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.

Extended treatment duration for treatment naïve chronic hepatitis C genotype 1 late viral responders: a meta-analysis comparing 48 weeks vs 72 weeks of pegylated interferon and ribavirin.

Patients with genotype I chronic hepatitis C virus (HCV) infection with late virological response to therapy have low sustained viral response (SVR) with standard 48 weeks of therapy and may benefit from extended therapy. We performed a systematic review and meta-analysis of five studies to compare the outcome of 48 weeks vs 72 weeks treatment in treatment naïve chronic hepatitis C genotype I patients with late virological response. The end of treatment response with extended 72 weeks of treatment compared to standard 48 weeks of treatment was similar 48% and 56%, respectively, with pooled odds ratio (OR) (0.85; 95% CI 0.52-1.37). However, the SVR rates were higher with 72 weeks of treatment compared to 48 weeks treatment 32%vs 25% with pooled OR of 1.67 in favour of extended duration therapy (95% CI 1.16-2.40). This was because of lower relapse rates with extended duration therapy (35%vs 55%) with OR of 0.39 in favour of 72 weeks therapy (95% CI 0.25-0.61). There was no heterogeneity. No publication bias was noted as assessed by Egger's test. Extending the treatment duration from 48 to 72 weeks in genotype 1 infected patients with late virological response improves SVR. Thus, therapy extension in genotype 1 late viral responders (LVR) may be a consideration to improve treatment response; however, the proportion of patients with LVR that might benefit from 72-week therapy appears to be small.

Occult hepatitis B virus infection: a covert operation.

Detection of occult hepatitis B requires assays of the highest sensitivity and specificity with a lower limit of detection of less than 10 IU/mL for hepatitis B virus (HBV) DNA and <0.1 ng/mL for hepatitis B surface antigen (HBsAg). This covert condition is relatively common in patients with chronic hepatitis C virus (HCV) that seems to exert some influence on the replicative capacity and latency of HBV. Detection of virus-specific nucleic acid does not always translate into infectivity, and the occurrence of primer-generated HBV DNA that is of partial genomic length in immunocompetent individuals who have significant levels of hepatitis B surface antibody (anti-HBs) may not be biologically relevant. Acute flares of alanine aminotransferase (ALT) that occur during the early phase of therapy for HCV or ALT levels that remain elevated at the end of therapy in biochemical nonresponders should prompt an assessment for occult hepatitis B. Similarly, the plasma from patients with chronic hepatitis C that is hepatitis B core antibody (anti-HBc) positive (+/-anti-HBs at levels of <100 mIU/mL) should be examined for HBV DNA with the most sensitive assay available. If a liver biopsy is available, immunostaining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) should be contemplated and a portion of the sample tested for HBV DNA. This is another reason for optimal collection of a specimen (e.g. two passes with a 16-guage needle under ultrasound guidance). Transmission of HBV to immunosuppressed orthotopic liver transplant recipients by donors with occult hepatitis B (OHB) will continue to occupy the interests of the transplant hepatologist. As patients with OHB may have detectable HBV DNA in serum, peripheral blood mononuclear cells (PBMC) and/or liver that can be reactivated following immunosuppression or intensive cytotoxic chemotherapy, the patient needs to be either monitored or treated depending on the pretreatment serological results such as an isolated anti-HBc reaction or a detectable HBV DNA.

Metastatic ovarian tumour in patient of carcinoma stomach.

Krukenberg tumour (KT) is a metastatic ovarian tumour with primary usually seen in the gastrointestinal tract. Here we report the case of a 50-year old menopausal patient with gastric tumour presenting with solitary metastasis to the ovary within 5 months of primary gastric surgery, for which total abdominal hysterectomy with bilateral salpingo-oophorectomy was done. This case stresses the urgent need for early detection and surveillance of treatable tumours metastasising to the ovary.

Ultrasound guided percutaneous nephrostomy for obstructive uropathy in benign and malignant diseases.

OBJECTIVE: Analyze the success rate, complications and overall benefit of ultrasound guided percutaneous nephrostomy (PCN) for the relief of obstructive uropathy in benign and malignant diseases. MATERIALS AND METHODS: PCN was performed in 50 kidneys of 32 patients. It was performed in emergency rooms totally under ultrasound guidance by general surgeons. Seldinger technique was used in all cases. Changes in renal function after the procedure were analyzed using paired t-test. RESULTS: The procedure was successfully completed in 42 out of 50 kidneys (84%). There has been no major complication and 28% minor complications. The renal function improved significantly when PCN was performed for benign conditions (mean creatinine 3.52 mg/dL before and 2.18 mg/dL after PCN), however in malignancy there has been no significant improvement in renal function (before PCN mean creatinine 6.39 mg/dL and after PCN 5.41 mg/dL). CONCLUSION: We conclude that PCN can be effectively performed under ultrasound guidance and should be the initial procedure in acutely obstructed kidneys with pyonephrosis and poor renal function. In malignant cases, however, improvement in renal function is possible only if the procedure is carried out at an early stage.

Ultrasound guided percutaneous nephrostomy for obstructive uropathy in benign and malignant diseases

OBJECTIVE: Analyze the success rate, complications and overall benefit of ultrasound guided percutaneous nephrostomy (PCN) for the relief of obstructive uropathy in benign and malignant diseases. MATERIALS AND METHODS: PCN was performed in 50 kidneys of 32 patients. It was performed in emergency rooms totally under ultrasound guidance by general surgeons. Seldinger technique was used in all cases. Changes in renal function after the procedure were analyzed using paired t-test. RESULTS: The procedure was successfully completed in 42 out of 50 kidneys (84 percent). There has been no major complication and 28 percent minor complications. The renal function improved significantly when PCN was performed for benign conditions (mean creatinine 3.52 mg/dL before and 2.18 mg/dL after PCN), however in malignancy there has been no significant improvement in renal function (before PCN mean creatinine 6.39 mg/dL and after PCN 5.41 mg/dL). CONCLUSION: We conclude that PCN can be effectively performed under ultrasound guidance and should be the initial procedure in acutely obstructed kidneys with pyonephrosis and poor renal function. In malignant cases, however, improvement in renal function is possible only if the procedure is carried out at an early stage.

Terconazole cream for non-Candida albicans fungal vaginitis: results of a retrospective analysis.

OBJECTIVE: Although it is FDA-approved for use in vulvovaginal candidiasis caused by non-Candida albicans species, terconazole cream has not been been studied in patients with these infections. We sought to assess the clinical and mycological efficacy of terconazole cream in women with non-C. albicans vaginitis. METHODS: The records of patients who had received a 7-day course of terconazole cream for culture-proved non-C. albicans vaginitis were reviewed. Data with regard to patient demographics, clinical and mycologic response to therapy within 1 month of treatment, and outcome with other antifungal therapies were analyzed. RESULTS: Twenty-eight patients received terconazole cream for non-C. albicans infections. Three patients did not return for follow-up. The median age was 45 years. Seven (28%) patients were nulliparous. The median duration of symptoms was 3 years. Nine patients (36%) had received terconazole within the 6 months prior to referral. Overall, there were 20 C. glabrata cases, 3 C. parapsilosis, and 2 C. lusitaniae. Fourteen (56%) patients achieved a mycologic cure; 11 (44%) noted a resolution of their symptoms. Prior terconazole use was not associated with treatment failure (P = 0.09). Ten failures received boric acid suppositories as subsequent treatment; a cure was effected in 4 (40%). Two of three patients (67%) were eventually cured with flucytosine cream. Five (20 %) patients remained uncured. CONCLUSIONS: Terconazole cream may be an appropriate first-line treatment for non C. albicans vaginitis, even in patients who have previously received the drug.

Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study.

Patients with primary sclerosing cholangitis (PSC) have a significantly increased risk of developing cholangiocarcinoma (CCA). Risk factors for developing such a complication are not well defined. We conducted a multicenter, case-control study to determine the risk factors and possible predictors for CCA in patients with PSC. The demographic, clinical, and laboratory features of 26 PSC patients with CCA diagnosed over a 7-year period at eight academic centers were compared with 87 patients with PSC but no CCA (controls). There was no statistically significant difference in demographics, smoking, signs or symptoms or complications of PSC, indices of disease severity (Mayo Risk score or Child-Pugh score), frequency or duration or complications of inflammatory bowel disease (IBD), frequency of biliary surgery, or therapeutic endoscopy between the two groups. Alcohol consumption was significantly associated with CCA in patients with PSC (odds ratio: 2.95; 95% CI: 1.04-8.3). Serum carbohydrate antigen 19-9 (CA 19-9) was significantly higher in patients with CCA than those without (177 +/- 89 and 61 +/- 58 U/mL, respectively; P =.002). A serum CA 19-9 level > 100 U/mL had 75% sensitivity and 80% specificity in identifying PSC patients with CCA. In conclusion, alcohol consumption was a risk factor for having CCA in PSC patients. The indices of severity of liver disease were not associated with CCA in patients with PSC. Serum CA 19-9 appeared to have good ability to discriminate PSC patients with and without CCA.

Predictors of large esophageal varices in patients with cirrhosis.

OBJECTIVE: Recent guidelines recommend that all cirrhotics undergo screening upper endoscopy to identify those patients at risk for bleeding from varices. However, this practice may not be cost effective as large esophageal varices are seen only in 9-36% of these patients. The aim of this study was to determine whether clinical variables were predictive of the presence of large esophageal varices. METHODS: This is a retrospective analysis of cirrhotics who had a screening upper endoscopy during an evaluation for liver transplantation at three different centers and who had not previously bled from varices. A multivariate model was derived on the combined cohort using logistic regression. Three hundred forty-six patients were eligible for the study. RESULTS: The prevalence of large esophageal varices was 20%. On multivariate analysis, splenomegaly detected by computed tomographic scan (odds ratio: 4.3; 95% confidence interval: 1.6-11.5) or by physical examination (odds ratio: 2.0; 95% confidence interval: 1.1-3.8), and low platelet count were independent predictors of large esophageal varices. On the basis of these variables, cirrhotics were stratified into high- and low-risk groups for the presence of large esophageal varices. Patients with a platelet count of > or = 88,000/mm3 (median value) and no splenomegaly by physical examination had a risk of large esophageal varices of 7.2%. Those with splenomegaly or platelet count < 88,000/mm3 had a risk of large esophageal varices of 28% (p < 0.0001). CONCLUSIONS: Our data show that clinical predictors could be used to stratify cirrhotic patients for the risk of large esophageal varices and such stratification could be used to improve the cost effectiveness of screening endoscopy.

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.

Duodenal ulcer. Calcium status in isolated parietal cells.

Although the etiology of duodenal ulcer is not known, its treatment with drugs that reduce acid secretion is well accepted. The central role of calcium in stimulus-secretion coupling resulting in acid secretion by gastric parietal cells is documented. However, the status of intracellular calcium in gastric parietal cells in the basal state in patients with duodenal ulcer is not known. Multiple endoscopic gastric mucosal biopsies from the corpus of the stomach of 52 patients were processed and isolated parietal cells were studied. Intracellular calcium was estimated using fura-2-acetoxymethyl ester. Influx and efflux were determined by using radioactive calcium. Acridine orange retention was used to assess acid production. Only calcium influx at 20 min was significantly (P < 0.01) more in patients with duodenal ulcer as compared to the control group. There was no difference between the groups in calcium influx at 0 and 60 min; calcium efflux at 0, 20, and 60 min; intracellular free calcium and acid secretion. We conclude that in the unstimulated state calcium homeostasis in isolated parietal cells of patients with duodenal ulcer shows only a minimal difference as compared to controls.

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.