New approach could reverse liver failure

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.

Liver Disease Survivors Guide Summary

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Hepatitis A Virus

Approximately 5 of patients develop cholestatic hepatitis with pruritis and steatorrhea. Fulminant hepatitis, characterized by precipitous loss of liver function rapidly leading to liver failure and death, occurs in approximately 0.01 of cases. Chronic disease and chronic excretion of virus does not occur. However, up to 10 of patients will relapse, that is, will suffer a recurrence within 1-4 months after acute disease, and these recurrences may persist for several months. The severity of hepatitis A disease is directly dependent on a number of factors age, underlying liver disease, immunosuppression, and pregnancy (13). Thus, jaundice occurs in less than 10 of children under 6 years of age, 40-50 of older children, and 70-80 of adults. The overall mortality in the United States is less than 0.1 , but mortality is somewhat higher in children less than 5 years of age (0.15 ) and even higher in older persons over 50 years of age (2.7 ). Similarly, increased...

Andy S Yu MDa Ramsey C Cheung MDbc Emmet B Keeffe MDc

More than 350 million people worldwide are infected with the hepatitis B virus (HBV), and more than 1 million of them die each year of liver failure or hepatocellular carcinoma (HCC) 1 . The HBV prevalence varies widely from 0.1 to 20 in different geographic regions in the world, depending on the predominant age of infection and major mode of transmission 2 . There are currently 1.25 million HBV carriers in the United States, contributing to 17,000 hospitalizations and 5000 deaths annually 3 . As HBV is transmitted by body fluids, infection can be minimized by proper infection control practices, risk-reduction counseling, virus deactivation of plasma-derived products, and screening donors of blood, solid organs, and semen 4 . However the most effective way to prevent transmission of HBV is by immunization 5 .

Adverse Reactions

Acute acetaminophen poisoning or toxicity can occur after a single 10- to 15-g dose of acetaminophen. Dosages of 20 to 25 g may be fatal. With excessive dosages the liver cells necrose or die. Death can occur due to liver failure. The risk of liver failure increases in patients who are chronic alcoholics.

Contraindications Precautions And Interactions

Naltrexone is contraindicated in those with a hyper-sensitivity to the narcotic antagonists. Naltrexone is contraindicated during pregnancy (Category C). Naltrexone is used cautiously in those with a narcotic addiction in patients with cardiovascular disease, acute hepatitis, liver failure, or depression and in patients who are suicidal. Naltrexone is used cautiously during lactation.

Clinical Applications

Despite the multitude of papers that have investigated the properties of IFN-y, the clinical use of IFN-y is still somewhat limited. In the USA, IFN-y has been approved for only two specific uses treatment of chronic granulomatous disorder (CGD), as these patients are more susceptible to fungal and bacterial infections, and severe osteoporosis. Current clinical trials are limited, with a major effort being made in the use of IFN-y for the treatment of idiopathic pulmonary fibrosis. In this condition, IFN-y administration resulted in a survival benefit in certain subgroups. Other trials involving IFN-y include analysis of the effects on lung immune function in Mycobacterium tuberculosis-infected patients tolerance and toxicity of IFN-y alone or in combination with tumor necrosis factor in AIDS-related complex patients the effects of IFN-y in hepatitis C patients that do not respond to IFN-a the use of adenovirus vectors expressing IFN-y in cancer patients and evaluation of antifibrotic...

Basic Overview of Course of Illness and Treatment of HCV

Approximately 4 million persons in the United States and probably more than 100 million persons worldwide are infected with HCV. The virus has the unique ability to cause persistent infection in a majority of infected people. The immunological correlates of protection and viral clearance and the pathogenesis of liver injury are yet to be defined, but recent studies suggest the importance of cell-mediated immune responses. Although a large proportion of infected persons become chronic carriers, most have relatively mild disease with slow progression. However, chronic and progressive HCV carries significant morbidity and mortality and is a major cause of cirrhosis, end-stage liver disease, and liver cancer. Development of an effective HCV vaccine is not imminent, but recent advances in technology and basic knowledge of molecular virology and immunology may engender novel approaches to the fundamental problems encountered in vaccine development. Vaccines continue to be pursued, since...

Accessing the Range of Hivhcvrelated Services That Psychiatric Patients Need

Screening for hepatitis viruses at mental health and substance abuse agencies appears to be spotty, as is screening for most medical problems. Mental health agencies that have established medical services on-site (e.g., inpatient units or shelters with co-located primary care clinics) may screen automatically for HCV and sometimes hepatitis B virus in routine laboratory examinations. In the vast majority of mental health agencies lacking on-site medical services, providers know about HCV infection only if patients self-report having been diagnosed or if they are in such advanced stages as to manifest signs of liver failure (e.g., spider angiomata, jaundice, ascites).

Rational Psychopharmacology for People With Hiv Hcv and Schizophrenia

Most psychiatric medications are metabolized by the liver and therefore may require more careful monitoring in those chronically infected with hepatitis C. In particular, for those who manifest clinical or laboratory signs of liver failure, medication metabolism can be dangerously reduced to the point where patients may accumulate toxic levels of drugs they normally can take.

Diseases of the digestive system K00K93

Alcoholic liver disease K70.0 Alcoholic fatty liver K70.1 Alcoholic hepatitis K70.2 Alcoholic fibrosis and sclerosis of liver K70.3 Alcoholic cirrhosis of liver Alcoholic cirrhosis NOS K70.4 Alcoholic hepatic failure Toxic liver disease with lupoid hepatitis K71.6 Toxic liver disease with hepatitis, not elsewhere classified K71.7 Toxic liver disease with fibrosis and cirrhosis of liver K71.8 Toxic liver disease with other disorders of liver Fibrosis and cirrhosis of liver Excludes alcoholic fibrosis of liver ( K70.2 ) cardiac sclerosis of liver ( K76.1 ) cirrhosis (of liver) K74.3 Primary biliary cirrhosis K74.4 Secondary biliary cirrhosis K74.5 Biliary cirrhosis, unspecified K74.6 Other and unspecified cirrhosis of liver Cirrhosis (of liver)

Laurie Haas and Luis Marsano

Patients with infections of the gastrointestinal (GI) tract may present with a range of complaints from vague symptoms such as malaise and anorexia to more serious manifestations such as severe diarrhea and sepsis. Although many GI infections require antibiotic therapy, others cause self-limited disease and only supportive care is needed. In the last decade, the recognition of the clinical importance of Helicobacter pylori and its cause and effect on peptic ulcer disease has changed what was once thought to be a disorder of excessive acid production to an infectious disease. The rising incidence of hepatitis C virus and progression to chronic active hepatitis and cirrhosis has also placed a tremendous burden on the health care system to find more effective and tolerable therapies for this disease. The emergence of resistance to antibiotics used to treat many of these infections, especially Helicobacter pylori infection and infectious diar-rheal syndromes, poses new challenges for...

Box 1 Indications and contraindications to therapy

Clinical trials have confirmed a twofold increase in efficacy of PEG-IFNs compared with standard IFN in HCV treatment-naive patients (Table 1). Zeuzem et al showed that in the SVR was 39 in patients treated with PEG-IFN 2a at a dose of 180 mg for 48 weeks compared with 19 in patients taking standard interferon 2a at a dose of 6 mU three times weekly for 12 weeks then 3 mU three times weekly for 36 weeks 18 . In this trial, 62 of the subjects had genotype 1 HCV, and 7 had cirrhosis. In their multivariate analysis, use of PEG-IFN 2a, younger age, smaller body surface area, absence of cirrhosis or bridging fibrosis, a lower HCV RNA level, and a nongenotype 1 infection were associated with higher SVR. Subsequent studies using PEG-IFN 2a have shown a somewhat reduced SVR of 29 . In a difficult-to-treat population of naive patients with advanced fibrosis, defined as bridging fibrosis or cirrhosis, PEG-IFN 2a again demonstrated superior SVR compared with IFN alfa 2a. Heathcote et al...

Hepaciviruses Hepatitis C and G

Hepatitis C resembles hepatitis B in many respects. One major difference is that it much more frequently produces a persistent infection (85 ) and, in 70 of cases, develops into a chronic hepatitis, resulting in cirrhosis of the liver within 20 years and a hepatocellular 8 carcinoma (HCC) in a further 10 years. The reason for the high level of viral persistence is thought to be a pronounced mutability facilitating evasion of the immune defenses (quasispecies of RNA viruses, p. 391). atitis B no immunization by vaccine is available. Especially in combination with ribavirin (Table 7.5), therapeutic use of interferon can lead to elimination of the virus in persistent infections and thus to prevention of cirrhosis of the liver and HCC.

Hbv As A Hepatocarcinogen

Circumstantial evidence that HBV is directly carcinogenic comes from three sources. Although most HBV-related HCCs coexist with cirrhosis, supporting the belief that virally induced chronic necroinflammatory hepatic disease plays an important part in the pathogenesis of HCC (31,32), the remaining tumors arise in an otherwise normal liver. Moreover, in populations with a high incidence of HBV-related HCC, markers of current infection with the virus are present as often in serum and liver and tumor tissue of HCC patients without cirrhosis as in those of those with cirrhosis (33,34). The demonstration that HBV DNA is integrated into cellular DNA in the great majority of these tumors provides further support for a direct oncogenic effect of the virus (35). Insertion of HBV DNA into chromosomal DNA precedes the development of HCC, and the presence of discrete hybridization bands in individual tumors indicates clonal expansion of cells with integrants. Nevertheless, integration of HBV DNA...

Hcv As A Hepatocarcinogen

Evidence for a causal role for HCV, a single-stranded RNA virus belonging to the Flaviviridae, in HCC is more recent but almost equally compelling. In common with HBV infection, the importance of chronic HCV infection as a risk factor for the tumor differs between developed and developing countries (74,75). In the former, whatever the incidence of HCC, HCV is a more important causal association of the tumor than is HBV, and in Japan, Italy, and Spain the virus accounts for as much as 80 of HCCs (74,75). For patients in these countries who have been referred to a hepatology clinic with chronic HCV infection, the annual risk of developing HCC ranges from 1.0 to 8.9 , with the risk being greater both in countries with higher incidences of the tumor and in patients with cirrhosis than in those with chronic hepatitis. Persistent HCV infection and alcohol abuse often (and chronic HBV infection and alcohol abuse less often) coexist as causal associations of HCC in developed countries...

Epidemiology Of Hcvassociated Lymphoma

The etiology of NHL is poorly understood but of considerable interest because of the increasing incidence of these malignancies worldwide (30). A possible causative link between hepatotropic viruses and malignant lymphomas had been hypothesized since 1971, when an autopsy study of 814 Belgian patients with neoplastic diseases reported a significant association between cirrhosis and lymphoproliferative disorders (31). With the identification of HCV as a triggering factor of MC (20-24), its potential role in NHL was suspected (12). In 1994, HCV infection was first demonstrated in a significant percentage of Italian patients with unselected B-cell NHL, regardless of the

Primary Sclerosing Cholangitis and Liver Transplantation

At present, PSC is the fifth most important indication for liver transplantation in the United States 5 . There are two major difficulties associated with predicting the course of the disease in each individual case as well as the increased risk for hepatobiliary malignancies, primarily cholangiocellular carcinoma (CCC). The risk for CCC is highest during the first year of diagnosis and is not linked to the stage of disease 6, 7 . A PSC patient with cirrhosis and a liver

Outcome after Liver Grafting

Survival rates are comparable with those achieved in patients with other autoimmune liver diseases, such as primary biliary cirrhosis and autoimmune hepatitis, with 1-year patient survival exceeding 90 in recently published series 14 . PSC patients are reported to have a slightly higher retransplantation rate without impact on long-term patient survival 4 . Again, this increased retransplantation rate has been ascribed to PSC-specific long-term complications, in particular, biliary strictures 17 . However, patient survival following Ltx has been shown to be

Treatment Of Hcvassociated Lymphoma

The treatment of HCV-associated lymphomas does not differ substantially from that of idiopathic B-cell NHL (97). However, the occurrence in the same subject of chronic viral infection and cancer and, in some cases, of other HCV-related disorders may be a conditioning factor for an optimal therapeutic strategy (Fig. 3). In all patients with B-cell NHL the detection of HCV-related markers (anti-HCV and HCV RNA) is obviously mandatory, together with histologic classification and staging of the disease. Before the treatment and during the patient's clinical follow-up, in HCV-positive NHL patients should be carefully evaluated for chronic hepatitis, cirrhosis, hepatocellular carcinoma, mixed cryoglobulinemia syndrome, and other HCV-related disorders, such as thyroiditis and glomerulonephritis. To date, there is not sufficient information on specific complications of cancer chemotherapy in HCV-positive NHL. In a series of patients with lymphoplasmocytoid lymphoma immunocytoma, the presence...

Clinical Focus Box 281

Chronic liver injury can lead to a sequence of changes that terminates with fatal bleeding from esophageal blood vessels. In most forms of chronic liver injury, stellate cells are transformed into collagen-secreting myofi-broblasts. These cells deposit collagen into the sinusoids, interfering with the exchange of compounds between the blood and hepatocytes and increasing resistance to portal venous flow. The resistance appears to be further increased when stellate cells contract. The increased resistance results in increased hepatic portal pressure and decreased liver blood flow. This disorder is seen in approximately 80 of patients with cirrhosis. In a compensatory effort, new channels are formed or dormant venous tributaries are expanded, resulting in the formation of varicose (unnaturally swollen) veins in the abdomen. Although varicose veins develop in many areas, portal Currently there are no well-recognized treatments to reverse cirrhosis, but numerous strategies are employed to...

Liver transplantation

The most common cause of liver damage requiring transplantation is chronic active non-A, non-B, viral, hepatitis. However, liver transplantation has been performed also in individuals with primary biliary cirrhosis, hepatitis B, cirrhosis, and inborn errors of metabolism.

Fibric Acid Derivatives

The fibric acid derivatives are contraindicated in patients with hypersensitivity to the drugs and those with significant hepatic or renal dysfunction or primary biliary cirrhosis because these drugs may increase the already elevated cholesterol. The drugs are used cautiously during pregnancy (Pregnancy Category C) and lactation and in patients with peptic ulcer disease or diabetes. Although it rarely occurs, when the fibric acid derivatives, particularly gemfibrozil, are administered with the HMG-CoA reductase inhibitors, there is an increased risk for rhabdomyolysis (see Nursing Alert). When clofibrate, fenofibrate, or gemfibrozil is administered with the anticoagulants, there is an increased risk for bleeding.

Box 1 Predictors of response in prior relapsers

Because most patients who relapse after a course of PEG IFN and RBV will have received 48 weeks of therapy, the only realistic option is to consider a repeat course of treatment for a longer duration (eg, 72 to 96 weeks). In apparent conformity with concepts of the kinetics of viral clearance, patients who clear HCV RNA on their initial course of PEG IFN and RBV have an enhanced risk of post-treatment relapse if clearance of HCV RNA requires longer than 12 weeks of therapy 41 . The concept of modifying the duration of therapy according to a patient's virologic response pattern to PEG IFN and RBV therapy has been evaluated in a preliminary study of nine HCV genotype 1, treatment-naive patients 50 . These nine patients all had delayed virologic clearance they were positive for HCV RNA by PCR but had a 2 log decline in HCV RNA by week 12 of therapy and had cleared virus by week 24. Patients were treated for 72 weeks, and 88 (7 8, with one lost to follow-up) had an SVR. As in patients...

Vibrio metschnikovii

The first significant clinical isolate was described in 1981 (80). It was isolated from a positive blood culture of an 82-year-old woman who had peritonitis and an inflamed gall bladder. Since the patient did not have a history of recent travel or of having eaten shellfish or crabs, the source of the pathogen could not be identified. The pathogen was also isolated from a blood culture of a 70-year-old patient who had liver cirrhosis, renal insufficiency, and diabetes (81). The patient did not have a history of recent travel or of having consumed seafood and died 5 days after admission. Blood culture of an 82-year-old lady who had septicemia, respiratory problems, and infected leg lesions yielded V. metschnikovii (81). Swab samples of the leg lesion revealed mixed flora that included V. metschnikovii. Another case of mixed bacteremia in an 83-year-old female who developed high fever, chills, and malaise after being admitted to a hospital for a suspected heart attack was reported by...

Scott W Biggins MD Norah A Terrault MD MPH

Chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States and Europe, and more than 20,000 patients worldwide have undergone transplantation for complications of chronic hepatitis C. In North America, HCV accounts for 15 to 50 of all liver transplants performed 1 . Available prevalence data predict that this proportion will likely increase as the number of persons with chronic hepatitis C developing cirrhosis and hepatocellular carcinoma in North America rises over the next 1 to 2 decades 2,3 . Recurrent HCV infection is universal in those with viremia before transplantation, and the rate of histologic disease progression after transplantation is more rapid. The risk of death and allograft failure is increased in HCV-positive transplant recipients (hazard ratio HR 1.23 and 1.30) compared with HCV-negative recipients 4 . The risk of cirrhosis is as high as 30 within 5 to 10 years after transplantation 5-7 . Retransplantation...

Pharmacology and mechanism of action

Steroids are metabolized in the liver. Their effects may be reduced by drugs that induce liver enzymes (eg, phenytoin, phenobarbitone and rifampicin). Blood levels of steroids may be raised in liver failure. Anticoagulant doses may need to be reduced when given concomitantly with steroids.

AGlucosidase Inhibitors

The a-glucosidase inhibitors are contraindicated in patients with a hypersensitivity to the drug, diabetic ketoacidosis, cirrhosis, inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or predisposition to intestinal obstruction, or chronic intestinal diseases. Acarbose and miglitol are used cautiously in patients with renal impairment or pre-existing gastrointestinal (GI) problems such as irritable

Xenotransplantation May Be the Answer to the Shortage of Donor Organs

The earliest transplants of chimpanzee kidneys into humans date back to 1964. Since that time, sporadic attempts at kidney, heart, liver, and bone-marrow transplantation from primates into humans have been made. No attempt has met with great success but several have received some attention. In 1993, T. E. Starzl performed two liver transplants from baboons into patients suffering from liver failure. Both patients died, one after 26 days and the other after 70 days. In 1994, a pig liver was transplanted into a 26-year-old suffering from acute hepatic failure. The liver functioned only 30 hours before it was rejected by a hyperacute rejection reaction. In 1995, baboon bone marrow was infused into an HIV-infected man with the aim of boosting his weakened immune system with the baboon immune cells, which do not become infected with the virus. Although there were no complications from the transplant, the baboon bone marrow did not appear to establish itself in the recipient.

Isolated angiitis of the central nervous systen is a recently recognized vasculitic disorder primarily involving the

Initial management of PAN without hepatitis B is with high-dose corticosteroids (40 to 60 mg d). CTX is added for severe cases. Traditionally, oral CTX has been used, but recent studies have shown that IV administration can be as effective as the oral with fewer side effects. In hepatitis B-related PAN, corticosteroids and CTX may allow the virus to persist, which can lead to chronic hepatitis and liver cirrhosis. Good results have been reported treating these patients with a combination of antiviral agents, plasma exchange, and corticosteroids. Relapses are rare in patients who achieve remission.

Abnormal findings

Enlarged Liver Causes

Secondary sexual hair appears at puberty its absence after this time suggests the possibility of hypopituitarism or hypogonadism (p. 38). Virilism in the female leads to a male distribution of pubic and body hair, whereas cirrhosis in the male may produce a female distribution of body hair. Veins. Collateral veins may be visible if the inferior vena cava is obstructed or if there is portal hypertension. These are usually tortuous dilated superficial epigastric veins in obstruction of the inferior vena cava, the blood flows upwards in the lower abdomen instead of downwards towards the groins. In cirrhosis, dilated collateral veins may also radiate from the umbilicus (caput Medusa), blood flowing away from the umbilicus as the portal vein drains through collateral vessels along the falciform ligament.

Pathophysiology Of Klinefelters Syndrome

Testicular Biopsy Klinefelter

The pathophysiology of KS-related gynecomastia is also not entirely clear. Individuals with KS do exhibit mildly elevated plasma levels of estradiol, probably from increases in peripheral aromatization and decreased clearance. However, histologic analysis of breast tissue from individuals with KS demonstrates intraductal hyperplasia rather than the ductal hyperplasia seen in high estrogen states in the male, such as cirrhosis (18).

Postoperative soft tissue and joint infection

If a history and physical examination will point to a disease predisposing to infection such as diabetes, liver cirrhosis, pneumonia, tuberculosis or to local changes (colostomy, psoriasis etc), we also resort to prophylactic antibiotics when performing a percutaneous screw fixation.

Platelets are essential for blood clotting

Platelet Plug

The clotting of blood requires many steps and many clotting factors. The absence of any one of these factors can impair clotting and cause excessive bleeding. Because the liver produces most of the clotting factors, liver diseases such as hepatitis and cirrhosis can result in excessive bleeding. The sex-linked genetic disorder hemophilia (see Chapters 10 and 17) is an example of a genetic inability to produce one of the clotting factors.

Abdominal distension bloating

Ascites, the accumulation of fluid in the peritoneal cavity, is usually due to cirrhosis of the liver, malignancy, nephrotic syndrome, tuberculous peritonitis, cardiac or pericardial disease. The acute development of tense ascites suggests intra-abdominal malignancy, infective peritonitis or the onset of hepatic or portal vein obstruction.

Marc G Ghany MDa Edward C Doo MDb

Infection with the hepatitis B virus (HBV) is a significant global public health problem. Over one third of the world population has been exposed to the virus, and an estimated 400 million people are chronically infected 1,2 . Up to 40 of chronically infected individuals will be at risk for cirrhosis, decompensated liver disease, and hepatocellular carcinoma (HCC), and each year, an estimated 500,000 deaths occur from these complications. Advances in molecular biology techniques have led to a better understanding of the natural history and pathogenesis of HBV-related liver disease, resulting in the development of potent antiviral agents. Some of these agents can be used safely as maintenance therapy for patients who fail to clear the virus following standard durations of treatment. Overall, the advent of newer therapies has provided a wider range of therapeutic options for chronic hepatitis B (CHB) infection. This article focuses on the natural history of CHB-related liver disease,...

Case 84 Bilateral Pleural Effusions Due To Intraabdominal Malignancy And Carcinomatous Peritoneii

Pleural Effusion

The CXR shows both costophrenic angles being blunted suggesting bilateral pleural effusions. The heart size is normal. In situations of bilateral pleural effusion, one must think in terms of a transudative state, e.g. congestive heart failure, nephrotic syndrome, or liver cirrhosis. If the fluid is exudative, an intraabdominal process has to be ruled out. In the CXR shown, another important finding is the small lung volumes, which may suggest an intra-abdominal process, e.g. malignant ascites tracking through the diaphragmatic foramina (Fig. 84.2).

The elderly accident victim

(decompensated liver cirrhosis with ascites, a severe chest wall or spine deformities). A properly performed local anesthesia would be under these circumstances the least stressful procedure (see Sect. 8.1.2). Here a carefully executed psychological preparation of the patient is mandatory.

Viral Hepatitis 21 Hepatitis A

Cancer and cirrhosis May worsen existing cirrhosis In addition to cirrhosis from chronic active hepatitis, one of the major complications of HBV infection is hepatocellular carcinoma. The length of time infected is an important factor in the development of cancer and, thus, elderly persons who have been infected for many years are at greatest risk (69). The rate of hepatocellular carcinoma rises from 197 100,000 in 30- to 39-yr olds to 927 100,000 in 60- to 69-yr-old chronic HBV carriers (62). The treatment of elderly persons with chronic HBV is largely supportive. Although a-interferon shows evidence of suppressing viral replication and may decrease the risk of progression to cirrhosis or cancer, side effects of therapy increase with advancing age (60). Therapy should be reserved for patients in overall good health except for their liver disease and who have evidence of active viral replication. Lamivudine, a nucleoside analogue, holds promise as a new anti-HBV agent. The clinical...

Postoperative Complications

Hepatic artery thrombosis (HAT) with an incidence of 1-5 following adult Ltx is a feared complication frequently leading to graft loss and retransplantation. The reason for the increased incidence of hepatic artery thrombosis in PSC patients is unclear 17 . New immunosuppressive regimens have significantly reduced rejection episodes in liver allograft recipients. Patients with PSC, PBC or autoimmune hepatitis seem to experience more acute rejections compared with patients with alcoholic cirrhosis or chronic viral hepatitis who are thus on a higher level of immunosuppression 23 . On the other hand, some centres have also reported fully satisfactory results after early steroid withdrawal in patients with PSC 24 . With regard to postoperative infection episodes, positive bacterial cultures are found in bile samples from a large portion of PSC patients at the time of Ltx 25 . Even in a graft biopsy, PSC recurrence can be difficult to identify. In some cases, typical fibrous cholangitis...

Clinical Features of Hepatitis B

There are a number of possible outcomes (Fig. 22-4). Less than 1 of the icteric cases die of fulminant hepatitis. Most recover uneventfully following complete regeneration of the damaged liver within 2-3 months, but some progress to chronic infection. This may take the form of an asymptomatic carrier state, defined as HBs antigenemia persisting for at least 6 months, or of chronic persistent hepatitis or chronic active hepatitis causing progressive liver damage, which may lead eventually to cirrhosis and or to primary hepatocellular carcinoma. A proportion of those with chronic persistent or chronic active hepatitis develop manifestations of immune-complex disease, systemic necrotizing vasculitis (polyarteritis nodosa) and membranoproliferative glomerulonephritis being the two most common.

Linked Lymphoproliferative Syndrome

Fulminant infectious mononucleosis (frequency 58 survival 4 ). It is characterized by infiltration of various organs with polyclonal B and T cells, production of inflammatory cytokines, and necrosis of liver, bone marrow, lymph nodes, and spleen caused by the invading cytotoxic T-cell and uncontrolled killer cell activity. Death is generally attributable to liver failure with hepatic encephalopathy or bone marrow failure with fatal hemorrhage in the lungs, brain, or gastrointestinal tract and occurs within 1 month of onset of symptoms. Secondary dysgammaglobulinemia (frequency 30 survival 55 ). B-cell lymphoproliferative disease including malignant lymphoma (extranodal non-

Approach to the Management of Patients with Chronic Hepatitis C Who Failed to Achieve Sustained Virologie Response

Therapy for chronic hepatitis C virus (HCV) infection has improved dramatically since interferon (IFN) was first introduced for treatment of non-A, non-B hepatitis over 15 years ago 1-3 . Historically, standard IFN monotherapy yielded a sustained virologic response (SVR) in less than 15 of patients. The addition of ribavirin (RBV) 4,5 , and later the substitution of peginterferon (PEGIFN) for standard IFN 6-9 , led to dramatic improvements in SVR rates, which can now be achieved in 45 to 50 of patients who have HCV genotype 1 and approximately 80 of patients who have genotypes 2 or 3 10-12 . As each new improvement in HCV therapy has emerged, many patients who had failed to achieve SVR with previous, less effective therapy have been retreated. Recently, several large multicenter clinical trials have demonstrated the impact of retreating such patients with PEGIFN RBV 13-16 . In the largest of these trials, 18 of patients who had a nonresponse (NR) after treatment with IFN or IFN RBV...

DCommon adverse effects

MTX-induced cirrhosis and liver failure are uncommon in RA patients. In a survey of more than 2,200 members of the American College of Rheumatology (ACR) who had treated 16,600 patients with MTX, Walker et al. found 24 cases of cirrhosis and liver failure, giving a 5-year cumulative incidence of approximately 1 in 1,000 treated patients. Late age at first use of MTX and duration of therapy with MTX were independent predictors of serious liver disease.

Pathogenesis and Immunity

Printable Coloring Doodles

Variants of HBV have been isolated from Mediterranean and Asian patients with chronic liver disease. Pre-S mutants with point mutations or deletions in the prc-S2 region produce higher viremia than is seen with wild-type virus. Pre-core mutants, which make no HBeAg, display enhanced aggressiveness and are commonly found in patients with severe chronic active hepatitis or cirrhosis, and even fulminant hepatitis. These cases are characterized by very high levels of HBcAg in hepatocyte nuclei and cytoplasm, unrelenting fibrosis, and a poor prognosis.

Evaluate Known Consequences of Exposure

In a cohort study designed to examine the effect of heavy alcohol use on the risk of myocardial infarction, we might examine the association between our measure of heavy alcohol use and risk of cirrhosis, motor vehicle injuries, or depression, since these are established with certainty as being associated with heavy alcohol use. If feasible, we might evaluate subclinical effects of alcohol on liver function. If the study participants classified as heavy alcohol users did not show any increased risk for health problems known to be associated with heavy alcohol use, the validity of our assessment of alcohol use would be called into question. If the expected associations were found, then confidence in the accuracy of the measure would be enhanced.

Areas of future research

Although MR antagonists are beneficial in CHF, the MR may play an important role in healthy cardiac function. Transgenic mice develop severe CHF when MR expression by the cardiomyocyte is reduced using a conditional MR antisense RNA restoration of MR expression reverses the CHF (65). Altering MR expression in the cardiomyocyte may have a different effect than activating MR in the vasculature. Furthermore, cardio-myocytes do not express 11 -HSD2. Therefore, cortisol may activate the MR in the heart. Transgenic mice that overexpress 11 -HSD2 in cardiomyocytes develop cardiac fibrosis that is reduced by MR antagonists (66). Thus, it is possible that in cardio-myocytes, activation of MR by aldosterone has adverse effects whereas activation by cortisol has beneficial effects. Further studies are needed to better define the role of MR in cardiomyocytes and the vasculature. Finally, whether aldosterone contributes to injury and fibrosis in other organs, such as retinopathy, pulmonary...

Natural History of HCV Disease

Patients infected with HCV should be advised to minimize or preferably discontinue intake of alcohol. Chronic HCV infection can cause inflammatory infiltration, particularly of the portal tracts, as well as focal liver cell necrosis and fibrosis that bridges between portal tracts. Hepatitis C is the leading cause of liver transplantation in the United States. About 10 -20 of patients progress to cirrhosis within 20-30 years of infection, and among those with cirrhosis, 1 -4 per year will develop hepatocel-lular carcinoma. Immunosuppression associated with HIV appears to significantly alter the natural history and clinical course of HCV, with HCV-associated cirrhosis occurring more frequently in patients with HCV-HIV co-infection (33 ) than in HCV alone (11 ). People with HCV do not tolerate HAART as well, which can interfere with effective HIV treatment. Data indicate that liver failure due to HCV is the leading non-AIDS cause of death in HIV-infected individuals (Community Research...

Hepadnaviridae and Deltavirus

Hepatitis B is one of the world's major unconquered diseases. Some 300 million people are chronic carriers of the virus, and a significant minority go on to develop cirrhosis or cancer of the liver from which over 1 million die every year. Although hepatitis B virus (HBV) has yet to be cultivated repro-ducibly nt vitro, reliable diagnostic procedures and a much-needed vaccine are available.

Pathogenetic Considerations

Glycogen storage disease type IV is highly heterogeneous as to clinical symptoms and age of onset. The latter varies between the early neonatal period through childhood to late adulthood. The classical type is characterized by early onset and rapidly progressive hepatosplenomegaly, progressive cirrhosis with portal hypertension, ascites, esophageal varices, and death between 3 and 5 years due to liver failure, unless liver transplantation is performed. Nonprogressive hepatic variants have also been described. Patients with neuromuscular involvement have a my-opathy with or without cardiomyopathy, neuropathy, and liver cirrhosis. The age at onset varies from neonatal to adulthood. Neonatal variants presenting with pronounced hypotonia are extremely rare. They resemble patients with the Werdnig-Hoffmann type of spinal muscular atrophy. They may have additional cardiomyopathy or hepatosplenomegaly. Presentation with hydrops fetalis is also very rare. APBD characterized by late onset and...

Virusassociated Malignancies

Epstein Barr Virus Infection Timeline

HBV replicates in the liver and causes hepatic dysfunction (80). Most HBV infections are self-limiting and are effectively controlled by the immune system. A small fraction of HBV infections can become persistent or chronic if the immune system fails to resolve the infection completely. Persons with chronic HBV infection are at substantially increased risk of developing cirrhosis and primary hepatocellular carcinoma. Although no specific HBV sequence has been implicated in the development of hepatocellular carcinoma, the virus appears to act as a mutagenic agent, and viral gene expression may not be required for tumor growth. IFN-a treatment is helpful in some cases, but a satisfactory medical treatment for chronic HBV infection is still unavailable. Immunologic intervention with the conventional hepatitis B vaccine relies on primary prevention. The vaccine is composed of a highly purified preparation of hepatitis B surface antigen (HbsAg). Virtually 100 of persons who develop HBsAg...

Localized amyloidosis

Increased intestinal iron absorption and visceral deposition can lead to the classic features of hepatic cirrhosis, cardiomyopathy, diabetes mellitus ( bronze diabetes), pituitary dysfunction, sicca syndrome, and skin pigmentation. Liver abnormalities are probably the most constant manifestation. However, hemochromatosis is usually symptomless and is often detected only accidentally. Other presenting manifestations include constitutional symptoms such as weakness, lethargy, and increased

Clinical Focus Box 241

Hyponatremia with hypoosmolality can occur in the presence of a decreased, normal, or even increased total body Na+. Hyponatremia and decreased body Na+ content may be seen with increased Na+ loss, such as with vomiting, diarrhea, and diuretic therapy. In these instances, the decrease in ECF volume stimulates thirst and AVP release. More water is ingested, but the kidneys form osmotically concentrated urine and plasma hypoosmolality and hyponatremia result. Hyponatremia and a normal body Na+ content are seen in hypothyroidism, cortisol deficiency, and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). SIADH occurs with neurological disease, severe pain, certain drugs (such as hypoglycemic agents), and with some tumors. For example, a bronchogenic tumor may secrete AVP without control by plasma osmolality. The result is renal conservation of water. Hyponatremia and increased total body Na+ are seen in edematous states, such as congestive heart failure, hepatic...

Immunotherapy Of Specific Bacterial Infections

No antisera directed against the polysaccharides or proteins of any of the hemolytic streptococci have been developed to date. In studies of the use of various intravenous immunoglobulin (IVIG) preparations in the prevention and treatment of sepsis in low-birth-weight and other neonates, there appeared to be a small, but significant effect on decreasing the mortality rate associated with sepsis (8,9). Group B streptococci are an important cause of neonatal sepsis, but these studies did not specifically address these organisms, and it is as yet unclear whether the use of standard IVIG preparations would prevent or augment the treatment of serious group B streptococcal infections. Group B streptococci can also cause serious disease in adults, especially those with underlying diabetes, cirrhosis, and malignancy, but these infections have not posed a threat in terms of antibiotic resistance, and it would seem unlikely that hyperimmune antisera to group B streptococcal antigens would...

Acquired Iron Deficiency

Organs responsible for development of iron-deficiency anaemia are the uterus (increased menstrual blood loss, pregnancy), the oesophagus (varicose veins in patients with liver cirrhosis), the stomach and bulbus duodeni (hiatus hernia, aspirin and detrimental effects of other non-steroidal antiinflammatory drugs, peptic ulcer, carcinoma, partial gastrectomy), the small intestine (hookworm, coeliac disease, diverticulosis, morbus Crohn, angiodysplasia), the colon and rectum (carcinoma, diverticulosis, angiodysplasia, varices, colitis) and, rarely, the kidney and lung. Increased demands for iron, not met by adequate iron intake, occur in premature infants, during any period associated with increased growth, and during pregnancy. Poor diet is also a cause of iron deficiency in some socioeconomic groups in developed countries. Female blood donors in particular may develop iron deficiency. Self-inflicted blood loss is a diagnosis that should be considered if no cause can be found for severe...

Factors Influencing Outcome from ARF

History Mechanical Ventilators

Preexisting comorbid diseases can be associated with increased mortality in ARF. In a multivariate analysis, Luhr et al. 13 reported that immunosuppression was associated with mortality in ARF patients. The SOFA database 29 identified a history of hematologic or chronic renal or liver failure as independent risk factors for death from ARF. Chronic liver disease has been associated with mortality from ARDS in several studies 2, 9, 13 . Zilberberg and Epstein 10 identified organ transplantation, human immunodeficiency virus (HIV) infection, cirrhosis, active malignancy, and sepsis as independent factors for hospital mortality in patients with ALI. Monchi et al. 9 reported that the length of mechanical ventilation prior to ARDS, cirrhosis, and the occurrence of right ventricular failure were associated with an increased risk of death.

Other Viruses

I he genome of onlv I 7 kb of covalenlly closed circular minus sense ssRNA contains regions of extensive base pairing and probably exisls as a partially double-stranded rodlike structure with self-cleaving ribonucleic (ribozyme) activity, similar to the plant virus satellites. Known only as a virus of humans who aie simultaneously infected vith hepatitis B virus, hepatitis D virus causes severe disease which often progresses to chronic hepatitis and or cirrhosis.

Hepatitis

Several viruses are capable of causing hepatic inflammation. These include the Epstein-Barr virus, cytomegalovirus, herpes simplex virus, mumps, rubella, rubeola and varicella-zoster viruses, yellow fever virus, Coxsackie viruses, and adenoviruses. In most cases, infection or inflammation of the liver is part of a systemic infection with the above agents. In addition, there are a number of viruses that are primarily hepatotropic and are given alphabetical designations hepatitis A-E. Several other viruses that were initially thought to cause posttransfusion hepatitis, including hepatitis G virus or GBV-C and SEN viruses, are not currently believed to be human pathogens. Of the truly hepatotropic viruses, hepatitis A and hepatitis E generally produce self-limited disease, although fulminant hepatic failure has been reported in up to 1 -2 of infected individuals. Hepatitis D virus (or the delta agent) can produce coinfections in patients who are infected with hepatitis B, but it appears...

Diagnosis

Some experts recommend needle biopsy under imaging guidance partly because lymphoma and nonmalignant lesions can masquerade as HCC 13 . Tissue diagnosis, however, is neither always necessary nor feasible. Biopsies entail some risk. Patients with HCC often have end-stage cirrhosis with coagulopathy, thrombocytopenia, or ascites, all of which increase the risk of bleeding. Small tumors may be difficult to reach by percutaneous biopsy. Cancer cells can rarely seed along the biopsy needle track. Earlier large studies reported a risk of about 0.003 to 0.009 of seeding 14 , but more recent studies report a 1 to 2 risk 15,16 . In some studies, the false-negative rate of biopsies is as high as 10 to 40 , particularly for small tumors, because of inadequate samples or sampling error 15,16 . The histo-pathologic criterion separating dysplastic regenerative nodules from malignancy can be ambiguous. Repeat biopsy does not significantly decrease the false-negative rate 13,16 . Generally accepted...

Treatment

Treatment for HCC depends on the stage of the tumor and of the chronic liver disease or cirrhosis. The former dictates the chance of cure or response to therapy, whereas the latter dictates the tolerability of therapy. Intolerabil-ity to therapy is more common for HCC than for other cancers because HCC typically evolves in the setting of cirrhosis, which increases both operative and chemotherapeutic risks. Moreover, advanced liver failure creates significant baseline mortality unrelated to HCC. Despite these problems, aggressive therapy may be successful, particularly for patients with early stage HCC and well-preserved hepatic function. The appropriate therapy is controversial and can vary from center to center. Perioperative mortality for HCC resection used to be prohibitively high (15 -20 ), but has decreased to less than 5 today because of improved patient selection and surgical techniques 43,44 . Surgical resection may be offered to patients with single-lesion HCC and...

Pyomyositis

Pyomyositis refers to purulent infection deep within a striated muscle group, often manifesting as an abscess. Infection does not result from a contiguous site but rather secondary to hematogenous seeding of injured muscle. Although usually involving one muscle group, multiple sites may be infected simultaneously in approximately 15 of cases 57 . Most commonly targeting the thigh, pyomyositis also can occur in the calf, upper extremity, gluteal, chest wall, and psoas muscles 57 . The incidence of this rare infection seems to be increasing in areas other than the tropics where it was originally described and it seems to be associated with immunocompromis-ing conditions, such as HIV infection, malnutrition, concomitant parasitic or viral infection, diabetes mellitus, intravenous drug use, immunosuppres-sive drugs, rheumatologic diseases, cirrhosis, and malignancy 58,59 . Patients initially present with fever, swelling, and crampy pain at the involved muscle site before developing edema,...

Acquired

In addition to a deficiency of coagulation factors of the prothrombin complex in liver disease, an abnormality of platelet function has been described. Platelet aggregation by ADP and thrombin is significantly delayed in patients with cirrhosis and prolonged thrombin time. This is due to the known inhibition of platelet function by fi-brinogen degradation products, resulting from excessive fibrinolysis occurring in advanced liver disease.

Chronic Infections

Hepatitis B is the most important chronic viral infection of humans, especially in Asia and Africa, where there are some 250 million carriers. During acute infections the virus replicates in the liver and circulates in the plasma, usually in association with a great excess of smaller particles composed of viral surface antigen (HBsAg). In most infected individuals HBsAg and virions are cleared from the circulation, but in 5-10 , including over 90 of those infected during infancy, a persistent infection is established which can extend for many years, often for life. The carrier state is characterized by continuous production of HBsAg and usually infectious particles, which are plentiful in the bloodstream and less so in semen and saliva, hence the danger of such persons as blood donors and sexual partners. Some carriers develop chronic hepatitis and cirrhosis, and hepatitis B virus (HBV) is an important cause of primary hepatocellular carcinoma. Hepatitis, cirrhosis,

HCV Treatment

Diagnostic testing to determine the presence of HCV viremia and the extent of liver pathology should be completed as early as possible in the care of a patient infected with HCV. Liver biopsy is useful in evaluating liver damage and deciding type of treatment elevation in serum transaminases in the absence of inflammation or fibrosis typically is not an indication for treatment. Patients with active HCV infection or evidence of chronic liver disease should be referred to a specialist with experience in treating hepatitis C for evaluation and guidance regarding possible treatment. Treatment recommendations should be individualized, and not all patients with HCV should receive treatment. Factors to be considered in the selection of patients for treatment include the patient's immune status the presence of moderate to severe inflammation and or fibrosis, which predicts the likelihood of progression to cirrhosis in the absence of treatment the likelihood of a favorable response to...

Herbal Alert Kava

Kava is a popular herbal remedy used to relieve stress, anxiety, and tension promote sleep and provide relief from menstrual symptoms. Although the FDA has not made a determination about the ability of kava dietary supplements to provide such benefits, it has issued an alert indicating that the use of kava may cause liver damage. Because kava-containingproducts have been associated with liver-related injuries (eg, hepatitis, cirrhosis, and liver failure), the safest use of kava is to take the herb occasionally for episodes of anxiety, rather than on a daily basis. It is important that individuals who use a kava-containing dietary supplement and experience signs of liver disease immediately consult their primary health care provider. Symptoms of liver disease includejaundice, urine with a brownish discoloration, nausea, vomiting, light-colored stools, weakness, and loss of appetite. Adverse effects experienced with the use of dietary supplements should be reported to the FDA's MedWatch...

Lcms Hiv1 and HCV

The SELDI ProteinChip approach has been employed to study the protein profiles of cells infected with viruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), HIV-1, and chronic hepatitis B virus infection (CHB) 31 . SARS is a viral respiratory illness caused by SARS-CoV. SARS was recognized as a global threat in March 2003, after first appearing in Southern China in November 2002 (http www.cdc.gov 20 ). Current serological methods used for laboratory diagnosis of SARS fail to guarantee early diagnosis since most are based on the detection of antibodies that are produced 17-20 days after the onset of symptoms. ELISA-based antigen detection tests offer high specificity and reproducibility, but they lack sensitivity. On the contrary, PCR-based methods, including reverse transcription-PCR, lack sensitivity and specificity 112 . For this reason, there is a need to develop a diagnostic methodology that can detect SARS before the onset of the symptoms to allow for...

Time After Exposure

To chronic active hepatitis and or cirrhosis. Acute superinfection is distinguished from acute coin feet ion by the absence of anti-HBc IgM. In chronic hepatitis delta infection, alanine aminotransferase levels fluctuate but remain elevated, whereas anti-HD IgM as well as total anti-HD and HDV RNA remain demonstrable in the serum for months or years. Table 22-5 summarizes the patterns of serological markers of HDV infection.

Low Risk Group

If a massively enlarged liver compromises respiratory function, a short course of low-dose oral cyclophosphamide (5 mg kg day for 5 days every 2-3 weeks as needed) can induce remission. In addition, low-dose radiation (150 cGy two or three times to the anterior two thirds of the liver through lateral oblique ports avoiding radiation to the kidneys, ovary, and spine) may be delivered to the tumor. This dose is generally sufficient to halt the progression of the tumor and induce regression. The disadvantage of delivering neonatal radiation to the liver is the possibility of subsequent hepatic fibrosis or cirrhosis.

Hepatitis C Virus

HCV, like HBV, is important globally. The World Health Organization (WHO) recently estimated that there are 170 million HCV carriers worldwide, and 80 of patients with acute HCV infection develop chronic hepatitis. Among them, up to 20 have been estimated to progress to liver cirrhosis, and 1-5 may develop HCC over a period of 20-30 yr (49). So far, the mechanism of hepatocarcinogenesis of HCV remains unclear. Although replicative HCV intermediates, such as minus-strand HCV RNA, have been detected in HCC tissues (68), HCV RNA does not integrate into the cellular genome as does HBV, and little is known about the biologic activities of HCV proteins. It is more likely that HCV-related HCC occurs against a background of repeat necroinflammation and regeneration, associated with liver injury due to chronic hepatitis, contributing to the complex multistep process of hepatocarcinogenesis (20). Most, if not all, cases of HCV-related HCC occur in the presence of cirrhosis, suggesting that it...

Pathology

Advanced HCC is classified on visual inspection into expanding (massive), nodular, and diffuse types (15,16). The expanding type consists of a large single tumor (although it may be accompanied by a few small satellite nodules) the nodular type of multiple nodules of different sizes, some of which may be confluent and the diffuse type of multiple small, ill-defined tumors throughout the liver. The expanding type usually arises in an otherwise normal liver, whereas the diffuse type is typically found in the presence of cirrhosis. In Japan, in particular, the expanding type may be surrounded by a thick fibrous capsule. Early (small) HCCs are divided into distinct nodular and indistinct nodular varieties. The majority of HCCs in all geographic regions arise in a cirrhotic liver. The morphologic features of HBV-induced cirrhosis differ from those of HCV-induced cirrhosis. In type B cirrhosis, the regenerative nodules are larger than those of type C cirrhosis, the fibrous septa are thin...

Sideeffect profile

Serious side effects include cytopenias (seen only rarely) or, most commonly, mild-to-moderate leucopenia, which responds to withdrawal of the drug. More severe bone marrow suppression may be treated with leukovorin or recombinant colony-stimulating factors. Mild transaminase elevations are common during treatment with methotrexate, but serious hepatotoxicity that can lead to fibrosis or frank cirrhosis is rare.

Genetic Aspects

Further possible evidence for a role for genetic factors is suggested by the occurrence of HCC in a number of inherited metabolic diseases, including hereditary hemochromatosis, ai-antitrypsin deficiency, hereditary tyrosinemia, glycogen storage disease (type I), and hypercitrullinemia (88). Some of these conditions are complicated by the development of cirrhosis in addition to HCC, and chronic necroinflammatory hepatic disease may contribute to the neoplastic process. In others the genetic defect results in the accumulation of chemicals that are mutagenic. The latter is best illustrated by hereditary hemochromatosis, in which excessive amounts of iron accumulate in the tissues (88). Excess hepatic iron is known to be mutagenic (89).

Indications

It is now generally accepted that small-bowel transplantation is indicated in patients suffering from irreversible small-intestinal failure coexisting with failure of parenteral nutrition. The main causes of parenteral nutrition failure are recurrent line related sepsis, loss of venous access due to thrombosis and PN-related liver disease. Medicare and Medicaid Services in the US have established indications that include impending or overt liver failure due to TPN-induced liver injury, thrombosis of two or more central veins, the development of two or more episodes of systemic sepsis secondary to line infection per year that require hospitalization, a single episode of line-related fungemia, septic shock and or acute respiratory distress, and frequent episodes of severe dehydration despite intravenous fluid supplementation in addition to TPN 13 .

Loop Diuretics

Loop diuretics are used in the treatment of edema associated with CHF, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. These drugs are particularly useful when a greater diuretic effect is desired. Furosemide is the drug of choice when a rapid diuresis is needed or if the patient has renal insufficiency. Furosemide and torsemide are also used to treat hypertension. Ethacrynic acid is also used for the short-term management of ascites caused by a malignancy, idiopathic edema, or lymphedema.

Tumor Markers

AFP and P-hCG levels are useful for clinical evaluation and for assessing disease activity. Table 24-4 lists the mean and standard deviation of normal serum AFP levels of infants at various ages. Increasing levels of serum AFP are not necessarily indicative of tumor progression because abrupt escalation in serum AFP can occur after chemotherapy-induced tumor lysis. Elevations of serum AFP could also be caused by alterations in hepatic function such as viral hepatitis, cirrhosis, hepatoblastoma, pancreatic and gastrointestinal (GI) malignancies, and lung cancers. P-hCG can also experience sudden increases secondary to cell lysis during chemotherapy or can be increased with malignancies of the liver, pancreas, GI tract, breast, lung, and bladder. The utility of CA-125 in monitoring ovarian germ cell tumors in children has not been thoroughly evaluated. LDH may also correlate with disease activity such as

Vibrio hollisae

In rare instances V. hollisae has also been associated with bacteremia and septicemia. It has been isolated from blood in a patient with hepatic encephalopathy, bronchopneumonia, and crypto-coccal sepsis (13). In addition, it has also been isolated from a patient who had a history of cirrhosis and splenectomy (41) and from another who had chronic active hepatitis, portal hypertension, and esophageal varices with gastrointestinal bleeding (42). In one case it was reported to cause both gastroenteritis and bacteremia (43).

Alkaloids

Sometimes domesticated animals that have not previously been exposed to alkaloid-containing plants do not have acquired avoidance mechanisms, and they become poisoned. For example, groundsel contains the alkaloid senecionine, which has resulted in many recorded cases of livestock fatalities due to liver failure. More frequently, over time, natural selection has resulted in animals developing biochemical mechanisms or behavioral traits that lead to avoidance of alkaloid-containing plants.

Gynaecomastia

Gynaecomastia is also found in cirrhosis of the liver and in conditions associated with increased oestrogen production (interstitial cell tumours of the testis, some adrenal tumours, thyrotoxicosis) or decreased androgen production (hypergonadotropic hypogonadism. Klinefelter's syndrome, orchitis).

Negligence

Consumers may have no grounds for bringing food poisoning lawsuits if they were aware of the health risks of consuming a specific food prior to consuming it and becoming ill (American Law of Products Liability, 1987). For example, a consumer with cirrhosis of the liver who became ill after consuming raw oysters despite being informed about the health hazards of a V. vulnificus infection is unlikely to recover damages from either the seafood company that produced the oysters or the restaurant that served them. Defendant firms have sometimes argued that a plaintiff was negligent in consuming a particular food because he or she had a preexisting medical condition that increased his her susceptibility to food-borne pathogens, but the effectiveness of this argument has not been established.

Enterococcus

Been reported to cause spontaneous peritonitis in patients with nephrosis and cirrhosis as well as in patients undergoing ambulatory peritoneal dialysis. Enterococcal meningitis is rare, occurring in patients with altered central nervous system anatomy from trauma or surgery. The respiratory tract is also rarely affected by enterococci, generally in severely debilitated patients.

Jaundice

Enterohepatic System And Urobilinogen

Typical symptoms include itching (pruritus), dark urine and pale stools. Obstruction of the biliary tract is usually extrahepatic in origin and caused by either gallstones or pancreatic carcinoma. The former is suggested by a history of fever, rigors, biliary colic or previous biliary surgery in the latter, chronic persistent back pain, aggravated by recumbency, and palpable enlargement of the gall bladder may occur. Intrahepatic obstruction is most often due to alcohol abuse, drug therapy and primary biliary cirrhosis (a disorder of middle-aged women often preceded by marked pruritus).

Hepatitis B

Patients who are chronically infected may be carriers and suffer almost no hepatic injury with minimal or nonexistent (nonreplicative phase) viral replication. Alternatively, they may have a more intense chronic hepatitis. Patients who are chronically infected and who have ongoing viral replication with elevated liver enzymes are at higher risk for progressive liver disease, and once cirrhosis develops, have a high risk for hepatocellular carcinoma. The development of cirrhosis, however, is not a prerequisite for the development of hepatocellular carcinoma. Interferon has traditionally been used as the treatment for HBV. The patients who have a better chance of response to this drug are those with well-compensated liver disease, moderately elevated liver enzymes (ALT of 100), and only moderate elevation of HBV-DNA ( 200 pg mL). Meta-analysis of the efficacy of interferon has shown that 33 of the patients who have chronic hepatitis B with significant viral replication may clear the...

Erysipelascellulitis

Vibrio vulnificus causes two distinct clinical syndromes involving the skin (7,8). Primary bacteremia occurs after ingestion of contaminated raw oysters or other shellfish. Infection usually occurs in the elderly with chronic underlying disease, especially cirrhosis. Onset of disease is rapid and characterized by high fever, chills, shock in about 30 , and characteristic bullous skin lesions in more than 50 of patients. Primary wound infection occurs after exposure to sea water, and also typically causes a bullous cellulitis that varies from a mild infection to severe necrosis mimicking gas gangrene. Fresh water exposure Cirrhosis

Abnormal Skin Color

Jaundice may be detected by a patient or by a member of the family. As a rule, hepatic congestion due to heart failure will not produce jaundice. When jaundice does occur in a patient with heart failure, it is appropriate to consider pulmonary infarction in addition to hepatic congestion or cirrhosis of the liver. Hemolysis of red blood cells may occur in patients with prosthetic valves and can produce jaundice.2

Facial and body hair

Pituitary Tumour

Secondary sexual hair on the face in the male, and in the axillae and on the pubis of both sexes, may fail to develop normally in hypogonadism it may diminish in quantity in old age or be lost in hypopituitarism or as a result of hepatic cirrhosis. In severe hypopituitarism (Fig. 2.14) the loss is ultimately complete, including the hair follicles, so that the axillae and pubis return to the smooth appearance seen in childhood.

Portal Hypertension

Mri Collaterals Portal Hypertension

Fig. 2a-c. 44-year-old patient with hepatic cirrhosis and repeated gastrointestinal haemorrhage. Three rotated MIP displays of the portal venous phase 3D data set depict the portal venous morphology to good advantage. The splenic vein is dilated and is draining into a convolute of gastroesophageal collaterals which can be seen to extent to the distal oesophagus. Contrast-enhanced 3D MRA provides an excellent mean for non-invasively evaluating the portal venous system. Use of Gd-BOPTA (MultiHance , Bracco) provides optimal image quality of the portal venous system owing to the transient albumin-binding of this particular contrast agent. Gastro-oesophageal collaterals are well visualized. Lack of enhancement of the intrahepatic portal venous system suggests retrograde flow in the portal vein with portal systemic shunting to the gastro-esophageal collaterals. Based on these imaging data this patient underwent TIPS in combination with embolisation of the gastro-oesophageal-collaterals...

Alcohol

Alcohol consumption plays a role in both acute and chronic medical illness through a variety of mechanisms, some or all of which may be operative in a specific individual (Schuckit 1998). Repeated exposure may lead to alcoholic hepatitis and eventually cirrhosis, with secondary cognitive impairment via hepatic encephalopathy in advanced cirrhosis due to the accumulation of nitrogenous compounds that are inadequately metabolized by the compromised liver. The cirrhotic changes of the liver are also manifested in impaired synthetic function (e.g., decreased production of clotting factors) and reduced metabolism of exogenous toxins such as medications. In the CNS, prolonged alcohol abuse leads to cerebellar degeneration in about 1 of chronic alcoholics, presenting as unsteady gait and mild nystagmus. These symptoms are irreversible and often accompanied by global cognitive decline from direct or indirect effects of chronic alcohol consumption (e.g., head injury, nutritional deficiency,...

Edema And Ascites

Edema is a common symptom or finding in patients with right- or left-sided heart failure. Fluid retention in heart failure results from increased venous pressure and abnormal activity of salt-retaining hormones (see Chap. 20). In an average-sized person, 5 to 10 lb of excess fluid is required for edema to become apparent a history of recent weight gain often will correlate with a deterioration in clinical status. The amount of weight loss in response to treatment for heart failure in the past will relate to the severity of the problem. Minor degrees of edema are evident only after a period of dependency of the legs and will decrease after rest. Presacral edema may be most obvious when the patient has been at bed rest. Although edema of cardiac origin may progress to anasarca, cardiac edema rarely involves the face or upper extremities. Edema mainly affecting the face and arms is more likely to be due to venous or lymphatic obstruction by clot or neoplasm. Facial edema is a feature of...

Prevention

Secondary prevention of HCC by control of viral replication and hepatic injury may be vital for the millions already chronically infected with hepatitis C or B virus. Treatment to eradicate or control the viruses decreases the chronic inflammation and regeneration of hepatocytes. In the United States, a large cohort has been infected with hepatitis C for 20 to 30 years during this time period the risk of cirrhosis and HCC increases significantly. Treatment has improved significantly during the last several years. Combined therapy with a long-acting pegylated interferon-a injected once a week and ribavirin taken daily by mouth can achieve long-term eradication of hepatitis C virus in 40 to 70 of cases, depending on the viral genotype. Eradication of hepatitis C virus infection should prevent progression to cirrhosis and decrease the risk of HCC. In a Japanese surveillance program of nearly 3000 cases of chronic hepatitis C followed since 1994, treated patients had a 50 reduction in HCC...

Cellulitis

Cellulitis is a diffuse skin infection that involves the deep dermis and the subcutaneous fat tissues. Unlike erysipelas, which demonstrates superficial skin involvement with distinct margins, cellulitis is diffuse and spreading with no distinct demarcations. Although the inciting event typically is not discernable, predisposing factors include traumatic skin lesions, including puncture wounds, lacerations, surgical wounds, and burns prior history of cellulitis dermatophyte infections, such as tinea pedis pressure ulcers eczema dermatitis vascular insufficiency lymphedema presence of a foreign body malnutrition and immunosuppressive conditions, such as diabetes mellitus and cirrhosis 22,23 . Any cutaneous surface may be involved, but the most common site of infection is the lower extremity 24,25 . In immu-nocompetent hosts, the microorganisms most commonly implicated include Gram-positive cocci such as beta-hemolytic streptococci (particularly S pyogenes) and S aureus. In...

Hepatitis C

In many developed countries today hepatitis A, B, and C are about equally common. Acute hepatitis C is clinically similar lo hepatitis A and B, and the reader is referred back to Chapters 22 and 23 for descriptions. The major differences are as follows. The incubation period of hepatitis C, though ranging up to several months, averages 6-8 weeks. About 75 of infections are subclinical. Clinical infections are generally less severe than hepatitis B, having a shorter preicteric period, milder symptoms, absent or less marked jaundice, and somewhat lower serum alanine aminotransferase (ALT) levels, which often fluctuate widely. The case-fatality rate from fulminant hepatitis is 1 or less. However, HCV leads much more commonly lo chronic liver disease than does HBV. At least 50 of all patients with hepatitis C remain continuously or erratically viremic with moderate elevation of ALT levels for at least a year or two, and often much longer. Most of these are asymptomatic carriers or mild...