Usefulness of ascites/serum lactic dehydrogenase activity ratio in the initial approach to ascites.

To investigate the usefulness of ascitic fluid protein and lactic dehydrogenase activity separating uncomplicated portal hypertension related ascites (PHRA) from non PHRA and complicated PHRA, 58 patients with full diagnosis of the cause of ascites were prospectively studied. Ascitic fluid protein led to misclassify 30% of non PHRA and complicated PHRA, and 13% uncomplicated PHRA. Ascites/serum protein ratio did not improve the diagnostic efficacy of ascites protein concentration alone. Lactic dehydrogenase activity classified properly all uncomplicated PHRA but only 64% of non PHRA and complicated PHRA. All PHRA without complications and 92% of non PHRA and PHRA with complications were correctly allocated by ascites/serum dehydrogenase activity ratio. This criteria had higher sensitivity and efficiency than total protein concentration (p < 0.05). Our data suggest that ascites/serum lactic dehydrogenase ratio may offer advantages over ascites total protein concentration discriminating uncomplicated PHRA from non PHRA and PHRA with complications in the initial approach to a peritoneal effusion.

Serum copper in intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy is characterised by clinical and biochemical fluctuations and further diagnostic tools are required. The aim of this study was to investigate serum copper and copper oxidase during the course of intrahepatic cholestasis of pregnancy (ICP). Twenty eight ICP patients and twenty healty pregnant women were included. Routine liver tests, fasting serum bile acids (FSBA), serum copper and serum copper oxidase were measured. In ICP, serum copper was significantly higher than in controls (274 +/- 49 micrograms/dl vs 176 +/- 34 micrograms/dl, p less than 0.001). Copper oxidase rose in ICP (78 +/- 15 mg/dl) different than healthy pregnant women (64 +/- 8 mg/dl); p less than 0.02. In contrast to marked oscillations in FSBA, serum copper remained elevated during the follow-up with only minor fluctuations and no correlation was demonstrated between changes in FSBA and those noted in serum copper (r:0.17, NS). At labor, a significant rise in serum copper was demonstrated in ICP (from 251 +/- 50 micrograms/dl to 297 +/- 55 micrograms/dl, p less than 0.01) and in controls (from 168 +/- 34 to 192 +/- 42 micrograms/dl, p less than 0.01). This increment in serum copper was associated with a peak in serum copper oxidase activity. Serum copper and copper oxidase are elevated in ICP and may be considered as adjuvant diagnostic tests. Disturbances in copper metabolism reported in this study are consistent with the hypothesis that normal pregnancy is associated with a mild cholestasis effect and ICP represent a form of improperly controlled response.

[Bacteriuria in patients with primary biliary cirrhosis]. / Bacteriuria en pacientes con cirrosis biliar primaria.

BACKGROUND: Controversies exist about the association between significant bacteriuria and primary biliary cirrhosis. There is evidence suggesting that infections by Gram negative bacteria may be implicated in the pathogenesis of this liver disease. AIM: To compare the incidence of bacteriuria in patients with primary biliary cirrhosis and those with autoimmune chronic hepatitis. PATIENTS AND METHODS: Twenty women with primary biliary cirrhosis and twenty three female patients with autoimmune chronic hepatitis were prospectively studied by routine bacteriological cultures of midstream urine specimens. Samples were obtained at three months intervals or when patients complained of symptoms suggesting urinary tract infection. Significant bacteriuria was defined as the growth of > 10(5) organisms/ml in pure culture. RESULTS: During 8 +/- 1 months of follow up. 60 urine samples from patients with primary biliary cirrhosis and 73 from autoimmune hepatitis cases were tested. Twenty one samples of patients with primary biliary cirrhosis (35%) were positive for significant bacteriuria compared with 7 from women with autoimmune hepatitis (9%); p < 0.01. In the follow up, ten patients with primary biliary cirrhosis (50%) and six with autoimmune hepatitis (26%) developed at least one episode of significant bacteriuria. CONCLUSION: These results suggest that female patients with primary biliary cirrhosis are in higher risk of significant bacteriuria than women with autoimmune hepatitis. Prospective studies evaluating the effects of long-term antibiotic therapy on cholestasis parameters in primary biliary cirrhosis are deserved.

[Morphology of the myenteric plexus of the small intestine in patients with liver cirrhosis]. / Morfologia de los plexos mientericos del intestino delgado en pacientes con cirrosis hepática.

BACKGROUND: Patients with liver cirrhosis develop small bowel dysmotility of unknown etiology. Morphological features in the enteric nervous system and the intestinal smooth muscle may shed light on pathophysiology of the gut motility disturbances in this disease. AIM: To investigate the morphology of the myenteric plexuses and smooth muscle layers of the small intestine in patients with liver cirrhosis. PATIENTS AND METHODS: Full thickness biopsies of duodenum, jejunum and ileum from seven cirrhotic patients and seven controls were stained with several techniques, including silver impregnation. Neuronal counting and light microscopy studies were stained performed. RESULTS: The neuronal count was not significantly different in patients with cirrhosis compared to controls in duodenal samples (1.6 +/- 0.4 cel/mm vs 1.6 +/- 0.2 cel/mm), jejunal tissue (1.2 +/- 0.3 cel/mm vs 1.4 +/- 0.2 cel/mm), and in ileal specimens (0.8 +/- 0.3 cel/mm vs 0.9 +/- 0.2 cel/mm). In both groups, evidence of fibrosis or inflammation in myenteric plexuses and in smooth muscle was not found. Also, intestinal neuronal dysplasia was absent in cirrhotic patients as in controls. CONCLUSION: These results suggest that small bowel dysmotility in patients with liver cirrhosis is not related to structural changes in myenteric plexuses or in intestinal smooth muscle noted by light microscopy.

[Effects of neomycin on intestinal digestion, absorption and fermentation of carbohydrates in patients with liver cirrhosis: evidence for an alternative therapeutic mechanism in hepatic encephalopathy]. / Efectos de neomicina sobre la digestion, absorción y fermentación intestinal de carbohidratos en pacientes con cirrosis hepatica: evidencia para un mecanismo terapeutico alternativo en la encefalopatia hepática.

BACKGROUND: Despite non absorbable antibiotics and neomycin may have antagonistic effects on intestinal bacterial environment, both have synergistic effects in the treatment of hepatic encephalopathy. This could be due to their action on different enteric flora or a neomycin induced carbohydrate malabsorption. AIM: To investigate the effects of neomycin on intestinal digestion, absorption and fermentation of carbohydrates in patients with liver cirrhosis. PATIENTS AND METHODS: Thirty eight Child B or C cirrhotic patients separated in three groups; subjects within each group were randomized to receive neomycin (2/g/day for 10 days, n = 8) or placebo (n = 4). Absorption of lactose and d-xylose and fermentation of d-xylose, lactose and lactulose (measured using hydrogen breath tests) were studied before and after the treatment period. RESULTS: Neomycin did not change lactose fermentation but reduced plasma glucose rise after lactose ingestion (38.8 +/- mg/dl to 22 +/- 6 mg/dl p < 0.05). Plasma d-xylose levels at 30 min and its 5 h urinary excretion were reduced by neomycin from 19 +/- 3 to 9 +/- 2 mg/dl and from 4.9 +/- 0, 8 to 2.6 +/- 0.3 g/5h respectively (p < 0.05). Fermentation of d-xylose, lactose and lactulose was not reduced by neomycin. No significant changes were observed after placebo treatment. CONCLUSIONS: Neomycin therapy is associated with a reduction of intestinal digestion and absorption of carbohydrates, preserving bacterial fermentation capacity, probably increasing the non absorbable carbohydrate load reaching the colon.

[Transvenous hepatic biopsy in patients with blood coagulation disorders]. / Biopsia hepatica transvenosa en pacientes con defectos de la coagulacion sanguinea.

Severe clotting defects represent the main contraindication to percutaneous liver biopsy. A transvenous liver puncture technique has been developed for patients suffering from blood coagulation disorders. This approach was attempted in 17 of 148 consecutive patients (12%) in whom a needle liver biopsy was indicated. Hepatic tissue samplings were successfully obtained in 16 subjects. The mean size of the specimens was 7 mm. The clinical diagnosis or therapy were modified in 7 patients when the histopathology report was available. No complications related to the procedure occurred. Our early experience suggests that transvenous liver biopsy is indicated in one/ninth of cases in whom hepatic tissue sample is required for diagnosis. This technique is safe, and it has a high success rate to provide liver tissue samples.

[The relationship between functional symptoms of the digestive tract and the motility of the small intestine]. / Relación entre síntomas functionales del aparato digestivo y motilidad del intestino delgado.

Although abnormalities of intestinal motility are usually considered to underly functional gastrointestinal symptoms, objective evidence of such a relation is controversial. We performed manometric studies using perfused catheters in 26 patients with such symptoms. A marked variation in duration of cyclic motor activity (range 34 to 168 min) was observed; motility was absent in 5 patients. No clear relation between symptoms and motility pattern was demonstrated. Thus, altered intestinal motility is not clearly related to functional gastrointestinal complaints.

[Lactulose fermentation and lactose absorption in Chilean patients with liver cirrhosis: importance for hepatic encephalopathy therapy]. / Fermentación de lactulosa y absorción de lactosa en pacientes chilenos con cirrosis hepática: importancia para la terapia de la encefalopatía hepática.

BACKGROUND: Non-absorbable carbohydrates are widely used in the therapy of hepatic encephalopathy. It has been argued that their effects depend on intestinal fermentation. In some geographic areas other than Chile up to 27% of healthy inhabitants are not able to increase breath hydrogen after a lactulose load, a parameter of intestinal fermentation of carbohydrate. Lactose has been proposed as an alternative to non-absorbable disaccharides in patients with lactase deficiency. AIM: To investigate intestinal fermentation of lactulose and lactose malabsorption in Chilean patients with liver cirrhosis. PATIENTS AND METHODS: 22 healthy controls and 52 patients with liver cirrhosis (16 with hepatic encephalopathy) were prospectively studied by means of lactulose or lactose hydrogen breath tests and lactose tolerance test. MAIN RESULTS: In the control group, 19% were non-hydrogen excretors after lactulose, meanwhile a significant rise in breath hydrogen concentration was observed in all cirrhotic patients (p < 0.01). Lactose tolerance test was indicative of lactase persistance in 37% of cirrhotics and in 43% of controls (NS). Finally, 41% of cirrhotics and 50% of controls had a normal lactose hydrogen breath test (NS). These results were not significantly modified by the presence of hepatic encephalopathy. CONCLUSION: Our data suggest that a lack in bacterial fermentation is not a cause of lactulose therapy failure in Chilean patients with hepatic encephalopathy. Lactose might be an inappropriate substitute to lactulose treating a significant proportion of patients with this condition in our country.

[Effect of hyperosmotic solutions on duodenal motility: a mechanism of resistance or of propulsion to the luminal flow?]. / Efecto de soluciones hiperosmóticas en la motilidad duodenal: un mecanismo de resistencia o de propulsión al flujo luminal?

Infusion of hyperosmotic solutions into the duodenum lead to increased motility. To investigate the mechanism of this effect, 9 healthy volunteers received small infusions of hypertonic (1250 mOsm/kg) NaCl or glucose. Intestinal motility was registered using manometric system with multiple lumens 3 cm apart. Nineteen glucose infusions did not modify intestinal motility. Of 43 NaCl infusions, motility was increased in 24, 7 of them with a typical migratory complex, phase III. In 17 cases, non propagated contractions increasing in a cephalo-caudal direction were noted. The latter may be related to delayed gastric emptying associated to hyperosmotic loads.

Abnormalities in proximal small bowel motility in patients with cirrhosis.

Because altered intestinal motility could be involved in the pathogenesis of small intestine bacterial overgrowth observed in some patients with cirrhosis, we investigated fasting proximal small bowel motility in 16 cirrhotic patients and 8 healthy controls. In addition, the effects of oral tetracycline administration on duodenal motility were investigated in seven cirrhotic patients with evidence of bacterial overgrowth. The mean duration and characteristics of the migrating motor complex were analyzed. Cyclic activity was observed in all healthy controls. It was absent in two cirrhotic patients showing a prolonged phase 2-like pattern. The duration of cycles was significantly longer in the remaining 14 patients with cirrhosis (166 +/- 19 min) compared with controls (81 +/- 14 min; p < 0.02). This difference was caused by a prolonged phase 2 (138 +/- 19 min in patients with cirrhosis vs. 52 +/- 11 min in controls; p < 0.02). Marked changes in the contraction pattern during phase 2 were noted in cirrhotic patients. They were characterized by multiple clusters (frequency, 12 +/- 1/hr; duration, 38 +/- 3 sec) of contractions (frequency, 11 +/- 1 cpm) separated by quiescent periods (duration, 2.4 +/- 0.2 min). This motility profile filled up 58% +/- 8% of the total duration of phase 2, and it was observed in patients with and without bacterial overgrowth. Treatment with tetracycline was followed by only mild modifications, such as a reduction of the fraction of phase 2 occupied by multiple-clustered contractions. In conclusion, an altered proximal small bowel motility has been observed in patients with cirrhosis. These disturbances appear not to be dependent on the presence of bacterial overgrowth.

Reduction of portal pressure by isosorbide-5-mononitrate in patients with cirrhosis. Effects on splanchnic and systemic hemodynamics and liver function.

The results of a study to characterize the effects of the oral administration of isosorbide-5-mononitrate (Is-5-Mn), the active metabolite of isosorbide dinitrate, on portal hypertension in 23 patients with cirrhosis are reported. Patients received 20 mg of Is-5-Mn (n = 10), 40 mg (n = 9), or a placebo (n = 4). No significant changes were observed after the administration of the placebo. However, both doses of Is-5-Mn significantly reduced portal pressure, as evaluated by measurements of the hepatic venous pressure gradient. The fall in portal pressure averaged 10% after the 20-mg dose and 18% after 40 mg and was maintained for the 2 h of observation. Reduction of portal pressure was due to a decrease in the wedged hepatic vein pressure, with no changes in the free hepatic venous pressure. After the 20-mg dose, the decrease in portal pressure was associated with an increase in hepatic blood flow (16%), suggesting a fall in hepatic vascular resistance. However, after the 40-mg dose, a reflex splanchnic vasoconstriction elicited by the fall in arterial pressure (-19%) appeared to contribute to the greater reduction in portal pressure, as suggested by a significant decrease in azygos blood flow (-15%). These beneficial effects on portal pressure were not associated with adverse effects on liver function, as evaluated by measurements of the hepatic clearance of indocyanine green and the hepatic intrinsic clearance. Neither dose of Is-5-Mn caused significant changes in these quantitative parameters of liver function. These findings suggest that Is-5-Mn could be a potentially useful and safe agent in the treatment of portal hypertension.

[Selective chemoembolization with adriamycin-Urografin-Lipiodol in the treatment of hepatocarcinoma]. / Quimioembolización selectiva con adriamicina-Urografin-Lipiodol, en el tratamiento del hepatocarcinoma.

Various methods of regional chemotherapy have been used in patients with non resectable heptic carcinoma. We report our preliminary experience with embolization using adriamycin-urographin-lipiodol in 2 patients with this cancer in whom a considerable reduction of tumoral mass was observed. The pertinent literature is briefly commented.

[Hepatotoxicity induced by valproic acid in adults. Report of 3 cases]. / Hepatotoxicidad inducida por ácido valproico en adultos. Presentación de tres casos.

Valproic acid is a useful antiepileptic drug, with occasional gastrointestinal side effects. Hepatotoxicity is the most serious adverse reaction and, although rare, it can be fatal. Risk factors for hepatotoxicity are an age of less than two years, polytherapy and mental retardation; it has been rarely reported in adults. We report three mentally retarded adult patients receiving polytherapy, who developed valproic acid induced hepatotoxicity. Two patients had a symptomatic hepatitis with a concomitant paradoxical increase in seizure frequency and one an asymptomatic alteration of hepatic function tests. After discontinuing the drug, the hepatitis subsided. We conclude that hepatotoxicity must be considered as a possible side effect of valproic acid and we suggest some recommendations for its early detection.

[Are disturbances of small intestinal motility associated with hyperglucagonemia in patients with liver cirrhosis?]. / Estan los trastornos motores del intestino delgado relacionados con la hiperglucagonemia en pacientes con cirrosis hepatica?

Patients with liver cirrhosis develop marked abnormalities in small bowel motility and high plasma glucagon levels. Disturbances in small intestinal motor activity could be related to hyperglucagonemia. To investigate the relationship between fasting plasma glucagon levels and changes in small bowel motility in patients with liver cirrhosis, eighteen cirrhotic patients and ten controls were studied. Plasma glucagon was measured by RIA. Mouth to cecum transit time was estimated by lactulose hydrogen breath test. Fasting small bowel motility was investigated by means of intraluminal manometry. Plasma glucagon levels were significantly higher in patients with cirrhosis (61 +/- 5 pmol/l) than in controls (32 +/- 3 pmol/l); p < 0.01. In patients with liver disease, plasma glucagon levels were not significantly correlated to mouth to cecum transit time (r: -0.32), duration of migrating motor complex (r: -0.24), nor to the frequency of multiple clustered contractions (r: -0.26). The degree of small bowel dysmotility is not related to plasma glucagon levels in patients with hepatic cirrhosis. These results do not support the hypothesis that hyperglucagonemia plays an important pathogenic role in the abnormalities of gut motility in cirrhosis.

Ranitidine disposition in severe hepatic cirrhosis.

The effect of severe liver disease on ranitidine disposition was evaluated by comparing its kinetics in 5 healthy subjects and 11 patients with alcoholic cirrhosis. Cirrhotic patients had severe liver disease as evidenced by the presence of ascites, hepatic encephalopathy, jaundice, muscle wasting, and low serum albumin, but creatinine clearance did not differ significantly between controls and cirrhosis. Following intravenous administration of ranitidine, systemic clearance was decreased in cirrhosis. These decrease may be associated with changes in renal function, and decrease in hepatic metabolism, usually present in patients with severe hepatic failure. The distribution volume of ranitidine was also decreased in cirrhotics, but the difference between patients and controls was not significant. Biological half-life was significantly longer in cirrhotic patients than volunteers. This difference may be due to decrease in total body clearance found in cirrhotic patients. It is concluded that patients with severe liver cirrhosis could have elevated plasma level of ranitidine and that a reduction of ranitidine dosage is warranted in these patients.

Effects of somatostatin in patients with portal hypertension.

Portal hypertension is a common complication of chronic liver disease. Conventional therapy consists of surgery and palliative measures for the hemodynamic problem. It has been recently reported that somatostatin may reduce portal pressure without altering the systemic circulation and so reducing hepatic blood flow. This peptide also causes a significant fall in azygos circulation in patients with esophageal varices. The mechanism of this effect is unclear although suppression of intestinal vasodilating hormones and of glucagon have been claimed to play a role. Comparative clinical studies have shown somatostatin to be superior to the standard vasopressin treatment. Recent findings suggest that the efficacy of somatostatin can be increased by administering this peptide in repeated intravenous bolus injections. New derivatives, specially long-acting peptides, may eventually prove beneficial in the chronic treatment of this complication.

Pharmacokinetics of cimetidine in patients with liver disease.

Pharmacokinetics of cimetidine were studied after 200 mg i.v. doses in 7 patients with liver cirrhosis and in 10 healthy volunteers. Serial blood samples were obtained before and after drug administration over 12 hours. Cimetidine blood concentrations were determined by high pressure liquid chromatography (HPLC). The mean total body clearance in patients with cirrhosis (414.3 +/- 69.7 ml/min) was significantly less than that of subjects without liver dysfunction (501.1 +/- 37.9 ml/min) (p less than 0.01). However, the mean steady-state volume of distribution (1.34 +/- 0.41 l/kg vs 1.40 +/- 0.24 l/kg), volume of central compartment (0.51 +/- 0.11 l/kg vs. 0.45 +/- 0.05 l/kg), area volume of distribution (1.69 +/- 0.46 l/kg vs. 1.81 +/- 0.43 l/kg) and mean half-life (2.56 +/- 0.58 h vs. 2.68 +/- 0.43 h) did not demonstrate any significant changes. Renal clearance was significantly decreased from 389.5 +/- 41.9 ml/min in healthy subjects to 279.1 +/- 57.8 ml/min in cirrhotic patients (p less than 0.01). However, the mean extrarenal clearance was not changed in both groups. Modification of cimetidine dosage is therefore presumably not necessary in patients with compensated liver disease.

[A giant diverticulum of the colon]. / Divertículo gigante del colon.

A male patient complaining of abdominal pain developed rectal bleeding and a painful mass located in the left side of the abdomen. Barium enema revealed a giant diverticulum of the colon. Surgical resection was performed successfully. A brief review of the literature follows.

[Primary biliary cirrhosis. The experience in 33 consecutive cases]. / Cirrosis biliar primaria. Experiencia en 33 casos consecutivos.

Primary biliary cirrhosis is a chronic, progressive and often fatal cholestatic liver disease. We report clinical characteristics and follow up in 33 consecutive patients studied at a single university hospital during the last 10 years. 31 were female (94%) and the mean age was 51 +/- 2 years. At diagnosis, itching was present in 26 cases (78%). Association with autoimmune mediated diseases was frequent. Liver function tests showed marked cholestasis (alkaline phosphatase levels of 439 +/- 58 IU/l, range 90-1335). High antimitochondrial antibody titers and elevation of IgM levels were shown in all cases. According to liver biopsy findings, the diagnosis of primary biliary cirrhosis was an early one during the prospective phase of the study and was made in 8 +/- 1.4% of liver biopsies performed during this period. After a follow up of 27 +/- 5 months, 10 patients have died (30%). Our experience suggests that primary biliary cirrhosis is not an uncommon cause of chronic liver diseases in Chile.

[Hepatitis B virus vaccine: early and late response in Chileans with high risk of infection]. / Vacuna contra el virus de la hepatitis B: respuesta precoz y tardía en Chilenos con alto riesgo de infección.

BACKGROUND: Hepatitis B vaccine has demonstrated to be very effective and safe preventing hepatitis B virus infection. Long term protection induced by hepatitis B vaccination depends on the initial immune response and the declining rate of anti-HBs titers. AIM. To investigate early and late response to hepatitis B vaccine in a sample of high risk Chilean population. MATERIAL AND METHODS: Thirty one subjects (20 relatives of hepatitis B chronic carriers, 10 health service workers and one HIV seropositive) were vaccinated with a plasma derivated hepatitis B vaccine. Early and late response were estimated by anti-HBs titers. RESULTS: Twenty eight subjects (90%) produced protective titers of anti-HBs after 2 months from the third dose of vaccine (early response), and they remained at these levels in 75% of vaccinated individuals after three years (late response). All the subjects without protective titers after the three year follow up had produced anti-HBs levels lower than 300 UI at the early response. Hepatitis B vaccination was not associated with significant side effects. CONCLUSIONS: This experience confirms that hepatitis B vaccine is safe and effective inducing immunity in high risk subjects. Our data suggest that the early response to hepatitis B vaccine is able to identify those subjects requiring closer surveillance for boosters.