Liver Disease Food List

The Liver Cirrhosis Freedom Cookbook

Without these information you almost no chance of planning a comprehensive dietary strategy without spending months on it. This is how The Liver Cirrhosis Freedom Cookbook will change your life: You will never eat a meal that aggravates your liver condition again. And you very likely did it today. You will gently soothe your endocrine system and shift the ravaging chemical imbalance that is eating away your organs. Boost the secretion of self-healing chemicals that will repair your organs before it's too late. Enjoy delicious meals while knowing every second that you are healing your body with every bite. You won't have to think about where to start in your healing, you will have all the work done for you. When you wake up in the morning you'll feel light and positive, knowing that healing chemicals in your body are doing their work every second. You won't have to spend endless hours in front of your computer or buy nutrition books to know what is completely safe for you. Never again buy another book about diet and health, because you have it all right here and written just for your condition, not general and vague, but laser precise and understandable. Start your healing today, without any procrastination. Once again, feel that health and energy you so desperately pursu

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Acute liver failure

Acute liver failure is the sudden development of liver parenchymal injury resulting in coagulopathy (INR > 1.5) in a patient who lacks underlying chronic liver disease. Progression to encephalopathy in such a patient is known as fulminant hepatic failure (FHF). The etiologies of acute liver failure include

Copper In Diseases And Genetic Diseases Of Copper Metabolism

In contrast to Menkes disease, Wilson disease occurs more gradually, and after birth. It results in the accumulation of excess copper in liver and some other tissues and oxidative damage (65). In this case the problem is excretion, because in the absence of the normal WND ATP7B protein, it is difficult for copper to enter the bile (see Section 1.5.). Accumulation of excess copper in tissues (although mitigated by binding to metallothionein) promotes formation of reactive oxygen species, eventually resulting in liver cirrhosis (65,181-184). The brain and some endocrine organs are also affected. Further details may be found in more recent reviews of these diseases (57,185-189).

Diseasespecific diets

Specifically formulated disease-specific diets have been developed for patients with disorders such as encephalop-athy associated with chronic liver disease, and respiratory failure. Malnourished patients with cirrhosis who present with encephalopathy, or who have a previous history of episodes of encephalopathy, present a difficult problem of nutritional management. Branched-chain amino acid-enriched diets have been advocated to normalize plasma amino acid profiles with the aim of improving nutritional state and preventing worsening of encephalopathy. Patients with respiratory failure on ventilators are adversely affected by diets with high carbohydrate loads which increase CO2 production. Diets with a higher fat energy component allow earlier weaning from artificial ventilator support as a result of decreased CO2 production and reduced respiratory quotient.

Materials And Methods

Carcinoma 153 Natural History of Hepatocellular Carcinoma 154 Chronic Hepatitis 155 Cirrhosis 155 Hepatocellular Carcinoma with or without Cirrhosis 174 Molecular Markers in the Differential Diagnosis of Hepatocellular Carcinomas 175 References 175 Introduction 207 Epidemiology of Liver Cancer 207 Hepatitis, Liver Cirrhosis, and Liver Pitfalls 248 Fine-Needle Aspiration Biopsy 249 Normal Liver, Cirrhosis, and Steatosis 249 Benign Hepatocellular Nodular Lesions 249 Well-Differentiated Hepatocellular Carcinoma 251 Ancillary Studies 253 Special Stains 253 Immunohistochemistry 254 Other Immunostains 256 CONCLUSIONS 257 References 258

Success and failure of treatment

Low CD4 cells at baseline as well as low viral load before the start of therapy are just two of many factors (Florence 2003, Kaufmann 2005, Moore 2005, Wolbers 2007). Age also plays an important role in older patients, immunological response is often only moderate in comparison to virological response. Several studies demonstrated that the probability of not achieving a rise in the CD4-cell count increases with patient age and with progressive decrease in thymus size as detected by computed tomography (Goetz 2001, Marimoutou 2001, Piketty 2001, Teixera 2001, Viard 2001, Wolbers 2007). Patients who are intravenous drug users also have relatively poor increases in CD4 cells (Dragstedt 2004). In the Swiss cohort, the CD4 cells increased more in women than in men (Wolbers 2007). Other causes for a lack of immunological response may be immuno- or myelosup-pressive concomitant therapies. We have seen patients, who have had a suppressed viral load below 50 CD4 cells l for years, who only...

Hepatitis C Virus and Hepatocellular Carcinoma

Virus to be expelled naturally, with the estimated annual rate being less than 0.2 at most. Many of the patients with persistent infection show the medical conditions of chronic hepatitis and develop cirrhosis in 20 to 30 years. Patients with cirrhosis develop HCC at a very high annual rate of 8 , while patients with early chronic hepatitis do so at an annual rate of only 0.5 . The estimated number of patients with HCV is about 1.7 million in Japan and about 1.7 billion in the world. It is a serious public health problem as many of these patients belong to a high-risk group for HCC.

Toxicity Associated With Traditional Use by Native Populations

In the United States and Europe, evidence of hepatic failure following the use of kava extracts is accumulating. A 50-year-old male, who had previously been well, experienced liver failure after consuming kava extract for 2 months. The dosage of kava extracts was at or slightly exceeded the maximum three-capsule-a-day dose recommended on the label. A liver transplant was performed and the individual survived (33). A US Food and Drug Administration (FDA) advisory letter dated March 25, 2002 warned health care providers of a total of 11 patients who had used kava products and developed liver failure requiring liver transplantation (34).

Chronic Diseases and Neurocognition

Negative cognitive outcomes are also associated with type I and type II diabetes mellitus, pulmonary diseases such as chronic obstructive pulmonary disease and asthma, hepatic diseases such as cirrhosis, kidney diseases, autoimmune diseases such as systemic lupus erythematosus, various cancers, sleep disorders such as obstructive sleep apnea, and the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome (AIDS) (see Bellia et al, 2007 Biessels et al, 2008 Borson et al, 2008 Kurella et al, 2005 Tarter et al, 2001 Zhang et al, 2007).

Clinical features

Patients with acute liver failure are jaundiced as the liver fails to conjugate and excrete bilirubin. Their laboratory values demonstrate marked transaminase elevation (AST and ALT in the range of 1000-5000), as liver cells are injured. Synthetic function is compromised and coagulopathy occurs as a consequence of clotting factor depletion. Disseminated intravascular coagulation (DIC) can also contribute to clotting abnormality. Importantly, hepatic encephalopathy in the acute setting differs from that of encephalopathy related to cirrhosis and chronic liver failure. In chronic hepatic failure, encephalopathy is related to increased ammonia levels. Conversely, encephalopathy in FHF is related to cerebral edema. Thus, worsening of encephalopathy in patients with FHF is a sign of progressive edema and a poor prognostic indicator. Progression to central herniation is possible in these patients.

Chronic liver disease

Superimposed acute hepatic failure also occurs in patients with chronic liver disease. Often times an event such as a new infection (spontaneous bacterial peritonitis) or GI bleed will tip a previously stable cirrhotic into fulminant liver failure. Treatment is supportive as described above. Generally such

HCV Infection of B Cells Induces Ig Hypermutation Altering B Cell Immunity

Besides chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, HCV infection is also frequently associated with B lymphocyte proliferative disorders, including mixed cryoglobulinemia, a disorder characterized by oligoclonal proliferation of B cells, and non-Hodgkin's B cell lymphoma (Silvestri et al. 1997). These B cell diseases may be the result of infection of B cells by HCV or the activation of B cells by HCV envelope proteins. The HCV envelope proteins E1 and E2 are type I transmembrane proteins, with N-terminal ectodomains and C-terminal hydrophobic anchors. It has been suggested that HCV infects human cells through the interaction of E2 with a tetraspanin molecule CD81. CD81 is thought to be a cellular receptor for HCV, based on its ability to bind E2 (Pileri et al. 1998 Hsu et al. 2003 McKeating et al. 2004 Zhang et al. 2004). CD81 is a member of the tetraspanin family and is a component of the multimeric B cell antigen receptor complex (Levy et al. 1998). It is...

Clinical manifestations

In the liver mitochondrial toxicity is associated with increased lipid deposits, resulting in micro or macrovesicular steatosis. Steatosis may be accompanied by elevated liver transaminases. Such steatohepatitis may be observed with even one NRTI such as DDI and progress to liver failure and lactic acidosis, a potentially fatal, but fortunately rare complication (Lambert 1990). Hepatotoxicity is now predominantly observed under treatment with dideoxynucleosides, i.e. with ddI, d4T, and ddC, but also with AZT. The onset of hepatic mtDNA-depletion is dependent on the time of NRTI exposure (Walker 2004a). On electron microscopy, morphologically abnormal mitochondria are observed. Adrenalin (iatrogenic, endogenous) Liver failure

Some Effects of Drug Abuse in the Brain Mimic Those of HIV

Drug abuse is clearly a confounding factor in assessing the effects of HIV in the brains of pre-symptomatic and some AIDS subjects, and the influence of drug abuse on the CNS must be considered together with HIV in this context. The problem of drugs as possible co-factors for AIDS progression has been explored in animal models and in vitro (52). Drug abuse is known to cause mild activation of microglia, possibly adding to the neuroinflammatory response observed in pre-symptomatic subjects (5). Axonal injury as shown by expression of pAPP is also evident in the brains of HIV-negative drug abusers (53, 54). A number of studies have demonstrated other neuronal and dendritic damage in HIV-negative drug abusers (53-56). Some of this CNS damage is undoubtedly hypoxic ischaemic in origin. Intravenous drug abusers are at risk of co-infection with hepatitis B or C. Liver dysfunction, particularly cirrhosis, can cause hepatic encephalopathy, contributing to cognitive problems in this group of...

Role Of Pina In Pineal Physiology

To determine a role for PINA in the normal pineal physiology, we have turned to the LEC rat, a strain in which PINA and ATP7B are mutated as a result of a large deletion in the C-terminal coding region (12). These rats are well-established models of Wilson's disease in which copper builds up in the liver, resulting in liver failure and death (13).

Nonpsychotic Disorders

Because alcohol is rich in carbohydrates but low in proteins and vitamins, long-term users can develop cirrhosis of the liver due to protein deficiency or Korsakoff's syndrome due to vitamin B deficiency. The symptoms of Korsakoff's syndrome, a chronic brain disorder occurring most often in chronic alcoholics in their fifties and sixties, include disorientation, impulsiveness, memory loss, confabulation,1 and inflammation of the peripheral nerves of the body.

Staging Investigations And Prognostic Factors

At Charing Cross Hospital, the routine staging investigation performed on these patients after their initial orchiectomy is computed tomography (CT) of the thorax and abdomen (usually omitting the pelvis, except in patients who have had a previous orchiopexy), to minimize the radiation to these patients. Patients are all routinely monitored with the three serum tumor markers hCG, AFP, and lactate dehydrogenase (LDH). Patients with pulmonary metastases routinely have a magnetic resonance imaging (MRI) brain scan performed. Baseline renal function is measured by ethylenediaminetetraacetic acid (EDTA) clearance. In patients with poor-prognosis NSGCTs, initial organ failure can be a problem at the initiation of treatment. Renal failure from ureteric obstruction, liver failure, and severely compromised pulmonary function can all be problems that need addressing at the start of treatment.

Other Possible Genetic Copper Toxicosis Disorders

A group of similar childhood copper-toxicosis conditions have been described and are often associated with excess intake of copper in infancy. Indian childhood cirrhosis (ICC) is a fatal disease characterized by massive hepatic copper accumulation resulting from the consumption of milk containing high concentrations of copper. Since the practice of boiling milk in brass vessels has been discouraged, the disease is disappearing (75). There is a high rate of parental consanguinity in families affected with this disease and up to 22 of siblings are affected, suggesting a genetic basis (75). Clinically, ICC can be distinguished from Wilson's disease by the characteristic liver histology, early age of onset, normal ceruloplasmin and absence of neurological involvement (75). Similar infantile copper-associated toxicity cases have been reported, and a clear autosomal recessive inheritance has been reported for the disease in Austria (76). This disease is indistinguishable clinically from ICC...

Animal Models of Wilsons Disease and ICC

Two other animal models of copper toxicosis are of interest, normal sheep and a breed of dog, the Bedlington terrier. These animals accumulate hepatic copper and this phenotype may be the result of mutations of novel copper homeostasis genes, perhaps the orthologs of the gene that is involved in Austrian childhood cirrhosis. Sheep are prone to accumulate hepatic copper, because of a reduction in biliary copper excretion and, in this respect, sheep resemble patients with WD (4). The molecular basis of this phenotype is unclear however, sheep have two forms of ATP7B, one that closely resembles the protein in other mammals and an other that has a novel N-terminal extension of 79 amino acids (86). It is possible that this novel form may play a part in the hepatic copper accumulation phenotype.

Portal Vein Embolization

Preoperative portal vein embolization (PVE) prior to extended liver resection is an option in selected patients if there is concern regarding possible postoperative liver failure or complications due to a small liver remnant volume. The rationale for this technique is to induce hypertrophy of the future liver remnant (FLR).

Secondary haemochromatosis

Chronic anaemia such as aplastic anaemia, sickle cell anaemia, and thalassaemia cause iron overload mostly because of frequent blood transfusions. Each 250 ml transfused red cells adds about 250 mg elemental iron to the body. Frequent transfusions may promote diabetes mellitus and cardiac failure when iron concentrations exceed 268 ymol g dry weight liver (15 mg g). The endorgan manifestations of iron overload, such as cirrhosis, cardiac failure, hepatocellular carcinoma, diabetes mellitus and hypopituitarism resemble the manifestations in hereditary haemochromatosis patients.

Umbilical Hernia In Adults

Umbilical hernias are an important complication of cirrhosis and ascites the ascites should be controlled either medically or with a shunt before hernia repair is undertaken. Umbilical herniation is sometimes a consequence of chronic ambulatory peritoneal dialysis (CAPD). In all patients that are to initiate CAPD, any hernia that is found prior to the insertion of the catheter must be repaired.

[2 Phenotype Changes of Fut8 Knockout Mouse Core Fucosylation Is Crucial for the Function of Growth Factor Receptors

GDP-l-Fuc N-acetyl- -d-glucosaminide a1,6-fucosyltransferase (Fut8, E.C.2.4.1.152) catalyzes the transfer of a fucose residue from GDP-fucose to position 6 of the innermost GlcNAc residue of hybrid and complex types of N-linked oligosaccharides on glycoproteins to form core fucosylation in mammals, as shown in Fig.1A. Fut8 is the only core FucT in mammals, but there are core a1,3-Fuc residues in plants, insects, and probably other species. The Fut8 gene is expressed in most rat organs with a relatively high level expression in brain and small intestine (Miyoshi et al., 1997). a1,6-Fucosylated glycoproteins are widely distributed in mammalian tissues and are altered under some pathological conditions. For example, the level of core fucosylation is elevated in both liver and serum during the process of hepatocarcinogenesis (Hutchinson et al., 1991). The presence of core fucosylation of a-fetoprotein, a well-known tumor marker for hepatocellular carcinoma (HCC), is known to distinguish...

Indications for Resection

The indications for resection of HCC have recently been reevaluated. Studies from the 1980s and early 1990s suggested that cirrhosis and mul tiple tumor nodes were harbingers of poor outcome after resection of HCC. However, these studies were performed when operative mortality rates in cirrhotic HCC patients were 6 to 15 and the need for intraoperative and postoperative blood transfusion was common. Current studies that have compared the outcome of patients undergoing surgery utilizing modern hepatic resection techniques with the outcome of patients operated on in the 1980s or early 1990s have demonstrated improved outcome for patients treated with modern techniques. Specifically, perioperative blood transfusion rates fell from 69 to 87 in the 1980s and early 1990s to 23 to 39 in the later period. The operative and hospital death rate was reduced from 13.2 to under 2 , and 5-year survival rates improved from 19 to 32 to 25 to 49 . All of the patients in these series had pathologic...

Repeat Hepatectomy for Recurrent Malignant Tumors

Repeat hepatic resection may help selected patients with HCC. Intra-hepatic recurrence as the only site of disease is more common in patients with HCC than those with metastatic liver tumors, but fewer than 10 of patients who develop recurrent disease are candidates for repeated surgical treatments. Patients who develop hepatic recurrence of HCC after hepatic resection of their primary tumor may not be candidates for repeat resection because of multifocality, vascular invasion by tumor, or the severity of underlying cirrhosis. In properly selected patients, however, repeat hepatic resection for HCC can be performed and results in long-term survival rates of up to 30 . The incidence of postresection liver failure is no higher in patients who undergo a second hepatic resection, indicating the importance of carefully selecting patients who will have adequate functional hepatic reserve after a second operation.

Clinical course and pathogenesis

The clinical course of hepatitis C coinfection is determined by the HIV-associated immunosuppression. Progression of immunosuppression accelerates the course of hepatitis C. The latent period until liver failure or hepatocellular carcinoma is exti-mated to be 10-20 years, whereas it is 30-40 years in HCV-monoinfection. The improved treatment options for HIV infection have increased the likelihood of patients actually living to experience the development of liver failure. The associ ated decrease in mortality with HIV infection has resulted in a relative increase in hepatitis-associated mortality. In many centers, liver failure is now the most frequent cause of death in HIV-infected patients. The unfavorable course of hepatitis C in HIV infection can be improved by treatment of HIV infection with HAART. In addition, the development of liver failure can be delayed by the improved immune function under HAART. This is particularly true for patients who achieve a good immune recovery.

Course of hepatitis B with concurrent HIV infection

In HIV-infected patients, chronic hepatitis B has an unfavorable course compared with monoinfected patients, and the risk of liver-associated mortality is significantly increased (about 15 times). Following the decrease in HIV mortality, an increase of liver-associated mortality has been observed (Thio 2002, Konopnicki 2005). In addition to increasing mortality, HIV coinfection accelerates the progression of hepatitis B and increases the risk of cirrhosis. Despite the worsening described, initially the clinical course is usually more benign in HIV-positive patients, although viral replication is increased. This seems contradictory at first, but can be explained by the impairment of cellular immunity, which may lead to an increase in viral replication, but at the same time also reduces hepatocyte damage. Therefore, transaminases in HBV HIV-coinfected patients are frequently only mildly increased. In contrast, HBV DNA, as a marker for viral replication, is higher than in immunocompetent...

Nicc In The Tyrol And Germany

Between 1900 and 1974, a group of 138 infants from the Austrian province of Tyrol suffered from childhood liver cirrhosis (13,33). All of the children with symptoms died before the age of 3 yr. The clinical features of the fatal liver cirrhosis observed in the Tyrol showed striking similarities to ICC and ICT. Although the hepatic copper content was not determined in these children, the hepatic morphology was characteristic of ICC ICT. The high levels of dietary copper were attributed to the formula milk used for feeding the infants it was routinely prepared in untinned copper and brass vessels until the early 1970s. The disappearance of the disease after 1974 coincided with a change in baby feeding practices and the replacement of untinned copper and brass kitchen vessels. These observations further supported the significant role played by copper cooking utensils. However, the fact that 231 siblings remained healthy although they had been exposed to the same copper-enriched diet as...

RFA of Primary Liver Tumors

In this study, procedure-related complications were minimal in patients with HCC. There were no treatment-related deaths, but 12.7 of the HCC patients had complications, including symptomatic pleural effusion, fever, pain, subcutaneous hematoma, subcapsular liver hematoma, and ventricular fibrillation. In addition, 1 patient with Child's class B cirrhosis developed ascites, and another with Child's class B cirrhosis developed bleeding in the ablated tumor 4 days after RFA, necessitating hepatic arterial embolization and transfusion of 2 units of packed red blood cells. All patient events resolved with appropriate clinical management within 1 week after RFA, with the exception of the development of ascites, which resolved with the use of diuretics within 3 weeks after RFA. No patient developed thermal injury to adjacent organs or structures, hepatic insufficiency, renal insufficiency, or coagulopathy following the application of RF energy to the target tumors. The overall complication...

Gene Mapping Based On Identity By Descent

More recently, founded populations (approx 8-15 generations ago) have become excellent resources for mapping rare diseases with a simple inheritance pattern We can search for segments that are shared by patients and then demonstrate that this sharing is IBD (Fig. 4). This haplotype sharing approach has been extremely useful in mapping a number of rare disease genes, including the gene involved in benign recurrent hepatic cholestasis (BRIC) (46), Byler's disease (47), and North American childhood cirrhosis (48). The BRIC gene, for example, was localized to chromosome 18 by performing a genomewide screen on only three patients from a religiously isolated fishing community in the Netherlands. Although the chromosomes of these three BRIC patients had undergone at least six meioses since their shared origin, the BRIC haplotype was still shared over a region of more than 20 cM (46). The situation for the Tyrolean NICC is, however, more complicated. The disease is lethal when left untreated,...

Complicating Factors In Mapping The Tyrolean Nicc Gene

The identification of an animal model with phenotypic similarities to Tyrolean NICC could prove a useful tool to studying the disease mechanism because it is usually easier to map genes in animal models because of (1) inbreeding of the strains, (2) the large size of pedigrees, and (3) the shorter generation time. There are a few current animal models in which ingestion of copper has produced cirrhosis of the liver the copper toxicosis in Bedlington terriers (57,58) and in sheep (59,60). Copper toxicosis in North Ronaldsay sheep (so-called Ronaldsay copper toxicosis or RCT) shows many

Routine tests for renal impairment

A decrease in renal function in patients with an HIV infection could be interpreted as a symptomatic HIV infection, and antiretroviral therapy might be considered. The use of a contrast medium (CM) for the urinary tract should be avoided, especially in cases of renal insufficiency, proteinuria and all forms of low intravasal volume (including cirrhosis of the liver), in order to avoid causing CM-induced renal failure.

Tubulotoxic damage Fanconis syndrome

When the substances filtered from the glomerulum in primary urine exceed the transport capacity of the reabsorbing tubular cells, they are excreted with the urine. The most prominent example is the glucose threshold of the kidneys (180 mg dl). However, a transport dysfunction in the tubular system can also be caused by drugs such as cidofovir, tenofovir and adefovir. This is then known as a secondary (drug-induced) Fanconi's syndrome and is distinguished by a malfunction of the tubular system without there necessarily being any impairment of the GFR. There is an increased amount of phosphate, amino acids and glucose in the urine, whereas phosphate in the blood is reduced. The loss of amino acids, phosphate, glucose, bicarbonate and other organic and inorganic substances, as well as water, can become clinically manifest in the form of increased urination, thirst or tiredness. In case reports, renal failure was above all described in patients with other reasons for renal insufficiency,...

Copper Homeostasis And Metabolism

When copper entry to the body is greater than the needs, it is deposited, mainly in the liver. However, deposit by itself does not necessarily mean tissue damage. It is well known that at birth, healthy full-term neonates have copper concentrations in their liver that may be similar to those observed in individuals with copper-associated cirrhosis (20). Understanding how copper is handled by the very young child remains a most challenging question.

Chronic Toxicity In Humans

In humans, chronic toxic effects of copper associated with specific gene mutations such as Wilson's disease are well known (95-98). Rare cases of childhood cirrhosis with fatal outcome have led to postulate that genes other than Wilson's would be associated with these cases (idiopathic copper cirrhosis, idiopathic copper toxicosis). In these patients, interaction between genes and the environment that provides normal higher copper exposure determine the appearance of clinical manifestation (99-102). In all of patients, the diagnosis is made when subclinical or clinical manifestations led to the suspicion of functional liver failure or altered copper metabolism and these are demonstrated by routine laboratory measurements. In contrast to genetic conditions, the effects of chronic high copper exposure are less clear, mainly in relation to the duration of exposure and the actual copper ingestion required for triggering the effects. There are well-characterized cases of copper-associated...

The Vasopressinergic System

Excess AVP plasma levels have been assessed in patients with head trauma, congestive heart failure, liver cirrhosis, and lung carcinomas, coinciding with inappropriate antidiuresis (Renaud, 2007). AVP has been considered to regulate male characteristic social behavior including aggression, territoriality, and stress reactivity (for an overview, see Heinrichs and Domes, 2008 Heinrichs et al, 2009).

Occurrence and Toxicology

Fumonisins have been shown to have diverse biological and toxicological effects. The mechanism of fumonisin toxicity is not well understood. Studies have shown that fumonisins inhibit ceramide synthase. Fumonisins have been shown to be hepatotoxic and carcinogenic in rats resulting in liver cirrhosis and hepatic nodules, adenofibrosis, hepato-cellular carcinoma, ductular carcinoma, and cholangio-carcinoma (Gelderblom et al. 1988 1991 1992b 1993 1994 Marasas 1996). Studies on rats by Riley et al. (1996) suggested that fumonisin B1 (FB1) might act primarily as a tumor promoter. The tumor promoting activity of fumonisins has also been proposed by Huang et al. (1995), Wattenberg et al. (1996) to have been resulted from the stimulation or

Sexual preferences can be explained by incentive motivation theory without any reference to the concept of homosexuality

A change of food habits may be beneficial both to personal and public health. A change of drinking habits might also be beneficial for personal and public health. The high incidence of cirrhosis in France, for example, could be reduced by convincing the French to drink less wine and more grapefruit juice. On the contrary, a change of the sex of our partner would not have the slightest consequence neither for individual nor for public health. Someone could argue that HIV infection is more common among people having sex with their own sex and therefore the abandonment of that habit would improve public health. This might be true in some cases, but again the improvement would be marginal compared to that potentially caused by improved eating habits. My point here is that there is no particular reason for changing sexual incentives even if that were possible. This statement applies both at the individual and at the societal level. Thus, the question that needs to be asked is not whether...

Potential Side Effects

In order to predict any potential toxicity to patients, proper preclinical toxicology testing is critical. However, the currently available preclinical models do not fully reflect clinical settings. In addition, because the latent period of the insertional muta-genesis in patients was more than 2 yr, long-term safety evaluation, which is not always practical for preclinical testing, needs to be improved. Furthermore, a large proportion of cancer patients have other comorbid diseases that might affect the biodistribution and toxicity of these gene therapy agents. Patients with liver function impairment (e.g., liver cirrhosis and or chronic hepatitis) might have an impaired hepatic clearance of viral vectors in contrast, pulmonary uptake might be increased in these patients, as shown in animal models (45). It is also unknown whether patients with chronic viral infection (hepatitis B virus HBV , Epstein-Barr virus EBV , etc) will have acute exacerbation resulting from activation by viral...

HDV Genetic Variability and Clinical Patterns

The wide radiation of HDV we describe might contribute to the spectrum of pathologies associated with HDV. For example, specific liver lesions, including morula cells, have been observed in severe hepatitis in African and Amazonian patients (Casey et al. 1993 Parana et al. 1995). It is therefore considered that the association of HDV-3-HBV F leads to severe acute hepatitis. By contrast HDV-2 and HDV-4 have been typically associated with less severe hepatitis disease than Type I-associated infections (Wu et al. 1995). However, a recent study among the Miyako island strains suggests that the HDV-4 Okinawa subgroup (labelled Ilb-M in the original paper) induces a greater progression to chronic hepatitis and to cirrhosis (Watanabe et al. 2003). Type-I viruses have a wide spectrum of pathologies, ranging from severe fulminant hepatitis in Sweden (Hansson et al. 1982 Zhang and Hansson 1996), Russia (Flodgren et al. 2000) and Taiwan (Wu et al. 1995) to very mild disease in the town of...

Functional and Clinical Significance of Hepatitis D Virus Genotype II Infection

Abstract Hepatitis D virus (HDV) infection is one of the important etiologies of fulminant hepatitis and may aggravate the clinical course of chronic HBV infection to cirrhosis and liver failure. HDV was classified into three genotypes. Recent molecular phylogenetic analysis of HDV suggests atleast seven major clades. The genotype I HDV is widely spread, genotype II is found in East Asia and genotype III HDV is prevalent in South America. The genomic size is 1682-1685 nucleotides (nt) for genotype II, and 1676 nt for genotype IV (IIb). The divergence in HDV nucleic acid sequences between genotype II and other genotypes varies from 13.8 to 35.3 . The divergences in the HDAg-coding region may range from 17.8 to 29.8 between genotype II and other genotypes. There is no genotypic or size restriction on the interactions of either the small or the large hepatitis delta antigens (HDAgs) between genotypes I and II, and there is also no genotypic incompatibility during co-package of HDAgs of...

Hepatic encephalopathy

Brain oedema frequently accompanies liver failure and represents cytotoxic, cellular oedema in its pure form. As a consequence of intoxication, astrocytes are primarily affected, and they are the only cells which show prominent morphological changes in postmortem analysis. Astroglial swelling is proportional to the blood

Comparison Between Genotypes I and II HDV

It hasbeenreportedthatgenotypeIIHDV infectionisrelativelylessfrequently associated with fulminant hepatitis at the acute stage and less unfavorable outcomes (cirrhosis or HCC) at the chronic stage as compared to genotype I of the same area 18 . This study was composed of symptomatic inpatients and asymptomatic outpatients for regular check up. In a longer follow-up for more than 15 years, about 45 of patients with chronic genotype I HDV infection survived, while more than 75 of patients with chronic genotype II HDV infection remained alive 63 . The difference is statistically significant. The long-term prognosis of patients with chronic genotype II HDV infection seems better than that reported previously in western countries where only genotype I HDV is currently found 10,11,17 . All the patients in the study by Ivaniushina et al. had a history of chronic liver disease, and all except two presented with grave liver disease or cirrhosis 26 . It is not surprising that there was no...

Influence of Replication and Genotypes of HBV

Smedile et al. reported that HBV replication modulates pathogenesis of HDV in chronic hepatitis D 16 . Wu et al. also reported that persistent replication of HBV or HDV are associated with elevated serum transaminase levels 14 . Based on an intergroup divergence of 8 or more in the complete nucleotide sequence, HBV can be classified into eight genotypes A-H 47 . Genotypes time of HBeAg seroconversion, HBV DNA levels, treatment response to interferon and long-term outcomes 47-62 . Because chronic hepatitis D patients still have underlying chronic hepatitis B, replication status, genotypes and mutations of HBV may also influence clinical course and outcomes of chronic HDV infection. In a recent study in our laboratory, persistent replication of HBV or HDV was associated with higher adverse outcomes (cirrhosis, HCC or mortality) compared to those who cleared both viruses from sera 63 . HBV genotype C is also a significant factor associated with adverse outcomes (cirrhosis, HCC or...

Other Medical and Viral Conditions Exacerbate Brain Dysfunction

Synergistic effects that may influence the effects of HIV on the brain. Hepatitis C virus (HCV) is a common coinfection occurring with HIV that affects many infected patients, particularly those with history of intravenous drug use (IDU). HCV infection is characterized by chronic inflammation of the liver and development of hepatic cancer in many cases (245, 246). HCV has been associated with cognitive impairments and cognitive decline in its own right, with impairments extending beyond effects that can be attributed to comorbid medical and psychiatric conditions, adverse effects of treatment effects, or hepatic cirrhosis by itself (247). Cortical electrophysiological changes have also been reported in this population, with HCV patients exhibiting delayed P300 latencies, which correlated with the severity of cognitive impairment (248, 249). Importantly, these cognitive changes were unrelated to treatment of HCV with interferon, a medication known to result in fatigue and cognitive...

Natural History of the Clinical Course of HDV Infection

HDV superinfection of chronically HBV-infected patients results in most cases in chronic infection. The course of HDV superinfection maybe divided into the following phases (1) an acute phase with active HDV replication and suppression of HBV with high ALT levels (2) a chronic phase characterized by decreasing HDV replication and increasing HBV replication with moderate or fluctuating ALT levels followed by development of cirrhosis and hepatocellular carcinoma or (3) elimination of HDV, or HBV and HDV (Wu et al. 1995).

Avoiding the Menace of Toxins in the Real World Outside the Laboratory

Our enthusiasm for using the toxins in biomedical research was tempered by news of a most tragic case of microcystin poisoning in 1996. More than 100 dialysis patients in Caruara, Brazil, were infused with microcystic water and most died of liver failure 26 . The scale of tumor promotion and liver damage worldwide is more difficult to assess. However, microcystin levels above the WHO limit (1 g liter) and suspected human and animal poisonings are often reported 8 .

Alexander W Tarr Ania M Owsianka Alexandra Szwejk Jonathan K Ball and Arvind H Patel

Hepatitis C virus (HCV) infection is a major cause of severe chronic liver disease including cirrhosis and hepatocellular carcinoma. HCV has been classified into six major genotypes that exhibit extensive genetic variability, particularly in the envelope glycoproteins E1 and E2. Knowledge of genotypic and quasispecies variation on viral glycoprotein properties is important in understanding the structure-function relationship of the proteins. Through their perceived role as components of the virion and mediators of virus attachment and entry, HCV glycoproteins are primary targets for the development of antiviral agents. In this chapter, we describe methods optimized to extract E1E2-encoding sequences of all the major genotypes from HCV-infected patient sera, and their amplification, cloning, expression, and biochemical characterization. Furthermore, we describe a method to generate retroviral nucleocapsid pseudotyped with HCV E1E2 of diverse genotypes (HCVpp) whereby infectivity of the...

Table 205 O Red Cell Morphologies Matched to Clinical Conditions

Megaloblastic anemias (vitamin B12 deficiency and folic acid deficiency) Pernicious anemia Folic acid deficiency Abetalipoproteinemia Neonatal hepatitis Postsplenectomy Heparin administration Cirrhosis of liver with associated hemolytic anemia Liver disease including cirrhosis Liver disease including cirrhosis Postsplenectomy Myeloproliferative syndromes Severe anemias

Modulation of retinoic acid receptor function by chromosomal translocation

In acute PML (APL), the retinoic acid receptor RARa forms a chimeric protein with PML protein as a result of t(15 17), and with PLZF gene product, as a result of t(ll 17) translocation (Z Chen et al., 1996). The PML gene was identified at the t(15 17) translocation point in APL. However, its expression is not restricted to leukaemia but it is also found in adenocarcinoma and squamous cell carcinoma of the lung. In NSCLC, the PML protein has not been detected but its mRNA has been shown to be present (Zhang et al., 2000). The protein is expressed in HCC, liver cirrhosis and liver abscesses (Chan et al., 1998).

Step 6 Safety Considerations

Safety of gene therapy clinical trials clearly is one of the key aspects. Two specific concerns unique to gene therapy include the use or development of replication competent viruses and the potential of inadvertent modifications of the patient's germline (36). To date the safety profile in clinical gene therapy trials for cancer is excellent. In cancer gene therapy trials, hundreds of patients have been treated worldwide with a variety of vectors and gene therapy strategies without a death resulting from the vector. Most toxicity has been grade I or II related to inflammatory responses to the vector and has been much lower than toxicity associated conventional chemotherapeutics. Viral dissemination to people exposed to the patient has been limited and transient and there has been little evidence for germ line changes or development of replication competent viruses in patients. Because of this encouraging safety profile, most gene therapy trials have been able to move to outpatient...

Lifethreatening Disorders

The 10 leading causes ofdeath in the United States in 1995 were, in order, diseases of heart, malignant neoplasms, cerebrovascular diseases, chronic obstructive pulmonary diseases, accidents and adverse effects, pneumonia and influenza, diabetes mellitus, HIV infection, suicide, and chronic liver disease and cirrhosis (Rosenberg, Ventura, Maurer, Heuser, & Freedman, 1996). With the exception of HIV infection, and chronic liver disease and cirrhosis, the death rates for all of these disorders increase steadily with age.1

Forensic and Chemical Warfare Toxicology

NMR is not widely used in forensic toxicology, probably due to the perceived poor sensitivity and the lack of routine access to high-field (> 500 MHz) NMR instrumentation. Some interesting historical examples using low-field magnets demonstrate the versatility of NMR for identifying biomarkers of poisoning. Cartigny and colleagues 36 reported on a 4-month-old girl who presented with agitation, fever, dehydration, and metabolic acidosis. Metabolites including o-hydroxyhippuric acid, 2,5-dihy-droxyhippuric acid, and 2-hydroxybenzoic acid (salicylic acid) were observed in XH NMR spectra of freeze-dried urine, which indicated that she had been poisoned with aspirin. The pattern of unusual metabolites can provide a biomarker of aspirin poisoning. This result was remarkable in that an 80-MHz system was employed. NMR has also been used to monitor progressive liver failure following paracetamol-related overdose (10 g) 37 . In addition, the second-ever known instance of acute intentional...

Risk factors diseases and comorbidities

Other possible risk factors are endocrine disorders, various neurological problems (i.e. disc prolapse) or infectious diseases. Frequent causes of ED in young men are chronic kidney or liver dysfunction (hepatitis, cirrhosis). Psychosocial problems, relationship conflicts and psychiatric illnesses (e.g., depression) are frequently related to sexual dysfunction. As a consequence, HIV patients have an increased risk for erectile dysfunction.

Approach and Materials for PVE

Necessary to surgically excise all of the malignant disease however, the lateral segment of the left lobe (arrows) comprises less than 20 of the total hepatic volume, and the risk of postoperative liver failure would be excessive. B, CT scan from the same patient 4 weeks after PVE. There has been significant compensatory hypertrophy of the left lateral segment, which on volumetric CT analysis now makes up between 25 and 30 of the total hepatic volume. The metallic coils used to embolize portal vein branches to the right lobe of the liver (black arrow) and the medial segment of the left lobe of the liver (white arrow) are clearly evident. Reprinted with permission from Curley SA, Cusack JC Jr, Tanabe KK, Stoelzing O, Ellis LM. Advances in the treatment of liver tumors. Curr Probl Surg 2002 39 449-571.

Selective Clamping of Segmental Branches Figs 520 to 523

Intersegmental Plane The Live

In patients with severe liver cirrhosis, alternate selective clamping of the segmental branches must be done during the dissection, to reduce liver damage and prevent congestion of the portal system. During the dissection between the middle and left segments, the left segmental branch of the Glissonean pedicle must be temporarily clamped, instead of using the Pringle maneuver. Likewise, at the time of dissection on the intersegmental plane between the middle and right segments, the right segmental branch must be clamped. In right segment or left segment resection, this selective clamping of the neighboring branch may be beneficial (Fig. 5.24).

Hepatitis B

Age-related processes play a very important role in the population dynamics of hepatitis B virus (HBV) (Medley et al., 2001). This infection has similarly been estimated to result in 1 million deaths each year, but mainly in adulthood as a result of liver cancer and cirrhosis as with measles, however, there is a safe and effective vaccine. In contrast to measles, infection with HBV can result in persistent infection over a period of decades, and additionally the probability of persistent infection is much greater if infection occurs in early childhood. The modes of transmission of HBV are similar to those of HIV (though HBV is very much more infectious), such as through sexual contacts, health interventions, intravenous drug use (IVU) or at birth from mother to child (Edmunds et al., 1996 Williams et al., 1996). These processes all have a strongly age-related or age-determined component. Also, in general, the endpoint of many persistent HBV infections, such as liver cancer or...

Hepatotoxicity

Elevated liver function tests are common with HAART, and severe hepatotoxicity occurs in up to 6 of patients (Becker 2004), but liver failure is rare (Nunez 2005). Occurrence of hepatotoxicity depends on the drug classes or agents used as well as on pre-existing liver dysfunction. Nevirapine, ritonavir and tipranavir have been associated with severe hepatotoxic-ity. Several fatalities due to liver failure habe been linked to nevirapine (Bjornson 2006, De Maat 2003, Law 2003). Case reports also exist about liver failure due to indinavir, atazanavir, efavirenz, nelfinavir and different nucleoside analogs (Carr 2001, Clark 2002). Risk factors for the occurrence of severe hepatotoxicity are baseline elevation in serum aminotransferases, chronic hepatitis B or C coinfection as well as concomitant hepatotoxic medication, protease inhibitor therapy, throm-bocytopenia and renal insufficiency (Servoss 2006, Sulkowski 2002). Patients with pre-existing liver disease should receive the above...

Nevirapine

Liver toxicity occurs more commonly on nevirapine than on other antiretroviral drugs. Clinically asymptomatic and symptomatic liver toxicity, including rapidly occurring fatal liver failure have been observed (Bjornsson 2006). Serious and fatal liver toxicity has been reported even during post-exposure prophylaxis, but not after single doses of nevirapine (Jackson 2003).

Prognosis

Prognosis in acute liver failure is related to the cause of the failure and the severity of the failure. Patients with acute liver failure due to paracetamol toxicity demonstrate an overall 50 survival rate. Liver failure caused by hepatitis A or B have survival rates in the 30-50 range. Finally, in FHF secondary to non-A, non-B, non-C hepatitis or Wilson's disease the survival rate may be less than 10 . Progressive encephalopathy is associated with a worse prognosis. Metabolic acidosis, renal failure, severe jaundice, or marked coagulopathy also suggest a worse prognosis.

DNA viruses

Cholangiocarcinoma, although commonest in Asia (where it is associated with parasitic infections), does not present on the same scale as hepatocellular cancer which in China alone causes 100 000 deaths each year. More prevalent in males, 80 of cases develop in livers affected by multinodular cirrhosis. Carriers of HbSAg have higher rates of both multinodular cirrhosis and hepatocellular carcinoma than non-carriers. Viral antigens have been identified in the liver cells of affected patients and the viral genome in cancer cells, suggesting that viral DNA may play a central role in the transforming process.

Final Remarks

Vn monoclonal antibodies will likely succeed in the prevention of HCV reinfection after liver transplantation. However, it should be noted that a small trial was recently performed where liver transplant recipients with HCV-associated liver failure received multiple infusions of high-dose immunoglobulin of 200 mg kg per dose over 14 weeks, but no viral load decrease was detected (Davis et al. 2005). However, this study should be considered with caution. In addition to the concern that the dosage used was based on the protective amount previously observed in chimpanzees (Krawczynski et al. 1996), there are a number of other issues. First, specific HCV antibodies are only a small fraction of the total Ig and of these only a smaller fraction will be directed to the important targets involved in entry, i.e., the E1E2 envelope glycoproteins. Second, not all antibodies to E1 or E2 mediate Vn (Keck et al. 2004a). Both Vn and non-Vn HMAbs to HCV E2 have been described. The existence of non-Vn...

Z49859

The pathogenesis of WD is thought to result from a systemic overload of copper, which accumulates primarily in the three major targets of WD the brain, eye, and liver. The etiological significance of copper is supported by the efficacy of treatments, which are principally aimed at chelation of free copper. Clearly, although multiple lines of experimental evidence have demonstrated that copper is toxic to hepatocytes and causes oxidative damage, it is less clearly established that copper is directly harmful to the neurons of the brain under normal circumstances. Could the case for copper toxicity in neurological WD be an oversimplification Several pieces of evidence suggest that the brain disorder seen in WD is caused by more than simple copper overload. It is known, for example, that in human subjects with Wilson's disease and liver diseases, brain copper is elevated but there is sometimes no evidence of the characteristic neurological disorder. In cases of copper toxicity (Indian...

Inflammation

Inflammatory response mounted by the host. In up to 50 of patients who appear 'septic' no source of infection can be found. This systemic inflammatory response can also result from several other insults such as acute pancreatitis, major trauma, burns, ischaemia reperfusion (e.g. repair of abdominal aortic aneurysm) and haemorrhagic shock (e.g. massive gastrointestinal bleed). It is best to use the term systemic inflammatory response syndrome (SIRS) to describe the systemic inflammatory response common to a variety of clinical insults and to reserve the term sepsis for the systemic response to proven infection. The underlying mechanisms of SIRS are the same as those responsible for creating local inflammation (i.e. endothelial cells, circulating blood cells and inflammatory mediators). There is generalized vasodilatation, capillary leak with extravasation of fluid into extracellular spaces, and inflammatory cells can be found sequestered in virtually all organs. It is unclear whether...

Wilsons Disease

Wilson's disease (WD) is a genetic copper-toxicosis disorder affecting both the liver and central nervous system. In this disease, mutations of ATP7B result in reduction of biliary excretion of copper and low incorporation of copper into ceruloplasmin in the liver (Fig. 4B) (4), but for unknown reasons, not all patients have low ceruloplasmin levels. Because the uptake of copper from the small intestine is normal in WD, the reduced copper excretion results in a net positive copper balance in the body and copper gradually accumulates to high concentrations in the liver (4). The excess copper eventually causes severe liver damage, liver failure, and death. Copper also deposits in the brain, and neurological abnormalities are a major clinical feature of some patients. Disease symptoms appear at various ages, but rarely before the age of 5 yr however, there are reported cases as young as 3 yr, which can be misdiagnosed because of the young age of the patient (71). The neurological form of...

Hepatic tumours

Hepatocellular carcinoma (HCC) is the commonest malignant tumour seen in humans. Incidence varies widely from 5 per 100 000 in UK and USA, to 70-80 per 100 000 in parts of Asia and Africa. The main risk factor is chronic liver disease, and HCC often arises from cirrhosis due to chronic hepatitis B and C infection, as well as alcoholic liver disease and haemochromatosis. The majority of HCC are asymptomatic, until such time as they become large and or multi-focal when they may cause a patient with cirrhosis to deteriorate with ascites, jaundice, and malaise. A palpable mass and pain from bleeding are other symptoms. While asymptomatic, HCC may be detected during ultrasonography for other reasons, or as part of a screening program. Measurement of a-fetoprotein will confirm the diagnosis if grossly elevated, but levels may be normal with small tumours, and mildly elevated in chronic liver disease. CT and MRI scanning provide further useful information over ultrasound, including detection...

Portal hypertension

If the pressure in the portal venous system is greater than 12 mmHg then portal hypertension exists. The commonest cause of this in Western countries is alcoholic cirrhosis causing obstruction to portal venous flow, but numerous other causes are recognised and are classified (as for jaundice) into pre-hepatic, hepatic, and post-hepatic (Table 12.12). The portal venous system has been described (see Anatomy), and in portal hypertension the sites of portal-systemic communication open up, commonly resulting in oesophageal and gastric varices that can bleed profusely. The other major complication of portal hypertension is ascites. The management of variceal bleeding has been described (see Upper GI Bleeding), and includes injection sclerotherapy, endoscopic banding, TIPSS, and oesophageal transection. Rarely, splenic vein thrombosis results in left-sided portal hypertension, leading to splenomegaly and gastric varices. Splenectomy with division of the short gastric vessels is an effective...

Conclusions

Neurological diseases discussed in the last section Are there other copper-related diseases yet to be recognized, because of mutations in the various copper chaperones or other components of the copper homeostatic system Despite these and many other questions, in contrast to even 10 yr ago, it is possible to believe that within another 10 yr the answers to these questions will be found and the molecular basis of copper transport will be substantially worked out. One can confidently expect that the discovery of gene(s) involved in the childhood copper-associated cirrhosis conditions, the Bedlington terrier, and the reason for the copper sensitivity of the sheep will be discovered and new genes will be added to the growing cast of players involved in copper homeostasis. The links between the molecules regulating cellular copper homeostasis and the physiological and pathophysiological effects of copper should be clarified. We hope that these discoveries will be accompanied by...

Indications for PVE

In patients with normal hepatic parenchyma, preservation of a perfused section of liver comprising 25 of the total hepatic volume is usually sufficient to prevent major postoperative complications and hepatic insufficiency. This 25 value has been determined somewhat empirically, and there is a paucity of data regarding the exact volume of liver that can be resected safely without postoperative liver failure when the remaining liver parenchyma is completely normal. In a recent series of 20 patients with normal liver parenchyma who underwent an extended right hepatic lobectomy, a future liver remnant of 25 or less of the total liver volume was associated with increased severity of postoperative liver insufficiency, longer hospital stay, and complications. We reviewed our experience with extended liver resection in 55 patients with normal hepatic parenchyma. On the basis of preoperative calculation of a future liver remnant that was 25 or less of the total liver volume, 18 of these...

Native Americans

In the eyes of the federal government, Native American have a different status than other minorities. They are viewed as a conquered people, poor unfortunates who must be protected, rather than independent citizens. They suffer from a variety of health problems, among which are high blood pressure, obesity, diabetes, lactose intolerance, alcoholism, cirrhosis of the liver, and tuberculosis. Although Native Americans have a lower than average risk for the three major killers of Americans heart disease, cancer, and stroke the high rate of other diseases and accidents during young and middle adulthood results in the shortest life span of all minority groups. Compared with a 70 rate for other Americans, only 42 of Native Americans reach age 65 (Singh et al., 1996).

Looking Ahead

The fact that Tyrolean NICC has almost disappeared since untinned copper vessels have been replaced by modern household vessels raises the question of why it is still important to search for the NICC gene. First, our knowledge on copper homeostasis in humans is still limited. The identification of the NICC gene and insight into the function of its product, the protein, may broaden our understanding of the cellular processes that occur after copper has been taken up by the body. Second, childhood cirrhosis as a result of copper toxicosis is not limited to the Tyrolean population. The identification of the gene could make it possible to identify people who are either a carrier of the disease or at risk of developing copper toxicosis because they have a mutation in both alleles of the gene. The identification of high-risk people is currently only possible in families who have been exposed to high environmental copper and who have already had a child suffering from NICC.

Patients

Between January 1999 and February 2005, 391 samples, collected from HDV infected patients that were positive in a routine search of HDV RNA detection in serum, were analysed. In the first part of the study (Radjef et al. 2004), we selected 25 patients whose preliminary examination suggested that the HDV viral strains varied from previously described HDV genotypes. Indeed, we selected the 25 samples for which (1) HDV cDNA could not be amplified using previously described primers 6A and 6S (Deny 1994) even though HDV serology was positive or (2)) the RO-DNA amplicon restriction pattern was atypical (Gordien et al., unpublished results, see Fig. 2). Interestingly, 22 samples were obtained from patients from Africa or who had travelled to Africa. The male to female ratio was 0.8 and the mean age was 35 years (range, 15-53 years). Most patients had chronic active hepatitis or cirrhosis and only one patient, aged 33 years, had acute HDV superinfection.

HHV6 and hepatitis

In addition to chronic hepatitis, HHV-6 also appears to cause some cases of fulminant hepatitis, a much more severe disease entity. We reported fatal fulminant hepatitis resulting from primary HHV-6 infection in a previously healthy 3-month-old boy in 1990. Despite full supportive care and exchange transfusion, the patient died 7 days after admission to our hospital. We confirmed primary HHV-6 infection by viral isolation and serological analysis (Asano et al., 1990). We also recently reported a non-fatal case of HHV-6-associated fulminant hepatitis treated with living donor liver transplantation (Ohashi et al., 2004). Individuals with fulminant hepatitis ultimately die from liver failure, and living donor liver transplantation could improve the prognosis of HHV-6-associated fulminant hepatitis. Three additional cases of HHV-6-associated fulminant hepatitis from other institutions have been reported. Aita et al. (2001) observed a clinical course similar to those we have reported, and...

T Levels And Aging

Serum SHBG levels are affected by several conditions. SHBG levels are inversely correlated with increased total body fat, subcutaneous and visceral adiposity (Couillard et al., 2000). Levels also vary inversely with hyperinsulinism in nondiabetic subjects. They seem to be an indicator of general adiposity rather than an index of altered insulin glucose homeostasis in morbidly obese subjects. Hyperinsulinism decreases SHBG synthesis by cultured hepatic cells. These observations have been interpreted to show that obesity causes insulin resistance and hyperinsulinism, and hyperinsulinism decreases SHBG levels. Hypothyroidism and the nephrotic syndrome also reduce SHBG levels. Estrogen, hyperthy-roidism, some anticonvulsants, a high phytoestrogen diet, hepatic cirrhosis, and aging increase SHBG levels (Anderson, 1974 Kley et al., 1975).

Discussion

Here, we report that in the LEC rat, the noncytosolic copper was mainly detected in lysosomes. Also in Wilson's disease, the localization of hepatic copper varies with the stage of the disease In the early stage, copper is diffuse in the cytoplasm of hepatocytes, whereas later, when fibrosis and cirrhosis are the predominant histopathological features, the metal is mainly located in hepatocyte lyso-somes (22).

Hepatitis B Virus

HBV is a partially double-stranded DNA virus that is transmitted by direct contact with infected bodily fluids (Hollinger and Liang 2001). In normal individuals, hepatitis B will generally induce a self-limited hepatitis, but it has the capacity to establish a chronic active state that can eventually lead to cirrhosis or hepatocellular carcinoma. In the United States, hepatitis B immune globulin (HBIG) is prepared from a small number of donors hyperimmunized with the HBsAg vaccine (Terrault and Vyas 2003). The main three categories of use for HBIG are (1) post-exposure prophylaxis for nonimmune contacts, (2) inhibition of vertical transmission of the virus at birth, and (3) prevention of relapse in HBV-positive patients following orthotopic liver transplantation. Following a suspected infected needle-stick or fluid exposure, HBIG is recommended to be administered in combination with the HBsAg vaccine (CDC 1984). Maternal-fetal transmission can be inhibited by administration of HBIG...

Mortality

Patterns of metastasis outlined above, with respiratory failure and liver failure being commonly seen.1112 Brain metastases may also be a cause of death. Bone metastases, although not fatal in and of themselves, may be signs of advanced and resistant disease, often with multiple organ involvement. Hemorrhagic complications from hemoptysis, intrapulmonary bleeding, gastrointestinal bleeding, rupture of the inferior vena cava, intrahepatic bleeding, and cerebral hemorrhage have all been reported.1112 Sepsis, when it occurs, is often the result of pneumonia or obstructive uropa-thy.11 Iatrogenic causes, such as pulmonary fibrosis from bleomycin toxicity, posttreatment liver failure or postirradiation pericarditis, postoperative pulmonary embolism, and sepsis, also contribute to the mortality rate of patients with germ cell tumors and accounted for 6 of deaths in one postmortem study.12 It is important to note, however, that iatrogenic numbers of this magnitude were reported in only one...

Nutrition

Infants and young children have relatively higher metabolic rate and energy requirements than adults. In addition to maintenance needs, the child requires nutrition for growth. Enteral feeding is the preferred method of providing fluid, calories (carbohydrate, protein and fat), minerals and vitamins but may not be possible in critically ill or postoperative patients having paralytic ileus. Refinements in parenteral nutrition have undoubtedly been a major factor in the improved outcome of major surgery for infants and children. As a rule, parenteral nutrition should be considered in neonates when there is a delay of > 4 days before adequate enteral feeding can be established. Long-term parenteral nutrition in infants carries the same risks as in adults (metabolic complications, sepsis, venous access problems, etc.) but infants appear to be particularly prone to develop cholestasis which can lead to liver failure.

Quinolones

The ecological consequences of ciprofloxacin have been evaluated in patients in connection with colorectal surgery (92), in patients with acute leukaemia in remission (96), in prevention of bacterial infections in cirrhosis (101,102) and in treatment of travelers' diarrhea (103). A number of studies have also been performed on healthy volunteers (93-95,97-100,104,105). Ciprofloxacin is excreted in feces in extremely high concentrations and has an activity mainly against Gram-negative aerobic rods. Marked suppression or elimination of enterobacteria has also been shown to occur, both in patients and in the healthy subjects examined. The extension of disturbances has varied depending on the doses. Minor alterations of numbers of Gram-positive aerobic cocci, mainly enterococci, have further been observed and in some studies minor alterations were detected also in the anaerobic microbiota. Ciprofloxacin-resistant species of Pseudomonas and Acinetobacter have been detected during treatment...

Perspective

The studies summarized in this chapter demonstrate that the WHV wood-chuck model of experimental chronic hepatitis infection can be applied to the analysis of aspects of the natural history of HDV infection, the development of HDV vaccine strategies, and therapeutic studies of chronic HDV superinfection. The relatively rapid progression to hepatocellular carcinoma in WHV-infected woodchucks does pose challenges for the use of this model for evaluating drug efficacy against chronic HDV disease. Further, HDV infection appears to increase the risk of hepatocellular carcinoma in patients with compensated cirrhosis type B (Fattovich et al. 2000) and the influence of chronic HDV on progression of end-stage liver disease in the woodchuck model has not been established. Indeed, many of the woodchucks in the clevudine study progressed to hepatocellular carcinoma, which precluded post-treatment follow-up studies. Perhaps these limitations can be overcome by the use of younger WHV-carrier...

Cisca Wijmenga

Inherited liver cirrhosis is rarely observed in infancy or childhood in Western countries, but, recently, 138 cases of an endemic form of infantile cirrhosis were reported from several families in the Tyrol, Austria. These infants had received high amounts of dietary copper released from copper vessels used to prepare their formula milk. Extensive studies in this Tyrolean population suggested that the so-called non-Indian childhood cirrhosis (NICC) occurred only in children with a genetic defect (in homozygous form). These Tyrolean NICC families could be traced back for 10 generations and it was shown that the majority of the families were related to each other. A founder effect was therefore suggested as the most likely reason for the increased frequency of NICC in the Tyrol (i.e., the patients are all descendants of one common ancestor, who introduced the disease mutation into the population many generations ago). Thus, all of the patients in this population should carry the same...