Lily H. Kim

Long-term follow-up and suboptimal treatment rates of treatment-eligible chronic hepatitis B patients in diverse practice settings: a gap in linkage to care

Background and aims Despite available effective therapies, only a minority of patients with chronic hepatitis B (CHB) receive treatment. Our goal is to study treatment rates and time to treatment initiation in patients who meet treatment criteria on long-term follow-up. Methods We performed a retrospective cohort study of 608 consecutive treatment-eligible patients with CHB (by 2008 US Panel or 2009 American Association for the Study of Liver Disease (AASLD) criteria) at a US community gastroenterology clinic and a university liver clinic between 2007 and 2011. Patients were observed until they started treatment or last follow-up if untreated. Results Mean age was 44 and most were Asian (96%) with community patients being younger and having lower alanine aminotransferase (ALT) levels. A total of 62% started treatment, and 38% remained untreated after median follow-up of 17 months (IQR=1–40 months). Overall, treatment rate was significantly higher at university liver clinic than in the community (66.7% vs 59.9%, p=0.01). In multivariate analysis, older age (HR 1.02, p=0.002), male gender (HR 1.37, p=0.02), and baseline ALT >45 U/L for males and >29 U/L for females (HR 2.24, p<0.0001) were significant predictors of treatment initiation, but not practice setting. Conclusions Approximately 40% of treatment-eligible patients still have not started treatment on longer follow-up. Treatment rates were higher at university clinics, but practice setting was not a predictor for treatment, but older age, male gender, and higher ALT levels were. Further studies are needed to determine the barriers for treatment initiation and to improve treatment rates in treatment-eligible patients.

Recurrent hepatocellular carcinoma and poorer overall survival in patients undergoing left-sided compared with right-sided partial hepatectomy.

Goals: We aimed to determine the incidence and predictors of recurrent hepatocellular carcinoma (HCC) after partial hepatectomy. Background: Liver transplantation is the preferred treatment for selected patients with HCC, but access to donor organs is limited. Partial hepatectomy is another accepted treatment option; however, postoperative recurrence is frequently observed. Methods: This is a retrospective cohort study of 107 consecutive patients who underwent partial hepatectomy for HCC between January 1993 and February 2011 at a US University Medical Center. Study endpoints were recurrent HCC, death, loss to follow-up, or last visit without HCC. Results: The study cohort was 78% male with a median age of 61 years and 59% Asians. A total of 50 patients developed recurrent HCC (46.7%) after a median follow-up of 12 (1 to 69) months postresection. Recurrent HCC was significantly higher in patients with left-sided resection (41% at year 1, 54% at year 2, 62% at year 3, 81% at year 4, and 90% at year 5) compared with right-sided resection (18% at year 1, 34% at year 2, 36% at year 3, 44% at year 4, and 72% at year 5). In multivariate Cox proportional hazards model also inclusive of anatomic resection and TNM stage 3/4, left-sided resection was significantly associated with increased HCC recurrence (hazard ratio, 2.13; P=0.02; 95% confidence interval, 1.08-4.2) compared with right-sided resection. Conclusions: HCC recurrence rate is higher among those undergoing left-sided resection: 54% at year 2 and 81% at year 4. Liver transplantation should be considered in patients who are at high risk for recurrence.

Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy.

Objectives It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV. Our goal was to examine virologic outcomes in such patients. Methods This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy, who were switched back to monotherapy with either ETV (n=16) or TDF (n=18), or continued on combination therapy (n=23). The majority of patients were Asian (91%) and male (65%), with a mean age of 41±12 years. Results The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs. 39%, P=0.004). Patients who remained on ETV+TDF also had virologic breakthrough, due to either confirmed or suspected nonadherence. On multivariate analysis inclusive of age, sex, and hepatitis B virus DNA levels at initiation of combination therapy, ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 112.7, P=0.03), as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 60.2, P=0.03). Conclusion TDF monotherapy, especially in those who have had CVS for at least 12 months on combination therapy, may be considered for some ETV partial responders who have achieved CVS with combination therapy, given the financial advantage and convenience of monotherapy.

Quantitative analysis of the safety and efficacy of microvascular decompression for patients with trigeminal neuralgia above and below 65 years of age

For medically-refractory trigeminal neuralgia (TN), microvascular decompression (MVD) is the first-line treatment, and has demonstrated the greatest efficacy and durability. However, due to potential surgical complications, a bias may exist against performing MVD in elderly patients. We sought to determine through a quantitative analysis whether MVD in the elderly is a safe and effective procedure for TN. We completed a Pubmed/SCOPUS literature search up to 12/2016 for eligible studies on MVD for TN. Only research articles with age stratification of results were included. In this quantitative analysis, we analyzed the data for the six articles identified in the literature comparing MVD for a group of patients ≥65 years with an elderly group <65 years. A total of 1483 were included. 455 patients were ≥65 years (mean 70.8 years, range 65-89 years) and 1028 patients were <65 years (mean 53.4 years, range 19-64 years). Composite mean follow-up time was 51.6 months for the elderly group, and 55.1 months for the young group. Following MVD, each group had 1 mortality (p = 0.43). There were 21 serious morbidities in the elderly group (4.62%) and 32 in the young group (3.11%) (p = 0.11). In addition, 15 patients (1.46%) in the elderly group and 24 patients (1.62%) in the young group experienced a cerebrospinal fluid leak (p = 0.23). TN recurrence rates 9.23% in the young group and 13.33% in the elderly group (p = 0.070). In conclusion, for properly-selected surgical candidates, MVD should not be ruled out on the basis of age ≥65 years.

Stereoelectroencephalography in children: a review

Stereoelectroencephalography (SEEG) is an intracranial diagnostic measure that has grown in popularity in the United States as outcomes data have demonstrated its benefits and safety. The main uses of SEEG include 1) exploration of deep cortical/sulcal structures; 2) bilateral recordings; and 3) 3D mapping of epileptogenic zones. While SEEG has gradually been accepted for treatment in adults, there is less consensus on its utility in children. In this literature review, the authors seek to describe the current state of SEEG with a focus on the more recent technology-enabled surgical techniques and demonstrate its efficacy in the pediatric epilepsy population.

Anterior Techniques in Managing Cervical Disc Disease

Surgical treatment may be indicated for select patients with cervical disc disease, whether it is cervical disc herniation or spondylosis due to degenerative changes, acute cervical injury due to trauma, or other underlying cervical pathology. Currently, there are various surgical techniques, including anterior, posterior, or combined approaches, in addition to new interventions being utilized in practice. Ideally, the surgical approach should be selected in consideration of each patient’s clinical presentation, imaging findings, and overall medical comorbidities on an individual basis. But the unique advantages and disadvantages of each surgical technique often complicate the therapy choice in managing cervical disc diseases. Although anterior cervical discectomy and fusion (ACDF) is the most widely accepted procedure performed for both single and multi-level cervical disc diseases, there are multiple modifications to this technique. Surgeons have access to different types of plates, screws, and cages and can adopt newer advances in the field such as stand-alone and minimally invasive techniques when indicated. In short, no consensus exists in terms of a single approach that is preferred for all patients. This article aims to review the standard of care for management of cervical disc disease with a focus on the surgical techniques and, in particular, the anterior approach, exploring the various surgical options within this technique.

P585 PATIENTS WITH HCC AND NONVIRAL DISEASES PRESENTED WITH MORE ADVANCED TUMOR, WITHOUT PRIOR HCC SCREENING, AND HAD POORER SURVIVAL, COMPARED WITH VIRAL HCC PATIENTS

lengths were significantly shorter in HCC patients (T/S = 0.71±0.24) compared to controls (T/S = 0.91±0.32) (P < 0.0001). Four heterozygous TERT mutations were identified in four patients. A novel TERT A243V mutation was found in a patient with severe disease (BCLC D). The second (T726M) and third (V1090M) mutations were identified in patients with early stage disease (BCLC A1). The fourth mutation (A1062T), previously described in leukemia and cirrhosis, was found in a patient with cirrhosis, Child–Pugh C, BCLC D. The four mutant patients had short telomeres for their age. Conclusions: These results suggest that telomerase mutations and telomere erosion are risk factors for the development of HCC in patients with cirrhosis.

Mo1045 Compared to HCC Patients With Chronic Viral Hepatitis (Viral HCC), Hcc Patients With Nonviral Etiologies (Nonviral HCC) Were Less Likely to Undergo HCC Screening, Presented With More Advanced Tumors, and Had Poorer Overall Survival

Purpose: HCC rarely occurs in patients without chronic liver disease, and the clinical outcomes of HCC patients may differ by etiologies of underlying liver disease. Routine HCC screening/surveillance is recommended for those with chronic hepatitis B and cirrhosis of all etiologies, but it is unclear if there are differences in adherence in different populations. Our goal was to compare screening adherence and clinical outcomes of viral vs. nonviral HCC patients. Methods: This is a retrospective cohort study of 200 consecutive nonviral HCC patients (67 with alcoholic liver disease [ALD], 73 with cryptogenic/nonalcoholic fatty liver disease [NAFLD] and 52 with others) and 396 patients with viral HCC (268 with chronic hepatitis C, 119 with chronic hepatitis B and 9 with both) randomly selected from a total cohort of 1,214 patients with viral HCC who presented at a U.S. medical center in 1991-2011. HCC patients were identified via ICD-9 electronic query with data collected in all cases by individual chart review and National Death Index search. HCC screening adherence was optimal if US or CT/MRI were done every 6-12 months. Results: Compared to viral HCC patients, those with nonviral HCC were older (65±13 vs. 57±11, p<0.0001) and more likely to be non-Asian (74% vs. 51%, p<0.001), but had similar CPT scores (6.6 ±1.7 vs. 6.9±1.8, p=0.13). While the majority of viral HCC patients had a history of optimal HCC screening (69%), almost none of the nonviral HCC patients did (1%). Compared to viral HCC patients, nonviral HCC patients were much more likely to present withBLCL Stage C/D (42% vs. 19%), p<0.001) and beyond the Milan criteria for liver transplantation (75% vs. 54%, p<0.001). Nonviral HCC patients had significantly lower 5-year survival compared to their viral HCC counterparts: 48% vs 57% (p=0.036) (Figure). Similarly, patients who received optimal screening had significantly higher 5-year overall survival compared to those with suboptimal or no screening (62% vs. 47%, p=0.012). Onmultivariate analysis also inclusive of age, sex and ethnicity, independent predictors for lower mortality were HCC screening (OR=0.50, p=0.015), in addition to viral liver disease etiology (OR= 0.39, p=0.002). Conclusions: Nonviral HCC patients were much less likely to have a history of HCC screening, presented with higher tumor stages, and had poorer survival. The lack of HCC screening in nonviral HCC patients may be due to poor adherence and access to care as may be seen in those with ALD or underdiagnosis of chronic liver disease/cirrhosis as may be seen in those with cryptogenic or NAFLD. Further studies and efforts should be focused on early diagnosis of underlying liver disease, cirrhosis, and improvingHCC screening compliance in at-risk patients; which is especially important with the rising obesity epidemic and projected increase of HCC incidence due to NAFLD.

Sa1005 Antiviral Treatment Eligibility and Treatment Rates in Patients With Chronic Hepatitis B (CHB) At Primary Care, Community and University Referral Clinics: A Comparative Study

Background: Liver cirrhosis is inevitable outcome triggered by consistent chronic inflammation. Recent studies have implied that liver cirrhosis accompanied with angiogenesis. Our previous studies demonstrated that celecoxib could reduce angiogenesis in hepatocellular carcinoma and gastric adenocarcinoma. However, the effect of celecoxib on the antiangiogenesis of cirrhotic liver is still controversial. Objective: To investigate the effect of celecoxib on angiogenesis of cirrhotic liver. Methods: Peritoneal injection of thiacetamide (TAA) was employed to induce liver cirrhosis (200 mg/kg every three days × 16 weeks). 36 male Sprague-Dawley rats were assigned to three groups: group 1 (TAA + celecoxib, n = 12) received TAA plus celecoxib (20 mg/kg/day) by gavage from the initiation of TAA administration on, group 2 (TAA, n = 12) received TAA plus placebo and group 3 (Control, n = 12) received injections of 0.9% saline (1mL i.p., every three days). Serum biochemistry for liver and kidney function parameters and serum prostaglandin E2 (PGE2) were determined. Portal pressure and mean artery pressure were also measured. Histopathological study and vascular casting by scanning electron microscope (SEM) of liver vascular were performed. Additionally, immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) and western blot for CD31, vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR2), and Cyclooxygenase-2 (COX-2) were determined. Results: Compared with TAA group, the fibrotic areas of liver tissues in TAA+celecoxib group were significantly decreased by one fold (20.8 ± 1.5% vs. 10.6 ± 0.9%, p , 0.001). Histological sections, vascular casts of hepatic portal vein by SEM, IHC and qRT-PCR for CD31 showed that hepatic fibrosis was accompanied with significant neoangiogenesis in TAA group when compared with Control group (0.1502 ± 0.0143 vs. 0.0325 ± 0.0086 mm2, p , 0.001). Impressively, the increased vascular areas were greatly reduced after celecoxib treatment (0.0485 ± 0.0097 vs. 0.1502 ± 0.0143 mm2, p , 0.001). The up-regulation of VEGF and VEGFR-2, COX-2 and PGE2 induced by TAA administration were significantly inhibited after celecoxib treatment. Compared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8% (14.88 ± 0.84 vs. 12.23 ± 1.09 mmHg, p , 0.001). No significant differences in arterial pressure, heart rate and liver and kidney function parameters were observed among three groups (p . 0.05). Conclusions: Anti-angiogenesis therapy with celecoxib ameliorated hepatic angiogenesis, portal pressure as well as fibrosis. This result suggested that celecoxib would be beneficial for the treatment of liver cirrhosis.

613 Hepatitis C Virus (HCV) Diagnosis and Clinical Outcomes of Patients With HCV-Related Hepatocellular Carcinoma (HCC): A Comparative Study of Asians Versus Non-Asians

BACKGROUND AND AIMS: In addition to hepatitis B virus, HCV is also an important cause of HCC in Asians; however, it is often overlooked. This study aims to examine baseline characteristics, timing of HCV diagnosis and long-term survival of HCV-related HCC in Asians compared to non-Asian patients. METHODS: We conducted a retrospective cohort study of 798 consecutive Asian (n=220) and non-Asian (n=572) patients with HCV-related HCC who were identified via computer query using ICD-9 diagnosis at a U.S. university medical center between 7/1996 and 6/2012. Individual records were reviewed. RESULTS: Asians were much older (66 [38-88] vs. 56 [31-87] years, P ,0.0001) and more likely to be female (33% vs. 19%, P,0.0001). A significantly larger proportion of Asians were also diagnosed with HCC within only 2 years of HCV diagnosis compared to non-Asians (35% vs. 20%, p=0.001). Non-Asians were more likely to have decompensated liver disease and had higher median Child-Turcotte-Pugh score (6 [5-11] vs. 7 [5-13], P ,0.0001). Asian patients were more likely to undergo liver-directed palliative therapy (46% vs. 28%) and much less likely to be listed for liver transplantation(20% vs. 48%) (P ,0.001), despite similar rates of meeting Milan criteria for liver transplantation (52 vs.58%, P=0.16). Overall, there was a trend for higher median survival rates in Asians compared to non-Asians (30 vs. 21 months, P=0.091). Among those who were listed for liver transplantation, there was no statistically significant difference in survival between Asians and non-Asians in the first 2 years (72% vs. 68%) but there was divergence with Asians having higher survival afterwards (61% vs. 51%) (Figure 1). However, among those undergoing liver-directed palliative therapy, Asians had significantly higher long-term survival compared to non-Asians (5-year survival: 28% vs. 10%, P,0.0001) (Figure 2). On multivariate Cox proportional hazards model also inclusive of age, sex, BCLC staging, Child-Pugh score, meeting Milan criteria, liver transplantation listing, non-Asian ethnicity was an independent predictor for lower overall survival (HR=0.70 [0.52-0.86]). CONCLUSIONS: Despite being older and having a lower rate of liver transplantation listing, Asian HCV/HCC patients had higher median survival compared to non-Asian patients, particularly among those undergoing palliative therapy. Non-Asians were more likely to have decompensated liver disease and non-Asian ethnicity was an independent predictor for poorer long-term survival. Compared to non-Asians, Asians with HCV-related HCCwere also muchmore likely to have delayed HCV diagnosis. Improved strategies in HCV screening in Asians are needed as it may lead to earlier diagnosis and treatment of HCV infection and possible prevention of HCC development in this ethnic population with a disproportionate HCC disease burden.