Liver cell failure remains a life-threatening complication after exposure to therapeutic procedures, especially in advanced liver disease. It can be predicted via assessing residual hepatic cell reserve which would be achieved by sophisticated and expensive procedures such as computed tomography (CT) volumetric studies and gadolinium based MRI imaging [15, 16]
The liver reserve involves an efficient and sufficient number of hepatocytes and fixed tissue macrophages (Kupffer cells) capable of maintaining the synthesis of hepatic proteins, and elements of the innate immune system, excretion of toxic metabolites which are expected to be largely affected by liver volume [17, 18]
Non-invasive biochemical tests that are used to evaluate the severity of hepatic parenchymal fibrosis through direct biomarkers of hepatic matrix elements as hyaluronic acid, or assessing the synthetic function of the liver, and severity of portal hypertension as AST to platelet ratio index (APRI), fibro test, fibrosis-4 test (FIB-4), and enhanced liver fibrosis (ELF) tests may show values that are not proportionate to the synthetic liver function [19, 20]
The current study aimed to assess easily applied variables which evaluate residual hepatic reserve to predict liability for complications and hepatic decompensation in cirrhotic patients with ablated HCC particularly when these patients were exposed to specific medical treatment such as DAAs and systemic therapy for HCC such as sorafenib. The results of the current study showed that patients with higher LS, PDW/MPV, gamma globulin, lower platelet count, and liver volume had significantly higher incidence of post-interventional complications (hepatic decompensation, HCC recurrence and HCV relapse after DAAs therapy); this can be explained by hepatocyte dysfunction associated with the severity of portal hypertension in this category of patients.
This goes in agreement with Lee et al who reported less HCC recurrence and better survival were associated with lower LS values. Also, Hegazy et al. reported more hepatic decompensation was seen with higher LS values after hepatic resection [21, 22].
Our results showed much more recurrence of HCC in DAAs therapy group mainly in patients with higher liver stiffness exceeding 25 kPa. This goes with many similar studies that reported increased prevalence of HCC recurrence after DAAs therapy [23, 24].
More hepatic decompensation and virological relapse were reported in our patients who received sorafenib and TACE, Park et al. and Lencioni et al. had reported much higher liver-related adverse events with sorafenib and TACE combination. However, Zhang et al reported better survival and good safety of Sorafenib& TACE in intermediate and advanced HCC [25, 26].
The current study had revealed that liver volume measurement by ultrasound with a cutoff value of (500 ml) reflects the more advanced liver disease associated with HCC. This is comparable to what was previously reported; liver volume at a cut-off value (495 ml) was predictive of complications after DAAs therapy mainly occurrence of HCC and reduced survival with sensitivity of 93.2%, specificity 72% [12].
Increased liver stiffness is associated with an increased risk of developing adverse events in liver cirrhosis and can be used as a valid non-invasive test for patient stratification. A study had enrolled 2052 patients who had developed hepatic complications or death during a median follow-up of 15.6 months; higher liver stiffness > 13.5 kPa was commonly associated with adverse events. The 2-year risk of death or complications were 19%, 34% in patients with liver stiffness 20–39.9, and ≥ 40 kPa, respectively [27, 28].
The platelet distribution width (PDW), reflects the variation in platelet size and was considered as a marker of platelet function and activation, higher value had been associated with increased cancer progression and metastasis and reduced overall survival [29]. A study had enrolled 241 patients with chronic HCV infection to assess the association between liver fibrosis, platelet counts, and platelet indices as MPV, PDW, and P-LCR and revealed that serum fibrosis markers as well as Fibroscan values were negatively correlated with PLT counts, but positively correlated with platelets indices [30], in the current study, a PDW/MPV > 2.74 was associated with more adverse outcome in patients with liver cirrhosis with HCC who were treated with sorafenib.
Ammonia is a byproduct of protein digestion by intestinal flora and is converted to glutamine in the liver before being converted to urea by renal metabolism. If ammonia bypasses the liver due to portosystemic collaterals or the inability of advanced liver cirrhosis to metabolize it, it causes hyperammonemia, which can pass through the blood-brain barrier, causing hepatic encephalopathy [31].
Previous researches had linked hyperammonemia to worsening Child-Pugh grade and the risk of hepatic encephalopathy [32, 33]. In the current study, plasma ammonia was significantly higher in patients with advanced cirrhosis and higher liver stiffness values > 25 kPa in patients treated with sorafenib or DAAs, and was associated with more complications and an unfavorable outcome at a cut-off value of 87 μg/dl mainly in cirrhotic patients with HCC who were treated with sorafenib.
These parameters should be applied to candidates for interventional hepatic procedures including surgical therapies for any other causes. A sufficient number of patients with liver cirrhosis were included in the study, so that clinical variables were carefully studied.
These non-invasive parameters included markers of portal hypertension, ammonia as a marker of liver metabolic capacity and liver stiffness by Fibroscan in addition to liver volume by bedside ultrasound, were efficient in appreciating residual hepatic reserve in liver cirrhosis with previously ablated HCC.