Primary Prophylaxis Patterns for Hepatic Encephalopathy in Patients with Liver Cirrhosis: What are the Current Prescribing Trends in Specialty Practice?

INTRODUCTION: Hepatic encephalopathy (HE) is a significant complication of severe chronic liver insufficiency characterized by altered sensorium, motor, and cognitive dysfunction. This was a cross-sectional multicenter, epidemiological study to understand the prescribing pattern for primary prophylaxis of overt HE (OHE) in patients with cirrhosis in India. METHODS: The study was conducted at eight centers across different geographical regions of India. A total of 200 patients (100%) were screened, of which 197 (98.50%) met all the inclusion criteria. The prescribing pattern of the physicians was studied by calculating the percentage (subject to availability of sufficient data) of OHE-naïve patients with cirrhosis who were prescribed with different classes of drugs as primary prophylaxis of HE (such as lactulose, rifaximin, neomycin, sodium benzoate, and L-ornithine L- aspartate). The risk factors responsible for initiation of primary prophylaxis of HE was also determined. RESULTS: All the 197 patients (100%) were prescribed with prophylactic treatment. The factors that were considered by treating physicians to pose a risk for precipitating OHE for which prophylaxis was initiated were constipation in 111 (56.35%), infections in 51 (25.89%) and gastrointestinal bleeding in 35 (17.77%). Of the total 197 patients, 122 (61.93%) patients were prescribed a monotherapy, and 75 (38.07%) were prescribed a combination therapy. Of the patients on combination therapy, 68 (34.52%) patients were prescribed with two primary prophylaxis agents (dual therapy), and seven (3.55%) patients were prescribed with three primary prophylaxis agents (triple therapy). Lactulose was the most commonly prescribed agent for primary prophylaxis, followed by rifaximin. CONCLUSION: These findings may guide recommendations on primary prophylaxis for OHE in patients with liver cirrhosis that may help reduce the occurrence of first episode of overt HE, and thereby prevent subsequent cognitive impairment in these patients.

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.

Obstetric anal sphincter injuries after episiotomy: systematic review and meta-analysis.

INTRODUCTION: There is conflicting evidence on whether mediolateral episiotomy (MLE) reduces the risk of obstetric anal sphincter injuries (OASI) in spontaneous vaginal deliveries (SVD). OBJECTIVES: A systematic review was undertaken to compare rates of OASI amongst women who had undergone mediolateral episiotomy versus those who did not. METHODS: ᅟ SEARCH STRATEGY: Electronic searches were performed in literature databases: CINAHL, Cochrane, EMBASE, Medline and MIDIRS from database inception to July 2015. Studies were eligible if MLE was compared to spontaneous tears and if OASI was the outcome of interest. Two reviewers independently selected and extracted data on study characteristics, quality and results. We computed events of OASI in those who did and did not have an episiotomy from individual studies and pooled these results in a meta-analysis where possible. MAIN RESULTS: Of the 2090 citations, 16 were included in the review. All were non-randomised, population based or retrospective cohort studies. There was great variation in quality amongst these studies. Data from 7 studies was used for meta-analysis. On collating data from these studies where the majority of women (636755/651114) were nulliparous, MLE reduced the risk of OASI (RR 0.67 95 % CI 0.49-0.92) in vaginal delivery. CONCLUSION: The pooled analysis of a large number of women undergoing vaginal birth, most of who were nulliparous, indicates that MLE has a beneficial effect in prevention of OASI. An accurately given MLE might have a role in reducing OASI and should not be withheld, especially in nulliparous women. Caution is advised as the data is from non-randomised studies.

Obstetric anal sphincter injuries: review of anatomical factors and modifiable second stage interventions.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injuries (OASIs) are the leading cause of anal incontinence in women. Modification of various risk factors and anatomical considerations have been reported to reduce the rate of OASI. METHODS: A PubMed search (1989-2014) of studies and systematic reviews on risk factors for OASI. RESULTS: Perineal distension (stretching) of 170 % in the transverse direction and 40 % in the vertical direction occurs at crowning, leading to significant differences (15-30°) between episiotomy incision angles and suture angles. Episiotomies incised at 60° achieve suture angles of 43-50°; those incised at 40° result in a suture angle of 22°. Episiotomies with suture angles too acute (<30°) and too lateral (>60°) are associated with an increased risk of OASI. Suture angles of 40-60° are in the safe zone. Clinicians are poor at correctly estimating episiotomy angles on paper and in patients. Sutured episiotomies originating 10 mm away from the midline are associated with a lower rate of OASIs. Compared to spontaneous tears, episiotomies appear to be associated with a reduction in OASI risk by 40-50 %, whereas shorter perineal lengths, perineal oedema and instrumental deliveries are associated with a higher risk. Instrumental deliveries with mediolateral episiotomies are associated with a significantly lower OASI risk. Other preventative measures include warm perineal compresses and controlled delivery of the head. CONCLUSIONS: Relieving pressure on the central posterior perineum by an episiotomy and/or controlled delivery of the head should be important considerations in reducing the risk of OASI. Episiotomies should be performed 60° from the midline. Prospective studies should evaluate elective episiotomies in women with a short perineal length and application of standardised digital perineal support.

Cutting an episiotomy at 60 degrees: how good are we?

INTRODUCTION AND HYPOTHESIS: Episiotomy is regarded as the most common maternal obstetric surgical procedure. It is associated with a significant increase in blood loss, lower pelvic floor muscle strength, dyspareunia, and perineal pain compared with a perineal tear. We tested the hypothesis that all doctors and midwives can perform an episiotomy when prompted to, specifically cut at 60° from the midline (in a simulation model). METHODS: Doctors and midwives attending the BMFMS Annual Meeting (2014), Croydon Perineal Trauma Course and staff at Poole General Hospital were invited to cut a paper replica of the perineum with a commonly used episiotomy incision pad. Participants were prompted to cut an episiotomy at 60° to the perineal midline with the anus as a reference point. The angles and distances were measured using protractors and rulers. A 58-62° band was deemed acceptable to account for measurement errors. RESULTS: A total of 106 delegates participated. Only 15 % of doctors and midwives cut an episiotomy between 58 and 62°. Over one third (36 %) cut the episiotomy between 55 and 65° (inclusive). Nearly two thirds either underestimated the angle (<55°; 44 %), or overestimated the angle (>66°; 18 %). Thirty-six and 7.5 % of episiotomies were cut at <50 and >70° respectively. The origination point of the episiotomy was 5 mm away from the midline (IQR 1-8 mm). CONCLUSIONS: This original observational study shows that doctors and midwives were poor at cutting at the prompted episiotomy angle of 60°. This highlights the need to develop structured training programmes to improve the visual accuracy of estimating angles or the use of fixed angle devices to help improve the ability to estimate the desired angle.

Management of Chronic Hepatitis B Infection in India.

Chronic hepatitis B (CHB) infection is a substantial global health problem with highest prevalence observed in the sub-Saharan Africa and East Asia. India lies in the intermediate endemicity zone with prevalence ranging from 0.1% to 11.7%. The predominant route of transmission is horizontal and the most commonly occurring genotypes are A and D. The high mortality and morbidity associated with CHB constitutes significant health and economic burden in developing countries like India. Antiviral agents decrease HBV DNA load and prevent disease progression. Several regional and country expert associations have developed treatment guidelines for appropriate management of CHB; however, various factors like prevalence, disease awareness, immunization status, cost implications, availability of resources, type of transmission and emerging significance of HBV genotypes have influenced the management of CHB in a country. This article focuses on expert's recommendations on CHB management including initiation, monitoring and termination of treatment with emphasis on borderline cases. The article also throws light on the challenges to optimum management and provides preferred therapeutic approaches in Indian perspective.

Infections After Liver Transplant -Timeline, Management and Prevention.

Liver transplantation (LT) is the standard treatment for end- stage liver disease. Patient and graft survival have improved significantly in the last three decades owing to improvement in surgical technique, better perioperative management and better immunosuppressive regimens. However, LT recipients are at increased risk of infections, particularly in the first year after transplantation. The risk of infection is directly proportional to immunosuppressive regimen and graft function. In this review, we will briefly discuss the timeline of infections after liver transplant, preventive strategies and management of infectious complications.

APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.

Preventing Small-for-size Syndrome in Living Donor Liver Transplantation: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

Small-for-size syndrome (SFSS) is a well-recognized complication following liver transplantation (LT), with up to 20% developing this following living donor LT (LDLT). Preventing SFSS involves consideration of factors before the surgical procedure, including donor and recipient selection, and factors during the surgical procedure, including adequate outflow reconstruction, graft portal inflow modulation, and management of portosystemic shunts. International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplant Society of India Consensus Conference was convened in January 2023 to develop recommendations for the prediction and management of SFSS in LDLT. The format of the conference was based on the Grading of Recommendations, Assessment, Development, and Evaluation system. International experts in this field were allocated to 4 working groups (diagnosis, prevention, anesthesia, and critical care considerations, and management of established SFSS). The working groups prepared evidence-based recommendations to answer-specific questions considering the currently available literature. The working group members, independent panel, and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and evidence-based recommendations provided by working group 2 that can be implemented to prevent SFSS in LDLT patients.

Profile and outcome of patients with liver cirrhosis requiring mechanical ventilation.

OBJECTIVE: Few studies have addressed the outcome of patients with cirrhosis requiring mechanical ventilation (MV). We aimed to investigate the short-term outcome of such patients. METHODS: Retrospective review of data of 73 consecutive patients with cirrhosis requiring MV over a 2-year period (2006-2008). Data on patient's characteristics, reason for MV, the presence of other organ failure, and first day Acute Physiology Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA), Child-Pugh (CP), and Model for End-Stage Liver Disease (MELD) scores were collected, with 30-day mortality being the primary outcome measure. RESULTS: Observed mortality in ICU and at 30 days was 75.3% and 87.7%, respectively. Area under curve was 0.77 (95% CI, 0.65-0.86) for APACHE II, 0.94 (95% CI, 0.85-0.98) for SOFA, 0.83 (95% CI, 0.7-0.96) for CP, and 0.93 (95% CI, 0.85-0.98) for MELD (P = .096) in predicting 30-day mortality. By univariate analysis, indication for intubation (P = .001), need for vasopressor support (P = .002), the presence of renal failure (P < .03), and duration of MV (P < .001) were significantly associated with mortality. On multivariate analysis, only duration of MV (adjusted odds ratio 0.63, 95% CI: 0.42-0.95, P = .03) was the independent predictor of mortality with a majority of patients, 51/64 (79.7%), dying in the first 48 hours of intubation. CONCLUSIONS: Patients with cirrhosis requiring MV have a dismal prognosis. Such patients and their families should be informed about the overall outcome to assist their decisions about life support and intensive care, outside the transplant setting. Prognostic scores, especially SOFA and MELD, may aid in determining which patients may benefit from aggressive therapy.

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.

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.

Erratum to 'Indian National Association for the Study of Liver Consensus Statement on Acute Liver Failure (Part-2): Management of Acute Liver Failure' [J Clin Exp Hepatol 10 (2020) 477-517].

[This corrects the article DOI: 10.1016/j.jceh.2020.04.011.].

Nutrition in Chronic Liver Disease: Consensus Statement of the Indian National Association for Study of the Liver.

Malnutrition and sarcopenia are common in patients with chronic liver disease and are associated with increased risk of decompensation, infections, wait-list mortality and poorer outcomes after liver transplantation. Assessment of nutritional status and management of malnutrition are therefore essential to improve outcomes in patients with chronic liver disease. This consensus statement of the Indian National Association for Study of the Liver provides a comprehensive review of nutrition in chronic liver disease and gives recommendations for nutritional screening and treatment in specific clinical scenarios of malnutrition in cirrhosis in adults as well as children with chronic liver disease and metabolic disorders.

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.

Two cases of Nocardia bacteraemia in solid organ transplant recipients.

Nocardiosis is an opportunistic infection occurring in immunosuppressed patients. While disseminated nocardiosis is common in immunosuppressed patients, Nocardia bacteraemia is rare. There are few reports of Nocardia bacteraemia following solid organ transplantation. We report two cases of Nocardia bacteraemia in solid organ transplant recipients-Nocardia cyriacigeorgica bacteraemia in liver transplant recipient and concomitant Nocardia farcinica bacteraemia and cyclosporiasis in a heart transplant recipient. Prompt recognition of early bacteraemia with initiation of antibiotic therapy may avoid the complications of disseminated disease in the solid organ transplant recipients.

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 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.

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.