https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.20701

Design and validation of a histological scoring system for nonalcoholic fatty liver disease

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.29367

The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases.

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Between the 1960s and 1980s, most life scientists focused their attention on studies of nucleic acids and the translation of the coded information. Protein degradation was a neglected area, conside...

The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.

The external pernicious influences of wind and dampness cause liver Qi to stagnate, and excess damp heat in liver and weakness of spleen Qi result. — From the teachings of traditional Chinese medic...

Hepatitis B e Antigen--the dangerous endgame of hepatitis B.

(See the editorial commentary by Tillmann on pages 6–8.)

Hepatitis C virus (HCV) infection affects 180 million persons worldwide and at least 3.2 million in the United States [1, 2]. It is one of the main causes of progressive liver diseases, such as cirrhosis and hepatocellular carcinoma, and the leading indication for liver transplantation [3]. Combination therapy of pegylated interferon and ribavirin is successful in approximately 50% of infected patients, resulting in clearance of HCV RNA from serum, which is accompanied by normalization of liver biochemical test results and improvement of liver histologic findings [4, 5]. A sustained virological response (SVR) is defined as the absence of detectable HCV RNA as measured by a sensitive reverse-transcription polymerase chain reaction (RT-PCR) at least 24 weeks after termination of treatment [4]. The majority of patients who have a SVR have resolution of their liver disease biochemically and histologically. These characteristics have led to the acceptance of a SVR as an appropriate end point of antiviral therapy for chronic hepatitis C.

Several groups have examined the durability of a SVR in patients with chronic hepatitis C after treatment [6–10]. SVR is maintained in almost all patients and is associated with long-term good prognosis. However, long-term follow up has indicated that relapse of infection, defined as detection of HCV RNA in serum, can occur, although at a rates of 24 weeks after stopping therapy) occurred in 4.2% [12]. These findings raise the issue of whether a sustained response to therapy results in permanent eradication of the virus and cure of the infection, as opposed to long-term suppression of viral replication maintained by immunological factors.

There are few data in the literature regarding the relapse of HCV infection in patients with resolved infection. Most reports are anecdotal and have not rigorously explored the nature of the virus in individuals with apparent reinfection. It is unclear whether these patients have true relapse and are persistently infected with the same HCV strain as before treatment or whether they have been reinfected with a completely novel HCV strain. To address this question, we analyzed HCV RNA sequences in specimens from 3 patients in whom HCV RNA was redetected in serum (by commercial assays) after they had achieved a SVR, and we compared the RNA sequences of HCV recovered during late relapse with those of HCV recovered from serum before treatment. In this article, these patients are referred to as “patients with late relapse” because HCV infection reappeared >6 months after termination of therapy and because it was unknown whether they had relapse or reinfection. Additionally, RNA was extracted from liver biopsy specimens obtained from these patients at the time they achieved a SVR to determine whether the liver was a reservoir for HCV in patients with a SVR.

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Sequence Analysis of Hepatitis C Virus From Patients With Relapse After a Sustained Virological Response: Relapse or Reinfection?

Replication of nearly all RNA viruses depends on a virus-encoded RNA-dependent RNA polymerase (RdRp). Our earlier work found that purified recombinant hepatitis C virus (HCV) RdRp (NS5B) was able to initiate RNA synthesis de novo by using purine (A and G) but not pyrimidine (C and U) nucleotides (G. Luo et al., J. Virol. 74:851-863, 2000). For most human RNA viruses, the initiation nucleotides of both positive- and negative-strand RNAs were found to be either an adenylate (A) or guanylate (G). To determine the nucleotide used for initiation and control of HCV RNA replication, a genetic mutagenesis analysis of the nucleotides at the very 5' and 3' ends of HCV RNAs was performed by using a cell-based HCV replicon replication system. Either a G or an A at the 5' end of HCV genomic RNA was able to efficiently induce cell colony formation, whereas a nucleotide C at the 5' end dramatically reduced the efficiency of cell colony formation. Likewise, the 3'-end nucleotide U-to-C mutation did not significantly affect the efficiency of cell colony formation. In contrast, a U-to-G mutation at the 3' end caused a remarkable decrease in cell colony formation, and a U-to-A mutation resulted in a complete abolition of cell colony formation. Sequence analysis of the HCV replicon RNAs recovered from G418-resistant Huh7 cells revealed several interesting findings. First, the 5'-end nucleotide G of the replicon RNA was changed to an A upon multiple rounds of replication. Second, the nucleotide A at the 5' end was stably maintained among all replicon RNAs isolated from Huh7 cells transfected with an RNA with a 5'-end A. Third, initiation of HCV RNA replication with a CTP resulted in a >10-fold reduction in the levels of HCV RNAs, suggesting that initiation of RNA replication with CTP was very inefficient. Fourth, the 3'-end nucleotide U-to-C and -G mutations were all reverted back to a wild-type nucleotide U. In addition, extra U and UU residues were identified at the 3' ends of revertants recovered from Huh7 cells transfected with an RNA with a nucleotide G at the 3' end. We also determined the 5'-end nucleotide of positive-strand RNA of some clinical HCV isolates. Either G or A was identified at the 5' end of HCV RNA genome depending on the specific HCV isolate. Collectively, these findings demonstrate that replication of positive-strand HCV RNA was preferentially initiated with purine nucleotides (ATP and GTP), whereas the negative-strand HCV RNA replication is invariably initiated with an ATP.

Effects of mutations of the initiation nucleotides on hepatitis C virus RNA replication in the cell.

Nat. Med. 11, 791–796 (2005) The chimpanzee used in this study is referred to as X0215 in several parts of the text and supplementary information. Its correct number is X0205.

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Corrigendum: Production of infectious hepatitis C virus in tissue culture from a cloned viral genome

The search for the ultimate screening test for hepatocellular carcinoma continues. Sato Y, Nakata K, Kato Y, Shima M, Ishii N, Koji T, Taketa K, Endo Y, Nagataki S. Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. N Engl J Med 1993;328: 1802-1806

T. Jake Liang

Papers

Hepatitis B e Antigen--the dangerous endgame of hepatitis B.

Sequence Analysis of Hepatitis C Virus From Patients With Relapse After a Sustained Virological Response: Relapse or Reinfection?

Effects of mutations of the initiation nucleotides on hepatitis C virus RNA replication in the cell.

Corrigendum: Production of infectious hepatitis C virus in tissue culture from a cloned viral genome

The search for the ultimate screening test for hepatocellular carcinoma continues. Sato Y, Nakata K, Kato Y, Shima M, Ishii N, Koji T, Taketa K, Endo Y, Nagataki S. Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. N Engl J Med 1993;328: 1802-1806