Mohamed G. Shoreibah

Management of hepatocellular carcinoma

AbstractPurpose Hepatocellular carcinoma (HCC), a common cause for cancer-related death, is increasing worldwide. Over the past decade, survival and quality of life of HCC patients have significantly improved due to better prevention strategies, early diagnosis, and improved treatment options. We performed this narrative review to synthesize current status on the HCC management.MethodsLiterature search for publications especially over the last decade, which has changed the paradigm on the management of HCC.ResultsHepatitis B vaccination and treatment of chronic hepatitis B and C are important measures for HCC prevention. Screening and surveillance for HCC using ultrasonogram and alpha-fetoprotein estimation are directed toward cirrhotics and hepatitis B patients at high risk of HCC. If detected at an early stage, curative treatments for HCC can be used such as tumor resection, ablation and liver transplantation. HCC patients without curative options are managed by loco-regional therapies and systemic chemotherapy. Loco-regional treatments include trans-arterial chemoembolization, radioembolization and combinations of loco-regional plus systemic therapies. Currently, sorafenib is the only FDA-approved systemic therapy and newer better chemotherapeutic agents are being investigated. Palliative care for terminally ill patients with metastatic disease and/or poor functional status focusses on comfort care and symptom control.ConclusionsIn spite of significant advancement in HCC management, its incidence continues to rise. There remains an urgent need to continue refining understanding of HCC and develop strategies to increase utilization of the available preventive measures and curative treatment modalities for HCC.

Diabetes Mellitus Predicts Occurrence of Cirrhosis and Hepatocellular Cancer in Alcoholic Liver and Non-alcoholic Fatty Liver Diseases.

Background and Aims Alcohol abuse and nonalcoholic fatty liver disease (NAFLD) are common causes of liver disease. Diabetes mellitus (DM) is a common comorbidity among NAFLD patients. We performed this study with the specific aim to examine the impact of DM on progression of alcoholic liver disease (ALD) liver and NAFLD. Methods Medical charts of 480 patients with ALD or NAFLD (2004–2011) managed at a tertiary center were retrospectively reviewed. NAFLD was diagnosed based on exclusion of other causes of liver disease and alcohol use of <10 g/d. ALD was diagnosed based on alcohol use of >40 g/d in women or >60 g/d in men for >5 years. Results Of 480 patients (307 NAFLD), 200 diabetics differed from nondiabetics for: age (52±11 vs. 49±11 years; p=0.004); male gender (48% vs. 57%; p=0.03); metabolic syndrome (49% vs. 30%; p=0.0002); NAFLD (80% vs. 56%; p<0.0001); cirrhosis (70% vs. 59%; p=0.005); and hepatocellular carcinoma (HCC; 8% vs. 3%; p=0.009). Over a 3 year median follow-up period, diabetics relative to nondiabetics had a higher probability to develop cirrhosis (60% vs. 41%; p=0.022) and HCC (27% vs. 10%; p=0.045). There was a trend for increased development of hepatic encephalopathy in diabetics compared to nondiabetics (55% vs. 39%; p=0.053), and there was no difference between the two groups in survival or other liver disease complications. Conclusions DM increased risk for cirrhosis and HCC among patients with ALD and NAFLD. Prospective studies with longer follow-up periods are needed to examine the impact of DM on survival and the role of aggressive HCC screening in diabetic cirrhotics.

Nutritional status of patients with alcoholic cirrhosis undergoing liver transplantation: time trends and impact on survival

Alcoholic cirrhotics evaluated for liver transplantation are frequently malnourished or obese. We analyzed alcoholic cirrhotics undergoing transplantation to examine time trends of nutrition/weight, transplant outcome, and effects of concomitant hepatitis C virus (HCV) and/or hepatocellular carcinoma (HCC). Nutrition and transplant outcomes were reviewed for alcoholic cirrhosis with/without HCV/HCC. Malnutrition was defined by subjective global assessment. Body mass index (BMI) classified obesity. A total of 261 patients receiving transplants were separated (1988–2000, 2001–2006, and 2007–2011) to generate similar size cohorts. Mean BMI for the whole cohort was 28 ± 6 with 68% classified as overweight/obese. Mean BMI did not vary among cohorts and was not affected by HCV/HCC. While prevalence of malnutrition did not vary among cohorts, it was lower in patients with HCV/HCC (P < 0.01). One‐year graft/patient survival was 90% and not impacted by time period, HCV/HCC, or malnutrition after adjusting for demographics and model end‐stage liver disease (MELD). Alcoholic cirrhotics undergoing transplantation are malnourished yet frequently overweight/obese. Among patients selected for transplantation, 1‐year post‐transplant graft/patient survival is excellent, have not changed over time, and do not vary by nutrition/BMI. Our findings support feasibility of liver transplantation for alcoholic cirrhotics with obesity and malnutrition.

Alcoholic hepatitis and concomitant hepatitis C virus infection

Hepatitis C virus (HCV) infection and alcohol abuse are two most important causes of chronic liver disease in the United States. Alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active alcohol abuse with a potential for high short-term mortality. About 20% of patients presenting with alcoholic hepatitis have concomitant HCV infection. Mortality from alcoholic hepatitis is increased in the presence of concomitant hepatitis C due to synergistic interaction between HCV and alcohol in causing hepatocellular damage. Large prospective randomized studies are needed to develop guidelines on the use of corticosteroids among patients with alcoholic hepatitis and concomitant HCV infection. The impact of antiviral therapy on mortality and outcome in the setting of alcoholic hepatitis remains a novel area for future research.

Surveillance for hepatocellular carcinoma: evidence, guidelines and utilization.

T his review article addresses the controversy surrounding surveillance for hepatocellular carcinoma (HCC), regarding the survival benefit of surveillance and the adequacy of the currently available evidence. In addition to reviewing the surveillance guidelines recommended by the American Association for the Study of Liver Disease (AASLD), the article explores the evidence supporting the survival benefits of surveillance. Currently available surveillance methods, including ultrasound imaging and serum markers, and their limitations are outlined. We also examine the issue of underutilization of surveillance for HCC. Based on our review of literature for HCC surveillance, the main conclusions include surveillance with ultrasound every 6 months in patients at high risk of HCC, such as patients with cirrhosis and high-risk hepatitis B infected patients without cirrhosis, whereas the use of Alpha-fetoprotein (AFP) is not endorsed by the AASLD. The GLOBOCAN Report, published by the International Agency for Research on Cancer ranks liver cancer as the 5th most common cancer in men with a current incidence of 523,000 cases (7.9% of all cancer cases) and the 7th most common in women with a current incidence of 226,000 cases (6.5% of all cancer cases). Over 80% of the cases arise in Southeast Asia and sub-Saharan Africa. In terms of death from cancer worldwide, liver cancer ranks as No. 3 because of its high fatality. The incidence of HCC is decreasing in certain regions in Asia, including Hong Kong, Shanghai and Singapore, whereas it is on the rise in the United States and Canada. In the United States, 8,500 to 11,500 new cases of HCC are diagnosed per year. Although the mean age remains 65 years, there has been a shift toward a younger age of diagnosis of HCC. This shift has occurred in both genders and among different races and ethnicities. The male to female ratio is 3:1. There is controversy surrounding the adequacy of the evidence rationalizing HCC surveillance. The only seminal randomized controlled trial (RCT) that has been conducted in this realm is the study of Chinese patients with hepatitis B virus (HBV) infection by Zhang et al. There has not been any large population RCT with robust results in the West to mirror the results of this study. The debate extends to the limitations of the currently available screening methods. Last but not least is the issue of underutilization of surveillance for HCC. This review examines the evidence for survival benefit of HCC surveillance, describes the categories of high risk patients for whom surveillance is recommended and discusses the current surveillance methods and intervals recommended by the AASLD, and their temporal patterns of utilization.

Orthotopic liver transplantation changes the course of gastric antral vascular ectasia: a case series from a transplant center

Background and aim Gastric antral vascular ectasia (GAVE) is an important cause of upper gastrointestinal bleeding and anemia in patients with cirrhosis. The aim of our study was to evaluate the effect of orthotopic liver transplantation (OLT) on GAVE and associated anemia. Patients and methods We performed a chart review and identified all cirrhotic patients with GAVE who underwent OLT at the University Of Alabama at Birmingham between 2005 and 2013. Population’s demographics, etiology of cirrhosis, comorbidities, presentation and treatment modalities of GAVE, endoscopic and histopathologic reports, hemoglobin values before and after transplant, and immunosuppressive regimens were collected. Results Twelve patients were identified, mean age 52.4±4.4 years; seven were men (58.3%); 11 (91.7%) were White; and 6 of 12 patients had biopsy-proven GAVE. The most common etiology of cirrhosis in the cohort was chronic hepatitis C and obesity was the most common chronic condition in 50 and 83.3%, respectively. Anemia resolution was observed in 9/12 (75%) patients who underwent OLT with an increase in hemoglobin from 8.1±2.4 (5.7–13.1) before transplant to 12.0±1.4 (10–15) after transplant (P<0.0001). Esophagogastroduodenoscopy after transplant was performed in all 12 (100%) patients. The mean time between transplant and post-OLT esophagogastroduodenoscopy was 13.8±18.28 (2–57) months; complete resolution of GAVE was observed in 10 (83.3%) patients, with resolving GAVE in one (8.3%) patient. Conclusion GAVE is an important cause of anemia and upper gastrointestinal bleeding in patients with liver cirrhosis. Our findings show that liver transplantation can resolve GAVE and related anemia.

Alcoholic liver disease presents at advanced stage and progresses faster compared to non-alcoholic fatty liver diseas.

BACKGROUND AND OBJECTIVE Steatohepatitis is a common cause of liver disease due to alcohol (ALD) or non-alcoholic fatty liver disease (NAFLD). We performed this study to compare natural history of ALD and NAFLD. MATERIAL AND METHODS Retrospective analysis of ALD or NAFLD patients managed at our center (2007-2011). ALD diagnosed by excluding other liver diseases (except HCV) and alcohol abuse of > 40 g/d in women and > 60 g/d in men for > 5 years. NAFLD diagnosed by excluding other liver diseases and a history of alcohol use of < 10 g/d. Cirrhosis was diagnosed using biopsy for uncertain clinical diagnosis. RESULTS Compared to patients with NAFLD (n = 365; mean age 50 yrs; 43% males; 53% diabetic), ALD patients (n = 206; mean age 51 yrs; 68% males; 24% diabetic) presented more often with cirrhosis or complications(46vs. 12%; P< 0.0001) with a higher MELD score (13 ± 7 vs. 8 ± 8; P<0.0001). On logistic regression, ALD diagnosis was associated with presence of cirrhosis by over 4-fold (4.1 [1.8-9.1]) even after excluding 23 patients with concomitant HCV. Over median follow up of about 3 and 4 yrs among ALD and NAFLD patients respectively, ALD patients more frequently developed cirrhosis or its complications including HCC with worse transplant free survival (90 vs. 95%; P = 0.038). CONCLUSIONS Compared to NAFLD, ALD patients present at an advanced stage of liver disease with a faster progression on follow-up. Prospective multicenter studies are needed to identify potential barriers to early referral of ALD patients as basis for development of strategies to improve outcome of patients with ALD.BACKGROUND AND OBJECTIVE Steatohepatitis is a common cause of liver disease due to alcohol (ALD) or non-alcoholic fatty liver disease (NAFLD). We performed this study to compare natural history of ALD and NAFLD. MATERIAL AND METHODS Retrospective analysis of ALD or NAFLD patients managed at our center (2007-2011). ALD diagnosed by excluding other liver diseases (except HCV) and alcohol abuse of > 40 g/d in women and > 60 g/d in men for > 5 years. NAFLD diagnosed by excluding other liver diseases and a history of alcohol use of < 10 g/d. Cirrhosis was diagnosed using biopsy for uncertain clinical diagnosis. RESULTS Compared to patients with NAFLD (n = 365; mean age 50 yrs; 43% males; 53% diabetic), ALD patients (n = 206; mean age 51 yrs; 68% males; 24% diabetic) presented more often with cirrhosis or complications(46 vs. 12%; P< 0.0001) with a higher MELD score (13 ± 7 vs. 8 ± 8; P<0.0001). On logistic regression, ALD diagnosis was associated with presence of cirrhosis by over 4-fold (4.1 [1.8-9.1]) even after excluding 23 patients with concomitant HCV. Over median follow up of about 3 and 4 yrs among ALD and NAFLD patients respectively, ALD patients more frequently developed cirrhosis or its complications including HCC with worse transplant free survival (90 vs. 95%; P = 0.038). CONCLUSIONS Compared to NAFLD, ALD patients present at an advanced stage of liver disease with a faster progression on follow-up. Prospective multicenter studies are needed to identify potential barriers to early referral of ALD patients as basis for development of strategies to improve outcome of patients with ALD.

Short article: Alcohol and substance use, race, and insurance status predict nontreatment for hepatitis C virus in the era of direct acting antivirals

Objective Direct acting antivirals (DAAs) have overcome many long-standing medical barriers to hepatitis C virus (HCV) treatment (i.e. host characteristics and medical contraindications) and treatment outcome disparities that were associated with interferon regimens. The public health and clinical benefit of current and forthcoming DAA discoveries will be limited if efforts are not made to examine racial, psychological, and socioeconomic factors associated with being treated with DAAs. This study examined racial, psychological, and socioeconomic factors that facilitate and inhibit patients receiving DAAs for HCV. Patients and methods This was a single-center retrospective cohort study at a large urban tertiary center of patients (n=747) who were referred for evaluation and treatment of HCV. Results Sixty-eight percent of patients were non-Hispanic White, 31% were African American, and 1% were of other ethnicities. The majority of patients received treatment, but 29% (218/747) did not. Patients who were older [odds ratio (OR)=1.02, 95% confidence interval (CI): 1.01–1.04] and insured (OR=2.73, 95% CI: 1.12–6.97) were more likely to receive HCV treatment. Patients who were African American (OR=0.46, 95% CI: 0.46–1.06), used drugs (OR=0.09, 95% CI: 0.04–0.17), smoked (OR=0.55, 95% CI: 0.37–0.81), and used alcohol (OR=0.11, 95% CI: 0.06–0.20) were less likely to receive HCV treatment. Conclusion Though DAAs have eliminated many historically, long-standing medical barriers to HCV treatment, several racial, psychological and socioeconomic barriers, and disparities remain. Consequently, patients who are African American, uninsured, and actively use drugs and alcohol will suffer from increased HCV-related morbidity and mortality in the coming years if deliberate public health and clinical efforts are not made to facilitate access to DAAs.

Case series on multimodal endoscopic therapy for gastric antral vascular ectasia, a tertiary center experience

AIM To study and describe patients who underwent treatment for gastric antral vascular ectasia (GAVE) with different endoscopic treatment modalities. METHODS We reviewed patients with GAVE who underwent treatment at University of Alabama at Birmingham between March 1, 2012 and December 31, 2016. Included patients had an endoscopic diagnosis of GAVE with associated upper gastrointestinal bleeding or iron deficiency anemia. RESULTS Seven out of 15 patients had classic watermelon description for GAVE, 1/15 with diffuse/honeycomb pattern and 6/15 with nodular GAVE per EGD description. Seven out of 15 patients required multimodal treatment. Four out of six of patients with endoscopically nodular GAVE required multimodal therapy. Overall, mean pre- and post-treatment hemoglobin (Hb) values were 8.2 ± 0.8 g/dL and 9.7 ± 1.6 g/dL, respectively (P ≤ 0.05). Mean number of packed red blood cells transfusions before and after treatment was 3.8 ± 4.3 and 1.2 ± 1.7 (P ≤ 0.05), respectively. CONCLUSION Patients with nodular variant GAVE required multimodal approach more frequently than non-nodular variants. Patients responded well to multimodal therapy and saw decrease in transfusion rates and increase in Hb concentrations. Our findings suggest a multimodal approach may be beneficial in nodular variant GAVE.

Resolution of ascites and hepatic encephalopathy and absence of variceal bleeding in decompensated hepatitis C virus cirrhosis patients: Improvement in decompensated cirrhosis after direct-acting antiviral

The aims of this study were to examine changes in the proportion of decompensated hepatitis C virus (HCV) cirrhosis patients with ascites, hepatic encephalopathy, and variceal bleeding at pretreatment compared to 3 and 12 months post‐sustained virological response (SVR) and to compare pretreatment and post‐SVR model of end‐stage liver disease and Child‐Pugh scores and alpha‐fetoprotein levels.