Effect of direct-acting antivirals on disease burden of hepatitis C virus infection in South Korea in 2007-2021: a nationwide, multicentre, retrospective cohort study.

Background: It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. Methods: This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. Findings: Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p < 0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p < 0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p < 0.0001). Interpretation: Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests. Funding: The Korea Disease Control and Prevention Agency.

Tenofovir alafenamide treatment may not worsen the lipid profile of chronic hepatitis B patients: A propensity score-matched analysis.

BACKGROUND/AIMS: Tenofovir alafenamide (TAF) has shown less favorable effect on lipids compared to tenofovir disoproxil fumarate (TDF) in clinical trials. However, data regarding these outcomes in patients with chronic hepatitis B (CHB) are scarce. Therefore, this study aimed to evaluate the effect of TAF on the lipid in patients with CHB. METHODS: A total of 237 TAF-treated CHB patients compared with TDF, inactive CHB, and non-hepatitis B virus (HBV)-infected control groups using propensity score matching (PSM). RESULTS: Following PSM, each analysis was conducted on cohorts via the matching of 70:140 (TAF:TDF), 89:89 (TAF:inactive CHB), 140:560 (TAF:non-HBV infected control), and 368:1,472 (TDF:non-HBV-infected control). A significant decrease in the total cholesterol (TC) level was noted at 48 weeks in the TDF group compared to the TAF group (176.3±32.9 vs. 156.7±27.7, P<0.001) and the non-HBV-infected control group (175.0±29.5 vs. 156.2±28.3, P<0.001). However, no significant change in TC was observed in the TAF group and inactive CHB or non-HBV-infected control groups at 48 weeks. For the subgroup analyses of TAF vs. non-HBV-infected control subjects and inactive CHB patients whose detailed lipid profile information were available, no between-group differences in TC, low-density lipoprotein (LDL)-cholesterol, highdensity lipoprotein (HDL)-cholesterol, TC/HDL ratio, and LDL/HDL ratio were observed at 48 weeks. CONCLUSION: TDF seems to have a lipid-lowering effect compared to the non-HBV-infected control and TAF-treated groups. However, in real practice, TAF might not worsen the lipid profiles of subjects compared to non-HBV-infected controls and patients with inactive CHB.

Clinical usefulness of noninvasive fibrosis indices for predicting hepatocellular carcinoma in treatment-naïve patients with chronic hepatitis B following entecavir therapy.

AIMS: This study aimed to evaluate the clinical usefulness of the aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4), and modified FIB-4 (mFIB-4) indices in predicting hepatocellular carcinoma (HCC) in patients receiving entecavir (ETV) treatment. METHODS: Among 1955 patients treated with ETV, a total of 857 treatment-naive chronic hepatitis B patients (424 with liver cirrhosis [LC], 433 without cirrhosis) treated with ETV for more than 1 year were analyzed. RESULTS: Of the 857 patients, 85 (9.9%) patients (77 in the LC group and 8 in the non-LC group) developed HCC during the follow-up period. The median observation period was 6.9 years. Multivariate regression analysis of HCC incidence revealed that the initial mFIB-4 index (hazard ratio [HR] 1.058; 95% confidence interval [CI], 1.007-1.112; p = 0.027) and improvement in the FIB-4 index after 1 year of ETV treatment (HR 0.531; 95% CI, 0.339-0.831; p = 0.006) were independent prognostic factors in the entire cohort. In the LC group, the improvement of the FIB-4 index following ETV treatment (HR 0.491; 95% CI, 0.280-0.861; p = 0.013) was negatively correlated with incidence of HCC. However, the area under the receiver operating characteristic curve of specific cut-off values of the FIB-4 index at baseline and 1 year after ETV treatment were 0.572 (95% CI, 0.504-0.640) and 0.615 (95% CI, 0.546-0.684), respectively. In the non-LC group, none of the invasive fibrosis indices could predict HCC incidence. CONCLUSIONS: The specific cut-off value of the FIB-4 index was not suitable for predicting HCC. However, the improvement in the FIB-4 index after 1 year of ETV therapy could be a predictor of HCC development in cirrhotic patients.

Microvascular invasion may be the determining factor in selecting TACE as the initial treatment in patients with hepatocellular carcinoma.

ABSTRACT: The aim of this study was to investigate factors affecting tumor necrosis with transcatheter arterial chemoembolization (TACE). Factors associated with early hepatocellular carcinoma recurrence after curative hepatectomy were also evaluated.Data of 51 patients who underwent surgery after a single session of TACE at a single university hospital were retrospectively analyzed. Factors that might affect tumor necrosis were determined by evaluating the TACE approach and by analyzing computed tomography and TACE findings, pathologic reports, and laboratory findings.In univariate analysis, microvascular invasion (MVI), radiological capsule appearance on the computed tomography, chronic hepatitis B, diabetes mellitus and serum albumin, MVI were significantly associated with tumor necrosis by TACE (P < .02). In multivariate analysis, MVI was the only statistically significant factor in TACE-induced tumor necrosis (P = .001). In univariate and multivariate analysis, MVI was the strongest factor for recurrence-free survival rate within 2 years (P = .008, P = .002).MVI could be a crucial factor in determining TACE as an initial treatment for hepatocellular carcinoma. MVI is also a strong indicator of recurrence within 2 years after curative hepatic resection.

Comparable Incidence of Hepatocellular Carcinoma in Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir.

BACKGROUND/AIMS: Adherence to medication and maintained virologic response (MVR) are related to the risk of adverse clinical outcomes. This study aimed to compare the efficacy of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) in relation to the adverse clinical outcomes among chronic hepatitis B (CHB) patients stratified according to adherence to medication and MVR. METHODS: A total of 1794 treatment-naive CHB patients treated with ETV (n = 894) or TDF (n = 900) for > 1 year were identified. RESULTS: Adherence rates were significantly higher in the TDF than in the ETV (93.4% vs. 89.1%, respectively; P < 0.001). The MVR of ETV and TDF were 64.5% and 71.7%, respectively (P = 0.001). The MVR of ETV and TDF in the good adherence group were 72.1% and 76.4%, respectively (P = 0.083); in the poor adherence group, the MVR of ETV and TDF were 63.0% and 54.0%, respectively (P = 0.384) Multivariate analysis showed that the risk of HCC and death or transplantation was similar between groups (HR 0.826, 95% CI 0.522-1.306; P = 0.413 and HR 0.636, 95% CI 0.258-1.569; P = 0.325, respectively) after adjusting for adherence to medication and MVR. In the 589 propensity-matched pairs of patients, risk of HCC and death or transplantation was similar between treatment groups after stratification according to adherence rates and MVR. CONCLUSIONS: After adjustment for adherence and MVR, ETV, and TDF did not differ in terms of the risk of HCC and death or transplantation in all patients and propensity score-matched cohorts.

Spinal anesthesia for urgent Cesarean section in a patient with uncontrolled hyperthyroidism due to Graves' disease - A case report.

BACKGROUND: Effective treatment of Graves' disease during pregnancy is important because uncontrolled hyperthyroidism is associated with increased fetal and maternal morbidity and mortality. While there have been case reports of patients with Graves' disease who failed to achieve euthyroid state during pregnancy, anesthesiologists rarely encounter patients with uncontrolled hyperthyroidism undergoing urgent Cesarean section. CASE: A 31-year-old pregnant patient had uncontrolled hyperthyroidism due to Graves' disease despite medical treatment. Her signs and symptoms suggested fetal distress and aggravation of the disease, leading to hospitalization. After a failed induction for vaginal delivery, an urgent Cesarean section was performed under spinal anesthesia via an interlaminar approach using 9 mg of 0.5% heavy bupivacaine and 20 µg of fentanyl. It resulted in successful delivery, with no perioperative complications for the mother and neonate. CONCLUSIONS: This case demonstrates that spinal anesthesia may provide clinical stability to patients with uncontrolled hyperthyroidism undergoing urgent Cesarean section.

Propofol alone prevents worsening hepatic encephalopathy rather than midazolam alone or combined sedation after esophagogastroduodenoscopy in compensated or decompensated cirrhotic patients.

BACKGROUND: This study was conducted to determine which type and dose of sedative drugs should be given to cirrhotic patients with compensation or decompensation during esophagogastroduodenoscopy (EGD) to prevent hepatic encephalopathy (HE) after sedation. METHODS: We reviewed the medical records of cirrhotic patients consecutively admitted to the hospital and conducted a number connection test (NCT) before and 2 h after EGD with moderate sedation. Sedation was performed using either propofol alone, midazolam alone, or combined propofol + midazolam. RESULTS: Sixty-seven patients were admitted for a screening EGD. The NCT before and after sedation were not significantly different in the propofol alone (pre-NCT = 47.3 ± 19.71 seconds vs. post-NCT = 49.4 ± 21.79 seconds, P = 0.6389). In the midazolam alone (pre-NCT = 50.3 ± 20.56 vs. post-NCT = 63.7 ± 33.17, P = 0.0021) and in the combined propofol + midazolam (pre-NCT = 47.4 ± 20.99 vs. post-NCT = 60.0 ± 30.79, P = 0.0002), NCT were significantly delayed. The propofol alone group received 52.3 ± 16.31 mg (0.82 ± 0.29 mg/kg). In 45 (67.2%) decompensated patients, only the propofol alone was not significantly different between pre-NCT (49.2 ± 22.92) and post-NCT (52.3 ± 24.90) (P = 0.4548). Serum sodium level was significantly correlated with delta-NCT (r = 0.3594, P = 0.0028). CONCLUSION: Propofol alone could be the best sedation strategy for cirrhotic patients with compensation or decompensation without aggravation of covert or overt HE. Hyponatremia could be a risk factor for developing or worsening HE after EGD with sedation.

Low-level viremia and cirrhotic complications in patients with chronic hepatitis B according to adherence to entecavir.

BACKGROUND/AIMS: Low-level viremia (LLV) after nucleos(t)ide analog treatment was presented as a possible cause of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). However, detailed information on patients' adherence in the real world was lacking. This study aimed to evaluate the effects of LLV on HCC development, mortality, and cirrhotic complications among patients according to their adherence to entecavir (ETV) treatment. METHODS: We performed a retrospective observational analysis of data from 894 consecutive adult patients with treatment-naïve CHB undergoing ETV treatment. LLV was defined according to either persistent or intermittent episodes of <2,000 IU/mL detectable hepatitis B virus DNA during the follow-up period. Good adherence to medication was defined as a cumulative adherence ≥90% per study period. RESULTS: Without considering adherence in the entire cohort (n=894), multivariate analysis of the HCC incidence showed that LLV was an independent prognostic factor in addition to other traditional risk factors in the entire cohort (P=0.031). Good adherence group comprised 617 patients (69.0%). No significant difference was found between maintained virologic response and LLV groups in terms of the incidence of liver-related death or transplantation, HCC, and hepatic decompensation in good adherence group, according to multivariate analyses. CONCLUSION: In patients with treatment-naïve CHB and good adherence to ETV treatment in the real world, LLV during treatment is not a predictive factor for HCC and cirrhotic complications. It may be unnecessary to adjust their antiviral agent for patients with good adherence who experience LLV during ETV treatment.

Risk factors associated with hypophosphatemia in chronic Hepatitis B patients treated with tenofovir disoproxil fumarate.

Tenofovir disoproxil fumarate (TDF) is thought to cause varying degrees of hypophosphatemia in patients with chronic hepatitis B (CHB). Therefore, we investigated factors that cause hypophosphatemia in patients treated with TDF and methods to increase serum phosphorus concentrations in clinical practice.We completed a retrospective review of patients with CHB treated with TDF initially at Kosin University Gospel Hospital, Busan, Korea from January 2012 to January 2017. Subclinical hypophosphatemia and hypophosphatemia were defined as serum phosphorus below 3.0 mg/dL and 2.5 mg/dL, respectively.We screened 206 patients with CHB treated with TDF, among which 135 were excluded for the following reasons: baseline malignancy (59), limited data (50), co-administered other antivirals (14), hypophosphatemia at baseline (7), and other reasons (5). The final study population comprised 71 patients. Subclinical hypophosphatemia developed in 43 (60.5%) patients. Hypophosphatemia occurred in 18 patients (25.3%). Liver cirrhosis was the most significant predictor of hypophosphatemia (P = .038, OR = 3.440, CI = 1.082-10.937) Patients diagnosed with subclinical hypophosphatemia were encouraged to increase their intake of nuts and dairy products (25 patients) or reduce their alcohol intake (2), dose reduction of TDF (4) or placed under observation (4). Among patients with subclinical hypophosphatemia, serum phosphorus concentrations were elevated (>3.0 mg/dL) in 23 of 36 patients (63.8%). Increased nut and dairy intake increased phosphorus concentrations to more than 3.0 mg/dl in 16 of 25 patients (64.0%).Entecavir or tenofovir alafenamide fumarate (TAF) should be considered rather than TDF in patients with liver cirrhosis because of the risk of hypophosphatemia. Instead of stopping TDF treatment, encouraging increased intake of phosphorus-rich foods could increase serum phosphorus concentrations in clinical practice.

The Effect of Anti-reflux Therapy on Patients Diagnosed with Minor Disorders of Peristalsis in High-resolution Manometry.

BACKGROUND/AIMS: Minor disorders of peristalsis are esophageal motility disorders categorized by the Chicago Classification (CC), version 3.0, which was announced in 2014. This study evaluated the efficacy of anti-reflux therapy in patients with minor peristaltic disorders. METHODS: Patients with minor peristaltic disorders in accordance with CC v3.0 were included. We reviewed the medical records of patients with esophageal high-resolution manometry findings, and investigated the demographic and clinical information as well as the medical therapy. Thereafter, the response to treatment was assessed after at least 4 weeks of treatment. RESULTS: A total of 24 patients were identified as having minor disorders of peristalsis from January 2010 to December 2015. The mean follow-up period was 497 days, and there were 17 patients (70.8%) patients with ineffective esophageal motility. In terms of anti-reflux therapy, proton pump inhibitors (PPIs) with prokinetic agents and PPIs alone were prescribed in 19 patients (79.2%) and 5 patients (20.8%), respectively. When the rate of response to the treatment was assessed, the responders rate (complete+satisfactory [≥50%] responses) was 54.2% and the non-responders rate (partial [<50%]+refractory responses) was 45.8%. Patients in the responder group were younger than those in the non-responder group (p=0.020). Among them, 13 patients underwent 24-hour multichannel intraluminal impedance-pH, and 10 patients (76.9%) were pathologic gastroesophageal reflux. CONCLUSIONS: The majority of esophageal minor peristaltic disorders were accompanied by gastroesophageal reflux, and therefore, they might respond to acid inhibitor. Further well-designed, prospective studies are necessary to confirm the effect of anti-reflux therapy in these patients.