Debra Guss

Clinical efficacy and tolerability of direct-acting antivirals in elderly patients with chronic hepatitis C

Background There is a lack of evidence-based data on aged patients with newer direct-acting antivirals (DAAs) and with shorter duration of treatment regimens involving DAAs with or without ribavirin (RBV) and pegylated interferon (Peg IFN). Patients and methods Medical records of 240 patients treated with DAAs with or without Peg IFN and RBV between January 2013 and July 2015 were retrospectively analyzed. Patients were divided into two groups: patients aged 65 years and older (N=84) and patients aged younger than 65 years (N=156). Pretreatment baseline patient characteristics, treatment efficacy, factors affecting sustained virologic response at 12 weeks after treatment, and adverse reactions were compared between the groups. Results No statistically significant difference was observed with end of treatment response (98.8 vs. 98%, P=0.667) and sustained virologic response at 12 weeks after treatment (93.1 vs. 94.1%, P=0.767) between patients aged 65 and older and those younger than 65 years of age. Fatigue was the most common adverse event recorded (32.5%), followed by anemia (19.6%), leukopenia (11.7%), thrombocytopenia (10%), skin rash (8.3%), and headache (7.9%). The RBV dose was reduced in eight (8%) patients and four patients discontinued the RBV treatment because of severe anemia. RBV dose reduction or discontinuation did not reach statistical significance (P=0.913). Increased fibrosis, cirrhosis, aspartate aminotransferase, alanine aminotransferase, hemoglobin, and platelet levels seem to affect the sustained virologic response in the elderly. Twelve (6.28%) patients failed to respond to treatment and the failure rate was not significant (P=0.767) between the groups. Conclusion DAAs with or without IFN and RBV in the standard recommended 12 or 24-week treatment regimens are effective, well tolerated, and may be safely extended to elderly patients infected with chronic hepatitis C.

Seronegative Autoimmune Hepatitis A Clinically Challenging Difficult Diagnosis

Autoimmune hepatitis (AIH) is a complex liver disease of unknown cause which results in immune-mediated liver injury with varied clinical presentations. Seronegative AIH follows a similar course to autoantibody-positive disease and diagnosis may be challenging. There are no single serologic tests of sufficient diagnostic specificity, and delay in appropriate treatment may lead to progression of the liver disease and liver failure. The revised conventional diagnostic criteria (RDC) scoring for AIH is complex and not routinely used in the clinical practice. The more recent simplified diagnostic criteria (SDC) scoring proposed by International Autoimmune Hepatitis Group in 2008 has wider application in routine practice facilitating the diagnosis of AIH with a specificity and sensitivity of ~90%. In this report, we describe a case of seronegative autoimmune hepatitis diagnosed using RDC. SDC score calculated in our case was 4 and was not diagnostic for AIH. We subsequently used the complex revised diagnostic criteria for definitive diagnosis. Some of the patients previously diagnosed as cryptogenic active hepatitis of unknown etiology probably had an unrecognized diagnosis of seronegative autoimmune hepatitis. SDC scoring may not be applicable in patients with seronegative autoimmune hepatitis. These patients should be reassessed by using RDC.

Glycogenic hepatopathy: A narrative review

Glycogenic hepatopathy (GH) is a rare complication of the poorly controlled diabetes mellitus characterized by the transient liver dysfunction with elevated liver enzymes and associated hepatomegaly caused by the reversible accumulation of excess glycogen in the hepatocytes. It is predominantly seen in patients with longstanding type 1 diabetes mellitus and rarely reported in association with type 2 diabetes mellitus. Although it was first observed in the pediatric population, since then, it has been reported in adolescents and adults with or without ketoacidosis. The association of GH with hyperglycemia in diabetes has not been well established. One of the essential elements in the pathophysiology of development of GH is the wide fluctuation in both glucose and insulin levels. GH and non-alcoholic fatty liver disease (NAFLD) are clinically indistinguishable, and latter is more prevalent in diabetic patients and can progress to advanced liver disease and cirrhosis. Gradient dual-echo MRI can distinguish GH from NAFLD; however, GH can reliably be diagnosed only by liver biopsy. Adequate glycemic control can result in complete remission of clinical, laboratory and histological abnormalities. There has been a recent report of varying degree of liver fibrosis identified in patients with GH. Future studies are required to understand the biochemical defects underlying GH, noninvasive, rapid diagnostic tests for GH, and to assess the consequence of the fibrosis identified as severe fibrosis may progress to cirrhosis. Awareness of this entity in the medical community including specialists is low. Here we briefly reviewed the English literature on pathogenesis involved, recent progress in the evaluation, differential diagnosis, and management.

Direct-Acting Antivirals in Chronic Hepatitis C Genotype 4 Infection in Community Care Setting

Background Limited data exists comparing the safety, tolerability, and efficacy of direct-acting antivirals (DAAs) in patients with chronic hepatitis C genotype 4 (HCV GT-4) in the community practice setting. We aim to evaluate the treatment response of DAAs in these patients. Methods All the HCV GT-4 patients treated with DAAs between January 2014 and October 2017 in a community clinic setting were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy with sustained virologic response (SVR) at 12 weeks post treatment (SVR12), and adverse reactions were assessed. Results Fifty-two patients of Middle Eastern (primarily Egyptian) descent were included in the study. Thirty-two patients were treated with ledipasvir/sofosbuvir (Harvoni®) ± ribavirin, 12 patients were treated with ombitasvir/paritaprevir/ritonavir/dasabuvir (ViekiraPak®) ± ribavirin, and eight patients were treated with sofosbuvir/Velpatasvir (Epclusa®). Ten patients (19.2%) had compensated cirrhosis. Overall, SVR at 12 weeks was achieved in 94% in patients who received one of the three DAA regimens (93.8% in Harvoni® group, 91.7 % in ViekiraPak® group and 100% in Epclusa® group). Prior treatment status and type of regimen used in the presence of compensated cirrhosis had no statistical significance on overall SVR achievement (P value = 0.442 and P value = 0.091, respectively). The most common adverse effect was fatigue (27%). Conclusions In the real-world setting, DAAs are effective and well tolerated in patients with chronic HCV GT-4 infection with a high overall SVR rate of 94%. Large-scale studies are needed to further assess this SVR in these groups.

Missed Diagnosis of Liver Cirrhosis Leads to Disparities in Care for Older Patients

Background Cirrhosis of the liver is often not recognized until late in the disease state, when patients decompensate or develop hepatocellular carcinoma (HCC). This inquiry considered factors associated with undiagnosed cirrhosis. Methods Patients with undiagnosed cirrhosis were compared to patients with known diagnosis of cirrhosis, to evaluate the differences between these two groups. The study population is patients with confirmed diagnosis of HCC, stratified into patients with known diagnosis of cirrhosis (n = 36) and patients without the known diagnosis of cirrhosis who have features of cirrhosis (n = 36). Results There was no significant difference in insurance, gender, race, etiology of liver disease, presence of splenomegaly, model for end stage liver disease (MELD) score, fibrosis-4 index (FIB-4) or aspartate aminotransferase (AST) to platelet ratio index (APRI) scores between groups. However, the strongest predictor of the diagnosis of cirrhosis was age, with older patients being less likely to be diagnosed with cirrhosis (OR: 0.924, P = 0.012). Furthermore, tumor size in patients without known cirrhosis was larger than those diagnosed with cirrhosis (median: 4.9 cm versus 3.5 cm, P = 0.015). Of note, 50% of cases with cirrhosis were undiagnosed. Conclusion Older age was the most significant predictor of the missed diagnosis of liver cirrhosis. This led to a larger tumor size at diagnosis, which may imply worse prognosis in these patients. Further evaluation of health disparities related to older age and outcomes of older patients with liver cirrhosis should guide the development of guidelines to prevent the missed diagnosis of cirrhosis.

An Unusual Presentation of Glycogenic Hepatopathy with Bridging Fibrosis

Glycogenic hepatopathy is a rare and under-recognized complication of poorly controlled diabetes mellitus. We report a patient who presented with predominant elevation in alkaline phosphatase and liver biopsy showing bridging fibrosis, which is an unusual presentation of glycogenic hepatopathy. This case emphasizes the fact that glycogenic hepatopathy can also present with a cholestatic pattern of liver abnormality and with liver fibrosis, which warrants further study because severe fibrosis can progress to cirrhosis.

Integrative review: patient and provider factors related to hepatocellular carcinoma surveillance in patients with liver cirrhosis

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and the fifth most prevalent cancer worldwide, with cirrhosis being the main risk factor for the development of HCC. The American Association for Study of Liver Disease (AASLD) recommends surveillance of patients with cirrhosis for HCC using ultrasound (US) of the abdomen every 6 months as a cost-effective intervention to reduce mortality and improve survival. However, it is widely known that surveillance is not consistently completed, and the rates of HCC surveillance are very low. The purpose of this integrative review was to evaluate and summarize the available data related to provider and patient factors that are associated with surveillance and missed surveillance for HCC in patients with cirrhosis of the liver, and to recommend interventions to improve these rates of surveillance and subsequently improving survival in patients with cirrhosis.

Gut microbia dysbiosis in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) represents the spectrum of fatty liver that ranges from simple steatosis to steatohepatitis leading to fibrosis and cirrhosis. NAFLD is often considered the hepatic manifestation of metabolic syndrome and it is closely associated with diabetes, insulin resistance and obesity. Prevalence of NAFLD ranges from 10–35% and the differences in prevalence are due to differences in diagnostic methods used to diagnose NAFLD, as well as differences in NAFLD prevalence amongst various ethnic groups. However, the progression of non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatits (NASH) is seen in 3–5% of the population, and this subgroup is at a high risk of progression to advanced fibrosis including cirrhosis and hepatocellular carcinoma (HCC) (1,2).

Liraglutide’s use in treatment of non-alcoholic fatty liver: an evaluation of the non-alcoholic steatohepatitis study

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver related morbidity and mortality and also is the second most common cause of liver transplantation in the United States (1).