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Lithium orotate in the treatment of alcoholism and related conditions.

The subjects were 42 alcoholic patients (33 males and 9 females) who were treated with lithium orotate during an alcohol rehabilitation program in a private clinical setting for at least six months. They derive from a total number of 105 patients who received this treatment initially, while the remainder discontinued the treatment within six months. The data were collected from a private practice record and the follow-up varied between six months and 10 years. The 42 patients studied displayed a multitude of complaints in addition to chronic alcoholism. These included liver dysfunction, seizure disorders, headaches, hyperthyroidism, affective disorders. Meniere's syndrome, liver and lung cancers. Thirty-six of the 42 patients studied had been hospitalized at least once for the management of their alcoholism. Lithium orotate was given, 150 mg daily, with a diet low in simple carbohydrates and containing moderate amounts of protein and fat. In addition, calcium orotate (for hepatic involvement), magnesium orotate, bromelaine, and essential phospholipids (for cardiac problems), and supportive measures were instituted, if required. Lithium orotate proved useful as the main pharmacologic agent for the treatment of alcoholism. Ten of the patients had no relapse for over three and up to 10 years, 13 patients remained without relapse for 1 to 3 years, and the remaining 12 had relapses between 6 to 12 months. Lithium orotate therapy was safe and the adverse side effects noted were minor, i.e., eight patients developed muscle weakness, loss of appetite or mild apathy. For these patients, the symptoms subsided when the daily dose was given 4 to 5 times weekly.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

Advances in prevention and treatment of hepatic disorders following hematopoietic cell transplantation.

Development of jaundice is an ominous prognostic sign, whether it occurs early or late in the months following hematopoietic cell transplant. In the first weeks after transplant, the dominant causes of liver injury are Sinusoidal Obstruction Syndrome (toxic damage resulting from myeloablative conditioning regimens) and cholangitis lenta (cholestasis of sepsis). Later after transplant, cholestasis is more commonly caused by acute graft-vs.-host disease and drugs. Hepatic infections have become uncommon because of the use of prophylactic anti-fungal and anti-viral drugs. Treatment of severe liver dysfunction is often futile in this setting, but prevention of liver injury is feasible. Hepatic sinusoidal injury can be prevented by avoiding sinusoidal toxins as part of conditioning therapy in patients at high-risk. Cholestatic liver damage can be minimized by prophylactic use of ursodiol and by careful drug monitoring. Anti-microbial drugs will prevent most fungal liver infections and viral hepatitis caused by herpesviruses and hepatitis B virus.

Drug Monitoring↗

Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial.

BACKGROUND/AIMS: Silymarin has protective effects in different experimental conditions, but its efficacy in human liver cirrhosis has not been completely established. Therefore, this study was carried out to determine the effect of silymarin in alcoholics with liver cirrhosis with respect to survival and clinical and laboratory changes. METHODS: From February 1986 to June 1989, we enrolled 200 alcoholics with histologically or laparoscopically proven liver cirrhosis in a randomized, double-blind multicenter trial comparing 450 mg of silymarin (150 mg/ three times per day) with placebo. The primary outcome was time to death, and the secondary outcome was the progression of liver failure. Additional analyses were also performed in 75 patients in whom anti-hepatitis C virus antibodies were measured after completion of the trial. RESULTS: One hundred and three patients were assigned to receive silymarin and 97 to receive placebo. The two groups were well matched for demographic and baseline clinical and laboratory features. A 2-year study period was completed in 125 patients (57 receiving silymarin and 68 receiving placebo). Twenty-nine patients (15 receiving silymarin, and 14 receiving placebo) died during the trial. Survival was similar in patients receiving silymarin or placebo. The effect of silymarin on survival was not influenced by sex, the persistence of alcohol intake, the severity of liver dysfunction or by the presence of alcoholic hepatitis in the liver biopsy. Silymarin did not have any significant effect on the course of the disease. No relevant side-effects were observed in any group. CONCLUSIONS: The results of this study indicate that silymarin has no effect on survival and the clinical course in alcoholics with liver cirrhosis.

Adult↗

Feline hepatic lipidosis.

Hepatic lipidosis occurs when lipid mobilized to the liver exceeds lipid leaving the liver via formation of very-low-density lipoproteins or by oxidation. Hepatic lipidosis in cats is associated with overt liver dysfunction. In affected cats, excess lipid is mobilized to the liver because of starvation. Removal of hepatic lipid may be impaired because of protein malnutrition, a relative carnitine deficiency, or oxidative damage to peroxisomes and other hepatic organelles. Hepatic lipidosis occurs in adult cats, and is manifest by signs of weight loss, depression, vomiting, and icterus. Diagnosis is achieved by evaluating laboratory and diagnostic imaging data, in conjunction with a liver biopsy. Aggressive tube feeding is the treatment of choice. With this treatment, survival rates are 60% to 80%.

Animals↗

Wernicke encephalopathy presented in the form of postoperative delirium in a patient with hepatocellular carcinoma and liver cirrhosis: a case report and review of the literature.

OBJECTIVE: Although Wernicke encephalopathy has been reported in the oncological literature, it has not previously been reported in postoperative cancer patients. METHODS: In this communication, we report a patient of hepatocellular carcinoma with liver cirrhosis who developed Wernicke encephalopathy in the form of postoperative delirium. Preoperatively, the patient had a very good appetite and had eaten all the food of an 1800 cal/day diet until 1 day before operation. The operation was done without any complications. The patient developed delirium 2 days after the lobectomy of the liver. The level of delirium remained unchanged until administration of thiamine starting on day 7 postoperatively, which resulted in palliation of delirium without brain damage. Laboratory data demonstrated that the serum thiamine level at day 6 postoperatively was below the lower limit of normal. As the mechanism of Wernicke encephalopathy, we thought that decreased ability to store thiamine due to liver cirrhosis led to depletion of thiamine faster than had been expected. RESULTS AND SIGNIFICANCE OF THE RESEARCH: In cancer patients, clinicians must always remain aware of the possibility of Wernicke encephalopathy, especially in patients with liver dysfunction, which decreases the ability to store thiamine in the liver. Early detection and intervention may alleviate the symptoms of delirium and prevent irreversible brain damage.

Aged↗

Enteroviral hepatitis in children.

BACKGROUND: The pathogen causing enteroviral hepatitis is often not found despite careful examination. METHODS: This study investigates the enterovirus genome in serum and liver tissue obtained from patients who showed abnormal liver function without negative data of usual studies and cytomegalovirus (CMV) serologically positive cases.' RESULTS: Nine out of 21 serum samples were positive by using reverse transcriptase-polymerase chain reaction (RT-PCR) for enterovirus. The 21 samples had CMV-IgM antibodies in five cases. These CMV serologically positive cases were all negative for enterovirus using RT-PCR. Therefore, nine out of 16 (60%) were of unknown etiology. Some cases showed liver dysfunction over a period of more than 6 months. The liver function revealed that all cases finally improved. The sequences coincided with those of Coxsackie B5 or B6 with the highest score by gene homology search. The liver pathology revealed that two of three subjected cases had mild fibrosis and small cell infiltration. RT-PCR of liver tissue for enterovirus were positive in all three cases comparing the house keeping gene. The viral load was high in acute phase and low in convalescent phase. CONCLUSIONS: In more than half of children with illnesses of unknown etiology, the pathogen was found to be enteroviruses, and RT-PCR and quantification of serum is an easy method to identify these diseases.

Child, Preschool↗

[Plasma-androgens following oral administration of testosterone. Influence of sex, age, and liver function (author's transl)].

The influence of sex, age, and liver function on the androgenmetabolizing capacity of the liver was investigated. To that end, testosterone was administered orally to healthy men, women and prepubertal boys as well as to men with liver dysfunction. While normal men (n = 17) and men with fatty liver (n = 9) showed no rise in circulating plasma testosterone levels and only a slight increase in androstenedione, a steep increase in both steroids was observed in men with liver cirrhosis (n = 7). Unlike adult men, boys (n = 7) and women (n = 6) also showed elevated testosterone levels after oral administration of this steroid. It is concluded that the hepatic capacity to metabolize testosterone is influenced by sex, stage of development, and liver function. It seems possible that peripheral concentration of testosterone after its oral administration can serve as a clinical test for liver function.

Administration, Oral↗

Diagnosis and therapy of alcoholic liver disease.

Alcoholic liver disease (ALD) presents considerable challenges to clinicians. Screening for alcohol abuse and alcoholism should be routine and repeated annually with close attention to signs and symptoms of liver disease. In patients with evidence of liver dysfunction or injury, consideration should be given to performance of liver biopsy for diagnosis and prognosis and prior to initiation of medication with the potential for significant side effects. Therapy depends on the spectrum of pathological liver injury: alcoholic fatty liver, alcoholic hepatitis, and cirrhosis. Abstention is the foundation of therapy for an alcohol problem. Alcoholic fatty liver should improve with abstention, but the similarity to the pathogenesis of nonalcoholic fatty liver and potential for progressive injury merits consideration of lipotropic agents. The continuing mortality, poor acceptance of corticosteroids, and identification of tumor necrosis factor-alpha (TNF-alpha) as an integral component has led to studies of pentoxifylline and, recently, anti-TNF antibody to neutralize cytokines in the therapy of severe alcoholic hepatitis. Antioxidant therapy of alcoholic cirrhosis has significant promise but will require large clinical trials.

Adrenal Cortex Hormones↗

Rats made cirrhotic by chronic CCl4 treatment still exhibit anticipatory activity to a restricted feeding schedule.

Food entrainment of clock genes in the liver suggests that this organ may underlie a food entrained oscillator (FEO), which manifests under restricted feeding schedule (RFS). In order to test the importance of a functional liver for the expression of FEO, chronic CCl4-treated cirrhotic rats and oil-treated controls were entrained to RFS and drinking behavior was continuously monitored. After 20 d of free-running conditions, food access was restricted to 2 h, followed by a refeeding-fasting protocol to test persistence of anticipatory drinking. Present data show no differences between groups for the onset and intensity of anticipation during RFS. After RFS, however, cirrhotic rats exhibited a significantly longer free-running period and a delay and lower intensity of the persistence of activity under fasting conditions. Histology confirmed injury of the liver chronically treated with CCl4. Present data indicate that a dysfunctional liver due to chronic CCl4 does not prevent animals from exhibiting anticipatory activity but may promote metabolic derangement of the clock mechanisms of the suprachiasmatic nucleus and the FEO.

Animals↗

Sonographic diagnosis of coeliac disease in a case with suspected acute liver failure.

Mild liver dysfunction occurs in patients with coeliac disease frequently, but severe liver diseases in combination with coeliac disease are rare. A 19-year-old woman was referred for evaluation for emergency liver transplantation with progressive jaundice and prolongation of prothrombin time. She had a history of non-bloody diarrhoea for 3 months and weight loss of 12 kg. At admission, abdominal ultrasound revealed liver enlargement with increased echogenicity and marked thickening of the circular folds of the small intestine, suggestive of coeliac disease. The diagnosis was confirmed by endoscopic biopsy from the second part of the duodenum. On a gluten-free diet the patient recovered within 1 week and remained in excellent health up to the present date. Liver tests normalized within 5 months and a repeat abdominal ultrasound after 20 months revealed a normal liver and small intestine. This case report suggests that coeliac disease should also be considered in patients with unexplained severe acute liver disease and that abdominal ultrasound may be a helpful step to obtain to the correct diagnosis.

Adult↗

Hepatic pyruvate dehydrogenase activity in humans: effect of cirrhosis, transplantation, and dichloroacetate.

The liver is the major site for lactate clearance, and liver disease exacerbates lactic acidosis during orthotopic liver transplantation (OLT). This study assessed pyruvate dehydrogenase (PDH) activity in control, cirrhotic, and graft liver to test the hypotheses that 1) liver disease decreases hepatic PDH activity, 2) graft PDH activity is inhibited due to protracted ischemia, and 3) dichloroacetate (DCA) reverses functional PDH inhibition in cirrhotic and graft liver. After having given their informed consent, 43 patients received either DCA (80 mg/kg) or aqueous 5% glucose during OLT. Six patients without apparent liver dysfunction that were undergoing subtotal hepatic resection served as controls. Liver biopsy PDH activity was assayed by measuring [14C]citrate synthesis from [14C]oxaloacetate and PDH-derived acetyl-CoA. PDH in the active form (PDHa) in cirrhotic and control liver was 5.6 +/- 1.3 (SE) and 57 +/- 10 nmol.g wet wt-1.min-1, respectively (P < 0.001). Total PDH activity (PDHt) was 21.5 +/- 3.6 and 264 +/- 27 nmol.g wet wt-1.min-1, respectively (P < 0.001). DCA increased PDHa in cirrhotic liver to 22.3 +/- 4.1 nmol.g wet wt-1.min-1 (P < 0.05 vs. no DCA) without altering PDHt. Graft liver PDHa was 166 +/- 19 nmol.g wet wt-1.min-1, which was not altered by DCA. We conclude that decreased hepatic PDH activity secondary to decreased content may underlie lactic acidosis during OLT, which can be partially compensated by DCA administration. There is no apparent inhibition of graft liver PDH activity after reperfusion.

Acid-Base Equilibrium↗

Increased epinephrine-induced cAMP response in severely diabetic BB/W rat liver.

The effect of prolonged diabetes on epinephrine-induced adenosine 3',5'-monophosphate (cAMP) response in the liver was examined in diabetes-prone BB/W rats. Basal and 1 microM epinephrine-induced cAMP release from isolated perfused liver was similar in non-diabetic and diabetic BB/W rats with preserved adipose tissue. In adipose tissue-absent diabetic rats losing intra- and retro-peritoneal adipose tissue completely, both basal and 1 microM epinephrine-induced cAMP release from the liver were enhanced (P<0.01, each case). Plasma epinephrine and norepinephrine were similar in non-diabetic, adipose tissue-preserved and -absent diabetic BB/W rats. The plasma free thyroxine level was similar in non-diabetic and adipose tissue-preserved diabetic BB/W rats, but was lower in adipose tissue-absent diabetic BB/W rats than in non-diabetic rats (P<0.01), but the frequency of lymphocytic thyroiditis was similar in these three groups, although plasma corticosterone was lower in adipose tissue-preserved diabetic BB/W rats (P<0.05) and the lowest in adipose tissue-absent diabetic BB/W rats (P<0.01). Lymphocytic infiltration was not observed in the adrenal or pituitary glands in any group. Plasma total protein and albumin were low in adipose tissue-absent diabetic BB/W rats (P<0.01, each case). In adipose tissue-absent diabetic BB/W rats, liver dysfunction and hepatomegaly, but no apparent histological change in the liver, were observed. Plasma glucose was higher (P<0.01) and plasma insulin lower (P<0.05) in adipose tissue-absent diabetic BB/W rats than in adipose tissue-preserved diabetic BB/W rats. In conclusion, epinephrine-induced cAMP response in the liver was enhanced only in adipose tissue-absent diabetic BB/W rats. Denervation supersensitivity was not likely to be responsible for the enhanced beta-adrenergic response. The observed reductions in plasma thyroxine and corticosterone seemed to result from severe diabetes. Although the severity of diabetes can vary continuously, severe diabetes with loss of adipose tissue appeared to cause significant changes in the metabolism and enhanced beta-adrenergic response in the liver.

Alanine Transaminase↗

Noni juice is not hepatotoxic.

Noni juice (Morinda citrifolia) has been approved for use as a safe food within the European Union, following a review of safety. Since approval, three cases of acute hepatitis in Austrian noni juice consumers have been published, where a causal link is suggested between the liver dysfunction and ingestion of anthraquinones from the plant. Measurements of liver function in a human clinical safety study of TAHITIAN NONI Juice, as well as subacute and subchronic animal toxicity tests revealed no evidence of adverse liver effects at doses many times higher than those reported in the case studies. Additionally, M. citrifolia anthraquinones occur in the fruit in quantities too small to be of any toxicological significance. Further, these do not have chemical structures capable of being reduced to reactive anthrone radicals, which were implicated in previous cases of herbal hepototoxicity. The available data reveals no evidence of liver toxicity.

Acute Disease↗

Combined small bowel and reduced auxiliary liver transplantation: case report.

AIM: To present a case of combined small bowel and reduced auxiliary liver transplantation. METHODS: A 55-year-old patient with short bowel syndrome and TPN-related liver dysfunction received small bowel transplantation combined with a reduced auxiliary liver graft. A liver was added to restore the patient's liver function and to protect the intestinal allograft from rejection. His own liver was not removed. RESULTS: Without donor pretreatment and by conventional immunosuppresive therapy following transplantation, the patient experienced had only one episode of mild intestinal rejection, which was easily reversed by treatment with Methylprednisolone. No liver rejection occurred. Unfortunately, the patient died of heart and lung failure 30d after transplantation, despite successful graft replacement. Histopathologic examination of specimens after death demonstrated normal structure in both intestinal and liver grafts. CONCLUSION: The auxiliary liver graft might play a role in preventing intestinal allograft rejection. However, the observation period in this case is short. Further study is needed to determine the risks, effect on the protecting the small-bowel from rejection, and feasibility of general application of this procedure.

Fatal Outcome↗

Liver failure in the critically ill.

The pathophysiology and manifestations of liver failure and fibrotic liver disease are discussed The management of patients with liver dysfunction is reviewed Indications for transplant and new modes of liver support are outlined

Acute Disease↗

Liver toxicity. Could this be a drug reaction?

BACKGROUND: Adverse reaction to prescription medications, over the counter medications and complementary medicines, are an important cause of liver toxicity. OBJECTIVE: To highlight the importance of drug induced liver toxicity in patients presenting with abnormal liver function tests. DISCUSSION: In patients who present with symptoms of liver dysfunction such as anorexia, itch or Jaundice and in whom liver function tests are abnormal, the possibility of an adverse reaction to medications should be considered. A detailed history of all medications taken in the past few months, including complementary medicines, should be obtained. After exclusion of other causes of liver disease such a viral hepatitis or gallstones, the cessation of the offending medication and the normalisation of liver tests is usually sufficient to establish a diagnosis. Occasionally, referral to a specialist and liver biopsy may be required.

Adult↗

Practical usefulness of bipolar scissors in hepatectomy.

BACKGROUND/AIMS: Because less surgical stress might preserve quality of life of patients, it is more desirable to decrease both intraoperative blood loss and liver injury especially in hepatectomy. For the patients with hepatocellular carcinoma based on chronic liver dysfunction, it is more essential to control bleeding and reduce liver injury in hepatectomy than in other diseases. In the present study, a retrospective comparison about usefulness was made in hepatectomy between using bipolar scissors and using conventional procedure. Before 1997, in our hospital, we had dissected the liver by using the crushing clamp method in combination with cauterization by microwave coagulator for the purpose of reducing intraoperative blood loss. Since 1998, bipolar scissors have been introduced toward hepatectomy as a new, simple and easy device to use. METHODOLOGY: Fifty-three consecutive patients with primary hepatocellular carcinoma at TNM stage I/II who underwent partial hepatectomy between 1996 and 1999 were enrolled in the study. Thirty-two patients (1996-1997) were treated by using a conventional method (group CM) and 21 patients (1998-1999) were treated by using bipolar scissors (group BS). The factors related to surgical stress were compared between the two groups. RESULTS: The amounts of blood loss/transfusion were lower in group BS (641/100 mL) than in group CM (1112/450 mL). The percentages of patients who lost more than 1000 mL of blood were lower in group BS (19%) than in group CM (47%) (P = 0.04). An intraabdominal drainage was needed for 9.0 +/- 6.6 days in group BS, and the drainage period was shorter than that in group CM (15.0 +/- 8.7 days) (P = 0.01). CONCLUSIONS: These results indicated the superiority of bipolar scissors in decreasing blood loss and liver injury to the conventional method, suggesting the worth of performing the prospective randomized study.

Aged↗

[Is ex situ surgery of the liver useful for difficult hepatic resections?].

Five cases of hepatic tumor deemed unresectable by conventional techniques are presented to illustrate the potential benefit offered by complete hepatic vascular exclusion (Pringle maneuver associated with inferior vena cava clamping below and above the liver). The most extensive and difficult liver resections may be achieved, with possible venous reconstruction, if the clamping period is not interrupted. Hepatic vascular exclusion may exceed one hour, up to 85 minutes in this series, with a good liver tolerance, in the absence of preoperative liver dysfunction. The advantages and disadvantages of the ex situ extracorporeal liver resections performed under similar circumstances are discussed. The authors consider that the role of ex situ liver procedures should be very limited.

Adult↗