Fatigue in Cirrhosis.

Fatigue is a common symptom in patients with liver disease and has a significant impact on the health-related quality of life (HR-QoL). Its pathogenesis is poorly understood and is considered multifactorial. The liver is central in the pathogenesis of fatigue because it uniquely regulates much of the production, storage, and release of substrate for energy generation. Also, the liver "cross-talks" with the key organs that are responsible for this symptom complex-gut, skeletal muscle, and brain. Fatigue can have both peripheral (i.e., neuromuscular) and central (i.e., resulting from changes in neurotransmission within the brain) components. The treatment strategies for the management of fatigue are behavioral changes and pharmacotherapy, along with dietetic intervention and exercise. However, there is no consensus on management strategies for fatigue in patients with liver disease. This article gives an overview of fatigue as a concept, its pathophysiology, measures to evaluate fatigue in patients with liver disease, the impact of fatigue on chronic liver disease, assessment of fatigue in an appropriate clinical setting, and various interventions to manage fatigue.

Living Donor Liver Transplantation in a Paediatric Patient With Citrullinaemia Type 2.

Citrullinaemia is a urea cycle defect that results from a deficiency of the enzyme arginosuccinate synthetase. Type 1 disease is diagnosed in childhood, whereas type 2 disease is adult onset. But, we report the outcome in a boy (13 years) with citrullinaemia type 2 who received a live donor liver transplant (LDLT) at our centre. One advantage of LDLT over deceased donor liver transplantation is the opportunity to schedule surgery, which beneficially affects neurological consequences. In conclusion, transplantation should be considered to be the definitive treatment for citrullinaemia type 2 at this stage, although some issues remain unresolved.

Indian National Association for the Study of Liver Consensus Statement on Acute Liver Failure (Part-2): Management of Acute Liver Failure.

Acute liver failure (ALF) is not an uncommon complication of a common disease such as acute hepatitis. Viral hepatitis followed by antituberculosis drug-induced hepatotoxicity are the commonest causes of ALF in India. Clinically, such patients present with appearance of jaundice, encephalopathy, and coagulopathy. Hepatic encephalopathy (HE) and cerebral edema are central and most important clinical event in the course of ALF, followed by superadded infections, and determine the outcome in these patients. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a crucial role in the pathogenesis, and several therapies aim to correct this abnormality. The role of newer ammonia-lowering agents is still evolving. These patients are best managed at a tertiary care hospital with facility for liver transplantation (LT). Aggressive intensive medical management has been documented to salvage a substantial proportion of patients. In those with poor prognostic factors, LT is the only effective therapy that has been shown to improve survival. However, recognizing suitable patients with poor prognosis has remained a challenge. Close monitoring, early identification and treatment of complications, and couseling for transplant form the first-line approach to manage such patients. Recent research shows that use of dynamic prognostic models is better for selecting patients undergoing liver transplantation and timely transplant can save life of patients with ALF with poor prognostic factors.

Indian National Association for the Study of the Liver Consensus Statement on Acute Liver Failure (Part 1): Epidemiology, Pathogenesis, Presentation and Prognosis.

Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.

International Consultation on Incontinence Questionnaire-Satisfaction: psychometric testing of a new patient-reported outcome measure for the evaluation of satisfaction after urological surgery.

OBJECTIVES: To evaluate the psychometric properties of a new patient-reported outcome measure (PROM), the International Consultation on Incontinence Questionnaire-Satisfaction (ICIQ-S), to assess satisfaction after urological surgery. SUBJECTS/PATIENTS AND METHODS: Following item development, the developmental ICIQ-S (dICIQ-S) was used within in a randomised control trial comparing two types of surgery for male prostatic obstruction at 1.5, 3, and 12 months after surgery. Reliability was assessed by Cronbach's α and construct validity by the correlation of scores with concurrently administered PROMs of known validity: ICIQ-Male Lower Urinary Tract Symptoms (LUTS), International Prostate Symptom Score, and the ICIQ-LUTS Quality of Life. RESULTS: A total of 410 men were included in the trial. Missing data was generally low for the dICIQ-S [mean (range) 1.6 (<1-3.1)%] except for the items 'complications' 6.8% and 'satisfaction with sex-life' 9.2%. High ceiling effects were found in all items. Factor analysis identified six items related to surgical outcomes (Cronbach's α 0.89), which have formed the scored part of the ICIQ-S, together with a standalone overall satisfaction item, scored 0-10. Seven additional unscored items, related to satisfaction with experiences and expectations, were also retained. As hypothesised, post-surgery dICIQ-S scores were correlated with reduced symptoms and improved quality of life as measured by the concurrent PROMs. CONCLUSION: The results support the validity and reliability of a scored six-item domain for evaluating satisfaction with surgical outcomes, together with a standalone scored overall satisfaction item. The further unscored seven standalone items are anticipated to be used as the basis for adaptation and further validation of the ICIQ-S in different patient populations.

INASL Position Statements on Prevention, Diagnosis and Management of Hepatitis B Virus Infection in India: The Andaman Statements.

Hepatitis B Virus (HBV) infection is one of the major causes of morbidity, mortality and healthcare expenditure in India. There are no Indian consensus guidelines on prevention, diagnosis and management of HBV infection. The Indian National Association for Study of the Liver (INASL) set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for diagnosis and management of HBV infection, relevant to disease patterns and clinical practices in India. The taskforce first identified contentious issues on various aspects of HBV management, which were allotted to individual members of the taskforce who reviewed them in detail. A 2-day round table discussion was held on 11th and 12th February 2017 at Port Blair, Andaman & Nicobar Islands, to discuss, debate, and finalize the consensus statements. The members of the taskforce reviewed and discussed the existing literature threadbare at this meeting and formulated the 'INASL position statements' on each of the issues. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong: 1, weak: 2) thus reflects the quality (grade) of underlying evidence (A, B, C, D). We present here the INASL position statements on prevention, diagnosis and management of HBV in India.

Does previous pelvic surgery hasten the onset of clinically bothersome urodynamic stress incontinence?

OBJECTIVE: To study the impact of previous pelvic surgery on the onset of clinically bothersome urodynamic stress incontinence (USI). STUDY DESIGN: Retrospective case-cohort study at a District General Hospital of 305 women undergoing surgery for urodynamic stress incontinence: case note and computer records review of patients undergoing USI surgery. The main outcome measures were age at index USI surgery, and duration from previous pelvic surgery to index surgery. RESULTS: 305 women were included, of whom 118 had previous pelvic surgery including abdominal hysterectomy (TAH) (n=74), vaginal hysterectomy (n=23), anterior colporrhaphy (n=27) and posterior colporrhaphy (n=25). The mean age in the previous surgery group was 62.4 years (95% CI 60.2-64.6, range 32-87) and 53.2 years in the no previous surgery group (95% CI 51.4-55, range 30-88). There were no differences in the mean BMI (28.4 vs. 27.5), or mean parity (2.4 vs. 2.5). The median duration from previous surgery to the index USI surgery was 222 months (abdominal hysterectomy), 96 months (vaginal hysterectomy), 78 months (anterior colporrhaphy), and 72 months (posterior colporrhaphy). CONCLUSION: Previous pelvic surgery does not seem to accelerate the onset of USI, as women without previous pelvic surgery presented at a significantly earlier age (53.2 years) with clinically bothersome USI than those who had previous surgery (62.4 years). Posterior colporrhaphy had the shortest interval to index USI surgery amongst previous operations.

Fractured metallic biliary stent causing obstruction and jejunal perforation.

Interventional internal drainage of the biliary tract has become an established procedure for both the temporary and definitive treatment of biliary obstruction due to malignant or benign disease. Biliary stent migration and stent fracture are known but rare complications. A 50-year-old man presented with acute onset pain in the abdomen and vomiting. He had undergone hepaticojejunostomy following a bile duct injury during open cholecystectomy 13 years before he presented at our institution. Subsequently, he developed a benign biliary stricture at the anastomotic site, which was stented transhepatically by a metallic stent. CT of his abdomen showed a fractured stent segment obstructing the jejunum with a localized perforation. Herein, we discuss his presentation and course of management, and review the factors influencing stent migration and fracture and the potential options for stent retrieval. The patient needed surgical intervention to retrieve the migrated fragment of metal stent and to resect the perforated jejunal segment. The role of endoscopic self-expanding metal stents for benign biliary disease remains controversial. A migrated stent that has become symptomatic should be removed endoscopically in early and accessible cases and surgically when endoscopic measures fail or when complicated by obstruction or perforation.

Maximum urethral closure pressure in women: normative data and evaluation as a diagnostic test.

INTRODUCTION AND HYPOTHESIS: Our goal was to identify correlates of maximum urethral closure pressure (MUCP) and MUCP as a diagnostic test for stress urinary incontinence (SUI). METHODS: This study was a retrospective review of women with non-neurological referrals for urinary incontinence between1995 and 2006. RESULTS: We studied the characteristics of 8,644 women who underwent urodynamics for non-neurological referrals. Mean MUCP was 48 cm H(2)O in urodynamic stress incontinence (USI), 50 cm H(2)O in mixed urinary incontinence (MUI), 65 cm H(2)O in detrusor overactivity incontinence (DOI) and 67 cm H(2)O for continent women . Age and MUCP were negatively correlated in all groups. Multiple regression analysis showed lower levels of MUCP in women with USI who also had previous hysterectomy or anti-incontinence surgery or who were in an older age group. Previous anti-incontinence surgery and older age were risk factors for lower MUCP in women with MUI and DOI. Receiver operator curves did not show MUCP to have utility as a diagnostic test despite age and parity stratification. MUCP < 20 cm H(2)O showed a sensitivity of 5 % and specificity of 98 % in diagnosing USI. CONCLUSIONS: MUCP failed to meet the criteria for a diagnostic test. Women with USI and MUI have lower MUCP than women with DOI and continent women in each decade of life. MUCP decreases with age.

Reoperation rate for traditional anterior vaginal repair: analysis of 207 cases with a median 4-year follow-up.

INTRODUCTION AND HYPOTHESIS: To determine the reoperation rate for symptomatic recurrence of cystoceles following traditional anterior colporrhaphy (without mesh). METHODS: Retrospective case note review of 207 cases of primary anterior colporrhaphy with/without other prolapse surgery. All patients received a 3-month clinic follow-up. Reoperation details for prolapse and/or urinary incontinence were obtained from patients general practitioners with a median follow-up of 50 months. RESULTS: The median age was 60 years (32-85), and median parity was 2. Twenty-nine of 207 (14%) patients had previous gynecological surgery. While the anatomical recurrence rate of cystoceles at 3 months postoperatively was 12%, the reoperation rate for recurrent cystocele by 50 months was 3.4%. Overall, 9.1% of the group underwent prolapse or incontinence surgery during this period. CONCLUSIONS: While the anatomical recurrence rates for cystocele following traditional anterior colporrhaphy might be high, the low reoperation rate at more than 4 years (3.4%) suggests that patient's symptoms might not be bothersome enough to require further surgery. Both subjective and anatomical outcomes are required to assess the outcome of both traditional and new prolapse procedures.

Conservative versus surgical management of prolapse: what dictates patient choice?

INTRODUCTION AND HYPOTHESIS: The aim of this study is to establish whether the presence of severe symptoms influences women's choice of pessaries or surgery for uterovaginal prolapse. METHODS: This is a prospective study using the validated Sheffield Prolapse Symptoms Questionnaire. RESULTS: Women choosing surgery (n = 251) were younger (58 versus 66 years), more bothered by dragging lower abdominal pain (33% versus 25%, P = 0.04), need for vaginal digitation (8% versus 3%, P = 0.02), and incomplete bowel emptying (27% versus 19%, P = 0.01) than women choosing pessaries (n = 429). More women opting for surgery were sexually active (51% versus 29%, P < 0.0001), perceived avoidance of sex due to prolapse (28% versus 17%, P = 0.000), and perceived prolapse interfering with sexual satisfaction as a severe problem (26% versus 15%, P = 0.000). CONCLUSIONS: Nearly two thirds of women with symptomatic prolapse initially opted for conservative management. Women choosing surgery over pessaries for treatment of prolapse describe more severe symptoms related to bowel emptying, sexual function, and quality of life and are bothered by them.

Effect of antifibrinolytic drugs on transfusion requirement and blood loss during orthotopic liver transplantation: Results from a single center.

BACKGROUND: During orthotopic liver transplantation (OLT), activation of the fibrinolytic system can contribute significantly to perioperative bleeding. Prophylactic administration of antifibrinolytic agents has been shown to reduce blood loss and the need for allogenic transfusion. OBJECTIVE: To study the effect of antifibrinolytics on requirement of blood components, blood loss and operative time during OLT in patients with end stage liver disease, reporting to a single centre. MATERIALS AND METHODS: Consecutive patients who underwent OLT at this centre during the period February 2003-October 2007 were the subjects of this study. Based on the individual anesthesiologist's preference, patients were assigned to receive either two million units of aprotinin (AP) as a bolus followed by 5,00,000 units/hour or 10 mg/kg tranexamic acid (TA) as a bolus followed by 10 mg/kg every six to eight hours, administered from the induction till the end of the surgery. Transfusion policy was standardized in all patients. Intraoperative red cell salvage was done wherever possible. The effect of these two antifibrinolytic drugs on transfusion requirement was evaluated as a whole and in a sub group of patients from each treatment group and compared with a concurrent control group that did not receive antifibrinolytic drugs. RESULTS: Fifty patients (40 M / 10 F, 44 adults, 6 pediatric patients) underwent OLT in the study period. Fourteen patients were given AP, 25 patients were given TA and 11 patients did not receive any of the agents(control group). The median volume of total blood components transfused in antifibrinolytic group (n = 39) was 4540 ml(0-19,200ml), blood loss 5 l(0.7-35l) and operative time 9h (4.5-17h) and that of control group(n = 11) was 5700 ml(0-15,500ml), 10 l(0.6-25 l) and 9h (6.4-15.8h) respectively. The median volume of blood transfusions, blood loss and operative time was lesser in AP group(n = 14) than that of TA group(n = 25). CONCLUSION: There is definite decrease in transfusion requirement, blood loss and operative time in the patients who received antifibrinolytic drugs than that of patients who did not receive. Because of the small sample size, comparisons carried between different groups did not show statistical significance. Prophylactic use of antifibrinolytics during OLT, possibly helps in blood conservation.

Pelvic floor dysfunction in morbidly obese women: pilot study.

OBJECTIVE: The objective of this study was to evaluate the impact of obesity on pelvic floor function in women. RESEARCH METHODS AND PROCEDURES: This was a prospective controlled study of 20 morbidly obese female patients planning to undergo gastric bypass surgery and 20 age-matched female controls. Subjects completed symptom and impact questionnaires, including the Incontinence Impact Questionnaire (IIQ-7), Urogenital Distress Inventory (UDI), the Kobashi Prolapse Symptom Inventory and Quality-of-Life Questionnaire (PSI-QOL), and Index of Female Sexual Function. Data were analyzed with Wilcoxon or ratio chi2 tests. RESULTS: Mean weight was 295.7 +/- 87.9 lbs in the study group and 144.79 +/- 33.07 lbs in the control group. Mean BMI was 52.65 +/-14.49 kg/m2 in the study group and 25.11 +/- 5.27 kg/m2 in the control group. According to the IIQ-7, urinary incontinence significantly affected lifestyle in the study group. The total IIQ-7 score was also significantly affected in the study group (p = 0.03). The UDI indicated more urinary leakage with activity (p = 0.04) and more incidents of small amounts of leakage (p = 0.02) in the study group. According to the PSI-QOL, women in the study group experienced constipation more often because of difficulty in emptying the rectum (p = 0.04). The PSI-QOL score was higher in the study group (6.75 +/- 6.84) than in the control group (2.65 +/- 3.03; p = 0.04). There were no significant differences between groups regarding sexual function. DISCUSSION: Morbid obesity is associated with a significant negative impact on urogenital health. Sexual function did not seem to be affected in women who are morbidly obese.

Isolated tuberculosis of the pancreas: a report of two cases and review of the literature.

We report two cases of pancreatic tuberculosis. The first patent (who tested positive for HIV) presented with abdominal pain, fever, weight loss, anorexia and tender epigastric lump. The CT scan revealed multiple small abscesses in the pancreas. The second patients, who had no evidence of immunodeficiency, presented with constitutional symptoms and obstructive jaundice. The CT scan revealed a mass in the pancreatic head with peripancreatic lymph nodes and dilatation of the intrahepatic and extrahepatic biliary tree. None of the patients had Mycobacterium tuberculosis infection of the lung or any other organ. Fine-needle aspiration biopsy clinched the diagnosis in both the patients, with caseation necrosis and plenty of acid-fast bacilli in the first patient, and characteristic granulomatous inflammation of the pancreas in the other. The first patient died during the index hospitalization, while the other responded well to antitubercular treatment with improvement in symptoms and radiological clearance of the initial lesions.

Profile of asymptomatic chronic HBV infection in India.

BACKGROUND & OBJECTIVES: In India, horizontal transmission in early childhood has been shown to be a significant mode of transmission of hepatitis B virus (HBV). This prospective, cross-sectional study was undertaken to study the biochemical, serological and histological profile of incidentally detected asymptomatic HBsAg positive subjects (IDAHS) picked up at a tertiary care referral centre. METHODS: In 157 (M:F::123:34) HBsAg positive subjects, clinical, biochemical, virological and histological assessment was done. The histological activity index (HAI) of > 3 was considered as chronic hepatitis. Serum was tested for HBsAg, HBeAg, HBeAb, HBV DNA and alanine transaminase (ALT). RESULTS: Seventy (45%) subjects were HBeAg and 83 (53%) anti-HBe positive. While 71 per cent of the subjects with elevated ALT had an HAI > 3, only 36 per cent with normal ALT showed significant histological changes (P < 0.001). Significant histopathological lesions in the liver biopsy were seen in 92 (59%) subjects, with moderate to severe lesions in 14. IDAHS who were HBeAg +ve were more likely to have significant histological lesion than those who were anti-HBe +ve (P < 0.01). In the anti-HBe +ve group, 35 of 57 (61%) subjects for whom HBV-DNA was available, were HBV-DNA positive. Anti-HBe+ve, HBV-DNA+ ve IDAHS with elevated ALT were more likely to have chronic hepatitis vis-a-vis those subjects in this group who had a normal ALT (P < 0.001). INTERPRETATION & CONCLUSION: ALT is a reliable discriminant of significant histological lesion in IDAHS. The relatively young mean age of Anti-HBe +ve IDAHS suggests an early age of infection and hence, early seroconversion or mutant virus infection in this cohort. A significant proportion of these IDAHS have HBV-DNA positivity and HAI > 3. Our results clearly demonstrate ongoing liver disease in asymptomatic, so-called "HBV carriers". We propose that the term hepatitis B 'carrier' should be abandoned and replaced by 'chronic HBV infection'.