Altered expressions of circulating microRNAs 122 and 192 during antitubercular drug induced liver injury indicating their role as potential biomarkers.

Drug induced liver toxicity is a serious health complication leading to high mortality rates and post marketing withdrawal of drugs. Although considered to be the gold standard biomarkers; aspartate aminotransferase, alanine aminotransferase, total bilirubin and alkaline phosphatase have been found to have specificities beyond liver, therefore more specific and predictive markers for the detection of antitubercular drug mediated liver damage are required. Unfortunately, the effectiveness of currently used first line antitubercular drugs namely isoniazid, rifampicin, pyrazinamide is often accompanied with liver injury, impeding the cure of patients. Keeping in view, the prognostic and diagnostic applications of microRNAs in various diseases, we tried to assess the importance of microRNAs 122 and 192 in antitubercular drug associated liver injuries. The study included subjects having tuberculosis of any type with antitubercular drug induced liver injury; naïve or newly diagnosed tuberculosis patients, tuberculosis patients on drugs not having toxicity and healthy controls. Observations from this study revealed that expression levels of miR-122 and miR-192 were significantly decreased in the serum of antitubercular drug induced liver injury patients only. Therefore, these microRNAs or the pathways associated with them can be used as a tool to predict or cure antitubercular drug associated liver injury in future.

Sofosbuvir plus ribavirin in treatment-naïve patients with chronic hepatitis C virus genotype 1 or 3 infection in India.

Until 2014, pegylated interferon plus ribavirin was the recommended standard of care for the treatment of chronic hepatitis C virus (HCV) infection in India. This open-label phase 3b study, conducted across 14 sites in India between 31 March 2014 and 30 November 2015, evaluated the efficacy and safety of sofosbuvir plus ribavirin therapy among treatment-naïve patients with chronic genotype 1 or 3 HCV infection. A total of 117 patients with genotype 1 or 3 HCV infection were randomized 1:1 to receive sofosbuvir 400 mg and weight-based ribavirin (1000 or 1200 mg) daily for 16 or 24 weeks. Among those with genotype 1 infection, the primary efficacy endpoint of sustained virologic response at 12 weeks post-treatment (SVR12) was reported in 90% (95% confidence intervals [CI], 73-98) and 96% (95% CI, 82-100) of patients following 16 and 24 weeks of treatment, respectively. For patients with genotype 3 infection, SVR12 rates were 100% (95% CI, 88-100) and 93% (95% CI, 78-99) after 16 and 24 weeks of therapy, respectively. Adverse events, most of which were mild or moderate in severity, occurred in 69% and 57% of patients receiving 16 and 24 weeks of treatment, respectively. The most common treatment-emergent adverse events were asthenia, headache and cough. Only one patient in the 24-week group discontinued treatment with sofosbuvir during this study. Overall, sofosbuvir plus ribavirin therapy achieved SVR12 rates ≥90% and was well tolerated among treatment-naïve patients with chronic genotype 1 or 3 HCV infection in India.

Prediction of sustained virological response to combination therapy with pegylated interferon alfa and ribavirin in patients with genotype 3 chronic hepatitis C.

BACKGROUND: Sustained virological response (SVR) rates in patients with hepatitis C are heterogeneous and are influenced by a wide range of host and viral factors. AIM: To evaluate the efficacy of combination therapy with pegylated interferon alfa (PEG-IFN-α) and ribavirin (RBV), and document the SVR rates taking into consideration various predictive factors in patients with chronic hepatitis C (CHC) genotype 3. METHODS: Ninety-seven treatment-naive patients with CHC genotype 3 (mean age 41.46±11.51 years, M:F ratio 79:18), who received a combination of PEG-IFN (α-2a or α-2b) and RBV were retrospectively analyzed (2006-2008) for the early virological response (EVR) at 12 weeks, end of treatment response (ETR), and SVR at 6 months. RESULTS: Eighty-four (86.6%) patients achieved EVR and 81 (83.5%) achieved ETR, while SVR was achieved in 65 (67.0%) patients. Of the 84 patients who achieved EVR, 77 (91.7%) achieved ETR and 61 (72.6%) achieved SVR at 6 months. Age and body mass index (BMI) were found to be important predictors (*P<0.05) of SVR. CHC patients with a history of alcohol intake showed decreased SVR (52%) (*P=0.035) as compared to nonalcoholics (80%). Cirrhotic versus noncirrhotic patients showed no difference in SVR (54.5% vs. 70.7%) (P=0.157). Serum alanine aminotransferase (ALT) (P=0.169) and hepatitis C virus (HCV) RNA levels (P=0.42) also did not have an influence on the SVR. CONCLUSION: Combination therapy with PEG-IFN-α and RBV demonstrated good tolerability in CHC genotype 3 infection. Age, BMI, and alcohol consumption play an important role in determining treatment outcome.

Hepatic osteodystrophy is common in patients with noncholestatic liver disease.

BACKGROUND: Patients with cirrhosis are more prone to develop metabolic bone disease. Scanty literature data are available on osteodystrophy in patients from India with noncholestatic liver diseases. METHODS: Patients diagnosed with cirrhosis were prospectively evaluated for bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry at the femoral neck, lumbar spine, and left forearm (distal radius). Correlation of BMD with age, sex, etiology of cirrhosis, Child's class, serum bilirubin, alkaline phosphatase (ALP), albumin, calcium, phosphate, 25-hydroxyvitamin D (25(OH)D), and parathyroid hormone (PTH) was studied. RESULTS: The study group comprised 115 cirrhotic patients (107 males and 8 females). Etiology of cirrhosis was alcohol in 67 (58.2%) and viral in 48 (41.7%). Hepatitis B was diagnosed in 29 (25.2%) and hepatitis C in 19 (16.5%). Mean age was 49 (± 5.5) years. Prevalence of osteodystrophy was significantly higher in males than in females; 97.1% and 75% respectively (P = .038). Both alcoholic and viral groups had similar baseline characteristics except albumin levels. Child's class was B in 72 patients and C in 43. Low BMD was present in 97% of patients with alcoholic cirrhosis and 93.7% with viral cirrhosis (P > .05). Low BMD was present at the femoral neck in 80.8% of patients, lumbar spine in 77.3%, and forearm in 59.9%. PTH correlated negatively with BMD. CONCLUSION: Osteodystrophy is common in alcoholic and viral cirrhosis patients.

Review article: the modern management of portal vein thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) is an important cause of portal hypertension. It may occur as such with or without associated cirrhosis and hepatocellular carcinoma. Information on its management is scanty. AIM: To provide an update on the modern management of portal vein thrombosis. Information on portal vein thrombosis in patients with and without cirrhosis and hepatocellular carcinoma is also updated. METHODS: A pubmed search was performed to identify the literature using search items portal vein thrombosis-aetiology and treatment and portal vein thrombosis in cirrhosis and hepatocellular carcinoma. RESULTS: Portal vein thrombosis occurs because of local inflammatory conditions in the abdomen and prothrombotic factors. Acute portal vein thrombosis is usually symptomatic when associated with cirrhosis and/or superior mesenteric vein thrombosis. Anticoagulation should be given for 3-6 months if detected early. If prothrombotic factors are identified, anticoagulation should be given lifelong. Chronic portal vein thrombosis usually presents with well tolerated upper gastrointestinal bleed. It is diagnosed by imaging, which demonstrates a portal cavernoma in place of a portal vein. Anticoagulation does not have a definite role, but bleeds can be treated with endotherapy or shunt surgery. Rarely liver transplantation may be considered. CONCLUSION: Role of anticoagulation in chronic portal vein thrombosis needs to be further studied.

Benign recurrent intrahepatic cholestasis (BRIC) in an adult.

Benign recurrent intrahepatic cholestasis is a rare hereditary disorder characterised by recurrent episodes ofcholestasis. We report the case of a young male patient with benign recurrent intrahepatic cholestasis who presented to us with recurrent cholestatic jaundice and pruritus with negative work up for all possible aetiologies and a liver biopsy consistent with intrahepatic cholestasis. He improved on treatment with ursodeoxycholic acid and ondansterone and is doing well on follow up.

Spectrum of clinico-pathological changes in Barrett oesophagus.

OBJECTIVES: Barrett oesophagus is replacement of squamous epithelium to specialised intestinal metaplasia. It is associated with an increased risk for adenocarcinoma which develops through dysplasia. The aim of this retrospective study was to determine the relative age of occurrence and incidence of dysplasia in this part of our country. METHODS: Between January 1999 and June 2002 we diagnosed 13 cases of Barrett oesophagus. Sections were stained with routine H and E and special stain alcian blue (AB)--PAS at pH 2.5. RESULTS: Out of 55 patients with symptoms of gastro-oesophageal reflux disease, 13 cases were diagnosed as Barrett oesophagus. There were 8 males and 5 females. Majority of the patients (77%) were between 20-40 years of age. At endoscopy, in 84.6% patients, lesions were in the form of islands of red mucosa. On histology examination, in 6 cases, squamous epithelium was replaced by intestinal epithelium containing goblet cells and in 7 cases it was replaced by gastric epithelium. Associated dysplasia was not seen in any of the case, while one case showed associated adenocarcinoma. CONCLUSION: Barrett oesophagus is seen in a younger population amongst Indians. A male predominance is noted, but is not as high as reported in Western literature. There is a paucity of patients with pure dysplasia in Barrett metaplasia. Despite the fact that there are a number of patients presenting with Barrett esophagus and carcinoma, very few patients present with dysplasia, indicating that Barrett oesophagus is a silent disease presenting later as a carcinoma.

Efficacy of endoscopic wire guided biliary brushing in the evaluation of biliary strictures.

Endoscopic brush cytology is a valuable technique for the evaluation of biliary strictures. The sensitivity of this technique varies from 30% to 83%, however, it can have specificity of 100%. We retrospectively evaluated the usefulness of wire-guided biliary brush cytology in biliary strictures in our hospital over a 3 years period from 1997 to 2000. Brushings from 58 biliary strictures were obtained during endoscopic retrograde cholangiography. They were compared with histological proof obtained by surgical biopsy or percutaneous fine-needle aspiration cytology and/or clinical findings. These were reported as benign or malignant. Eleven patients were excluded due to incomplete data. Eighteen patients had benign brushings. Fourteen of the 29 patients in whom histological confirmation of malignancy brushings was obtained were also reported as malignant. The sensitivity of endoscopic brushings was 48.2%, specificity 100% and diagnostic accuracy 55.2%. No major complications were seen in our study group.

Decompressive shunts and hepatic encephalopathy.

Encephalopathy is a major complication of all decompressive procedures done to reduce portal pressure. There are two major groups of decompressive procedures: surgical portosystemic shunts and transjugular intrahepatic portosystemic shunts (TIPS). Surgical decompressive shunts are of three types: total, partial and selective, depending on the amount of hepatopetal flow that is maintained in each of them. Encephalopathy with these shunts occurs because of reduction in hepatopetal flow. These shunts have failed to reduce mortality; in fact, some studies have shown an increase in mortality following shunts. TIPS has more or less replaced the need for surgical shunts, but their risk to cause encephalopathy is almost equivalent to that of selective shunts and in some series is even more. Lactulose, antibiotics and protein restriction can easily control severe encephalopathy as a consequence of decompressive shunts.

Helicobacter pylori and hepatic encephalopathy.

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.

Minimal hepatic encephalopathy: natural history, impact on daily functioning, and role of treatment.

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.

Circadian pattern in cerebro vascular disorders.

Over the last decade, various studies have been reported to evaluate the circadian pattern of cardiovascular and cerebro-vascular diseases. The data from Indian population is lacking. We undertook this prospective observational study to evaluate the circadian variation in disorders like cerebro-vascular accidents and transient ischemic attacks. Total of 146 patients (events) were studied. Only 10 patients had TIA's. 55% had hemorrhage and 45% had infarction. The 24 hours period was divided into 6 equal portions of 4 hours each. The maximum events were seen between 4 am to 8 am and 12 noon to 4 pm (23.28%) each. Minimum events were seen between 12 midnight to 4 am 14/146 - 9.58%). The circadian variation in occurrence of cerebro-vascular disorders was present with two equal peaks.

Hepatitis B and C virus--prevalence and prevention in health care workers.

BACKGROUND: Hepatitis B and C viruses are important causes of liver related morbidity and mortality. We aimed at determining the presence of hepatitis B and C virus infections in the health care workers (HCWs) and their compliance for the HBV vaccination. METHODS: Three thousand five hundred and fifty six health care workers were screened for HBsAg and 115 for anti-HCV by ELISA. HBsAg negative individual were offered HBV vaccination and record of their compliance was kept. Anti-HBs titers were determined one month after 2nd or 3rd dose of vaccine in 273 subjects. RESULTS: Out of 3556 health care workers, 61 (1.7%) were found to be positive for HBsAg. One out of 115 HCWs (0.87%) was found to be positive for anti-HCV. Fifteen percent of HCWs received only one dose, 26% received two doses 59% received three doses and 2.5% also received the booster dose of the HBV vaccine. All those tested had anti-HBs titers more than 10 mUI/ml. CONCLUSION: In HCWs, HBsAg and anti-HCV prevalence was found to be 1.7% and 0.87% respectively. HCWs in our hospital, despite the awareness on HBV and HCV infection are noncompliant for HBV vaccination.