Transmission of LDLR mutation from donor through liver transplantation resulting in hypercholesterolemia in the recipient.

Donor-transmitted disease in organ transplantation is uncommon, but possible. The LDL receptor (LDLR), a key regulator of lipoprotein metabolism, is abundant in the liver. Mutations in the LDLR gene, leading to reduced LDLR activity, are the main cause for familial hypercholesterolemia (FH). The estimated prevalence of FH is 1/200-1/500 in the population indicating that there are 14-34 million individuals with FH worldwide. We describe a patient who developed severe hypercholesterolemia after liver transplantation (LT). The 42-year-old female, who was transplanted because of hepatic epithelioid hemangioendothelioma with normal liver function, exhibited an increase in plasma total cholesterol from 5.6 mmol/L (217 mg/dL) pretransplant to 11.7 mmol/L (452 mg/dL) at 6 months posttransplant. The respective increase in LDL cholesterol was from 3.30 (128 mg/dL) to 8.99 mmol/L (348 mg/dL). At 1 year, total and LDL cholesterol levels were 11.0 (425 mg/dL) and 7.81 (302 mg/dL), respectively. Sequencing of the coding region of LDLR from a liver graft biopsy revealed a splicing heterozygous mutation of LDLR, whereas no FH-related mutation was found in DNA extracted from the patient's blood white cells. This confirmed the first reported case of a patient receiving a mutation in LDLR through LT. The case shows that a donor-transmitted disorder should not be overlooked as a possible cause for severe hypercholesterolemia.

Immobilization of Lactococcus lactis to cellulosic material by cellulose-binding domain of Cellvibrio japonicus.

AIMS: Immobilization of whole cells can be used to accumulate cells in a bioreactor and thus increase the cell density and potentially productivity, also. Cellulose is an excellent matrix for immobilization purposes because it does not require chemical modifications and is commercially available in many different forms at low price. The aim of this study was to construct a Lactococcus lactis strain capable of immobilizing to a cellulosic matrix. METHODS AND RESULTS: In this study, the Usp45 signal sequence fused with the cellulose-binding domain (CBD) (112 amino acids) of XylA enzyme from Cellvibrio japonicus was fused with PrtP or AcmA anchors derived from L. lactis. A successful surface display of L. lactis cells expressing these fusion proteins under the P45 promoter was achieved and detected by whole-cell ELISA. A rapid filter paper assay was developed to study the cellulose-binding capability of these recombinant strains. As a result, an efficient immobilization to filter paper was demonstrated for the L. lactis cells expressing the CBD-fusion protein. The highest immobilization (92%) was measured for the strain expressing the CBD in fusion with the 344 amino acid PrtP anchor. CONCLUSIONS: The result from the binding tests indicated that a new phenotype for L. lactis with cellulose-binding capability was achieved with both PrtP (LPXTG type anchor) and AcmA (LysM type anchor) fusions with CBD. SIGNIFICANCE AND IMPACT OF THE STUDY: We demonstrated that an efficient immobilization of recombinant L. lactis cells to cellulosic matrix is possible. This is a step forward in developing efficient immobilization systems for lactococcal strains for industrial-scale fermentations.

Nateglinide combination therapy with basal insulin and metformin in patients with Type 2 diabetes.

AIMS: To compare the effect of adding nateglinide or placebo on postprandial glucose excursions (PPGEs), glycated haemoglobin (HbA(1c)), diurnal glucose profiles and hypoglycaemia in patients with Type 2 diabetes treated with the combination of basal insulin and metformin. RESEARCH DESIGN AND METHODS: This was an investigator-initiated, double-blind, randomized, parallel-group, study in five centres. Patients with Type 2 diabetes (n = 88, age 56.0 +/- 0.9 years, duration of diabetes 9.4 +/- 0.5 years, HbA(1c) 7.8 +/- 0.1%, body mass index 32.4 +/- 0.5 kg/m(2)) treated with basal insulin and metformin entered a 24-week period, during which basal insulin was titrated to optimize glucose control. Thereafter, the patients were randomized to receive either nateglinide (120 mg three times daily) or placebo before their main meals for 24 weeks. RESULTS: During the optimization period, HbA(1c) decreased by -0.3 +/- 0.1 and -0.4 +/- 0.2% (NS) and insulin doses increased by 10.0 IU (2.0-32.0) [0.09 IU/kg (0.02-0.34)] and 10.0 IU (0.0-19.0) [0.11 IU/kg (0.0-0.25)] (NS) in the nateglinide and placebo groups. Mean postprandial glucose during weeks 20-24 averaged 9.0 +/- 0.3 and 10.0 +/- 0.3 mmol/l in the nateglinide and placebo groups (P = 0.025) and mean PPGE averaged 2.4 +/- 0.2 and 3.1 +/- 0.2 mmol/l, respectively (P = 0.019). At 24 weeks as compared with 0 weeks, mean HbA(1c) had decreased by 0.41 +/- 0.12% in the nateglinide group and by 0.04 +/- 0.12% in the placebo group (P = 0.023). The frequency of confirmed, symptomatic hypoglycaemia was 7.7 episodes/patient-year vs. 4.7 episodes/patient-year in the nateglinide and placebo groups (P = 0.031). CONCLUSIONS: Addition of a short-acting insulin secretagogue at main meals improves postprandial hyperglycaemia during combination therapy with basal insulin and metformin, but increases the frequency of hypolycaemia.

Liver transplantation modifies serum cholestanol, cholesterol precursor and plant sterol levels.

Proportions of cholesterol precursors (squalene, delta 8-cholestenol, desmosterol and lathosterol), plant sterols (campesterol and sitosterol) and cholestanol to cholesterol in serum were measured before and serially after liver transplantation in eight patients with primary biliary cirrhosis (PBC) and three with acute liver necrosis. The preoperative proportions of cholestanol were 12 and 3-times higher in the PBC and necrosis groups, respectively, than in a control group of 27 individuals, while those of lathosterol were low in both groups and the campesterol/sitosterol ratio in the PBC group. During the operation the proportions of cholestanol fell sharply and those of lathosterol rose especially in the PBC group. During the postoperative follow-up of 5 weeks the proportions of the non-cholesterol sterols were markedly improved especially in the necrosis group yet those of cholestanol remained high and the campesterol/sitosterol ratios low, particularly in the PBC group. The proportions of lathosterol increased gradually almost to the control limits within the postoperative 5-week period, whereas those of desmosterol decreased. The non-cholesterol sterol values were not related to acute rejections, while significant correlations of cholestanol to liver function tests was found especially at the end of the follow-up.

Carotenoid pigments as tracers of cyanobacterial blooms in recent and postglacial sediments of the Baltic Sea.

The distributions of carotenoid pigments were studied in recent and postglacial sediments collected in the Gotland Basin, in the northern part of the Baltic proper, and in the eastern Gulf of Finland in May 1999. The aim was to provide a systematic, historical review of the occurrence and intensity of cyanobacterial blooms in the Baltic Sea in recent centuries. The presence of pigments was determined using high-pressure liquid chromatogrpahy (HPLC), with attention mainly focused on pigments considered as markers for cyanobacteria. The pigment concentrations in sediments from the 3 sampling locations were found to differ markedly. In general, concentrations were highest in sediments from the Gotland Basin, and lowest in sediments from the eastern Gulf of Finland. In all 3 cores echinenone was the dominant carotenoid in the topmost layer of the sediment (0-1 cm). In the deeper sections of the cores, myxoxanthophyll and zeaxanthin dominated. To our knowledge, this is first time that myxoxanthophyll and echinenone have been detected in Baltic Sea sediments from the early Litorina stage. The decrease in the pigment content with sediment depth coincides with a decrease in carbon content, and also fits in with general historical records of the occurrence and intensity of cyanobacterial blooms in the Baltic Sea, which show that cyanobacterial blooms were seldom recorded before World War II.

Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.

AIMS/HYPOTHESIS: In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA(1c); secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia. METHODS: In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA(1c) >or=8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups. RESULTS: During the last 12 weeks, FPGs averaged 5.75+/-0.02 and 5.96+/-0.03 mmol/l (p<0.001) and insulin doses were 68+/-5 and 70+/-6 IU/day (0.69+/-0.05 and 0.66+/-0.04 IU kg(-1) day(-1), NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA(1c) was 7.14+/-0.12 and 7.16+/-0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1+/-0.8 episodes/patient-year) than in the NPH+MET group (9.0+/-2.3 episodes/patient-year, p<0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1+/-0.3 mmol/l) than in the G+MET group (8.6+/-0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA(1c) <7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7+/-0.2 vs 6.7+/-0.3 mmol/l for patients reaching vs those not reaching target, p<0.01). CONCLUSIONS/INTERPRETATION: Good glycaemic control can be achieved with both G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinner time hyperglycaemia compared with NPH+MET.

Liver transplantation restores low serum levels of very low density and high density lipoproteins in end-stage primary biliary cirrhosis.

Amounts of serum lipids were determined in 10 women suffering from end-stage primary biliary cirrhosis (PBC) in order to evaluate the concentrations of and changes in very low density (VLDL), high density (HDL) lipoprotein cholesterol and apoprotein A-I before and after liver transplantation. The concentrations of some preoperative serum total lipids, especially HDL cholesterol and VLDL triglyceride, and apoprotein A-I, were significantly lower, but those of serum total triglycerides and cholestanol (a metabolite of cholesterol) were higher in the PBC patients than in 12 controls matched for age, sex, and body mass index. The relation between the serum concentrations of HDL cholesterol and cholestanol was markedly different before transplantation in the PBC group and in the control group. Liver transplantation was followed by a significant and rapid increase in serum apoprotein A-I and HDL cholesterol concentrations, which were affected by CMV and Klebsiella infections and acute rejections and immunosuppressive treatments. As a result the patients serum values did not quite return to normal during the three month follow up. The concentrations of serum VLDL cholesterol, triglycerides and cholestanol returned to normal during the follow up, and the changes in cholestanol were inversely related to the increases in amounts of HDL cholesterol. Thus, the restoration of low HDL concentrations after liver transplantation suggests that the liver plays a key role in HDL metabolism and indicates that concentrations of serum HDL cholesterol may be useful in monitoring the recovery of liver function.

Glibenclamide and gliquidone in the treatment of non-insulin-dependent diabetes mellitus.

The effect of glibenclamide and gliquidone on fasting blood glucose, 24-hour urinary glucose excretion, HbA1 concentrations and on the blood glucose and plasma insulin responses to an oral glucose load were investigated in 11 patients with non-insulin-dependent diabetes mellitus. The study was carried out as an open, ambulatory, cross-over trial during 24 weeks. After a 4-week diet period the patients were randomly allocated to treatment with either glibenclamide or gliquidone. After a 8-week period on a constant drug dose, they switched over to the corresponding dose of the other drug, each patient thus being his own control. Glibenclamide and gliquidone reduced fasting blood glucose values (p less than 0.001), diurnal urine glucose concentrations (p less than 0.001, resp. p less than 0.01) and HbA1 concentrations (p less than 0.02 resp. p less than 0.05) compared to the values in the diet period. Glibenclamide proved more effective than gliquidone in lowering fasting blood glucose concentrations (p less than 0.01), but no difference in 24-hour urine glucose and HbA1 concentrations was seen between the two drugs. Glibenclamide and gliquidone improved the glucose tolerance after an oral glucose load (p less than 0.01 resp. p less than 0.05) compared to diet values. The improved glucose tolerance during sulfonylurea treatment was, however, not associated with significant changes in insulin levels.

Serum cholesterol precursors, cholestanol, and plant sterols in primary biliary cirrhosis.

We measured serum cholesterol precursors (squalene, delta 8-cholestenol, desmosterol, lathosterol, cholestanol) and plant sterols (campesterol, sitosterol, and avenasterol) from 11 patients (one man) with primary biliary cirrhosis (PBC) and 13 healthy women matched for age and weight. In PBC serum total cholesterol was increased (9.4 versus 5.9 mmol/l; p less than 0.05), whereas serum cholestanol in terms of mmol/mol of cholesterol was elevated fourfold. In similar terms, serum plant sterols, especially sitosterol and avenasterol, were modestly increased, whereas most of serum cholesterol precursors were decreased. The serum contents of cholestanol were negatively associated with those of serum cholesterol precursors and positively with those of sitosterol and avenasterol with the serum cholesterol concentration. The liver function tests were positively related to serum cholestanol contents (r value ranged from 0.588 to 0.839 for alkaline phosphatase, aspartate aminotransferase, alanine amino-transferase, and bilirubin). The findings suggest that in cholestatic liver disease reduced serum cholesterol precursor contents reflect reduced cholesterol synthesis, whereas increased serum plant sterol and cholestanol contents are determined mainly by impaired biliary elimination.

High cholestanol and low campesterol-to-sitosterol ratio in serum of patients with primary biliary cirrhosis before liver transplantation.

Serum levels of cholesterol precursors (squalene, delta 8-cholestanol, desmosterol and lathosterol), plant sterols (campesterol and sitosterol), cholestanol and cholestanol/noncholesterol sterol ratios were related to liver damage and liver transplantation indications in healthy controls (n = 26) and in 31 patients with primary biliary cirrhosis divided into group I (S-bilirubin less than 21 mumol/L; n = 14), group II (S-bilirubin 21 to 108 mumol/L; n = 7) and group III (elected for liver transplantation; S-bilirubin 109 to 520 mumol/L; n = 10). The mean serum respective lathosterol levels in controls and in group I were three and two times higher than those in groups II and III, respectively. The plant sterol contents were higher in group II than in groups I and III and the campesterol/sitosterol ratios were lowest in group III. The serum cholestanol levels were high even in group I (i.e., in patients without icterus) and increased progressively to group III, up to 6 and 13 times those in group I and the control group, respectively. The cholestanol/noncholesterol sterol ratios increased progressively from the controls to groups I, II and III. The serum cholestanol levels were positively related to serum bilirubin levels in all primary biliary cirrhosis patients (n = 31, r = 0.906) and to the plant sterol levels in the control group and group I, but significantly negatively in group III. The cholestanol vs. precursor sterol correlations were negative in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum and hepatic cholestanol, squalene and noncholesterol sterols in man: a study on liver transplantation.

Serum noncholesterol sterols indicate overall cholesterol metabolism in a variety of experimental and clinical conditions. In patients with advanced primary biliary cirrhosis serum cholestanol, a 5 alpha-derivative of cholesterol, is markedly increased, and cholesterol precursors, which are indicators of cholesterol synthesis, are clearly reduced, as is the ratio of plant sterols (campesterol/sitosterol). Therefore these variables were studied in the livers and sera of 23 patients undergoing liver transplantation (16 patients with chronic liver disease, 4 with acute liver failure and 3 receiving second liver) and in 10 healthy controls. A most striking finding was the markedly high liver and serum levels of cholestanol in patients with chronic end-stage liver disease, a finding specific for cholestanol but not for other sterols. Of the cholesterol precursor sterols, lathosterol exhibited low contents in both the serum and liver of the cirrhotic patient group, supposedly reflecting decreased cholesterol synthesis. In contrast to the largely similar levels of noncholesterol sterols in serum and liver and the positive correlations between the two sources, the serum squalene levels were markedly lower than the hepatic levels, with a negative correlation between the serum and the liver, suggesting that serum squalene content poorly reflects cholesterol synthesis. In contrast to campesterol, serum and liver sitosterol tended to show increases, and the serum and hepatic campesterol/sitosterol ratios were lower in the chronic liver disease patients than in the controls, probably because of the more consistently impaired biliary elimination of sitosterol in those patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Causes of weight gain during insulin therapy with and without metformin in patients with Type II diabetes mellitus.

AIMS/HYPOTHESIS: To determine causes of weight gain during insulin therapy with and without metformin in Type II (non-insulin-dependent) diabetes mellitus. METHODS: Twenty-six patients with Type II diabetes (body mass index 28+/-1 kg/m2) were treated with insulin alone (n = 13) or insulin and with metformin (n = 13). Components of energy balance (basal metabolic rate, energy intake, glucosuria) were measured at 0 and 12 months. RESULTS: Glycaemic control improved similarly in patients using (HbA1c 10.5+/-0.3 vs 7.6+/-0.2%, p<0.001) and not using (10.2+/-0.3 vs 7.8+/-0.3%, p < 0.001) metformin. The metformin group required 47 % less insulin than the group not using metformin (p < 0.001). Body weight increased by 3.8+/-0.8 and 7.5+/-1.6 kg (p < 0.05), respectively. Basal metabolic rate and glucosuria were similar at 0 and 12 months in both groups but the metformin group decreased energy intake by 1.12+/-0.46 MJ/day, whereas it remained unchanged in the other group (0.15+/-0.42 MJ/day). Changes in body weight and glycaemia were statistically significant independent determinants of basal metabolic rate. Their change in opposite directions explained why basal metabolic rate remained unchanged. CONCLUSION/INTERPRETATION: Improved glycaemia promotes weight gain by decreasing both basal metabolic rate and glucosuria. Use of metformin decreases weight gain by reducing energy intake and is therefore a useful adjunct to insulin therapy in patients with Type II diabetes.

Serum squalene and noncholesterol sterols before and after delivery in normal and cholestatic pregnancy.

Mechanisms of hyperlipidemia were studied by measurement of serum lipid concentrations and the ratios of cholesterol precursors (squalene, delta 8-cholestenol, desmosterol, and lathosterol), plant sterols (campesterol and sitosterol), and cholestanol (a 5 alpha-derivative of cholesterol) to cholesterol in nonpregnant women, and normal and cholestatic pregnancies near term, and a few days and 6 weeks after delivery. The ratios of the precursors are known to reflect cholesterol synthesis, those of plant sterols and cholestanol the absorption efficiency and biliary sterol secretion of cholesterol. In normal pregnancy, increased serum cholesterol was associated with up to 2-fold increases in squalene, desmosterol, and lathosterol proportions, and the values remained elevated, especially for desmosterol, during the lactation period. These findings suggest that pregnancy and lactation are associated with increased cholesterol synthesis. The proportions of plant sterols were slightly lower, but that of cholestanol was 2-fold that of the nonpregnant women. In contrast to the latter group, the cholestanol proportions were not related to those of plant sterols or the campesterol/sitosterol ratio. The values, especially of cholestanol, became normal during lactation. In cholestatic pregnancy the changes were basically similar, but the serum values of delta 8-cholestenol increased more, and those of squalene, desmosterol and lathosterol less markedly, and the mean cholestanol proportion was 40% higher and the campesterol/sitosterol ratio 15% lower than in the normal pregnancy. Cholestanol was positively related to serum bilirubin and bile acids in cholestatic pregnancy, yet only one-third of the cholestatic pregnant women exhibited cholestanol values higher than in the healthy pregnant women.

Oral guar gum, a gel-forming dietary fiber relieves pruritus in intrahepatic cholestasis of pregnancy.

BACKGROUND: Guar gum is a gel-forming fiber, which increases fecal elimination of bile acids. It may therefore be beneficial in the treatment of intrahepatic cholestasis of pregnancy. METHODS: Forty-eight patients with intrahepatic cholestasis of pregnancy were randomized double-blind to receive either guar gum or placebo until delivery. Serum bile acid concentration was measured. Pruritus was assessed by both the investigator and the patient. RESULTS: At baseline, the intensity of pruritus and the serum bile acid concentration were significantly related. Guar gum diminished or prevented worsening of pruritus, while in the placebo group pruritus was enhanced (p<0.05). In the placebo group serum bile acid concentration increased significantly, whereas in the guar gum group it remained unchanged (p<0.05 between the groups). Guar gum treatment-induced changes of the pruritus score and serum bile acid concentrations were significantly related (p<0.01). CONCLUSIONS: Guar gum relieved the intensity of pruritus without any side effects and prevented the rise in serum bile acid concentration in this placebo-controlled and double-blind study of patients with intrahepatic cholestasis of pregnancy.

Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial.

BACKGROUND: Compared with other insulin regimens, combination therapy with oral hypoglycemic agents and bedtime insulin produces similar improvement in glycemic control but induces less weight gain. OBJECTIVE: To determine whether bedtime insulin regimens differ with respect to their effects on weight gain in patients with type 2 diabetes. DESIGN: Randomized, controlled trial. SETTING: Four outpatient clinics at central hospitals. PATIENTS: 96 patients (mean age, 58 +/- 1 years; mean body mass index, 29 +/- 1 kg/m2) whose type 2 diabetes was poorly controlled with sulfonylurea therapy (mean glycosylated hemoglobin value, 9.9% +/- 0.2%; mean fasting plasma glucose level, 11.9 +/- 0.3 mmol/L [214 +/- 5 mg/dL]). INTERVENTION: Random assignment to 1 year of treatment with bedtime intermediate-acting insulin plus glyburide (10.5 mg) and placebo, metformin (2 g) and placebo, glyburide and metformin, or a second injection of intermediate-acting insulin in the morning. Patients were taught to adjust the bedtime insulin dose on the basis of fasting glucose measurements. MEASUREMENTS: Body weight, biochemical and symptomatic hypoglycemias, and indices of glycemic control. RESULTS: At 1 year, body weight remained unchanged in patients receiving bedtime insulin plus metformin (mean change, 0.9 +/- 1.2 kg; P < 0.001 compared with all other groups) but increased by 3.9 +/- 0.7 kg, 3.6 +/- 1.2 kg, and 4.6 +/- 1.0 kg in patients receiving bedtime insulin plus glyburide, those receiving bedtime insulin plus both oral drugs, and those receiving bedtime and morning insulin, respectively. The greatest decrease in the glycosylated hemoglobin value was observed in the bedtime insulin and metformin group (from 9.7% +/- 0.4% to 7.2% +/- 0.2% [difference, -2.5 +/- 0.4 percentage points] at 1 year; P < 0.001 compared with 0 months and P < 0.05 compared with other groups). This group also had significantly fewer symptomatic and biochemical cases of hypoglycemia (P < 0.05) than the other groups. CONCLUSIONS: Combination therapy with bedtime insulin plus metformin prevents weight gain. This regimen also seems superior to other bedtime insulin regimens with respect to improvement in glycemic control and frequency of hypoglycemia.

Oral guar gum treatment of intrahepatic cholestasis and pruritus in pregnant women: effects on serum cholestanol and other non-cholesterol sterols.

BACKGROUND: Our aim was to investigate whether intestinal binding of bile acids by guar gum, a dietary fibre, relieves cholestasis and pruritus in intrahepatic cholestasis of pregnancy. METHODS: Forty-eight pregnant women with cholestasis and pruritus were randomized double-blind to guar gum and placebo until the time of delivery, and 20 healthy pregnant women were used as control subjects. The pruritus score and serum bile acids, lipids and non-cholesterol sterols were measured at baseline, at least 2 weeks after treatment, just before delivery and up to 4 weeks after delivery. RESULTS: The increase in serum bile acids and worsening of pruritus were prevented by guar gum in relation to placebo (P < 0.05). Serum cholesterol was unchanged, but increased cholesterol precursor sterol values suggested that cholesterol synthesis was increased by guar gum. Serum cholestanol proportion, an indicator of cholestasis, was related to pruritus but was unaffected by guar gum. CONCLUSION: We conclude that in intrahepatic cholestasis of pregnancy and pruritus, guar gum treatment is beneficial in relieving pruritus, even although indicators of cholestasis are only partially reduced.