Blood Testing for Phosphatidylethanol.

A 36-year-old man with obesity and dyslipidemia presented with elevated liver enzymes following a liver transplant to treat acute-on-chronic liver failure due to alcohol-associated hepatitis. What would you do next?

Lean body mass index is a marker of advanced tumor features in patients with hepatocellular carcinoma.

BACKGROUND: Obesity is an independent risk factor for the development of hepatocellular carcinoma (HCC) and may influence its outcomes. However, after diagnosis of HCC, like other malignancies, the obesity paradox may exist where higher body mass index (BMI) may in fact confer a survival benefit. This is frequently observed in patients with advanced HCC and cirrhosis, who often present late with advanced tumor features and cancer related weight loss. AIM: To explore the relationship between BMI and survival in patients with cirrhosis and HCC. METHODS: This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical centers. Patient and tumor characteristics were extracted manually from medical records of each institutions' cancer registries. Patients were stratified according to BMI classes: < 25 kg/m2 (lean), 25-29.9 kg/m2 (overweight), and > 30 kg/m2 (obese). Patient and tumor characteristics were compared according to BMI classification. We performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria. A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and HCC. RESULTS: A total of 2548 patients with HCC were included in the analysis of which 11.2% (n = 286) were classified as non-cirrhotic. The three main BMI categories: Lean (n = 754), overweight (n = 861), and obese (n = 933) represented 29.6%, 33.8%, and 36.6% of the total population overall. Within each BMI class, the non-cirrhotic patients accounted for 15% (n = 100), 12% (n = 94), and 11% (n = 92), respectively. Underweight patients with a BMI < 18.5 kg/m2 (n = 52) were included in the lean cohort. Of the obese cohort, 42% (n = 396) had a BMI ≥ 35 kg/m2. Out of 2262 patients with cirrhosis and HCC, 654 (29%) were lean, 767 (34%) were overweight, and 841 (37%) were obese. The three BMI classes did not differ by age, MELD, or Child-Pugh class. Chronic hepatitis C was the dominant etiology in lean compared to the overweight and obese patients (71%, 62%, 49%, P < 0.001). Lean patients had significantly larger tumors compared to the other two BMI classes (5.1 vs 4.2 vs 4.2 cm, P < 0.001), were more likely outside Milan (56% vs 48% vs 47%, P < 0.001), and less likely to undergo transplantation (9% vs 18% vs 18%, P < 0.001). While both tumor size (P < 0.0001) and elevated alpha fetoprotein (P < 0.0001) were associated with worse survival by regression analysis, lean BMI was not (P = 0.36). CONCLUSION: Lean patients with cirrhosis and HCC present with larger tumors and are more often outside Milan criteria, reflecting cancer related cachexia from delayed diagnosis. Access to care for hepatitis C virus therapy and liver transplantation confer a survival benefit, but not overweight or obese BMI classifications.

Which patient should have preference for liver transplantation: ALD?

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Changing Trends of Cirrhotic and Noncirrhotic Hepatocellular Carcinoma in the Era of Directly-Acting Antiviral Agents.

INTRODUCTION: The impact of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) on burden of cirrhotic and noncirrhotic hepatocellular carcinoma (HCC) has not been examined. We assessed recent trends in liver disease etiologies of HCC and proportion of noncirrhotic HCC since DAAs introduction. METHODS: Clinical characteristics including presence or absence of underlying cirrhosis were collected from 2,623 patients diagnosed with HCC between 2009 and 2019 at 2 large US centers. Logistic regression was performed to investigate the annual trends of HCC due to different liver diseases and proportions of noncirrhotic cases. RESULTS: In the DAA era (2014-2019), annual decline in HCV-HCC (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.88-0.99, P = 0.019), without change in trends of other liver diseases-related HCC, was observed. Annual increase in noncirrhotic HCC (OR 1.13, 95% CI 1.03-1.23, P = 0.009) and decline in cirrhotic HCC (OR 0.89, 95% CI 0.81-0.97, P = 0.009) along with similar trends for HCV-HCC-increase in noncirrhotic cases (OR 1.35, 95% CI 1.08-1.69, P = 0.009) and decrease in cirrhotic cases (OR 0.92, 95% CI 0.86-0.98, P = 0.012)-were observed during the DAA era. Compared with the pre-DAA era, HCC resection rate increased (10.7% vs 14.0%, P = 0.013) whereas liver transplantation rate decreased (15.1% vs 12.0%, P = 0.023) in the DAA era. DISCUSSION: Since introduction of DAAs, proportions of cirrhotic HCC have decreased, whereas proportions of noncirrhotic HCC have increased. These new trends were associated with change in utilization of liver resection and transplantation for HCC. The impact of changing patterns of DAA use on these trends will require further study.

Systematic review: non-invasive prognostic tests for primary sclerosing cholangitis.

BACKGROUND: Several prognostic tests for primary sclerosing cholangitis (PSC) have been developed, including biochemical models, elastography and magnetic resonance imaging scores. AIM: To conduct a systematic review of non-invasive prognostic tests for PSC. METHODS: A systematic review was conducted from 1987 to 2020 of blood tests, biochemical models, elastography and imaging scores associated with outcomes in PSC. RESULTS: Forty studies of prognostic tests that collectively included 16 094 subjects with PSC were reviewed, of which 26 studies of non-invasive tests including 13 759 subjects with PSC were included. Normalisation or reduction of alkaline phosphatase with or without therapy was associated with transplant-free survival and reduced risk of hepatobiliary cancers but cut-off values for alkaline phosphatase were not consistent among studies. The most studied prognostic biochemical model was the Mayo Risk Score (MRS) evaluated in 18 studies with a c-statistic from 0.63 to 0.85 for clinical outcomes. One study demonstrated that the UK-PSC score outperforms MRS for predicting clinical outcomes with a c-statistics of 0.81and 0.75 respectively. A transient elastography score greater than 11.1 kPa is associated with survival and liver-related complications. The Anali score, derived from specific MRI and MRCP features, is associated with the development of cholangiocarcinoma and decompensated cirrhosis. Promising prognostic models include the enhanced liver fibrosis (ELF) score, ELF test and PREsTo scores. CONCLUSION: MRS is the most studied prognostic score for clinical outcomes in PSC but the UK-PSC score and PREsTo have better test performance. Further studies comparing MRS to UK-PSC score, PREsTo or ELF with elastography or imaging-based scores are warranted.

Cardiovascular Factors Associated with Septic Shock Mortality Risks.

CONTEXT: The presence of at least one underlying chronic health condition, such as long-term care facility residence, malnutrition, immunosuppression, or prosthetic device use, are well known factors increasing infection risks and progression to severe sepsis. Furthermore, some degree of cardiovascular dysfunction occurs in the majority of septic patients and this prognostic significance has become increasingly recognized. Since septic shock carries the highest mortality risk on the sepsis spectrum, it is important to evaluate the cardiovascular risk impact on mortality in this subset of patients. METHODS: The retrospective parent study contributing these electronic health record data was IRB approved and conducted across four hospital intensive care units within the authors' Michigan healthcare system. Patients with cardiopulmonary arrest or transfers from an outside facility were excluded. The authors evaluated the presence of modifiable and non-modifiable cardiovascular risk factors in septic shock patients upon admission to an emergency department. RESULTS: The authors' final analytic sample included n = 109 adults who were discharged alive compared to those who died during hospitalization. Those patients who died were more often male with an underlying history of hypertension, congestive heart failure, coronary artery disease, or peripheral arterial diseases, were taking pre-admission beta-blocker medications, and had higher APACHE II scores at admission compared to the patients who survived to discharge. Significantly higher mortality risks were found in sample patients with increased troponin levels on admission and atrial fibrillation. CONCLUSIONS: Appropriate triage and prompt treatment of these patient groups with tailored therapy to stabilize and improve cardiac dysfunction in the emergency department could potentially lead to improved survival outcomes. Clinicians need more studies to determine therapeutic targets most impacting underlying pathophysiologic mechanisms such as elevated troponin and atrial fibrillation that greatly increase mortality risks.

A Rare Association of Congenital Asplenia with Jejunal Arteriovenous Malformation.

BACKGROUND Isolated congenital asplenia is a poorly understood and rare form of primary immunodeficiency, often associated with life-threatening infections. CASE REPORT We encountered a unique case of a 22-year-old asplenic male who presented with severe iron-deficiency anemia secondary to occult gastrointestinal bleeding since age 15. Our extensive work-up confirmed jejunal arteriovenous malformations as the source of the bleed. Six months after the treatment, the patient has reported no further episodes of gastrointestinal bleeding and his hemoglobin has remained stable. CONCLUSIONS A comprehensive literature review confirmed that this is the first reported case of adult congenital asplenia associated with arteriovenous malformation in the United States. The relationship of isolated congenital asplenia and arteriovenous malformation-associated bleeding remains unknown at this time; we postulate that this may be a congenital syndrome on its own. Obscure bleeding in the presence of rare anomalies such as asplenia should be investigated as one of the important causes of unexplained intestinal arteriovenous malformations.