Pregnancy outcome in Budd Chiari Syndrome--a tertiary care centre experience.

BACKGROUND: Pregnancy management is a crucial issue in women with Budd-Chiari Syndrome (BCS) and there are no established guidelines on the management. AIM: To report our experience of pregnancy outcome with BCS. MATERIAL AND METHODS: We report outcome of 13 pregnancies in three women, with favourable outcome after the diagnosis of the condition and its treatment using intervention to bypass obstruction and anticoagulant therapy during pregnancy. RESULTS: Three women had a total of 13 pregnancies; three after the diagnosis and decompressive treatment of the disease. Disease was diagnosed during index pregnancy in two women. Anticoagulation was given in all the three pregnancies (Robertson et al., Br J Haematol, 132:171-196, 2006). Pregnancies prior to diagnosis and treatment resulted in a live birth. CONCLUSION: Pregnancy does not seem to be a contraindication in well treated and controlled BCS. Maternal outcome is good with close multidisciplinary surveillance. Foetal outcome, however, may still be poor due to underlying prothrombotic condition.

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.

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.

Non-hepatic insults are common acute precipitants in patients with acute on chronic liver failure (ACLF).

INTRODUCTION: Acute-on-chronic liver failure (ACLF) is a newly coined term to describe simultaneous coexistence of two liver conditions, one of them being chronic or long-standing and the other acute or recent. There is limited data on the entity of ACLF. This study was performed to review our experience in ACLF patients from a tertiary care centre. PATIENTS AND METHODS: ACLF was defined as per the Asian Pacific Association for the Study of the Liver (APASL) criteria, except for including the non-hepatic insults as precipitating events. Based on the type of acute insult, patients were divided into type I (non hepatic injury) and type II (hepatic injury-further divided in to IIA-acute viral hepatitis (AVH) on underlying chronic liver disease (CLD), IIB-other acute hepatitic insults like drugs/toxins and IIC-same disease responsible for worsening). Patients were also analyzed for the mode of presentation, severity of liver illness, presence of acute kidney injury and other organ failure, hospital stay and final outcome. RESULTS: One hundred two patients with ACLF (85 males, mean age 44 ± 12.5 years) were included in the study; they accounted for 49% of all liver failures and 27% of all admissions during the study period. Sixty patients (59%) had known cirrhosis whereas 42 (41%) patients presented for the first time as ACLF, unaware of the underlying CLD. Sixty-two (60%) patients had type I ACLF while 40 (40%) patients had type II ACLF. Infections (47%) were the most common non-hepatic causes of acute deterioration in type I ACLF. Amongst type II, acute viral hepatitis (IIA) accounted for six patients (4 hepatitis E virus, 2 hepatitis A virus) and type II C was the most common with alcoholic hepatitis accounting for 30 (29%) patients. Acute kidney injury was present in 47 (46%) and hypotension in 36 (35%) patients. Hypoxemia with ventilatory support was required in 22 (21%) patients. Mean hospital stay of patients was 9.7 ± 6 days (2-27 days). Forty-seven (46%) patients either died or left hospital in a very sick state. CONCLUSION: ACLF is a common problem in our clinical practice. Non-hepatic insults like non-hepatotropic infections/sepsis are common acute precipitating events.

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.

Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models. METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922). RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001). CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

Gross anatomy of the retrohepatic segment of the inferior vena cava in northwest Indians.

BACKGROUND AND OBJECTIVES: Information regarding the size and position of the ostia of veins opening into the retrohepatic segment of inferior vena cava (HIVC) in northwest Indians is not available. Knowledge of gross anatomy of this segment is of importance in cases of segmental resection of the liver involving the groove for inferior vena cava (IVC) and when performing selective hepatic venography. We carried out this study to provide information on gross anatomy of HIVC in northwest Indians. METHODS: Livers were obtained from 500 adult autopsy subjects. The HIVC was opened posteriorly by a vertical cut and its circumference at the upper and lower cut ends was measured. To study the position of the ostia of the hepatic veins, HIVC was divided transversely into upper, middle and lower thirds. The anterior and anterolateral walls of HIVC were also divided into four equal parts longitudinally. The venous ostia were classified according to the size of their openings. In addition, in 100 livers the openings were injected with a 20 per cent solution of cellulose acetate butyrate (CAB) in acetone and veins were dissected. RESULTS: The HIVC extended upwards and to the left either obliquely (66.4%) or by describing a gentle curve (33.6%) in its upper half or upper third. Its average length was about 71 mm. Mean diameter at the upper cut end was about 19 mm. The posterior aspect of the upper half or upper one third of HIVC was covered by an extension of the caudate lobe completely (4%) or incompletely (7.4%). The ostia of the left, middle and right hepatic veins were large (>10 mm) and were located in the upper third segment of HIVC. In 87 per cent of specimens the left and middle hepatic veins had a common opening on the left anterior area. The ostium of the right hepatic vein was present in the right anterior area. INTERPRETATION AND CONCLUSION: In conclusion, our study provided gross measurements of HIVC in northwest Indians. A knowledge of the anatomy of HIVC and hepatic venous ostia will help the clinician interventional operator in planning the treatment by choosing a balloon of correct size and at correct site. The measurements helps in determining the fall in portal pressure with pharmacotherapy given for the prevention of variceal bleed.

Prevalence & significance of hepatitis C virus (HCV) seropositivity in blood donors.

BACKGROUND & OBJECTIVES: The clinical significance of anti HCV antibodies in healthy blood donors remains uncertain. These donors are usually asymptomatic and it is difficult to elicit risk factors of acquiring HCV infection during pre-donation questioning. Limited information on donor recall and follow up studies on anti HCV positive blood donors have been reported from India. Paucity of data which is likely to have an impact on safe blood transfusion programme has prompted us to undertake this study to assess the significance of HCV seropositivity in blood donors with respect to their clinical, biochemical and virological profile. METHODS: A total of 16,250 blood units were screened for the mandatory tests using third generation ELISA (anti HIV 1&2, anti HCV, HBsAg), VDRL and peripheral smear for malaria. Donors reactive for anti HCV were informed. Repeat anti HCV reactive donors were subjected to detailed clinical history focusing on risk factors for HCV transmission. The blood tests included liver function tests (LFT), coagulation and autoimmune profile, qualitative serum cryoglobulins and HCV RNA detection. These donors were followed at 2-3 monthly intervals for a minimum period of six months by LFT. RESULTS: An overall seropositivity of 0.44 per cent (72/16,250) was observed in our donors which was significantly lower in first time, young voluntary donors as compared to replacement donors (0.27 vs. 0.60%). In contrast to drug abuse (6.4%) we found minor percutaneous routes like sharing of shaving kits or visit to a road side barber (32%) as the major risk factor for HCV transmission. There was no prior history of blood transfusion in any of these donors; however history of some surgical procedures was present in 25.8 per cent. Raised transaminases and HCV viraemia were observed in 87 and 71 per cent donors respectively. An association was observed between HCV RNA when the ELISA ratio was >5. INTERPRETATION & CONCLUSION: Voluntary donors form a safe source of blood supply and efforts should be made to increase this precious source to 100 per cent. Abbreviated behavioural donor screening questionnaire for repeat donors is not advisable. Awareness and education of donors is required regarding modes of HCV transmission. HCV positive donors should be informed about their disease, counselled and referred to hepatologist, and permanently deferred for future donations.

Virological investigation of a hepatitis E epidemic in North India.

INTRODUCTION: Hepatitis E virus (HEV) infection is of major public health concern in the developing countries, including the Indian subcontinent, due to epidemics of large proportions, increased morbidity and high mortality, especially in pregnant women. This study shows the findings of two different epidemics that occurred due to HEV. METHODS: Blood samples were collected from 116 suspected HEV patients. Sera were separated and tested for hepatitis A virus HAV immunoglobulin M (IgM), hepatitis B virus surface antigen, hepatitis C virus (HCV) antibody and HEV IgM by Micro ELISA. 15 acute samples were subjected to reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of HEV ribonucleic acid (RNA). RESULTS: Of the 116 blood samples collected, 68 (58.6 percent) were positive for HEV IgM antibodies. Mixed infections of HEV with HAV and HCV were detected in three (4.4 percent) and five (7.4 percent) cases, respectively. 15 HEV IgM-positive acute blood samples subjected to RT-PCR showed the presence of specific 343 bp amplified HEV ORF1 gene product in five cases. No untoward effects were observed in the five HEV-infected pregnant women during their follow-up. CONCLUSION: This study confirms the HEV aetiology and highlights a major disease outbreak that occurred due to mixing of drinking water with sewerage.

Vascular endothelial growth factor: Evidence for autocrine signaling in hepatocellular carcinoma cell lines affecting invasion.

BACKGROUND AND AIM: Vascular endothelial growth factor (VEGF) is a well-known pivotal regulator of tumor angiogenesis. Apart from endothelial cells, it is also expressed in nonendothelial cells, including tumor cells themselves. Hence the aim of this study was to investigate the autocrine effects of VEGF in hepatocellular carcinoma (HCC) -derived cell lines. MATERIALS AND METHODS: Two hepatocellular carcinoma cell lines (Hep3B and HepG2) were screened for expression of VEGF by quantitative real-time polymerase chain reaction (PCR) and its receptors VEGF-R1, VEGF-R2, and neuropilin-1 expression by reverse transcriptase-PCR, respectively. Furthermore, VEGF transcript was silenced by siRNA and the effects on cell migration, viability, and proliferation were determined by the wound healing assay, MTT assay, and propidium iodide staining, respectively. RESULTS: Both Hep3B and HepG2 cell lines expressed VEGF and all the three receptors at high levels. VEGF siRNA inhibited VEGF expression significantly in both Hep3B and HepG2 cell lines. Silencing of VEGF showed decreased migration in the Hep3B cell line. In both cell lines tested, there was decreased cell viability but no effect on cellular proliferation. CONCLUSION: Our data indicates that autocrine signaling of VEGF through its receptors exists in HCC cell lines, which has important implications for tumor invasion, metastasis, and for designing interventional strategies.

Pharmacokinetics of omeprazole in patients with liver cirrhosis and extrahepatic portal venous obstruction.

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.

Prescribing drugs for patients with liver disease.

BACKGROUND: Adverse reactions to prescribed drugs are a common cause of morbidity in patients receiving medical care. Pre-existing or underlying liver dysfunction is one of the commonest factors that enhance the risk of such adverse events in medical practice. Most textbooks of medicine contain no guidelines on special precautions to be taken in prescribing to a patient with pre-existing liver disease. METHODS: To provide a ready reckoner for modifying drug dosage in liver diseases, a literature search was carried out. All papers related to human studies were reviewed and relevant material extracted for preparing the guidelines. RESULTS: Most adverse drug reactions in the presence of liver disease are related to altered pharmacokinetics, pharmacodynamics and susceptibility to drugs. The influence of hepatic disease on various drugs is highly variable. However, many such adverse events are predictable and preventable. Ideally, drug dosage should be modified with the help of serum drug concentrations, which unfortunately, are not available in most Indian hospitals. Hence, some broad guidelines are presented to assist the treating physician to be aware of the risk of adverse drug reactions and modify drug dosage empirically to avoid such events. CONCLUSION: The altered metabolism of pharmacological agents in patients with liver disease may induce several undesirable effects. A large number of adverse drug reactions can be prevented by modifying drug prescribing habits for patients who have pre-existing liver disease.

Effect of isosorbide dinitrate on non-cirrhotic portal hypertension.

Among the many drugs including propranolol that have been evaluated for the pharmacological control of portal hypertension, isosorbide dinitrate (ISDN) fulfils the criteria of patient acceptability, ease of administration and production of the desired effect. Forty-three consecutive patients with uncomplicated noncirrhotic portal hypertension (NCPH) caused by extrahepatic portal venous obstruction (EHO=32) and non-cirrhotic portal fibrosis (NCPF=l1) were given 20 mg of ISDN sublingually and in the supine position the intrasplenic pulp pressure (ISPP) was monitored for 10 minutes. The fall in mean ISPP became significant at 4 minutes in patients with EHO (p

Preoperative bile salt administration versus bile refeeding in obstructive jaundice.

BACKGROUND: Endotoxaemia due to intraluminal bile salt depletion may be a cause of renal failure in patients with obstructive jaundice. Administration of bile salts to these patients has been reported to decrease portal and systemic endotoxaemia during surgery and improve renal function. However, such changes have not been shown with bile refeeding. We compared the effect of preoperative bile salt administration with preoperative bile refeeding on renal function in patients with obstructive jaundice. METHODS: Sixteen patients with obstructive jaundice underwent percutaneous transhepatic biliary drainage--eight received oral bile salts (500 mg of sodium deoxycholate 8-hourly for 48 hours preoperatively) and the other 8 were refed the total bile output for the entire period of biliary drainage (median 13 days). Blood endotoxin levels and renal function were assessed before, during and after the operation. RESULTS: The number of patients with intraoperative portal and postoperative systemic endotoxaemia decreased after both forms of therapy. Renal function also improved in both the groups--all 4 patients with renal failure recovered. There was a significant increase in creatinine clearance postoperatively after bile salt therapy (from 65 ml/minute preoperatively to 87 ml/minute postoperatively). CONCLUSION: Refeeding of bile obtained by percutaneous catheter drainage is an effective, cost-free substitute for oral bile salts in patients with obstructive jaundice.

Sexual behaviour, drug use and hepatitis B infection in Chandigarh students.

BACKGROUND: The relationship of hepatitis B virus infection with drug use and sexual activity in Indian college students has not been studied earlier. METHODS: We studied this relationship in Chandigarh, using a prospective, cross-sectional questionnaire-based survey and blood tests for hepatitis B markers. The responders were assured of the confidentiality of their responses and blood test results. RESULTS: Of the 1311 students who participated, 192 (15%) were sexually active. Eight-four per cent of them were heterosexual, 7.3% homosexual and 8.7% bisexual. Thirty-seven per cent of heterosexuals and 36% of homosexuals had more than one partner. Condoms were used by 24% heterosexuals, 11% bisexuals and 7% homosexuals. Of the sera tested, 2.9% were hepatitis B surface antigen positive and 10.4% were positive for the antibody to hepatitis B surface antigen. Fifteen per cent consumed alcohol, but only 1.6% were addicted to other drugs. Two students were intravenous drug users. Eleven per cent had donated blood at least once and a third of these had suffered from jaundice in the past. CONCLUSION: The pattern of sexual behaviour, low condom use and the small but definite prevalence of hepatitis B virus infection in this population of students suggests that the human immunodeficiency virus infection may spread rapidly when it enters this community.

Endoscopic nasobiliary drainage in acute suppurative cholangitis.

BACKGROUND: Acute suppurative cholangitis is associated with significant mortality. It is best managed by drainage of the biliary tree, endoscopic, percutaneous or surgical. AIMS: To study the effect of emergency endoscopic nasobiliary drainage (ENBD) in acute suppurative calculous cholangitis. METHODS: In 37 patients with calculous cholangitis, an endoscopic nasobiliary drain (7 F) was placed in the biliary tree above the site of obstruction to ensure continuous biliary drainage. RESULTS: Success rate was 100% and there was no mortality. ENBD was performed in 4 very sick patients without the aid of fluoroscopy. Cholangitis improved in 36 of 37 patients within 12-24 hours. When the clinical condition improved, all the 36 patients were taken up for elective biliary surgery or endoscopic sphincterotomy and stone extraction. CONCLUSIONS: Emergency endoscopic nasobiliary drainage is an effective method in managing patients with acute suppurative calculous cholangitis.