Long-term health and economic benefits of switching to tenofovir alafenamide versus continuing on entecavir in chronic hepatitis B patients with low-level viremia in Saudi Arabia.

BACKGROUND: Despite the success of current treatments, many chronic hepatitis B (CHB) patients still live with low-level viremia [LLV] resulting in liver disease progression. This study evaluated the long-term health and economic impact of switching to tenofovir alafenamide (TAF) from entecavir (ETV) in Saudi Arabia (SA) in chronic hepatitis B (CHB) LLV patients. METHODS: A hybrid decision tree Markov state-transition model was developed to simulate a cohort of patients with CHB LLV treated with ETV and switched to TAF over a lifetime horizon in SA. While on treatment, patients either achieved complete virologic response (CVR) or maintained LLV. CVR patients experienced slower progression to advanced liver disease stages as compared to LLV patients. Demographic data, transition probabilities, treatment efficacy, health state costs, and utilities were sourced from published literature. Treatment costs were sourced from publicly available databases. RESULTS: Base case analysis found that over a lifetime horizon, switching to TAF versus remaining on ETV increased the proportion of patients achieving CVR (76% versus 14%, respectively). Switching to TAF versus remaining on ETV resulted in a reduction in cases of compensated cirrhosis (-52%), decompensated cirrhosis (-5%), hepatocellular carcinoma (-22%), liver transplants (-12%), and a 37% reduction in liver-related deaths. Switching to TAF was cost-effective with an incremental cost-effectiveness ratio of $57,222, assuming a willingness-to-pay threshold of three times gross national income per capita [$65,790/QALY]. CONCLUSIONS: This model found that switching to TAF versus remaining on ETV in SA CHB LLV patients substantially reduced long-term CHB-related morbidity and mortality and was a cost-effective treatment strategy.

Tandem mass tag-based quantitative proteomic analysis of cervical cancer.

BACKGROUND: Cervical cancer is a common cancer in women caused by high-risk human papillomavirus (Hr-HPV). Many potential biomarkers have been proposed for precancerous lesions and cancer diagnosis and some of these markers studied for prognosis. This study determined potential biomarkers for cervical cancer diagnosis in regard to HPV genotype by using isobaric labeling quantitative proteomics. METHODS: in the current study, there were 75 formalin fixed paraffin embedded (FFPE) uterine cervical samples that used to determine the 14 HPV genotypes and the viral load of each genotype was determined. The tandem mass tag (TMT) proteomic work was performed on four FFPE samples of cervical cancer and four FFPE of control samples. The validation of biomarkers from cervical proteome were evaluated using Immunohistochemistry (IHC) testing. RESULTS: The most frequent HPV genotype among all other genotypes was HPV 16. There were 2753 proteins quantified by TMT and 336 of these proteins had significant differential abundances. KPNA2, MCM2, COL1A1, and DCN were selected based on functional enrichment analysis and validated by Immunohistochemistry (IHC) testing. The staining of IHC confirmed the upregulation of KPNA2 and MCM2 expression in cervical neoplasia and the downregulation of DCN and COL1A1 in some cervical cancer group subjects. CONCLUSION: The KPNA2 marker was compared to other previously reported biomarkers and is a putative biomarker to be validated in further studies, specifically the relationship with HPV load.

Saudi association for the study of liver diseases and transplantation position statement on the hepatology workforce in Saudi Arabia.

The field of hepatology has evolved significantly over the last two decades. Hepatology practice in Saudi Arabia (SA) was dominated by hepatitis B and C viruses but is now being overtaken by patients with non-alcoholic fatty liver disease. These patients require greater medical attention as their care is more complex compared to patients with viral hepatitis. In addition, liver transplantation (LT) has expanded significantly in SA over the last three decades. There is a necessity to increase the hepatology workforce to meet the demand in SA. The time has come to reinforce the transplant hepatology fellowship program, that was launched recently, and to develop a nurse practitioner practice model to meet these demands. In addition, SA is going through a health care reform to enhance health care delivery which may affect the financial compensation polices of various specialties including gastroenterology and hepatology. Therefore, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) established a task force to discuss the current and future demands in the hepatology workforce in SA, as well as to discuss different avenues of financial compensation for transplant hepatologists in LT centers.

A Rare Case of Rapid Onset Thrombocytopenia Induced by Piperacillin/Tazobactam in a Liver Transplant Recipient.

Drug-induced thrombocytopenia is a relatively common clinical condition. However, acute thrombocytopenia after initiation of piperacillin/tazobactam is rare, with only a few cases reported in the literature. The mechanism by which it happens is still unclear but it is thought to be immune-mediated. We present the first case of rapid-onset thrombocytopenia induced by piperacillin/tazobactam in a liver transplant recipient. Our patient had previous exposure to the antibiotic, and thrombocytopenia was treated by merely stopping the culprit antibiotic (piperacillin/tazobactam). The patient had a successful challenge with cefepime afterward despite possible cross-reactivity, making this the second case report of successful re-challenging with cefepime.

Salvage liver transplantation after resection of colorectal cancer liver metastasis with favorable outcomes: a case report and review of the literature.

BACKGROUND: Approximately 50% of patients with colorectal cancer (CRC) develop metastases most commonly in the liver. Liver transplantation (LT) can be used in certain cases of primary liver malignancy or in metastatic diseases, such as Neuroendocrine tumors. However, there are controversies regarding LT as a treatment option for liver metastasis from CRC due to poor outcomes in previously reported cases. CASE PRESENTATION: We report a 37-year-old male who underwent resection of the left-sided colon due to cancer and was found to have synchronous liver metastasis for which he received chemotherapy. Later, he underwent a right hepatectomy, which was complicated by insufficient liver remnant function despite the preserved liver perfusion. Therefore, salvage liver transplantation was performed successfully with a good long-term outcome. CONCLUSIONS: Many studies examined the survival and quality of life in patients undergoing liver transplantation for unresectable colorectal liver metastasis; these studies include the SECA Study (secondary cancer) and others with favorable outcomes. We reviewed the literature and compared the outcomes of some of these studies in this article. Our case emphasizes that liver transplantation could be an option for some colon cancer liver metastasis (CLM) patients, specifically, as a salvage procedure. Thus, more research is needed to develop selection criteria for patients who may benefit from liver transplantation.

Principles of Care for Patients with Liver Disease During the Coronavirus Disease 2019 (COVID-19) Pandemic: Position Statement of the Saudi Association for the Study of Liver Disease and Transplantation.

In December 2019, a novel coronavirus was identified in patients in Wuhan, China. The virus, subsequently named severe acute respiratory syndrome coronavirus-2, spread worldwide and the disease (coronavirus disease 2019 or COVID-19) was declared a global pandemic by the World Health Organization in March 2020. Older adults and individuals with comorbidities have been reported as being more vulnerable to COVID-19. Patients with chronic liver disease (CLD) have compromised immune function due to cirrhosis and are more susceptible to infection. However, it is unclear if patients with CLD are more vulnerable to COVID-19 and its complications than other populations. The high number of severe cases of COVID-19 has placed an unusual burden on health systems, compromising their capacity to provide the regular care that patients with CLD require. Hence, it is incredibly crucial at this juncture to provide a set of interim recommendations on the management of patients with CLD during the current COVID-19 outbreak.

Menotrophin Induced Autoimmune Hepatitis.

Menotrophin is a protein-based hormonal therapy. It is used as a fertility medication that is given as injection either subcutaneously or intramuscularly. Menotrophin has not been previously reported to cause drug-induced liver injury. Drug-induced liver injury (DILI) is commonly seen nowadays with the expansion of the drug industry. It is associated with prescribed medications, over the counter drugs, herbal and dietary supplements. We report the first case of Menotrophin-induced autoimmune hepatitis in a 26-year-old Caucasian woman who was diagnosed with primary infertility due to failure to conceive after five years of marriage. She had received several cycles of Menotrophin, then developed new onset jaundice and fatigue associated with increase in transaminases. She had normal baseline liver function and enzymes prior to receiving treatment with Menotrophin. Evaluation showed no evidence of viral hepatitis, metabolic, alcoholic or vascular causes of liver injury. Autoimmune screening was positive for antinuclear antibody (ANA) with titer of 1 : 640 fine speckled, immunoglobulin G (IgG) level was 1900 mg/dl. Antimitochondrial antibodies (AMA) and antismooth muscle antibodies were negative. Liver biopsy showed features of chronic hepatitis with interface hepatitis and prominence of plasma cells, which best reflects autoimmune hepatitis. Her liver enzymes and bilirubin completely normalized after discontinuation of further Menotrophin therapy and starting treatment with prednisolone and Azathioprine.

Real life efficacy of ledipasvir/sofosbuvir in hepatitis C genotype 4-infected patients with advanced liver fibrosis and decompensated cirrhosis.

Limited clinical trial data has shown high efficacy of co-formulated ledipasvir/sofosbuvir (LDV/SOF) in the treatment of hepatitis C virus (HCV) genotype (GT)-4 infected cirrhotic patients. We assessed real-world safety and efficacy of LDV/SOF with or without ribavirin (RBV) in GT4-infected patients with compensated and decompensated cirrhosis. PATIENTS & METHODS: This observational cohort (n = 213) included GT4 treatment-naïve (59.6%) and -experienced (40.4%) patients with advanced fibrosis (F3, Metavir; n = 30), compensated (F4, n = 135) and decompensated cirrhosis (n = 48) treated for 12 (n = 202) or 24 weeks (n = 11) with LDV/SOF. RBV was dosed by physician discretion between 600-1200 mg daily. Patients with prior DAA failure were excluded from the analysis. The primary efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12) on an intention-to-treat analysis, and occurrence of serious adverse events (SAEs). RESULTS: The mean age of the overall cohort was 59.6 ±â€¯12.1 years and 125 (58.7) were female. Overall, 197 (92.5%) of the patients achieved SVR12, including 93.3% of F3 fibrosis, 93.3% of compensated cirrhotics and 89.6% of the decompensated cirrhotics (P = 0.686). Addition of RBV (68.5%) did not enhance efficacy (91.8% vs. 94.0% without RBV, P = 0.563), including in F3 fibrosis, compensated and decompensated cirrhosis (P > 0.05, for all). There was no difference in SVR12 rates with 24 and 12 weeks therapy (90.9% and 92.6%, respectively; P = 0.586). Treatment failure (n = 16) was mostly related to relapse (n = 11), while on-treatment death (n = 3) and breakthrough (n = 2) comprised a minority. SAEs occurred in 9 (4.2%) patients requiring early treatment discontinuation in 4 (3 on-treatment deaths and 1 pregnancy). CONCLUSION: LDV/SOF therapy yielded high SVR12 rates in both compensated and decompensated cirrhotic GT4 patients. The addition of RBV to this regimen did not improve efficacy. The safety profile of this regimen was comparable with that reported for other HCV genotypes.

Transient elastography in Canada: current state and future directions.

BACKGROUND: Transient elastography (TE) is a safe and effective technology to noninvasively assess hepatic fibrosis in patients with numerous liver conditions. TE is not readily available to all Canadians, and data regarding how this technology is incorporated into clinical practice are lacking. OBJECTIVE: To describe TE practices in Canada, and to identify strategies to optimize access and usage. METHODS: All Canadian centres with TE devices were invited to complete a survey after obtaining purchasing data from the national distributor of the device. Descriptive statistics were generated. RESULTS: Forty-two devices were available in Canada as of January 2015. Seventy-one percent are used in academic settings, 74% are hospital based and 26% are in private clinics. The test is performed by trained nurses in 48% of centres, physicians in 19%, technicians in 9.5% and by any member of the health care team in 19%. Nineteen percent of centres provide satellite clinics to perform the test. While the majority of the centres perform the test at no additional cost to patients, 29% charge a variable fee. CONCLUSION: In Canada, most TE devices are used in academic and/or hospital-based settings, thus limiting access to this technology to many patients. A sizeable minority of centres mandate patients pay variable out-of-pocket fees. Satellite clinics offered by some centres could increase access, but are not widespread. The lack of uniformity with TE practices in Canada suggests that a national policy is needed.

Percutaneous liver biopsy practice patterns among Canadian hepatologists.

BACKGROUND: Percutaneous liver biopsy (PLB) is the standard procedure to obtain histological samples essential for the management of various liver diseases. While safe, many hepatologists no longer perform their own PLBs; the reasons for this practice shift are unknown. OBJECTIVE: To describe the attitudes, practice patterns and barriers to PLB among hepatologists in Canada. METHODS: A survey was distributed to all hepatologists in Canada. RESULTS: Thirty-two of 40 (80%) hepatologists completed the survey; the majority of respondents were male (72%) and had been in practice for >5 years in an academic setting. Fifty-six per cent of hepatologists referred all PLBs to radiology, and only 19% of hepatologists reported performing their own PLBs most or all of the time. There were no sex differences nor were there differences based on years in practice. Fifty per cent of respondents who performed PLB routinely used ultrasound, and PLBs are performed in equal frequency in an ambulatory procedure area (50%) versus the endoscopy suite (36%). For almost one-half of hepatologists (47%), their performance of PLBs decreased in the past five years. The majority of respondents at an academic centre (75%) reported access to FibroScan (Echosens, France), and most estimated a resultant 25% to 50% reduction in the need for PLBs. Lack of resources, patient preference and suboptimal reimbursement were the most common reasons cited for not performing PLBs. CONCLUSION: Most hepatologists in Canada do not perform PLBs to the extent that they did in the past, but refer to radiology. The reasons for this shift in practice include lack of resources, improved perception of safety and patient preference. Where available, FibroScan resulted in a perceived 25% to 50% reduction in required liver biopsies.

Ephrin b2 receptor and microsatellite status in lymph node-positive colon cancer survival.

BACKGROUND: Ephrin B2 receptor (EphB2) is a target of the canonical wnt pathway implicated in colorectal carcinogenesis, and its down-regulation may be associated with adverse prognosis. We evaluated its prognostic value in resected colon cancer stratified by microsatellite status and other clinicopathologic characteristics. METHODS: We identified all cases of resected stage III colon cancer from 1995 to 2009 managed in the Capital Health district of Nova Scotia. Tissue microarrays were constructed and immunohistochemistry (IHC) for tumor EphB2 staining assigned into quartiles. Microsatellite status was evaluated by IHC for MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2). Microsatellite stable tumors were defined as both MLH1/MSH2 (+/+); tumors staining otherwise were classified with microsatellite instability (MSI-H). Primary and secondary outcomes were disease-free survival (DFS) and overall survival (OS), respectively. RESULTS: We identified 159 cases with sufficient tissue for microarray analysis having a median follow-up of 3.47 years (range, 0.14-14). Median age was 61, 52% were male, 40% had an event, and 29% died. MSI-H was present in 18 (13%). Univariate analysis of EphB2 expression on DFS and OS showed a hazard ratio (HR) of 2.00 (P = .01) and 2.14 (P = .03), respectively. Multivariate analysis of EphB2 expression on DFS and OS showed an HR of 2.24 and 2.23, respectively, with tumor IHC ≤ 50%. CONCLUSIONS: In this cohort, decreased EphB2 expression was an independent prognostic factor for recurrence and death and may have prognostic relevance in tumors with MSI-H. However, this would require prospective validation in a larger study.

Liver transplantation for alcoholic liver disease among Canadian transplant centres: a national study.

UNLABELLED: BACKGROUND/ OBJECTIVE: Alcoholic liver disease (ALD) is a controversial yet established indication for liver transplantation (LT), and there is emerging evidence supporting a survival benefit in selected patients with severe acute alcoholic hepatitis. The aim of the present survey was to describe policies among Canadian transplant centres for patients with ALD. METHODS: A survey was distributed to the medical directors of all seven liver transplant centres in Canada. RESULTS: All seven liver transplant programs in Canada participated in the survey. Every centre requires patients to have a minimum of six months of abstinence from alcohol before listing for LT. Completion of a rehabilitation program is only mandatory in one program; the remaining programs do not mandate this if patients have demonstrated prolonged abstinence, and sufficient insight and social supports. No program considers LT for patients with severe acute alcoholic hepatitis, although six of the seven programs are interested in exploring a national policy. Random alcohol checks for waitlisted patients are performed routinely on patients listed for ALD at only one centre; the remaining centres only perform checks if there is clinical suspicion. In the past five years, the mean (± SD) number of patients per centre with graft dysfunction from recidivism was 10±4.36; a mean of 2.5±4.36 patients per centre developed graft failure. CONCLUSIONS: With minor exceptions, LT policies for subjects with ALD are uniform across Canadian transplant programs. Presently, no centres perform LT for acute alcoholic hepatitis, although there is broad interest in exploring a national policy. Recidivism resulting in graft loss is a rare phenomenon.