National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma.

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

Performance of HCV core antigen and PCR testing in a predominantly genotype 3 population.

Hepatitis C core antigen (HCVcAg) is becoming increasingly recognized as an alternative to molecular testing for the confirmation of chronic hepatitis C. However, there are limited data on the performance of this assay in a genotype 3 (GT3) predominant country like Pakistan. We conducted a study to evaluate the diagnostic performance of HCVcAg against the HCV polymerase chain reaction (PCR) molecular test. HCV antibody-positive patients requiring confirmatory testing were recruited from August to October 2018 at the Pakistan Kidney and Liver Institute and Research Center (PKLI&RC), Lahore, Pakistan. Patients with previously known diagnoses or treatment histories were excluded. The Abbott HCV Ag assay was used for HCVcAg testing. Results ≥3.00 fmol/L were considered positive for HCVcAg. The Abbott RealTime HCV assay was used for PCR testing with a lower detection limit of ≥12 IU/mL. We computed the sensitivity, specificity and correlation of HCVcAg against HCV PCR. A total of 394 patients were recruited. The median age of the patients was 42 years. Most participants were females (51.5%, n = 203), 30.7% (n = 121) had HTN, 10.4% DM (n = 41) and 5% had APRI ≥2. The overall sensitivity was 98.0% and the specificity was 98.6%. The lowest detection limit of cAg was an HCV RNA value of 4657 IU/mL. The levels of cAg were highly correlated with those of HCV RNA by Spearman's rank correlation test (r = 0.935, p < .001). HCVcAg represents a suitable alternative with high sensitivity and specificity compared with HCV PCR in the GT3-predominant population and can be incorporated into algorithms to improve linkage to care.

Exploring safety and efficacy of rivaroxaban after living donor liver transplantation: a retrospective study.

PURPOSE: Thromboembolic complications remain a significant concern in postoperative patients, particularly those who have undergone liver transplantation. Warfarin has been the standard oral anticoagulant. Direct oral anticoagulants (DOACs) have several advantages over warfarin, including rapid onset of action and standardized dose guidelines. We aimed to assess the safety of rivaroxaban in living donor liver transplantation (LDLT) recipients. METHODS: This study was a single-center, retrospective descriptive analysis of LDLT recipients who received rivaroxaban between December 2020 and April 2022. A total of 27 recipients received rivaroxaban postoperatively. Liver function tests, immunosuppression levels, serum creatinine, and INR were recorded before the initiation of rivaroxaban and then on post-therapy days 1, 7, 14, 28, 90, and 180. RESULTS: Among the 27 recipients receiving rivaroxaban postoperatively, portal venous thrombosis was the most prevalent indication for anticoagulation (44.4%), followed by Budd-Chiari syndrome (29.6%). Nine patients had a twofold increase in either ALT or AST values, two of whom were treated for biliary strictures and the others for rejection. Eighteen patients were given tacrolimus, and eight were on cyclosporine, with one patient switched from tacrolimus to cyclosporine due to insufficient therapeutic levels. There were no incidents of bleeding or re-thrombosis during the 180-day follow-up period. CONCLUSION: Rivaroxaban may be a safe and effective alternative in LDLT recipients with no significant adverse incidents. Further studies with larger sample sizes are needed to confirm these findings and determine this population's optimal dose and duration of rivaroxaban therapy.

Diagnosis and monitoring of hepatocellular carcinoma in Hepatitis C virus patients using attenuated total reflection Fourier transform infrared spectroscopy.

BACKGROUND: Current diagnostic methods for assessment of hepatitis C virus related hepatocellular carcinoma and subsequent categorization of hepatocellular carcinoma into non-angio-invasive hepatocellular carcinoma and angio-invasive hepatocellular carcinoma, to establish appropriate treatment strategies, are costly, invasive and requires multiple screening steps. This demands alternative diagnostic approaches that are cost-effective, time-efficient, and minimally invasive, while maintaining their efficacy for screening of hepatitis c virus related hepatocellular carcinoma. In this study, we propose that attenuated total reflection Fourier transform infrared in conjunction with principal component analysis - linear discriminant analysis and support vector machine multivariate algorithms holds a potential as a sensitive tool for the detection of hepatitis C virus-related hepatocellular carcinoma and the subsequent categorization of hepatocellular carcinoma into non-angio-invasive hepatocellular carcinoma and angio-invasive hepatocellular carcinoma. METHODS: Freeze-dried sera samples collected from 31 hepatitis c virus related hepatocellular carcinoma patients and 30 healthy individuals, were used to acquire mid-infrared absorbance spectra (3500-900 cm-1) using attenuated total reflection Fourier transform infrared. Chemometric machine learning techniques were utilized to build principal component analysis - linear discriminant analysis and support vector machine discriminant models for the spectral data of hepatocellular carcinoma patients and healthy individuals. Sensitivity, specificity, and external validation on blind samples were calculated. RESULTS: Major variations were observed in the two spectral regions i.e., 3500-2800 and 1800-900 cm-1. IR spectral signatures of hepatocellular carcinoma were reliably different from healthy individuals. Principal component analysis - linear discriminant analysis and support vector machine models computed 100% accuracy for diagnosing hepatocellular carcinoma. To classify the non-angio-invasive hepatocellular carcinoma/ angio-invasive hepatocellular carcinoma status, diagnostic accuracy of 86.21% was achieved for principal component analysis - linear discriminant analysis. While the support vector machine showed a training accuracy of 98.28% and a cross-validation accuracy of 82.75%. External validation for support vector machine based classification observed 100% sensitivity and specificity for accurately classifying the freeze-dried sera samples for all categories. CONCLUSIONS: We present the specific spectral signatures for non-angio-invasive hepatocellular carcinoma and angio-invasive hepatocellular carcinoma, which were prominently differentiated from healthy individuals. This study provides an initial insight into the potential of attenuated total reflection Fourier transform infrared to diagnose hepatitis C virus related hepatocellular carcinoma but also to further categorize into non-angio-invasive and angio-invasive hepatocellular carcinoma.

Use of ATR-FTIR spectroscopy to differentiate between cirrhotic/non-cirrhotic HCV patients.

BACKGROUND: Conventional techniques to diagnose (HCV) and assess non-cirrhotic/cirrhotic status of the patient for appropriate treatment regime are expensive and invasive. Present available diagnostic tests are expensive as they include multiple screening steps. Therefore, there is a need of cost-effective, less time consuming and minimally invasive alternative diagnostic approaches can be used for effective screening. We propose that (ATR-FTIR) in conjunction with (PCA-LDA),(PCA-QDA) and (SVM) multivariate algorithms can be used as a sensitive tool for detection of HCV infection and to assess non-cirrhotic/cirrhotic status of patients. METHODS: We used 105 sera samples, of which, 55 were from healthy and 50 were from HCV positive individuals. These 50 HCV positive patients were further classified into cirrhotic and non-cirrhotic categories using serum markers and imaging techniques. These samples were freeze dried prior to spectral acquisition then multivariate data classification algorithms were employed to classify these sample types. RESULTS: PCA-LDA and SVM model computed the diagnostic accuracy of 100% for detection of HCV infection. To further classify the non-cirrhotic/cirrhotic status of a patient, diagnostic accuracy of 90.91% for PCA-QDA and 100% for SVM was observed. Internal and external validation for SVM based classifications observed 100% sensitivity and specificity. The confusion matrix generated by PCA-LDA model computed the validation and calibration accuracy showed 100% sensitivity and specificity, by using 2 PCs for HCV infected and healthy individuals. However, when the PCA QDA analysis was done to classify the non-cirrhotic sera samples from cirrhotic sera samples the diagnostic accuracy achieved was 90.91% based on 7 PC's. SVM was also employed for classification and developed model showed the best results with 100% sensitivity and specificity when external validation was applied. CONCLUSIONS: This study provides an initial insight that ATR-FTIR spectroscopy in conjugation with multivariate data classification tools holds a potentialnot onlytoeffectively diagnosis HCV infection but also to assess non-cirrhotic/cirrhotic status of patients.

Practical considerations when treating chronic hepatitis E in solid organ transplant recipients.

Hepatitis E virus (HEV) can lead to chronic infections in immunosuppressed patients. The use of ribavirin to treat chronic HEV has been well-established in case reports and guidelines. However, practical approaches to the use of this antiviral treatment in a post-transplant patient, including drug interactions, dosing adjustments, and monitoring parameters, are lacking. Thus, we present our real-world approach to the use of ribavirin to treat chronic HEV in a solid organ transplant recipient.

Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysis.

BACKGROUND: The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence. METHODS: We adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018-30. We calibrated the model to country-level demographic data for 1960-2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007-08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs. FINDINGS: One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13·8 million (95% UI 13·4-14·1) individuals being screened and 350 000 (315 000-385 000) treatments started annually, decreasing hepatitis C incidence by 26·5% (22·5-30·7) over 2018-30. Prioritised screening of high prevalence groups (PWID and adults aged ≥30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46·8% and decrease incidence by 50·8% (95% UI 46·1-55·0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8·1 billion, reducing to $3·9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm. INTERPRETATION: Pakistan will need to invest about 9·0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030. FUNDING: UNITAID.

Hemorrhagic complications of paracentesis: a systematic review of the literature.

Introduction. Large volume paracentesis is considered a safe procedure carrying minimal risk of complications and rarely causing morbidity or mortality. The most common complications of the procedure are ascitic fluid leakage, hemorrhage, infection, and perforation. The purpose of this study was to evaluate all hemorrhagic complications and their outcomes and to identify any common variables. Methods. A literature search for all reported hemorrhagic complications following paracentesis was conducted. A total of 61 patients were identified. Data of interest were extracted and analyzed. The primary outcome of the study was 30-day mortality, with secondary endpoints being achievement of hemostasis after intervention and mortality based on type of intervention. Results. 90% of the patients undergoing paracentesis had underlying cirrhosis. Three types of hemorrhagic complications were identified: abdominal wall hematomas (52%), hemoperitoneum (41%), and pseudoaneurysm (7%). Forty percent of the patients underwent either a surgical (35%) or an IR guided intervention (65%). Patients undergoing a surgical intervention had a significantly higher rate of mortality at day 30 compared to those undergoing IR intervention. Conclusion. Abdominal wall hematomas and hemoperitoneum are the most common hemorrhagic complications of paracentesis. Transcatheter coiling and embolization appear to be superior to both open and laparoscopic surgery in treatment of these complications.