrial iron is essential for the biosynthesis of heme and iron-sulfur ([Fe-S]) clusters in mammalian cells. In developing erythrocytes, iron is imported into the mitochondria by MFRN1 (mitoferrin-1, SLC25A37). Although loss of MFRN1 in zebrafish and mice leads to profound anemia, mutant animals showed no overt signs of porphyria, suggesting that mitochondrial iron deficiency does not result in an accumulation of protoporphyrins. Here, we developed a gene trap model to provide in vitro and in vivo evidence that iron regulatory protein-1 (IRP1) inhibits protoporphyrin accumulation. Mfrn1+/gt;Irp1−/− erythroid cells exhibit a significant increase in protoporphyrin levels. IRP1 attenuates protoporphyrin biosynthesis by binding to the 5′-iron response element (IRE) of alas2 mRNA, inhibiting its translation. Ectopic expression of alas2 harboring a mutant IRE, preventing IRP1 binding, in Mfrn1gt/gt cells mimics Irp1 deficiency. Together, our data support a model whereby impaired mitochondrial [Fe-S] cluster biogenesis in Mfrn1gt/gt cells results in elevated IRP1 RNA-binding that attenuates ALAS2 mRNA translation and protoporphyrin accumulation. PMID:24509859

  6. Iron regulatory protein-1 protects against mitoferrin-1-deficient porphyria.

    PubMed

    Chung, Jacky; Anderson, Sheila A; Gwynn, Babette; Deck, Kathryn M; Chen, Michael J; Langer, Nathaniel B; Shaw, George C; Huston, Nicholas C; Boyer, Leah F; Datta, Sumon; Paradkar, Prasad N; Li, Liangtao; Wei, Zong; Lambert, Amy J; Sahr, Kenneth; Wittig, Johannes G; Chen, Wen; Lu, Wange; Galy, Bruno; Schlaeger, Thorsten M; Hentze, Matthias W; Ward, Diane M; Kaplan, Jerry; Eisenstein, Richard S; Peters, Luanne L; Paw, Barry H

    2014-03-14

    Mitochondrial iron is essential for the biosynthesis of heme and iron-sulfur ([Fe-S]) clusters in mammalian cells. In developing erythrocytes, iron is imported into the mitochondria by MFRN1 (mitoferrin-1, SLC25A37). Although loss of MFRN1 in zebrafish and mice leads to profound anemia, mutant animals showed no overt signs of porphyria, suggesting that mitochondrial iron deficiency does not result in an accumulation of protoporphyrins. Here, we developed a gene trap model to provide in vitro and in vivo evidence that iron regulatory protein-1 (IRP1) inhibits protoporphyrin accumulation. Mfrn1(+/gt);Irp1(-/-) erythroid cells exhibit a significant increase in protoporphyrin levels. IRP1 attenuates protoporphyrin biosynthesis by binding to the 5'-iron response element (IRE) of alas2 mRNA, inhibiting its translation. Ectopic expression of alas2 harboring a mutant IRE, preventing IRP1 binding, in Mfrn1(gt/gt) cells mimics Irp1 deficiency. Together, our data support a model whereby impaired mitochondrial [Fe-S] cluster biogenesis in Mfrn1(gt/gt) cells results in elevated IRP1 RNA-binding that attenuates ALAS2 mRNA translation and protoporphyrin accumulation.

  7. Autoimmune hepatitis.

    PubMed

    Heneghan, Michael A; Yeoman, Andrew D; Verma, Sumita; Smith, Alastair D; Longhi, Maria Serena

    2013-10-26

    Autoimmune hepatitis is a disease of the hepatic parenchyma that can present in acute or chronic forms. In common with many autoimmune diseases, autoimmune hepatitis is associated with non-organ-specific antibodies in the context of hepatic autoimmunity. This dichotomy has made definition of a unifying hypothesis in the pathophysiology of the disease difficult, although data from the past 8 years have drawn attention to the role of regulatory T cells. Several triggers have been identified, and the disease arises in genetically susceptible individuals. Clinical and biochemical remission is achievable in up to 85% of cases. For the remaining patients, alternative immunosuppression strategies are an option. Liver transplantation provides an excellent outcome for patients with acute liver failure or complications of end-stage liver disease, including hepatocellular carcinoma. Variant or overlapping syndromes are worthy of consideration when unexpected disease features arise.

  8. Enhancing the detection and management of acute hepatitis C virus infection.

    PubMed

    Martinello, Marianne; Matthews, Gail V

    2015-10-01

    Acute HCV infection refers to the 6-month period following infection acquisition, although this definition is somewhat arbitrary. While spontaneous clearance occurs in approximately 25%, the majority will develop chronic HCV infection with the potential for development of cirrhosis, end stage liver disease and hepatocellular carcinoma. Detection of acute HCV infection has been hampered by its asymptomatic or non-specific presentation, lack of specific diagnostic tests and the inherent difficulties in identifying and following individuals at highest risk of transmitting and acquiring HCV infection, such as people who inject drugs (PWID). However, recognition of those with acute infection may have individual and population level benefits and could represent an ideal opportunity for intervention. Despite demonstration that HCV treatment is feasible and successful in PWID, treatment uptake remains low with multiple barriers to care at an individual and systems level. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment, treatment and prevention in this group are urgently needed. As the therapeutic landscape of chronic HCV management is revolutionised by the advent of simple, highly effective directly-acting antiviral (DAA) therapy, similar opportunities may exist in acute infection. This review will discuss issues surrounding improving the detection and management of acute HCV infection, particularly in PWID. PMID:26254495

  9. Magnetic hydroxyapatite nanoworms for magnetic resonance diagnosis of acute hepatic injury

    NASA Astrophysics Data System (ADS)

    Xu, Yun-Jun; Dong, Liang; Lu, Yang; Zhang, Le-Cheng; An, Duo; Gao, Huai-Ling; Yang, Dong-Mei; Hu, Wen; Sui, Cong; Xu, Wei-Ping; Yu, Shu-Hong

    2016-01-01

    Inorganic non-metallic biomaterials, including the silicon frustule of a unicellular diatom, the carbonate shell of a mollusk and the calcium skeleton of the vertebrate, which are the main constituent part of an organism, serve as the supportive and protective components of soft tissue. Among them, hydroxyapatite, which primarily makes up the enamel and bone, is widely used in tissue engineering. Recently, the inorganic nonmetallic biomaterials, especially the applications of hydroxyapatites have attracted great attention. Herein, we report a novel synthesis method of magnetic functionalized hydroxyapatite nanocomposites. By simply tuning the ratios of reactants, a series of hydroxyapatite-Fe3O4 worm-shaped nanocomposites (HAP-ION nanoworms) are obtained. In addition, layer-by-layer surface modifications with chitosan (CH) and sodium alginate (SA) were employed to improve the solubility and biocompatibility, and low cytotoxicity and no hemolysis were observed. With the increase of iron oxide nanocrystals, the magnetic properties of the magnetic assembled nanoworms were enhanced, which resulted in better performance of magnetic resonance (MR) imaging. Owing to the intravenous injection of HAP-ION nanoworms, the contrast to noise ratio (CNR) of hepatic MR imaging in vivo was enhanced obviously, which should be beneficial for hepatic injury grading and further therapeutic treatment.Inorganic non-metallic biomaterials, including the silicon frustule of a unicellular diatom, the carbonate shell of a mollusk and the calcium skeleton of the vertebrate, which are the main constituent part of an organism, serve as the supportive and protective components of soft tissue. Among them, hydroxyapatite, which primarily makes up the enamel and bone, is widely used in tissue engineering. Recently, the inorganic nonmetallic biomaterials, especially the applications of hydroxyapatites have attracted great attention. Herein, we report a novel synthesis method of magnetic

  10. [Autoimmune hepatitis].

    PubMed

    Marcais, O; Larrey, D

    1994-01-01

    Acute and chronic autoimmune hepatitis are uncommon inflammatory liver diseases, mainly occurring in young women, in association with hypergammaglobulinemia and serum autoantibodies. Different types have been described: type 1 characterized by anti-smooth muscle and anti-nuclear antibodies; type 2 characterized by anti-LKM1 antibodies; type 3 characterized by anti-SLA antibodies. Other types, still not clearly defined, may exist. Autoimmune hepatitis are associated with HLA A1 B8 DR3 and HLA DR4. Without any treatment, the disease leads to cirrhosis and, uncommonly, to fulminant hepatitis. Large doses of corticosteroids usually allow to control the disease. Relapse of hepatitis is frequent after corticosteroid withdrawal. Concomitant administration of immunosuppressive agents such as azathioprine allows to reduce corticosteroid dosage and contributes to maintain the remission of the disease. Liver transplantation may be indicated in cases of severe cirrhosis or fulminant hepatitis.

  11. A novel hypothesis for an alkaline phosphatase 'rescue' mechanism in the hepatic acute phase immune response.

    PubMed

    Pike, Adrianne F; Kramer, Nynke I; Blaauboer, Bas J; Seinen, Willem; Brands, Ruud

    2013-12-01

    The liver isoform of the enzyme alkaline phosphatase (AP) has been used classically as a serum biomarker for hepatic disease states such as hepatitis, steatosis, cirrhosis, drug-induced liver injury, and hepatocellular carcinoma. Recent studies have demonstrated a more general anti-inflammatory role for AP, as it is capable of dephosphorylating potentially deleterious molecules such as nucleotide phosphates, the pathogenic endotoxin lipopolysaccharide (LPS), and the contact clotting pathway activator polyphosphate (polyP), thereby reducing inflammation and coagulopathy systemically. Yet the mechanism underlying the observed increase in liver AP levels in circulation during inflammatory insults is largely unknown. This paper hypothesizes an immunological role for AP in the liver and the potential of this system for damping generalized inflammation along with a wide range of ancillary pathologies. Based on the provided framework, a mechanism is proposed in which AP undergoes transcytosis in hepatocytes from the canalicular membrane to the sinusoidal membrane during inflammation and the enzyme's expression is upregulated as a result. Through a tightly controlled, nucleotide-stimulated negative feedback process, AP is transported in this model as an immune complex with immunoglobulin G by the asialoglycoprotein receptor through the cell and secreted into the serum, likely using the receptor's State 1 pathway. The subsequent dephosphorylation of inflammatory stimuli by AP and uptake of the circulating immune complex by endothelial cells and macrophages may lead to decreased inflammation and coagulopathy while providing an early upstream signal for the induction of a number of anti-inflammatory gene products, including AP itself.

  12. Hepatic Sulfotransferase as a Nephropreventing Target by Suppression of the Uremic Toxin Indoxyl Sulfate Accumulation in Ischemic Acute Kidney Injury

    PubMed Central

    Saito, Hideyuki; Yoshimura, Misato; Saigo, Chika; Komori, Megumi; Nomura, Yui; Yamamoto, Yuko; Sagata, Masataka; Wakida, Ayaka; Chuman, Erina; Nishi, Kazuhiko; Jono, Hirofumi

    2014-01-01

    Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is evoked by diverse pathophysiological conditions and/or surgical procedures. Here, we evaluated the nephropreventive effect of sulfotransferase (SULT) inhibitors, quercetin, and resveratrol, which hamper hepatic indoxyl sulfate (IS) production. I/R of the kidney caused severe renal injury with marked accumulation of serum and renal IS and urinary excretion of kidney injury molecule-1. Oral administration of AST-120 resulted in a significant restoration of kidney injury, suggesting that uremic toxins, which can be suppressed or adsorbed by AST-120 in the intestine, contribute to the progression or development of I/R-induced AKI. Oral administration of resveratrol or quercetin, SULT inhibitors, suppressed IS accumulation, accompanied by significant amelioration of renal dysfunction. The expression of nuclear factor E2-related factor 2 (Nrf2) in the renal nuclear fractions was markedly elevated by renal I/R, but suppressed by treatment with SULT inhibitors. IS is primarily taken up by HK-2 cells derived from human proximal tubular cells via organic anion transporters, which then evokes activation of Nrf2, most likely due to intracellular oxidative stress. Renal basolateral organic anion transporters OAT1 and OAT3, which mediate renal tubular uptake of IS in basolateral membrane, were markedly downregulated by renal I/R, but restored by SULT inhibitors. Our results suggest that renal accumulation of IS in ischemic AKI induces oxidative stress and downregulation of organic anion transporters resulting in kidney damage, which could be restored to some extent by inhibiting hepatic SULT activity as a nephropreventive target. PMID:24958931

  13. [A case of porphyria cutanea tarda in an 11-year-old boy].

    PubMed

    Pindycka-Piaszczyńska, M; Danik, E; Bendkowski, W

    1995-06-01

    A rare case of porphyria cutanea tarda (PCT) in an 11-year-old boy is presented. The clinical manifestations were typical. Results of porphyrin analyses of urine and serum with a fluorescence emission maximum around 398 nm revealed a pattern consistent with PCT. PMID:8692611

  14. A case of cholestatic hepatitis associated with histologic features of acute cholangitis

    PubMed Central

    Takeuchi, Hajime; Kaneko, Toru; Otsuka, Toshikazu; Tahara, Kumiko; Motoori, Tadashi; Ohbu, Makoto; Oda, Masaya; Yokomori, Hiroaki

    2011-01-01

    This report describes a case showing histologic features of acute cholangitis with an over-the-counter drug. A 48-year-old woman was diagnosed with general malaise and progressive jaundice. A thorough review of her medical history revealed that the patient had taken an over-the-counter drug, Pabron Gold®, which she had used previously, that may have caused liver injury. Laboratory investigations revealed jaundice and liver dysfunction. Endoscopic retrograde cholangiography detected no extrahepatic biliary duct dilatation or stones. Liver biopsy indicated acute cholangitis involving neutrophils and eosinophils. Electron microscopy revealed fragmented nuclei, indicating that the degenerative bile duct-related epithelial cells were in an apoptotic process. PMID:22162934

  15. Serum iron increases with acute induction of hepatic heme oxygenase-1 in mice.

    PubMed

    Mostert, Volker; Nakayama, Akihiro; Austin, Lori M; Levander, Ximena A; Ferris, Christopher D; Hill, Kristina E; Burk, Raymond F

    2007-01-01

    Heme oxygenase (HO)-1 is induced by oxidative stress and protects against oxidant injury. We examined the effect of rapid induction of hepatic HO-1 on serum iron level. Serum iron was approximately doubled within 6 h when HO-1 was induced by phenobarbital treatment of selenium-deficient mice. Blocking heme synthesis with diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) prevented the induction of HO-1 and the rise in serum iron. DDC did not block HO-1 induction by hemin. Inhibition of HO activity by tin protoporphyrin prevented a rise in serum iron that occurred following phorone treatment. These results indicate that heme synthesis or an exogenous source of heme is needed to allow induction of HO-1. Further, they link HO-1 induction with a rise in serum iron, suggesting that the iron resulting from catabolism of heme by HO-1 is released by the liver.

  16. Acute allograft rejection following interferon therapy for hepatitis C in recipients who have returned to dialysis after kidney transplant failure: case study.

    PubMed

    Fabrizi, Fabrizio; D'Ambrosio, Roberta; Pallotti, Francesco; Berardinelli, Luisa; Messa, Piergiorgio; Martin, Paul; Aghemo, Alessio

    2014-11-01

    Interferon-based therapy remains the gold standard for hepatitis C in patients with chronic kidney disease; however, due to the high rate of IFN-induced rejection after transplant, treatment of HCV-infected kidney transplant recipients is recommended only in particular circumstances. We report the case of a 45-year-old Caucasian female with chronic hepatitis C (genotype 1b) who returned to hemodialysis following the complete functional loss of her kidney transplant. She started combination antiviral therapy with peg-IFN-α2a (135 mcg sc weekly) plus ribavirin (200 mg daily) nine months after the re-initiation of hemodialysis. Antiviral therapy was neither effective nor safe; ribavirin was stopped at week 38 due to hemolytic anemia; on-treatment HCV breakthrough was observed at week 48; and acute rejection occurred after four months of IFN-based therapy. Diagnosis of acute allograft rejection was suspected on the grounds of clinical, radiographic, and laboratory data. Allograft nephrectomy was then performed and histology showed acute-on-chronic rejection. This is an uncommon case of IFN-associated kidney rejection in an allograft recipient who had functional loss of her graft and had returned to hemodialysis. In view of the risk of rejection of renal allograft, and the limited efficacy of IFN-based treatment of hepatitis C, physicians should be aware of effective treatment with oral anti-viral agents and avoid the use of IFN in patients on maintenance dialysis with failed renal allograft.

  17. Comparative analysis of viral genomes from acute and chronic hepatitis B reveals novel variants associated with a lower rate of chronicity.

    PubMed

    Chook, Jack Bee; Ngeow, Yun Fong; Khang, Tsung Fei; Ng, Kee Peng; Tiang, Yee Peng; Mohamed, Rosmawati

    2013-03-01

    Infection with the hepatitis B virus (HBV) may lead to an acute or chronic infection. It is generally accepted that the clinical outcome of infection depends on the balance between host immunity and viral survival strategies. In order to persist, the virus needs to have a high rate of replication and some immune-escape capabilities. Hence, HBVs lacking these properties are likely to be eliminated more rapidly by the host, leading to a lower rate of chronicity. To test this hypothesis, 177 HBV genomes from acute non-fulminant cases and 1,149 from chronic cases were retrieved from GenBank for comparative analysis. Selection of candidate nucleotides associated with the disease state was done using random guess cut-off and the Bonferroni correction. Five significant nucleotides were detected using this filtering step. Their predictive values were assessed using the support vector machine classification with five-fold cross-validation. The average prediction accuracy was 61% ± 1%, with a sensitivity of 24% ± 1%, specificity of 98% ± 1%, positive predictive value of 92% ± 4% and negative predictive value of 56% ± 1%. BCP/X, enhancer I and surface/polymerase variants were found to be associated almost exclusively with acute hepatitis. These HBV variants are novel potential markers for non-progression to chronic hepatitis. PMID:23297244

  18. Therapeutic potential of proteasome inhibitors in congenital erythropoietic porphyria

    PubMed Central

    Blouin, Jean-Marc; Duchartre, Yann; Costet, Pierre; Lalanne, Magalie; Ged, Cécile; Lain, Ana; Millet, Oscar; de Verneuil, Hubert; Richard, Emmanuel

    2013-01-01

    Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder characterized by uroporphyrinogen III synthase (UROS) deficiency resulting in massive porphyrin accumulation in blood cells, which is responsible for hemolytic anemia and skin photosensitivity. Among the missense mutations actually described up to now in CEP patients, the C73R and the P248Q mutations lead to a profound UROS deficiency and are usually associated with a severe clinical phenotype. We previously demonstrated that the UROSC73R mutant protein conserves intrinsic enzymatic activity but triggers premature degradation in cellular systems that could be prevented by proteasome inhibitors. We show evidence that the reduced kinetic stability of the UROSP248Q mutant is also responsible for increased protein turnover in human erythroid cells. Through the analysis of EGFP-tagged versions of UROS enzyme, we demonstrate that both UROSC73R and UROSP248Q are equally destabilized in mammalian cells and targeted to the proteasomal pathway for degradation. We show that a treatment with proteasomal inhibitors, but not with lysosomal inhibitors, could rescue the expression of both EGFP-UROS mutants. Finally, in CEP mice (UrosP248Q/P248Q) treated with bortezomib (Velcade), a clinically approved proteasome inhibitor, we observed reduced porphyrin accumulation in circulating RBCs and urine, as well as reversion of skin photosensitivity on bortezomib treatment. These results of medical importance pave the way for pharmacologic treatment of CEP disease by preventing certain enzymatically active UROS mutants from early degradation by using proteasome inhibitors or chemical chaperones. PMID:24145442

  19. Therapeutic potential of proteasome inhibitors in congenital erythropoietic porphyria.

    PubMed

    Blouin, Jean-Marc; Duchartre, Yann; Costet, Pierre; Lalanne, Magalie; Ged, Cécile; Lain, Ana; Millet, Oscar; de Verneuil, Hubert; Richard, Emmanuel

    2013-11-01

    Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder characterized by uroporphyrinogen III synthase (UROS) deficiency resulting in massive porphyrin accumulation in blood cells, which is responsible for hemolytic anemia and skin photosensitivity. Among the missense mutations actually described up to now in CEP patients, the C73R and the P248Q mutations lead to a profound UROS deficiency and are usually associated with a severe clinical phenotype. We previously demonstrated that the UROS(C73R) mutant protein conserves intrinsic enzymatic activity but triggers premature degradation in cellular systems that could be prevented by proteasome inhibitors. We show evidence that the reduced kinetic stability of the UROS(P248Q) mutant is also responsible for increased protein turnover in human erythroid cells. Through the analysis of EGFP-tagged versions of UROS enzyme, we demonstrate that both UROS(C73R) and UROS(P248Q) are equally destabilized in mammalian cells and targeted to the proteasomal pathway for degradation. We show that a treatment with proteasomal inhibitors, but not with lysosomal inhibitors, could rescue the expression of both EGFP-UROS mutants. Finally, in CEP mice (Uros(P248Q/P248Q)) treated with bortezomib (Velcade), a clinically approved proteasome inhibitor, we observed reduced porphyrin accumulation in circulating RBCs and urine, as well as reversion of skin photosensitivity on bortezomib treatment. These results of medical importance pave the way for pharmacologic treatment of CEP disease by preventing certain enzymatically active UROS mutants from early degradation by using proteasome inhibitors or chemical chaperones. PMID:24145442

  20. [Clinical, biochemical and histopathological development of post-transfusional non-A, non-B hepatitis from the acute picture to chronicity during 13.3 years].

    PubMed

    de Andrade Júnior, D R; Câmara Lopes, L H; de Souza, F C; de Andrade, D R

    1989-01-01

    This case was of a 45 year old female patient with a post-transfusion non-A non-B hepatitis which was accompanied since an acute phase to hepatic cirrhosis during a period of 159.7 months or 13.3 years. Four hepatic biopsies were carried out and they divided the follow-up into 5 evolutive periods. The biopsies revealed a progressive histologic from chronic persistent hepatitis to an active chronic hepatitis and cirrhosis. The aminotransferases followed a floating course in the whole period, with ALT greater than AST starting from the 3rd period. The 3rd period (from 5th to 8th year) was of least activity of the aminotransferases, and the 4th and 5th periods (from 8th to 13th year) showed the highest activity of ALT. The 2nd period (from 3rd to 5th year) showed the least portion of gamma globulin and the highest of albumin in comparison with the others. There was no connection between the levels of aminotransferases and the values of gamma globulin and albumin in the follow up process. The treatment employed in the 5th evolutive period (prednisone and colchicine) did not present any biochemical improvement.

  1. Inhibitory effects of fermented brown rice and rice bran on the development of acute hepatitis in Long-Evans Cinnamon rats.

    PubMed

    Shibata, Toshiyuki; Nagayasu, Hiroki; Kitajo, Hiroyuki; Arisue, Makoto; Yamashita, Tomomi; Hatakeyama, Daijiro; Iwasaki, Teruaki; Kobayashi, Hiroshi

    2006-04-01

    To investigate the effects of fermented brown rice (FBRA) on the development of hereditary hepatitis in Long-Evans Cinnamon (LEC) rats, we compared the incidence and grades of acute hepatitis among rats fed 5% and 10% FBRA in the conventional diet and the conventional diet alone. Both the 5% and 10% FBRA-supplemented diets indicated a tendency to prevent the development of hepatitis, and the significant effect of 10% FBRA was observed until 16-17 weeks of age in the accumulated incidence and survival ratio compared with the unsupplemented conventional diet, although no significant difference was observed between 5% and 10% FBRA-supplemented diets. At the age of 12 weeks, which is just before the rats develop hepatitis, serum copper levels in rats fed either of the test diets were similar to those in rats fed the conventional diet. Furthermore, the copper concentration in liver tissue at 12 weeks of age was not changed by the test diet. These results suggest that FBRA has preventive effects on the development of hepatitis in LEC rats and may play an important role in protecting the liver against the free radicals induced by copper accumulation in the liver.

  2. Molecular characterization of hepatitis A virus isolated from acute gastroenteritis patients in the Seoul region of Korea.

    PubMed

    Park, S-H; Kim, E-J; Lee, J-H; Choi, S-S; Kim, M-S; Jung, S-S; Han, G-Y; Yun, H-S; Chun, D-S; Oh, S-S; Kim, H-S

    2009-10-01

    Hepatitis A virus (HAV) is a major public health problem throughout the world. As a result of declining HAV endemic in Korea, an increasing number of children and adolescents have become susceptible to HAV infection. HAV is related with sanitation conditions of the environment and is transmitted via the fecal-oral route, either through person-to-person contact or by contaminated water and food. The present study has been carried out to determine the phylogenetic analysis and circulating patterns of HAV strains detected from hospitalized patients with acute gastroenteritis (AGE) in the Seoul region of Korea. In total, 2,782 stool specimens from hospitalized patients with AGE collected in October 2006 to September 2007 in Seoul were tested for HAV. A pair comparison of the nucleic acid sequence of a 159-bp base region at the putative VP1/2A junction of 85 Seoul isolates revealed that the most common HAV strain circulating in the region during 2006-2007 was subgenotype IA. HAV phylogenetic studies can provide important information on the genetic characteristics of HAV from AGE patients who may subsequently become the source of infection in Korea.

  3. Hypothyroidism minimizes the effects of acute hepatic failure caused by endoplasmic reticulum stress and redox environment alterations in rats.

    PubMed

    Blas-Valdivia, Vanessa; Cano-Europa, Edgar; Martinez-Perez, Yoalli; Lezama-Palacios, Ruth; Franco-Colin, Margarita; Ortiz-Butron, Rocio

    2015-10-01

    The aim of this study was to investigate if a protective effect from hypothyroidism in acute liver failure resulted from reduced endoplasmic reticulum stress and changes to the redox environment. Twenty male Sprague-Dawley rats were divided in four groups: (1) euthyroid (sham surgery), (2) hypothyroid, (3) euthyroid (sham surgery)+thioacetamide and (4) hypothyroid+thioacetamide. Hypothyroidism was confirmed two weeks after thyroidectomy, and thioacetamide (TAA) (400mg/kg, ip) was administrated to the appropriate groups for three days with supportive therapy. Grades of encephalopathy in all animals were determined using behavioral tests. Animals were decapitated and their blood was obtained to assess liver function. The liver was dissected: the left lobe was used for histology and the right lobe was frozen for biochemical assays. Body weight, rectal temperature and T4 concentration were lower in hypothyroid groups. When measurements of oxidative stress markers, redox environment, γ-glutamylcysteine synthetase and glutathione-S-transferase were determined, we observed that hypothyroid animals with TAA compensated better with oxidative damage than euthyroid animals treated with TAA. Furthermore, we measured reduced expressions of GADD34, caspase-12 and GRP78 and subsequently less hypothyroidism-induced cellular damage in hypothyroid animals. We conclude that hypothyroidism protects against hepatic damage caused by TAA because it reduces endoplasmic reticulum stress and changes to the redox environment.

  4. Hypothyroidism minimizes the effects of acute hepatic failure caused by endoplasmic reticulum stress and redox environment alterations in rats.

    PubMed

    Blas-Valdivia, Vanessa; Cano-Europa, Edgar; Martinez-Perez, Yoalli; Lezama-Palacios, Ruth; Franco-Colin, Margarita; Ortiz-Butron, Rocio

    2015-10-01

    The aim of this study was to investigate if a protective effect from hypothyroidism in acute liver failure resulted from reduced endoplasmic reticulum stress and changes to the redox environment. Twenty male Sprague-Dawley rats were divided in four groups: (1) euthyroid (sham surgery), (2) hypothyroid, (3) euthyroid (sham surgery)+thioacetamide and (4) hypothyroid+thioacetamide. Hypothyroidism was confirmed two weeks after thyroidectomy, and thioacetamide (TAA) (400mg/kg, ip) was administrated to the appropriate groups for three days with supportive therapy. Grades of encephalopathy in all animals were determined using behavioral tests. Animals were decapitated and their blood was obtained to assess liver function. The liver was dissected: the left lobe was used for histology and the right lobe was frozen for biochemical assays. Body weight, rectal temperature and T4 concentration were lower in hypothyroid groups. When measurements of oxidative stress markers, redox environment, γ-glutamylcysteine synthetase and glutathione-S-transferase were determined, we observed that hypothyroid animals with TAA compensated better with oxidative damage than euthyroid animals treated with TAA. Furthermore, we measured reduced expressions of GADD34, caspase-12 and GRP78 and subsequently less hypothyroidism-induced cellular damage in hypothyroid animals. We conclude that hypothyroidism protects against hepatic damage caused by TAA because it reduces endoplasmic reticulum stress and changes to the redox environment. PMID:26238033

  5. Digenic inheritance of mutations in the coproporphyrinogen oxidase and protoporphyrinogen oxidase genes in a unique type of porphyria.

    PubMed

    van Tuyll van Serooskerken, Anne Moniek; de Rooij, Felix W; Edixhoven, Annie; Bladergroen, Reno S; Baron, Jens M; Joussen, Sylvia; Merk, Hans F; Steijlen, Peter M; Poblete-Gutiérrez, Pamela; te Velde, Kornelis; Wilson, J H Paul; Koole, Rita H; van Geel, Michel; Frank, Jorge

    2011-11-01

    The simultaneous dysfunction of two enzymes within the heme biosynthetic pathway in a single patient is rare. Not more than 15 cases have been reported. A woman with a transient episode of severe photosensitivity showed a biochemical porphyrin profile suggestive of hereditary coproporphyria (HCP), whereas some of her relatives had a profile that was suggestive of variegate porphyria (VP). HCP and VP result from a partial enzymatic deficiency of coproporphyrinogen oxidase (CPOX) and protoporphyrinogen oxidase (PPOX), respectively. DNA analysis in the index patient revealed mutations in both the CPOX and PPOX genes, designated as c.557-15C>G and c.1289dupT, respectively. The CPOX mutation leads to a cryptic splice site resulting in retention of 14 nucleotides from intron 1 in the mRNA transcript. Both mutations encode null alleles and were associated with nonsense-mediated mRNA decay. Given the digenic inheritance of these null mutations, coupled with the fact that both HCP and VP can manifest with life-threatening acute neurovisceral attacks, the unusual aspect of this case is a relatively mild clinical phenotype restricted to dermal photosensitivity.

  6. Acute effects of moderate Fluosol-DA hemodilution on hepatic microsomal and nonmicrosomal metabolism in rats.

    PubMed

    Shrewsbury, R P

    1992-01-01

    Fluosol has been shown to alter the disposition of several drugs immediately after its administration. Investigations in this laboratory established that the disposition of several drug markers requiring the hepatic microsomal cytochrome P-450 isoenzymes was time dependent for 72 hours. It was an additional purpose of the research to determine if the nonmicrosomal sulfation and acetylation pathways were also influenced by Fluosol hemodilution in a time dependent manner. Rats were moderately hemodiluted with Fluosol and received an intravenous dose of a drug marker 24, 48, or 72 hours after hemodilution. The formation clearance (ClF) of specific metabolites was used as the pharmacokinetic measure of a specific enzymatic activity. 3-Hydroxymethyl antipyrine ClF (phenobarbital inducible microsomal cytochrome P-450 isoenzymes) increased 300% only at 48 hours. Acetylsulfamethazine ClF (nonmicrosomal acetylation) increased 287% and 162% at 24 and 48 hours, respectively. Acetaminophen sulfate ClF (nonmicrosomal sulfation) decreased 30% only at 48 hours. Substantial evidence shows that cytochrome P-450 content is induced at 72 hours and remains induced for an unprecedented length of time by the PFCs in Fluosol. Therefore, it was unexpected that 3-hydroxymethyl antipyrine ClF was not increased at 72 hours. Several possible explanations are discussed for the unexpected findings.

  7. The antioxidant effect of DL-alpha-lipoic acid on copper-induced acute hepatitis in Long-Evans Cinnamon (LEC) rats.

    PubMed

    Yamamoto, H; Watanabe, T; Mizuno, H; Endo, K; Fukushige, J; Hosokawa, T; Kazusaka, A; Fujita, S

    2001-01-01

    The Long-Evans Cinnamon (LEC) rats, due to a genetic defect, accumulate excess copper (Cu) in the liver in a manner similar to patients with Wilson's disease and spontaneously develop acute hepatitis with severe jaundice. In this study we examined the protective effect of DL-alpha-Lipoic acid (LA) against acute hepatitis in LEC rats. LA was administered to LEC rats by gavage in doses of 10, 30 and 100 mg/kg five times per week, starting at 8-weeks-old and continuing till 12-weeks-old. Although LA had little effect against the increases in serum transaminase activities, it suppressed the loss of body weight and prevented severe jaundice in a dose-dependent manner. Antioxidant system analyses in liver showed that LA treatment significantly suppressed the inactivations of catalase and glutathione peroxidase, and the induction of heme oxygenase-1, an enzyme which is inducible under oxidative stress. Furthermore, LA showed dose-dependent suppressive effect against increase in nonheme iron contents of both cytosolic and crude mitochondrial fractions in a dose-dependent manner. Although at the highest dose, LA slightly suppressed the accumulation of Cu in crude mitochondrial fraction, it had no effect on the accumulation of Cu in cytosolic fraction. While LA completely suppressed the increase in lipid peroxidation (LPO) in the microsomal fraction at the highest dose, the suppressive effect against LPO in crude mitochondrial fractions was slight. From these results, it is concluded that LA has antioxidant effects at the molecular level against the development of Cu-induced hepatitis in LEC rats. Moreover, mitochondrial oxidative damage might be involved in the development of acute hepatitis in LEC rats.

  8. Role of p38 Mapk in development of acute hepatic injury in Long-Evans Cinnamon (LEC) rats, an animal model of human Wilson's disease.

    PubMed

    Kadowaki, Shingo; Meguro, Saori; Imaizumi, Yoshitaka; Sakai, Hiroshi; Endoh, Daiji; Hayashi, Masanobu

    2013-12-30

    The Long-Evans Cinnamon (LEC) rat, an animal model of human Wilson's disease, spontaneously develops fulminant hepatitis associated with severe jaundice at about 4 months of age. In this study, we examined the changes in gene expression during progression of acute hepatic injury. When levels of gene expression in the liver of LEC rats at 13 weeks of age were compared to those in rats at 4 weeks of age using oligonucleotide arrays, 1,620 genes out of 7,700 genes analyzed showed more than 2-fold differences. Expression levels of 11 of 29 genes related to stress-activating protein kinase (SAPK) changed by more than 2-fold in the liver of LEC rats, but none of the SAPK-related genes showed changes in expression levels in the liver of control rats. Activity of p38 mapk in the liver of LEC rats at 13 weeks of age was about 8.1-fold higher than that in rats at 4 weeks of age. When LEC rats were administered SB203580, a p38 mapk-specific inhibitor, by s.c. injection twice a week from 10 to 13 weeks of age, activities of p38 mapk in the liver, activities of AST and ALT and concentrations of bilirubin in sera of rats administered SB203580 significantly decreased compared to those in rats not administered. These results showed that the increase in activities of p38 mapk was related to the occurrence of acute hepatic injury in LEC rats.

  9. Acute Central Neuropeptide Y Administration Increases Food Intake but Does Not Affect Hepatic Very Low-Density Lipoprotein (Vldl) Production in Mice

    PubMed Central

    Havekes, Louis M.; Romijn, Johannes A.; Rensen, Patrick C. N.

    2013-01-01

    Objective Central neuropeptide Y (NPY) administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL)-triglyceride (TG) in rats. As hypertriglyceridemia is an important risk factor for atherosclerosis, for which well-established mouse models are available, we set out to validate the effect of NPY on hepatic VLDL-TG production in mice, to ultimately investigate whether NPY, by increasing VLDL production, contributes to the development of atherosclerosis. Research Design and Methods Male C57Bl/6J mice received an intracerebroventricular (i.c.v.) cannula into the lateral (LV) or third (3V) ventricle of the brain. One week later, after a 4 h fast, the animals received an intravenous (i.v.) injection of Tran35S (100 µCi) followed by tyloxapol (500 mg/kg body weight; BW), enabling the study of hepatic VLDL-apoB and VLDL-TG production, respectively. Immediately after the i.v. injection of tyloxapol, the animals received either an i.c.v. injection of NPY (0.2 mg/kg BW in artificial cerebrospinal fluid; aCSF), synthetic Y1 receptor antagonist GR231118 (0.5 mg/kg BW in aCSF) or vehicle (aCSF), or an i.v. injection of PYY3–36 (0.5 mg/kg BW in PBS) or vehicle (PBS). Results Administration of NPY into both the LV and 3V increased food intake within one hour after injection (+164%, p<0.001 and +367%, p<0.001, respectively). NPY administration neither in the LV nor in the 3V affected hepatic VLDL-TG or VLDL-apoB production. Likewise, antagonizing central NPY signaling by either PYY3–36 or GR231118 administration did not affect hepatic VLDL production. Conclusion In mice, as opposed to rats, acute central administration of NPY increases food intake without affecting hepatic VLDL production. These results are of great significance when extrapolating findings on the central regulation of hepatic VLDL production between species. PMID:23460782

  10. Viral hepatitis: Indian scenario.

    PubMed

    Satsangi, Sandeep; Chawla, Yogesh K

    2016-07-01

    Viral hepatitis is a cause for major health care burden in India and is now equated as a threat comparable to the "big three" communicable diseases - HIV/AIDS, malaria and tuberculosis. Hepatitis A virus and Hepatitis E virus are predominantly enterically transmitted pathogens and are responsible to cause both sporadic infections and epidemics of acute viral hepatitis. Hepatitis B virus and Hepatitis C virus are predominantly spread via parenteral route and are notorious to cause chronic hepatitis which can lead to grave complications including cirrhosis of liver and hepatocellular carcinoma. Around 400 million people all over the world suffer from chronic hepatitis and the Asia-Pacific region constitutes the epicentre of this epidemic. The present article would aim to cover the basic virologic aspects of these viruses and highlight the present scenario of viral hepatitis in India. PMID:27546957

  11. Cost-effective Screening for Acute Hepatitis C Virus Infection in HIV-Infected Men Who Have Sex With Men

    PubMed Central

    Linas, Benjamin P.; Wong, Angela Y.; Schackman, Bruce R.; Kim, Arthur Y.; Freedberg, Kenneth A.

    2012-01-01

    Background. We used a Monte Carlo computer simulation to estimate the effectiveness and cost-effectiveness of screening for acute hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)–infected men who have sex with men. Methods. One-time screening for prevalent HCV infection was performed at the time of enrollment in care, followed by either symptom-based screening, screening with liver function tests (LFTs), HCV antibody (Ab) screening, or HCV RNA screening in various combinations and intervals. We considered both treatment with pegylated interferon and ribavirin (PEG/RBV) alone and with an HCV protease inhibitor. Outcome measures were life expectancy, quality-adjusted life expectancy, direct medical costs, and cost-effectiveness, assuming a societal willingness to pay $100 000 per quality-adjusted life-year (QALY) gained. Results. All strategies increased life expectancy (from 0.49 to 0.94 life-months), quality-adjusted life expectancy (from 0.47 to 1.00 quality-adjusted life-months), and costs (from $1900 to $7600), compared with symptom-based screening. The incremental cost-effectiveness ratio of screening with 6-month LFTs and a 12-month HCV Ab test, compared with symptom-based screening, was $43 700/QALY (for PEG/RBV alone) and $57 800/QALY (for PEG/RBV plus HCV protease inhibitor). The incremental cost-effectiveness ratio of screening with 3-month LFTs, compared with 6-month LFTs plus a 12-month HCV Ab test, was $129 700/QALY (for PEG/RBV alone) and $229 900/QALY (for PEG/RBV plus HCV protease inhibitor). With HCV protease inhibitor–based therapy, screening with 6-month LFTs and a 12-month HCV Ab test was the optimal strategy when the HCV infection incidence was ≤1.25 cases/100 person-years. The 3-month LFT strategy was optimal when the incidence was >1.25 cases/100 person-years. Conclusions. Screening for acute HCV infection in HIV-infected MSM prolongs life expectancy and is cost-effective. Depending on incidence

  12. Titration of hepatitis B virus infectivity in the sera of pre-acute and late acute phases of HBV infection: transmission experiments to chimeric mice with human liver repopulated hepatocytes.

    PubMed

    Tabuchi, Ayako; Tanaka, Junko; Katayama, Keiko; Mizui, Masaaki; Matsukura, Harumichi; Yugi, Hisao; Shimada, Takashi; Miyakawa, Yuzo; Yoshizawa, Hiroshi

    2008-12-01

    Studies of hepatitis B virus (HBV) infection in non-human primates such as chimpanzees are no longer possible due to ethical considerations and the endangered status of chimpanzees since April 2007 in Japan. A human hepatocyte transplanted chimeric mouse was used to characterize HBV infectivity in serial stages of acute infection. Chimeric mice were inoculated intravenously with serum samples obtained from an experimentally infected chimpanzee with HBV. Sera from the pre-acute phases (i.e., rump-up viremia prior to anti-HBc) and late acute phases (i.e., declining phase of HBsAg and anti-HBcAb positive) were collected from the chimpanzees 57 and 244 days after inoculation. These sera contained 2.6 x 10(6) and 2.8 x 10(6) copies/ml of HBV DNA, respectively. Three chimeric mice inoculated intravenously with 100 microl of pre-acute serum (equivalent to 10(0) copy of HBV DNA) developed an HBV infection. The three chimeric mice that received 100 microl of pre-acute serum (equivalent to 10(1) copies of HBV DNA), developed high levels of serum HBV DNA. None of the three chimeric mice inoculated with 100 microl of 1:10(4) dilution (equivalent to 10(1) copies of HBV DNA) of late-acute serum was infected, while only one of three chimeric mice inoculated with 100 microl of 1:10(3) dilution (equivalent to 10(2) copies of HBV DNA) of late-acute serum developed an HBV infection. Based on these results, chimeric mice can be used as animal models for the study of HBV infectivity, pathogenesis and control. The results show that pre-acute phase HBV serum is about 100-times more infectious than late acute phase serum.

  13. The nsp2 Replicase Proteins of Murine Hepatitis Virus and Severe Acute Respiratory Syndrome Coronavirus Are Dispensable for Viral Replication

    PubMed Central

    Graham, Rachel L.; Sims, Amy C.; Brockway, Sarah M.; Baric, Ralph S.; Denison, Mark R.

    2005-01-01

    The positive-stranded RNA genome of the coronaviruses is translated from ORF1 to yield polyproteins that are proteolytically processed into intermediate and mature nonstructural proteins (nsps). Murine hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) polyproteins incorporate 16 protein domains (nsps), with nsp1 and nsp2 being the most variable among the coronaviruses and having no experimentally confirmed or predicted functions in replication. To determine if nsp2 is essential for viral replication, MHV and SARS-CoV genome RNA was generated with deletions of the nsp2 coding sequence (MHVΔnsp2 and SARSΔnsp2, respectively). Infectious MHVΔnsp2 and SARSΔnsp2 viruses recovered from electroporated cells had 0.5 to 1 log10 reductions in peak titers in single-cycle growth assays, as well as a reduction in viral RNA synthesis that was not specific for any positive-stranded RNA species. The Δnsp2 mutant viruses lacked expression of both nsp2 and an nsp2-nsp3 precursor, but cleaved the engineered chimeric nsp1-nsp3 cleavage site as efficiently as the native nsp1-nsp2 cleavage site. Replication complexes in MHVΔnsp2-infected cells lacked nsp2 but were morphologically indistinguishable from those of wild-type MHV by immunofluorescence. nsp2 expressed in cells by stable retroviral transduction was specifically recruited to viral replication complexes upon infection with MHVΔnsp2. These results demonstrate that while nsp2 of MHV and SARS-CoV is dispensable for viral replication in cell culture, deletion of the nsp2 coding sequence attenuates viral growth and RNA synthesis. These findings also provide a system for the study of determinants of nsp targeting and function. PMID:16227261

  14. The nsp2 replicase proteins of murine hepatitis virus and severe acute respiratory syndrome coronavirus are dispensable for viral replication.

    PubMed

    Graham, Rachel L; Sims, Amy C; Brockway, Sarah M; Baric, Ralph S; Denison, Mark R

    2005-11-01

    The positive-stranded RNA genome of the coronaviruses is translated from ORF1 to yield polyproteins that are proteolytically processed into intermediate and mature nonstructural proteins (nsps). Murine hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) polyproteins incorporate 16 protein domains (nsps), with nsp1 and nsp2 being the most variable among the coronaviruses and having no experimentally confirmed or predicted functions in replication. To determine if nsp2 is essential for viral replication, MHV and SARS-CoV genome RNA was generated with deletions of the nsp2 coding sequence (MHVDeltansp2 and SARSDeltansp2, respectively). Infectious MHVDeltansp2 and SARSDeltansp2 viruses recovered from electroporated cells had 0.5 to 1 log10 reductions in peak titers in single-cycle growth assays, as well as a reduction in viral RNA synthesis that was not specific for any positive-stranded RNA species. The Deltansp2 mutant viruses lacked expression of both nsp2 and an nsp2-nsp3 precursor, but cleaved the engineered chimeric nsp1-nsp3 cleavage site as efficiently as the native nsp1-nsp2 cleavage site. Replication complexes in MHVDeltansp2-infected cells lacked nsp2 but were morphologically indistinguishable from those of wild-type MHV by immunofluorescence. nsp2 expressed in cells by stable retroviral transduction was specifically recruited to viral replication complexes upon infection with MHVDeltansp2. These results demonstrate that while nsp2 of MHV and SARS-CoV is dispensable for viral replication in cell culture, deletion of the nsp2 coding sequence attenuates viral growth and RNA synthesis. These findings also provide a system for the study of determinants of nsp targeting and function. PMID:16227261

  15. Association between Serum Bilirubin and Acute Intraoperative Hyperglycemia Induced by Prolonged Intermittent Hepatic Inflow Occlusion in Living Liver Donors

    PubMed Central

    Han, Sangbin; Jin, Sang-Man; Ko, Justin Sangwook; Kim, Young Ri; Gwak, Mi Sook; Son, Hee Jeong; Joh, Jae-Won; Kim, Gaab Soo

    2016-01-01

    Background Intermittent hepatic inflow occlusion (IHIO) is associated with acute hyperglycemia during living donor hepatectomy when the ischemia is prolonged. Bilirubin is a potent antioxidant to play an important role for maintaining insulin sensitivity and preventing hyperglycemia. Thus, we aimed to test whether serum bilirubin level is associated with prolonged IHIO-induced intraoperative hyperglycemia. Methods Seventy-five living liver donors who underwent a prolonged IHIO with a >30 minute cumulative ischemia were included. The association between preoperative serum bilirubin concentrations and the risk of intraoperative hyperglycemia (blood glucose concentration >180 mg/dl) was analyzed using binary logistic regression with adjusting for potential confounders including age and steatosis. Results The number of donors who underwent 3, 4, 5, and 6 rounds of IHIO was 41, 22, 7, and 5, respectively. Twenty-nine (35%) donors developed intraoperative hyperglycemia. Total bilirubin concentration was inversely associated with hyperglycemia risk (odds ratio [OR] 0.033, 95% confidence interval [CI] 0.004–0.313, P = 0.003). There was an interaction between age and total bilirubin concentration: the effect of lower serum total bilirubin (≤0.7 mg/dl) on the development of hyperglycemia was greater in older donors (>40 years) than in younger donors (P = 0.0.028 versus P = 0.212). Both conjugated bilirubin (OR 0.001 95% CI 0.001–0.684) and unconjugated bilirubin (OR 0.011 95% CI 0.001–0.246) showed an independent association with hyperglycemia risk. Conclusions Lower preoperative serum bilirubin was associated with greater risk of prolonged IHIO-induced hyperglycemia during living donor hepatectomy particularly in older donors. Thus, more meticulous glycemic management is recommended when prolonged IHIO is necessary for surgical purposes in old living donors with lower serum bilirubin levels. PMID:27367602

  16. Acute hepatitis C in a chronically HIV-infected patient: Evolution of different viral genomic regions

    PubMed Central

    Flichman, Diego; Kott, Veronica; Sookoian, Silvia; Campos, Rodolfo

    2003-01-01

    AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up. METHODS: Serum samples of a chronically HIV infected patient that seroconverted to anti HCV antibodies were sequenced, from the event of superinfection through a period of 17 mo and in a late sample (42nd month). Hypervariable genomic regions of HIV (V3 loop of the gp120) and HCV (HVR-1 on the E2 glycoprotein gene) were studied. In order to analyze genomic regions involved in different biological functions and with the cellular immune response, HCV core and NS5A were also chosen to be sequenced. Amplification of the different regions was done by RT-PCR and directly sequenced. Confirmation of sequences was done on reamplified material. Nucleotide sequences of the different time points were aligned with CLUSTAL W 1.5, and the corresponding amino acid ones were deduced. RESULTS: Hypervariable genomic regions of both viruses (HVR1 and gp120 V3 loop) presented several nonsynonymous changes but, while in the gp120 V3 loop mutations were detected in the sample obtained right after HCV superinfection and maintained throughout, they occurred following a sequential and cumulative pattern in the HVR1. In the NS5A region of HCV, two amino acid changes were detected during the follow-up period, whereas the core region presented several amino acid replacements, once the HCV chronic infection had been established. CONCLUSION: During the HIV-HCV superinfection, each genomic region analyzed shows a different evolutionary pattern. Most of the nucleotide substitutions observed are non-synonymous and clustered in previously described epitopes, thus suggesting an immune-driven evolutionary process. PMID:12854149

  17. Intrahepatic endothelial and Kupffer cells involved in immunosuppressive cytokines and natural killer (NK)/NK T cell disorders in viral acute hepatitis

    PubMed Central

    Jacques, A; Bleau, C; Martin, J-P; Lamontagne, L

    2008-01-01

    During acute viral hepatitis, the intrahepatic tolerance sustained by immunosuppressive cytokines such as interleukin (IL)-4, IL-10, transforming growth factor (TGF)-β and prostaglandin E2 (PGE2), produced by Kupffer cells (KC), liver sinusoidal endothelial cells (LSEC), natural killer (NK) T cells and natural regulatory T cells may be disturbed. NK cells are recruited normally in the liver and produce interferon (IFN)-γ to control viral replication. The use of mouse hepatitis virus type 3 (MHV3) attenuated variants showing selected tropisms for KC or LSEC have allowed determining their roles in the disturbances of immune tolerance during viral hepatitis. Groups of C57BL/6 mice were infected with the pathogenic L2-MHV3 (KC+, LSEC+), low attenuated 51·6-MHV3 (KC+, LSEC−) or high attenuated CL12-MHV3 (KC−, LSEC−) variants for the first 3 days. Results showed that IL-10, TGF-β and PGE2 production in the liver decreased in L2-MHV3-infected mice and increased in 51·6-MHV3- and CL12-MHV3-infected mice. The ratio of IFN-γ/IL-4 in liver decreased in L2-MHV3-infected mice, while it was not (or low) altered in mice infected with the attenuated MHV3 variant mice. Phenotypic analysis of intrahepatic mononuclear cells revealed that apoptotic NK and NK T cells increased in mice infected with the L2-MHV3, but were minor in 51·6-MHV3- and CL12-MHV3-infected mice. The numbers of CD4+ forkhead box P3+ cells increased in the livers from low pathogenic CL12-MHV3 and YAC-MHV3-infected mice. These results indicate that viral permissivity of KC and LSEC is involved in the decrease of IL-10 and PGE2, while KC may play an additional role in the apoptosis of NK and NK T cells during acute viral hepatitis. PMID:18336588

  18. Multiplex ligation-dependent probe amplification: a novel approach for genetic diagnosis of Porphyria.

    PubMed

    Di Pierro, Elena; Brancaleoni, Valentina; Besana, Valeria; Cappellini, Maria Domenica

    2009-08-01

    Porphyrias are disorders caused by the genetic defects of enzymes of the heme pathway and are characterized by such a wide genetic heterogeneity that even the molecular analysis is not always decisive for a correct diagnosis. In the past few years, deletion with a size range of few kilobase pairs have been reported. These peculiar mutations, missed by both sequencing and cytogenetic techniques, have been identified by time consuming and technically demanding methods. To provide a rapid and sensitive method for the detection of deletions responsible for porphyria, we successfully designed and tested seven chemically synthesized probe sets specific for each heme gene and their flanking regions, to be used in multiplex ligation-dependent probe amplification technique.

  19. Utility of plasma fluorometric emission scanning for diagnosis of the first 2 cases reports of variegate porphyria: a very rare type of porphyrias in Thai.

    PubMed

    Chularojanamontri, Leena; Tuchinda, Chanisada; Srisawat, Chatchawan; Neungton, Neelobol; Junnu, Sarawut; Kanyok, Surin

    2008-12-01

    Two Thai women who are siblings presented with a history of recurrent pruritic vesicles on dorsum of both hands and extensor surface of forearms where the sun-exposed areas are. The excoriated vesicles were healed with depressed scars. They had no previous history of intense abdominal pain, seizure, or psychiatric disorder Urinary porphyrins were analyzed by High Performance Liquid Chromatography (HPLC). The level of coproporphyrin III was detected to be higher than the uroporphyrin level. Fluorescence emission scanning of both patients' plasma was performed and demonstrated typical emission peak at 626 nm, that confirmed the diagnosis of variegate porphyria.

  20. Manifestations of Perihepatic Lymph Nodes in Acute Flare of Chronic Hepatitis B: Association with HBeAg Status and with HBeAg Seroconversion

    PubMed Central

    Ko, Yen-Ling; Sun, Chi-Shu; Chung, Kun-Ming; Lin, Yu-Min; Feng, I-Che; Sheu, Ming-Jen; Koay, Lok-Beng; Lin, Ching-Yih; Ho, Chung-Han; Kuo, Hsing-Tao

    2015-01-01

    It has been observed that enlargement of perihepatic lymph nodes may be seen in patients with chronic hepatitis B, particularly during acute flares of CHB. We hypothesized that there may be a correlation between the nodal change patterns in CHB patients with acute flare and HBeAg status. Perihepatic lymph node sizes of 87 patients with acute flares of CHB were documented, with a median follow up of 43 months. Patients were separated into 3 groups, HBeAg-positive with HBe seroconversion (group 1), HBeAg-positive without HBe seroconversion (group 2), and HBeAg-negative (group 3). Group 1 has the highest incidence of enlarged lymph nodes (92.3%) compared with group 2 (75.8%) and group 3 (46.8%) (p = 0.003). And if nodal width at acute flare was > 8mm and interval change of nodal width was >3mm, the incidence of HBeAg seroconversion will be 75% (p<0.001). Conclusion Larger perihepatic lymph nodes are seen in CHB acute flare patients with positive HBeAg and the magnitude of nodal width change may predict HBeAg seroconversion at recovery. PMID:25689069

  1. Full-length genome characterization and genetic relatedness analysis of hepatitis A virus outbreak strains associated with acute liver failure among children.

    PubMed

    Vaughan, Gilberto; Forbi, Joseph C; Xia, Guo-Liang; Fonseca-Ford, Maureen; Vazquez, Roberto; Khudyakov, Yury E; Montiel, Sonia; Waterman, Steve; Alpuche, Celia; Gonçalves Rossi, Livia Maria; Luna, Norma

    2014-02-01

    Clinical infection by hepatitis A virus (HAV) is generally self-limited but in some cases can progress to liver failure. Here, an HAV outbreak investigation among children with acute liver failure in a highly endemic country is presented. In addition, a sensitive method for HAV whole genome amplification and sequencing suitable for analysis of clinical samples is described. In this setting, two fatal cases attributed to acute liver failure and two asymptomatic cases living in the same household were identified. In a second household, one HAV case was observed with jaundice which resolved spontaneously. Partial molecular characterization showed that both households were infected by HAV subtype IA; however, the infecting strains in the two households were different. The HAV outbreak strains recovered from all cases grouped together within cluster IA1, which contains closely related HAV strains from the United States commonly associated with international travelers. Full-genome HAV sequences obtained from the household with the acute liver failure cases were related (genetic distances ranging from 0.01% to 0.04%), indicating a common-source infection. Interestingly, the strain recovered from the asymptomatic household contact was nearly identical to the strain causing acute liver failure. The whole genome sequence from the case in the second household was distinctly different from the strains associated with acute liver failure. Thus, infection with almost identical HAV strains resulted in drastically different clinical outcomes.

  2. Uroporphyrinogen decarboxylase: Complete human gene sequence and molecular study of three families with hepatoerythropoietic porphyria

    SciTech Connect

    Moran-Jimenez, M.J.; Ged, C.; Verneuil, H. de

    1996-04-01

    A deficiency in uroporphyrinogen decarboxylase (UROD) enzyme activity, the fifth enzyme of the heme biosynthetic pathway, is found in patients with sporadic porphyria cutanea tarda (s-PCT), familial porphyria cutanea tarda (f-PCT), and hepatoerythropoietic porphyria (HEP). Subnormal UROD activity is due to mutations of the UROD gene in both f-PCT and HEP, but no mutations have been found in s-PCT. Genetic analysis has determined that f-PCT is transmitted as an autosomal dominant trait. In contrast, HEP, a severe form of cutaneous porphyria, is transmitted as an autosomal recessive trait. HEP is characterized by a profound deficiency of UROD activity, and the disease is usually manifest in childhood. In this study, a strategy was designed to identify alleles responsible for the HEP phenotype in three unrelated families. Mutations of UROD were identified by direct sequencing of four amplified fragments that contained the entire coding sequence of the UROD gene. Two new missense mutations were observed at the homoallelic state: P62L (proline-to-leucine substitution at codon 62) in a Portuguese family and Y311C (tyrosine-to-cysteine substitution at codon 311) in an Italian family. A third mutation, G281E, was observed in a Spanish family. This mutation has been previously described in three families from Spain and one from Tunisia. In the Spanish family described in this report, a paternal uncle of the proband developed clinically overt PCT as an adult and proved to be heterozygous for the G281E mutation. Mutant cDNAs corresponding to the P62L and Y311C changes detected in these families were created by site-directed mutagenesis. Recombinant proteins proved to have subnormal enzyme activity, and the Y311C mutant was thermolabile. 24 refs., 7 figs., 4 tabs.

  3. Acute kidney injury induced by protein-overload nephropathy down-regulates gene expression of hepatic cerebroside sulfotransferase in mice, resulting in reduction of liver and serum sulfatides.

    PubMed

    Zhang, Xiaowei; Nakajima, Takero; Kamijo, Yuji; Li, Gang; Hu, Rui; Kannagi, Reiji; Kyogashima, Mamoru; Aoyama, Toshifumi; Hara, Atsushi

    2009-12-25

    Sulfatides, possible antithrombotic factors belonging to sphingoglycolipids, are widely distributed in mammalian tissues and serum. We recently found that the level of serum sulfatides was significantly lower in hemodialysis patients than that in normal subjects, and that the serum level closely correlated to the incidence of cardiovascular disease. These findings suggest a relationship between the level of serum sulfatides and kidney function; however, the molecular mechanism underlying this relationship remains unclear. In the present study, the influence of kidney dysfunction on the metabolism of sulfatides was examined using an established murine model of acute kidney injury, protein-overload nephropathy in mice. Protein-overload treatment caused severe proximal tubular injuries within 4days, and this treatment obviously decreased both serum and hepatic sulfatide levels. The sphingoid composition of serum sulfatides was very similar to that of hepatic ones at each time point, suggesting that the serum sulfatide level is dependent on the hepatic secretory ability of sulfatides. The treatment also decreased hepatic expression of cerebroside sulfotransferase (CST), a key enzyme in sulfatide metabolism, while it scarcely influenced the expression of the other sulfatide-metabolizing enzymes, including arylsulfatase A, ceramide galactosyltransferase, and galactosylceramidase. Pro-inflammatory responses were not detected in the liver of these mice; however, potential oxidative stress was increased. These results suggest that down-regulation of hepatic CST expression, probably affected by oxidative stress from kidney injury, causes reduction in liver and serum sulfatide levels. This novel mechanism, indicating the crosstalk between kidney injury and specific liver function, may prove useful for helping to understand the situation where human hemodialysis patients have low levels of serum sulfatides.

  4. Dietary polyunsaturated fatty acids suppress acute hepatitis, alter gene expression and prolong survival of female Long-Evans Cinnamon rats, a model of Wilson disease.

    PubMed

    Du, Chunyan; Fujii, Yoichi; Ito, Masafumi; Harada, Manabu; Moriyama, Emiko; Shimada, Ryo; Ikemoto, Atsushi; Okuyama, Harumi

    2004-05-01

    In the Long-Evans Cinnamon rat, copper accumulates in the liver because of a mutation in the copper-transporting ATPase gene, and peroxidative stresses are supposed to be augmented. We examined the effects of dietary fatty acids on hepatitis, hepatic gene expression, and survival. Rats were fed a conventional, low-fat diet (CE2), a CE2 diet supplemented with 10 wt% of lard (Lar), high-linoleic soybean oil (Soy), or a mixture of docosahexaenoic acid (DHA)-rich fish oil and soybean oil (DHA/Soy). Among female rats, the mean survival times of the DHA/Soy and the Soy groups were longer by 17 approximately 20% than in the Lar and the CE2 groups. Among male rats, the survival times were much longer than in the females, but no significant difference in survival was observed among the dietary groups. Serum ceruloplasmin levels in female and male rats of all of the dietary groups were similar. Serum transaminase levels of the DHA/Soy group tended to be lower than in the CE2 group. Histological examinations revealed a marked degeneration in hepatic tissue integrity in the Lar and CE2 groups but not in the DHA/Soy group. Hepatic levels of metal-related genes, transferrin and ceruloplasmin, as well as those related to bile acid synthesis were up-regulated, and an inflammation-related gene (cyclooxygenase [COX]-2) was down-regulated in the DHA/Soy group. Some proliferation-related genes were also affected by the dietary fatty acids. These results indicate that polyunsaturated fatty acids suppress the development of acute hepatitis and prolong survival in females, regardless of whether they are of the n-6 or n-3 type, which are associated with altered gene expressions.

  5. Hepatoerythropoietic Porphyria Caused by a Novel Homoallelic Mutation in Uroporphyrinogen Decarboxylase Gene in Egyptian Patients.

    PubMed

    Farrag, M S; Mikula, I; Richard, E; Saudek, V; De Verneuil, H; Martásek, P

    2015-01-01

    Porphyrias are metabolic disorders resulting from mutations in haem biosynthetic pathway genes. Hepatoerythropoietic porphyria (HEP) is a rare type of porphyria caused by the deficiency of the fifth enzyme (uroporphyrinogen decarboxylase, UROD) in this pathway. The defect in the enzymatic activity is due to biallelic mutations in the UROD gene. Currently, 109 UROD mutations are known. The human disease has an early onset, manifesting in infancy or early childhood with red urine, skin photosensitivity in sun-exposed areas, and hypertrichosis. Similar defects and links to photosensitivity and hepatopathy exist in several animal models, including zebrafish and mice. In the present study, we report a new mutation in the UROD gene in Egyptian patients with HEP. We show that the homozygous c.T163A missense mutation leads to a substitution of a conserved phenylalanine (amino acid 55) for isoleucine in the enzyme active site, causing a dramatic decrease in the enzyme activity (19 % of activity of wild-type enzyme). Inspection of the UROD crystal structure shows that Phe-55 contacts the substrate and is located in the loop that connects helices 2 and 3. Phe-55 is strictly conserved in both prokaryotic and eukaryotic UROD. The F55I substitution likely interferes with the enzyme-substrate interaction.

  6. Pathogenesis of Hepatic Encephalopathy

    PubMed Central

    Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

    2012-01-01

    Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

  7. Circadian Rhythms in Acute Intermittent Porphyria—a Pilot Study

    PubMed Central

    Larion, Sebastian; Caballes, F. Ryan; Hwang, Sun-Il; Lee, Jin-Gyun; Rossman, Whitney Ellefson; Parsons, Judy; Steuerwald, Nury; Li, Ting; Maddukuri, Vinaya; Groseclose, Gale; Finkielstein, Carla V.; Bonkovsky, Herbert L.

    2013-01-01

    Acute intermittent porphyria (AIP) is an inherited disorder of heme synthesis wherein a partial deficiency of porphobilinogen [PBG] deaminase [PBGD], with other factors may give rise to biochemical and clinical manifestations of disease. The biochemical hallmarks of active AIP are relative hepatic heme deficiency and uncontrolled up-regulation of hepatic 5-aminolevulinic acid [ALA] synthase-1 [ALAS1] with overproduction of ALA and PBG. The treatment of choice is intravenous heme, which restores the deficient regulatory heme pool of the liver and represses ALAS1. Recently, heme has been shown to influence circadian rhythms by controlling their negative feedback loops. We evaluated whether subjects with AIP exhibited an altered circadian profile. Over a 21 h period, we measured levels of serum cortisol, melatonin, ALA, PBG, and mRNA levels [in peripheral blood mononuclear cells] of selected clock-controlled genes and genes involved in heme synthesis in 10 Caucasian [European-American] women who were either post-menopausal or had been receiving female hormone therapy, 6 of whom have AIP and 4 do not and are considered controls. Four AIP subjects with biochemical activity exhibited higher levels of PBG and lower levels and dampened oscillation of serum cortisol, and a trend for lower levels of serum melatonin, than controls or AIP subjects without biochemical activity. Levels of clock-controlled gene mRNAs showed significant increases over baseline in all subjects at 5 am and 11 pm, whereas mRNA levels of ALAS1, ALAS2, and PBGD were increased only at 11 pm in subjects with active AIP. This pilot study provides evidence for disturbances of circadian markers in women with active AIP that may trigger or sustain some common clinical features of AIP. PMID:23650938

  8. Hepatitis E virus: do locally acquired infections in Australia necessitate laboratory testing in acute hepatitis patients with no overseas travel history?

    PubMed Central

    Shrestha, Ashish C.; Faddy, Helen M.; Flower, Robert L. P.; Seed, Clive R.; Keller, Anthony J.

    2015-01-01

    Summary Hepatitis E virus (HEV) is emerging as a global public health threat. Water-borne HEV outbreaks are common in developing countries and are associated with genotypes 1 and 2. In industrialised countries, sporadic cases of zoonotic transmission associated with genotypes 3 and 4 are increasingly being reported. Transfusion- and transplantation-transmitted HEV have been documented, although ingestion of contaminated food is thought to be the major transmission route. Severe disease is possible and chronic hepatitis infection occurs in solid-organ-transplant recipients and in patients with immunosuppressive disorders. In Australia, HEV cases are mainly travellers returning from disease endemic countries. Indeed, there are few reported cases of locally acquired HEV. Pigs in Australia have been shown to be infected with HEV, which indicates the possibility of zoonotic transmission. The extent of locally acquired infection is not known, however it may be greater than expected and may necessitate laboratory testing in patients reporting no overseas travel. PMID:25560836

  9. Hepatic transcriptomic and metabolic responses of hybrid striped bass (Morone saxatilis×Morone chrysops) to acute and chronic hypoxic insult.

    PubMed

    Beck, Benjamin H; Fuller, S Adam; Li, Chao; Green, Bartholomew W; Zhao, Honggang; Rawles, Steven D; Webster, Carl D; Peatman, Eric

    2016-06-01

    Striped bass (Morone saxatilis), white bass (Morone chrysops), and their hybrid are an important group of fish prized for recreational angling in the United States, and there and abroad as a high-value farmed fish. Regardless of habitat, it is not uncommon for fish of the genus Morone to encounter and cope with conditions of scarce oxygen availability. Previously, we determined that hybrid striped bass reared under conditions of chronic hypoxia exhibited reduced feed intake, lower lipid and nutrient retention, and poor growth. To better understand the molecular mechanisms governing these phenotypes, in the present study, we examined the transcriptomic profiles of hepatic tissue in hybrid striped bass exposed to chronic hypoxia (90days at 25% oxygen saturation) and acute hypoxia (6h at 25% oxygen saturation). Using high-throughput RNA-seq, we found that over 1400 genes were differentially expressed under disparate oxygen conditions, with the vast majority of transcriptional changes occurring in the acute hypoxia treatment. Gene pathway and bioenergetics analyses revealed hypoxia-mediated perturbation of genes and gene networks related to lipid metabolism, cell death, and changes in hepatic mitochondrial content and cellular respiration. This study offers a more comprehensive view of the temporal and tissue-specific transcriptional changes that occur during hypoxia, and reveals new and shared mechanisms of hypoxia tolerance in teleosts. PMID:26851735

  10. Protective effects of protostemonine on LPS/GalN-induced acute liver failure: Roles of increased hepatic expression of heme oxygenase-1.

    PubMed

    Cheng, Zhuo; Yue, Ling; Zhao, Wenhao; Yang, Xinzhou; Shu, Guangwen

    2015-12-01

    Here, we explored protective effects of protostemonine (PSN), on mouse acute liver failure induced by lipopolysaccharide/d-galactosamine (LPS/GalN). PSN dose-dependently declined LPS/GalN-induced lethality of mice as well as increase of ALT/AST activities in their serum. Hepatoprotective effects of PSN were also supported by liver histopathological examinations. After LPS/GalN treatment, severe oxidative stresses in the liver could be detected by boosted MDA and ROS as well as decreased GSH. Moreover, hepatic expression of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, were sharply elevated. These symptoms were dose-dependently ameliorated by PSN. Mechanistically, PSN promoted the transcription and translation of heme oxygenase-1 (HO-1) in hepatocytes and liver Kupffer cells. Nrf2 is a master transcription factor contributing to the expression of HO-1. PSN elevated Nrf2 nuclear accumulation and enhanced Nrf2/HO-1 promoter interaction. Suppressing enzyme activity of HO-1 by co-treating mice with HO-1 inhibitor ZnPP abolished protective effects of PSN. ZnPP also abrogated alleviative impacts of PSN on LPS/GalN-mediated hepatic oxidative stresses and inflammatory responses. Finally, we showed that PSN exhibited undetectable toxic effects on vital organs of mice. Our findings suggested that PSN is able to attenuate LPS/GalN-induced acute liver failure and upregulating HO-1 expression is implicated in its hepatoprotective activity.

  11. Hepatic transcriptomic and metabolic responses of hybrid striped bass (Morone saxatilis×Morone chrysops) to acute and chronic hypoxic insult.

    PubMed

    Beck, Benjamin H; Fuller, S Adam; Li, Chao; Green, Bartholomew W; Zhao, Honggang; Rawles, Steven D; Webster, Carl D; Peatman, Eric

    2016-06-01

    Striped bass (Morone saxatilis), white bass (Morone chrysops), and their hybrid are an important group of fish prized for recreational angling in the United States, and there and abroad as a high-value farmed fish. Regardless of habitat, it is not uncommon for fish of the genus Morone to encounter and cope with conditions of scarce oxygen availability. Previously, we determined that hybrid striped bass reared under conditions of chronic hypoxia exhibited reduced feed intake, lower lipid and nutrient retention, and poor growth. To better understand the molecular mechanisms governing these phenotypes, in the present study, we examined the transcriptomic profiles of hepatic tissue in hybrid striped bass exposed to chronic hypoxia (90days at 25% oxygen saturation) and acute hypoxia (6h at 25% oxygen saturation). Using high-throughput RNA-seq, we found that over 1400 genes were differentially expressed under disparate oxygen conditions, with the vast majority of transcriptional changes occurring in the acute hypoxia treatment. Gene pathway and bioenergetics analyses revealed hypoxia-mediated perturbation of genes and gene networks related to lipid metabolism, cell death, and changes in hepatic mitochondrial content and cellular respiration. This study offers a more comprehensive view of the temporal and tissue-specific transcriptional changes that occur during hypoxia, and reveals new and shared mechanisms of hypoxia tolerance in teleosts.

  12. Acute, fatal Sarcocystis calchasi-associated hepatitis in Roller pigeons (Columbia livia f. dom.) at Philadelphia Zoo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four Roller pigeons (Columba livia f. dom.) at the Philadelphia Zoo died suddenly. Necropsy examination revealed macroscopic hepatitis. Microscopically, the predominant lesions were in liver, characterized with necrosis and mixed cell inflammatory response. Sarcocystis calchasi-like schizonts and fr...

  13. Trouble with Bleeding: Risk Factors for Acute Hepatitis C among HIV-Positive Gay Men from Germany—A Case-Control Study

    PubMed Central

    Schmidt, Axel J.; Rockstroh, Jürgen K.; Vogel, Martin; An der Heiden, Matthias; Baillot, Armin; Krznaric, Ivanka; Radun, Doris

    2011-01-01

    Objectives To identify risk factors for hepatitis C among HIV-positive men who have sex with men (MSM), focusing on potential sexual, nosocomial, and other non-sexual determinants. Background Outbreaks of hepatitis C virus (HCV) infections among HIV-positive MSM have been reported by clinicians in post-industrialized countries since 2000. The sexual acquisition of HCV by gay men who are HIV positive is not, however, fully understood. Methods Between 2006 and 2008, a case-control study was embedded into a behavioural survey of MSM in Germany. Cases were HIV-positive and acutely HCV-co-infected, with no history of injection drug use. HIV-positive MSM without known HCV infection, matched for age group, served as controls. The HCV-serostatus of controls was assessed by serological testing of dried blood specimens. Univariable and multivariable regression analyses were used to identify factors independently associated with HCV-co-infection. Results 34 cases and 67 controls were included. Sex-associated rectal bleeding, receptive fisting and snorting cocaine/amphetamines, combined with group sex, were independently associated with case status. Among cases, surgical interventions overlapped with sex-associated rectal bleeding. Conclusions Sexual practices leading to rectal bleeding, and snorting drugs in settings of increased HCV-prevalence are risk factors for acute hepatitis C. We suggest that sharing snorting equipment as well as sharing sexual partners might be modes of sexual transmission. Condoms and gloves may not provide adequate protection if they are contaminated with blood. Public health interventions for HIV-positive gay men should address the role of blood in sexual risk behaviour. Further research is needed into the interplay of proctosurgery and sex-associated rectal bleeding. PMID:21408083

  14. XTC-induced hepatitis.

    PubMed

    Oranje, W A; von Pol, P; vd Wurff, A; Zeijen, R N; Stockbrügger, R W; Arends, J W

    1994-02-01

    An increasing number of severe complications associated with the use of XTC is being reported. After 11 earlier case reports we describe an acute hepatitis due to occasional use of XTC in a 25-year-old woman.

  15. Cellular and humoral immune reactions in chronic active liver disease. II. Lymphocyte subsets and viral antigens in liver biopsies of patients with acute and chronic hepatitis B.

    PubMed Central

    Eggink, H F; Houthoff, H J; Huitema, S; Wolters, G; Poppema, S; Gips, C H

    1984-01-01

    The characteristics and distribution of the inflammatory infiltrate in liver biopsies of 25 patients with hepatitis B viral (HBV) infection were studied in relation to the distribution and expression of HBV antigens. Mononuclear subsets were characterized with monoclonal (OKT, OKM, Leu) antibodies to surface antigens. For the demonstration of viral antigens directly conjugated antibodies to surface (HBsAg), core (HBcAg) and 'e' (HBeAg) antigen were used. For the study of mutual relations all methods were performed on serial cut tissue sections. In chronic active hepatitis B (CAH-B, n = 12) OKT8+ lymphocytes of T cell origin were the only cell type present in areas with liver cell degeneration and T cell cytotoxicity appears to be the only immune mechanism. In chronic persistent hepatitis B (CPH-B, n = 7) the only conspicuous feature was the presence of many Leu 3+ lymphocytes of the helper/inducer population in the portal tracts. In acute hepatitis B (AHB, n = 6) OKT8+ cells of non-T origin (OKT1-,3-) and Leu 7+ cells of presumed natural killer (NK) potential predominated in the areas with liver cell necrosis, and non-T cell cytotoxicity appears to be the predominant immune mechanism. In none of these disease entities a positive spatial relation could be established between the cytotoxic cells and the demonstrable expression of HBV antigens in hepatocytes. It is concluded that differences in immunological reaction pattern may explain the different course in the three forms of HBV infection studied. Images Fig. 1 Fig. 2 PMID:6713726

  16. Protective effect of panax notoginseng saponins on acute ethanol-induced liver injury is associated with ameliorating hepatic lipid accumulation and reducing ethanol-mediated oxidative stress.

    PubMed

    Ding, Ren-Bo; Tian, Ke; Cao, Yi-Wei; Bao, Jiao-Lin; Wang, Meng; He, Chengwei; Hu, Yuanjia; Su, Huanxing; Wan, Jian-Bo

    2015-03-11

    The aim of present study was to evaluate the effects of Panax notoginseng saponins (PNS) against acute ethanol-induced liver injury and further to elucidate its probable mechanisms. Mice were treated with PNS (100 or 300 mg/kg) once daily for seven consecutive days priors to ethanol gavage (4.7 g/kg) every 12 h for a total of three doses. Acute alcohol gavage dramatically significantly increased serum activities of alanine aminotransferase (ALT) (23.4 ± 5.0 IU/L vs 11.7 ± 4.1 IU/L) and aspartate aminotransferase (AST) (52.6 ± 14.9 IU/L vs 31.1 ± 12.9 IU/L), and hepatic triglyceride level (4.04 ± 0.64 mg/g vs 1.92 ± 0.34 mg/g), these elevations were significantly diminished by pretreatment with PNS at dose of 100 mg/kg or 300 mg/kg. Alcohol exposure markedly induced the lipolysis of white adipose tissue (WAT), up-regulated protein expression of the phosphorylated hormone-sensitive lipase (p-HSL, p < 0.01), and total HSL (p < 0.01), and enhanced fatty acid uptake capacity in liver as indicated by increasing hepatic CD36 expression (p < 0.01), these effects were attenuated by PNS treatment. Additionally, PNS suppressed the elevation of reactive oxygen species (ROS) production and malondialdehyde (MDA) content, reduced TNF-α and IL-6 levels, restored glutathione (GSH) level, enhanced the superoxide dismutase (SOD) activity in liver, and abrogated cytochrome P450 2E1 (CYP2E1) induction. These data demonstrated that pretreatment with PNS protected against acute ethanol-induced liver injury, possibly through ameliorating hepatic lipid accumulation and reducing CYP2E1-mediated oxidative stress. Our findings also suggested that PNS may be potential to be developed as an effective agent for acute ethanol-induced liver injury. PMID:25665731

  17. Hepatitis C

    PubMed Central

    Mehta, Bharti; Kumar Dharma, Vijay; Chawla, Sumit; Jindal, Harashish; Bhatt, Bhumika

    2014-01-01

    Hepatitis C Virus (HCV) infection is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Following acute infection, 20% of people eliminate the virus over weeks or months and are often asymptomatic. The remaining 80% of people will develop chronic disease, of which approximately 20% will eventually develop liver cirrhosis and 1–5% will develop liver cancer. About 150 million people are chronically infected with HCV, and more than 350 000 people die every year from hepatitis C related liver diseases. The economic cost of hepatitis C is significant both to the individual and to the society. In the United States the average lifetime cost of the disease was estimated at $33 407 USD with the cost of a liver transplant approximately $200 000 USD. PEG-IFN and ribavirin treatment is also expensive and, at an average cost of approximately GB £7000 in the UK for a treatment course, is unaffordable in developing countries. Hepatitis C, not only brings down the quality of the life of individuals but also affect progress of the nation by adding financial burden. If we prevent the disease from occurring or find a perfect cure of the disease, in form of a prophylactic or therapeutic vaccine, it will be a boon to not only to the individual but to the nation as a whole. PMID:24165512

  18. Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence

    PubMed Central

    Schulze zur Wiesch, Julian; Ciuffreda, Donatella; Lewis-Ximenez, Lia; Kasprowicz, Victoria; Nolan, Brian E.; Streeck, Hendrik; Aneja, Jasneet; Reyor, Laura L.; Allen, Todd M.; Lohse, Ansgar W.; McGovern, Barbara; Chung, Raymond T.; Kwok, William W.; Kim, Arthur Y.

    2012-01-01

    Vigorous proliferative CD4+ T cell responses are the hallmark of spontaneous clearance of acute hepatitis C virus (HCV) infection, whereas comparable responses are absent in chronically evolving infection. Here, we comprehensively characterized the breadth, specificity, and quality of the HCV-specific CD4+ T cell response in 31 patients with acute HCV infection and varying clinical outcomes. We analyzed in vitro T cell expansion in the presence of interleukin-2, and ex vivo staining with HCV peptide-loaded MHC class II tetramers. Surprisingly, broadly directed HCV-specific CD4+ T cell responses were universally detectable at early stages of infection, regardless of the clinical outcome. However, persistent viremia was associated with early proliferative defects of the HCV-specific CD4+ T cells, followed by rapid deletion of the HCV-specific response. Only early initiation of antiviral therapy was able to preserve CD4+ T cell responses in acute, chronically evolving infection. Our results challenge the paradigm that HCV persistence is the result of a failure to prime HCV-specific CD4+ T cells. Instead, broadly directed HCV-specific CD4+ T cell responses are usually generated, but rapid exhaustion and deletion of these cells occurs in the majority of patients. The data further suggest a short window of opportunity to prevent the loss of CD4+ T cell responses through antiviral therapy. PMID:22213804

  19. Acute liver graft failure due to emergence of lamivudine resistant hepatitis B virus: rapid resolution during treatment with adefovir

    PubMed Central

    Mutimer, D; Feraz-Neto, B; Harrison, R; O'Donnell, K; Shaw, J; Cane, P; Pillay, D

    2001-01-01

    BACKGROUND—Strategies for prevention of liver graft reinfection by hepatitis B virus (HBV) have been developed during recent years. Initially, passive immunoprophylaxis with high titre HBV immunoglobulin (HBIg), followed by lamivudine prophylaxis, and then the combination of lamivudine and HBIg have been employed. However, suboptimal use of the combination may be associated with failure of prophylaxis reflected by the emergence of HBV species with genetic changes that confer resistance to lamivudine and HBIg. Reinfection of the graft by HBV can be associated with rapid development of liver failure.
CASE REPORT—A 43 year old HBV infected man received lamivudine before transplantation, and lamivudine and HBIg after transplantation. Despite prophylaxis, graft reinfection and severe hepatitis were observed. The observed serological evolution and genetic sequencing of the emergent HBV species suggested selection of lamivudine resistant and surface antigen escape mutants consecutively. Adefovir treatment began after the devlopment of graft failure.
OUTCOME—A rapid exponential decline in serum HBV titre was observed. Liver function tests normalised and signs of liver failure resolved.
CONCLUSION—The use of HBIg and lamivudine permits prevention of graft reinfection by HBV for the majority of patients. Adefovir, a potent inhibitor of lamivudine resistant HBV, should be used when failure of prophylaxis is associated with graft hepatitis.


Keywords: hepatitis B virus; adefovir; liver graft; lamivudine PMID:11709523

  20. Hepatic and Pulmonary Toxicogenomic Profiles in Mice Intratracheally Instilled With Carbon Black Nanoparticles Reveal Pulmonary Inflammation, Acute Phase Response, and Alterations in Lipid Homeostasis

    PubMed Central

    Bourdon, Julie A.; Halappanavar, Sabina; Saber, Anne T.; Jacobsen, Nicklas R.; Williams, Andrew; Wallin, Håkan; Vogel, Ulla; Yauk, Carole L.

    2012-01-01

    Global pulmonary and hepatic messenger RNA profiles in adult female C57BL/6 mice intratracheally instilled with carbon black nanoparticles (NPs) (Printex 90) were analyzed to identify biological perturbations underlying systemic responses to NP exposure. Tissue gene expression changes were profiled 1, 3, and 28 days following exposure to 0.018, 0.054, and 0.162 mg Printex 90 alongside controls. Pulmonary response was marked by increased expression of inflammatory markers and acute phase response (APR) genes that persisted to day 28 at the highest exposure dose. Genes in the 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase pathway were increased, and those involved in cholesterol efflux were decreased at least at the highest dose on days 1 and 3. Hepatic responses mainly consisted of the HMG-CoA reductase pathway on days 1 (high dose) and 28 (all doses). Protein analysis in tissues and plasma of 0.162 mg Printex 90–exposed mice relative to control revealed an increase in plasma serum amyloid A on days 1 and 28 (p < 0.05), decreases in plasma high-density lipoprotein on days 3 and 28, an increase in plasma low-density lipoprotein on day 28 (p < 0.05), and marginal increases in total hepatic cholesterol on day 28 (p = 0.06). The observed changes are linked to APR. Although further research is needed to establish links between observations and the onset and progression of systemic disorders, the present study demonstrates the ability of NPs to induce systemic effects. PMID:22461453

  1. Cholestatic hepatitis due to Salmonella typhi.

    PubMed

    Albayrak, Ayse; Seda Gunbey, Sibel; Aktas, Ferda

    2011-03-29

    Salmonella infection occurs worldwide and is still an important public health problem in many developing countries. The infection can affect almost all major organs including the liver. Severe hepatic involvement with a clinical feature of acute hepatitis is a rare complication. In this paper, a 39-year-old male with acute cholestatic typhoid hepatitis is presented. The case had a tender hepatomegaly and elevated serum alanine and aspartate transaminase, alkaline phosphatase, and gamma glutamyl transferase levels; these features cannot been distinguished from those of acute viral hepatitis. Serological and viral markers of acute viral hepatitis were negative. No pathology could be determined in abdomen Ultrasonography (USG) or Magnetic Resonance (MR) Cholangiography. As enteric fever is a common infection, the recognition of salmonella hepatitis is of clinical importance. When patients from an endemic or outbreak area present acute febrile hepatitis, typhoid fever should be a consideration. PMID:24765267

  2. Hepatitis C.

    PubMed

    Liddle, C

    1996-04-01

    The hepatitis C virus (HCV) genome was isolated during the late 1980s using molecular cloning techniques. It is recognized as the cause of most cases of percutaneously transmitted non-A, non-B hepatitis. Prevalence of antibodies to HCV(anti-HCV) in the general Australian population is 0.3%. However, among regular intravenous drug users the prevalence exceeds 90%. The predominant risk factors for HCV are intravenous drug use, tattoos, exposure to blood products, occupational risk and ethnicity. In contrast to hepatitis B, sexual spread and vertical transmission of HCV from mother to neonate are relatively uncommon. The risk of acquiring HCV from a single HCV-contaminated needlestick accident is about 5%. Most cases of acute HCV infection are asymptomatic, but 50 to 80% progress to chronic disease. The percentage of those with chronic HCV progressing to cirrhosis is not accurately known, but is probably 20%. Treatment strategies for HCV, utilizing recombinant interferons, are proving useful in patients with mild to moderate liver disease, but fare less well in patients with cirrhosis. Currently, there is no vaccine for hepatitis C, so pre-exposure prophylaxis is not possible. Equally, no post-exposure intervention, for example with gamma globulin, has been shown to be beneficial, though there may be a role for early interferon therapy.

  3. Metabolic Correction of Congenital Erythropoietic Porphyria with iPSCs Free of Reprogramming Factors

    PubMed Central

    Bedel, Aurélie; Taillepierre, Miguel; Guyonnet-Duperat, Véronique; Lippert, Eric; Dubus, Pierre; Dabernat, Sandrine; Mautuit, Thibaud; Cardinaud, Bruno; Pain, Catherine; Rousseau, Benoît; Lalanne, Magalie; Ged, Cécile; Duchartre, Yann; Richard, Emmanuel; de Verneuil, Hubert; Moreau-Gaudry, François

    2012-01-01

    Congenital erythropoietic porphyria (CEP) is due to a deficiency in the enzymatic activity of uroporphyrinogen III synthase (UROS); such a deficiency leads to porphyrin accumulation and results in skin lesions and hemolytic anemia. CEP is a candidate for retrolentivirus-mediated gene therapy, but recent reports of insertional leukemogenesis underscore the need for safer methods. The discovery of induced pluripotent stem cells (iPSCs) has opened up new horizons in gene therapy because it might overcome the difficulty of obtaining sufficient amounts of autologous hematopoietic stem cells for transplantation and the risk of genotoxicity. In this study, we isolated keratinocytes from a CEP-affected individual and generated iPSCs with two excisable lentiviral vectors. Gene correction of CEP-derived iPSCs was obtained by lentiviral transduction of a therapeutic vector containing UROS cDNA under the control of an erythroid-specific promoter shielded by insulators. One iPSC clone, free of reprogramming genes, was obtained with a single proviral integration of the therapeutic vector in a genomic safe region. Metabolic correction of erythroblasts derived from iPSC clones was demonstrated by the disappearance of fluorocytes. This study reports the feasibility of porphyria gene therapy with the use of iPSCs. PMID:22795135

  4. Coupled plasma filtration adsorption reduces serum bilirubine in a case of acute hypoxic hepatitis secondary to cardiogenic shock.

    PubMed

    Caroleo, Santo; Rubino, Antonino S; Tropea, Francesco; Bruno, Orlando; Vuoto, Domenico; Amantea, Bruno; Renzulli, Attilio

    2010-10-01

    Hypoxic hepatitis (HH) is a severe complication of postoperative low output syndrome, associated with high mortality rates despite appropriate drug therapy. Recently several extracorporeal supportive techniques have become available. We describe the case of a 70-year-old woman who developed HH secondary to cardiogenic shock after cardiac surgery. CPFA proved to be a valid tool for concomitant hemodynamic support and organ replacement therapy.

  5. Extrahepatic manifestations of hepatitis E virus.

    PubMed

    Kamar, Nassim; Marion, Olivier; Abravanel, Florence; Izopet, Jacques; Dalton, Harry R

    2016-04-01

    Hepatitis E virus can cause acute, fulminant and chronic hepatitis and has been associated with a range of extrahepatic manifestations. Guillain-Barré syndrome, neuralgic amyotrophy and encephalitis are the main neurological manifestations associated with acute and chronic hepatitis E virus infection. Renal injuries have been also reported, including membranoproliferative glomerulonephritis with or without cryoglobulinemia and membranous glomerulonephritis. Acute pancreatitis, haematological disorders and other autoimmune extrahepatic manifestations of hepatitis E virus, such as myocarditis and thyroiditis, have been also reported. In this comprehensive article, we review all published reports describing hepatitis E virus-associated extrahepatic manifestations.

  6. Extrahepatic manifestations of hepatitis E virus.

    PubMed

    Kamar, Nassim; Marion, Olivier; Abravanel, Florence; Izopet, Jacques; Dalton, Harry R

    2016-04-01

    Hepatitis E virus can cause acute, fulminant and chronic hepatitis and has been associated with a range of extrahepatic manifestations. Guillain-Barré syndrome, neuralgic amyotrophy and encephalitis are the main neurological manifestations associated with acute and chronic hepatitis E virus infection. Renal injuries have been also reported, including membranoproliferative glomerulonephritis with or without cryoglobulinemia and membranous glomerulonephritis. Acute pancreatitis, haematological disorders and other autoimmune extrahepatic manifestations of hepatitis E virus, such as myocarditis and thyroiditis, have been also reported. In this comprehensive article, we review all published reports describing hepatitis E virus-associated extrahepatic manifestations. PMID:27005692

  7. Protective Role of Silymarin on Hepatic and Renal Toxicity Induced by MTX Based Chemotherapy in Children with Acute Lymphoblastic Leukemia

    PubMed Central

    Hagag, Adel A.; Elgamsy, Mohamed A.; El-Asy, Hassan M.; Mabrouk, Maaly M.

    2016-01-01

    Background ALL is the most common childhood malignancy. The children with ALL are treated with methotrexate (MTX) based chemotherapy protocols. MTX causes unpredictable serious hepatic and renal side effects. Silymarin has antioxidant and anti-inflammatory activities and stimulates tissue regeneration. This study aims to evaluate the protective effects of Silymarin on MTX-based chemotherapy-induced Hepatic and renal toxicity in children with ALL. Patients and Methods 80 children with newly diagnosed ALL were enrolled in the study. They were randomly divided into two groups. Group I included 40 children with ages ranging from 4–13 years and the mean age of 6.85± 2.89 years, who received Silymarin 420 mg/day in 3 divided doses for one week after each MTX dose. Group II included 40 children, with ages ranging from 4–12 years and the mean age of 7.30±2.6 years, who received placebo for one week after MTX therapy. For all patients liver functions including serum bilirubin, total proteins, albumin, globulin and albumin-globulin ratio, alkaline phosphatase, ALT and AST, prothrombin time and activity and renal functions including blood urea and serum creatinine, serum cystatin C and urinary N-acetyl-beta-D-glucosaminidase were done to assess hepatic and renal toxicity before and after chemotherapy. Results There were no significant differences between group I and II as regard liver and renal functions before chemotherapy. After chemotherapy, there were significantly higher values of ALT and AST and alkaline phosphatase, and significantly lower Prothrombin activity in group II compared with group I. No significant differences between group I and II were found in total bilirubin, serum protein, and albumin levels. There was significantly lower blood urea, serum creatinine, and cystatin C and urinary N-acetyl-beta-D-glucosaminidase in group I compared with group II. Conclusion Silymarin improved some hepatic and renal functions in children with ALL who received MTX

  8. Protective Role of Silymarin on Hepatic and Renal Toxicity Induced by MTX Based Chemotherapy in Children with Acute Lymphoblastic Leukemia

    PubMed Central

    Hagag, Adel A.; Elgamsy, Mohamed A.; El-Asy, Hassan M.; Mabrouk, Maaly M.

    2016-01-01

    Background ALL is the most common childhood malignancy. The children with ALL are treated with methotrexate (MTX) based chemotherapy protocols. MTX causes unpredictable serious hepatic and renal side effects. Silymarin has antioxidant and anti-inflammatory activities and stimulates tissue regeneration. This study aims to evaluate the protective effects of Silymarin on MTX-based chemotherapy-induced Hepatic and renal toxicity in children with ALL. Patients and Methods 80 children with newly diagnosed ALL were enrolled in the study. They were randomly divided into two groups. Group I included 40 children with ages ranging from 4–13 years and the mean age of 6.85± 2.89 years, who received Silymarin 420 mg/day in 3 divided doses for one week after each MTX dose. Group II included 40 children, with ages ranging from 4–12 years and the mean age of 7.30±2.6 years, who received placebo for one week after MTX therapy. For all patients liver functions including serum bilirubin, total proteins, albumin, globulin and albumin-globulin ratio, alkaline phosphatase, ALT and AST, prothrombin time and activity and renal functions including blood urea and serum creatinine, serum cystatin C and urinary N-acetyl-beta-D-glucosaminidase were done to assess hepatic and renal toxicity before and after chemotherapy. Results There were no significant differences between group I and II as regard liver and renal functions before chemotherapy. After chemotherapy, there were significantly higher values of ALT and AST and alkaline phosphatase, and significantly lower Prothrombin activity in group II compared with group I. No significant differences between group I and II were found in total bilirubin, serum protein, and albumin levels. There was significantly lower blood urea, serum creatinine, and cystatin C and urinary N-acetyl-beta-D-glucosaminidase in group I compared with group II. Conclusion Silymarin improved some hepatic and renal functions in children with ALL who received MTX

  9. Revised criteria for classification of the etiologies of acute liver failure and late-onset hepatic failure in Japan: A report by the Intractable Hepato-biliary Diseases Study Group of Japan in 2015.

    PubMed

    Mochida, Satoshi; Nakayama, Nobuaki; Ido, Akio; Takikawa, Yasuhiro; Yokosuka, Osamu; Sakaida, Isao; Moriwaki, Hisataka; Genda, Takuya; Takikawa, Hajime

    2016-03-01

    In 2011, the Intractable Liver Diseases Study Group of Japan, established novel diagnostic criteria for "acute liver failure ", and published the classification criteria for the etiologies of acute liver failure and late-onset hepatic failure (LOHF) in 2013. According to this classification, HBV carriers showing acute hepatitis exacerbation were divided into 3 subgroups; asymptomatic or inactive HBV carriers without drug exposure, asymptomatic or inactive HBV carriers developing HBV reactivation during and after immunosuppressive therapies and/or antineoplastic chemotherapies and those with previously resolved HBV infection showing iatrogenic HBV reactivation. In an annual nationwide survey in 2013, however, a patient with previously resolved HBV infection was enrolled, in whom LOHF developed as a result of HBV reactivation despite in the absence of immunosuppressive therapies and/or antineoplastic chemotherapies. Thus, the study group revised the classification criteria in 2015; HBV carriers developing acute hepatitis exacerbation were classified into asymptomatic or inactive HBV carriers and patients with previously resolved HBV infection, and both groups were further sub-classified into those receiving immunosuppressive therapies and/or antineoplastic chemotherapies and those without such drugs exposure.

  10. Hepatic encephalopathy: a review.

    PubMed

    Lizardi-Cervera, Javier; Almeda, Paloma; Guevara, Luis; Uribe, Misael

    2003-01-01

    Hepatic encephalopathy (HE) is a complication that presents in as many as 28% of patients with cirrhosis, and reported up to ten years after the diagnosis of cirrhosis. Commonly, it is observed in patients with severe hepatic failure and is characterized by neuropsychiatric manifestations that can range in severity from a mild alteration in mental state to a coma; additionally, some neuromuscular symptoms can be observed. This complication of either acute or chronic hepatic disease is the result of a diminished hepatic reservoir and inability to detoxify some toxins that originate in the bowel. Today, the role of astrocytes, specifically the Alzheimer type II cells, is known to be very important in the pathogenesis of the hepatic encephalopathy, and will be reviewed later. In conclusion, the objectives of this review are: To understand the pathogenesis of hepatic encephalopathy, To recognize the precipitating factors, as well as preventive measures for the development of the hepatic encephalopathy, To describe the new classification of hepatic encephalopathy and its clinical implications, To recognize the clinical manifestations and stages of the disease, To understand the main diagnostic tests used to detect the hepatic encephalopathy, To describe the main therapeutic treatments of hepatic encephalopathy. PMID:15115963

  11. Viral Hepatitis

    MedlinePlus

    ... Public Home » For Veterans and the Public Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... the Public Veterans and Public Home How is Hepatitis C Treated? Find the facts about the newest ...

  12. A model to predict 3-month mortality risk of acute-on-chronic hepatitis B liver failure using artificial neural network.

    PubMed

    Zheng, M-H; Shi, K-Q; Lin, X-F; Xiao, D-D; Chen, L-L; Liu, W-Y; Fan, Y-C; Chen, Y-P

    2013-04-01

    Model for end-stage liver disease (MELD) scoring was initiated using traditional statistical technique by assuming a linear relationship between clinical features, but most phenomena in a clinical situation are not linearly related. The aim of this study was to predict 3-month mortality risk of acute-on-chronic hepatitis B liver failure (ACHBLF) on an individual patient level using an artificial neural network (ANN) system. The ANN model was built using data from 402 consecutive patients with ACHBLF. It was trained to predict 3-month mortality by the data of 280 patients and validated by the remaining 122 patients. The area under the curve of receiver operating characteristic (AUROC) was calculated for ANN and MELD-based scoring systems. The following variables age (P < 0.001), prothrombin activity (P < 0.001), serum sodium (P < 0.001), total bilirubin (P = 0.015), hepatitis B e antigen positivity rate (P < 0.001) and haemoglobin (P < 0.001) were significantly related to the prognosis of ACHBLF and were selected to build the ANN. The ANN performed significantly better than MELD-based scoring systems both in the training cohort (AUROC = 0.869 vs 0.667, 0.591, 0.643, 0.571 and 0.577; P < 0.001, respectively) and in the validation cohort (AUROC = 0.765 vs 0.599, 0.563, 0.601, 0.521 and 0.540; P ≤ 0.006, respectively). Thus, the ANN model was shown to be more accurate in predicting 3-month mortality of ACHBLF than MELD-based scoring systems. PMID:23490369

  13. Viral Hepatitis

    MedlinePlus

    ... with hepatitis? How does a pregnant woman pass hepatitis B virus to her baby? If I have hepatitis B, what does my baby need so that she ... Can I breastfeed my baby if I have hepatitis B? More information on viral hepatitis What is hepatitis? ...

  14. Upregulated Expression of A20 on Monocytes is Associated With Increased Severity of Acute-on-Chronic Hepatitis B Liver Failure

    PubMed Central

    Guo, Yonghong; He, Yu; Zhang, Ying; Zhou, Yun; Qin, Yuan; Fan, Chao; Ji, Guangxi; Zhang, Peixin; Jia, Zhansheng

    2015-01-01

    Abstract A20 expression is increased in various inflammatory diseases. However, the role of A20 in acute-on-chronic liver failure is unknown. This study was to evaluate A20 expression on monocytes and its associations with the severity of acute-on-chronic hepatitis B liver failure (ACHBLF). Thirty-seven patients with ACHBLF, 20 patients with chronic hepatitis B (CHB), and 15 healthy controls (HC) were enrolled in this case-control study. A20-positive monocytes were identified using flow cytometry. Serum levels of interleukin (IL)-10, IL-12p70, and TNF-α were determined using bead cytometry. A20 and IL-10 expressions were examined in THP-1 cells stimulated by lipopolysaccharide (LPS). The frequency of A20+ monocytes was significantly increased in patients with ACHBLF compared with HC (median [interquartile range, IQR]: 15.7 [22.8]% vs 2.5 [4.7]%, P < 0.001). Increased monocyte A20 expression was detected during the progression phase (including the mild/moderate and severe grades of ACHBLF) compared with patients in the recovery phase (both P < 0.05), and in the ACHBLF worsening group compared with patients in the improvement group (P < 0.001). LPS treatment upregulated A20 and IL-10 expressions in THP-1 cells. A20 expression on monocytes from patients with ACHBLF was positively correlated with total bilirubin (r = 0.60, P = 0.0001), direct bilirubin (r = 0.63, P < 0.0001), and MELD score (r = 0.43, P = 0.008), and inversely with prothrombin activity (r = −0.33, P = 0.046). IL-10 and TLR4 expression levels in monocytes, and serum levels of IL-10, IL-12p70, and TNF-α were increased in patients with ACHBLF compared with patients with CHB and HC. Increased A20 expression on monocytes was associated with the severity of ACHBLF. PMID:26426612

  15. Analysis of Hepatitis B Virus Intrahepatic Covalently Closed Circular DNA and Serum Viral Markers in Treatment-Naive Patients with Acute and Chronic HBV Infection

    PubMed Central

    Zou, Zhengsheng; Liu, Yan; Li, Baosen; Sun, Ying; Li, Xiaodong; Liu, Shuhong; Cai, Shaoping; Yao, Weimin; Xin, Shaojie; Lu, Fengmin; Xu, Dongping

    2014-01-01

    Background This study aimed to investigate the relationships of intrahepatic cccDNA with serum HBsAg and with HBV DNA in treatment-naive patients throughout acute and chronic HBV infection. Methods A total of 120 patients who had a liver biopsy were enrolled, including 19 with acute hepatitis B (AHB), and 101 patients with chronic HBV infection (CHB) of whom were 10 in immune-tolerant (IT) phase, 59 in immune-clearance (IC) phase, 8 in low-replicative (LR) phase, and 24 in HBeAg-negative hepatitis (ENH) phase. Intrahepatic cccDNA, serum HBsAg and serum HBV DNA levels were comparatively analyzed. Results The median intrahepatic cccDNA levels were 0.18 4.80, 3.81, 0.22 and 0.97 copies/cell for patients with AHB, CHB-IT, CHB-IC, CHB-LR, and CHB-ENH, respectively. In AHB patients, intrahepatic cccDNA was positively correlated with serum HBsAg (r = 0.665, P = 0.003), as well as serum HBV DNA (r = 0.536, P = 0.022). In CHB patients, intrahepatic cccDNA was positively correlated with serum HBsAg in the IC phase (r = 0.392, P = 0.005), and with serum HBV DNA in the IC phase (r = 0.301, P = 0.036) and ENH phase (r = 0.588, P = 0.013). HBV replicative efficiency, defined as the ratio of serum HBV DNA to intrahepatic cccDNA, was obviously lower in AHB and CHB-LR patients than in CHB-IT, CHB-IC and CHB-ENH patients (0.70 and 0.53 vs. 1.12, 1.09 and 0.99, P<0.001, values were logarithmic transformed for analysis). In CHB-IC patients, HBV replicative efficiency was positively correlated with histological activity index of liver inflammation (r = 0.308, P = 0.009). Conclusion Serum HBsAg and HBV DNA levels may reflect the amount of active intrahepatic cccDNA in treatment-naive AHB and CHB-IC patients. Reduced intrahepatic cccDNA and HBV replicative efficiency may imply effective immune control of HBV infection. PMID:24551214

  16. Inducing iron deficiency improves erythropoiesis and photosensitivity in congenital erythropoietic porphyria.

    PubMed

    Egan, Daniel N; Yang, Zhantao; Phillips, John; Abkowitz, Janis L

    2015-07-01

    Congenital erythropoietic porphyria (CEP) is an autosomal recessive disorder of heme synthesis characterized by reduced activity of uroporphyrinogen III synthase and the accumulation of nonphysiologic isomer I porphyrin metabolites, resulting in ineffective erythropoiesis and devastating skin photosensitivity. Management of the disease primarily consists of supportive measures. Increased activity of 5-aminolevulinate synthase 2 (ALAS2) has been shown to adversely modify the disease phenotype. Herein, we present a patient with CEP who demonstrated a remarkable improvement in disease manifestations in the setting of iron deficiency. Hypothesizing that iron restriction improved her symptoms by decreasing ALAS2 activity and subsequent porphyrin production, we treated the patient with off-label use of deferasirox to maintain iron deficiency, with successful results. We confirmed the physiology of her response with marrow culture studies. PMID:25972160

  17. Lamin aggregation is an early sensor of porphyria-induced liver injury.

    PubMed

    Singla, Amika; Griggs, Nicholas W; Kwan, Raymond; Snider, Natasha T; Maitra, Dhiman; Ernst, Stephen A; Herrmann, Harald; Omary, M Bishr

    2013-07-15

    Oxidative liver injury during steatohepatitis results in aggregation and transglutaminase-2 (TG2)-mediated crosslinking of the keratin cytoplasmic intermediate filament proteins (IFs) to form Mallory-Denk body (MDB) inclusions. The effect of liver injury on lamin nuclear IFs is unknown, though lamin mutations in several human diseases result in lamin disorganization and nuclear shape changes. We tested the hypothesis that lamins undergo aggregation during oxidative liver injury using two MDB mouse models: (i) mice fed the porphyrinogenic drug 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and (ii) mice that harbor a mutation in ferrochelatase (fch), which converts protoporphyrin IX to heme. Dramatic aggregation of lamin A/C and B1 was noted in the livers of both models in association with changes in lamin organization and nuclear shape, as determined by immunostaining and electron microscopy. The lamin aggregates sequester other nuclear proteins including transcription factors and ribosomal and nuclear pore components into high molecular weight complexes, as determined by mass-spectrometry and confirmed biochemically. Lamin aggregate formation is rapid and precedes keratin aggregation in fch livers, and is seen in liver explants of patients with alcoholic cirrhosis. Exposure of cultured cells to DDC, protoporphyrin IX or N-methyl-protoporphyrin, or incubation of purified lamins with protoporphyrin IX, also results in lamin aggregation. In contrast, lamin aggregation is ameliorated by TG2 inhibition. Therefore, lamin aggregation is an early sensor of porphyria-associated liver injury and might serve to buffer oxidative stress. The nuclear shape and lamin defects associated with porphyria phenocopy the changes seen in laminopathies and could result in transcriptional alterations due to sequestration of nuclear proteins.

  18. Update on Alcoholic Hepatitis.

    PubMed

    Torok, Natalie J

    2015-11-02

    Alcoholic liver disease is one of the most prevalent liver diseases worldwide, and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%-50% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies.

  19. Update on Alcoholic Hepatitis

    PubMed Central

    Torok, Natalie J.

    2015-01-01

    Alcoholic liver disease is one of the most prevalent liver diseases worldwide, and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%–50% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies. PMID:26540078

  20. Screening, detecting and enhancing the yield of previously undiagnosed hepatitis B and C in patients with acute medical admissions to hospital: A pilot project undertaken at the Vancouver General Hospital

    PubMed Central

    Kapeluto, Jordanna E; Kadatz, Matthew; Wormsbecker, Andrew; Sidhu, Kiran; Yoshida, Eric M

    2014-01-01

    BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) represent an increasing health burden and morbidity in Canada. Viral hepatitis, specifically HCV, has high prevalence among persons born between 1945 and 1965, with 45% to 85% of infected adults asymptomatic and unaware of their infection. Screening has been shown to be cost effective in the detection and treatment of viral hepatitis. OBJECTIVE: To quantify incidence and identify undocumented HBV and HCV infection in hospitalized patients at a single centre with secondary analysis of risk factors as part of a quality improvement initiative. METHODS: A one-time antibody test was conducted in patients admitted to the acute medicine and gastroenterology services. RESULTS: Over a 12-week period, hospital screening for HBV and HCV was performed in 37.3% of 995 admitted patients. There was identification of 15 previously undiagnosed cases of HCV (4%) and 36 undocumented cases of occult (ie, antihepatitis B core antigen seropositive) or active (ie, hepatitis B surface antigen seropositive) HBV (9.7%). Among patients with positive screens, 60% of seropositive HCV patients had no identifiable risk factors. CONCLUSIONS: The prevalence of HBV and HCV infection among hospitalized patients in Vancouver was higher than that of the general population. Risk factors for contraction are often not identified. These results can be used as part of an ongoing discussion regarding a ‘seek and treat’ approach to the detection and treatment of chronic blood-borne viral illnesses. PMID:24945186

  1. Bioactive phytochemicals of leaf essential oils of Cinnamomum osmophloeum prevent lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced acute hepatitis in mice.

    PubMed

    Tung, Yu-Tang; Huang, Chi-Chang; Ho, Shang-Tse; Kuo, Yueh-Hsiung; Lin, Chi-Chen; Lin, Chien-Tsong; Wu, Jyh-Horng

    2011-08-10

    The purpose of this study was to investigate the bioactive phytochemicals of leaf essential oils of Cinnamomum osmophloeum on lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced acute hepatitis. The results revealed that post-treatment with 100 μmol/kg trans-cinnamaldehyde, (-)-aromadendrene, T-cadinol, or α-cadinol significantly decreased the aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) levels in serum. Moreover, both T-cadinol and α-cadinol treatments decreased the expressions of cleaved caspase-3 and cleaved poly-ADP ribose polymerase (PARP) in the liver tissues when compared with the LPS/D-GalN group. Liver histopathology also showed that silymarin, trans-cinnamaldehyde, (-)-aromadendrene, T-cadinol, or α-cadinol significantly reduced the incidence of liver lesions induced by LPS/D-GalN. These results suggest that the above phytochemicals exhibit potent hepatoprotection against LPS/D-GalN-induced liver damage in mice, and their hepatoprotective effects may be due to the modulation of anti-inflammatory activities. PMID:21699244

  2. Reversible laminar signal intensity in deep cortical gray matter in T1-weighted images and FLAIR after mild acute hyperammonemic hepatic encephalopathy.

    PubMed

    Treusch, N A; van de Loo, S; Hattingen, E

    2012-12-01

    Soporific acute hyperammonemic hepatic encephalopathy (aHE) can induce considerable changes in cerebral white and gray matter. This report describes a patient in the subacute phase of aHE grade I without disturbed consciousness and with reversible fine laminar cortical involvement on magnetic resonance imaging (MRI). The 59-year-old patient had esophageal varices bleeding due to primary biliary cirrhosis (ammonium blood level: 140 mmoL/L) and presented with sensory Jacksonian seizures, dysarthria, and increased drowsiness and fatigue. MRI revealed patchy hyperintense (T2-weighted, T2w) white-matter lesions and bilateral signal intensities in the striatum (T1w). During a rise of ammonium blood level to 220 mmoL/L, the patient had increased drowsiness, persistent dysarthria and mild temporary hemiparesis without loss of consciousness. Two weeks later, the patient was asymptomatic and blood ammonium level had reverted to normal value. MRI at that time revealed bihemispheric fine laminar subcortical hyperintensities on T2w and fluid-attenuated inversion recovery (FLAIR) imaging, and partially on T1w sequences, with no swelling or restricted diffusion; the hyperintensities were fully reversible a month later. Such a distinct cortical signal increase not only on T2w images, but also on T1w, in a patient after a mild form of aHE is a new MR finding.

  3. Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

    PubMed Central

    Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; de Almeida, Adilson José; Pelajo-Machado, Marcelo; de Castro, Tatiana Xavier; do Nascimento, Jussara Pereira; Brown, Kevin E; Pinto, Marcelo Alves

    2016-01-01

    This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group. PMID:27074255

  4. Cytomegalovirus Reactivation Induced Acute Hepatitis and Gastric Erosions in a Patient with Rheumatoid Arthritis under Treatment with an Anti-IL-6 Receptor Antibody, Tocilizumab.

    PubMed

    Komura, Takuya; Ohta, Hajime; Nakai, Ryotaro; Seishima, Jun; Yamato, Masatoshi; Miyazawa, Masaki; Kaji, Kiichiro; Marukawa, Yohei; Kagaya, Takashi; Kitagawa, Kiyoki; Kawashima, Atsuhiro; Kaneko, Shuichi; Unoura, Masashi

    2016-01-01

    Tocilizumab, an anti-human interleukin 6 receptor (IL-6R) monoclonal antibody, is widely used to treat rheumatoid arthritis (RA) and is expected to exhibit clinical efficacy when used to treat other autoimmune diseases. However, a risk of opportunistic infection is occasionally recognized. A 54-year-old woman had received an oral corticosteroid and methotrexate to treat RA. Despite receiving these treatments, she received additional treatment with tocilizumab due to poor control of the disease activity. She presented at our hospital with a high fever and epigastralgia 19 days after receiving this treatment. A laboratory evaluation revealed liver injury and cytomegalovirus (CMV) viremia. Abdominal ultrasonography and computed tomography (CT) revealed hepatosplenomegaly, but no ascites. Upper gastrointestinal endoscopy revealed gastric erosions induced by CMV, which were confirmed immunohistochemically. Hence, we diagnosed the patient with CMV reactivation-induced acute hepatitis and gastric erosions under tocilizumab treatment. She received an anti-cytomegalovirus drug, ganciclovir, for 14 days due to her viremia and impaired general condition, which was suggestive of a severe infection. Her general condition subsequently improved, the liver function test results normalized, and the gastric erosions disappeared. In conclusion, although tocilizumab is very useful for treating certain autoimmune and inflammatory diseases, and will be prescribed more widely in the future, associated CMV infections must be closely monitored, as these can be lethal. PMID:27432105

  5. ASS and SULT2A1 are Novel and Sensitive Biomarkers of Acute Hepatic Injury-A Comparative Study in Animal Models.

    PubMed

    Prima, Victor; Cao, Mengde; Svetlov, Stanislav I

    2013-01-10

    Liver and kidney damage associated with polytrauma, endotoxic shock/sepsis, and organ transplantation, are among the leading causes of the multiple organ failure. Development of novel sensitive biomarkers that detect early stages of liver and kidney injury is vital for the effective diagnostics and treatment of these life-threatening conditions. Previously, we identified several hepatic proteins, including Argininosuccinate Synthase (ASS) and sulfotransferases which were degraded in the liver and rapidly released into circulation during Ischemia/Reperfusion (I/R) injury. Here we compared sensitivity and specificity of the newly developed sandwich ELISA assays for ASS and the sulfotransferase isoform SULT2A1 with the standard clinical liver and kidney tests Alanine Aminotransferase (ALT) and Aspartate Transaminase (AST) in various pre-clinical models of acute injury. Our data suggest that ASS and SULT2A1 have superior characteristics for liver and kidney health assessment in endotoxemia, Ischemia/Reperfusion (I/R), chemical and drug-induced liver injury and may be of high potential value for clinical applications.

  6. National Trend and Characteristics of Acute Hepatitis C among HIV-Infected Individuals: A Matched Case-Control Study—Taiwan, 2001–2014

    PubMed Central

    Lo, Yi-Chun; Tsai, Mao-Song; Sun, Hsin-Yun; Hung, Chien-Ching; Chuang, Jen-Hsiang

    2015-01-01

    Background Hepatitis C virus (HCV) infection has been increasingly recognized among HIV-infected men who have sex with men (MSM) worldwide. We investigated the trend of and factors associated with acute hepatitis C (AHC) among HIV-infected individuals in Taiwan. Methods The National Disease Surveillance System collects characteristics of AHC, HIV, syphilis, and gonorrhea cases through mandatory reports and patient interviews. Reported AHC patients in 2014 were interviewed additionally on sexual and parenteral exposures. Information on HCV genotypes were collected from the largest medical center serving HIV-infected Taiwanese. We defined an HIV/AHC case as a documented negative HCV antibody test result followed within 12 months by a positive test in a previously reported HIV-infected individual. Each case was matched to two HIV-infected, non-AHC controls for age, age of HIV diagnosis, sex, transmission route, HIV diagnosis date, and county/city. Conditional logistic regression was used to identify associated characteristics. Results During 2001–2014, 93 of 6,624 AHC reports were HIV/AHC cases; the annual case count increased from one in 2009 to 34 in 2014. All were males (81 [87%] MSM) aged 21–49 years with AHC diagnosed 2–5,923 days after HIV diagnoses. Sixty-eight (73%) lived in the Taipei metropolitan area. Detected HCV genotypes were 2a (n = 6), 1b (n = 5), 1b + 2a (n = 1) and 2b (n = 1). Among 28 HIV/AHC patients interviewed in 2014, 13 (46%) reported engaging in unprotected sex ≤3 months before AHC diagnosis. Seventy-nine HIV/AHC cases were matched to 158 controls. HIV/AHC was associated with recent syphilis (adjusted odds ratio [aOR], 10.9; 95% confidence interval [CI], 4.2–28.6) and last syphilis >6 months (aOR, 2.9; 95% CI, 1.2–6.9). Conclusions HIV/AHC cases continued to increase particularly among sexually active HIV-infected MSM with a syphilis diagnosis in northern Taiwan. We recommend surveillance of associated behavioral and virologic

  7. Delta hepatitis in Malaysia.

    PubMed

    Sinniah, M; Dimitrakakis, M; Tan, D S

    1986-06-01

    Sera from one hundred and fifty nine Malaysian individuals were screened for the prevalence of delta markers. These included 15 HBsAg positive homosexuals, 16 acute hepatitis B cases, 9 chronic hepatitis B patients, 13 healthy HBsAg carriers and 106 intravenous (i.v.) drug abusers, of whom 27 were positive for HBsAg only and the rest were anti-HBc IgG positive but HBsAg negative. The prevalence of delta markers in the homosexuals was found to be 6.7%, in the HBsAg positive drug abusers 17.8%, in acute hepatitis B cases 12.5%. No evidence of delta infection was detected in healthy HBsAg carriers, chronic hepatitis B cases and HBsAg negative i.v. drug abusers. With reference to i.v. drug abusers, the prevalence of delta markers was higher in Malays (23%) than in Chinese (7%) although the latter had a higher HBsAg carrier rate. Although the HBsAg carrier rate in the homosexuals was high, their delta prevalence rate was low as compared to drug abusers. In Malaysia, as in other non-endemic regions, hepatitis delta virus transmission appeared to occur mainly via the parenteral and sexual routes. This is the first time in Malaysia that a reservoir of delta infection has been demonstrated in certain groups of the population at high risk for hepatitis B. PMID:3787309

  8. Metabonomic analysis of liver tissue from BALB/c mice with d-galactosamine/lipopolysaccharide-induced acute hepatic failure

    PubMed Central

    2013-01-01

    Background Compared with biofluids, target tissues and organs more directly reflect the pathophysiological state of a disease process. In this study, a D-galactosamine (GalN) / lipopolysaccharide (LPS)-induced mouse model was constructed to investigate metabonomics of liver tissue and directly characterize metabolic changes in acute liver failure (ALF). Methods After pretreatment of liver tissue, gas chromatography coupled to time-of-flight mass spectrometry (GC/TOFMS) was used to separate and identify the liver metabolites. Partial least squares – discriminant analysis models were constructed to separate the ALF and control groups and to find those compounds whose liver levels differed significantly between the two groups. Results Distinct clustering was observed between the ALF and control mice. Fifty-eight endogenous metabolites were identified. Compared with the control mice, many metabolites, including sugars, amino acids, fatty acids, and organic acids, underwent significant changes in the ALF group, some of which differed from changes observed in plasma. Significant reduction of some important intermediate metabolites indicates that production of ketone bodies, the tricarboxylic acid and urea cycles, gluconeogenesis, glycolysis and pentose phosphate pathways are inhibited after GalN/LPS administration. Conclusions GC/TOFMS can be a powerful technique to perform metabonomic studies of liver tissue. GalN/LPS treatment can severely disturb substance metabolism in the liver, with different effects on metabolites compared with those observed in the plasma. PMID:23627910

  9. Hepatitis B Virus Genotype Distribution and Genotype-Specific BCP/preCore Substitutions in Acute and Chronic Infections in Argentina

    PubMed Central

    González López Ledesma, María Mora; Mojsiejczuk, Laura Noelia; Rodrigo, Belén; Sevic, Ina; Mammana, Lilia; Galdame, Omar; Gadano, Adrian; Fainboim, Hugo; Campos, Rodolfo; Flichman, Diego

    2015-01-01

    Aim In order to assess Hepatitis B Virus genotype (g) and subgenotype (sg) implications in the course of infection, 234 HBsAg positive patients in different infection stages were characterized (66 acute infections, 63 HBeAg positive chronic infections and 105 anti-HBe positive chronic infections). Results Overall, sgA2 (17.9%), gD (20.9%), sgF1b (34.2%) and sgF4 (19.7%) were the most prevalent. Subgenotype F1b was overrepresented in acute and chronic HBeAg infections (56.1%), whereas gD was the most frequent (40.0%) in anti-HBe positive chronic infections. Among chronic infections, HBeAg positivity rates were 50.0, 12.5, 62.8 and 35.3% for sgA2, gD, sgF1b and sgF4, respectively (p <0.05). A bias toward BCP/preCore mutations was observed among genotypes. In anti-HBe positive chronic infections, sgF1b was more prone to have A1762T/G1764A mutation than sgA2, sgF4 and gD (75.0, 40.0, 33.3 and 31.8%, p<0.005), whereas in the pC region, gD and sgF4 were more likely to have G1896A than sgA2 and sgF1b (81.0, 72.7, 0.0 and 31.3%, p <0.001). The unexpected low frequency of the G1896A mutation in the sgF1b (despite carrying 1858T) prompted us to perform a further analysis in order to identify genotype-specific features that could justify the pattern mutations observed. A region encompassing nucleotides 1720 to 1920 showed the higher dissimilarity between sgF1b and sgF4. Genotypes and subgenotypes carrying the 1727G, 1740C and 1773T polymorphisms were prevented to mutate position 1896. Discussion HBeAg seroconversion is a critical event in the natural history of HBV infection. Differences in the HBeAg positivity rate might be relevant since different studies have observed that delayed HBeAg seroconversion is associated with a more severe clinical course of infection, highlighting the critical role that genotypes/subgenotypes might play in the progression of HBV infection. Polymorphisms in the regions 1720 to 1920 could be involved in the molecular mechanisms underlying

  10. Neospora caninum and Toxoplasma gondii: relationship between hepatic lesions, cytological and biochemical analysis of the cavitary liquid during the acute phase of the diseases in experimental models.

    PubMed

    Bottari, Nathieli B; Tonin, Alexandre A; Fighera, Rafael; Flores, Mariana M; França, Raqueli T; Camillo, Giovana; Toscan, Gustavo; Vogel, Fernanda S F; Sangoi, Manuela B; Bochi, Guilherme V; Moresco, Rafael N; Lopes, Sonia T A; Da Silva, Aleksandro S

    2014-01-01

    The objective of this study was to evaluate the pathogenesis of ascites in mice infected with Toxoplasma gondii and gerbils infected with Neospora caninum during the acute phase disease. For that, 12 gerbils [Experiment I: not infected/control (n=6) and infected (n=6)] and 12 mice [Experiment II: control (n=6) and infected (n=6)] were used. Infected gerbils and mice showed marked ascites on days 5-7 post-infection (PI), while the not-infected animals had not ascites. Peritoneal liquid was collected from the all mice with uninfected animals receiving 1.5mL of saline solution into their abdominal cavity, allowing the recovery of cavity liquid. As a result, it was possible to observe differences in physics, chemistry and cytological analysis of the fluid cavity of animals infected with N. caninum and T. gondii, when they were compared with uninfected animals, as well as between animals experimentally infected. Additionally both, N. caninum and T gondii, caused an increase in the levels of nitric oxide (NOx-nitrate/nitrite), protein oxidation (AOPP) and lipid peroxidation (TBARS), while serum total protein and albumin were reduced in infected gerbils and mice. Gerbils infected with N. caninum showed multiple large cells with multilobulated nucleus, lytic necrosis and abundant amount of eosinophilic cytoplasm into the hepatic parenchyma. By the other hand, mice infected with T. gondii developed myriad foci of lytic necrosis combined with tachyzoites and cysts containing bradyzoites in liver. Both experimental models for N. caninum and T. gondii showed inflammatory foci and tachyzoites the peritoneum, which could be a major cause of ascites. Toxoplasmosis and neosporosis were able to cause clinical signs in experimental models with similar alterations in peritoneal fluid; however the toxoplasmosis histological changes were much more evident. Therefore, the pathogenesis of ascites appears to be directly related to liver damage, which strongly suggests alteration in the

  11. Peritoneal Albumin Dialysis as a Novel Approach for Liver Support: Study in a Porcine Model of Acute Hepatic Failure.

    PubMed

    Defterevos, Georgios; Nastos, Constantinos; Papalois, Apostolos; Kalimeris, Konstantinos; Margelos, Vassileios; Fragulidis, George; Pafiti, Agathi; Mikrovas, Aggeliki; Nomikos, Tzortzis; Smyrniotis, Vassilios; Arkadopoulos, Nikolaos

    2016-08-01

    Artificial liver support gained considerable interest in recent years due to the development of various albumin dialysis systems, which prolong survival of some patients with acute liver failure (ALF). Τhis study aims to examine the role of peritoneal albumin dialysis in a postoperative ALF model. ALF was induced in 14 female Landrace pigs by a combination of major liver resection (70-75% of total parenchyma) and ischemic-reperfusion injury on the liver remnant. Animals were randomly divided in two groups (n = 7 each). Both were monitored for 12 h of reperfusion and received peritoneal dialysis for 6 h, beginning 6 h after reperfusion. The albumin group received an albumin-rich solution and the control group received albumin-free solution. The control group gradually developed intracranial hypertension, whereas, in the albumin group, rise in the intracranial pressure was substantially attenuated (P < 0.01, t = 12 h). Albumin-treated animals had significantly lower levels of ammonia (P < 0.01), total bile acids (P < 0.01), free fatty acids (P < 0.05), lactate (P < 0.01), and total bilirubin (P < 0.05). Liver malondialdehyde and protein carbonyl were significantly reduced (P = 0.007 and P = 0.001 at t = 12 h) after albumin dialysis. Results suggest that this method may become a useful adjunct in the management of ALF, thus, justifying further study. PMID:27094211

  12. Transmission of Hepatitis C Virus during Computed Tomography Scanning with Contrast

    PubMed Central

    Rius, Cristina; Caylà, Joan A.

    2008-01-01

    Six cases of acute hepatitis C related to computed tomography scanning with contrast were identified in 3 hospitals. A patient with chronic hepatitis C had been subjected to the same procedure immediately before each patient who developed acute infection. Viral molecular analysis showed identity between isolates from cases with acute and chronic hepatitis C. PMID:18258135

  13. Successful cord blood stem cell transplantation for congenital erythropoietic porphyria (Gunther's disease).

    PubMed

    Zix-Kieffer, I; Langer, B; Eyer, D; Acar, G; Racadot, E; Schlaeder, G; Oberlin, F; Lutz, P

    1996-07-01

    Congenital erythropoietic porphyria (Gunther's disease, GD) is a rare autosomal recessive disease. It results from the deficiency of uroporphyrinogen III synthase, the fourth enzyme on the metabolic pathway of heme synthesis. GD leads to severe scarring of the face and hands as a result of photosensitivity and fragility of the skin due to uroporphyrin I and coproporphyrin I accumulation. It also causes erythrocyte fragility leading to haemolytic anaemia. The other clinical features include hirsutism, red discolouration of teeth, finger-nails and urine and stunted growth. The outcome is poor, and the disfiguring nature of GD may partly explain the legend of the werewolf. No curative treatment was known until 1991, when the first case of BMT in GD was reported. The clinical and biological outcome after transplantation was encouraging, with an important regression of the symptoms of the disease, but the child died of CMV-infection 11 months after BMT. We report the second case of GD treated successfully by stem cell transplantation using umbilical cord blood from an HLA-identical brother in a 4-year-old girl suffering from severe GD. Our patient is very well 10 months after transplantation. We confirm that stem cell transplantation is curative for GD.

  14. Vasculitis as a Presenting Manifestation of Chronic Hepatitis B Virus Infection: A Case Report

    PubMed Central

    Singh, Harpreet; Sukhija, Gagandeep; Kaur, Parminder; Govil, Nikhil

    2016-01-01

    Hepatitis B virus is responsible for causing hepatic complications like acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma along with some uncommon immune mediated extrahepatic manifestations. Vasculitis remains an uncommon extrahepatic complication of hepatitis B virus infection. Herein we report a case of hepatitis B infection that presented with leucocytoclastic vasculitis as an initial manifestation and managed successfully with entacavir therapy. PMID:27042512

  15. Hepatitis virus panel

    MedlinePlus

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... or past infection, or immunity to hepatitis A Hepatitis B tests: Hepatitis B surface antigen (HBsAg), you have ...

  16. Hepatitis C and HIV

    MedlinePlus

    ... Problems : Hepatitis C Subscribe Translate Text Size Print Hepatitis C What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis B . Hepatitis C and HIV About 25% of people living ...

  17. Hepatitis B and HIV

    MedlinePlus

    ... Problems : Hepatitis B Subscribe Translate Text Size Print Hepatitis B What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis C . Hepatitis B and HIV About 10% of people living ...

  18. Linkage between the variegate porphyria (VP) and the alpha-1-antitrypsin (PI) genes on human chromosome 14.

    PubMed

    Bissbort, S; Hitzeroth, H W; du Wentzel, D P; Van den Berg, C W; Senff, H; Wienker, T F; Bender, K

    1988-07-01

    From family studies close linkage between the gene locus for variegate porphyria (VP) and the alpha-1-antitrypsin (PI) gene became evident. The maximal lod score from male meioses was 4.33 at theta = 0.04 and from both sexes combined 3.56 at theta = 0.12. Three pedigrees were triple informative regarding loci VP, PI, and IGHC (immunoglobulin heavy chain cluster, Gm polymorphism). In two of the respective meioses recombinations were observed, and in both cases the co-segregating VP and PI alleles were separated from the Gm haplotypes. These findings argue in favour of gene order either VP:PI:IGHC or PI:VP:IGHC.

  19. Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis.

    PubMed Central

    Ehata, T; Omata, M; Chuang, W L; Yokosuka, O; Ito, Y; Hosoda, K; Ohto, M

    1993-01-01

    Infection with hepatitis B virus leads to a wide spectrum of liver injury, including self-limited acute hepatitis, fulminant hepatitis, and chronic hepatitis with progression to cirrhosis or acute exacerbation to liver failure, as well as an asymptomatic chronic carrier state. Several studies have suggested that the hepatitis B core antigen could be an immunological target of cytotoxic T lymphocytes. To investigate the reason why the extreme immunological attack occurred in fulminant hepatitis and severe exacerbation patients, the entire precore and core region of hepatitis B virus DNA was sequenced in 24 subjects (5 fulminant, 10 severe fatal exacerbation, and 9 self-limited acute hepatitis patients). No significant change in the nucleotide sequence and deduced amino acid residue was noted in the nine self-limited acute hepatitis patients. In contrast, clustering changes in a small segment of 16 amino acids (codon 84-99 from the start of the core gene) in all seven adr subtype infected fulminant and severe exacerbation patients was found. A different segment with clustering substitutions (codon 48-60) was also found in seven of eight adw subtype infected fulminant and severe exacerbation patients. Of the 15 patients, 2 lacked precore stop mutation which was previously reported to be associated with fulminant hepatitis. These data suggest that these core regions with mutations may play an important role in the pathogenesis of hepatitis B viral disease, and such mutations are related to severe liver damage. Images PMID:8450049

  20. Interactions between Hepatitis C Virus and the Human Apolipoprotein H Acute Phase Protein: A Tool for a Sensitive Detection of the Virus.

    PubMed

    Stefas, Ilias; Tigrett, Sylvia; Dubois, Grégor; Kaiser, Marco; Lucarz, Estelle; Gobby, Delphine; Bray, Dorothy; Ellerbrok, Heinz; Zarski, Jean Pierre; Veas, Francisco

    2015-01-01

    The Hepatitis C virus (HCV) infection exhibits a high global prevalence frequently associated with hepatocellular carcinoma, taking years to develop. Despite the standardization of highly sensitive HCV quantitative RT-PCR (qRT-PCR) detection methods, false-negative diagnoses may be generated with current methods, mainly due to the presence of PCR inhibitors and/or low viral loads in the patient's sample. These false-negative diagnoses impact both public health systems, in developing countries, and an in lesser extent, in developed countries, including both the risk of virus transmission during organ transplantation and/or blood transfusion and the quality of the antiviral treatment monitoring. To adopt an appropriate therapeutic strategy to improve the patient's prognosis, it is urgent to increase the HCV detection sensitivity. Based upon previous studies on HBV, we worked on the capacity of the scavenger acute phase protein, Apolipoprotein H (ApoH) to interact with HCV. Using different approaches, including immunoassays, antibody-inhibition, oxidation, ultracentrifugation, electron microscopy and RT-PCR analyses, we demonstrated specific interactions between HCV particles and ApoH. Moreover, when using a two-step HCV detection process, including capture of HCV by ApoH-coated nanomagnetic beads and a home-made real-time HCV-RT-PCR, we confirmed the presence of HCV for all samples from a clinical collection of HCV-seropositive patients exhibiting an RT-PCR COBAS® TaqMan® HCV Test, v2.0 (COBAS)-positive result. In contrast, for HCV-seropositive patients with either low HCV-load as determined with COBAS or exhibiting HCV-negative COBAS results, the addition of the two-step ApoH-HCV-capture and HCV-detection process was able to increase the sensitivity of HCV detection or more interestingly, detect in a genotype sequence-independent manner, a high-proportion (44%) of HCV/RNA-positive among the COBAS HCV-negative patients. Thus, the immune interaction between ApoH and

  1. Interactions between Hepatitis C Virus and the Human Apolipoprotein H Acute Phase Protein: A Tool for a Sensitive Detection of the Virus

    PubMed Central

    Dubois, Grégor; Kaiser, Marco; Lucarz, Estelle; Gobby, Delphine; Bray, Dorothy; Ellerbrok, Heinz; Zarski, Jean Pierre; Veas, Francisco

    2015-01-01

    The Hepatitis C virus (HCV) infection exhibits a high global prevalence frequently associated with hepatocellular carcinoma, taking years to develop. Despite the standardization of highly sensitive HCV quantitative RT-PCR (qRT-PCR) detection methods, false-negative diagnoses may be generated with current methods, mainly due to the presence of PCR inhibitors and/or low viral loads in the patient’s sample. These false-negative diagnoses impact both public health systems, in developing countries, and an in lesser extent, in developed countries, including both the risk of virus transmission during organ transplantation and/or blood transfusion and the quality of the antiviral treatment monitoring. To adopt an appropriate therapeutic strategy to improve the patient’s prognosis, it is urgent to increase the HCV detection sensitivity. Based upon previous studies on HBV, we worked on the capacity of the scavenger acute phase protein, Apolipoprotein H (ApoH) to interact with HCV. Using different approaches, including immunoassays, antibody-inhibition, oxidation, ultracentrifugation, electron microscopy and RT-PCR analyses, we demonstrated specific interactions between HCV particles and ApoH. Moreover, when using a two-step HCV detection process, including capture of HCV by ApoH-coated nanomagnetic beads and a home-made real-time HCV-RT-PCR, we confirmed the presence of HCV for all samples from a clinical collection of HCV-seropositive patients exhibiting an RT-PCR COBAS® TaqMan® HCV Test, v2.0 (COBAS)-positive result. In contrast, for HCV-seropositive patients with either low HCV-load as determined with COBAS or exhibiting HCV-negative COBAS results, the addition of the two-step ApoH-HCV-capture and HCV-detection process was able to increase the sensitivity of HCV detection or more interestingly, detect in a genotype sequence-independent manner, a high-proportion (44%) of HCV/RNA-positive among the COBAS HCV-negative patients. Thus, the immune interaction between Apo

  2. Scleral necrosis in congenital erythropoietic porphyria: A case report and review of the literature

    PubMed Central

    Agarwal, Shweta; Majumder, Parthopratim Dutta; Srinivasan, Bhaskar; Iyer, Geetha

    2015-01-01

    A 28-year-old presented with complaints of severe pain and redness in the left eye since 2 weeks. He had similar complaints in the right eye 2 years back for which he had undergone a scleral patch graft. Best corrected visual acuity was 20/20 in both eyes. The right had a well vascularized scleral graft and rest of the anterior segment was normal. The left eye had inferior conjunctival congestion with an area of the scleral melt with uveal show just temporal to the limbus in the interpalbebral area. The cornea was clear and anterior chamber was quiet in the left eye. Applanation tonometry and fundus evaluation were normal in both eyes. Physical examination revealed hyperpigmented skin lesion, hypertrichosis and absorption of distal phalanges. Laboratory, ocular and physical findings confirmed the diagnosis of congenital erythropoietic porphyria. He was on oral steroids 40 mg/day since 2 weeks and topical antibiotics and lubricants. He was advised to continue the same and was taken up for scleral patch graft with fibrin glue in the left eye. Postoperatively he was continued on topical and oral steroids and lubricants.3 weeks later the left eye had stabilized however patient came with a melt in the right eye. Since it was an early melt, we went ahead with cyanoacrylate glue and bandage contact lens in the right eye and started him on topical steroids for the right eye also. Three months later both the eyes were stable, and the patient was gradually tapered off the steroids. PMID:26903733

  3. Pericholecystic hepatic activity in cholescintigraphy

    SciTech Connect

    Smith, R.; Rosen, J.M.; Gallo, L.N.; Alderson, P.O.

    1985-09-01

    Gallbladder nonvisualization in cholescintigraphy has been shown to be a reliable finding in acute cholecystitis. In some cholescintigrams, the authors have observed faintly increased pericholecystic hepatic activity in conjunction with gallbladder nonvisualization. To determine the frequency and significance of the pericholecystic hepatic activity finding, they evaluated 334 consecutive adult patients who had cholescintigrams with technetium-99m diisopropylphenylcarboamoyl iminodiacetic acid. Pericholecystic hepatic activity was seen in 21% of the abnormal scans demonstrating gallbladder nonvisualization but in none of the other scans. Thirteen of these patients underwent surgery; 11 (85%) were found to have acute cholecystitis, and two (15%) had chronic cholecystitis. The pericholecystic hepatic activity sign is not specific for gangrenous cholecystitis or gallbladder perforation but does reliably indicate inflammatory gallbladder disease and is associated with a relatively high incidence of cholecystitis complicated by perforation.

  4. Faster clearance of omeprazole in rats with acute renal failure induced by uranyl nitrate: contribution of increased expression of hepatic cytochrome P450 (CYP) 3A1 and intestinal CYP1A and 3A subfamilies.

    PubMed

    Lee, Dae Y; Jung, Young S; Shin, Hyun S; Lee, Inchul; Kim, Young C; Lee, Myung G

    2008-07-01

    It has been reported that omeprazole is mainly metabolized via hepatic cytochrome P450 (CYP) 1A1/2, CYP2D1 and CYP3A1/2 in male Sprague-Dawley rats, and the expression of hepatic CYP3A1 is increased in male Sprague-Dawley rats with acute renal failure induced by uranyl nitrate (U-ARF rats). Thus, the metabolism of omeprazole would be expected to increase in U-ARF rats. After intravenous administration of omeprazole (20 mgkg(-1)) to U-ARF rats, the area under the plasma concentration-time curve from time zero to infinity (AUC) was significantly reduced (371 vs 494 microg min mL(-1)), possibly due to the significantly faster non-renal clearance (56.6 vs 41.2 mL min(-1) kg(-1)) compared with control rats. This could have been due to increased expression of hepatic CYP3A1 in U-ARF rats. After oral administration of omeprazole (40 mgkg(-1)) to U-ARF rats, the AUC was also significantly reduced (89.3 vs 235 microg min mL(-1)) compared with control rats. The AUC difference after oral administration (62.0% decrease) was greater than that after intravenous administration (24.9% decrease). This may have been primarily due to increased intestinal metabolism of omeprazole caused by increased expression of intestinal CYP1A and 3A subfamilies in U-ARF rats, in addition to increased hepatic metabolism.

  5. NKP30-B7-H6 Interaction Aggravates Hepatocyte Damage through Up-Regulation of Interleukin-32 Expression in Hepatitis B Virus-Related Acute-On-Chronic Liver Failure

    PubMed Central

    Pan, Xingfei; Lu, Ying; Liao, Sihong; Wang, Xicheng; Wang, Guoying; Lin, Dongjun

    2015-01-01

    Background and Aims Previous work conducted by our group has shown that the accumulation of hepatic natural killer (NK) cells and the up-regulation of natural cytotoxicity receptors (NKP30 and NKP46) on NK cells from patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) were correlated with disease progression in HBV-ACLF. The natural cytotoxicity receptors expressed on NK cells are believed to be probable candidates involved in the NK cell-mediated hepatocyte damage in HBV-ACLF. However, the underlying mechanisms remain to be elucidated. In the present study, we aimed to discover the role of NKP30-B7-H6 interaction in NK cells-mediated hepatocyte damage in HBV-ACLF. Methods Hepatic expressions of B7-H6 and interleukin-32 (IL-32) were examined by immunochemistry staining in samples from patients with HBV-ACLF or mild chronic hepatitis B (CHB). The cytotoxicity of NK-92 cell against target cells (Huh-7 and LO2) was evaluated by CCK8 assay. Expression of IL-32 in liver NK cell, T cells and NK-92 cell line was detected by the flow cytometric analysis. The effect of IL-32 on the apoptosis of Huh7 cells was evaluated using Annexin V/PI staining analysis. Results An enhancement of hepatic B7-H6 and IL-32 expression was associated with the severity of liver injury in HBV-ACLF. And there was a positive association between hepatic B7-H6 and IL-32 expression. Expressions of IL-32 in liver NK cells and T cells were increased in HBV-ACLF patients. In vitro NK-92 cells are highly capable of killing the high B7-H6 expressing Huh7 cells and B7-H6-tansfected hepatocyte line LO2 cells dependent on NKP30 and B7-H6 interaction. Furthermore, NK-92 cells exhibited elevated IL-32 expression when stimulated with anti-NKP30 antibodies or when co-cultured with Huh7 cells. IL-32 can induce the apoptosis of Huh7 cells in a dose-dependent manner. Conclusion Our results suggest that NKP30-B7-H6 interaction can aggravate hepatocyte damage, probably through up

  6. Histologic features in autoimmune hepatitis.

    PubMed

    Dienes, H P; Popper, H; MAnns, M; Baumann, W; Thoenes, W; Meyer Zum Büschenfelde, K H

    1989-06-01

    In order to see if the term of "plasma cell hepatitis", dating back to the early sixties, is still valid as a morphological diagnosis for autoimmune chronic hepatitis (AICH), and to find out if the existence of several subgroups is reflected by histopathology, we investigated 26 patients with chronic hepatitis, who met the criteria of autoimmune hepatitis based on tests for antinuclear, anti-smooth muscle antibodies (SMA) and on immunoassays for liver-kidney-microsomal (LKM) antigen, liver membrane antigen (LMA), and soluble liver antigen (SLA). In our material autoimmune hepatitis represent the entire spectrum of chronic hepatitis with variable inflammatory activity ranging from chronic persistent hepatitis to severe inflammatory lesions in chronic active hepatitis with transition to cirrhosis. When compared to viral chronic hepatitis A and non-A, non-B, however, characteristic features can be evaluated consisting in broad hypocellular areas of collapse and microacinar transformation of hepatocytes with hydropic swelling being the predominant type of cell lesion. Eosinophilic clumping and acidophilic necrosis were insignificant. Plasma cells were not a constituent feature of AICH. From this histopathologic pattern it may be concluded that the disease seems to run a sluggish course in most patients, however, in few cases a dramatic development may determine the disease with fatal acute episodes which are terminated by death or fade into slow progression. The different subgroups could not be distinguished by histopathology.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Diagnosis of hepatitis B

    PubMed Central

    Song, Jeong Eun

    2016-01-01

    Hepatitis B virus (HBV) infection is a major global health problems leading to severe liver disease such as cirrhosis and hepatocellular carcinoma (HCC). HBV is a circular, partly double-stranded DNA virus with various serological markers: hepatitis B surface antigen (HBsAg) and anti-HBs, anti-HBc IgM and IgG, and hepatitis B e antigen (HBeAg) and anti-HBe. It is transmitted by sexual, parenteral and vertical route. One significant method to diminish the burden of this disease is timely diagnosis of acute, chronic and occult cases of HBV. First step of HBV diagnosis is achieved by using serological markers for detecting antigens and antibodies. In order to verify first step of diagnosis, to quantify viral load and to identify genotypes, quantitative or qualitative molecular tests are used. In this article, the serological and molecular tests for diagnosis of HBV infection will be reviewed. PMID:27761442

  8. Hepatitis C: Treatment

    MedlinePlus

    ... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...

  9. Hepatitis C and Incarceration

    MedlinePlus

    HEPATITIS C & INCARCERATION What is hepatitis? “Hepatitis” means inflammation or swelling of the liver. The liver is an important ... viral hepatitis: Hepatitis A, Hepatitis B, and Hepatitis C. They are all different from each other and ...

  10. Hepatitis A

    MedlinePlus

    ... an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... washed in untreated water Putting into your mouth a finger or object that came into contact with ...

  11. Hepatitis D

    MedlinePlus

    ... if the hepatitis B virus is also present. Transmission Hepatitis D can be found in the blood, ... other body fluids of people who are infected. Transmission happens when infected body fluid enters another person’s ...

  12. Hepatitis C

    MedlinePlus

    ... 2014 Select a Language: Fact Sheet 507 Hepatitis C WHAT IS HEPATITIS C? HOW IS IT DIAGNOSED? ... treatment may be less likely to work. Hep C treatment is less effective for coinfected people. Cure ...

  13. Hepatitis A

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Español Hepatitis A Page Content On this page: What is ... Nutrition Points to Remember Clinical Trials What is hepatitis A? Hepatitis * A is a virus , or infection, ...

  14. Autoimmune Hepatitis

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Autoimmune Hepatitis Page Content On this page: What is autoimmune ... Points to Remember Clinical Trials What is autoimmune hepatitis? Autoimmune hepatitis is a chronic—or long lasting— ...

  15. Hepatitis C

    MedlinePlus

    ... an inflammation of the liver. One type, hepatitis C, is caused by the hepatitis C virus (HCV). It usually spreads through contact with ... childbirth. Most people who are infected with hepatitis C don't have any symptoms for years. If ...

  16. The hepatic-arterial/portal-venous scintiangiogram in alcoholic hepatitis

    SciTech Connect

    Stewart, C.; Sakimura, I.; Siegel, M.E.; Harley, H.; Lee, K.

    1984-01-01

    This study was designed to identify abnormalities in the hepatic-arterial/portal-venous scintiangiogram (SA) in alcoholic hepatitis (AH). SA's were performed in 35 patients with acute alcoholic hepatitis (AAH), 8; acute alcoholic hepatitis superimposed on cirrhosis (A/C), 14; and cirrhosis (C), 13. Posterior flows were done with a bolus of 10 mCi Tc-99m sulfur colloid with computer time-activity curves over the liver and left kidney. Curves were analyzed for per cent of hepatic arterial (HA) and portal venous contribution using the slope ratio method. Hepatic arterialization was estimated from the angle of the HA component of the curve. Reversal of the relative contribution of the hepatic and portal components of total flow were seen in all groups. Although quite severe in AH, the degree of reversal could not be used to differentiate among the groups. The average HA angle in AAH was 48.3 +- 8.1, in A/C 41.5 +- 10.6, and in C 30.4 +- 12.1. In reviewing the data of only those in the acute clinical phase of AH and not the recovery phase (1 AAH, 3 A/C) and those without other causes of alteration in hepatic arterialization (1 hepatoma, 1 portalcaval shunt, 6 renal failure), the average HA angle in AAH was 50.1 +- 6.6, 45.4 +- 8.2 in A/C, and 23.2 +- 4.2 in C. In 6 with renal failure (2 C, 2AAH, 2 A/C) the HA angle ws 52.7 +- 5.7. In all cases cirrhosis could be differentiated from both A/C (P=.05) and AAH (P<.01) using the HA angle. In absence of renal failure, portal shunt, or hepatoma, P was <.01 in both comparisons.

  17. Acute Exposure to Tris(1,3-dichloro-2-propyl) Phosphate (TDCIPP) Causes Hepatic Inflammation and Leads to Hepatotoxicity in Zebrafish

    PubMed Central

    Liu, Chunsheng; Su, Guanyong; Giesy, John P.; Letcher, Robert J.; Li, Guangyu; Agrawal, Ira; Li, Jing; Yu, Liqin; Wang, Jianghua; Gong, Zhiyuan

    2016-01-01

    Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been frequently detected in environmental media and has adverse health effect on wildlife and humans. It has been implicated to have hepatotoxicity, but its molecular mechanisms remain unclear. In the present study, adult male zebrafish were exposed to TDCIPP and global hepatic gene expression was examined by RNA-Seq and RT-qPCR in order to understand the molecular mechanisms of TDCIPP-induced hepatotoxicity. Our results indicated that TDCIPP exposure significantly up-regulated the expression of genes involved in endoplasmic reticulum stress and Toll-like receptor (TLR) pathway, implying an inflammatory response, which was supported by up-regulation of inflammation-related biomaker genes. Hepatic inflammation was further confirmed by histological observation of increase of infiltrated neutrophils and direct observation of liver recruitment of neutrophils labeled with Ds-Red fluorescent protein of Tg(lysC:DsRed) zebrafish upon TDCIPP exposure. To further characterize the hepatotoxicity of TDCIPP, the expression of hepatotoxicity biomarker genes, liver histopathology and morphology were examined. The exposure to TDCIPP significantly up-regulated the expression of several biomarker genes for hepatotoxicity (gck, gsr and nqo1) and caused hepatic vacuolization and apoptosis as well as increase of the liver size. Collectively, our results suggest that exposure to TDCIPP induces hepatic inflammation and leads to hepatotoxicity in zebrafish. PMID:26743178

  18. Acute Exposure to Tris(1,3-dichloro-2-propyl) Phosphate (TDCIPP) Causes Hepatic Inflammation and Leads to Hepatotoxicity in Zebrafish

    NASA Astrophysics Data System (ADS)

    Liu, Chunsheng; Su, Guanyong; Giesy, John P.; Letcher, Robert J.; Li, Guangyu; Agrawal, Ira; Li, Jing; Yu, Liqin; Wang, Jianghua; Gong, Zhiyuan

    2016-01-01

    Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been frequently detected in environmental media and has adverse health effect on wildlife and humans. It has been implicated to have hepatotoxicity, but its molecular mechanisms remain unclear. In the present study, adult male zebrafish were exposed to TDCIPP and global hepatic gene expression was examined by RNA-Seq and RT-qPCR in order to understand the molecular mechanisms of TDCIPP-induced hepatotoxicity. Our results indicated that TDCIPP exposure significantly up-regulated the expression of genes involved in endoplasmic reticulum stress and Toll-like receptor (TLR) pathway, implying an inflammatory response, which was supported by up-regulation of inflammation-related biomaker genes. Hepatic inflammation was further confirmed by histological observation of increase of infiltrated neutrophils and direct observation of liver recruitment of neutrophils labeled with Ds-Red fluorescent protein of Tg(lysC:DsRed) zebrafish upon TDCIPP exposure. To further characterize the hepatotoxicity of TDCIPP, the expression of hepatotoxicity biomarker genes, liver histopathology and morphology were examined. The exposure to TDCIPP significantly up-regulated the expression of several biomarker genes for hepatotoxicity (gck, gsr and nqo1) and caused hepatic vacuolization and apoptosis as well as increase of the liver size. Collectively, our results suggest that exposure to TDCIPP induces hepatic inflammation and leads to hepatotoxicity in zebrafish.

  19. Hepatitis B virus infection.

    PubMed

    Chang, Mei-Hwei

    2007-06-01

    Hepatitis B virus (HBV) infection is a worldwide health problem and may cause acute, fulminant, chronic hepatitis, liver cirrhosis, or hepatocelullar carcinoma (HCC). Infection with HBV in infancy or early childhood may lead to a high rate of persistent infection (25-90%), while the rates are lower if infection occurs during adulthood (5-10%). In most endemic areas, infection occurs mainly during early childhood and mother-to-infant transmission accounts for approximately 50% of the chronic infection cases. Hepatitis B during pregnancy does not increase maternal mortality or morbidity or the risk of fetal complications. Approximately 90% of the infants of HBsAg carrier mothers with positive hepatitis B e-antigen (HBeAg) will become carriers if no immunoprophylaxis is given. Transplacental HBeAg may induce a specific non-responsiveness of helper T cells and HBcAg. Spontaneous HBeAg seroconversion to anti-HBe may develop with time but liver damage may occur during the process of the immune clearance of HBV and HBeAg. Mother-to-infant transmission of HBV from HBeAg negative but HBsAg positive mothers is the most important cause of acute or fulminant hepatitis B in infancy. Although antiviral agents are available to treat and avoid the complications of chronic hepatitis B, prevention of HBV infection is the best way for control. Screening for maternal HBsAg with/without HBeAg, followed by three to four doses of HBV vaccine in infancy and hepatitis B immunoglobulin (HBIG) within 24h of birth is the most effective way to prevent HBV infection. In areas with a low prevalence of HBV infection or with limited resources, omitting maternal screening but giving three doses of HBV vaccine universally in infancy can also produce good protective efficacy. The first universal HBV immunisation programme in the world was launched in Taiwan 22 years ago. HBV infection rates, chronicity rates, incidence of HCC and incidence of fulminant hepatitis in children have been effectively

  20. Hepatitis Vaccines