How I Healed my Liver Disease

Liver Disease Survivors Guide

Renowned Health Specialist experienced in working with numerous people with liver disorders share with you and: Explains how the liver works and how liver disorders develop in Simple English without Medical Jargon. Shares the facts about cirrhosis of the liver. Explains complications and treatments in simple language. Talks about Nutrition in Liver Disease. Explains Alternative Treatments available. Talks about the latest research developments in liver disease treatment. Shares resources for Liver disease forums and help-lines. Gives you the true in-depth stories from survivors and how they coped with the challenges of liver disorder. Shares touching stories of family members who had to cope with their loved ones suffering from cirrhosis of the liver, and the strategies they used to cope with them. With Liver Disease Survivors Guide, you will discover : Credible information on Liver disease obtained from detailed interviews with specialist doctors, explained in simple language. Healthy steps in dealing with liver disorders. What to do and what not to do while learning to adapt to the liver disorder. Remarkable stories in patients own words. It gives you a real emotional experience of a person with serious liver disorder and how they view the world. Latest research on liver disorders. Best resources and direct links to forums. Direct links to get professional help and identify the best experts in your area. Alternative treatments and therapies available for liver disorders. No medical jargon or difficult language, the book is written in simple and easy to understand language. Read more here...

Liver Disease Survivors Guide Overview

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My Liver Disease Survivors Guide Review

Highly Recommended

This is one of the best ebooks I have read on this field. The writing style was simple and engaging. Content included was worth reading spending my precious time.

As a whole, this e-book contains everything you need to know about this subject. I would recommend it as a guide for beginners as well as experts and everyone in between.

Liver Cirrhosis

It is now generally accepted that in alcoholic patients with advanced liver cirrhosis, hepatic SAMe concentration is greatly decreased (Lieber 2002). While transient SAMe depletion is necessary for the liver to regenerate, chronic hepatic SAMe depletion may lead to malignant transformation (Lu & Mato 2005). Studies with primates have found that the decreased hepatic SAMe concentrations and the associated liver lesions, including mitochondrial injury, can be corrected with SAMe supplementation (Lieber et al 1990).

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

Dysfunctional Platelets

Appropriate treatment of severe bleeding believed due to abnormal platelet function is platelet transfusion. Desmopressin may augment platelet function in a number of disorders. However, desmopressin has been associated with thrombosis in older patients and should be used cautiously. Raising the hematocrit to more than 30 by transfusion or by use of erythropoietin will also improve hemostasis in uremia and perhaps in other disorders. Cryoprecipitate will shorten the bleeding time in uremia and liver failure.

Evaluation Of The Vasculature

EVALUATION OF LYMPHATIC VESSELS Under normal circumstances, only the thoracic duct and its main tributaries can be evaluated. Distended small lymphatic vessels can be identified in conditions such as lymphatic carcinomatosis, congestive heart failure, and cirrhosis of the liver.

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).

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

Liver And Hepatoduodenal Ligament

Posterior view of portions of liver, pancreas, and spleen. Note presence of micronodular cirrhosis. The splenic vein has been opened and the confluence with the portal vein the superior mesenteric vein is shown, together with the partially opened inferior vena cava. Fig. 5-4. Posterior view of portions of liver, pancreas, and spleen. Note presence of micronodular cirrhosis. The splenic vein has been opened and the confluence with the portal vein the superior mesenteric vein is shown, together with the partially opened inferior vena cava. SLICING It is almost impossible to slice livers with normal-sized knives without leaving knife marks on the cut surface. Smooth cut sections of cirrhotic livers are even more difficult to prepare. We use a knife with a 78-cm blade (its use for lungs is illustrated Chapter 4, Fig. 4-5), which in most instances permits slicing of the whole organ with an uninterrupted pulling motion.

Pathological Conditions

Patients with liver disease may present with signs of liver failure or complications of it, e.g., oesophageal varices, or because of biochemically detected abnormal LFTs. The latter can indicate whether the pattern of damage is hepatic (parenchymal), extra-hepatic (obstructive) or mixed in nature. Hepatic assault is typified by viral hepatitis, alcohol or drug damage and extra-hepatic disease by duct obstruction due to stones or tumour, e.g., head of pancreas. Mixed biochemical profiles are not infrequently seen in these various disorders. Needle core biopsy is interpreted in close correlation with full clinical information that includes a detailed history and wide range of investigations (see above). Its aims are to distinguish between a surgical and medical cause for the damage, and in non-neoplastic conditions to assess the degree of necroinflammatory activity that is present and the repairative response of the liver to it. It also establishes a baseline against which subsequent...

Neoplastic Conditions

Adenomatous hyperplastic or macroregenerative nodules irregular nodules in background cirrhosis, 2-3 cm diameter with cytoarchitectural atypia and potentially premalignant. Hepatocellular carcinoma often in background cirrhosis and serum AFP is elevated in 25-40 of cases. Single, diffuse or multifocal, bile stained and prone to venous invasion with metastases to lung, adrenal gland and bone. The commonest patterns are trabecular, plate-like or sinusoidal comprising variably differentiated hepatoid cells. Note that carcinoma rarely metastases to a cirrhotic liver, i.e., the tumour is more likely to be primary. Prognosis in hepatocellular carcinoma this relates to size (> 5 cm), differentiation, encapsulation, multifocality, high serum AFP levels, vascular invasion and the presence of background cirrhosis (adverse). The majority die within several months of presentation and five-year survival is at most 5-10 . Chemotherapy is used palliatively. Small tumours, encapsulated,...

Atazanavir and Indinavir

Besides serological tests for viral hepatitis, an abdominal ultrasound should be performed to recognize structural liver dysfunction early, e.g. non-alcoholic steato-hepatitis or liver cirrhosis, before initiating HAART. Liver function should be monitored biweekly at the start of treatment with nevirapine and PIs and even more frequently in patients with pre-existing liver disease. Monthly tests are generally sufficient for all other drugs. If liver enzymes (ALT, AST) are moderately elevated (< 3.5 times ULN) in the absence of clinical symptoms, treatment can be continued under close monitoring. If liver enzymes are elevated to more than 3.5 times ULN, additional diagnostic tests should be performed, including an abdominal ultrasound. In cases of co-infection with hepatitis B or C, treatment of these conditions should be considered. With other pre-existing liver conditions, it may be useful to determine drug plasma levels. Discontinuation of treatment may not be necessary (exception...

Clinical Presentation

Umbilical disease can present with a lump, discharge or inflammation (omphalitis) and infection leading to pain and abscess formation. Caput medussa results from dilatation of periumbilical veins secondary to increased portal venous pressure usually due to liver cirrhosis.

Intermediate Filaments

These defects have also been induced experimentally by mutations in intermediate filament genes in laboratory animals. Changes in neurofilaments within brain tissue are characteristic of Alzheimer's disease, which produces neurofibrillary tangles containing neurofilaments and other microtubule-associated proteins. A prominent feature of alcoholic liver cirrhosis is the presence of eosinophilic intracytoplasmic inclusions composed predominantly of keratin intermediate filaments. These inclusions, called Mallory bodies, are visible in light microscopy within the he-patocyte cytoplasm (Fig. 2.47).

Death Ligands Receptors

CD95L is probably too toxic for a systemic application in human patients because the systemic activation of CD95 results in liver failure within a few hours 67 . The local application of adenoviral vectors expressing CD95L may be a strategy to circumvent systemic side effects in gliomas 68 . Transferring the gene encoding an adaptor protein of the CD95-dependent killing cascade, Fas-associated protein with death domain (FADD), into glioma

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 transaminases. Such steatohepatitis may progress to liver failure and lactic acidosis, a potentially fatal, but fortunately rare complication. Although steatohepatitis and lactic acidosis were already described in the early 90s in patients receiving didanosine monotherapy (Lambert 1990), mitochondrial liver toxicity is now observed under treatment with all NRTIs that have a relatively strong potential to inhibit gamma-polymerase, especially with the so called D-drugs didanosine (VidexTM), stavudine (ZeritTM) and zalzitabine (HIVIDTM). TMHowever, liver complications were also described with zidovudine (RetrovirTM). It has been demonstrated in the hepatic tissue of HIV-patients, that each of the D-drugs leads to a time dependent mtDNA-depletion. On electron microscopy, morphologically abnormal mitochondria were...

Antiretroviral agents in pregnancy

So far, severe mitochondriopathies have been observed at least twice in pregnant women taking a combination therapy of the nucleoside analogues d4T+ddI plus nelfinavir or nevirapine (Sarner 2002). For this reason, the combination d4T+ddI is advised against in pregnancy (Bristol-Myers 2001). Hepatic toxicity with hyperbilirubinemia was described under AZT+3TC+efavirenz therapy. Following the administration of AZT+3TC+nelfinavir, one pregnant woman died of sudden acute liver failure (Hill 2001). Tenofovir did not show any maternal toxicity in animal experiments, but did cause a fetal growth retardation of 13 as well as a slight decrease in the bone mineral density (Tarantal 2002).

Dexamethasone Decadron

Adverse effects delayed wound healing, seizures, osteoporosis, hyperglycemia, diarrhea, nausea, GI bleeding, cushingoid effects. Comments use with caution in patients with hypothyroidism, cirrhosis, hypertension, CHF, ulcerative colitis, thromboembolic disorders may cause adrenocortical insufficiency (Addison's crisis) with abrupt withdrawal.

Viiiclinical Considerations

Hepatitis C virus leads to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. It may be the leading cause of chronic hepatitis in the Western world. B. Primary biliary cirrhosis is caused by a granulomatous destruction of medium-sized intrahepatic bile ducts, with cirrhosis appearing late in the course of the disease. It is characterized by mitochondrial pyruvate dehydrogenase autoantibodies, the role of which is not clear.

Selected Photomicrographs

Light micrograph of normal liver and alcoholic liver cirrhosis (Figure 16-4). Figure 16-4. (A) Light micrograph of normal liver. The classic liver lobules (outlined) with central vein (circle) are clearly delineated. (B-D) Light micrographs of alcoholic cirrhosis. (B) Broad bands of fibrous septae (fib) are present in alcoholic cirrhosis that bridge regions of the liver from central vein to portal triad and from portal triad to portal triad. This fibrotic activity entraps sections of hepatic parenchyma that undergo regeneration to form nodules (nod). (C) Neutrophil, lymphocyte, and macrophage infiltration (asterisk) is prominent at the periphery of the liver lobule. (D) Some hepatocytes accumulate tangled masses of cytokeratin intermediate filaments within the cytoplasm known as Mallory bodies (arrow). (B-D Reprinted with permission from East Carolina University, School of Medicine, Department of Pathology slide collection.)

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.

Contraindications And Precautions

Herbs with choleretic and cholagogue activity should be used with caution by people with bile duct obstruction (Blumenthal et al 2000), acute or severe hepatocellular disease (e.g. cirrhosis), septic cholecystitis, intestinal spasm or ileus, liver cancer or with unconjugated hyperbilirubinaemia (Mills & Bone 2005).

Selective Clamping of Segmental Branches Figs 520 to 523

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).

Biomedical Importance

While ammonia, derived mainly from the a-amino nitrogen of amino acids, is highly toxic, tissues convert ammonia to the amide nitrogen of nontoxic glutamine. Subsequent deamination of glutamine in the liver releases ammonia, which is then converted to nontoxic urea. If liver function is compromised, as in cirrhosis or hepatitis, elevated blood ammonia levels generate clinical signs and symptoms. Rare metabolic disorders involve each of the five urea cycle enzymes.

Occupies A Central Position In Nitrogen Metabolism

The ammonia produced by enteric bacteria and absorbed into portal venous blood and the ammonia produced by tissues are rapidly removed from circulation by the liver and converted to urea. Only traces (10-20 g dL) thus normally are present in peripheral blood. This is essential, since ammonia is toxic to the central nervous system. Should portal blood bypass the liver, systemic blood ammonia levels may rise to toxic levels. This occurs in severely impaired hepatic function or the development of collateral links between the portal and systemic veins in cirrhosis. Symptoms of ammonia intoxication include tremor, slurred speech, blurred vision, coma, and ultimately death. Ammonia may be toxic to the brain in part because it reacts with a-keto-glutarate to form glutamate. The resulting depleted levels of a-ketoglutarate then impair function of the tri-carboxylic acid (TCA) cycle in neurons.

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).

Physical Examination

Abdomen Scars, bowel sounds, right upper quadrant tenderness liver span, hepatomegaly liver margin texture (blunt, irregular, firm), splenomegaly (hepatitis) or hepatic atrophy (cirrhosis), ascites. Umbilical venous collaterals (Caput medusae). Courvoisier's sign (palpable nontender gallbladder with jaundice pancreatic or biliary malignancy). Labs CBC with differential, LFTs, amylase, lipase, hepatitis serologies (hepatitis B surface antibody, hepatitis B surface antigen, hepatitis A IgM, hepatitis C antibody), antimitochondrial antibody (primary biliary cirrhosis), ANA, ceruloplasmin, urine copper (Wilson's disease), alpha-1-antitrypsin deficiency, drug screen, serum iron, TIBC, ferritin (hemochromatosis), liver biopsy.

Does He have an Endocrinological Cause to His ED

Androgen and prolactin levels are of particular concern. Hyperprolactinaemia occurs secondary to stress, drugs (such as neuroleptics and infertility treatments), cirrhosis, breast manipulation, or pituitary adenoma tumour. A high level of circulating prolactin causes inhibition of gonadotrophin releasing hormone which lowers levels of testosterone. Men with low testosterone levels may exhibit a decrease in sexual interest. Causes of low testosterone include renal failure, hypogonadism, bilateral cryptorchidism, other hypothalamic-pituitary-gonadal axis

Physical complications

Liver damage includes acute hepatitis, fatty infiltration, and cirrhosis. In men, cirrhosis seldom develops until heavy drinking has continued for at least 5 years, but women are more vulnerable. Cirrhosis has a high mortality rate even in those who become totally abstinent.

Differential Diagnosis of Jaundice

Intrahepatic Causes of Jaundice Viral hepatitis, medication-related hepatitis, acute fatty liver of pregnancy, alcoholic hepatitis, cirrhosis, primary biliary cirrhosis, autoimmune hepatitis, Wilson's disease, right heart failure, total parenteral nutrition Dubin Johnson syndrome, Rotor's syndrome (direct hyperbilirubinemia) Gilbert's syndrome, Crigler-Niger syndrome (indirect) sclerosing cholangitis, sarcoidosis, amyloidosis, tumor.

Demographic Socioeconomic and Health Characteristics

In terms of mortality, Indians and Natives under 54 have a death rate 1.4 to 1.8 times higher than the overall U.S. rate. Although the leading causes of death for the population as a whole are heart disease and cancer, young Indians and Natives are significantly more likely than their U.S. counterparts to die from nondisease-related conditions (e.g., homicide, cirrhosis). (See Table I for a list-

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...

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.

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.

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...

Applications Of Human Hepatocytes In Toxicology

A large number of naturally occurring and man-made chemicals are hepatotoxins. In many cases, the toxicity is a function of the metabolic conversion (bioactiva-tion) of the parent compound into highly reactive metabolites. AAP, carbon tetrachloride, dimethylnitrosamine, and halothane are examples of xenobiotics that are ''bioactivated'' by CYP mixed-function monooxygenases in the liver. Species differences in xenobiotic metabolism are therefore important factors contributing to the known species differences in chemical toxicity. Most of the xenobiotic metabolic enzymes of the liver reside in the parenchymal cells or hepatocytes. The hepatocytes therefore are usually the first cell types that are damaged upon hepatotoxic insult. Primary hepatocytes therefore represent a useful experimental system to evaluate acute hepatic injury. The nonparenchymal cells are important in the progression of pathological events. For instance, inflammation of the liver is primarily a function of the...

Clinical course and pathogenesis

Hemophilia Cohort Study (MHCS), in which 10 of adult hemophiliacs with HCV coinfections developed hepatic failure after a latent period of 10-20 years, even before the onset of AIDS-defining opportunistic infections or neoplasms. Rapid progression of liver disease was found particularly in patients with CD4 T-cell counts below 100 l. In the group of HIV-negative but HCV-positive patients, there was not a single case of liver failure during the same period of observation. In this group, the latent period until liver failure or hepatocellular carcinoma develop is estimated to be 30-40 years. Several studies, some of which included histological analyses, have confirmed the accelerated course of hepatitis C with concurrent HIV infection. The improved treatment options for HIV infection have increased the likelihood of patients actually living to experience the development of liver failure. The associated decrease in mortality with HIV infection has resulted in a relative increase in...

Course of hepatitis B with concurrent HIV infection

In addition to increasing mortality, HIV coinfection accelerates the progression of hepatitis B and increases the risk of cirrhosis. Histological analysis of a series of 132 homosexual men with chronic hepatitis B, of which 65 were HIV-coinfected, showed a higher prevalence of liver cirrhosis in HBV HIV-coinfected patients. No difference was observed in the extent of inflammatory activity. Interestingly, several patients developed severe fibrosis and cirrhosis, in the presence of only minimal inflammatory activity. This phenomenon has also been described in other immunocompromised patient populations (e.g. organ transplant recipients). HIVpositive patients possibly experience more frequent reactivation episodes of chronic hepatitis B than HIV-negative patients.

Factors Unique To Older Minorities

More importantly, the profiles of disease and disability vary substantially across ethnic and cultural groups. Whereas the most prevalent chronic conditions among older non-Hispanic whites are cardiovascular disease, stroke, and cancer, African American elderly evidence elevated rates of hypertension and renal disease, and Hispanic elderly evidence increased rates of diabetes, cirrhosis, and gallbladder disease (Fried & Wallce, 1992 Markides, Rudkin, Angel, & Espino, 1997). Differences in disability rates are also apparent. In comparison to older non-Hispanic whites, for example, older African Americans and Hispanics appear to experience greater rates of disability, whereas the rates among older Asian Americans appear to be lower (Guralnik & Simonsick, 1993). Differences in other factors such as health behaviors associated with mental disorders are also evident. Older African American males, for example, have higher rates of smoking, and older Hispanics have elevated rates of...

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 IIb-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

Preoperative Imaging For Curative Resection Of Hepatocellular Carcinomamm

Recent progress in imaging techniques has facilitated the recognition of early HCC as a principal tumor in at-risk subjects who undergo regular medical check-ups for chronic viral hepatitis or cirrhosis (18). Both dynamic CT and dynamic MRI are highly sensitive methods that are useful for detecting hypervascular HCC (19,20). The recent development of multi-detector-row CT may further increase the sensitivity of this modality.

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...

Preoperative Portal Vein Embolization For Hepatocellular Carcinoma

PVE was first developed by Makuuchi et al. in 1990 (29) for the treatment of hilar cholangiocar-cinoma. PVE induces homolateral atrophy of the portion of the liver scheduled for resection and contralateral compensatory hypertrophy in the remnant liver, thereby decreasing the risk of postoperative liver failure. In 1986, Kinoshita began applying this technique in HCC patients scheduled to undergo hepatic resection (30). The indications for PVE in patients with HCC are controversial for several reasons (1) the livers of most HCC patients are compromised by an underlying liver disease, and the capacity for liver regeneration after hepatic resection is thought to be impaired under such conditions, making it difficult to predict whether sufficient hypertrophy of the future remnant liver segments can be achieved after PVE (2) most HCCs are hypervascular tumors fed mainly by arterial blood flow, and the cessation of the portal flow induces a compensatory increase in arterial flow in the...

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 andcorepromotermutations ofHBVhavebeenreportedtobeassociatedwith 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...

Secondary Deficiency

This may develop in conditions associated with diarrhoea, cirrhosis or malabsorption, as well as after extensive postoperative use of parenteral nutrition lacking adequate niacin. Pellagra may occur during prolonged isoniazid therapy (the drug replaces niacinamide in NAD), in malignant carcinoid tumour (tryptophan is diverted to form 5-hydroxytryptamine), and in Hartnup disease, an autosomal recessive disorder in which there is defective conversion of tryptophan to niacin (Beers & Berkow 2003). It has also been observed in Crohn's disease, most likely due to malnutrition and intestinal malabsorption (Abu-Qurshin et al 1997).

Pierre Chan Ching Lung Lai and Man Fung Yuen

Hepatocellular carcinoma (HCC) can be treated by surgical and nonsurgical means. However, only around 20 to 30 of patients with HCC are resectable on presentation because of advanced disease or impaired liver reserve secondary to underlying cirrhosis (1). Patients usually present late because HCC smaller than 8 cm is usually asymptomatic. The tumors are also often multifocal. Recurrence after complete resection is common, either due to micrometastases undetected during operation or to the development of new foci of tumors. Therefore, most HCC are managed by nonsurgical means.

Transarterial Chemoembolization

TACE is indicated for inoperable hepatocellular carcinoma and can also be used as neoadjuvant therapy prior to other forms of treatment, including surgical resection, radiofre-quency ablation, and liver transplantation. Contraindications include extrahepatic metastases, vascular complications (portal vein thrombosis, hepatic artery thrombosis, and severe arteriovenous shunting) and poor hepatic function (Child's C liver cirrhosis, Okuda stage III, serum bilirubin level > 50 mol L, severe ascites, history of hepatic encephalopathy, and recent variceal bleeding). Complications include fever, nausea and vomiting, abdominal pain, gastrointestinal bleeding due to ischemia to the gastrointestinal tract, liver or spleen abscess, acalculous cholecystitis, and, most importantly, liver failure. Postembolization syndrome, including fever and elevated transaminases, is described in a prospective study (21), with 41 of patients having a fever > 38.5 C and 93 of patients developing elevated...

Systemic Chemotherapy

Systemic chemotherapy is not used routinely for advanced HCC. There are factors related to the tumors. HCC is relatively chemoresistant, partly due to the presence of drug-resistant genes, including p-glycoprotein, glutathione-S-transferase, heat shock proteins and mutations in p53. There are also factors related to the patients. Patients often do not tolerate chemotherapy well because of the underlying liver dysfunction and liver cirrhosis.

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 .

Primary Deficiency

This may result from malabsorption syndromes, cancer, liver cirrhosis and alcoholism, hyperthyroidism, congestive heart failure or medicine use, such as OCP, isoniazid, hydralazine, penicillamine, theophylline or MAO inhibitors (Beers & Berkow 2003, Bratman & Kroll 2000, Wardlaw et al 1997).

Nonneoplastic Conditions

Varicose veins abnormally dilated, tortuous veins due to prolonged intraluminal pressure or loss of support of the vessel wall. They affect a wide range of patients but particularly obese females over 50 years of age. There is also a familial tendency. Varicosities also occur in the oesophagus secondary to portal hypertension in association with liver cirrhosis. Haemorrhoids are varicose dilatations of the haemorrhoidal plexus of veins at the anorectal junction.

Therapy of Thrombosis in Myeloproliferative Syndromes

Intravenous heparin followed by warfarin is indicated for most patients with acute venous thromboembolism complicating the myeloproliferative disorders. Catheter-based thrombolytic therapy should be considered in patients who have acute occlusion of the hepatic or portal veins. Long-term oral anticoagulants (INR 2-3) are usually recommended for prevention of recurrent thromboses. In a few instances, liver transplantation has been successful in treating liver failure due to Budd-Chiari syndrome. Hepatic veno-occlusive disease (VOD) is a relatively common complication of bone marrow transplantation and is seen in 1-50 of patients, but the frequency seems to vary widely from center to center. The clinical syndrome includes weight gain, hepatic tenderness and jaundice soon after transplantation which can progress to liver failure and the hepatorenal syndrome. In one large study of 355 patients, hepatic VOD developed in 54 with a mortality rate of 39 in severe cases. Early thrombosis of...

Pregnancy Related Thrombotic Microangiopathies

The first sign is a drop in the platelet count followed by elevated liver function tests such as the AST. Schistocytes are abundant on the peripheral smear. HELLP can progress to liver failure and deaths are reported due to hepatic rupture. Unlike TTP, fetal involvement is present in HELLP syndrome with fetal thromb-ocytopenia reported in 30 of cases. In severe cases, elevated D-dimers consistent with DIC are also found. Delivery of the child will often result in cessation of the TTP, but refractory cases will require plasma exchange. A variant of HELLP syndrome is seen in patients with antiphospholipid antibody disease who may present at 20-24 weeks with HELLP. These patients may have heparin-refractory thrombosis and require delivery to stop the HELLP.

Hepatic And Renal Osteodystrophy

Both chronic liver disease and those conditions exhibiting end-stage renal disease result in compromised hydroxylation of vitamin D to produce its active metabolite. It has been reported that 50 of patients with chronic liver disease, especially those with primary or secondary biliary cirrhosis, present with associated osteodystrophy. This frequently leads to a vitamin D deficiency and manifests most commonly as metabolic bone disorders, hypocalcaemia and secondary hyperparathyroidism (Wills & Savory 1984). The resultant hypovitaminosis D can result in bone loss, cardiovascular disease, immune suppression and increased mortality in patients with end-stage kidney failure (Andress 2006). Consequently, correction of this deficiency has been one of many first line treatments in these situations.

Unopette White Blood Cellplatelet Count

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

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...

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...

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.

Critical Thinking Questions

Cirrhosis of the liver, emphysema, and heart disease are all conditions that can be caused by a faulty gene or by a dangerous lifestyle habit (drinking alcohol, smoking, following a poor diet). When gene therapies become available for these conditions, should people with gene-caused disease be given priority in receiving the treatments If not, what other criteria should be used for deciding who should receive a limited medical resource

HIV and HBV coinfection Introduction

In general, patients with chronic hepatitis B should be screened for hepatocellular carcinoma (HCC) every 6 to 12 months. Serum alpha fetoprotein and an ultrasound of the liver should be performed. This recommendation is independent of apparent cirrhosis, as 10 to 30 of patients who develop HCC do not have pre-existing cirrhosis.

Transplantation and Tissue Rejection

Immune Suppressing Drugs For Transplants

Less drastic than an organ transplant is a cell implant, which consists of small pieces of tissue. Implants of liver cells may treat cirrhosis pancreas cells may treat diabetes skeletal muscle cells may replace heart muscle damaged in a heart attack or treat muscular dystrophy adrenal gland cells may treat Parkinson disease and brain cell implants may treat Alzheimer and Huntington diseases.

Liver Resection Vs Transplantation For Hepatocellular Carcinoma

Liver transplantation is the optimal treatment for HCC because it provides the widest possible resection margins for the cancer, removes the underlying cirrhotic liver tissue that is at risk for the development of de novo HCC, and restores normal hepatic function (41). With the refinement of the selection criteria mentioned in the previous section, several studies have shown

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.

The face as a mirror of disease

A fascinating aspect of the art of clinical medicine is the clinical interpretation of the patient's facies. Not only are specific skin lesions common on the face but the face may also mirror endocrine disorders and organ failure such as respiratory, cardiac, renal and liver failure. Jaundice may be masked by the natural colour of the cheeks but the yellow conjunctivae will be distinctive. A marked plethoric complexion may be seen in chronic alcoholics (alcohol may produce a pseudo-Cushing's syndrome), in Cushing's disease or in polycythaemia. Thickening of the subcutaneous tissues may be seen in chronic alcoholism, acromegaly and myxoedema, and the puffiness of the eyelids in the latter condition may simulate the true subcutaneous oedema of renal disease.

Isolation And Culturing Of Human Hepatocytes

The liver is estimated to be approximately 2.6 of the human body weight, consisting of both parenchymal and nonparenchymal cells. The parenchymal cells, commonly known as hepatocytes, comprise the majority of cells of the liver (ap-prox. 60 by cell number and 80 by weight). These cells are the major sites of xenobiotic metabolism and often are the cells injured by chemical toxicants. The nonparenchymal cells include the endothelial cells, which line the sinusoidal space kupffer cells, which are the stationary macrophages believed to be responsible for the scavenging of endotoxins, and lipocytes or Ito cells, which normally serve as vitamin A storing cells but upon liver injury differentiate into collagen-producing and rapidly proliferating fibroblasts, leading to fibrosis and, upon chronic injury, cirrhosis. Endothelial cells and kupffer cells are also cytokine-producing cells believed to play major roles in both the regeneration of the liver and the progression of liver diseases.

Gross Description

The general signs and symptoms include paroxysmal episodes of dyspnea on exertion, and syncope particularly associated with exercise. The infants and children have central cyanosis. They characteristically often squat, following minimal exercise. This posture is spontaneous and it is thought to result from an attempt to maximize central blood flow to the lungs by decreasing blood flow to the legs and increasing venous return to the heart. With age and more severe cyanosis, the red blood cell mass increases, leading to secondary polycythemia. Hematocrits of 65 to 70 vol. or higher are possible, although there are consequences to this compensatory mechanism (discussed below). Also secondary to the oxygen de-saturation (and possibly the intra-pulmonary collateral circulation) is the development of clubbing. Clubbing is a growth of connective tissue and thickening of periosteal bone at the junction between the nail and soft tissue of the fingers and toes. It is not unique to TOF, but...

The Catabolism of AcetylCoA

The Catabolism Release Co2

The citric acid cycle is the final common pathway for the aerobic oxidation of carbohydrate, lipid, and protein because glucose, fatty acids, and most amino acids are metabolized to acetyl-CoA or intermediates of the cycle. It also has a central role in gluconeogenesis, lipogenesis, and interconversion of amino acids. Many of these processes occur in most tissues, but the liver is the only tissue in which all occur to a significant extent. The repercussions are therefore profound when, for example, large numbers of hepatic cells are damaged as in acute hepatitis or replaced by connective tissue (as in cirrhosis). Very few, if any, genetic abnormalities of citric acid cycle enzymes have been reported such abnormalities would be incompatible with life or normal development.

Antiinflammatory

Chondroitin exerts an anti-inflammatory action with an inhibitory effect over complement (Pipitone 1991). In an in vitro study of bovine cartilage, chondroitin alone and in combination with glucosamine was found to regulate gene expression and synthesis of NO and PGE2, suggesting a basis for its anti-inflammatory properties (Chan et al 2005). Chondroitin sulfate has been found to increase the levels of antioxidant enzymes and reduce inflammation and cirrhosis of liver tissue in an ovariectomised rat model, suggesting that it enhances antioxidant activity (Ha 2004).

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...

Pancreas

Preparation for angiography and cholangiography. (A) Straight and bifurcated nozzles for hilar vessels and bile ducts rubber hose for attaching specimens to perfusion apparatus, cotton wads for plugging hepatic veins, and ligature with needle to secure nozzles. Two identification tags are also shown. (B) Cirrhotic liver with nozzle tied into portal vein. Adapted with permission from ref. (10). Fig. 5-6. Preparation for angiography and cholangiography. (A) Straight and bifurcated nozzles for hilar vessels and bile ducts rubber hose for attaching specimens to perfusion apparatus, cotton wads for plugging hepatic veins, and ligature with needle to secure nozzles. Two identification tags are also shown. (B) Cirrhotic liver with nozzle tied into portal vein. Adapted with permission from ref. (10).

Transplantation

The first successful human liver transplant was carried out in 1967 and today over 80 of recipients survive one year. Not only can adult livers be transplanted to adult recipients, but the shortage of donor organs has led to adult donor organs being transplanted to children. This is facilitated by resecting and transplanting only part of the donor liver, e.g., left liver (segments I-IV). General indications for transplantation are acute liver failure, end-stage chronic liver disease and neoplasms. Conditions encountered in the explant specimen can therefore be diverse including viral, autoimmune and alcoholic hepatitis primary biliary and sclerosing cholangitis end-stage cirrhosis and primary hepatocellular or cholangiocarcinoma.

Hepatoprotection

Dong quai is said to improve abnormal protein metabolism in people with chronic hepatitis or hepatic cirrhosis. Evidence comes from an in vivo study in which 5 dong quai was added to the daily diet of rats, resulting in enhanced metabolism, increased hepatic oxygen utilisation, and increased glutamic acid and cysteine oxidation (Micromedex 2003). Dong quai has been found to have antioxidant activity (Wu et al 2004), as well as antiproliferative and pro-apoptotic activities in hepatic stellate cells in vitro, suggesting a potential antifibrotic action (Chor et al 2005). Dong quai 361

Hepatotoxicity

Elevated liver function tests are common with HAART, and severe hepatotoxicity occurs in up to 6 of patients (Becker 2004). Their occurrence depends on the drug classes or agents used as well as on pre-existing liver dysfunction. The level of liver toxicity ranges from mild and fully reversible liver enzyme elevation to rare but rapidly occurring, occasionally fatal, liver failure. Severe hepatotoxicity and hepatic failure have been observed during treatment with nevirapine and ritonavir (De Maat 2003, Law 2003). Case reports also exist about liver failure occurring with indinavir, atazanavir, efavirenz, nelfinavir and different nucleoside analogs (Abrescia 2002, Carr 2001, Clark 2002). Patients with pre-existing liver disease should receive these drugs only under strict monitoring (Sulkowski 2002, 2004). Hepatotoxic reactions occur at different time points for different drug classes nu-cleoside analogs lead to hepatic steatosis, which is probably caused by mitochon-drial toxicity and...

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. Serious and fatal liver toxicity has been reported during post-exposure prophylaxis (MMWR 2001), but not after single doses of nevirapine. Females and patients with higher CD4 cell counts are at increased risk of liver toxicity with nevirapine. The risk of symptomatic hepatotox-icity for females is more than three-fold that of males, and in females with CD4 cell counts > 250 cells l, the risk is 12-fold in comparison to females with CD4+ cell counts < 250 (11 vs. 0.9 ). Males with CD4+ cell counts > 400 cells l have a

HELLP Syndrome

Weinsten introduced the acronym HELLP syndrome to describe a variant of pre-eclampsia. The acronym HELLP syndrome (Hemolysis, Elevated Liver tests, Low Platelets) describes a variant of pre-eclampsia. Classically, HELLP syndrome occurs after 28 weeks of gestation in a patent suffering from pre-eclampsia. The pre-eclampsia need not be severe. The first sign is a drop in the platelet count followed by abnormal liver function tests. Signs of hemolysis are present with abundant schistocytes on the smear and a high LDH. HELLP can progress to liver failure and deaths are also reported due to hepatic rupture. Unlike TTP, fetal involvement is present in the HELLP syndrome with fetal thrombocytopenia reported in 30 of cases. In severe cases, elevated D-dimers consistent with DIC are also found. Delivery of the child will most often result in cessation of the HELLP syndrome, but refractory cases will require dexamethasone and plasma exchange. Patients should be closely observed for 1-2 days...

Amiodarone Cordarone

Adverse effects may cause severe sinus bradycardia, ventricular arrhythmias, AV block, liver and thyroid function test abnormalities, hepatitis, cirrhosis pulmonary fibrosis may follow long-term use increases serum levels of digoxin, oral anticoagulants, diltiazem, quinidine, procainamide, and phenytoin. Comments avoid during pregnancy and while breast feeding use with caution in renal failure.

Waterjet

The loss of blood during transaction of the hepatic parenchyma can be easily reduced with ajet pressure of 15 to 16kg cm2. This preserves the fine vessels, more than 0.2 mm in diameter, without injury. When the same pressure is applied in the cutting of a cirrhotic liver, it takes a longer time compared with that of a non-cirrhotic normal liver parenchyma. A disadvantage is the formation of air bubbles, which obscure the operative field. In addition, after the vessels are isolated, conventional ligation or clipping is still required and is time consuming.

For 3 days Dose ped

Acute spinal cord injury 30 mg kg IV over 15 minutes, followed in 45 minutes by a continuous infusion of 5.4 mg kg hr for 23 hrs. Clearance hepatic metabolism renal elimination. Contraindications serious infections except septic shock or tuberculous meningitis. Adverse effects may cause hypertension, pseudotumor cerebri, acne, Cushing's syndrome, adrenal axis suppression, GI bleeding, hyperglycemia, and osteoporosis. Comments use caution in hyperthyroidism, cirrhosis, nonspecific ulcerative colitis, hypertension, osteoporosis, thromboembolic tendencies, CHF, convulsive disorders, myasthenia gravis, thrombophlebitis, peptic ulcer, diabetes.

Budd Chiari Syndrome

Patients with Budd-Chiari syndrome or hepatic vein thrombosis present with the onset of a painful swollen liver and ascites and may progress to liver failure. Several hypercoagulable states are associated with Budd-Chiari syndrome (Table 16.1). These are myeloproliferative syndromes, antiphospholipid antibodies, paroxysmal nocturnal hemoglobinuria, and Befhet's disease. Budd-Chiari may be the presenting sign of a myeloproliferative syndrome and can occur with normal blood counts. This presentation is discussed further in Chapter 27.

Clinical Features

Yellow fever is named for the jaundice it causes secondary to liver dysfunction failure. The disease has a spectrum of presentation from a viral-like illness to fulminant liver failure and hemorrhage leading to death. Up to 50 of infected individuals may be asymptomatic. Mild cases present with fevers, headaches, con-junctival injection, facial flushing, and a relative bradycardia. Initial infection may resolve or become biphasic with the more ominous complications bleeding, liver failure, shock, renal failure, myocardial dysfunction, coma, seizures, and death. With severe cases mortality approaches 50 .

Diagnostic workup

The tumor marker CA 125 may assist in evaluation. Sustained elevation of CA 125 levels occurs in more than 80 of patients with nonmucinous epithelial ovarian carcinomas but in only 1 of the general population. Levels of CA 125 in serum also may be elevated in patients with conditions such as endometriosis, leiomyomata, pelvic inflammatory disease, hepatitis, congestive heart failure, cirrhosis, and malignancies other than ovarian carcinomas. In postmenopausal patients with pelvic masses, CA 125 levels in serum greater than 65 U mL are predictive of a malignancy in 75 of cases.

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...

Figure 176

Liver injury may be triggered by hemodynamic changes in the circulatory system. In congestive heart failure, the heart is unable to provide sufficient oxygenated blood to meet the metabolic requirements of many tissues and organs, including the liver, which is readily affected by hypoperfusion and hypoxia (low blood oxygen content). Zone 3 of the liver acinus is the first to be affected by this condition. The hepatocytes in this zone are the last to receive blood as it passes along the sinusoids as a result, these cells receive a blood supply already depleted in oxygen. Examination of a liver biopsy specimen from an individual with congestive heart failure shows a distinct pattern of liver necrosis. Hepatocytes in zone 3, which is located around the central vein, undergo ischemic necrosis. Typically, no noticeable changes are seen in zones 1 and 2, representing the periphery of a classic lobule. Necrosis of this type is referred to as centrilobular necrosis. Figure 17.7 shows the...

Conclusions

We discussed the progress made in our understanding of the mechanisms of interferon action and interferon resistance from basic research on HCV. Chronic hepatitis C virus infection is the major cause of liver cirrhosis and liver cancer in the United States and in many developed nations. The most effective way of preventing HCV-associated liver cancer is to eradicate chronic hepatitis C virus infection from the human population by developing effective antiviral strategies. Interferon therapy is a highly effective first line of treatment available against hepatitis C virus infection. The most challenging task is to cure those chronically infected patients

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).

Natural History

The vast majority of patients with unresectable bile duct cancer die within six months to a year of diagnosis, usually from liver failure or infectious complications secondary to biliary obstruction (2,4,12,13). The prognosis has been considered worse for lesions affecting the confluence of the bile ducts and better for lesions of the distal bile duct close to the papilla, which probably reflects the greater complexity and difficulty in effectively managing proximal lesions more so than differences in biologic behavior. Indeed, it has been shown that location within the biliary tree (proximal vs. distal) has no impact on survival provided that complete resection is achieved (5). On the other hand, anatomic site-related differences in biological

Autopsy Diagnoses

Autopsy diagnoses can be reported and listed 1) in a standard sequence (for example, cardiovascular system, respiratory system, digestive system, and so forth) to facilitate anatomic orientation, statistical analysis, and coding 2) in order of causal relationships and relative importance (for example, chronic alcoholism, alcoholic cirrhosis, ruptured esophageal varices, and gastrointestinal hemorrhage) or 3) in a problem-oriented fashion. The first method is preferred by statisticians and those charged with coding, whereas the latter two methods appeal most to the clinician because more interpretative information is provided. Problem-oriented autopsy diagnoses and protocols (see below) are essential wherever problem-oriented medical records are used (1,2).

Treatment Options

Medically unfit or otherwise unable to tolerate a major operation Hepatic cirrhosis Local tumor-related factors Tumor extension to secondary biliary radicles bilaterally Encasement or occlusion of the main portal vein proximal to its bifurcation Atrophy of one hepatic lobe with contralateral portal vein branch encasement or occlusion Atrophy of one hepatic lobe with contralateral tumor extension to secondary biliary radicles Unilateral tumor extension to secondary biliary radicles with contralateral portal vein branch encasement or occlusion Metastatic disease Histologically proven metastases to N2 lymph nodes Lung, liver, or peritoneal metastases

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.

Application

At the other end of the hepatitis spectrum is fulminant hepatitis, which is rare and can be caused by any of several viruses. Symptoms start suddenly and severely, and behavior and personality may change. Without medical attention, the condition progresses to kidney and liver failure, or coma.

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, l974 Kley et al., l975).

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...

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...

Ascites

Diuretics and sodium restriction are often used to control ascites in patients with cirrhosis however, this regimen is not very effective for patients with malignant ascites. A comparison of plasma volume with ascites volume was undertaken in nine patients with peritoneal carcinomatosis, four with chylous malignant ascites, and three with portal hypertension and massive hepatic metastases. All patients were placed on diuretics and a sodium restricted diet. Both plasma and ascites volumes were calculated using an isotope dilution technique. The 13 patients with carcinomatosis or chylous ascites demonstrated approximately 0.4 to 0.5 kg day weight loss with no significant change in the volume of ascites. The patients with portal hypertension and massive liver metastatses fared slightly better, with approximately 0.2 L day improvement in ascites (55). Although diuretics and salt restriction will assist in total body water excretion, they typically result in dehydration without...

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