Gallbladder Contractility in Liver Cirrhosis: Comparative Study in Patients with and Without Gallbladder Stones

An increased prevalence of gallstones was demonstrated in patients with liver cirhosis, higher in the advanced stages of the disease. Some studies have found impaired emptying of the gallbladder in cirrhotic patients. Our aim here was to investigate gallbladder emptying in cirrhotic patients with and without gallstones to find out whether emptying is further impaired in the presence of gallstones. The study group comprised 24 patients with liver cirrhosis and gallstones, 8 in each Child class. The controls were represented by 18 cirrhotic patients without gallstones, 6 in each Child class. Fasting gallbladder volume was calculated by ultrasound using the ellipsoid formula. Gallbladder emptying was evaluated for 90 min after ingestion of a solid-liquid meal (14 g fat, 425 kcal), by assessing minimal residual volume, gallbladder ejection fraction, and area under emptying curve at 15-min intervals. Statistical analysis was performed using the two-tailed Students' t test and Pearson's correlation coefficient. In controls, gallbladder fasting and residual volumes increased with the severity of cirrhosis, but gallbladder emptying did not change significantly. In cirrhotics with gallstones, gallbladder emptying decreased in Child C compared with Child A class patients and, also, compared to Child C controls. The number or size of gallstones, as well as the thickness of the gallbladder wall, did not correlate with gallbladder emptying parameters. Gallbladder contractility is impaired in patients with liver cirrhosis and gallstones. Hypomotility is proportional to the severity of liver disease. Gallbladder hypomotility might contribute to the increased gallstone formation in patients with advanced cirrhosis.     

Factors influencing the prevalence of gallstones in liver cirrhosis

BACKGROUND AND AIMS: To investigate the prevalence of gallstone disease in Chinese patients with liver cirrhosis and to identify risk factors for cholelithiasis. METHODS: Blood samples were tested and ultrasonographic examination of the upper abdomen was conducted to observe the prevalence of gallstones in 90 compensated cirrhotic patients (Child-Pugh A), 180 decompensated cirrhotic patients (Child-Pugh B, C) and 300 controls. Risk factors for gallstone formation (age, sex, pregnancy, family history) and the characteristics of liver cirrhosis (Child class, inside diameter of portal vein), and gallbladder (wall thickness) were assessed. RESULTS: Gallstones were found more often in cirrhotic patients (23.7%) than in controls (7.33%, P < 0.001). The prevalence of gallstones in decompensated cirrhotic patients was higher than that of the compensated cirrhotic patients (P < 0.001). Advanced age, female sex, family history of gallstones, gallbladder wall thickness 4 mm or greater and inside diameter of portal vein 13 mm or greater were significantly associated with gallstone disease in patients with liver cirrhosis. Multivariate analysis revealed that age (P < 0.001), sex (P = 0.0005) and thickness (4 mm or greater) of the gallbladder wall (P = 0.0064) were independently associated with gallstone disease in such patients. CONCLUSIONS: This study confirms the high prevalence of cholelithiasis in liver cirrhosis. Age and sex are risk factors for gallstones and gallbladder wall thickness could be an additional risk factor for the development of gallstone in patients with liver cirrhosis.     

Gallbladder motility in diabetic patients with and without cardiovascular neuropathy]

In 50 diabetic patients without gallstones, including 26 patients with cardiovascular autonomic dysfunction, and 60 normal volunteers the fasting volume and volume reduction of the gallbladder after a liquid fatty meal were determined ultrasonically in intervals of ten minutes up to one hour. Simultaneously the gastric emptying of the liquid meal was followed by ultrasound imaging. Despite an association of other complications of diabetic disease (peripheral neuropathy, retinopathy) with autonomic cardiovascular dysfunction, an altered gallbladder resting volume or impaired fat-induced volume reduction was not evident in this group of patients when compared the diabetics without cardiovascular dysfunction or controls. The time to reach the minimal residual gallbladder volume was only tendentiously prolonged in diabetics with autonomic cardiovascular dysfunction. The residual volume of the stomach showed no significant difference between the three study groups using a liquid test meal. In conclusion neuropathic dysfunction of the gallbladder is unlikely to play a major pathogenetic role in the development of gallstones in diabetic patients.     

Peripheral and cardiovascular autonomic impairment in chronic liver disease: prevalence and relation to hepatic function.

We have evaluated autonomic function using standard cardiovascular tests and a test of peripheral autonomic denervation, the acetylcholine sweatspot test, in 104 patients with biopsy proven chronic liver disease and 35 age- and sex-matched controls. Cardiovascular autonomic dysfunction was significantly more frequent in advanced liver disease compared with early liver disease (71.8% Child B or C vs. 39.7% Child A; p < 0.0006), and a strong correlation between the number of abnormal tests and Child-Pugh score could be demonstrated (Rs = 0.5; p < 0.0001). On multiple logistic regression analysis, cardiovascular autonomic dysfunction was related to age and to Child-Pugh score and occurred independently of the aetiology of liver disease. Peripheral autonomic denervation was found in 39% of patients, was significantly associated with cardiovascular abnormalities (p < 0.009) and correlated with the number of abnormal cardiovascular tests in each patient (Rs = 0.48; p < 0.0001). In chronic liver disease, the prevalence and severity of cardiovascular autonomic dysfunction is related to the severity of hepatic dysfunction and is independent of aetiology, suggesting a common pathogenetic basis related to hepatic damage; the association with peripheral autonomic denervation indicates that at least some of the abnormalities may be due to a true autonomic neuropathy. The possible significance of these findings to the complications of cirrhosis is discussed.     

Presence of autonomic neuropathy is a poor prognostic indicator in patients with advanced liver disease

Autonomic neuropathy (AN) is seen in both alcohol-induced and non-alcohol-induced liver disease, and when present is an independent predictor of mortality. We postulated that patients who were awaiting liver transplantation are likely to have a high prevalence of autonomic neuropathy with an associated increase in mortality. To test our hypothesis, we evaluated the presence of autonomic neuropathy using a battery of tests in 33 patients awaiting liver transplantation and prospectively followed them to determine their prognosis. Twenty-two of 33 (67%) patients with liver disease had evidence of autonomic neuropathy; of these, 12 (36%) had evidence of definite and 10 (31%) had early autonomic neuropathy. The prevalence of AN was similar in alcohol-induced and non-alcohol-induced liver disease. Using Child-Pugh classification, 14.3% Child A, 31.3% Child B, and 60% Child C had definite autonomic neuropathy. Six patients died during a median observation period of 10 months, and all had AN. Kaplan-Meier survival analysis showed a significantly higher mortality (P=.05) in patients with AN. On the basis of this observation, we suggest that consideration should be given for early liver transplantation in patients with advanced liver disease and autonomic neuropathy. (Hepatology 1996 Mar;23(3):471-5)     

Evaluation of Gallbladder Motility in Patients with Liver Cirrhosis

To investigate the postprandial gallbladder motility, including emptying and refilling, in cirrhotic patients and to evaluate the relationship to the presence of gallstones and various humoral mediators, 82 patients with liver cirrhosis and 40 age- and sex-matched healthy subjects were enrolled into this study. Postprandial gallbladder volumes were measured with ultrasonography every 15 min for 2 hr. Plasma levels of estradiol, testosterone, substance P, and nitrate/nitrite were also measured. Cirrhotic patients showed a higher prevalence of gallstones than healthy subjects (41% vs 15%, P = 0.003), and the prevalence increased with the progression of liver cirrhosis (Child-Pugh class A: 26%, B: 44%, and C: 65%, P = 0.02). Plasma levels of estradiol, testosterone, and substance P, and nitrate/nitrite and estradiol/testosterone ratios were not different between cirrhotic patients with and without gallstones. However, postprandial refilling of the gallbladders was significantly impaired in patients with cirrhosis, especially in those combined with gallstones. There was no significant difference in the postprandial gallbladder motility between cirrhotic patients with and without elevated plasma levels of estradiol, testosterone, and substance P and nitrate/nitrite, and estradiol/testosterone ratios. Gallstones were common in patients with liver cirrhosis and the prevalence increased with the progression of liver diseases. Sex hormones, substance P, and nitrate/nitrite did not play major roles in the formation of gallstones in cirrhotic patients. Refilling of the gallbladder was significantly impaired in patients with liver cirrhosis, especially in those with gallstones, and may play an important role in the pathogenesis of gallstones.     

Gallbladder volume and emptying in insulin-requiring male diabetics

Gallbladder function was evaluated in 27 healthy male volunteers and 47 male insulin-requiring diabetics from a diabetic clinic. Three groups of patients were studied: 18 patients without neuropathy or retinopathy (A); 17 patients with evidence of peripheral neuropathy (B); and 12 patients with evidence of peripheral and autonomic neuropathy (C). Eleven patients complained of gastrointestinal symptoms (three in group B, eight in group C). Thirty minutes after a standard breakfast, fasting gallbladder volumes and gallbladder emptying rates were measured using a real-time mechanical sector ultrasound scanner. Fasting gallbladder volume in diabetic patients was similar to controls (24.9 +/- 2.7 N; 28.9 +/- 3.9 A; 23.7 +/- 2.2 B; 16.7 +/- 3.4 C ml mean +/- SEM). Postprandial gallbladder emptying was not significantly different in any groups (47.4 +/- 5.1% N; 43.2 +/- 7.7% A; 50.7 +/- 7.7% B; 46.8 +/- 11.1% C). Seven diabetics and two controls had poor gallbladder emptying. One screened patient had cholecystectomy, three patients had stones, and two had sludge with a thickened gallbladder wall for a total of 12.5% gallbladder disease. These data suggest that gallbladder dysfunction in male insulin-requiring diabetics is rare.     

Impairment of gallbladder emptying in diabetes mellitus

Individuals with diabetes mellitus are reported to have a twofold to threefold increase in the incidence of cholesterol gallstones. A frequently cited but unproven pathophysiologic mechanism for this phenomenon is reduced gallbladder muscle function, which results in stasis and allows for cholesterol gallstone crystal formation and gallstone growth. To date, gallbladder motor function has not been investigated in a well-characterized diabetic population. Therefore, using radionuclide cholescintigraphy, gallbladder filling and subsequent emptying produced in response to an infusion of the octapeptide of cholecystokinin in 30 diabetic patients and 20 control individuals were studied. No difference in any parameter used to assess gallbladder filling was demonstrated in the diabetics when compared with controls. In contrast, gallbladder emptying induced with cholecystokinin-octapeptide (20 ng/kg body wt . h) was reduced in diabetics compared with controls (55% +/- 5% vs. 74% +/- 4%, p less than 0.01). The peak emptying rate in the diabetics was also decreased (5.0% +/- 0.5% per minute) compared with the controls (7.0% +/- 0.6% per minute, p less than 0.02). The observed decreased gallbladder emptying found in diabetics was not related to obesity, type of diabetes, diabetic control, or presence or absence of peripheral neuropathy. The most severe impairment of gallbladder emptying occurred, however, in diabetics with an associated autonomic neuropathy. This subgroup demonstrated a significant reduction in the percentage of gallbladder emptying (40% +/- 8% vs. 62% +/- 5%, p less than 0.04) and the peak ejection rate (3.5% +/- 0.5% per minute vs. 5.6% +/- 0.6%, p less than 0.02) compared with the diabetics without autonomic neuropathy.     

Gastric emptying time and the effect of cisapride in cirrhotic patients with autonomic neuropathy

GOALS To investigate the relationships between gastric emptying and autonomic dysfunction in hepatic cirrhosis and to assess the effects of cisapride on gastric emptying in cirrhotic patients.STUDY Twenty-four cirrhotic patients (8 patients in each Child-Pugh classification) and 25 healthy controls were enrolled. All the patients had viral (B or C) hepatitis. Patients with DM, alcoholic cirrhosis, active peptic ulcer, gastric malignancy and pyloric obstruction were excluded by esophagogastroduodenoscopy. Parasympathetic and sympathetic functions were assessed by the criteria set forth by Ewing and Clark. Drugs affecting GI motility and smoking were discontinued 48 hours and 12 hours prior to the study respectively. A solid-phase of gastric emptying study was conducted by scintigraphic method for the calculation of gastric half-emptying time (GET1/2). RESULTS The study revealed that 9 patients with Child-Pugh B and C cirrhosis had autonomic neuropathy and none of Child-Pugh A cirrhosis had autonomic neuropathy. Prolonged GET1/2 was noted in cirrhotics compared with the control group (p < 0.05). However, there was significant difference between 9 patients (Child B-C) with autonomic neuropathy compared with patients 15 patients without autonomic neuropathy. Again there was a significant difference in GET1/2 between Child A cirrhotic and Child B-C cirrhotic whether they had autonomic neuropathy or not. Cisapride decreased GET1/2 significantly in cirrhotic patients (Child B-C cirrhotic). Clearly, patients with autonomic neuropathy in Child B-C cirrhosis had significantly reduced GET1/2 after cisapride administration. Even though cisapride decreased GET1/2 in patients with Child B-C cirrhosis without autonomic neuropathy, this was not significant. CONCLUSION Autonomic neuropathy in advanced cirrhosis from viral hepatitis may cause prolonged gastric emptying. Cisapride can shorten gastric emptying time in such patients.     

Helicobacter pylori Infection and Peptic Ulcer Disease in Cirrhosis

An increased frequency of peptic ulcer diseaseis noted in patients with cirrhosis, but the role of H.pylori in this disorder remains to be determined. Thediagnosis of cirrhosis was confirmed by a combination of clinical, biochemical, radiological, andhistological methods. The severity of cirrhosis wasassessed by Pugh's modification of Child's criteria.Upper gastrointestinal endoscopy was performedconsecutively to evaluate the presence of varices andgastroduodenal mucosa. H. pylori status was assessed byhistology, urease test, and serology. In all, 130patients with cirrhosis were recruited into the study;there were 86 males and 44 females with a mean (SD)age of 54.4 (12.7) years. The H. pylori prevalence was76.2% . There was no difference in age between the H.pylori-positive and -negative cirrhotics (P = 0.29). The H. pylori prevalence revealed no differenceamong cirrhotics with Child A (77.8%), Child B (72.9%),and Child C (78.6%) (P = 0.8), and neither was there adifference in H. pylori prevalence in cirrhotics with and without congestive gastropathy (77% vs73.7% , P = 0.84). The prevalence of H. pylori incirrhotics with and without varices did not show astatistical difference (75% vs 81.8%, P = 0.68). There also was no difference in the H. pyloriprevalence between cirrhotic patients with and withoutpeptic ulcers (84.4% vs 69.7% , P = 0.09). Inconclusion, the prevalence of H. pylori or peptic ulceris independent of the severity of cirrhotic liver disease. Theassociation between H. pylori infection and peptic ulcerdisease is weak in cirrhosis.     

Baroreceptor sensitivity and baroreceptor effectiveness index in cirrhosis: the relevance of hepatic venous pressure gradient

Background: Autonomic dysfunction has been reported as one of the complications of cirrhosis. Aims: The aim of this study was to test autonomic dysfunction in cirrhotic patients by analysing the baroreflex sensitivity and the baroreceptor effectiveness index (BEI), in order to determine its correlation with the severity and the aetiology of liver disease. Moreover, we explored the relationship between baroreceptor function and mortality in our cohort of patients. Methods: Clinical and laboratory evaluation, hepatic venous pressure gradient (HVPG) and haemodynamic setting and baroreceptor function were assessed in 45 cirrhotic patients (median age 55, range 38–72 years) divided in groups according to the severity of their disease (26 patients Child A, 13 patients Child B and six patients Child C). Results: Baroreceptor sensitivity and BEI were impaired in more advanced cirrhotic patients compared with subjects with milder disease (P<0.001). HVPG was significantly, independently and inversely correlated with baroreceptor sensitivity (P=0.003). More severe impairment of baroreceptor function was associated with a higher mortality (P=0.04) and subjects with alcohol‐related cirrhosis presented worse baroreceptor function (P=0.032) and poorer survival (P=0.003) compared with subjects with post‐viral liver disease. Conclusions: These data support the hypothesis that liver disease severity and particularly portal hypertension have an important role in the derangement of baroreceptor function. The aetiology of cirrhosis seems to be related to baroreceptor impairment as well. Mortality rate is higher in subjects with a more damaged autonomic system, strengthening the idea of a worse prognosis in cirrhotic patients with autonomic neuropathy.     

Risk factors for symptomatic gallstones in patients with liver cirrhosis: a case-control study

OBJECTIVES: Liver cirrhosis is a well-documented risk factor for the formation of gallstones. In cirrhotic patients, gallstones are almost always "silent," and surgery is rarely required. When indicated (symptoms or complications), cholecystectomy implies a high morbidity risk in these patients, especially in the advanced stages of cirrhosis. The aim of this study was to estimate the risk factors for symptom development in cirrhotic patients with gallstones to identify the subgroup of patients at risk of undergoing surgery. METHODS: A total of 140 patients with liver cirrhosis and gallstones were studied: 97 with asymptomatic and 43 with symptomatic gallstone disease. The risk factors for gallstone formation (age, gender, family history, parity, obesity, diabetes mellitus, hyperlipoproteinemia) and the characteristics of liver cirrhosis (etiology, duration, Child class, hypersplenism), gallstones (duration, number, size), and gallbladder (size, wall thickness) were assessed in all patients. In 12 patients (four symptomatic, eight asymptomatic), gallbladder emptying was also evaluated by ultrasound. The association of asymptomatic and symptomatic gallstones with all these parameters was statistically evaluated by Student's t, Mann-Whitney, and chi(2) tests, as well as by means of multiple logistic regression. The causal relationship between these characteristics and gallstone symptoms was also examined by means of the KDD (knowledge discovery from databases) method, with an algorithm for learning Bayesian networks. RESULTS: Advanced age, female gender, viral etiology of cirrhosis, family history of gallstones, and duration of gallstone disease were significantly associated with symptomatic gallstone disease. The number or size of gallstones and the size or emptying of the gallbladder did not differ in symptomatic versus asymptomatic patients. Male gender and alcoholic cirrhosis were inversely correlated with symptom presence. In the multivariate analysis, family history (p = 0.0098) and advanced age (p = 0.0422) were positively correlated and male gender (p = 0.0049) and alcoholic etiology of cirrhosis (p = 0.0116) negatively correlated with symptom presence. These relationships (except for age) were also evidenced by the KDD method. CONCLUSIONS: The risk of gallstones becoming symptomatic is significantly lower in men and in alcoholic cirrhosis. In cirrhotic women, and especially in the presence of a positive family history and of advanced age, the risk of developing symptoms and undergoing surgery was significantly greater.     

Prevalence of metabolic syndrome, obesity and diabetes type 2 in cryptogenic cirrhosis

AIM： To evaluate the prevalence of metabolic syndrome （MS）, obesity and type 2 diabetes mellitus （T2DM） in a group of Mexican Mestizo patients with cryptogenic cirrhosis （CC） and to compare this group with patients with cirrhosis secondary to other causes （disease controls）. METHODS： Patients with CC, diagnosed between January, 1990 and April, 2005, were included in a retrospective study. Patients with cirrhosis caused by chronic hepatitis C, alcohol abuse or autoimmune hepatitis （AIH） served as disease controls. RESULTS： A total of 134 patients with CC were analyzed. Disease controls consisted of 81 patients with chronic hepatitis C, 33 with alcohol abuse and 20 with AIH. The median age of patients with CC was 57 years （range, 16-87）; 83 （61.9%） patients were female; 53 （39.6%） were Child A, 65 （48.5%） Child B, and 16 （11.9%） were Child C cirrhosis. The prevalence of MS （29.1% vs 6%; P 〈 0.001）, obesity （16.4% vs 8.2%; P = 0.04） and T2DM （40% vs 22.4%; P = 0.013） was higher in CC patients than in disease controls. There were no differences in sex, age or liver function tests between the two groups. CONCLUSION： The prevalence of MS, obesity and T2DM were higher in patients with CC than in patients with cirrhosis secondary to others causes. Our findings support the hypothesis that non-alcoholic steatohepatitis （NASH） plays an under-recognized role in CC.     

Prevalence of metabolic syndrome,obesity and diabetes type 2 in cryptogenic cirrhosis

AIM: To evaluate the prevalence of metabolic syndrome (MS),obesity and type 2 diabetes mellitus (T2DM) in a group of Mexican Mestizo patients with cryptogenic cirrhosis (CC) and to compare this group with patients with cirrhosis secondary to other causes (disease controls).METHODS: Patients with CC,diagnosed between January,1990 and April,2005,were included in a retrospective study.Patients with cirrhosis caused by chronic hepatitis C,alcohol abuse or autoimmune hepatitis (AIH) served as disease controls.RESULTS: A total of 134 patients with CC were analyzed.Disease controls consisted of 81 patients with chronic hepatitis C,33 with alcohol abuse and 20 with AJH.The median age of patients with CC was 57 years (range,16-87); 83 (61.9%) patients were female; 53 (39.6%) were Child A,65 (48.5%) Child B,and 16 (11.9%) were Child C cirrhosis.The prevalence of MS (29.1% vs 6%; P ＜ 0.001),obesity (16.4% vs 8.2%; P = 0.04) and T2DM (40% vs 22.4%; P = 0.013)was higher in CC patients than in disease controls.There were no differences in sex,age or liver function tests between the two groups.CONCLUSION: The prevalence of MS，obesity and T2DM were higher in patients with CC than in patients with cirrhosis secondary to others causes.Our findings support the hypothesis that non-alcoholic steatohepatitis (NASH) plays an under-recognized role in CC.     

HCV infection is a risk factor for gallstone disease in liver cirrhosis: an Italian epidemiological survey

We assessed the prevalence of gallbladder disease (i.e. gallstones plus cholecystectomy) among patients with liver disease and its association with the severity and aetiology of hepatic injury. Subjects, referred to 79 Italian hospitals, were enrolled in a 6-month period. The independent effect of the severity and aetiology of liver disease on gallstone disease prevalence was assessed by multiple logistic regression analysis. Overall, 4867 subjects tested anti-hepatitis C virus (HCV) positive alone, 839 were hepatitis B virus surface antigen (HBsAg) alone, and 652 had an excessive alcohol intake. The prevalence of gallstone disease was 23.3% in anti-HCV-positive patients, 12.4% in HBsAg positive and 24.2% in subjects reporting excessive alcohol intake, respectively. Gallstone disease prevalence increased by age in each aetiological category. The proportion of patients with gallstone disease who had a cholecystectomy was the highest in HCV+ subjects. After adjusting for the confounding effect of age and body mass index, compared with patients with less severe liver disease, subjects with HCV-related cirrhosis, but not those with alcohol-related cirrhosis, were more likely to have gallstone disease. Subjects with HCV-related cirrhosis (OR 2.13, 95% CI: 1.38-3.26) were more likely to have gallstone disease when compared with those with HBV-related cirrhosis. HCV infection is a risk factor for gallstone disease. In Italy, the high prevalence of HCV infection among cirrhotic patients has important implications, as cholecystectomy in these subjects is associated with high risk of morbidity and mortality.     

Gastrointestinal involvement in insulin-requiring diabetes mellitus

Gastrointestinal (GI) dysfunction in diabetes mellitus has never been evaluated systematically in all parts of the digestive system in a group of diabetics. Therefore, we have evaluated the frequency, extent, and clinical significance of GI complications in 75 consecutive, male, insulin-requiring diabetics (46 with neuropathy). Nineteen percent of the 75 patients and 30% of those with neuropathy had one or more GI symptoms. Esophageal, gastric, gallbladder, and small intestinal functions were studied in 30 patients using radionuclide esophageal and gastric emptying, postprandial gallbladder emptying, and intestinal transit of lactulose. We divided them into three groups: (1) 10 without neuropathy, (2) 10 with peripheral neuropathy, and (3) 10 with autonomic and peripheral neuropathy. Twenty-five patients (83%) had abnormalities of at least one GI organ, and 57% had abnormalities of two. Nineteen of the 25 patients (76%) with GI involvement and 8 of 9 (89%) symptomatic diabetics had delayed esophageal emptying. Symptomatic diabetics had more diabetic retinopathy, neuropathy, and autonomic dysfunction than asymptomatic diabetics and also had more widespread and more severe gastrointestinal involvement than asymptomatic diabetics. Therefore, our results indicate that in diabetics, (1) gastrointestinal motor abnormalities are common even though they are usually asymptomatic and (2) gastrointestinal dysfunction, especially in symptomatic diabetics, is often widespread and usually includes the esophagus.     

Pathogenesis of osteoporosis in liver cirrhosis

BACKGROUND/AIMS: Osteoporosis has been recognized in patients with liver cirrhosis, although the prevalence and the exact mechanisms vary considerably in the literature. We have studied the prevalence of bone disease in cirrhotic patients, the pathogenesis and the relation to the etiology and the severity of liver failure. METHODOLOGY: The study included 83 hospitalized patients with various types of cirrhosis, where 25 healthy individuals served as controls. Patients were classified according to Child-Pugh's stages as follows: Child A: 49, Child B: 20, Child C: 14. Serum levels of iPTH, 250HD, LH, FSH, SHBG, testosterone, estradiol, IGF-I, osteocalcin and urine levels of cross-linked N-telopeptides of collagen type 1 (NTX) were measured in all patients. Bone mineral density (BMD) was measured by DEXA at the spine of both patients and controls. RESULTS: The prevalence of osteoporosis was higher in patients (26/83) 31.3% than in controls (4/25) 16%. Osteopenia was positively related with the elevated levels of crosslinked N-telopeptides (p=0.048). There were no differences in BMD between the types of cirrhosis. BMD was found to be significantly lower in Child B and C male patients than in Child A (p=0.043). Patients' groups B, and C had lower testosterone levels with a trend to contribute to the low BMD (p=0.15). 250HD and IGF-1 were significantly lower in decompensated cirrhosis (p<0.002), but did not correlate with BMD. CONCLUSIONS: Cirrhosis is a major cause of osteoporosis and the degree of osteopenia is related to the severity and not the etiology of the liver disease. The biochemical markers of bone remodeling suggest a high-turnover osteoporosis in cirrhosis.     

Prolonged QTc interval and its relationship to autonomic cardiovascular reflexes in patients with cirrhosis

BACKGROUND/AIMS: We have previously shown that an abnormality in cardiac autonomic reflexes (AN) is an independent predictor of mortality in patients with chronic liver disease. Aim of this study was to determine whether there was an association between prolonged QTc interval and cardiac AN. METHODS: Cardiac AN and QTc interval were determined in 130 patients (Child A 42, B 53, C 35) with alcoholic and non-alcoholic liver disease. RESULTS: Prolonged QTc (>440ms) was seen in 58 (Child A 30%, B 46%, C 60%, P=0.04) patients. Autonomic tests were normal in 21%, borderline abnormal in 36% and definitely abnormal in 43%. QTc correlated with albumin (P<0.001), prothrombin time (P=0.003) and Child-Pugh score (P<0.001), but not with Valsalva ratio, heart rate variation with 6 breath/min breathing, tilt table or isometric exercise. By logistic regression analysis, QTc correlated only with Child-Pugh score (P<0.001). Mean QTc of 34 who died during the follow up was higher than survivors. Cox regression analysis showed that only Child-Pugh score and AN were independent predictors of mortality. CONCLUSIONS: Prolonged QTc seen in liver disease is independent of their cardiac autonomic function, but is related to the severity of the liver disease.     

Cognitive impairment in primary biliary cirrhosis: symptom impact and potential etiology

Qualitative studies suggest that patients with primary biliary cirrhosis (PBC) experience significant problems with memory and concentration. Studies of nonhepatic disease have linked hypotension and cognitive impairment. In this study, we determined the prevalence of cognitive symptoms in PBC, examined the relationship between symptoms and overt cognitive impairment and structural brain lesions, and explored the role of autonomic dysfunction. The prevalence of cognitive symptoms was determined in 198 patients with PBC. Twenty-eight representative early-stage female patients with PBC and 11 matched controls underwent formal cognitive testing at baseline and after 2 years of follow-up. Autonomic nervous system function was assessed according to heart rate variability and baroreflex sensitivity. Eleven subjects with PBC had structural brain lesions quantified via magnetic resonance imaging. Cognitive symptoms were frequent in our PBC population, with 53% of patients experiencing moderate or severe problems with concentration and/or memory, which were unrelated in their severity to biochemical and histological makers of liver disease severity, suggesting that this symptom burden is largely or entirely unrelated to hepatic encephalopathy. Perceived cognitive symptoms correlated with objectively assessed cognitive impairment (r(2) = 0.2, P < 0.05). Cognitive deficits were seen in the PBC cohort compared with controls, with significant decline detected over 2 years of follow-up. Correlations were seen between cognitive performance (full-scale intelligence quotient) and systolic blood pressure (P = 0.01, r(2) = 0.2) with decline in cognitive function associated with autonomic abnormalities. Structural brain lesions were found in PBC, the density of which correlated with degree of cognitive impairment (P = 0.01, r(2) = 0.5) and autonomic function (P = 0.03, r(2) = 0.2). CONCLUSION: Cognitive symptoms are prevalent in PBC independent of liver disease severity and are associated with poorer performance on objective cognitive testing. Cognitive impairment is, in turn, associated with structural brain lesions and autonomic dysfunction, which may predict risk of cognitive decline.     

Gallbladder dysfunction in diabetes mellitus

To further elucidate the mechanism of impaired gallbladder emptying in diabetics with and without neuropathy, gallbladder function was assessed by ultrasonography following a medium-chain triglyceride (lipomul, 1.5 mg/kg) infusion into the duodenum and compared to that during intravenous infusion of cholecystokinin in diabetic women. Results were compared with five healthy control women. Mean (±sd) maximal percent gallbladder volume in diabetics following lipomul was reduced to 49±8% and after intravenous cholecystokinin to 47±9%, which was less than those in controls, 21±9% and 24±6%, respectively, but not significantly different. Further analysis of gallbladder emptying to lipomul differentiated two subgroups of diabetics: one subgroup (N=5) had emptying comparable to controls (responders), while the other (N=5) had very modest emptying (nonresponders). Two of the patients in the latter group had normal gallbladder emptying during exogenous cholecystokinin and their response would be compatible with visceral neuropathy. Blood levels of cholecystokinin, measured by bioassay, following lipomul and exogenous cholecystokinin were similar in controls and diabetics. Presence of diabetic neuropathy did not correlate with impaired gallbladder emptying. Follow up at 6 and 12 months of the three nonresponder diabetics revealed that no gallstones had developed and that two of them became responders to exogenous cholecystokinin. We conclude that: (1) following lipomul, about 50% of diabetics in this study have impaired gallbladder emptying, which is not strictly correlated with diabetic neuropathy; (2) this was not due to abnormal cholecystokinin release; (3) in diabetic patients with impaired gallbladder emptying another abnormality may be present in the gallbladder; and (4) impaired gallbladder contraction may not lead to gallstone formation in one-year follow-up.