Background: Previous research has shown variation in the effects of patient factors, including hepatic necroinflammatory activity, on liver stiffness measurement (LSM). This prospective study attempts to identify explanatory factors for LSM in patients with chronic hepatitis C (CHC) using acoustic radiation force impulse (ARFI) technology. Methods: A cohort of 127 Taiwanese patients with CHC underwent ARFI LSM and immediate percutaneous liver biopsy. This study compares the concurrent diagnostic performances of LSM and FibroTest using receiver operating characteristic (ROC) curves. Three multiple linear regression models were used to evaluate the significance of concurrent patient factors in explaining LSM. Results: To classify METAVIR fibrosis (F) stages, the areas under ROC curves (AUCs) were ARFI LSM, 0.847 (95% confidence interval (CI), 0.779-0.914) and FibroTest, 0.823 (95% CI, 0.748-0.898), for F1 versus F2-4; ARFI LSM, 0.902 (95% CI, 0.835-0.970) and FibroTest, 0.812 (95% CI, 0.735-0.888), for F1-2 versus F3-4; ARFI LSM, 0.831 (95% CI, 0.723-0.939) and FibroTest, 0.757 (95% CI, 0.648-0.865), for F1-3 versus F4. After adjusting for other demographic and biological covariates, biochemical and histological necroinflammatory factors consistently explained LSM. Factors included serum alanine aminotransferase (ALT)/upper limit of normal (ULN) categories (model R² = 0.661, adjusted R² = 0.629), ActiTest A scores (R² = 0.662, adjusted R² = 0.636), and METAVIR activity (A) grades (R² = 0.651, adjusted R² = 0.620). METAVIR F stages, body mass index, and platelet count were also independently associated with LSM. Necroinflammatory degrees, including ALT/ULN, ActiTest A scores, and METAVIR A grades, explained the false positivity of liver fibrosis staging using ARFI LSM. Conclusions: The degree of hepatic necroinflammatory activity independently and significantly exaggerated liver fibrosis evaluation using ARFI LSM. However, comparisons with concurrent FibroTest indicate that ARFI LSM may be a promising alternative, or adjunctive single indicator, for liver fibrosis evaluation in patients with CHC.

Data on noninvasive liver fibrosis staging after viral eradication is unclear. This histology-based study validated the performance of liver stiffness (LS) measurement after viral eradication. Consecutive participants with chronic hepatitis C (CHC) who received concomitant LS measurement through acoustic radiation force impulse (ARFI) elastography and percutaneous liver biopsy were prospectively screened and analyzed. Of the 644 patients, 521 (80.9%) underwent a biopsy at treatment baseline, and the remaining 123 (19.1%) underwent a biopsy at 3 (median) (interquartile range: 0.1) years after the sustained virological response (SVR) to pegylated interferon-based and direct-acting antiviral treatments. The proportions of histological fibrosis stages did not differ significantly between the pretreatment and post-SVR groups (P = .0615). However, the LS values differed significantly (P <.0001). The median LS values (presented as shear wave velocity in meters per second) were 1.51 (0.92) for the pretreatment group and 1.22 (0.77) for the post-SVR group. The cutoffs (areas under the receiver operating characteristic curve obtained using the bootstrap method) to dichotomize between METAVIR fibrosis stage F1 versus F2–F4, F1–F2 versus F3–F4, and F1–F3 versus F4 were 1.47 (0.8333 [95% confidence interval = 0.7981 – 0.8663]), 1.81 (0.8763 [0.8376 – 0.9107]), and 1.86 (0.8811 [0.8378 – 0.9179]) in the pretreatment group and 1.22 (0.7872 [0.7001 – 0.8624]), 1.59 (0.8808 [0.8034 – 0.9422]), and 1.75 (0.9018 [0.8201 – 0.9644]) in the post-SVR group, respectively. The performance of LS measurements through ARFI elastography is promising to stage the liver fibrosis on necro-inflammation resolved histology in CHC after viral eradication.

To compare on-treatment and off-treatment parameters acquired using acoustic radiation force impulse elastography, the Fibrosis-4 (FIB-4) index, and aspartate aminotransferase-to-platelet ratio index (APRI) in patients with chronic hepatitis C (CHC). Patients received therapies based on pegylated interferon or direct-acting antiviral agents. The changes in paired patient parameters, including liver stiffness (LS) values, the FIB-4 index, and APRI, from baseline to sustained virologic response (SVR) visit (24 weeks after the end of treatment) were compared. Multiple regression models were used to identify significant factors that explained the correlations with LS, FIB-4, and APRI values and SVR. A total of 256 patients were included, of which 219 (85.5%) achieved SVR. The paired LS values declined significantly from baseline to SVR visit in all groups and subgroups except the nonresponder subgroup (n = 10). Body mass index (P = 0.0062) and baseline LS (P < 0.0001) were identified as independent factors that explained the LS declines. Likewise, the baseline FIB-4 (P < 0.0001) and APRI (P < 0.0001) values independently explained the declines in the FIB-4 index and APRI, respectively. Moreover, interleukin-28B polymorphisms, baseline LS, and rapid virologic response were identified as independent correlates with SVR. Paired LS measurements in patients treated for CHC exhibited significant declines comparable to those in FIB-4 and APRI values. These declines may have correlated with the resolution of necroinflammation. Baseline LS values predicted SVR.

A multitude of laboratory and clinical interferences influence the utility of platelet-based diagnostic indices, including immature platelet fraction, in longitudinal monitoring and prognostication of patients with chronic liver disease (CLD). The complex yet highly regulated molecular basis of platelet production and clearance kinetics becomes dysregulated in liver pathogenesis. These underlying molecular mechanisms, including premature platelet clearance and bone marrow suppression in parallel with the progressive (e.g., treatment-naïve) or regressive (e.g., on-treatment and off-treatment) disease courses, involved in CLDs, may further confound the changes in platelet–liver correlations over time. Platelet count and function are commonly and secondarily altered in vivo in CLDs. However, the precise characterization of platelet functions during cirrhosis, including in vitro platelet aggregation, has proven challenging due to interferences such as thrombocytopenia. A flow cytometric approach may help monitor the unstably rebalanced hyper- and hypoaggregable states in patients with cirrhosis at risk of hyperaggregable, prothrombotic, or bleeding events. Studies have attempted to stratify patients with cirrhosis by substages and prognosis through the use of novel indices such as the ratio of in vitro endogenous platelet aggregation to platelet count. This review attempts to highlight clinical and laboratory precautions in the context of platelet-assisted CLD monitoring.

Objectives: The impact of viral eradication on hepatic angiogenesis is unknown. This study aimed to analyze the correlations of liver angiogenesis with liver fibrosis progression or regression in chronic hepatitis C (CHC) after viral eradication. Methods: From 2003 to 2020, a cohort of 130 eligible participants underwent paired percutaneous liver biopsies (median = 48 months apart; range = 46–62) at the treatment baseline and after sustained virological response to CHC treatment at the tertiary referral center. The collagen proportionate area (CPA) of liver tissue sections was determined using picrosirius red staining through digital image analysis. CD34 and α-smooth muscle actin (α-SMA) phenotypically quantitated liver angiogenesis and myofibroblasts, respectively, through immunohistochemistry staining, to correlate the total, portal, and extraportal liver angiogenesis with fibrogenesis. Results: Paired histology manifested significant regressions in fibrosis stages, and necroinflammatory grades (both P < 0.001). The median of changes in CPAs (follow-up minus baseline) was −6.12% (interquartile range = −12.35 to −2.05%). The median of CPA changes per year was −1.38%/year (interquartile range = −2.98 to −0.51%/year). The significance of declines in total CD34 [coefficient (95% confidence interval), 5.577 (3.286–7.868); P < 0.001] outweighed α-SMA declines, when explaining (R ² = 0.522; adjusted R ² = 0.502) the CPA declines through multiple regression analysis adjusting for other histological variables. Conclusion: Through viral eradication in CHC, the downregulated liver angiogenesis significantly explains the CPA regression.

Rationale: Transcatheter arterial chemoembolization (TACE) is a widely adopted treatment for advanced stage hepatocellular carcinoma (HCC). Nevertheless, several complications may occur, such as hepatic artery injury, nontarget embolization, pulmonary embolism, hepatic abscess, biloma, biliary strictures, and hepatic failure. However, bronchobiliary fistula is rarely mentioned before. Patient concerns: A 65-year-old man with HCC underwent the TACE procedure, and then he encountered fever, dyspnea, abdominal pain, and abundant yellowish purulent bronchorrhea. Diagnosis: Bronchobiliary fistula was diagnosed based on the computed tomography (CT) scan of his chest, which revealed the right lower lobe of his lung was connected to a hepatic cystic lesion. Interventions: Percutaneous transhepatic cystic drainage was performed, and we obtained yellowish bile, showing the same characteristics as the patient’s bronchorrhea. Outcomes: We kept drainage of his biloma and provided supportive care as the patient wished. Unfortunately, the patient passed away due to progressive right lower lobe pneumonia 2 weeks later. Lessons: This case exhibits a typical CT scan image that was helpful for the diagnosis of post-TACE bronchobiliary fistula. Post-TACE bronchobiliary fistula formation hypothesis includes biliary tree injuries with subsequent biloma formation and diaphragmatic injuries. Moreover, the treatment of bronchobiliary fistula should be prompt to cease pneumonia progression. Therefore, we introduce this rare complication of post-TACE bronchobiliary fistula in hopes that future clinicians will keep earlier intervention in mind.