Interferon-associated retinopathy during the treatment of chronic hepatitis C: a systematic review.

The incidence of retinopathy in patients with chronic hepatitis C treated with interferon-based regimens has been variably reported in the literature. There is no consensus regarding ophthalmologic screening before and during treatment with interferon-based therapy. To assess the incidence of retinopathy in patients with chronic hepatitis C being treated with interferon-based regimens and estimate the rate of resolution. A systematic literature search was performed to locate all relevant publications. Pooled incidence of retinopathy was calculated in patients treated with interferon or pegylated interferon. We also estimated the rate of discontinuation of treatment and resolution after the treatment was stopped. A total of 21 studies fulfilled the inclusion criteria. The overall incidence of retinopathy using random effect model was 27.7% (95% confidence interval [CI] 20.9-34.5%). The pooled incidence of retinopathy in 10 studies that only used pegylated interferon was 20.9% (95% CI: 11.6-29.8). The incidence of retinopathy with pegylated interferon in diabetic and hypertensive patients (high-risk group) was 65.32% and 50.7%, respectively. This was significantly higher compared with the incidence of retinopathy (11.7%) in patients without these risk factors. Overall pooled estimate for the resolution of retinopathy was 87% (95% CI 75.7-98.4%). The rate of discontinuation of treatment was 6.3%. The incidence of retinopathy with pegylated interferon in patients without hypertension and diabetes is low, but the risk is higher in patients with diabetes and hypertension. Routine pretreatment fundoscopic screening may not be warranted in all patients and can be limited to the patients with these risk factors.

Capsule endoscopy with PILLCAM ESO for detecting esophageal varices: a meta-analysis.

AIM: The aim of the present study was to perform meta-analysis of studies that compare diagnostic capabilities of esophageal capsule endoscopy (ECE) against conventional esophago-gastro-duodenoscopy (EGD) in detecting esophageal varices. METHODS: A literature search is done for studies that compared the performance of ECE and EGD in screening and surveillance of esophageal varices. Data was extracted to estimate the pooled sensitivity, pooled specificity, positive diagnostic ratio, negative diagnostic ratio and diagnostic odds ratio. RESULTS: We included 9 studies and total number of patients was 631. There were 12 capsule failures so data was available for 619 patients. The pooled sensitivity and specificity of CE for detecting esophageal varices were 83% and 85% respectively. The pooled positive likelihood and negative likelihood ratios are 4.09 and 0.25, respectively. Pooled diagnostic odds ratio was 24.92. CONCLUSION: In our meta- analysis PillCam ESO performed well in detecting esophageal varices but it was not comparable to EGD; it can be an acceptable alternative in certain situations but cannot be recommended to replace EGD.

Tacrine. A cause of fatal hepatotoxicity?

Tacrine, an acetyl cholinesterase inhibitor used in the treatment of Alzheimer's disease, often causes reversible abnormalities in liver enzymes, but significant hepatotoxicity is uncommon. We describe fatal hepatic failure associated with tacrine administration. A 75-year-old woman with Alzheimer's disease, taking tacrine for 14 months, developed progressive jaundice. Liver function abnormalities developed during tacrine treatment and led to hepatic failure and death. An extensive evaluation for other etiologies of liver disease was negative. Other potentially hepatotoxic medicines had been administered for at least 2 years before beginning tacrine, and postmortem examination of the liver was consistent with drug-induced hepatotoxicity. Approximately half the patients treated with tacrine have liver enzyme abnormalities develop, primarily in the first 12 weeks of therapy, that resolve with discontinuation of drug or dosage adjustment. Our case of tacrine-associated hepatotoxicity 14 months after the initiation of treatment despite regular biochemical evaluation suggests the potential for delayed and fatal hepatotoxicity with tacrine.

Polymorphism of human transcobalamin II: substitution of proline and/or glutamine residues by arginine.

The sequence of transcobalamin II (TC II) cDNA amplified from human fibroblast and colon adenocarcinoma (Caco-2) and the electrophoretic mobility of TC II secreted by these cell lines were analyzed to get some insights into the structural basis for the expression of various polymorphic forms of human TC II. Based on relative anodic mobilities of TC II phenotypes expressed in human serum, TC II expressed in the fibroblast cell line studied and Caco-2 cells were assigned as the MX (medium/extremely slow) and S (slow) types, respectively. Nucleotide sequence analysis of TC II cDNA amplified from these cells revealed that residues Arg and Arg, Gln and Arg, and Gln and Pro were present at positions 234 and 259, respectively, in TC II alleles encoding the X, S and M types. Based on these results, we suggest that differences in the anodic mobilities of the various polymorphic forms of TC II such as the X, S and M types are due to charge difference on the protein caused by the replacement of uncharged residues by arginine at positions 234 and/or 259.

Hepatic outflow obstruction (Budd-Chiari syndrome). Experience with 177 patients and a review of the literature.

Budd-Chiari syndrome (BCS) may not be as uncommon as was once believed. Our study has substantiated the existence of 2 major clinical forms. The acute syndrome is invariably associated with extensive blockage of the major hepatic veins, resulting in congestive liver cell necrosis. In a small, but significant, number of patients the inferior vena cava (IVC) is also occluded. The important etiologic factors are related to hypercoagulability of blood. Immediate placement of a shunt improves survival. The chronic syndrome is characterized by portal hypertension and is associated with a variable abnormal vascular anatomy. The causes of the chronic syndrome are not clear, but a substantial number of cases are related to the presence of an IVC membrane. Shunt surgery is effective but procedures aimed at the primary pathology are likely to be even more so. The natural history of BCS should be viewed over a long period of time. The very long survival of several patients urges a more cautious approach to surgical remedies. Budd-Chiari syndrome probably represents a spectrum of disease caused primarily by a hypercoagulable state and having a varied presentation depending on the balance between rate of formation and the extent of the thrombosis and the body's own rate of thrombolysis and recanalization. The extent and efficacy of the individual's collateral circulation and the rate of development of liver fibrosis are other determinants. It is thus possible to view BCS as a continuum of a single pathogenetic spectrum. Pregnancy-related BCS in India probably has strong social determinants, and is usually acute and fulminant. We have, however, documented a chronic form not described earlier. Children usually do not have acute BCS, but chronic BCS in children and adolescents is similar to that in adults. Membranous obstruction of the inferior vena cava (MOVC) is common and was found even at a young age. The association of MOVC with hepatocellular carcinoma, however, did not appear to be as clear as was previously believed. There has been a wide geographical variability in the causes and manifestations of BCS. Our study has clearly shown that--Kipling's categorical statement to the contrary--East and West do meet in India, in the Budd-Chiari syndrome.

Long term results of endoscopic dilatation for corrosive oesophageal strictures.

Although dilatation is the treatment of choice for most patients with benign oesophageal strictures, there is little information on its efficacy and safety in corrosive oesophageal strictures. Of 123 adults with benign oesophageal strictures treated by endoscopic dilatation, 52 (42.3%) had strictures after corrosive ingestion and 39 (31.7%) had peptic strictures. Treatment was considered adequate if the oesophageal lumen could be dilated to 15 mm and there was complete relief of dysphagia. If dysphagia recurred after adequate initial dilatation, the stricture was dilated again up to 15 mm. Initial dilatation was adequate in 93.6% of patients with corrosive strictures and this success rate was comparable with that of the peptic stricture group (100%, p > 0.05). Long term success after adequate initial dilatation was studied in 36 patients with corrosive strictures (mean follow up 32.36 (17.12) months, range 6-60) and 33 patients with peptic strictures (mean follow up 36.32 (17.9) months, range 6-60). The mean (SEM) number of symptomatic recurrences per patient month during the total follow up period in the corrosive group was significantly higher than that in the peptic group (0.27 (0.04) v 0.07 (0.02), p < 0.001). The recurrence rate in the corrosive group, however, decreased over time, and after 12 months it was significantly (p < 0.001) lower than the recurrence rate in the first six months. After 36 months, the difference in the recurrence rate in the two groups was not significant (p > 0.05). Only nine oesophageal perforations occurred during a total of 1373 dilatation treatments (procedure related incidence 0.66%), and eight of these were in the corrosive stricture group. These patients were managed conservatively and subsequently strictures were dilated adequately in all. Endoscopic dilatation is safe and effective for short and long term relief of dysphagia in patients with corrosive oesophageal strictures.

Primary hepatic lymphoma mimicking fulminant hepatic failure.

A patient with clinical presentation mimicking fulminant hepatic failure was found to have primary non-Hodgkin's lymphoma of liver on autopsy. He had tender nodular hepatomegaly, elevated liver enzymes and appearance of a diffuse infiltrative disorder on sonography. Extensive diffuse infiltration may be the dominant factor for the rapid hepatocellular failure in this case.

Abnormal gallbladder function in patients with irritable bowel syndrome.

Abnormalities of the autonomic nervous system function and cholecystokinin release have been described in patients with irritable bowel syndrome. Because the autonomic nervous system and cholecystokinin have an important role in the normal functioning of the gallbladder, we studied gallbladder contraction in response to a meal, using real time ultrasonography in irritable bowel syndrome patients (n = 20) and healthy controls (n = 15). The following parameters were studied: 1) fasting gallbladder volume, 2) residual volume after maximal contraction and at the end of 2 h, 3) maximum percent of gallbladder emptied, and 4) the time taken for maximal contraction. Fasting gallbladder volume (26.21 +/- 1.81 ml vs 15.21 +/- 1.63 ml, p < 0.001), and residual volume after maximal contraction (14.2 +/- 1.69 ml vs. 5.86 +/- 0.98 ml, p < 0.001) and at the end of 2 h (18.81 +/- 1.73 ml vs. 11.65 +/- 1.45 ml, p < 0.01) were significantly higher in the patient group, compared with controls. The maximum emptying was less (49.55 +/- 2.75% vs. 63.98 +/- 4.55%, p < 0.01) and the time taken for maximal contraction (59.25 +/- 3.8 min vs. 42.33 +/- 2.04 min, p < 0.001) was longer in the patient group than in the controls. Based on these observations, we conclude that patients with irritable bowel syndrome have significant abnormalities of gallbladder motor function.

Isolated portal hypertension in sarcoidosis. A report of two Indian patients.

Two patients with portal hypertension due to sarcoidosis are described. While one of them had severe bleeding from varices the other was asymptomatic. Endoscopic sclerotherapy obliterated the bleeding varices and is planned for the other patient if he bleeds.

Magnetic resonance imaging in pancreatic diseases: comparison with other imaging techniques.

Magnetic resonance imaging (MR) was performed in 14 healthy subjects and 16 patients with pancreatic disease. All the 16 patients were subjected to ultrasonography (USG), computed tomography (CT) and MR while endoscopic retrograde cholangiopancreatography (ERCP) was performed in 10 cases. In one patients with adenocarcinoma and two with gastrinoma, MR demonstrated abnormalities while USG and CT were normal. MR was, however, inferior to ERCP in demonstrating ductal abnormalities in chronic pancreatitis. Our initial experience suggests that MR is superior to other imaging modalities in the diagnosis and staging of pancreatic tumors; however, it is inferior to ERCP in the diagnosis of pancreatitis.

Small bowel adenocarcinoma mimicking tubercular stricture. Role of enteroscopy in early diagnosis.

We report a patient with high jejunal stricture initially thought to be tubercular in origin. There was, however, no response to antitubercular treatment and enteroscopic biopsy revealed it to be an adenocarcinoma. This case illustrates the role of enteroscopy and biopsy in the definitive diagnosis of high small bowel strictures.

Caroli disease: computed tomographic diagnosis.

Computed tomographic (CT) scan findings in patients with cavernous ectasia of the biliary tract (Caroli disease) have been described. Our patient had the isolated form of Caroli disease characterized by saccular dilatation of intrahepatic bile ducts and no evidence of portal hypertension. CT scan of the liver showed tiny dots with strong contrast enhancement within dilated intrahepatic bile ducts (the central dot sign). This finding when correlated with sonogram indicated portal radicles surrounded by dilated intrahepatic bile ducts.

Primary sclerosing cholangitis with chronic pancreatitis.

We report a patient with primary sclerosing cholangitis and associated pancreatitis. She had exocrine and endocrine pancreatic insufficiency.

Comparative evaluation of visual, somatosensory, and auditory evoked potentials in the detection of subclinical hepatic encephalopathy in patients with nonalcoholic cirrhosis.

To objectively determine the incidence of subclinical hepatic encephalopathy (SHE) and the relative sensitivity of different evoked potentials for its detection, 22 nonalcoholic cirrhotics without clinically detectable neurological abnormality and an equal number of matched healthy controls were studied. Of the three evoked potentials, visual evoked potential (VEP) studied by the pattern shift reversal method was not found to be abnormal in any patient. Short latency somatosensory evoked potential (SSEP) was abnormal in one (4.5%) and brain stem auditory evoked potential (BAEP) in nine (41%) patients. There was little advantage of performing both BAEP and SSEP in a patient, since the two together were abnormal in 10 (45.5%) patients, with SSEP adding only one more patient. Interpeak latencies I-III, III-V, and I-V in BAEP test were found to be the most sensitive parameters for the detection of SHE. Our results argue in favor of BAEP as the single investigation of choice for the objective assessment of SHE in patients with cirrhosis of the liver.

Ulcers after intravariceal sclerotherapy: correlation of symptoms and factors affecting healing.

Esophageal variceal ulcers have been held responsible for most postsclerotherapy complaints. To investigate a possible relation between these ulcers and symptoms, we followed for 4 weeks 40 patients with portal hypertension who had received a single course of intravariceal sclerotherapy. All 40 patients were found to have mucosal variceal ulcers on the day after sclerotherapy. One or more symptoms were given by 26 (65%) patients; dysphagia by 53% (mean duration 4.6 +/- 2.2 days), retrosternal pain by 28% (mean duration 3.0 +/- 2.5 days), and fever by 15% (mean duration 2.1 +/- 0.4 days). A gastric variceal ulcer was responsible for bleeding in one (2.2%) patient. We found no correlation between the occurrence and duration of symptoms and the presence of variceal ulcers. While symptoms were transient, ulcers persisted for several days to weeks in most patients. Patients who had received a higher amount of sclerosant developed larger ulcers (greater than 1 cm) with more symptoms and healing was more delayed than in those who had received lesser amounts and developed smaller ulcers (less than 1 cm). In patients with a serum albumin level greater than 3.0 g/dl, ulcers healed more often than in those with a less than 3.0 g/dl albumin (72 versus 18%, p less than 0.05). Development of mucosal ulcers is a natural consequence of intravariceal sclerotherapy and it appears unrelated to symptoms. The chemical nature and the volume of the injected sclerosant are probably responsible for the symptoms after sclerotherapy. Further, postsclerotherapy ulcers heal spontaneously, more often in patients with good nutritional status.

Seasonal variations of arterial blood pressure in normotensive and essential hypertensives.

Marked seasonal variations in environmental fluid losses and arterial blood pressure (BP) have been observed by us. Factors causing these changes in BP have been investigated. Effect of seasonal variation on BP was studied in 15 controls and 15 essential hypertensives. Mean temperature and relative humidity in well defined 5 local seasons was recorded. Monthly observations included the plasma levels and 24 hours urinary excretion of norepinephrine (NE), epinephrine (E), sodium (Na+) and potassium (K+). Average systolic, diastolic and mean BP were higher in winter season in both the groups (P less than 0.01). In hypertensives this variation was observed despite a significant increase in drug consumption during winter season (P less than 0.001). Both the groups revealed higher plasma levels and daily urinary excretion of NE and E during winter months, (P less than 0.05 - less than 0.001). 24 hrs urinary volume, Na+ and K+ were significantly higher in winter season (P less than 0.05 - less than 0.001). These parameters showed a negative correlation with mean ambient temperature. Increased sympathetic nervous activity as documented by increased NE and E in plasma and urinary, and decreased environmental loss of fluids and sodium may be contributory to this rise in blood pressure during winter season.