Serum iron levels and hepatic iron overload in patients with nonalcoholic steatohepatitis.
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Publications and source records attributed to R K Dhiman.
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AIM: To study the association between chronic hepatitis C virus (HCV) and Mooren's type keratitis. METHOD: A total of 50 patients with chronic HCV were screened for any evidence of corneal ulceration. Detailed ocular examination was conducted by slit-lamp biomicroscopy. Patients with history of trauma to the eye or previous herpetic keratitis were excluded from the study. RESULTS: There were 37 males and 13 females. The age of the patients ranged from 10 to 70 years. There was no evidence of Mooren's ulcer in any of our patients. CONCLUSION: No association between chronic HCV and Mooren's ulcer was found in our study. Screening therefore in such cases is not necessary.
Omeprazole is frequently used in patients with cirrhosis of the liver to treat peptic ulcer disease. It is also used for the healing of mucosal lesions after endoscopic sclerotherapy of esophageal varices in cirrhosis and extraheptic portal vein obstruction (EHPVO). This study was carried out with the aim of determining the pharmacokinetics of omeprazole in different degrees of liver cirrhosis and in patients with EHPVO, compared with healthy volunteers. Ten healthy volunteers, 30 patients with cirrhosis of the liver, divided into 3 groups of 10 depending on severity (according to Child-Pugh classification A, B and C) and ten patients with EHPVO participated in the study. The subjects received an omeprazole 20 mg capsule after an overnight fast. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 6, 9 and 24 h after drug administration. Omeprazole level in plasma was estimated by reverse-phase high performance liquid chromatography (HPLC). The elimination half-life was significantly (p < 0.05) increased to 2.38 +/- 0.16, 3.26 +/- 0,12, 3.58 +/- 0.31 and 2.59 +/- 0.22 h in patients with different grades of cirrhosis (A, B and C) and also in patients with EHPVO, respectively, compared with 1.054 + 0.10 h in healthy volunteers. A similar significant increase (p < 0.05) was observed in the AUC(0alpha), while C(max) was significantly increased to 400.40 +/- 27.89 and 602 +/- 55.13 ng/ml in only grade C cirrhosis patients and EHPVO patients, compared with 303.5 +/- 36.42 ng/ml in healthy volunteers. No significant difference was observed in T(max). It was concluded that the metabolism of omeprazole was significantly impaired in both liver cirrhosis and EHPVO in comparison with healthy volunteers.
Several extrahepatic manifestations have been associated with infection with Hepatitis C virus (HCV) infection. It has been associated with Sjogren's syndrome (SS) and inflammatory myositis (IM). The objective was to look at the prevalence of anti-HCV antibodies in the serum of SS and IM patients of Indian origin. Individuals satisfying the European Economic Community criteria for the diagnosis of SS and those satisfying the criteria of Bohan and Peter for the diagnosis of IM were recruited in the study. Routine evaluation for liver functions was made. Anti-HCV antibodies were tested by a third generation ELISA, using microplate HCV3.0 ELISA. Of the 23 patients with SS studied, 14 had extraglandular features. The commonest were anaemia and arthritis in six each, followed by in lymphopenia in two. One patient each had interstitial lung disease, hypothyroidism and chronic active hepatitis. Twenty-two patients with IM were studied alongside. None of the patients had abnormal liver functions. One patient with primary SS tested positive for anti-HCV antibodies. None of the patients with inflammatory myositis tested positive for anti-HCV antibodies. The presence of anti-HCV antibodies in our cohort of patients with SS and IM is low and more in keeping with the generally low prevalence of the infection in the Indian population.
Several extra-intestinal diseases have been associated with Helicobacter pylori infection. Hepatic encephalopathy has been linked to H. pylori infection because of the ammonia produced by the organism in the stomach. H. pylori infection is commoner in cirrhotic patients with hepatic encephalopathy than in those without. Increased ammonia levels have been observed in the gastric juice and blood more commonly in cirrhotics with H. pylori infection than in those without. Though the amount of ammonia produced by H. pylori may be too small to contribute to hepatic encephalopathy, eradication of H. pylori has been shown to improve the blood ammonia levels and hepatic encephalopathy.
Cirrhosis of liver is often complicated by minimal hepatic encephalopathy (mHE), which is detected by neuropsychiatric and neurophysiological tests. mHE develops more commonly in cirrhotics with severe liver disease and in those with esophageal and gastric varices. On follow up, these patients more often develop overt encephalopathy as compared to cirrhotics without mHE. mHE may affect daily activities like sleep, driving ability, alertness, social interaction, and communication. It is probably also an independent predictor of survival. The most practical treatment strategy for mHE has not been established; however, it can be treated as effectively as overt encephalopathy with similar agents. Treatment improves mHE in terms of psychometric tests, but improvement in daily functioning has not been well documented.
Hepatic encephalopathy (HE) is a potentially reversible neuropsychiatric syndrome secondary to cirrhosis and other severe liver diseases. Magnetic resonance imaging (MRI) and MR spectroscopy (MRS) have been explored to provide new insight into the pathophysiology, diagnosis and treatment of HE. MRI shows brain atrophy especially in the frontal region. Globus pallidus, putamen and portions of the internal capsule appear hyperintense on T1-weighted images; this is likely to be due to deposition of manganese as a result of portosystemic shunting and liver dysfunction. MRS permits the detection and quantification of certain brain metabolites in vivo. There is decrease in myoinositol and choline concentrations and increase in glutamine concentrations. There is no change in n-acetyl-aspartate. Depletion of myoinositol is the most sensitive and specific spectroscopic marker in HE. Its loss is most likely a compensatory mechanism for the accumulation of glutamine. In conclusion, MRI and MRS examine different aspects of hepatocerebral disease.
OBJECTIVE: To comprehend the correlation between the in vitro activity of hepatic omeprazole (OMZ) hydroxylase and genotype of North Indians with respect to CYP2C19. METHODS: Microsomes were prepared from the livers of 15 North Indians. Assay of OMZ hydroxylase was performed by incubating the microsomes with OMZ in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH). The 5-OH-OMZ formed was assayed using high-performance liquid chromatography. Genomic DNA isolated from the blood of the same individuals was employed for genotyping of CYP2C19*2 and *3 using polymerase chain reaction-based diagnostic tests. RESULTS: Thirteen subjects demonstrated an average OMZ hydroxylase activity of 138 pmol 5-OH-OMZ formed/min/mg protein. They were designated as extensive metabolisers (EMs). Eight EMs were homozygous with CYP2C19*1/*1 genotype and demonstrated the highest average activity of OMZ hydroxylase (169 pmol 5-OH-OMZ formed/min/mg protein). Five heterozygous EMs (CYP2C19*1/*2) demonstrated 52% activity of OMZ hydroxylase compared with eight homozygous EMs (CYP2CI9*1/*1). Two subjects demonstrated 11% activity of OMZ hydroxylase (15 pmol 5-OH-OMZ formed/min/mg protein) compared with EMs. Hence, these individuals were designated as poor metabolisers (PMs). Both PMs had genotype CYP2C19*2/*2. None of the subjects had CYP2C19*3/*3 genotype. CONCLUSION: The results of the present study demonstrated concordance between the in vitro activity of OMZ hydroxylase and the CYP2C19 genotype in North Indians.
OBJECTIVE: To study the outcome of pregnancy in women with non-cirrhotic portal hypertension (NCPH). METHOD: A retrospective analysis of 50 pregnancies in 27 women with NCPH was carried out. Pregnancy outcome was compared in extra hepatic portal vein obstruction (EHPVO) and non-cirrhotic portal fibrosis (NCPF). RESULTS: The mean maternal age was 24.60+/-2.857 years, and the disease was diagnosed during pregnancy in 15 (55.6%) patients. Variceal bleeding occurred in 17/50 (34%) pregnancies and the majority (88.2%) of them responded to endoscopic sclerotherapy. Incidence of variceal bleeding during pregnancy was lower in pregnancies where the disease was diagnosed prior to pregnancy (8.6%), and it was 43.5% in EHPVO and 25.9% in NCPF. The mean birth weight of the neonates was 2668.4+/-427.42 g, and the incidence of abortion, prematurity, small for gestational age babies and perinatal death was 20, 17.5, 12.5 and 20%, respectively. Variceal bleeding during pregnancy was associated with a higher incidence of abortion (29.4%) and perinatal death (33.3%). CONCLUSION: Variceal bleeding is the most common complication in pregnancies with NCPH. Pregnancies can be allowed and managed successfully in patients with NCPH.
Portal hypertension usually occurs in patients with fulminant hepatic failure (FHF). There is, however, no information on portal venous hemodynamics in patients with FHF. Therefore, we studied the portal venous hemodynamics in patients with FHF using duplex Doppler ultrasonography. We measured the portal vein diameter, flow velocity, and volume flow with duplex Doppler ultrasonography in 29 patients with FHF and 15 patients with uncomplicated acute viral hepatitis. No significant difference was observed in the portal vein parameters in the two groups. Nineteen patients with FHF survived. No difference in portal flow velocity and flow rate was observed between survivors and nonsurvivors. A significantly lower portal flow velocity was observed in nine patients of FHF with ascites compared with those without ascites (12.29+/-2.81 vs 16.26+/-4.87 cm/sec; P < 0.01). Portal hemodynamics do not significantly change in fulminant hepatic failure; therefore, it has no prognostic significance.
BACKGROUND: Pleural effusion in cirrhotic patients (hepatic hydrothorax) may result from migration of ascitic fluid across defects in the diaphragm. Biochemical analysis of ascitic and pleural fluid provides only indirect information about the nature and origin of the effusion. The present study was performed in order to demonstrate the presence/absence of peritoneo-pleural communication by radioisotope imaging. METHODS: Ten patients with cirrhotic ascites and pleural effusion were studied with 99mTc sulfur colloid scintigraphy to look for movement of the radiotracer from the peritoneal to the pleural cavity. Serum-ascitic albumin gradient (SAAG) and serum-pleural fluid albumin gradient (SPAG) values were determined in eight patients to examine the nature of the ascitic and pleural fluids. RESULTS: Transdiaphragmatic movement of ascitic fluid into the pleural space was demonstrated (generally within 2 h of intraperitoneal injection of the radiotracer) in eight of 10 patients; six on the right side, one on the left and one bilaterally. Two patients in whom pleural fluid was transudative on SPAG values were negative for peritoneo-pleural communications. CONCLUSIONS: Radionuclide scintigraphy is a simple, safe and relatively non-invasive method to confirm passage of ascitic fluid across the diaphragm.
BACKGROUND AND AIMS: The natural history of subclinical hepatic encephalopathy (SHE) is unknown. The present study was conducted to study the prevalence and the natural history of SHE in patients with cirrhosis of the liver. METHODS: One hundred and sixty-five patients with cirrhosis of the liver were studied. A total of nine psychometric tests (trail making and Wechsler adult intelligence scale-performance (WAIS-P) tests) were administered. Subclinical hepatic encephalopathy was present if two or more psychometric tests were abnormal. Seventy-two patients (SHE 40, without SHE 32) also underwent serial psychometric testing on follow-up visits at 6-8 week intervals. RESULTS: Subclinical hepatic encephalopathy was present in 103 (62.4%) patients. The number and figure connection, block design and picture completion tests were the most useful in the detection of SHE. Severity of SHE, as assessed by the number of abnormal tests, was greater in patients with more severe liver disease. During follow up, SHE tended to persist or worsen in patients with poorer liver function. Although other clinical complications were similar in different groups, overt hepatic encephalopathy developed more commonly in those patients who had SHE at entry compared to those who did not (22.6 vs 5.6%, P = 0.044). Among the patients with SHE, the development of overt hepatic encephalopathy was more common in patients with Child's score of > 6 than with Child's score of <or= 6 (40 vs 5%, P = 0.019). CONCLUSIONS: We conclude that SHE is common in cirrhosis. The natural history of SHE is worse in patients with advanced cirrhosis and SHE probably predisposes the cirrhotic patient to overt hepatic encephalopathy.
BACKGROUND AND AIM: Biliary cholesterol supersaturation, gallbladder stasis and delayed intestinal transit are the key events in cholesterol gallstone formation. We studied the effect of cisapride, a prokinetic drug, on gallbladder emptying and bile composition in patients with gallstone disease undergoing cholecystectomy. METHODS: Gallbladder emptying, cholesterol saturation index (CSI) and nucleation time were studied in 21 patients with gallstone disease. Eleven patients (cisapride group, age 41.9 +/- 2.9 years) received tablet cisapride 10 mg t.i.d. for 2 weeks, while 10 patients (placebo group, age 42.1 +/- 1.9 years) received placebo for the same duration. Gallbladder emptying was repeated in all patients after a 2-week treatment with cisapride or placebo. Gallbladder bile was obtained at the time of surgery for the measurement of CSI and nucleation time. RESULTS: Residual volume of the gallbladder decreased (mean +/- SE, 18.6 +/- 2.5 mL vs 10.0 +/- 1.1 mL, P = 0.007), and the ejection fraction increased (43.5 +/- 5.3% vs 60.0 +/- 3.2%, P = 0.007) in patients in the cisapride group, while no change was observed in placebo group patients. Nucleation time was higher in the cisapride group than in the placebo group (14.9 +/- 1.3 days vs 8.0 +/- 0.9 days, P = 0.003). Patients in the cisapride group had a significantly lower cholesterol concentration (molar percentage, 5.1 +/- 0.3% vs 6.8 +/- 0.8%, P = 0.049) and CSI (1.0 +/- 0.1 vs 1.36 +/- 0.11, P = 0.034) than patients in the placebo group. CONCLUSION: Cisapride improves gallbladder emptying and bile lithogenicity in patients with gallstone disease.
BACKGROUND AND AIMS: Hyposplenism has been described in patients with alcoholic cirrhosis (AC). However, no data are available regarding hyposplenism in patients with non-alcoholic cirrhosis (NAC) and other forms of portal hypertension such as extrahepatic portal venous obstruction (EHPVO). The aim is to study the splenic functions in patients with AC, NAC, and EHPVO. METHODS: Splenic functions were assessed consecutively in 22 patients with AC, 21 with NAC, and 23 with EHPVO. The tests included pitted red blood cells (RBC; %) and Howell-Jolly bodies in the peripheral smear. Pitted RBCs > 2% with or without the presence of Howell-Jolly bodies were taken as indicators of hyposplenism. The splenic function in each group was compared with age-matched controls. RESULTS: Hyposplenism was found in 10 (45.45%) patients with AC, six (28.57%) with NAC and one (4.34%) with EHPVO. The mean pitted RBCs were significantly increased in patients with AC (mean 4.93 +/- 1.36% vs control 1.22 +/- 0.17%, P < 0.05), but not so with NAC (2.01 +/- 0.69%) and EHPVO (mean 0.99 +/- 0.1% vs control 0.66 +/- 0.1%, P > 0.05). Howell-Jolly bodies were seen in only four patients. The mean pitted RBCs were significantly higher among patients who were actively consuming alcohol (9.14 +/- 3.35%) compared to those who abstained at least for more than 24 weeks (2.0 +/- 1.3%, P < 0.05). CONCLUSION: Hyposplenism is more common in AC patients, particularly those who are actively consuming alcohol compared with those who abstain. Patients with NAC have a lower incidence of hyposplenism, while in EHPVO patients, it is uncommon.
BACKGROUND AND AIMS: Gallbladder motor function is impaired in many patients with diabetes, and may be related to cholinergic nerve damage. Cisapride is a prokinetic drug of the gastrointestinal tract and acts by releasing acetylcholine from cholinergic nerve endings. The aim of this study was to determine the effect of cisapride on gallbladder emptying in patients with type 2 diabetes mellitus (DM). METHODS: Gallbladder emptying and tests for autonomic neuropathy (AN) were performed in 27 patients with type 2 DM and in 10 healthy subjects. Gallbladder emptying was studied by using real-time ultrasonography after an overnight fast, and after the subjects received a breakfast that contained 2500 J. Gallbladder emptying was repeated after the treatment with cisapride (10 mg t.i.d.) for 1 week in all subjects. RESULTS: Abnormal gallbladder emptying was present in 14 (51.9%) patients. The residual gallbladder volume (mean +/- SEM) was higher (9.3 +/- 1.0 vs 4.6 +/- 0.6; P = 0.002), and ejection fraction was lower (57.4 +/- 4.0 vs 74.2 +/- 2.4; P = 0.015) in diabetic patients than it was in healthy subjects. Cisapride produced a reduction in fasting and residual volumes (24.6 +/- 2.4 vs 20.0 +/- 1.4; P = 0.034 and 9.3 +/- 1.0 vs 5.9 +/- 1.1; P = 0.00003, respectively), and an improvement in ejection fraction (57.4 +/- 4.0 vs 72.6 +/- 3.8; P = 0.000007). The improvement in gallbladder emptying after cisapride therapy was confined to the patients with AN (n = 13) (57.3 +/- 5.4 vs 80.4 +/- 2.9; P = 0.0017), suggesting denervation supersensitivity with an upregulation of cholinergic receptors. There was no significant change in the ejection fraction in patients without AN (57.5 +/- 6.1 vs 65.4 +/- 6.5; P = NS). Sex, duration of diabetes, peripheral neuropathy, diabetic retinopathy and serum cholesterol level did not influence gallbladder emptying. CONCLUSION: Impaired gallbladder emptying is common in patients with type 2 DM. Cisapride significantly improves gallbladder emptying in patients with autonomic neuropathy.