ACR Appropriateness Criteria® Right Upper Quadrant Pain: 2022 Update.

Acute right upper quadrant pain is one of the most common presenting symptoms in hospital emergency departments, as well as outpatient settings. Although gallstone-related acute cholecystitis is a leading consideration in diagnosis, a myriad of extrabiliary sources including hepatic, pancreatic, gastroduodenal, and musculoskeletal should also be considered. This document focuses on the diagnostic accuracy of imaging studies performed specifically to evaluate acute right upper quadrant pain, with biliary etiologies including acute cholecystitis and its complications being the most common. An additional consideration of extrabiliary sources such as acute pancreatitis, peptic ulcer disease, ascending cholangitis, liver abscess, hepatitis, and painful liver neoplasms remain a diagnostic consideration in the right clinical setting. The use of radiographs, ultrasound, nuclear medicine, CT, and MRI for these indications are discussed. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

American Association for the Study of Liver Diseases Expert Panel Consensus Statement: Vaccines to Prevent Coronavirus Disease 2019 Infection in Patients With Liver Disease.

The aim of this document is to provide a concise scientific review of the currently available COVID-19 vaccines and those in development, including mRNA, adenoviral vectors, and recombinant protein approaches. The anticipated use of COVID-19 vaccines in patients with chronic liver disease (CLD) and liver transplant (LT) recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and LT about vaccine prioritization and administration. The Pfizer and Moderna mRNA COVID-19 vaccines are associated with a 94%-95% vaccine efficacy compared to placebo against COVID-19. Local site reactions of pain and tenderness were reported in 70%-90% of clinical trial participants, and systemic reactions of fever and fatigue were reported in 40%-70% of participants, but these reactions were generally mild and self-limited and occurred more frequently in younger persons. Severe hypersensitivity reactions related to the mRNA COVID-19 vaccines are rare and more commonly observed in women and persons with a history of previous drug reactions for unclear reasons. Because patients with advanced liver disease and immunosuppressed patients were excluded from the vaccine licensing trials, additional data regarding the safety and efficacy of COVID-19 vaccines are eagerly awaited in these and other subgroups. Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with CLD and LT recipients. The online companion document located at https://www.aasld.org/about-aasld/covid-19-resources will be updated as additional data become available regarding the safety and efficacy of other COVID-19 vaccines in development.

Hepatocellular Carcinoma in Acute Hepatic Porphyrias: Results from the Longitudinal Study of the U.S. Porphyrias Consortium.

BACKGROUND AND AIMS: The risk for hepatocellular carcinoma (HCC) is increased in acute hepatic porphyrias (AHP). The aim of this study was to explore the clinicopathologic characteristics, outcomes, and frequency of HCC in patients with AHP in the United States. APPROACH AND RESULTS: This cross-sectional analysis evaluated patients with HCC in a multicenter, longitudinal study of AHP. Among 327 patients with AHP, 5 (1.5%) were diagnosed with HCC. Of the 5 HCC cases, 4 had acute intermittent porphyria and 1 had variegate porphyria, confirmed by biochemical and/or genetic testing. All patients were white females, with a median age of 27 years (range 21-75) at diagnosis. The median age at HCC diagnosis was 69 years (range 61-74). AHP was asymptomatic in 2 patients; 2 reported sporadic attacks; and 1 reported recurrent attacks (>4 attacks/year). All patients had a single HCC lesion on liver imaging that was 1.8-6.5 centimeters in diameter. Serum alpha fetoprotein levels were below 10 ng/mL in all 4 patients with available results. Four patients underwent liver resection, and 1 was treated with radioembolization. No significant inflammation or fibrosis was found in adjacent liver tissues of 3 patients who underwent liver resection. Two patients developed recurrence of HCC at 22 and 26 months following liver resection. All patients are alive with survival times from HCC diagnosis ranging from 26-153 months. CONCLUSION: In this U.S. study, 1.5% of patients with AHP had HCC. HCC in AHP occurred in the absence of cirrhosis, which contrasts with other chronic liver diseases. Patients with AHP, regardless of clinical attacks, should be screened for HCC, beginning at age 50. The pathogenesis of hepatocarcinogenesis in AHP is unknown and needs further investigation.

Hepatocellular carcinoma surveillance: An evidence-based approach.

Hepatocellular carcinoma (HCC) makes up 75%-85% of all primary liver cancers and is the fourth most common cause of cancer related death worldwide. Chronic liver disease is the most significant risk factor for HCC with 80%-90% of new cases occurring in the background of cirrhosis. Studies have shown that early diagnosis of HCC through surveillance programs improve prognosis and availability of curative therapies. All patients with cirrhosis and high-risk hepatitis B patients are at risk for HCC and should undergo surveillance. The recommended surveillance modality is abdominal ultrasound (US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with non-alcoholic fatty liver disease (NAFLD). With the current obesity epidemic and rise in the prevalence of NAFLD, abdominal computed tomography or magnetic resonance imaging may be indicated as the primary screening modality in these patients. The addition of alpha-fetoprotein to a surveillance regimen is thought to improve the sensitivity of HCC detection. Further investigation of serum biomarkers is needed. Semiannual screening is the suggested surveillance interval. Surveillance for HCC is underutilized and low adherence disproportionately affects certain demographics such as non-Caucasian race and low socioeconomic status.

Orthotopic liver transplantation changes the course of gastric antral vascular ectasia: a case series from a transplant center.

BACKGROUND AND AIM: Gastric antral vascular ectasia (GAVE) is an important cause of upper gastrointestinal bleeding and anemia in patients with cirrhosis. The aim of our study was to evaluate the effect of orthotopic liver transplantation (OLT) on GAVE and associated anemia. PATIENTS AND METHODS: We performed a chart review and identified all cirrhotic patients with GAVE who underwent OLT at the University Of Alabama at Birmingham between 2005 and 2013. Population's demographics, etiology of cirrhosis, comorbidities, presentation and treatment modalities of GAVE, endoscopic and histopathologic reports, hemoglobin values before and after transplant, and immunosuppressive regimens were collected. RESULTS: Twelve patients were identified, mean age 52.4±4.4 years; seven were men (58.3%); 11 (91.7%) were White; and 6 of 12 patients had biopsy-proven GAVE. The most common etiology of cirrhosis in the cohort was chronic hepatitis C and obesity was the most common chronic condition in 50 and 83.3%, respectively. Anemia resolution was observed in 9/12 (75%) patients who underwent OLT with an increase in hemoglobin from 8.1±2.4 (5.7-13.1) before transplant to 12.0±1.4 (10-15) after transplant (P<0.0001). Esophagogastroduodenoscopy after transplant was performed in all 12 (100%) patients. The mean time between transplant and post-OLT esophagogastroduodenoscopy was 13.8±18.28 (2-57) months; complete resolution of GAVE was observed in 10 (83.3%) patients, with resolving GAVE in one (8.3%) patient. CONCLUSION: GAVE is an important cause of anemia and upper gastrointestinal bleeding in patients with liver cirrhosis. Our findings show that liver transplantation can resolve GAVE and related anemia.

Sorafenib use for recurrent hepatocellular cancer after resection or transplantation: Observations from a US regional analysis of the GIDEON registry.

Treatment of unresectable recurrent hepatocellular carcinoma (HCC) in patients who recur after resection or orthotopic liver transplantation (OLT) remains a clinical challenge. One option is sorafenib, although little is known about its safety and tolerance in this unique patient population; therefore, we analyzed patients who underwent prior surgical resection and/or OLT and were treated with sorafenib in US cohort of GIDEON registry. In US, 645 patients were enrolled; 553 for intent to treat and 563 for safety. Data were analyzed in the safety population of 479 patients no surgery and 56 for resection or OLT. Forty-one patients underwent resection prior to the initiation of sorafenib, 15 patients had previously received an OLT, and 6 patients had both resection and OLT. Initial low starting doses (400 mg/day) were observed for more patients with prior OLT (71%) than prior resection (36%), resection and OLT (50%), concomitant OLT (25%), and no surgery (36%). Most AEs occurred in the first 4 weeks of treatment. Drug-related AEs were higher in patients with prior resection (87%), prior OLT (100%), or both (100%) than in patients with concomitant OLT (63%) or no surgery (70%). However, incidence of AEs resulting in permanent discontinuation were similar in all groups (19-38%).

Heat stroke leading to acute liver injury & failure: A case series from the Acute Liver Failure Study Group.

BACKGROUND & AIMS: In the United States, nearly 1000 annual cases of heat stroke are reported but the frequency and outcome of severe liver injury in such patients is not well described. The aim of this study was to describe cases of acute liver injury (ALI) or failure (ALF) caused by heat stroke in a large ALF registry. METHODS: Amongst 2675 consecutive subjects enrolled in a prospective observational cohort of patients with ALI or ALF between January 1998 and April 2015, there were eight subjects with heat stroke. RESULTS: Five patients had ALF and three had ALI. Seven patients developed acute kidney injury, all eight had lactic acidosis and rhabdomyolysis. Six patients underwent cooling treatments, three received N-acetyl cysteine (NAC), three required mechanical ventilation, three required renal replacement therapy, two received vasopressors, one underwent liver transplantation, and two patients died-both within 48 hours of presentation. All cases occurred between May and August, mainly in healthy young men because of excessive exertion. CONCLUSIONS: Management of ALI and ALF secondary to heat stroke should focus on cooling protocols and supportive care, with consideration of liver transplantation in refractory patients.

A SEER Database Analysis of the Survival Advantage of Transarterial Chemoembolization for Hepatocellular Carcinoma: An Underutilized Therapy.

PURPOSE: To measure transarterial chemoembolization utilization and survival benefit among patients with hepatocellular carcinoma (HCC) in the Surveillance, Epidemiology, and End Results (SEER) patient population. MATERIALS AND METHODS: A retrospective study identified 37,832 patients with HCC diagnosed between 1991 and 2011. Survival was estimated by Kaplan-Meier method and compared by log-rank test. Propensity-score matching was used to address an imbalance of covariates. RESULTS: More than 75% of patients with HCC did not receive any HCC-directed treatment. Transarterial chemoembolization was the most common initial therapy (15.9%). Factors associated with the use of chemoembolization included younger age, more HCC risk factors, more comorbidities, higher socioeconomic status, intrahepatic tumor, unifocal tumor, vascular invasion, and smaller tumor size (all P < .001). Median survival was improved in patients treated with chemoembolization compared with those not treated with chemoembolization (20.1 vs 4.3 mo; P < .0001). Similar findings were demonstrated in propensity-scoring analysis (14.5 vs 4.2 mo; P < .0001) and immortal time bias sensitivity analysis (9.5 vs 3.6 mo; P < .0001). There was a significantly improved survival hazard ratio (HR) in patients treated with chemoembolization (HR, 0.42; 95% confidence interval, 0.39-0.45). CONCLUSIONS: Patients with HCC treated with transarterial chemoembolization experienced a significant survival advantage compared with those not treated with transarterial chemoembolization. More than 75% of SEER/Medicare patients diagnosed with HCC received no identifiable oncologic treatment. There is a significant public health need to increase awareness of efficacious HCC treatments such as transarterial chemoembolization.

Current guidelines for chemoembolization for hepatocellular carcinoma: Room for improvement?

Transarterial chemoembolization (TACE) is the most common oncologic therapy used according to the American Association for the Study of Liver Diseases (AASLD) guidelines established in 2005, revised in 2011. The purpose of this study was to determine how AASLD criteria for the management of hepatocellular carcinoma (HCC) have impacted TACE practice in the community. Clinical, demographic, and cause of death information were collected for patients diagnosed with HCC in the 2012 linkage of the Surveillance, Epidemiology, and End Results Medicare database. Propensity score survival analysis was used to compare survival outcomes in patients whose HCC tumor characteristics were less than, met, or were beyond AASLD criteria. The proportion of patients with HCC receiving TACE who met the AASLD-recommended criteria increased after the 2005 guidelines were published. Up to 17% of patients treated with TACE had tumor characteristics less than the AASLD criteria and were not offered potentially curative therapies. Propensity score matching demonstrated the largest survival advantage in patients with HCC whose tumor characteristics met the AASLD criteria (hazard ratio, 0.42; 95% confidence interval, 0.38-0.47). A significant survival advantage was also observed in patients with HCC whose tumor characteristics exceeded the AASLD criteria. Conclusion: The AASLD criteria successfully identify a population of patients with HCC that maximally benefit from TACE therapy. However, patients with HCC with tumor characteristics beyond the AASLD criteria also appear to receive a significant survival advantage with TACE. Further studies are necessary to improve referral patterns and appropriate use of chemoembolization in the management of unresectable HCC. (Hepatology Communications 2017;1:338-346).

Acute liver injury and acute liver failure from mushroom poisoning in North America.

BACKGROUND & AIMS: Published estimates of survival associated with mushroom (amatoxin)-induced acute liver failure (ALF) and injury (ALI) with and without liver transplant (LT) are highly variable. We aimed to determine the 21-day survival associated with amatoxin-induced ALI (A-ALI) and ALF (A-ALF) and review use of targeted therapies. METHODS: Cohort study of all A-ALI/A-ALF patients enrolled in the US ALFSG registry between 01/1998 and 12/2014. RESULTS: Of the 2224 subjects in the registry, 18 (0.8%) had A-ALF (n = 13) or A-ALI (n = 5). At admission, ALF patients had higher lactate levels (5.2 vs. 2.2 mm, P = 0.06) compared to ALI patients, but INR (2.8 vs. 2.2), bilirubin (87 vs. 26 µm) and MELD scores (28 vs. 24) were similar (P > 0.2 for all). Of the 13 patients with ALF, six survived without LT (46%), five survived with LT (39%) and two died without LT (15%). Of the five patients with ALI, four (80%) recovered and one (20%) survived post-LT. Comparing those who died/received LT (non-spontaneous survivors [NSS]) with spontaneous survivors (SS), N-acetylcysteine was used in nearly all patients (NSS 88% vs. SS 80%); whereas, silibinin (25% vs. 50%), penicillin (50% vs. 25%) and nasobiliary drainage (0 vs. 10%) were used less frequently (P > 0.15 for all therapies). CONCLUSION: Patients with mushroom poisoning with ALI have favourable survival, while around half of those presenting with ALF may eventually require LT. Further study is needed to define optimal management (including the use of targeted therapies) to improve survival, particularly in the absence of LT.

Diagnosis and Management of Hepatic Encephalopathy in Fulminant Hepatic Failure.

Hepatic encephalopathy (HE) is associated with cerebral edema (CE), increased intracranial pressure (ICP), and subsequent neurologic complications; it is the most important cause of morbidity and mortality in fulminant hepatic failure. The goal of therapy should be early diagnosis and treatment of HE with measures to reduce CE. A combination of clinical examination and diagnostic modalities can aid in prompt diagnosis. ICP monitoring and transcranial Doppler help diagnose and monitor response to treatment. Transfer to a transplant center and intensive care unit admission with airway management and reduction of CE with hypertonic saline, mannitol, hypothermia, and sedation are recommended as a bridge to liver transplantation.

Screening and detection of hepatocellular carcinoma.

The increasing incidence of hepatocellular carcinoma (HCC) has led to the need to identify patients at risk for HCC so that a program of screening can be undertaken. Screening for HCC has led to earlier diagnosis of tumors and thus has aided in initiating optimal medical treatment earlier in the disease course. Advances in radiological techniques and the identification of more accurate serum tests to diagnose HCC continue to be important areas of study and exploration. In particular, there have been efforts to develop new tumor markers to aid in the diagnosis of HCC and guide therapy of tumors.

Equivalent survival following liver transplantation in patients with non-alcoholic steatohepatitis compared with patients with other liver diseases.

BACKGROUND: Orthotopic liver transplantation (LT) in non-alcoholic steatohepatitis (NASH) is increasing in parallel with the obesity epidemic. METHODS: This study retrospectively reviewed the clinical outcomes of LTs in NASH (n = 129) and non-NASH (n = 775) aetiologies carried out at a single centre between 1999 and 2009. RESULTS: Rates of 1-, 3- and 5-year overall survival in NASH (90%, 88% and 85%, respectively) were comparable with those in non-NASH (92%, 86% and 80%, respectively) patients. Mortality within 4 months of LT was twice as high in NASH as in non-NASH patients (8.5% vs. 4.2%; P = 0.04). Compared with non-NASH patients, post-LT mortality in NASH patients was more commonly caused by infectious (38% vs. 26%; P < 0.05) or cardiac (19% vs. 7%; P < 0.05) aetiologies. Five-year survival was lower in NASH patients with a high-risk phenotype (age >60 years, body mass index >30 kg/m(2), with hypertension and diabetes) than in NASH patients without these characteristics (72% vs. 87%; P = 0.02). Subgroup analyses revealed that 5-year overall survival in NASH was equivalent to that in Laennec's cirrhosis (85% vs. 80%; P 0.87), but lower than that in cirrhosis of cryptogenic aetiology (85% vs. 96%; P = 0.04). CONCLUSIONS: Orthotopic LT in NASH was associated with increased early postoperative mortality, but 1-, 3- and 5-year overall survival rates were equivalent to those in non-NASH patients.

Comparing the aspartate aminotransferase (AST) to platelet ratio index (APRI) between African American and White veterans with chronic hepatitis C.

OBJECTIVES: The study of noninvasive markers of fibrosis, such as aspartate aminotransferase (AST) to platelet ratio index (APRI), have been limited in African American populations. Given the disparate outcomes of chronic hepatitis C in African American populations, comparative analyses of the APRI score should be undertaken. Compare the diagnostic accuracy of the APRI score for significant fibrosis and cirrhosis in a sample of African American and white veterans with chronic hepatitis C in the southeastern United States. METHODS: We identified 268 veterans with chronic hepatitis C who had received a liver biopsy. The APRI score was calculated using laboratory values obtained within 180 days of liver biopsy and compared to the fibrosis stage (F0-F4). Performance characteristics of the APRI score for determining stages of fibrosis were compared in African American (n = 142) and white (n = 117) individuals. RESULTS: An APRI score of 0.99 had a comparably high negative predictive value for significant fibrosis (F3-F4) in African American 0.90 and white veterans (0.83). For cirrhosis (F4), an APRI score of 1.0 provided a negative predictive value of 0.96 in the African American subset and 0.94 in the white subset. We did not detect any difference in the performance of the APRI score for predicting stages of fibrosis between the two groups. CONCLUSION: The APRI score displayed similar performance in African Americans and whites. A threshold of 1.0 can reliably exclude cirrhosis in African American veterans with chronic HCV infection.

Current trends in the treatment of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a common reversible neuropsychiatric syndrome associated with chronic and acute liver dysfunction and significant morbidity and mortality. Although a clear pathogenesis is yet to be determined, elevated ammonia in the serum and central nervous system are the mainstay for pathogenesis and treatment. Management includes early diagnosis and prompt treatment of precipitating factors (infection, gastrointestinal bleeding, electrolyte disturbances, hepatocellular carcinoma, dehydration, hypotension, and use of benzodiazepines, psychoactive drugs, and/or alcohol). Clinical trials have established the efficacy of lactulose and lactitol enemas in the treatment of acute hepatic encephalopathy. Extensive clinical experience has demonstrated the efficacy of oral lactulose and lactitol with the goal of two to three soft bowel movements a day for the treatment of chronic HE. However, lactulose and lactitol have significant gastrointestinal side effects. For patients unable to tolerate lactulose or lactitol or who still have persistent chronic HE with lactulose or lactitol, neomycin, metronidazole and rifaximin are second-line agents. More recent data supports the benefits of rifaximin used solely and as an additional agent with fewer side effects than neomycin or metronidazole. Newer therapies being investigated in humans with clinical promise include nitazoxanide, the molecular adsorbent recirculating system (MARS), L-ornithine phenylacetate, sodium benzoate, and/or sodium phenylacetate and Kremezin((R)) (AST-120).

HFE hemochromatosis and hepatic sarcoid.

A 57-year-old white woman had serum ferritin 793 ng/mL, HFE C282Y homozygosity, elevated serum angiotensin-converting enzyme (ACE) levels, 3+ hepatocyte iron, cirrhosis, hepatic granulomas, and portal hypertension. Her 37-year-old son had ferritin 869 ng/mL, C282Y/wt, elevated ACE levels, 2+ hepatocyte iron, bridging fibrosis, and hepatic granulomas. Her daughters had HFE C282Y/H63D and C282Y/wt, respectively; neither had a hemochromatosis phenotype, sarcoid, or severe liver disease. All 4 subjects had nonalcoholic hepatic steatosis. Sarcoid did not segregate with the human leukocyte antigen-A and -B haplotype shared by the proband, her son, and 1 daughter. Phlebotomy to achieve iron depletion in the proband and her son yielded 1.6 and 1.5 g iron, respectively; their ACE levels remained elevated. We reviewed previous reports of 4 patients with hemochromatosis and sarcoid. We conclude that a combination of sarcoid, steatosis, and excessive hepatocyte iron caused cirrhosis or hepatic fibrosis in the proband and her son.