Early Tumor Response and Safety of Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma in Real-World Practice

The aim of this study was to investigate the early tumor response and safety of atezolizumab plus bevacizumab for patients with unresectable hepatocellular carcinoma in real-world practice. Forty patients with Child-Pugh class A liver function and eastern cooperative oncology group performance status 0 or 1 were enrolled. The objective response rate (ORR) at six weeks after the start of treatment, changes in α-fetoprotein (AFP) and des-γ-carboxyprothrombin, incidence of adverse events (AEs), and changes in albumin-bilirubin (ALBI) score and serum ammonia level, were evaluated. Among 40 patients, 24 had histories of prior molecular targeted agents (MTAs). The ORR was 22.5% based on mRECIST. Multivariate analysis showed that an AFP ratio <1.0 at three weeks (odds ratio 39.2, 95% confidence interval CI 2.37–649.0, p = 0.0103) was the only significant factor for predicting early response. There was no significant difference in the frequency of AEs between patients receiving first-line treatments and others. Fatigue, proteinuria, and ascites were more frequent in patients who experienced prior treatment. No decrease in ALBI score or increase in serum ammonia level was observed. Our study demonstrated that AFP may be useful in assessing early response and that this treatment is safe, including in patients with prior MTA treatments.

Type B hepatic encephalopathy due to a congenital superior mesenteric-caval shunt: clinical scenario and therapeutic approach

Type B Hepatic encephalopathy (HE) due to a congenital extra-hepatic porto-systemic shunt is an extremely rare condition. We report the case of a 57-year-old woman, with recurrent episodes of confusion and neuropsychiatric symptoms, who had an elevated serum ammonia level and a superior mesenteric-caval shunt documented on abdominal computed topography (CT) scan. There was no evidence of cirrhosis or portal hypertension. A diagnosis of non-cirrhotic, non-portal hypertension hepatic encephalopathy was made after excluding other causes of confusion and cognitive impairment. The patient was successfully treated by radiologically guided endovascular shunt closure and during 9 months follow up, her neuropsychiatric symptoms did not recur and repeated serum ammonia level results were normal.

Serum ammonia is a strong prognostic factor for patients with acute-on-chronic liver failure

Ammonia is thought to be central to the pathogenesis of hepatic encephalopathy (HE), but its prognostic role in acute-on-chronic liver failure (ACLF) is still unknown. We aimed to determine the association between serum ammonia level and short-term prognosis in ACLF. Furthermore, we performed an in-depth evaluation of the independent effect of serum ammonia level on the short-term prognosis of hepatitis B virus (HBV) reactivation-induced ACLF patients. We identified 174 patients as part of prospective observational studies in patients with ACLF. Plasma ammonia levels were measured on admission, and several prognostic scores were used to determine the prognostic effect of ammonia. The 28-day patient survival was determined. Receiver operating characteristic analysis was used to identify the cut-off points for ammonia values, and multivariable analysis was performed using the Cox proportional hazard regression model. Plasma ammonia was significantly higher in nonsurvivors (83.53 ± 43.78 versus 67.13 ± 41.77 µmol/L, P = 0.013), and ACLF patients with hyperammonemia had significantly higher 28-day mortality than those without hyperammonemia. Ammonia was also closely related to ACLF grade (P < 0.001) and organ failure, including liver (P = 0.048), coagulation (P < 0.001) and brain (P < 0.001). HBV reactivation serves as the main precipitating factor in the ACLF population. Subgroup analysis showed that ammonia is also a strong prognostic factor in the HBV reactivation-induced ACLF population. Ammonia level is closely correlated with failure of other organs and is an independent risk factor for mortality in ACLF and the special population defined as HBV reactivation-related ACLF. Based on the results from our study, we measured serum ammonia in the population with ACLF, which strongly indicates their prognosis. It serves as an important biomarker and a therapeutic target.

Serum ammonia as an early predictor of in-hospital mortality in patients with glufosinate poisoning

Background: The mortality rate associated with human glufosinate poisoning is high. We evaluated the usefulness of serum ammonia and sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) scores for early prediction of in-hospital mortality in glufosinate ammonium poisoning. Methods: A prospectively collected pesticide poisoning registry at a single academic medical center was retrospectively analyzed. Data were collected from consecutive patients diagnosed with glufosinate ammonium poisoning between May 2007 and February 2018. The initial serum ammonia level was defined as the highest serum ammonia level measured within 12 h after emergency department (ED) arrival. The SOFA and APACHE II scores were calculated using data obtained within the first 12 h after ED arrival. The patients were divided into survivor and nonsurvivor groups by in-hospital death status. Results: In total, 110 patients were included. Ten patients (9.1%) died in the hospital despite treatment. Median initial serum ammonia level was significantly higher in the nonsurvivor group than in the survivor group (219 (range: 158–792) versus 100.5 (range: 25–317) µg/dL, p < 0.001). Median SOFA and APACHE II scores in the survivor and nonsurvivor groups were 2 (range: 0–10) versus 5 (range: 1–8) ( p = 0.044) and 7 (range: 0–28) versus 16 (range: 8–22) ( p = 0.001), respectively. In the multiple logistic regression analysis, the initial serum ammonia level was the only independent predictor (cutoff value: 151 µg/dL). Conclusion: An initial serum ammonia level >151 µg/dL was an independent early predictor of in-hospital mortality in glufosinate ammonium poisoning.

Seizure Disorder Exacerbated by Hepatic Encephalopathy: A Case Report

BACKGROUND: Hepatic encephalopathy is a serious complication of cirrhosis that presents with a variety of neuropsychiatric abnormalities, including disorientation, asterixis, and coma. Seizures are an uncommon and potentially dangerous complication of hepatic encephalopathy. We present a unique case of a 42-year-old female with a history of well-controlled seizure disorder suddenly become refractory to anticonvulsant therapy following the development of hepatic encephalopathy secondary to liver decompensation. CASE PRESENTATION: A 42-year-old female presented to our hospital following a seizure accompanied by loss of consciousness, urinary incontinence, and the prolonged postictal state. She reports her seizures were initially well-controlled with Levetiracetam 500 mg twice a day but recently began experiencing seizures every other day despite up-titration of Levetiracetam to 1500 mg twice a day over a few weeks. On arrival, her serum ammonia level was 116 μmol/L. CT brain was negative while CT liver was consistent with cirrhotic morphology. An electroencephalogram revealed irregular, diffuse, delta/theta slowing consistent with mild to moderate encephalopathy. The patient was started on lactulose 40mg and Rifaximin 550 mg twice a day. Her symptoms of disorientation and lethargy resolved over 3 days. CONCLUSION: Though uncommon, hepatic encephalopathy should be considered in patients presenting with convulsions, especially if there is a known history of liver disease. Until the underlying liver issues are addressed, patients may not respond to traditional anti-convulsant therapy for their seizures.

Optimal Prescriptions of Continuous Renal Replacement Therapy in Neonates with Hyperammonemia

Background/Aims: The aim of this study was to evaluate patients’ outcomes, determine the prescriptions of continuous renal replacement therapy (CRRT) that effectively reduce serum ammonia levels, and analyze the prognostic factors in neonates with hyperammonemia. Methods: The medical records of 12 Korean neonates with inborn error of metabolism (IEM) who underwent CRRT for hyperammonemia were retrospectively analyzed. Results: All patients received continuous venovenous hemodiafiltration. The median ultrafiltration rate (UFR) at the initiation of CRRT was 2,288.4 mL/h/1.73 m2. The median ammonia level at CRRT initiation was 1,320 µmol/L, and the median time to reduce the initial ammonia level by at least 50% was 12.8 h. The survival rate during hospitalization was 83.3%. There were significant differences between patients with neurologic sequelae and those without poor outcomes in peak serum ammonia level before CRRT and serum ammonia level at CRRT initiation. Conclusion: This study suggested that CRRT could be a therapeutic option for neonates with IEM. However, it is necessary to raise the UFR above 4,000 mL/h/1.73 m2 in patients with high initial ammonia level.