Background & Aims
There is no histologic classification system to determine prognoses
of patients with alcoholic hepatitis (AH). We identified histologic features
associated with disease severity and created a histologic scoring system to
predict short-term (90 day) mortality.
Methods
We analyzed data from 121 patients admitted to the Liver Unit
(Hospital Clinic, Barcelona, Spain) from January 2000 through January 2008
with features of AH, and developed a histologic scoring system to determine
risk of death using logistic regression. The system was tested and updated
in a test set of 96 patients from 5 academic centers in the US and Europe,
and a semi-quantitative scoring system was developed, called the alcoholic
hepatitis histologic score (AHHS). The system was validated in an
independent set of 109 patients. Inter-observer agreement was evaluated by
weighted statistic analysis.
Results
Degree of fibrosis, neutrophil infiltration, type of
bilirubinostasis, and presence mega-mitochondria were independently
associated with 90 day mortality. We used these 4 parameters to develop the
AHHS to identify patients with low (0–3 points), moderate
(4–5 points), and high (6–9 points) risks of death within 90
days (3%, 19%, and 51%, respectively;
P<.0001). The AHHS estimated 90 day
mortality in the training and test sets with an area under the receiver
operating characteristic value of 0.77 (95% confidence interval,
0.71–0.83). Inter-rate agreement values were 0.65 for fibrosis, 0.86
for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for
megamitochondria. Interestingly, the type of bilirubinostasis predicted the
development of bacterial infections.
Conclusions
We identified histologic features associated with severity of AH and
developed a patient classification system that might be used in clinical
decision making.
Recently published studies have found an impaired immune response after SARS‐CoV‐2 vaccination in solid organ recipients. However, most of these studies have not assessed immune cellular responses in liver and heart transplant recipients. We prospectively studied heart and liver transplant recipients eligible for SARS‐CoV‐2 vaccination. Patients with past history of SARS‐CoV‐2 infection or SARS‐CoV‐2 detectable antibodies (IgM or IgG) were excluded. We assessed IgM/IgG antibodies and ELISpot against the S protein 4 weeks after receiving the second dose of the mRNA‐1273 (Moderna) vaccine. Side effects, troponin I, liver tests and anti‐HLA donor‐specific antibodies (DSA) were also assessed. A total of 58 liver and 46 heart recipients received two doses of mRNA‐1273 vaccine. Median time from transplantation to vaccination was 5.4 years (IQR 0.3–27). Sixty‐four percent of the patients developed SARS‐CoV‐2 IgM/IgG antibodies and 79% S‐ELISpot positivity. Ninety percent of recipients developed either humoral or cellular response (87% in heart recipients and 93% in liver recipients). Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation. Local and systemic side effects were mild or moderate, and none presented DSA or graft dysfunction after vaccination. Ninety percent of our patients did develop humoral or cellular responses to mRNA‐1273 vaccine. Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation, highlighting the need to further protect these patients.
In conclusion, SVR post-LT induces fibrosis regression in most patients, leading to significant clinical benefits. Pretreatment HVPG and LSM are significant determinants of the likelihood of fibrosis regression. Finally, LSM accurately predicts the presence of AF and PH 1 year after SVR and thus can be used to determine monitoring strategies. (Hepatology 2018;67:1683-1694).
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