Characterization of Patients with COVID-19 Admitted to a Community Hospital of East Harlem in New York City.

Background New York City was the epicenter for the coronavirus disease 2019 (COVID-19) in the United States. Accordingly, the aim of this study was to characterize the population of patients admitted with this condition to a community hospital in East Harlem located in the northeast part of the city. Methods A retrospective review of medical records of patients at least 18 years of age, admitted to the hospital with COVID-19 disease from March 14 to April 30 of 2020. Results Three hundred and seventy-one patients were identified. The majority was comprised of men. Obesity, hypertension, and hyperlipidemia were the most prevalent comorbidities. Most patients were treated with a combination of hydroxychloroquine, azithromycin, zinc, and vitamin C. Twenty-three percent of the patients died from the disease during the study period. Conclusion Morbidity and mortality were substantial in patients with COVID-19 admitted to a community hospital in East Harlem.

Elevated serum alkaline phosphatase · generalized pruritus · Dx?

A 34-year-old woman was referred to the hepatology clinic for evaluation of an increased serum alkaline phosphatase (ALP) level. She was gravida 5 and in her 38th week of gestation. Her obstetric history was significant for 2 uncomplicated spontaneous term vaginal deliveries resulting in live births and 2 spontaneous abortions. The patient reported generalized pruritus for 2 months prior to the visit. She had no comorbidities and denied any other symptoms. She reported no family history of liver disease or complications during pregnancy in relatives. The patient did not smoke or drink, and had come to our hospital for her prenatal care visits. The physical exam revealed normal vital signs, no jaundice, a gravid uterus, and acanthosis nigricans on the neck and axilla with scattered excoriations on the arms, legs, and abdomen. Her serum ALP level was 1093 U/L (normal: 50-136 U/L). Immediately before this pregnancy, her serum ALP had been normal at 95 U/L, but it had since been increasing with a peak value of 1134 U/L by 37 weeks' gestation. Serum transaminase activities and albumin and bilirubin concentrations were normal, as was her prothrombin time. The rest of her lab tests were also normal, including her fasting serum bile acid concentration, which was 9 mcmol/L (normal: 4.5-19.2 mcmol/L).

The pruritus of cholestasis: From bile acids to opiate agonists: Relevant after all these years.

The pruritus of cholestasis is a maddening complication of liver disease. Increased opioidergic tone contributes to the pruritus of cholestasis, as evidenced by the amelioration of the symptom by opiate antagonists. Obeticholic acid, an agonist of the farnesoid receptor, has been approved for the treatment of primary biliary cholangitis, a disease characterized by cholestasis; this drug is associated with pruritus, the cause of which is unknown. In animal models, bile acids, which accumulate in the body as a result of cholestasis, have been reported to cause scratching behavior mediated by the TGR5 receptor, in an opioid-dependent manner, in laboratory animals. As obeticholic acid also binds to TGR5, the pruritus caused by this drug is likely to be mediated by the opioid system. Lisophosphatidic acid, which has been reported to be increased in patients with cholestasis and pruritus, has been described to cause scratching behavior that is prevented by an opiate antagonist in laboratory animals, suggesting an opioid-receptor mediated mechanism of scratching. In summary, evidence continues to support a role of the endogenous opioid system in the pathogenesis of the pruritus of cholestasis.

Assessment of the Visual Analogue Score in the Evaluation of the Pruritus of Cholestasis.

Background and Aims: A visual analogue score (VAS), based on application of a visual analogue scale, has been widely used to assess pruritus in clinical studies of patients with cholestatic liver disease. A VAS is a numerical score of the severity of the perception of pruritus, and, hence, is inherently subjective. The objective of this study was to assess the reliability of a VAS as an index of pruritus in cholestatic patients. Methods: In 8 patients with chronic pruritus due to primary biliary cholangitis, values for a VAS of pruritus were compared with corresponding measurements of scratching activity, which were generated by a monitoring system specifically designed to quantitate this activity. The relationship between individual values for the VAS and corresponding values for scratching activity during a specific interval immediately preceding the recording of the VAS was examined by determining the Spearman's rank correlation coefficient. Results: The mean Spearman's rank correlation coefficient between individual values for the VAS and corresponding mean values for scratching activity was 0.072; the range of these coefficients was -0.04 to 0.26. A VAS of pruritus is an unreliable index of scratching activity, and, hence, of the pathophysiological process responsible for the pruritus of cholestasis. Conclusions: It is concluded that the use of a VAS as a primary quantitative endpoint in trials of the efficacy of potential therapies for the pruritus of cholestasis may be inappropriate.

Hepatocellular carcinoma in a patient with chronic lymphocytic leukaemia involving the liver.

A relationship between hepatocellular carcinoma and chronic lymphocytic leukaemia has been reported. This is a case of a 75-year-old woman with stable chronic lymphocytic leukaemia, not on treatment with an increased activity of serum alkaline phosphatase and negative liver disease work up. A liver biopsy revealed leukaemic infiltration without evidence of cirrhosis or fatty liver. Four years later, she presented with a rapidly progressive liver mass which was diagnosed as hepatocellular carcinoma histologically.

Acute cytomegalovirus hepatitis in an immunocompetent host.

A 52-year-old woman presented with a 1-week history of recurrent fevers and joint pains accompanied by abdominal and low back discomfort. She has a history of hypoparathyroidism and is on calcium supplements. Physical examination revealed fever and tachycardia. The rest of the examination was normal. Laboratory tests showed newly increased transaminase activity. Serum bilirubin and prothrombin time were normal. She was admitted for evaluation of acute hepatitis. Serology for hepatitis A, B, C and HIV were negative. Her serum acetaminophen and alcohol were undetected. Abdominal imaging was normal. Cultures were sterile. Additional tests for uncommon viral hepatitis included herpes simplex virus, cytomegalovirus and Epstein-Barr virus. Liver biopsy revealed non-specific inflammation. Subsequently, cytomegalovirus serology showed an IgM positive and negative IgG titre. Cytomegalovirus DNA qualitative PCR was also positive. No antiviral medication was given. She continued to have intermittent daily fever but reported no associated symptoms. She was discharged 9 days after admission in stable condition per her request with the advice to follow-up in the clinic in 1 week. Her serum hepatic profile returned to normal and she reported no more episodes of fever. Repeated titres of cytomegalovirus serology showed seroconversion.

Sleep-Wake profiles in patients with primary biliary cirrhosis.

BACKGROUND: Impaired sleep quality and daytime sleepiness have been described in patients with primary biliary cirrhosis (PBC). However, no information is available on their sleep timing/diurnal preference. AIMS: To evaluate such variables and determine their relationship with sleep quality, fatigue, pruritus and quality of life. METHODS: Seventy-four patients with PBC (58 ± 12 years), 79 healthy volunteers (56 ± 8 years) and 60 patients with cirrhosis (58 ± 12 years) underwent formal assessment of sleep quality/timing, diurnal preference and daytime sleepiness. Patients with PBC also underwent assessment of fatigue, quality of life and the daytime course of sleepiness/pruritus. RESULTS: Sleep timing was significantly delayed in both patients with PBC and with cirrhosis, compared to healthy volunteers (sleep onset time: 23:18 ± 01:00 vs. 23:30 ± 01:00 vs. 22:54 ± 00:54 hours, respectively; P < 0.05). In patients with PBC, delayed sleep timing was associated with impaired sleep quality (P < 0.05). Sleepiness showed a physiological daily rhythm, with early afternoon/evening peaks. Pruritus was absent in the morning and increased over the afternoon/evening hours. Both the daytime course of pruritus and sleepiness changed in relation to diurnal preference. Patients with PBC and significant pruritus (upper quartile) had prolonged sleep latency (39 ± 37 vs. 21 ± 23 min, P = 0.05) and earlier wake-up times (5.9 ± 0.8 vs. 6.7 ± 0.9 min, P < 0.05). Significant correlations were observed between sleep timing and quality of life. CONCLUSIONS: Patients with PBC exhibited a delay in sleep timing that was associated with impaired sleep quality/quality of life. In addition, an interplay was observed between diurnal preference and the daytime course of pruritus/sleepiness.

Hepatic Methionine-enkephalin may interfere with response to antiviral therapy in chronic hepatitis C.

BACKGROUND: The immunoreactivity of methionine-enkephalin (Met-enkephalin), one of the endogenous opioid peptides, is expressed in the liver in different types of chronic diseases. This finding suggests that the liver may be a source of endogenous opioids in disease state. In-vitro studies have shown that morphine, which exerts its effect by binding to opioid receptors, enhances hepatitis C virus replication and that it interferes with the antiviral effects of interferon. Thus, it was hypothesized that liver-derived endogenous opioids, which also bind to opioid receptors, may interfere with the response to antiviral therapy with interferon. AIM: To correlate the expression of Met-enkephalin immunoreactivity (MEIR) in the liver of patients with chronic hepatitis C with their response to treatment with pegylated interferon and ribavirin. METHODS: We sought to investigate the expression of the immunoreactivities of Met-enkephalin and of the δ-opioid receptor 1 (DOR1), to which Met-enkephalin binds, preferentially, in liver samples from 23 patients with chronic hepatitis C who had undergone antiviral therapy. Twelve patients obtained a sustained virological response, and 11 patients were relapsers after or nonresponders to treatment. Among the 12 patients with sustained virological response, one patient (8.3%) expressed MEIR and another one expressed DOR1 immunoreactivity (8.3%), whereas none of the patients expressed both immunoreactivities. Among the group of nonresponders/relapsers, one patient expressed MEIR (9%), two patients expressed DOR1 immunoreactivity (18.2%), and seven patients expressed both (63.6%). The difference between responders and nonresponders in the expression of both immunoreactivities was significantly different (P<0.001). CONCLUSION: Our data are in favor of the hypothesis that enhanced expression of MEIR and DOR1 immunoreactivity correlates with poor response to antiviral therapy that includes interferon. Thus, this study provides a rationale to study the effect of opiate antagonists in combination with antiviral therapy with interferon and ribavirin in patients who express MEIR in the liver and who have not responded to or who have relapsed after treatment with those antiviral medications.

The itch of liver disease.

Itch is a complication of liver disease. It is hypothesized that this type of itch is mediated, at least in part, by increased central opioidergic tone; a peripheral component may coexist. The role of serotonin, bile acids, substance P, and lipophosphatidic acid and the activity of the enzyme that generates it, autotoxin, has been proposed in the pathogenesis of itch. Scratching activity was significantly suppressed in association with the placebo tablet in a controlled, double-blind study; this finding supports the exploration of the placebo effect on the itch sensation and the inclusion of behavioral methodology in clinical trials in patients with this complication of liver disease.

Serum concentrations of substance P in cholestasis.

Substance P (SP) is an excitatory neuropeptide that acts via the neurokinin-1 receptor (NK-1) in the nervous system. Pruritus, a complication of cholestasis, is a nociceptive stimulus; thus, we hypothesized that cholestasis would be associated with increased neurotransmission via SP as evidenced, in part, by increased serum concentrations of this neuropeptide. Accordingly, the aim of this study was to determine the serum concentration of SP in patients with pruritus secondary to cholestasis and in the serum of rats with cholestasis secondary to bile duct resection (BDR). The mean serum SP concentration of patients with chronic liver disease (CLD) and pruritus was 9.09 pg/mL SD +/- 6.5, significantly higher than 0.74 pg/mL SD +/- 0.77, the mean serum concentration of SP from patients with CLD without pruritus (p = 0.0001), and from that of the control group, which was 0.65 pg/mL SD +/- 0.37 (p = 0.0001). The mean serum SP concentration from six rats with cholestasis secondary to BDR six and fourteen days after surgery was 57.9 pg/mL, SD +/- 17.3, and 56.3 pg/mL, SD +/- 21.4, respectively, as compared to the concentration from the sham resected control group, which was 3.5 pg/mL SD +/- 0.59 (p = 0.002) at six days post surgery. In conclusion, in cholestasis, there is increased availability of SP. These data provide a rationale for the study of SP release and metabolism in cholestasis, and in the mediation of the pruritus.

Hepatic expression of endocannabinoid receptors and their novel polymorphisms in primary biliary cirrhosis.

BACKGROUND: The endocannabinoid system (EC) has emerged as a crucial mediator in a variety of pathophysiological conditions. AIMS: To evaluate: (1) whether the EC system is activated in the livers of patients with primary biliary cirrhosis (PBC); (2) if genetic variations in human EC receptor genes (CB1 and CB2) may be associated with a different phenotypic expression of the disease and response to therapy. METHODS: The expression of CB1 and CB2 receptors was studied by immunohistochemistry in liver biopsy specimens from 13 patients with PBC, and CB1 and CB2 mRNA expression was studied by real-time polymerase chain reaction testing (RT-PCR) in liver samples. In addition, genetic polymorphisms in the EC receptor gene were sought in 68 patients with PBC from Italy, 84 patients who were residents of the United States (US), and 70 controls matched for sex, age, and for geographical area with the Italian PBC patients. Genomic DNA was extracted from peripheral venous blood leucocytes with standard methods. PCR was used to amplify the coding regions of the CB1 and CB2 genes with specific primers. RESULTS: CB1 was markedly expressed in hepatocytes and biliary epithelial cells in the livers of patients with PBC; conversely in control liver samples, it was virtually absent. CB2 was expressed in hepatocytes and in cholangiocytes, whereas it was absent from mesenchymal cells. The mRNA of both CB1 and CB2 was detected in the PBC liver samples, as demonstrated by RT-PCR. The CB1 polymorphism (1359 G/A) was present in 26.5% of Italian patients, in 22.9% of healthy controls, and in 27.4% of patients from the US (p = n.s.). The CB2 polymorphism (188-189 AA/GG) was present in 24.4 versus 30.4% of Italian and US patients with PBC, respectively, and in 28.0% of Italian controls samples (p = n.s.). Logistic regression analysis showed that advanced histological stage and the lack of response to ursodeoxycholic acid treatment were significantly correlated with the CB1 polymorphism. CONCLUSIONS: The EC system is markedly up-regulated in the livers of patients with PBC and it may exert a role regulating adaptive mechanisms in cholestasis.

Prevalence of hepatitis C virus infection in patients with cardiomyopathy.

Chronic hepatitis C can be associated with extrahepatic manifestations; thus, we explored the association of this viral infection with dilated cardiomyopathy in a group of sixty-three patients with a cardiac ejection fraction of less than 40% determined by an echocardiogram in a prospective study. Two of the forty-one patients with non-ischemic cardiomyopathy (4.8%) had serum antibodies to the hepatitis C virus and one of those had hepatitis C virus RNA (2.4%) in serum, consistent with chronic hepatitis C. One of the 22 patients with ischemic cardiomyopathy (4.5%) had serum antibodies to the hepatitis C virus but the hepatitis C virus RNA was not detected in their serum, consistent with prior infection but not chronic hepatitis C. In this study, chronic hepatitis C was not prevalent in the group of patients, although the only patient with chronic hepatitis C had non-ischemic cardiomyopathy. As a genetic predisposition to develop cardiomyopathy secondary to chronic hepatitis C has been suggested to be relevant in this type of complication, studies that include different racial and ethnic groups are warranted, as treatment of the hepatitis may lead to resolution of the cardiomyopathy.