Citations

The NCCN Guidelines for Biliary Tract Cancers (BTCs) provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts is convened at least once annually to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. This manuscript focuses on the adjuvant chemotherapy and chemoradiation treatment options for BTCs as well as the systemic treatment recommendations for patients with advanced BTCs.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

AbstractBackground & AimsNonalcoholic fatty liver disease (NAFLD) has been associated with sarcopenia. However, mortality in the setting of NAFLD‐related sarcopenia remains undefined. We aim to determine the all‐cause and cause‐specific mortality from sarcopenia among adults with NAFLD in the USA.Methods11 065 individuals in the Third National Health and Nutrition Examination Survey were studied and linked mortality through 2015 was analysed. NAFLD was diagnosed based on presence of ultrasonographic hepatic steatosis without other known liver diseases. Sarcopenia was defined as skeletal muscle index determined by bioelectrical impedance analysis. The Cox proportional hazard model was used to assess all‐cause mortality and cause‐specific mortality, and hazard ratio (HR) adjusted for known risk factors.ResultsDuring a median follow‐up of 23 years or more, sarcopenia was associated with increased all‐cause mortality (HR 1.27, 95% confidence interval [CI] 1.11‐1.44). Only in individuals with NAFLD, sarcopenia was associated with a higher risk for all‐cause mortality, while this association was absent in those without NAFLD. Individuals with both sarcopenia and NAFLD had a higher risk for all‐cause mortality (HR 1.28 95% CI 1.06‐1.55) compared with those without sarcopenia and NAFLD. Furthermore, sarcopenia was associated with a higher risk for cancer‐ and diabetes‐related mortality among those with NAFLD. This association was not noted in those without NAFLD.ConclusionIn this nationally representative sample of US adults, sarcopenia was associated with a higher risk for all‐cause, cancer‐ and diabetes‐related mortality in individuals with NAFLD.

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long‐term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer‐related factors on multivariable analysis. A dose‐response effect of age on survival was observed, with every 5‐year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non–HCC‐related mortality (P = 0.004), and not HCC‐related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single‐center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer‐related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non–HCC‐related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.

Background/aims The number of cases with coronavirus disease 2019 (COVID-19) has exceeded seven million worldwide. However, the data describing the global prevalence of liver injury associated with COVID-19 is lacking secondary to the novelty of this ongoing pandemic. Therefore, we conducted a meta-analysis to determine the association between COVID-19 and liver injury. Methods A systematic literature search of indexed databases including, PubMed, Medline, and Embase databases from inception to 14 April 2020, was used to identify studies that reported data of liver chemistry in patients diagnosed with COVID 19. The overall prevalence of abnormal liver chemistry and relevant 95% confidence interval was used to estimate the pooled results studies. Results Sixty-four studies with 11 245 patients with COVID-19 were included. The pattern of abnormal liver enzymes was notable for higher aspartate aminotransferase (AST) than alanine aminotransferase (ALT) levels. The overall global prevalence of elevated AST, ALT, total bilirubin, gamma-glutamyltransferase (GGT), and alkaline phosphatase was 23.2, 21.2, 9.7, 15.0, and 4.0%, respectively. The prevalence of elevated AST was substantially higher among those with severe cases (45.5%) compared to non-severe cases (15.0%). Co-existing chronic liver disease presented up to 37.6% of patients with COVID-19. Conclusion A fourth of COVID-19 patients had elevated liver enzymes and associated with disease severity. Our study may be used as a guide for clinicians and epidemiologists to proactively identify other sources of injury and illness in patients diagnosed with COVID-19. Intensive monitoring for liver injury may be needed in cases with severe COVID-19.

Abstract Background and Aim The association between palatin‐like phospholipase domain‐containing 3 ( PNPLA3 ) I148M ( rs738409 ) polymorphism and mortality is not well understood. We investigated the impact of PNPLA3 I148M ( rs738409 ) polymorphism on overall and cardiovascular mortality based on the presence of nonalcoholic fatty liver disease (NAFLD). Methods The third National Health and Nutrition Examination Survey (NHANES) from 1991 to 1994 and National Health and Nutrition Examination Survey III‐linked mortality data through 31 December 2015 were utilized in this study. Results Of 4814 participants, 50.7% were homozygous for the C‐allele and 12.6% were homozygous for the G‐allele. During a follow up of 20 years, there were a total of 1255 deaths, 422 attributed to cardiovascular disease. There was a significant association with overall mortality among those with the PNPLA3 I148M ( rs738409 ) GG genotype (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.02–1.77) or G‐allele (HR 1.22, 95% CI 1.09–1.36) in the general population. NAFLD with homozygous PNPLA3 I148M ( rs738409 ) GG genotype had higher overall mortality after adjusting for multiple metabolic risk factors (HR 1.45, 95% CI 1.01–2.08). The PNPLA3 I148M ( rs738409 ) G‐allele had a tendency of increased cardiovascular mortality in the total population. This association was not noted in those with NAFLD. Conclusions The homozygous PNPLA3 I148M ( rs738409 ) GG genotype showed an increase in overall mortality in the general population and NAFLD independent of multiple metabolic risk factors.

Liver transplantation (LT) for alcohol associated hepatitis (AH) remains controversial. We convened a consensus conference to examine various aspects of LT for AH. The goal was not to unequivocally endorse LT for AH; instead, it was to propose recommendations for programs that perform or plan to perform LT for AH. Criteria were established to determine candidacy for LT in the setting of AH and included the following: (1) AH patients presenting for the first time with decompensated liver disease that are nonresponders to medical therapy without severe medical or psychiatric comorbidities; (2) a fixed period of abstinence prior to transplantation is not required; and (3) assessment with a multidisciplinary psychosocial team, including a social worker and an addiction specialist/mental health professional with addiction and transplantation expertise. Supporting factors included lack of repeated unsuccessful attempts at addiction rehabilitation, lack of other substance use/dependency, acceptance of diagnosis/insight with a commitment of the patient/family to sobriety, and formalized agreement to adhere to total alcohol abstinence and counseling. LT should be avoided in AH patients who are likely to spontaneously recover. Short‐term and longterm survival comparable to other indications for LT must be achieved. There should not be further disparity in LT either by indication, geography, or other sociodemographic factors. Treatment of alcohol‐use disorders should be incorporated into pre‐ and post‐LT care. The restrictive and focused evaluation process described in the initial LT experience for AH worldwide may not endure as this indication gains wider acceptance at more LT programs. Transparency in the selection process is crucial and requires the collection of objective data to assess outcomes and minimize center variation in listing. Oversight of program adherence is important to harmonize listing practices and outcomes.

Background and aim Nonalcoholic fatty liver disease (NAFLD) may be associated with sarcopenia. This study aims to determine whether sarcopenia is independently associated with NAFLD and advanced fibrosis. Participants and methods Cross-sectional data from 11 325 participants in the third National Health and Nutrition Examination Survey were analyzed. NAFLD was defined as the presence of hepatic steatosis from the ultrasound. Sarcopenia was defined as the skeletal muscle index. Results NAFLD was more common in participants with sarcopenia than in those without (46.7 vs. 27.5%). Univariate analysis showed that sarcopenia was associated with NAFLD [odds ratio (OR): 2.31; 95% confidence interval (CI): 2.01–2.64], which remained significant after adjustment for age, sex, ethnicity, metabolic risk factors (OR: 1.24; 95% CI: 1.03–1.48). This finding persisted after adjustment for C-reactive protein as a marker of chronic inflammation. NAFLD-associated advanced fibrosis was more common in participants with sarcopenia than in those without (7.8 vs. 1.6%). Sarcopenia was associated with NAFLD-associated advanced fibrosis independent of metabolic risk factors (OR: 1.79; 95% CI: 1.18–2.72). Conclusion Sarcopenia was independently associated with increased odds of NAFLD and NAFLD-associated advanced fibrosis independent of well-defined risk factors. Interventions to strengthen muscle mass may reduce the burden of NAFLD and advanced fibrosis.