Cirrhotic Liver of the Digestive System
The commonest cause of portal hypertension is cirrhosis secondary to alcoholic liver disease or chronic hepatitis B or C (see Fig. 6.24), further causes are listed in Table 6.3. Imaging features of cirrhosis and portal hypertension include liver nodularity, reversal of portal blood flow (demonstrated on ultrasound), porto-systemic colateral vessels, splenomegaly, ascites and complications such as hepatoma. Porto-systemic colateral vessels occur at many sites (see Table 6.4) as a consequence of portal hypertension (see Fig. 6.25). Fig. 6.24 Liver cirrhosis complicated by hepatoma. The liver has an irregular, nodular outline which is typical of cirrhosis. Hepatomas, such as this example, have avid arterial enhancement. Cirrhosis (Fig. 6.24)
The net result of chronic hepatic disease that leads to cirrhosis is that pathophysiologic alterations may result in both decreased hepatocyte function, with as much as a 50 decrease in cytochrome P450 content, and or shunting of blood away from optimally functioning hepatocytes. Accordingly, cirrhosis affects drug metabolism more than does any other form of liver disease. In fact, cirrhosis may decrease the clearance of drugs that are nonrestrictively eliminated in subjects with normal liver function, to the extent that it no longer approximates hepatic blood flow but is influenced to a greater extent by hepatic intrinsic clearance (22). By reducing first-pass hepatic metabolism, cirrhosis also may cause a clinically significant increase in the extent to which nonrestrictively eliminated drugs are absorbed. Because Q and Qp are both reduced in patients with severe cirrhosis, in whom portocaval shunting is most pronounced, hepatic clearance will be reduced more for nonrestrictively...
Cirrhosis occurs most frequently in the setting of alcoholic liver disease and represents the final common pathway of a number of chronic liver diseases. The development of cirrhosis is characterized by the appearance of fibroblasts and collagen deposition. This is accompanied by a reduction in liver size and the formation of nodules of regenerated hepatocytes. As a result, total liver content of cytochrome P450 is reduced in these patients. Initially, fibroblasts deposit collagen fibrils in the sinusoidal space, including the The deposition of fibrous bands also disrupts the normal hepatic vascular architecture and increases vascular resistance and portal venous pressure. This reduces portal venous flow that normally accounts for 70 of total liver blood flow (19). However, the decrease in portal venous flow is compensated for by an increase in hepatic artery flow, so that total blood flow reaching the liver is maintained at the normal value of 18 mL min kg in patients with either...
PSC is a chronic cholestatic disease characterized by obliterative fibrosis of the bile ducts, leading to biliary cirrhosis and liver failure. Survival models have been developed based on such variables as age, serum bilirubin, histologic stage, and presence or absence of splenomegaly. The natural history of this disease includes recurrent cholangitis, progressive jaundice, or cholangiocarcinoma. The latter complication is an absolute contraindication for LT. Cirrhosis due to hepatitis C virus (HCV) infection is now the most common indication of LT in Western Europe and the United States. Although recurrent HCV infection was suspected to be the cause of posttransplant hepatitis in many of these patients, the actual incidence of reinfection was indeterminate until the development of polymerase chain reaction (PCR) tests for HCV in the early 1990s. It has become clear that graft reinfection is universal after LT for HCV. Recent data show that, despite universal reinfection of...
Fulminant hepatic failure (FHF) is defined as acute liver failure complicated by encephalopathy in patients with no evidence of previous liver disease. Despite maximal medical supportive therapy, mortality rates in FHF approach 75 , depending on the cause of liver injury. Artificial liver support systems are currently experimental, undergoing controlled evaluations. In patients with FHF, the results of urgent LT have been remarkable. The evaluation of a patient with FHF for urgent LT depends on careful assessment of the prognosis for survival without LT. O'Grady and colleagues at the King's College Liver Unit (Gastroenterology 1989 97 439-445) found that the most important variables predicting prognosis included patient age, disease etiology, encephalopathy grade, duration of jaundice, admission serum bilirubin level, and prothrombin time. In patients with acetaminophen-induced FHF, arterial pH on admission and serum creatinine level were closely associated with prognosis. When the...
The clinical features of acute infection resemble those of the other viral hepatitides. The virus persists in approximately 5-10 of immunocompetent adults, and in as many as 90 of infants infected perinatally. Persistent carriage of hepatitis B, defined by the presence of hepatitis B surface antigen (HBsAg) in the serum for more than 6 months, has been estimated to affect about 350 million people worldwide, although not all carriers are infectious. Long-term continuing virus replication may lead to progression to chronic liver disease, cirrhosis and hepatocel-lular carinoma. Primary liver cancer is one of the 10 most
This is a condition that is recognized at birth but may occur in utero. It is characterized by heavy parenchymal iron deposition in several organs and irreversible liver failure. The only therapeutic option used to be liver transplantation. Neonatal haemo-chromatosis has been linked in some cases to the presence of a maternal factor, e.g. an antiribonuclear factor antibody. Infusions of gammaglobulin in pregnancy appear to reduce the severity of the condition and it has been proposed that the disease is due to an alloantibody (as rhesus incompatibility) but the target antigen is unknown. No mutations in the HFE gene are reported and chromosome 1q linkage has been excluded.
Gene have been excluded but mutations of the ferroportin gene may play a role (see above). Iron deposition, as in type 4 haemochromatosis, occurs both in hepatocytes and in reticu-loendothelial cells. Serum ferritin is usually elevated, but transferrin saturation may be normal. The condition occurs in sub-Saharan Africa. It is a cause of hepatic fibrosis and cirrhosis, and associations with diabetes mellitus, peritonitis, scurvy and osteoporosis have been described. The iron overload is associated with a poor outcome in tuberculosis, an infection that is highly prevalent in sub-Saharan Africa.
Between 50 and 80 of patients do not clear the virus by 6 months and develop chronic hepatitis. The rate of progression of chronic hepatitis is highly variable. Chronic hepatitis C infection leads to cirrhosis within two decades of the onset of infection in at least 20 of patients. Chronic infection is also associated with an increased risk of hepatocellular carcinoma, which occurs on a background of inflammation and regeneration related to chronic hepatitis over three or more decades. The risk of developing hepatocellular carcinoma is estimated at 1-5 after 20 years, but this varies considerably in different areas of the world. Hepatocellular carcinoma develops more commonly in men than in women.
Treatment with interferon a has been shown to yield good and sustained responses in 25-40 of selected patients. Studies indicate that younger patients without cirrhosis, with genotype 2 and 3 infection, are more likely to respond to treatment for several months than patients with genotype 1, and better response is obtained in patients with a lower viral load. Combination therapy with ribavirin, a synthetic guanosine nucleoside analogue, indicates that up to 50 of patients who have relapsed after treatment with interferon a have a sustained biochemical and virological response to combined treatment.
African Americans have excess death because of seven conditions. Excess deaths are defined as the number of deaths among minorities that would not have occurred had mortality rates for minorities equaled that of nonminorities. These conditions are (1) heart disease and stroke (2) homicide and accidents (3) cancer (4) infant mortality (5) cirrhosis (6) diabetes and (7) AIDS (U.S. Department of Health and Human Services,
When diuretic therapy does result in effective fluid removal in cirrhotic patients, it is associated with a very high incidence of adverse reactions. In one study of diuretic therapy in cirrhosis, furosemide therapy precipitated the hepatorenal syndrome in 12.8 , and hepatic coma in 11.6 , of the patients (56). Although daily doses of this drug did not differ, patients who had adverse drug reactions received total furosemide doses that averaged 1384 mg, whereas patients without adverse reactions received lower total doses that averaged 743 mg. Accordingly, when spironolactone therapy does not provide an adequate diuresis, only small frequent doses of loop diuretics should be added to the spironolactone regimen (55). Cirrhotic patients also appear to be at an increased risk of developing acute renal failure after being treated with angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs (57).
The liver can be affected by intrahepatic trapping of sickle cells, transfusion-acquired infection and transfusional haemosiderosis. Episodes of cholestasis due to intrahepatic sickling can lead to liver failure in rare instances. Pigmented gallstones are seen in two-thirds of patients, particularly those with HbSS, and can occur in young children. Patients with abdominal symptoms attributable to gallstones should undergo cholecystectomy, although the management of asymptomatic gallstones is less
Persons with chronic HBV infection serve as the primary source of infection for others (McQuillan et al., 1999 CDC, 2005). The majority of persons with chronic HBV infection are asymptomatic, and one third have no evidence of liver disease, despite high levels of viral replication (Lee, 1997). Chronic HBV infection can lead to cirrhosis and HCC. Lifetime risk of death from chronic liver disease or HCC is 15-25 (Beasley, Hwang, Lin, & Chien, 1981 Beasley, 1988 Chang et al., 1997 McMahon, 1997 McMahon, Holck, Bulkow, & Snowball, 2001). Rates of progression to cirrhosis and HCC are approximately 25 for persons who acquire infection during childhood and 15 for persons who acquire infection at older ages. Other factors that influence rates of progression include HBeAg status coinfection with HDV, HIV, HCV and alcohol abuse (Rizzetto, 1983 McMahon, 1997 Ockenga et al., 1997 Zarski et al., 1998 Monto & Wright, 2001 Gao, 2002). HBV-related liver disease and HCC cause approximately 4000-5000...
Imaging Abdominal ultrasound may identify a fixed lesion within a cirrhotic liver. CT scan or MRI is the gold standard for staging. Angiography If transarterial embolisation is being considered. Histology Ascites may be aspirated and sent for cytology. Staging Chest, abdomen and pelvic CT scans. Consider bone scan. M Medical Chemotherapy and radiotherapy have limited role as adjuvant therapy to surgery, but may be used to control unresectable disease temporarily. Examples of chemotherapeutic agents include doxorubicin and carboplatin. Surgical Liver resection is indicated if localised to a single lobe. Liver transplantation can be considered if the tumour is small and the liver cirrhotic. Embolisation Useful for single solitary lesions in cirrhosis. Ablation Useful to shrink tumours not amenable to resection. Radiofrequency, cryoablation, or percutaneous ethanol injection are used. C Biliary tree obstruction, acute liver failure, hepatic rupture and haemoperito-neum, reactive pleural...
HLT has been occasionally used in cases of fulminant liver failure (FHF), in which attempts at removal of the native liver led to prohibitive increases in intracranial pressure. In these cases, the liver is often implanted in a location different from the native liver location. HLT in FHF cases has the appeal of leaving the native liver in place, which may allow for late regeneration of the liver and eventual withdrawal of immunosuppression. Technical points that should be considered include reduction in graft size, graft perfusion with portal venous and
Shortly after the introduction of nucleoside analogue treatment for acquired immunodeficiency due to HIV infection, it became clear that some patients receiving AZT (azydothymidine) developed a mitochondrial myopathy due to mtDNA depletion. mtDNA is replicated by pol y, which is inhibited by a variety of nucleoside analogues (part of the HAART, or highly active anti-retroviral therapy regime) (Lewis et al., 2003). Acute and subacute nucleoside toxicity can be life-threatening, due to the lactic acido-sis and liver failure. A number of studies have described mtDNA depletion in peripheral blood immediately preceding the clinical deterioration, raising the possibility that measuring mtDNA levels (relative to a single copy nuclear gene), might be used to monitor therapy and prevent fatal complications (de Mendoza et al., 2004) or the more chronic complications such as lipodystrophy (McComsey et al., 2005b). However, not all studies are in agreement, and it may be necessary to study a...
And removal of large portions of the bowel results in malabsorption even after they have recovered. Occasionally, the injury is so extensive, that the small amount of intestines left is insufficient for growth and development or incompatible with life. Long-term morbidities can include ileostomy, colostomy, repeated surgical procedures, prolonged parenteral nutrition, liver failure, poor nutrition, malabsorption syndromes, failure to thrive, and multiple hospitalizations.
An important part of advising any immunocompromised traveler is providing detailed education about the risks of their particular journey. They should know how some risks could be avoided, such as receiving advice about drinking water, and they should be instructed about when and how to seek medical help. There are few absolute contraindications to their travel plans, however each person should be counseled on an individual basis. Attention to PPD skin testing upon return of all travelers who spend time in endemic regions for tuberculosis is of paramount importance. Other chapters in this book are dedicated to an approach to other important immunocom-promised groups, such as pregnant travelers, and HIV-infected travelers (Mileno and Bia, 1998). Here we address an approach to persons with immunologic compromise from asplenia, transplantation, cancer chemotherapy, high-dose corticosteroid use, diabetes mellitus, and chronic renal or liver failure.
Acute fatty liver of pregnancy (AFLP) is a condition characterized by microvesicular fatty infiltration of the liver, developing in the latter half of pregnancy. The incidence is approximately 1 12,000 deliveries. Clinical disease severity varies with some patients having only mild right-upper quadrant discomfort associated with prodromal nausea and vomiting. Others develop fulminant liver failure leading to coma. A depressed level of consciousness may arise from either hypoglycemia or the onset of hepatic encephalopathy. Hypoglycemia is a common feature of AFLP and should alert the clinician to the possible diagnosis. More than 50 of affected patients will have mild hypertension and pro-teinuria, making the distinction from HELLP syndrome difficult. Jaundice is often present at the time of diagnosis. Liver enzymes are increased and transaminases may rise above 1000 IUl 1 in severe cases. Liver failure leads to severe coagulo-pathy and a prolonged partial thromboplastin time and INR....
In patients with normal liver function, safe hepatic resection should preserve at least 25 of total hepatic volume in patients submitted to per-operative chemotherapy with chronic liver disease at least 40 of total liver volume should be preserved due to a higher risk of post-operative liver failure 50, 51 . When planned resection exceeds these values, peroperative PVE may be utilised to reduce the risk of post-operative liver failure. PVE was described for the first time in 1990 by Makuuchi et al. 52 .
Core biopsy is a method of obtaining a sample which is suitable for histological analysis as is required for assessment of lymphoma, prostate, diffuse liver disease (cirrhosis) or where FNAB has failed to establish a diagnosis. The biopsy needle is inserted using ultrasound guidance to the edge of the lesion before taking the sample. Automated guns are most often used to take the sample. The throw of the biopsy needle varies - this is the distance (once fired) the needle advances into the lesion. 315
Of functional small bowel by surgically bypassing a large segment of it. Various surgical configurations have been devised to achieve this goal. The radiographic findings will vary depending on which type of operation has been performed. By 1980, however, the JIB had been generally abandoned owing to the development of serious late complications in a fairly high percentage of patients. These included diarrhea, electrolyte disturbances, nephrolithiasis, cholelithiasis, liver abnormalities, and cirrhosis.
Drug therapy in patients with advanced cirrhosis is further complicated by the fact that renal blood flow and glomerular filtration rate are frequently depressed in these patients in the absence of other known causes of renal failure. This condition, termed the hepatorenal syndrome, occurs in a setting of vasodilation of the splanchnic circulation that results in underfilling of the systemic circulation. This activates pressor responses, causing marked vasoconstriction of the renal circulation (44). The functional nature of this syndrome is indicated by the observations that it reverses following successful liver transplantation and is not accompanied by significant histological evidence of kidney damage. Gin s et al. (45) monitored 234 patients with cirrhosis, ascites, and a glomerular filtration rate (GFR) of more than 50 mL min. These authors found that the hepatorenal syndrome developed within 1 year in 18 , and within 5 years in 39 , of these patients. Although the Pugh score was...
Severe pre-eclampsia is also associated with an increased risk of maternal mortality (0.2 ), and increased rates of maternal morbidity (5 ) with conditions such as convulsions, intracranial hemorrhage infarction, pulmonary edema, acute renal or liver failure, liver hemorrhage, pancreatitis, and disseminated intravascular coagulopathy (DIC). These complications are usually seen in women who develop pre-eclampsia before 32 weeks' gestation and in those with pre-existing medical conditions (Sibai, 2003).
Hepatic disease and damage clearly have the potential to be major factors in the metabolism of foreign compounds. Thus, in patients with liver necrosis due to paracetamol, the half-life of the latter was increased from 2 to 8 h and that of antipyrine from 12 to 24 h. Acute hepatic necrosis in animals caused by the administration of hepatotoxins resulted in the plasma half-lives of barbiturates, diphenylhydantoin and antipyrine being approximately doubled. However, there may be several factors operating such as displacement of a drug from plasma-protein binding sites by bilirubin. In liver damage, plasma-bilirubin levels may be high due to lack of conjugation with glucuronic acid. This may alter elimination of some drugs such as tolbutamide. The level of plasma albumin may often be reduced by liver disease as this is the site of synthesis of albumin, the hence binding to plasma albumin will tend to be reduced. However, the effects of liver disease can be somewhat unpredictable. For...
In the porta hepatis, separated from the gallbladder and communicated with the biliary ductal system (to differentiate extrahepatic biliary atresia) (Fig. 1.78). Complications include cholelithiasis, choledocholi-thiasis, pancreatitis, malignant degeneration, and cirrhosis.
Hepatic Artery Thrombosis and Stenosis. Approximately 4 of transplant recipients develop hepatic artery thrombosis, and half the time this occurs in patients with long-term follow-up. Risk factors for hepatic artery thrombosis include pediatric cases (because of small vessel size), vascular reconstructions (such as for a donor accessory right hepatic artery originating from the superior mesenteric artery), anastomotic technical imperfections, intimal injuries (such as from clamping, traction, or long cold ischemia), poor inflow, and high outflow resistance (such as during rejection or other forms of allograft dysfunction). Recently, more attention is being paid to the role of hypercoagulable states predisposing to hepatic artery thrombosis. Hepatic artery thrombosis presents with a spectrum of manifestations ranging from insidious allograft dysfunction to overt hepatic necrosis with fulminant liver failure. The most common presentation involves biliary complications,...
The indications for resection of hepatic metastases are obtained from the analysis of the prognostic elements described above. The pre-operative evaluation of the patient should consider general examinations for abdominal general surgery and evaluation of liver function 36 . In patients with normal liver function, resections of 70-80 of the total hepatic mass can be safely performed. In patients submitted to per-oper-ative chemotherapy or with chronic liver disease, resection should be limited to 50-60 of total liver volume to reduce the risk of post-operative liver failure. Perihepatic abscesses Liver failure Post-operative bleeding Renal failure Portal thrombosis
Dysregulation of cytotoxic - and or NK-cell function - can cause tissue damage during infection, often with bone marrow failure. For example, the dramatic expansion of CD8 cytotoxic T cells in X-linked lymphoproliferative syndrome (XLP) during Epstein-Barr virus (EBV) infection may cause acute liver failure,
The last three decades have witnessed an explosion in knowledge of viral hepatitis, a major public health problem throughout the world affecting several hundreds of millions of people. Viral hepatitis is an important cause of morbidity and mortality, both from acute infection and chronic sequelae which include, with hepatitis B, hepatitis C and hepatitis D (delta) infection, chronic active hepatitis and cirrhosis, and primary liver cancer with hepatitis B and hepatitis C. The hepatitis viruses include a range of unrelated human pathogens.
To cirrhotic patients with ascites actually impairs rather than promotes sodium excretion (58). Since coagulation disorders are common in patients with advanced cirrhosis, alternatives should be sought for therapy with -lactam antibiotics that contain the N-methylthiotetrazole side chain (e.g., cefotetan), which inhibits g-carboxylation of vitamin K-dependent clotting factors (57). TABLE 7.6 Some Drugs Requiring at Least a 50 Dose Reduction in Patients with Moderate Cirrhosis Parameter values or changes in cirrhosis TABLE 7.6 Some Drugs Requiring at Least a 50 Dose Reduction in Patients with Moderate Cirrhosis Parameter values or changes in cirrhosis
Cardiac failure accounts for a 7-21 mortality rate after liver transplantation. Therefore, recognition and proper treatment of cirrhotic cardiomyopathy are essential. Such dysfunction can occur independent of prior alcohol abuse. It may be missed by standard echocardiographic techniques. The liver transplantation procedure, with its attendant hemodynamic and volume shifts, stresses the heart significantly. Acid-base abnormalities, hypothermia, and electrolyte disturbances can also affect myocardial function. As the hyperdynamic physiology of cirrhosis is corrected postprocedure, vasoconstriction causes increased afterload and may precipitate heart failure. Management strategies include diuretics, salt restriction, afterload reduction, and possibly mechanical ventilation. Cirrhotic cardiomyopa-thy may improve after liver transplant.
The goal of immunosuppression in transplant patients is to prevent acute and chronic rejection of the transplanted organ, while avoiding opportunistic infections and the adverse effects of immunosuppressive therapy (see Fig. 17.1). Combinations of immunosuppressants are used to affect different immune-system activators and to provide immunosuppressive synergy, using the lowest effective doses of immunosuppressants to reduce the potential for adverse drug events and drug interactions. Superiority of one regimen over another has not been demonstrated, and immunosuppressive protocols are largely program-specific. Familiarity with the immunosuppressants used in a particular programs' protocol is critical, along with a concordant understanding of therapeutic drug monitoring through serum levels and graft evaluation, adverse drug reaction monitoring, and judicious use of auxiliary medications that prevent and treat the consequences of immunosuppression. However, regimens should be flexible...
Urea and ammonia removal are needed m kidney failure, liver failure, environmental decontamination and regeneration of water supply in space travel. Standard dialysis machines are usually complex and expensive. Several alternatives have not been sufficiently effective. Prakash and Chang therefore studied the use of bioencapsulated genetically engineered E coli DH5 cells containing K. aerogens urease gene (26,27). The bioencapsuiation of the genetically engineered bacteria was prepared by the general procedure using the apparatus assembly shown m Fig. 1. The details of the bioencapsuiation process parameters are described m Section 5.
In the percentage of subjects with either raised serum transaminase activity or fibrosis cirrhosis in the C282Y homozygous group. Furthermore, population surveys have shown that less than 5 of subjects homozygous for C282Y ever receive a diagnosis of haemochromatosis. Despite much debate about ascertainment bias in family and population surveys, it is becoming clear that most men who are homozygous for C282Y will have a raised transferrin saturation before the age of 30 years a proportion will have an elevated serum ferritin concentration, but only a minority will eventually develop fibrosis and cirrhosis of the liver. Only about 50 of homozygous women have a raised transferrin saturation, and progression through iron accumulation and tissue damage is usually, but not always, slower. In one population study in the USA, the clinical penetrance was estimated to be as low as 1 .
Peritonitis is often secondary to perforated appendicitis. Primary bacterial peritonitis is an inflammatory process ofthe peritoneum without an identifiable intraabdominal source. Although this rare entity has been typically associated with underlying systemic processes such as nephrotic syndrome, liver failure, and the presence of ventriculoperitoneal shunt catheter, primary bacterial peritonitis may also occur in otherwise healthy children. The sonographic and CT finding of complex ascites is relatively nonspecific, most commonly thought to be associated with perforated appendicitis. However, when the imaging findings of peritonitis are disproportionately greater than the degree of abnormal appendiceal changes or are associated with non-visualization of the appendix, the diagnosis of primary bacterial peritonitis should be considered in addition to that of perforated appendicitis. The diagnosis can be confirmed by paracentesis and demonstration of a single species of gram-positive...
There is evidence that 50-80 or more of infections with HCV progress to chronic liver disease. Histological examination of liver biopsies from asymptomatic 'healthy' blood donor carriers of HCV show that none has normal liver histology and up to 70 have chronic active hepatitis and or early cirrhosis. Histological changes at the time of the first biopsy in patients with biochemical chronic hepatitis C also show chronic active hepatitis in the majority. Characteristic histological changes include heavy lymphocytic infiltration in the portal and periportal areas. Progression to cirrhosis is common, and in a number of countries such as Japan, progression to hepatocellular carcinoma is an important feature of chronic hepatitis C. The mechanism underlying carcinogenesis is likely to be associated with the process of fibrosis and regeneration of liver cells, as there is no DNA intermediate in the replication cycle of HCV or integration of viral nucleic acid.
Folate deficiency causes reduced regeneration of cirrhotic liver. Patients with gluten-induced enteropathy and those with sickle cell anaemia have also been reported to show stunted growth, which has been improved coincidentally with commencement of folic acid therapy, but it is not certain how much the growth improvement in these children was due to folic acid and how much to other, simultaneously administered vitamins. In the fragile X syndrome, sister chromatid exchange and DNA breaks are increased in vitro in a folate-deficient medium, apparently at the Xq28 site. No in vivo abnormality of folate metabolism can be detected.
Acute hepatitis is an inflammatory condition of the liver that is caused by viruses or hepatotoxins. In acute viral hepatitis, inflammatory changes in the hepatocyte are generally mild and transient, although they can be chronic (chronic active hepatitis) and severe, resulting in cirrhosis or death. Blaschke and Williams and their colleagues (12-15) have conducted informative studies of the effects of acute viral hepatitis on drug disposition. These investigators used a longitudinal study design in which each of a small number of patients was studied initially during the time that they had acute viral hepatitis and subsequently after recovery (Table 7.1). The drugs that were administered included phenytoin (12), tolbutamide (13), warfarin (14), and lidocaine (15). The most consistent significant finding was that the plasma protein binding of both phenytoin and tolbu-tamide was reduced during acute hepatitis. For both drugs, this was partly attributed to drug displacement from protein...
In the well-transfused child, early growth and development are normal and splenomegaly is minimal. However, without adequate iron chelation therapy, there is a gradual accumulation of iron and the effects of tissue siderosis start to appear by the end of the first decade. The adolescent growth spurt fails to occur and hepatic, endocrine and cardiac complications of iron overloading produce a variety of complications, including diabetes, hypoparathyroidism, adrenal insufficiency and progressive liver failure. Secondary sexual development is delayed, or does not occur at all. The short stature and lack of sexual development may lead to serious psychological problems. By far the commonest cause of death, which usually occurs towards the end of the second or early in the third decade, is progressive cardiac damage. Ultimately, these patients die either in protracted cardiac failure or suddenly due to an acute arrhythmia, often precipitated by infection.
Popular and has well proven efficacy 3-5 . Intolerance resulting from a necessarily large volume of oral water intake (41) may appear occasionally in a group of patients. The symptoms include nausea, discomfort, vomiting, abdominal pain and distension 6, 7 . Sodium phosphate is equally effective with the benefit of no adverse events 7, 8 , but causes a huge electrolyte imbalance, sodium phosphate should not be used in patients with chronic renal failure, cirrhosis of the liver, advanced heart failure and in patients with symptoms of ascites 9 . Patients tolerate sodium phosphate better but polyethylene glycol was proved to be safer.
Local recurrence, and hepatic disease can be eradicated with a resection margin of 5 mm, leaving at least three normal hepatic segments (or more if cirrhosis). Infections Occasionally need resection (e.g. hydatid cysts). Live-related liver donation Involving partial resection from donor and transplantation of the resected portion into the recipient. Patients need to be selected through very strict eligibility criteria. Imaging CT, MRI, USS may be necessary for staging and planning resections. Pre-op liver function score For example, Childs-Pugh scoring (based on bilirubin, albumin, prothrombin time, presence of encephalopathy or ascites) cirrhosis precludes large resections due to the limited reserve of the residual cirrhotic liver. Haemorrhage, biliary leakage, liver failure, sepsis (biliary or peritonitis), associated pulmonary complications (e.g. pleural effusion).
Chest wall lesions (following chest surgery, herpes zoster, nipple piercing) as well as prolonged nipple stimulation can increase serum PRL levels as well as cause galactorrhea. This occurs via a reduction in hypothalamic dopamine. Notably, routine breast exams are not associated with increased PRL. Chronic renal failure, due to a decreased clearance of PRL, can result in hyperprolactinemia. Renal transplant reverses it. Forty percent of patients with hypothyroidism have mildly elevated PRL levels, due to the increase in thyroid releasing hormone, which is also a PRL releasing factor. Some rare causes of ectopic hyperprolactinemia include small cell carcinoma of the lung as well as colorectal cancer. Liver cirrhosis can also cause an elevation of PRL, possibly secondary to decreased clearance.
Hepatitis C infection is on the rise. Travel-associated risks include exposure to blood that has not been screened, sexual transmission, tattooing and occupational exposures of volunteer health care workers or missionaries to blood products or contaminated needles used for administration of medications or intravenous drug use. There is no evidence that pregnancy alters the natural history of hepatitis C or that it interferes with normal pregnancy, unless the woman already has cirrhosis and its associated complications (Reinus and Leikin, 1999). Vertical transmission is uncommon. Pregnant travelers should be advised of at-risk behaviors to decrease risk of infection. Immune globulin is not thought to be effective postexposure.
An amino sugar which causes hepatic damage similar to viral hepatitis (non-zonal) and focal necrosis. It may also cause cirrhosis and tumours. It causes inhibition of DNA and protein synthesis. Levels of UTP and UDP-glucose fall and other UDP-hexosamines and acetylhexosamines rise. Galactosamine forms UDP-galactosamine which leads to depletion of UTP so synthesis of RNA and protein are disrupted. Abnormal membrane glycoproteins may be produced leading to membrane damage. Ethionine. An hepatotoxic analogue of methionine causing fatty liver (accumulation of triglycerides). Chronic exposure causes cirrhosis, bile duct proliferation and heptatocellular carcinoma. It forms S-adenosyl ethionine which traps adenosyl leading to ATP depletion which reduces triglyceride export from the liver. It also leads to ethylated bases in DNA.
Differential diagnosis for CE includes benign cystic lesions, cavitary tuberculosis, mycoses, abscesses and benign or malignant neoplasms in the case of MAE, it is important to eliminate hepatic carcinoma and cirrhosis, which have similar clinical presentations (Schantz, 1997).
The direct interface between man and bioreactors represents another significant challenge in the bioreactor field. On one hand, the patient is increasingly viewed as a potential in vivo bioreactor, providing an optimal environment for cell growth and differentiation to yield neotissues (Warnke et al., 2006). There also are circumstances in which a bioreactor may serve as a bioartificial organ, attached directly to a patient's circulation. The most significant case is the effort to develop a bioartificial liver that can be used to sustain life during acute liver failure, until the patient's endogenous organ regenerates or can be replaced by orthotopic transplantation (Jasmund and Bader, 2002 Sauer et al., 2001, 2003). Most designs to date have focused on the use of hollow-fiber bioreactors seeded either with human hepatic lineage cell lines or xenogeneic (e.g., porcine) hepa-tocytes. Despite intensive efforts, leading to at least nine clinical trials, no bioartificial liver assist...
Two-stage hepatectomy should not be considered when radical resection is not possible even with the second liver resection. The aim of this procedure is to reduce the risk of post-operative liver failure, as the second liver resection is performed only after adequate hypertrophy of remnant liver.
Arroyo V, Gines P, Gerbes AL, Dudley FJ, Gentilini P, Laffi G, Reynolds TB, Ring-Larsen H, Scholmerich J. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis International Ascites Club. Hepatology 1996 23 164-176. Bernard B, Lebrec D, Mathurin P, Opolon P, Poynard T. Propranolol and sclerotherapy in the prevention of gastrointestinal rebleeding in patients with cirrhosis A meta-analysis. J Hepatol 1997 26 312-324. D'Amico G, Morabito A, Pagliaro L, Marubini E. Survival and prognostic indicators in compensated and decompensated cirrhosis. Dig Dis Sci 1986 31 468-475. Hillaire S, Labianca M, Borgonovo G, Smadja C, Grange D, Franco D. Peritoneovenous shunting of intractable ascites in patients with cirrhosis Improving results and predictive factors of failure. Surgery 1993 113 373-379. Kim WR, Wiesner RH, Therneau TM, et al. Optimal timing of liver transplantation for primary biliary cirrhosis. Hepatology 1998 28(l) 33-38. Kleber G, Sauerbruch...
Chemical estimation is the gold standard but can be inaccurate if fibrosis is present. Levels 15 mg g dry weight have been associated in DFX-treated patients with a high risk of cardiac disease, liver fibrosis and cirrhosis. Levels between 7 and 15 mg g dry weight are associated with liver damage only if there is also hepatitis C infection and have been considered relatively safe from cardiac disease but associated with damage to the endocrine organs. Levels less than 7 mg g are found in carriers of haemochromatosis.
3 Protein alterations, especially increased globulin levels with reduced albumin, result in an alteration in colloid cellular osmotic pressure. This has been suggested as a factor in tropical splenomegaly and in cirrhosis. In blood dyscrasias, the increase in plasma volume is directly proportional to the size of the spleen, less so in cirrhosis.
Endoscopic management of biliary strictures is aimed at preventing complications of strictures such as choledocholithiasis, cholangitis, and biliary cirrhosis, while avoiding the need for surgery. Stricture dilation using balloon dilators is performed. Subsequently, stent placement is performed.
Because of the liver's many functions, contaminants can act in a variety of ways to cause liver injury. The principal types of liver damage are necrosis (tissue destruction), cirrhosis (hardening of tissue), and the accumulation of abnormal amounts of fat. A particularly important function of the liver from the standpoint of poisons is the detoxification of compounds by transforming them into a more water-soluble form. Whereas this is an important protection mechanism for some compounds, others that are relatively benign in their administered form can be transformed into more toxic species. This process, known as metabolic activation,
Jaundice, ascites and encephalopathy are manifestations of hepato-cellular decompensation and are unusual in pure schistosomiasis (Elliott, 1996b). Because patients with portal hypertension secondary to schistoso-miasis tolerate episodes of variceal bleeding much better than those with cirrhosis, repeated non-fatal episodes of bleeding are common (Raia et al., 1984). In addition, asymptomatic infection, e.g. travelers, should be actively screened for. Suspicion should be particularly high in an individual with esophageal varices, hepatic enlargement and normal liver function tests (El Rooby, 1985 Raia et al., 1984). Most other etiologies for bleeding varices result in small cirrhotic livers, elevation in transaminases and low serum albumin. Travel history, history of contact with fresh water, skin rash or acute febrile episodes should be specifically elicited. A definitive diagnosis is made by identification of the characteristic schistosome eggs in feces,...
It is a very lipid-soluble compound and is consequently well distributed throughout the body, but despite this its major toxic effect is on the liver, irrespective of the route of administration. It should be noted that it does have other toxic effects, and there are species and sex differences in toxicity. Chronic administration or exposure causes liver cirrhosis, liver tumours and also kidney damage. The reason for the liver being the major target is that the toxicity of carbon tetrachloride is dependent on metabolic activation by the cytochromes P-450 system. Therefore, the liver becomes the target as it contains the greatest concentration of cytochromes P-450, especially in the centrilobular region which is where the damage is greatest. Low doses of carbon tetrachloride cause only fatty liver and destruction of cytochromes P-450. Interestingly, a low dose of carbon tetrachloride protects the animals against the hepatotoxicity of a subsequent larger dose due to...
Preoperative, routine computed tomography (CT) scan evaluation is useful in determining the presence of ascites, varices, and other signs of portal hypertension, liver volume, and focal or diffuse lesions. CT arterial portography has aided in detecting liver neoplasms, especially metastases. However, its usefulness in liver transplantation has been limited due to altered hepatic hemodynamics secondary to cirrhosis, and it requires placement of a selective catheter in the splenic or superior mesenteric arteries. Three-dimensional, helical CT angiography (CTA) is a noninvasive technique that is useful to evaluate the normal and variant arterial supply of the liver. The need for intravenous (IV) conventional radiographic contrast may limit the use of CT scan techniques in patients with renal insufficiency or contrast allergies.
Some cases have presented with anaemia and or jaundice at birth, and this should be considered in the evaluation of nonimmune hydrops fetalis. The clinical manifestations include a variable degree of jaundice, hepatomegaly and splenomegaly, cirrhosis, and diabetes, even in patients who have neither been transfused nor treated with iron. A few patients have been mentally retarded. The serum iron and transferrin saturations are increased.
Cirrhosis (81 ), including SBP acute hepatitis cirrhosis (AFTP 2.5 g dl) If portal hypertensive etiology, consider standard cirrhosis w u (see Cirrhosis ) Hepatorenal syndrome (see Cirrhosis ) Etiologies cirrhosis, neoplasm (pancreas. HCC). intra-abdominal inflammation infection.
Ethionine is a hepatotoxic analogue of the amino acid methionine (figure 7.41). Ethionine is an antimetabolite which has similar chemical and physical properties to the naturally occurring amino acid. After acute doses ethionine causes fatty liver but prolonged administration results in liver cirrhosis and hepatic carcinoma. Some of the toxic effects may be reversed by the administration of methionine. The effects may be produced in a variety of species, athough there are differences in response. The rat also shows a sex difference in susceptibility, the female animal showing the toxic response rather than the level. Initially the fat droplets accumulate on the endoplasmic reticulum in periportal hepatocytes and then in more central areas of the liver. Some species develop hepatic necrosis as well as fatty liver, and nuclear changes and disruption of the endoplasmic reticulum may also be observed. Chronic administration causes proliferation of bile duct cells leading to hepatocyte...
D-Galactosamine is an amino sugar (figure 7.40a) normally found in vivo only in acetylated form in certain structural polysaccharides. Administration of single doses of this compound to certain species results in a dose-dependent hepatic damage resembling viral hepatitis, with focal necrosis and periportal inflammation. As well as a reversible hepatitis after acute doses, galactosamine may also cause chronic progressive hepatitis, cirrhosis and liver tumours. As all the liver cells are affected the damage tends to be diffuse throughout the lobule. A number of biochemical events have been found to occur. RNA and protein synthesis are inhibited, membrane damage can be observed 2 h after dosing. Thee is also an increase in intracellular calcium which may be the crucial event which leads to cell death (see Chapter
Liver failure may arise from conditions that mimic pre-eclampsia such as thrombotic throm-bocytopenic purpura and acute fatty liver of pregnancy (see below) (Atlas et al., 1982 Kaplan, 1985). Obstetric cholestasis and viral hepatitis may also enter the differential diagnosis in milder cases of HELLP syndrome. Distinguishing between these conditions may be difficult but the hallmark
Many patients have a mild degree of encephalopathy, which is of little concern. Severe encephalopathy places patients at risk for aspiration due to depression of protective airway reflexes. In severe liver failure, especially fulminant hepatic failure, patients are at risk for cerebral edema and elevated intra-cranial pressure (ICP). ICP monitoring and treatment may be necessary preopera-