Portal hypertension is the most common cause of complications in cirrhotic patients. While certain symptoms of it are obvious (e.g., ascites), others are more subtle. EVs, for example, are asymptomatic until they bleed. Patients with PH should be identified and offered endoscopic screening before bleeding develops. In addition to cirrhotic consequences, portal hypertension is linked to a higher risk of death in individuals with various liver diseases [4].
Our finding was roughly close to Abd El-Wahab et al. [12], who showed that males were 50.7% and females were 49.3%, whereas in our study, males represent 40% and 30% in group A and group B, and females represent 60% and 70% of groups A and B, respectively. Disparately, Mehrez et al. [13] studied 50 Egyptian patients with HCV genotype 4 infection and showed that 54% were males and 46% were females.
Regarding the mean age of patients, both were similar to our study; it was 52 years ± 10.3 at Abd El-Wahab et al. and 52.92 years at Mehrez et al., while for our patients, it was 55.98 ± 11.46 and 57.45 ±10.21 years in groups A and B, respectively.
All of our patients achieved successful HCV eradication with 100% SVR at EOT, persisted to SVR 24 and SVR 48. Giannini et al. [2], Ebeid et al. [14], and Przekop et al. [15], showed similar results by achieved SVR nearly in 100% of patients.
This study showed significant improvement of AST, ALT, serum albumin, INR, and platelet count, particularly between baseline and SVR 24, in all patients in the main groups of the study. This matched with Mehrez et al. [13] and Ippolito et al. [16], which followed their patients at SVR 12, and also Puente et al. [17], who followed the patients at week 8 during treatment and at SVR 72 posttreatment and reported significant improvement in all laboratory values with minor differences.
Another study by Elsharkawy et al. [18] showed significant improvement in AST, ALT, serum albumin, and INR, but it was insignificant for platelets and total bilirubin. The difference in comparison with other studies was pointed to efficacy of SOF/DAC combination in improving the liver necro-inflammatory more than SOF/SIM or SOF/RIB combination in cirrhotic patients, as only 23.5% of his study population received SOF/DAC, in contrast to our study where 92.5% has received SOF/DAC-based combinations.
This study is in concordance with Elsayed et al. [19], which was carried on 100 patients with chronic HCV-induced liver disease with early stage of cirrhosis, found a significant improvement at 6 months after DAAs (at SVR 24) in laboratory values (platelet count, albumin, bilirubin, AST, ALT), PVV, APRI score, and PC/SD ratio, with contrast to our results regarding PVD that was not significantly decreased after DAAs (p-value = 0.345). The difference between our findings and results of Elsayed et al. regarding PVD could be due to difference in inclusion criteria as we included patients with compensated liver cirrhosis and early CSPH, and majority of our patients were child B, while Elsayed et al. exclude them from his study. This explained the noticeable improvement in PVD and PVV in our results due to decrease in the intrahepatic pressure as a sequelae of improvement of necroinflammation by the DAAs.
Our results illustrated a significant difference between main groups of the study at baseline regarding Child-Pugh score, with mean ± SD for group A (7.68 ± 1.27) and for group B (5.7 ± 0.46). Also, Child-Pugh score showed significant difference in each group independently.
In group A, it improved from 7.68 ± 1.27 at baseline to 6.8 ± 1.14 at SVR 24 and to 6.5 ± 1.18 at SVR 48. However, this improvement was noticed to be more significant in the 1st 6 months early after DAA’s therapy. Furthermore, Child-Pugh score showed significant difference between group I and group II. These findings are in agreement with Ali et al. [20], who found significant improvement on Child-Pugh score from mean 7.3 to 5.9, and also Ji et al. [21], who found significant improvement on it from 6.30 ± 1.60 to 5.87 ± 1.14 at SVR 24. This findings was in concordance with Knop et al. [22] and Ippolito et al. [16]. This is referred to prevention of further stress on liver parenchyma by viral replication after eradication by DAAs.
Also, Knop et al. [22], Giannini et al. [2], and Cheng et al. [23] reported significant improvement of APRI score between baseline and SVR 24 in compensated HCV cirrhotic patients (p < 0.001*). These findings were in line with our results, in which there were significant improvement of all noninvasive scores after treatment with DAAs in both main study groups.
Regarding FIB-4 score, King’s score, and Lok index, they showed significant difference between both groups at baseline and significant improvement after DAA’s therapy. These results were similar to Abd El-Wahab et al. [12], with regard to King’s score; however, Lok’s index did not improve significantly after treatment (p = 0.987). Abd El-Wahab et al. suggested that these scores are affected by the variations in platelets count, AST, ALT, and ɣGT levels, and the resolution of established liver necroinflammation and fibrosis is a dynamic process may take several years. However, this remained controversial as other studies stated that the inflammatory activity did not contribute to liver stiffness.
About ascites detected by abdominal US, it has improved mainly between baseline and SVR 24. This study found that ascites has significantly resolved in group A 45% at SVR 24 versus 12.5% at baseline, with p-value ≤ 0.001*). This finding is close to Romano et al. [24], whereas ascites were resolved in 29% of patients 3 months posttreatment (65% versus 36%, p-value < 0.001*). Our finding suggest that DAAs can attenuate further hepatic decompensation by resolving ascites, and several studies have demonstrated that HCV patients who achieve SVR with DAAs experience significant improvements in their quality of life (social functioning, work productivity).
Regarding portal vein velocity, our results are in line with Soliman et al. [25], where PVV improved significantly from 11.889 ± 3.529 cm/s to 15.094 ± 4.250 cm/s, with (p-value ≤ 0.001*), as well as Mahmoud et al. [26], where PVV was increased significantly from 13.61 ± 2.53 cm/s at baseline to 14.72±2.67 cm/s at EOT and to 15.81±2.067 cm/s at SVR 48, with p-value ≤ 0.001*.
In our results, portal vein diameter showed 82.50% sensitivity and 95% specificity at cutoff value (> 13.8 mm), to predict the presence of CSPH in HCV-related liver cirrhosis, while showed 50% sensitivity and 100% specificity, at cutoff value (≤ 14 mm), to predict reversibility of CSPH. These findings are similar to Hagen-Ansert [27], who reported that a diameter (> 13 mm) was considered as a predictor of PH in patients with cirrhosis, but unlike Mahmoud et al. [26] and Mihai et al [28], as their results were insignificant regarding PVD.
Agha et al. [29] showed that PC/SD ratio had noninvasive relevance in diagnosis of EVs in a large population of HCV-infected cirrhotic patients; although previous studies limited their efficacy only to detect the presence of EVs, our study showed that it is still a useful noninvasive tool for the detection of CSPH in patients with HCV-related liver disease, as it is cheap, accurate, and easy applicable tool especially in developing countries where endoscopies are costly. This study showed that regarding prediction of CSPH in HCV-related liver disease, PC/SD ratio has the advantage, followed by Child score and platelet count as a most significant parameters; however, newly developed scores as FIB-4 index, King’s score, and Lok index were significant also with AUROC 0.665, 0.646, and 0.637, respectively.
Our findings concerning the best performing noninvasive serum biomarker of liver fibrosis in prediction of the presence of CSPH in HCV-related liver cirrhosis using the ROC curve (AUROC) were the FIB-4 score (AUROC = 0.665; PPV = 86.4%; NPV = 63.8%), followed by King’s score (AUCROC = 0.637; PPV = 69.4%; NPV = 65.9%), and then Lok index (AUROC = 0.665; PPV = 65%; NPV = 65%). This was in line with Ishida et al. [30], who found that FIB-4 score provided the greatest diagnostic accuracy in predicting both EVs and CSPH.
The current study was in agreement with Abd El-Wahab et al. [12], as regard best performing test for prediction of the presence of CSPH in HCV-related liver cirrhosis was for FIB-4 (AUROC = 0.791; CI = 73.4%–84.8%), followed by King’s score (AUCROC = 0.786; CI = 72.7%–84.5%), and then Lok index (AUROC = 0.762; CI = 69.9%–82.5%), but they were not in agreement regarding APRI score.
In accordance with Wang et al. [31], King’s score and Lok index were exhibited the best performance, as indicated by AUROCs of 0.755 and 0.740, respectively, although performed on different etiologies causes liver fibrosis, and also, combination between King’s and Lok index may be used as an initial screening tool to identify cirrhosis patients who are at very high risk of CSPH and to determine the need for further evaluation, but they were not in agreement regarding APRI score.
Limitation
The limitations of our study were its relatively small sample size due to covid-19 precautionary measures which limited the endoscopy and ultrasonography lists and made many patients to miss their follow-up appointments. Also, being only a single-center experience was a week point.
On the other hand, our study had relatively longer period of follow-up with combination of various important tools including noninvasive serum biomarkers, ultrasonography and duplex studies, and endoscopic evaluation, so the results may differ from those in previous publications.
