Indocyanine green clearance test (using spectrophotometry) and its correlation with Model for End Stage Liver Disease (MELD) score in Indian patients with cirrhosis of liver.

Background: Child Turcotte Pugh (CTP) score and Model for End Stage Liver Disease (MELD) are used commonly to assess the prognosis of liver disease but the disadvantage of these static tests is their inability to identify the functional reserve of the liver. Among all quantitative liver function tests indocyanine green (ICG) clearance test is most widely used and has been used to determine operative risk before hepatectomy and to assess prognosis of patients with cirrhosis. Aim: To correlate indocyanine green (ICG) clearance test with MELD score in patients with cirrhosis of liver. Methods: Forty patients with cirrhosis of liver were included and divided into two groups according to their CTP scores. Group A had 20 patients with CTP class A and group B had 20 patients with CTP class B. After ICG injection, ICG retention at 15 minutes (ICGR15) and ICG clearance rate were calculated. Results: In group A, the mean ICGR15 was 32.86% + 6.4% while in group B it was 51.08% + 12.8% (p <0.001). ICG clearance rates were 4.3% + 2.8% and 3.5% + 3.8% per minute in group A and B respectively. MELD score had a strong positive correlation with ICGR15 but a negative correlation with ICG clearance rate. On ROC curve analysis, AUC for MELD was 0.805 vs. 0.88 for ICGR15 in assessing prognosis of patients with cirrhosis. The sensitivity and specificity of MELD score was 60% and 80% respectively while that of ICGR15 was 85% and 90% respectively. Conclusion: ICGR15 has a higher sensitivity and specificity than MELD score in assessing the prognosis of patients with cirrhosis of liver.

Hepatitis E epidemic with bimodal peak in a town of north India.

INTRODUCTION: An epidemic of viral hepatitis occurred in Mandi Gobindgarh town of Punjab in northern India during year 2005-06. An attempt was made to study the outbreak clinically, serologically, and etiologically. METHODS: Line listing and spot mapping of all cases of jaundice presented to civil hospital was done. An active search of cases was made through house-to-house visit with the help of 33 teams and 6 supervisors. Twenty two blood samples collected from acute cases were tested for anti-HAV IgM and anti-HEV IgM by ELISA. HEV specific PCR was also carried out. Sanitary survey was also done and water samples were tested for coliforms. RESULTS: In house to house survey 3170 cases of jaundice were reported; of them 2171 (68.5%) were males. Mean age was 28.8 years. Overall attack rate was 5.2%. The epidemic continued for more than a year and bimodal peak was observed. Civil hospital campus which has separate water supply had no jaundice case. About 95% blood samples from icteric patients were found to be positive for IgM and IgG antibodies of HEV. Eighteen persons died during the epidemic, mostly in old age group. Case fatality ratio was 0.57%. No deaths occurred among 17 pregnant women who had developed hepatitis. CONCLUSION: The epidemic was caused by hepatitis E virus, which was transmitted due to faecal contamination of municipal water supply.

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.

Insulin tolerance test is comparable to homeostasis model assessment for insulin resistance in patients with nonalcoholic fatty liver disease.

INTRODUCTION: Insulin resistance (IR) is common in patients with nonalcoholic fatty liver disease (NAFLD). We compared the performance of insulin tolerance test and the homeostasis model assessment (HOMA) for measuring IR in such patients. METHODS: In a prospective study, IR was determined using both insulin tolerance test and HOMA in 22 patients with NAFLD. Rate constant for insulin tolerance test (KITT) was calculated using the formula KITT (%/min) = 0.693/t(1/2), where t(1/2) was calculated from the slope of plasma glucose concentration during 3-15 minutes after administration of intravenous insulin. IR was assessed using HOMA as the product of fasting insulin (microU/L) and fasting plasma glucose (mmol/L) levels divided by 22.5. RESULTS: All the 22 patients had IR. Results of KITT and HOMA-IR for determining IR showed a fair correlation (r = 0.55; p = 0.03). CONCLUSIONS: Insulin tolerance test may be a useful method for assessing IR in patients with NAFLD.

Unconjugated hyperbilirubinemia in nonalcoholic steatohepatitis--is it Gilbert's syndrome?

BACKGROUND: Patients with nonalcoholic steatohepatitis (NASH) have normal liver function tests except for raised transaminases until they have progressed to cirrhosis of liver. The objective of this study was to evaluate patients of NASH for the presence of hyperbilirubinemia at presentation. METHOD: Sixty-seven patients of NASH were studied for the presence of hyperbilirubinemia at presentation. All patients were worked up for the presence of cirrhosis and hemolytic work up and fasting test were done in those found with unconjugated hyperbilirubinemia. RESULTS: Five out of 67 patients (7.5%) of NASH were found to have unconjugated hyperbilirubinemia. Though the fasting test was not positive, they all had a negative hemolytic workup and none of them had underlying cirrhosis. Clinical characteristics of patients with unconjugated hyperbilirubinemia were similar to those with normal serum bilirubin levels. CONCLUSION: Unconjugated hyperbilirubinemia in patients with NASH may suggest an associated Gilbert's syndrome.

Is vaccination against hepatitis A virus required in patients with cirrhosis of the liver?

Hepatitis A virus (HAV) superinfection can cause decompensation in patients with chronic liver disease. The risk of HAV superinfection depends on the endemicity of HAV in that particular population. Recommendations of vaccination against HAV in patients with cirrhosis of the liver in India are lacking. Our aim was to assess the seroprevalence of anti-HAV antibodies in our population of patients with cirrhosis of the liver. In a retrospective analysis, the serum of 55 patients with cirrhosis of the liver was tested for total anti-HAV antibodies by ELISA. In the 35 patients who presented with acute decompensation, the serum was also analysed for IgM anti-HAV antibodies. Fifty-four of the 55 cirrhotics (99%) were positive for total anti-HAV antibodies. All 35 patients with decompensated liver disease were also positive for total anti-HAV antibodies, and none of them tested positive for IgM anti-HAV antibodies. Most of the patients with cirrhosis of the liver in the population studied were already exposed to HAV. Routine vaccination against HAV cannot be recommended in these patients.

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.

Magnetic resonance imaging and spectroscopy in hepatic encephalopathy.

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.

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.

Paucity of anti-hepatitis C virus antibodies in the serum of Indian patients with Sjogren's syndrome and inflammatory myositis.

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.

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.

Pharmacokinetics of ciprofloxacin in patients with liver cirrhosis.

BACKGROUND: Bacterial infections are common in patients with cirrhosis of liver and are frequently treated with ciprofloxacin. Literature on pharmacokinetics of ciprofloxacin in patients with cirrhosis of the liver is scanty. The present study compared the pharmacokinetics of ciprofloxacin in cirrhotic patients with that in healthy volunteers. METHODS: In 20 patients with cirrhosis of liver (all Child-Pugh class B) and 10 healthy volunteers, plasma levels of ciprofloxacin were measured using high-performance liquid chromatography at several time points after a 500-mg oral dose. Various pharmacokinetic parameters were calculated. RESULTS: No significant differences were observed in maximum plasma levels reached (mean [SD] 2.6 [0.6] vs 2.6 [1.3] microg/ml), time taken for maximum plasma levels to be reached (1.3 [0.6] vs 1.5 [0.9] h), t1/2a (0.7 [0.3] vs 0.4 [0.9] h), elimination half-life (3.6 [1.2] vs 3.2 [1.8] h), and area under the curve (19.3 [3.8] vs 21.9 [4.5] microg/mL x h) in healthy volunteers and cirrhotic patients, respectively. CONCLUSIONS: Pharmacokinetics of ciprofloxacin is unaltered in patients with liver cirrhosis. Ciprofloxacin can be safely administered in the usual doses in such patients.

Immunohistochemistry for core and surface antigens in chronic hepatitis.

BACKGROUND: Hepatitis B virus infection constitutes a significant proportion of patients presenting with chronic hepatitis. Chronic hepatitis is said to be due to HBV if HBsAg is demonstrated in the serum with or without replication as determined by the presence of HBeAg in the serum. Immunohistochemical staining for HBsAg and HBcAg in liver tissue has been reported to improve the detection rate of HBV. AIM: To study positivity of immunohistochemical staining of liver tissue for HBsAg and HBcAg in patients of chronic hepatitis and correlate it with histological activity index. METHODS: One hundred consecutive patients of chronic hepatitis were selected for this study. Histological scoring of liver biopsies was done using Knodell's numerical scoring system. Immunohistochemical staining was done by the Indirect immunoperoxidase technique using goat polyclonal anti-HBsAg and rabbit polyclonal anti-HBsAg. ELISA was used to detect HBsAg in the serum. RESULTS: Serum HBsAg was positive in only 40 patients whereas tissue HBsAg was positive in 48 patients. Thirteen of these forty-eight tissue positive HBsAg patients also showed HBcAg on immunohistochemical staining of liver tissue. Patients with higher grades of histological activity index (HAI) score had higher values of serum bilirubin and prothrombin time as compared to the patients with a low HAI score. Significantly higher levels of serum transaminases (AST/ALT) were observed in patients who were positive for both HBsAg and HBcAg when compared with patients positive for HBsAg or HBsAg negative patients. A mixed pattern (diffuse/focal cytoplasmic and membranous) of surface antigen expression was seen in 83.3% patients, whereas expression of core antigen was predominantly nuclear (77%). There was no significant correlation between the pattern of antigen expression and HAI score.

Non-cirrhotic portal fibrosis in a patient with rheumatoid arthritis.

A 53-year-old man suffering from rheumatoid arthritis for 15 years presented with bleeding esophageal varices, hepatosplenomegaly and normal splenoportal venous axis. Liver biopsy revealed mild fibrosis, suggestive of non-cirrhotic portal fibrosis (NCPF). There are reports of the association of idiopathic portal hypertension, a condition similar to NCPF, with progressive systemic sclerosis, Hashimoto's thyroiditis and systemic lupus erythematosus.

Hepatitis B virus co-infection in HIV infected patients.

AIM: Human immunodeficiency virus (HIV) and Hepatitis B virus (HBV) share the same routes of transmission. Co-infection with the two viruses has been reported to occur in upto 90% of HIV infected patients, depending on the prevailing risk factors for acquiring infection in a given population. We studied our HIV positive patients for the prevalence of HBV co-infection in them. METHODS: Eighty consecutive HIV positive patients underwent ELISA for HBsAg and antiHBc antibodies. HBeAg was tested for in all HBsAg positive patients. Polymerase chain reaction for HBV DNA was carried out in 40 randomly selected patients who showed no serological evidence of HBV infection. RESULTS: There were 56 males and 24 females (mean age 33.2 +/- 8.3 years). Twenty seven (33.8%) patients (23 males, 4 females) had evidence of co-infection with HBV. Of these 6 (22.2%) were HBsAg positive, 22 had antiHBc antibodies and HBV DNA was positive in one. Four patients had evidence of replicating virus (3 HBeAg+ve, 1 DNA+ve). All 4 had normal transaminases and advanced HIV infection. HBV co-infection was significantly higher among males (p < 0.05). There was no significant difference in the liver functions of HBV positive and negative individuals. The risk factor for acquiring infection was heterosexual exposure in al HBV+ve patients except one. CONCLUSIONS: Hepatitis B virus co-infection was seen in 33.8% of our HIV positive patients. Males were more likely to be co-infected. All except one of the patients acquired infection through heterosexual exposure.

Pulmonary function changes after large volume paracentesis.

OBJECTIVE: To study the effect of large volume paracentesis (LVP) on pulmonary function in patients with cirrhosis of liver and tense ascites. METHODS: Ten patients having alcoholic cirrhosis with ascites were subjected to LVP (mean 6.3 +/- 0.3 L). Pre and post paracentesis spirometry and arterial blood gas analysis were performed and compared. RESULTS: Baseline mean lung volumes and arterial pO2 were reduced from normal predicted values. Air flow was found normal. After LVP, an increase in absolute values of vital capacity, forced expiratory flow in first second (FEV1) and peak expiratory flow was observed; only the improvement in FEV1 was significant p 0.05). Arterial pO2 also showed significant (p < 0.01) improvement after LVP. CONCLUSION: LVP leads to improvement in measured pulmonary function.

Immunogenicity of plasma-derived hepatitis B vaccine in preterm infants.

The objective was to determine whether plasma-derived hepatitis B vaccine is immunogenic in preterm appropriate for gestation babies when administered at birth and to compare the immunogenicity between 5 micrograms and 10 micrograms doses of the vaccine in these babies. Fifty preterm neonates (31-36 weeks gestation) were randomized to receive 5 micrograms or 10 micrograms doses of plasma-derived hepatitis B vaccine at birth, with subsequent doses 1 and 6 months later. Serum specimens were obtained a month after each dose of the vaccine and were tested for antibody to hepatitis B surface antigen (anti-HBs). Thirty six babies (gestation 31-36 weeks), 18 from each group competed the study. While 89.2% of the babies seroconverted, 82.1% achieved seroprotective titres of anti-HBS (> 10 mIU/ml). There was no difference between weight, gestational age, age of administration of vaccine and age of estimation of anti-HBs between 5 micrograms and 10 micrograms groups. The difference in the seroprotective rates were not statistically different between the groups (5 micrograms 78.5%; 10 micrograms--85.7%). Although immune response to plasma derived hepatitis B vaccine in preterm babies is suboptimal when the first dose is administered at birth, the full course achieves adequate seroprotective levels.