Minor salivary gland biopsy for the diagnosis of familial amyloid polyneuropathy.

The diagnosis of Val30Met familial amyloidotic polyneuropathy (FAP) is based on genetic tests, clinical manifestations, familial history and biopsy of peripheral tissues (e.g. rectum, abdominal fat pad, sural nerve, and minor salivary gland) to confirm the presence of amyloid deposits. The aim of this study was to determine the frequency of amyloid deposits in minor salivary glands biopsied from FAP patients and to investigate whether an association exists between the presence of these deposits and clinical features. Seventeen patients with FAP were submitted to minor salivary gland biopsy to confirm the presence of amyloid deposits. The histopathology of the salivary glands confirmed glandular amyloid deposits in nine symptomatic patients (sensitivity of 75.0%). In general, FAP patients who tested positive for glandular amyloid deposits exhibited significantly higher frequencies of sensorimotor and dysautonomic dysfunctions (p = 0.001) compared with those who tested negative. None of the patients reported xerostomia. Minor salivary gland biopsy may help confirm the diagnosis of FAP in symptomatic cases, as it is noninvasive, easy to execute, and causes minimal discomfort to patients.

Acute-on-chronic liver failure: a retrospective review of cases at a transplantation center in Brazil.

PURPOSE: Acute-on-chronic liver failure (ACLF) is a leading cause of death in cirrhotic patients. This study aims to describe the outcomes of in-patients with ACLF at a liver transplantation (LT) center in Brazil. METHODS: Retrospective study analyzing patient data from 2017 to 2022. Re-transplant cases and patients without previous chronic liver disease were excluded. The ACLF diagnosis was based on the European Association for the Study of the Liver-Chronic Liver Failure criteria and assessments repeated on days 3 and 7 after the initial diagnosis. RESULTS: Among 381 patients, 10.49% (n = 40) were diagnosed with ACLF. Bacterial infection was the most common precipitating factor (45%). Kidney failure occurred in 65% of the cases. The 28-day mortality rate was 35% and varied according to ACLF severity at diagnosis, from single organ failure (ACLF-1) at 22% to three organ failures (ACLF-3) at 60%. Eighteen patients (45%) were transplanted with a 100% 28-day survival rate. For ACLF-3 cases at diagnosis (n = 15), the 28-day and 1-year survival rates with a transplant (n = 4) were 100% and 80%, respectively, and without transplant (n = 11), 10 and 0%, respectively. CONCLUSIONS: ACLF was associated with high mortality rates. LT was an effective therapeutic option, particularly for ACLF-3 cases.

Exercise training as an intervention for frailty in cirrhotic patients on the liver transplant waiting list: A systematic review.

BACKGROUND: The existing literature suggests that exercise for cirrhotic patients is safe and favours significant improvement to their physical capacity. However, exercise training for this population and how to deliver activities, especially in severe stages of the disease and while waiting for a liver transplant (LT), remain undefined. AIM: To review the existing exercise prescriptions for cirrhotic patients on the waiting list for LT, their results for frailty evolution and their effect on clinical outcomes. METHODS: A systematic review was performed following the Preferred Reporting Review and Meta-Analysis guidelines and searching the PubMed, MEDLINE, and Scopus databases. The keyword "liver transplant" was used in combination with the free terms "frailty" and "exercise" for the literature review. Clinical studies that evaluated the effect of a regular training program, independent of supervision or the duration or intensity of physical exercise, in cirrhotic patients on the waiting list for LT were reviewed. The data on safe physical activity prescriptions following Frequency, Intensity, Time, and Type recommendations were extracted and summarised. RESULTS: Nine articles met the inclusion criteria for this review. Various instruments for frailty assessment were used, frequently in combination. Five studies prescribed physical activity for patients, one in-person and four to be performed remotely and unsupervised. The remaining four studies only used a self-report instrument to assess the level of physical activity. None reported adverse events related to exercise training. The exercise frequency mainly varied from daily to a minimum of twice per week. The intensity depended on frailty and included increasing levels of activity. The type of exercise was predominantly a combination of aerobic and resistance training. The duration of exercise varied from 4 to 12 wk. Three articles evaluated the effect of the exercise program on clinical outcomes, reporting a reduction in 90-d readmission rates post-transplant and improved frailty scores, as well as improved survival of cirrhotic patients waiting for LT. CONCLUSION: Routine frailty assessment is essential for this population. Although more robust evidence is required, the prescription of exercise is safe and can improve patients' functional capacity, improving pre- and post-LT outcomes.

Establishing a HOPE Program in a Real-life Setting: A Brazilian Case Series.

Background: Although hypothermic oxygenated perfusion (HOPE) improves posttransplant outcomes, setting up machine perfusion programs may be subjected to specific obstacles under different conditions. This study aims to describe the establishment of HOPE in a real-life setting in Brazil. Methods: Extended criteria donors in donation after brain death organs preserved by HOPE were accepted for higher-risk candidates needing expedited transplantation, perceived as those who would benefit most from the technique because of its limited availability. Extended criteria donors was defined by the Eurotransplant criteria. High-risk transplant candidates were characterized by suboptimal surgical conditions related to the recipient or the procedure. Results: Six HOPE-preserved grafts were transplanted from February 2022 to August 2022. The mean donor risk index was 1.7 (SD 0.5). One organ was severely steatotic, and 3 had an anticipated cold ischemia time above 12 h. Recipients' mean model for end-stage liver disease was 28.67 (SD 6.79), with 1 case of retransplant, 1 of refractory ascites, and 1 of acute-on-chronic liver failure. The mean cold ischemia time was 5 h 42 min (SD 82 min), HOPE 6 h 3 min (SD 150 min), and total preservation time 11 h 46 min (SD 184 min). No case had early allograft dysfunction. The mean length of hospital stay was 10 d with 100% graft and patient survival and no ischemic cholangiopathies at a median follow-up of 15 mo (min 12, max 18). Costs and country-specific legal regulations for device utilization were the major hurdles to implementing the program. Conclusion: We presented a pathway to introduce and rationalize the use of HOPE in a scenario of challenging donor-recipient matching with good results. These findings may aid in implementing machine perfusion programs, especially in settings with limited resources or complex transplant logistics.

Current and future perspectives on acute-on-chronic liver failure: Challenges of transplantation, machine perfusion, and beyond.

Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation, organ failure and high short-term mortality. Partially due to the lack of universal diagnostic criteria, the actual ACLF prevalence remains unclear; nevertheless, it is expected to be a highly prevalent condition worldwide. Earlier transplantation is an effective protective measure for selected ACLF patients. Besides liver trans-plantation, diagnosing and treating precipitant events and providing supportive treatment for organ failures are currently the cornerstone of ACLF therapy. Although new clinical specific therapies have been researched, more studies are necessary to assess safety and efficacy. Therefore, future ACLF management strategies must consider measures to improve access to liver transplantation because the time window for this life-saving therapy is frequently narrow. Thus, an urgent and global discussion about allocation and prioritization for transplantation in critically ill ACLF patients is needed because there is evidence suggesting that the current model may not portray their waitlist mortality. In addition, while donor organ quality is meant to be a prognostic factor in the ACLF setting, recent evidence suggests that machine perfusion of the liver may be a safe tool to improve the donor organ pool and expedite liver transplantation in this scenario.

Update on the management and treatment of viral hepatitis.

This review aims to summarize the current evidence on the treatment of viral hepatitis, focusing on its clinical management. Also, future treatment options and areas of potential research interest are detailed. PubMed and Scopus databases were searched for primary studies published within the last ten years. Keywords included hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus, hepatitis D virus (HDV), hepatitis E virus, and treatment. Outcomes reported in the studies were summarized, tabulated, and synthesized. Significant advances in viral hepatitis treatment were accomplished, such as the advent of curative therapies for hepatitis C and the development and improvement of hepatitis A, hepatitis B, and hepatitis E vaccination. Drugs that cure hepatitis B, going beyond viral suppression, are so far unavailable; however, targeted antiviral drugs against HBV (immunomodulatory therapies and gene silencing technologies) are promising approaches to eradicating the virus. Ultimately, high vaccination coverage and large-scale test-and-treat programmes with high screening rates may eliminate viral hepatitis and mitigate their burden on health systems. The development of curative hepatitis C treatment renewed the enthusiasm for curing hepatitis B, albeit further investigation is required. Novel therapeutic options targeting HDV life cycle are currently under clinical investigation.

Acute-on-chronic liver failure: a retrospective review of cases at a transplantation center in Brazil

ABSTRACT Purpose: Acute-on-chronic liver failure (ACLF) is a leading cause of death in cirrhotic patients. This study aims to describe the outcomes of in-patients with ACLF at a liver transplantation (LT) center in Brazil. Methods: Retrospective study analyzing patient data from 2017 to 2022. Re-transplant cases and patients without previous chronic liver disease were excluded. The ACLF diagnosis was based on the European Association for the Study of the Liver-Chronic Liver Failure criteria and assessments repeated on days 3 and 7 after the initial diagnosis. Results: Among 381 patients, 10.49% (n = 40) were diagnosed with ACLF. Bacterial infection was the most common precipitating factor (45%). Kidney failure occurred in 65% of the cases. The 28-day mortality rate was 35% and varied according to ACLF severity at diagnosis, from single organ failure (ACLF-1) at 22% to three organ failures (ACLF-3) at 60%. Eighteen patients (45%) were transplanted with a 100% 28-day survival rate. For ACLF-3 cases at diagnosis (n = 15), the 28-day and 1-year survival rates with a transplant (n = 4) were 100% and 80%, respectively, and without transplant (n = 11), 10 and 0%, respectively. Conclusions: ACLF was associated with high mortality rates. LT was an effective therapeutic option, particularly for ACLF-3 cases.

Liver transplant outcome: a comparison between high and low MELD score recipients.

OBJECTIVE: To compare low and high MELD scores and investigate whether existing renal dysfunction has an effect on transplant outcome. METHODS: Data was prospectively collected among 237 liver transplants (216 patients) between March 2003 and March 2009. Patients with cirrhotic disease submitted to transplantation were divided into three groups: MELD > or = 30, MELD < 30, and hepatocellular carcinoma. Renal failure was defined as a +/- 25% decline in estimated glomerular filtration rate as observed 1 week after the transplant. Median MELD scores were 35, 21, and 13 for groups MELD > or = 30, MELD < 30, and hepatocellular carcinoma, respectively. RESULTS: Recipients with MELD > or = 30 had more days in Intensive Care Unit, longer hospital stay, and received more blood product transfusions. Moreover, their renal function improved after liver transplant. All other groups presented with impairment of renal function. Mortality was similar in all groups, but renal function was the most important variable associated with morbidity and length of hospital stay. CONCLUSION: High MELD score recipients had an improvement in the glomerular filtration rate after 1 week of liver transplantation.