Hypercalcemia of primary hyperparathyroidism was treated by cinacalcet in a patient with liver cirrhosis.

Cinacalcet is a type II calcimimetic agent which is an allosteric modulator of the calcium-sensing receptor (CaR) located on the surface of the parathyroid cells. Cinacalcet increases the sensitivity of CaR via binding to the transmembrane region of CaR. Increasing sensitivity of CaR causes reduced secretion of parathyroid hormone (PTH) and suppression of serum calcium levels. Cinacalcet has recently been approved by Federal Drug Administration (FDA) for the treatment of patients with secondary hyperparathyroidism on maintenance dialysis and hypercalcemia in patients with parathyroid cancer. It is used also in Europe for both indications. Several controlled studies have shown that cinacalcet is effective in normalizing serum calcium levels also in primary hyperparathyroidism. Cinacalcet is metabolized primarily in the liver by N-dealkylation leading to carboxylic acid and oxidation of naphthalene ring to form dihydrodiols. The safety and optimal dosage of the drug in hypercalcemic patients with liver impairment remains unclear. We present a patient with Child-Pugh B class primary biliary cirrhosis who presented with moderate hypercalcemia and was diagnosed as primary hyperparathyroidism. As she refused having parathyroid surgery for her parathyroid adenoma at first, her hypercalcemia was treated successfully with 30 mg/day cinacalcet for 6 months. Cinacalcet was discontinued after 6 months. Her calcium level increased gradually. As she accepted surgery this time, her parathyroid adenoma was removed by minimally invasive parathyroidectomy. Parathyroid adenoma was confirmed pathologically. Her calcium levels maintained within the normal ranges after surgery.

Plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor levels in non-alcoholic steatohepatitis.

AIM: This study was conducted to demonstrate the plasminogen activator inhibitor- 1 (PAI-1) and thrombin activatable fibrinolysis inhibitor antigen (TAFI-Ag) levels in non-alcoholic steatohepatitis (NASH). MATERIALS AND METHODS: Twenty-seven patients with biopsy-proven NASH and 18 healthy controls (HC) were recruited for the study. Anthropometric data, liver histology (no.=20) and laboratory parameters including PAI-1 and TAFI-Ag assessments were recorded. RESULTS: When compared with HC, patients with NASH had higher body weight, higher waist circumference, elevated blood pressure, higher fasting plasma glucose (FPG) levels and higher homeostasis model assessment (HOMA) scores. The mean plasma PAI-1 levels of patients was found to be higher than HC (87.60 ng/ml vs 30.84 ng/ml p=0.000) and mean plasma TAFI-Ag levels of patients was found to be significantly lower (8.69 microg/ml vs 12.19 microg/ml p=0.000). PAI-1 levels were correlated with systolic blood pressure, age, body weight, transaminases, waist circumference, FPG, body mass index, and HOMA score. TAFI-Ag levels were found to be negatively correlated with transaminases, waist circumference, and body weight. In multiple regression analysis, BMI was the independent variable effecting PAI-1 levels. We did not show any association between PAI-1, TAFI-Ag, disease activity score and fibrosis score. HOMA was the independent variable effecting liver fibrosis in our patients. CONCLUSION: In this study we demonstrated that patients with biopsy-proven NASH had higher PAI-1 and lower TAFI-Ag expression than HC. Elevated levels of PAI-1 in NASH is the consequence of insulin resistance state. Lower TAFI-Ag levels may be related to the overactivation of TAFI pathway resulting in TAFI-Ag depletion. Furthermore, liver function disturbances may impair TAFI production in NASH. We also showed that NASH patients even with slight elevations of transaminases feature marked insulin resistance and components of metabolic syndrome.

Prophylactic use of low-dose, on-demand, intramuscular hepatitis B immunoglobulin and lamivudine after liver transplantation.

The combination of hepatitis B immunoglobulin (HBIG) and antivirals (nucleos[t]ide analogs) has extended the applicability of orthotopic liver transplantation (OLT) for patients with hepatitis B virus (HBV)-related liver disease. However, HBIG administrations have an extremely high cost. Herein, we evaluated our results with low-dose, on-demand, intramuscular HBIG plus lamivudine (LAM) prophylaxis after OLT. The HBV DNA status in 40 patients at the time of OLT determined the treatment: group A (n = 22), HBV DNA (-), no antiviral pretreatment; group B (n = 11), HBV DNA (-), after LAM; group C (n = 3), HBV DNA (+) after LAM (LAM resistance/Adefovir [ADV] unavailable); group D (n = 2), HBV DNA (+), no antiviral pretreatment; and group E (n = 2), HBV DNA (-) after LAM + ADV (LAM resistance/ADV available). Five patients died within 12 months after OLT unrelated to HBV infection. The remaining 35 patients were followed for a median duration of 16 months (range, 6-93 months). Only two recipients from group C, who were transplanted despite LAM resistance + no ADV pretreatment, revealed recurrent HBV infections at 14 and 16 months posttransplantation; they were then treated successfully with ADV as it became available. The third group C recipient had undetectable HBV DNA at 18 months after OLT. The mean cumulative doses of HBIG administered within the first, second, and third years were 34,014, 5258, and 5090 IU, respectively. In conclusion, low-dose, on-demand, intramuscular HBIG plus (LAM +/- ADV) prophylaxis is a safe, efficient, and cost-effective regimen to prevent recurrent HBV infection following OLT. OLT despite untreated LAM resistance may require sustained higher serum HBsAb levels after surgery.

Toxic hepatitis associated with paroxetine.

Hepatotoxicity is a rare complication of paroxetine, a selective serotonin reuptake inhibitor. Regarded as safe in therapeutic use, there have been reports of cases of severe hepatic dysfunction with gross elevations of transaminase levels that may be related to this drug. We report here severe adverse cholestatic and hepatocellular injury in a patient taking paroxetine probably due to an immune-mediated hypersensitivity reaction.

The effect of interferon alpha administration on acute attacks of familial Mediterranean fever: A double-blind, placebo-controlled trial.

BACKGROUND: About a quarter of familial Mediterranean fever (FMF) patients are partially or totally resistant to colchicine. A previous observation reported that acute attacks may be shortened by administration of interferon alpha (IFN). OBJECTIVE: We designed a double-blind, placebo-controlled trial to test our initial observations of a beneficial response with IFN in FMF attacks. METHODS: We treated 34 acute abdominal attacks with IFN 5 million IU or placebo sc in the early phase of the attack. Leucocytes, thrombocytes, the erythrocyte sedimentation rate, fibrinogen, C-reactive protein (CRP), serum amyloid A protein (SAA), haptoglobin, transferrin, IL-1beta and TNF-alpha were measured at hours 0, 6, 12, 24 and 48. RESULTS: The median time to recovery in those treated with IFN and placebo was not significantly different, while the leucocytosis and high levels of fibrinogen were significantly more prolonged in placebo-treated patients. CRP and SAA were extremely elevated and peaked at 24h, remaining less marked in the IFN-treated patients but the difference was not statistically significant. Observations regarding the other parameters were unremarkable. CONCLUSIONS: Although there were some clues indicating a depressed inflammatory response with IFN, we could not demonstrate a definitive effect of this agent in this double-blind trial. The drug may suppress the acute inflammation of FMF only if administered at the earliest phase. CRP and SAA may be more sensitive indicators of an attack than ESR or fibrinogen.

Serum leptin levels in patients with liver cirrhosis and chronic viral hepatitis.

BACKGROUND: The aim of the present study was to investigate serum leptin levels in relation to anthropometric features in patients with liver cirrhosis (LC) and chronic viral hepatitis (CVH), and to determine the effect of the severity and aetiology of the LC on serum leptin levels. METHODS: Forty-nine patients with LC, 32 patients with CVH and 69 control subjects were age, body mass index (BMI) and sex-matched and included in the study. Plasma glucose, serum leptin and insulin levels were determined. Insulin resistance was assessed using homoeostasis model assessment (HOMA). Body composition was estimated by skinfold thickness. RESULTS: Female patients with Child-A LC had higher levels of leptin, and female and male patients with Child-A LC had higher absolute leptin (leptin/BFM) levels compared to patients with Child-C LC and control subjects. Serum leptin levels of the patients with alcohol LC were higher than the control subjects, but the absolute leptin levels were comparable. When alcoholic and post-viral hepatitis cirrhotic patients were compared with each other on an aetiologic basis, there was no significant difference between them in leptin and absolute leptin levels. There were significant correlations between leptin and BMI, body fat percentage (BFP), BFM (body fat mass) in all three groups in both sexes. CONCLUSIONS: These data suggest that the physiologic correlations among serum leptin level, sex, BMI and BFM were well preserved in patients with chronic liver disease. Patients with alcohol LC had higher leptin levels. In early stages of liver disease, leptin levels and absolute leptin levels are higher than in normal subjects. However, in advanced stages of the disease the significant decline in leptin levels and similar levels of leptin expressed in relation to BFM compared to control subjects predominantly represent the expression of fat mass.

Risk factors for hepatocellular carcinoma in Turkey.

The contribution of hepatitis B, hepatitis C, and excess alcohol intake to the development of hepatocellular carcinoma in Turkey was assessed. The study was conducted through a questionnaire sent to seven major medical referral centers in different regions of Turkey and is based on 207 patients seen in the period 1994-1997. Of the seven centers, two were located in West Turkey (54 patients), two were in Central Turkey (85 patients), and two were in south and southeast Turkey (68 patients). In 196 of the 207 patients (94.7%), there was a history of chronic liver disease, and in 180 patients (87%) liver cirrhosis was documented. Of the 207 patients, 116 (56%) had hepatitis B, 48 (23.2%) had hepatitis C, and 33 (15.9%) had a history of excess alcohol intake. Anti-delta testing was available in 69 of 116 patients with hepatitis B, and anti-HDV was positive in 13 of these patients (13/69, 18.8%). Of the 33 patients with a history of heavy alcohol intake, 18 had concomitant chronic viral hepatitis infection, and alcohol alone was the etiology of hepatocellular carcinoma in only 15 cases (7.2%). The distribution of etiologic factors was not homogenous in different geographical regions in Turkey. In central, south, and southeastern Turkey, the predominant etiology of hepatocellular carcinoma was hepatitis B, whereas in western Turkey the impact of hepatitis B, hepatitis C, and alcohol was similar. This study indicates that hepatitis B virus infection is the leading cause of hepatocellular carcinoma in Turkey, followed by hepatitis C infection and alcoholic liver disease.

Mirizzi's syndrome: diagnostic and surgical considerations in 25 patients.

Mirizzi's syndrome is a rare complication of long-standing cholelithiasis. Many surgical approaches of varying complexity have been advocated for treatment. However, the distorted extrahepatic biliary anatomy continues to be threatening, with a high risk of biliary complications. Presented here is a series of 25 patients with Mirizzi's syndrome who were treated at the Dokuz Eylul University Hospital since 1985. Type I lesion (without cholecystocholedochal fistula) was encountered in 11 patients, while the remaining 14 had type II lesions (with cholecystocholedochal fistula). Preoperative diagnoses were made in 14 of the 25 patients (56%). Follow-up in 17 patients ranged from 1 to 96 months (mean, 40 months). Unfortunately, the remaining 8 patients were lost to follow-up after discharge. The morbidity rate in our series was 32%, while no mortality was encountered. During long-term follow-up, no biliary stricture was diagnosed. Following an uneventful postoperative course, all of our patients are symptom-free and doing well, with normal liver function. We conclude that partial cholecystectomy alone is a safe and sound surgical approach for the treatment of type I lesions. For type II lesions, depending on the size of the fistula, either primary closure over a T-tube, or bilio-digestive anastomosis, preferably Roux-en-Y, can be an appropriate treatment modality, with a low morbidity rate.

Serum concentrations of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in patients with chronic hepatitis.

BACKGROUND: Insulin-like growth factor-I is a liver-derived humoral factor, which has important anabolic and metabolic actions and is predominantly bound by insulin-like growth factor binding protein-3. Low serum concentrations of both insulin-like growth factor-I and insulin-like growth factor binding protein-3 have been reported in patients with chronic liver disease, especially cirrhosis, but their conditions in chronic hepatitis are uncertain. The aim of this study was to evaluate the effect of chronic hepatitis on serum concentrations of insulin-like growth factor-I and insulin-like growth factor binding protein-3 and their association with hepatic inflammation activity and fibrosis. METHODS: Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 were measured by RIA (ng/ml) in 17 patients with mild to severe chronic viral hepatitis (12 chronic hepatitis C, 5 chronic hepatitis B) and 16 healthy subjects. The hepatic inflammation activity and the severity of fibrosis were evaluated using Desmet classification. RESULTS: Both insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels did not correlate with inflammation activity, fibrosis or transaminase levels. In the chronic hepatitis group, insulin-like growth factor-I levels were significantly higher than the control group (mean, 263.8 +/- 27.33 versus 127.14 +/- 10.83 ng/ml, P < 0.001, respectively), whereas insulin-like growth factor binding protein-3 levels were significantly lower when compared with the controls (1643.47 +/- 60.68 versus 2728.87 +/- 284.61 ng/ml, P < 0.05, respectively). CONCLUSIONS: These results suggest that the concomitant states of serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels in patients with chronic hepatitis may be different from cirrhotic patients and high serum IGF-I levels may be a specific finding of the stage of chronic hepatitis before developing cirrhosis.

Endoscopic sphincterotomy in the management of biliary leakage after partial hepatectomy.

We present the case of a 22 year-old man with biliary leakage caused by partial hepatectomy. He was successfully treated with endoscopic sphincterotomy alone.

The efficacy of interferon alpha on colchicine-resistant familial Mediterranean fever attacks: a pilot study.

About a quarter of familial Mediterranean fever (FMF) patients have recurrent painful attacks of polyserositis despite regular colchicine treatment. There is no known alternative drug for colchicine-resistant cases. We had previously observed a patient with FMF whose painful attacks disappeared during the 6 month period of interferon alpha (IFN) treatment for his chronic hepatitis B. The objective of the present study was to investigate the possible beneficial effect of IFN on these episodes. Twenty-one consecutive attacks in seven adult patients with FMF were treated at early onset with IFN, the dosage being 3-10 million I U s.c. Eighteen of the 21 attacks could be halted in a mean time of 3.05 h, while the intensity of abdominal pain remained very low. Observed side-effects were generally mild and acceptable. IFN may be a useful adjunct for the treatment of colchicine-resistant attacks in FMF patients.

The prokinetic effect of domperidone in gallbladder--not upon dopaminergic receptors.

The mechanism of the contractile effect of domperidone on gallbladder smooth muscle has been investigated by using an in-vivo and an in-vitro model. In the in-vivo part of the study 14 healthy males were administered 20 mg domperidone or two placebo tablets orally and gallbladder emptying was measured by ultrasonography. The reduction in the gallbladder volume was significant compared to the placebo at 45 and 55 min. In the in-vitro part of the study, the gallbladder strips isolated from guinea pigs were field stimulated and 10(-6)-10(-4) M concentrations of dopamine were administered before electrical field stimulation (EFS) was repeated. Dopamine exerted no significant effect upon the contractions obtained by EFS. The effect of dopamine and domperidone under basal conditions were also explored. Under basal conditions, dopamine neither contracted nor relaxed the gallbladder muscle between 10(-6) and 10(-4) M concentrations when added directly to the organ bath. Besides, a significant contraction was observed with 10(-4) M concentration of domperidone whereas 10(-7), 10(-6) and 10(-5) M concentrations exerted no effect. This effect of domperidone was thought to be nonspecific but inhibited by 10(-6) M atropine, 10(-5) M pirenzepine and abolished by 10(-6) M tetrodotoxin. In summary, domperidone produces a modest contraction in human gallbladder. This effect does not seem to occur upon dopaminergic receptors in guinea pig models.

Modulation of gallbladder contraction by pirenzepine in humans.

OBJECTIVES: The mechanism(s) by which cholinergic innervation modulates gallbladder contraction are not fully understood. To elucidate the role of muscarinic M1 receptors in the mediation of gallbladder contraction, we investigated gallbladder volume reduction, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) responses in humans during cephalic and intestinal phases of a meal under M1 muscarinic receptor blockade with pirenzepine. METHODS: In eight healthy subjects, intraduodenal meal- and in seven subjects, sham feeding-induced gallbladder volume reduction was measured by real-time ultrasonography during saline or pirenzepine administration. Plasma CCK and PP were measured by radioimmunoassay. RESULTS: Pirenzepine partially inhibited gallbladder volume reduction in response to an intraduodenal fatty meal. The integrated gallbladder volume reduction over 120 min was 4462 +/- 445%.min compared with 6879 +/- 279%.min in the saline control group (p < 0.01). Integrated plasma CCK and PP responses were unchanged in the presence of pirenzepine. Pirenzepine abolished sham feeding-induced gallbladder contraction and plasma PP response. Sham feeding with either isotonic saline or pirenzepine infusion did not modify fasting plasma CCK levels. CONCLUSION: M1 muscarinic receptors play an important role in the intestinal and cephalic phases of gallbladder contraction. Plasma CCK response to intraduodenal meal is not influenced by M1 muscarinic receptor blockade with pirenzepine.