The risk for HCC, liver decompensation, and death in patients with liver cirrhosis related to HCV was markedly reduced after SVR, but a long-term risk of developing HCC remains for up to 8 years. Cirrhotic patients with HCV who achieve SVR should therefore maintain long-term surveillance for HCC. Future studies aimed to better identify those with remaining long-term risk for HCC are needed.

Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes Coronavirus disease 2019 (COVID-19). This study aimed to determine if SARS-CoV-2 RNA in serum at admission correlated with clinical outcome in COVID-19. Methods COVID-19 patients admitted to the Infectious Diseases department of a tertiary level Swedish hospital, and sampled for SARS-CoV-2 RNA in serum at admission, April 10 to June 30 2020 were included in a cohort. Primary outcomes were day 28 all-cause mortality and progress to critical disease. Results The cohort (N=167) consisted of 106 SARS-CoV-2 RNA serum negative and 61 positive patients. Median sampling time for initial SARS-CoV-2 in serum was 1 (IQR 1-2) day after admission corresponding to day 10 (IQR 8-12) after symptom onset. Median ages were 53 (IQR 44-67) and 63 (IQR 52-74) years for the PCR-negative and positive patients, respectively. In the serum PCR negative and positive groups 3/106 and 15/61 patients died, respectively. The hazard ratios for critical disease and all-cause mortality were 7.2 (95% CI 3.0-17) and 8.6 (95% CI 2.4-30), respectively for patients that were serum PCR positive compared to serum PCR negative. Conclusion: SARS-CoV-2 RNA in serum at hospital admission indicates a high-risk of progression to critical disease and death.

Diabetes mellitus and cirrhosis are strong risk factors for HCC development after SVR has been achieved. The risk to develop HCC diminishes significantly 2 years after SVR. Patients without cirrhosis have a low risk to develop HCC after SVR, and the benefit of HCC surveillance for this group is questionable.

It has long been suggested that NO may inhibit an early stage in viral replication. Furthermore, in vitro tests have shown that NO inhibits the replication cycle of severe acute respiratory syndrome coronavirus. Despite smoking being listed as a risk factor to contract Covid-19, only a low proportion of the smokers suffered from SARS-corona infection in China 2003, and from Covid-19 in China, Europe and the US. We hypothesize, that the intermittent bursts of high NO concentration in cigarette smoke may be a mechanism in protecting against the virus. Mainstream smoke from cigarettes contains NO at peak concentrations of between about 250 ppm and 1350 ppm in each puff as compared to medicinal use of no more than 80 to a maximum of 160 ppm. The diffusion of NO through the cell wall to reach the virus should be significantly more effective at the very high NO concentration in the smoke, according to classic laws of physics. The only oxide of nitrogen in the mainstream smoke is NO, and the NO 2 concentration that is inhaled is very low or undetectable, and methemoglobin levels are lower in smokers than non-smokers, reasonably explained by the breaths of air in between the puffs that wash out the NO. Specialized iNO machines can now be developed to provide the drug intermittently in short bursts at high concentration dose, which would then provide both a preventative drug for those at high risk, as well as an effective treatment, without the health hazards associated with smoking.

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Background. Patients with recurrent Clostridium difficile infections (CDIs) constitute an increasing treatment problem. Fecal microbiota transplantation (FMT) has shown promising results of treating recurrent CDI, where treatment with antibiotics fails repeatedly. Our study describes retrospective cohort treated with FMT at two major hospitals in Stockholm. Methods. Medical records of all patients with recurrent CDI treated with FMT during the period 2013–2017 were reviewed. We evaluated cure of CDI-related diarrhea without relapse 10 weeks after FMT. Results. 47 patients were included. One treatment cured 25 patients (53%), and more than one treatment cured 32 patients (68%). Treatment outcome did not vary significantly with treatment with fresh donor feces or frozen fecal culture, days of use of antibiotics or days of hospitalization prior to CDI, and renal function or time from the first CDI to therapy. Treatment failure was associated with a significantly lower Karnofsky performance status score (70 points vs 90, p=0.02). Conclusion. Fecal instillation, for the treatment of relapsing CDI, is a promising approach, with 68% success rate reported in this study. The success rate of FMT is high, regardless of multiple comorbidities, extended use of antibiotics, or long time hospitalization. Although generally FMT is performed with fresh donor feces, our data show that the usage of frozen fecal culture could be an effective treatment alternative in recurrent CDI.

Summary Background A sustained viral response (SVR) after interferon‐based therapy of chronic hepatitis C virus (HCV) infection is regarded to represent a cure. Previous studies have used different markers to clarify whether an SVR truly represents a cure, but no study has combined a clinical work‐up with highly sensitive HCV RNA detection, and the determination of immune responses. Aim To determine clinical, histological, virological and immunological markers 5–20 years after SVR. Methods In 54 patients, liver biochemistry, histology and elastography were evaluated. Liver biopsies, plasma and peripheral blood mononuclear cells (PBMCs) were tested for minute amounts of HCV RNA. HCV‐specific T‐cell responses were monitored by ELISpot and pentamer staining, and humoral responses by measuring HCV nonstructural (NS)3‐specific antibodies and virus neutralisation. Results Liver disease regressed significantly in all patients, and 51 were HCV RNA‐negative in all tissues tested. There was an inverse association between liver disease, HCV‐specific T‐cell responses and HCV antibody levels with time from SVR, supporting that the virus had been cleared. The three patients, who all lacked signs of liver disease, had HCV RNA in PBMCs 5–9 years after SVR. All three had HCV‐specific T cells and NS3 antibodies, but no cross‐neutralising antibodies. Conclusions Our combined data confirm that a SVR corresponds to a long‐term clinical cure. The waning immune responses support the disappearance of the antigenic stimulus. Transient HCV RNA traces may be detected in some patients up to 9 years after SVR, but no marker associates this with an increased risk for liver disease.

We aimed to assess fibrosis with liver stiffness measurement long-term after sustained virological response of chronic hepatitis C and to identify risk factors associated with persisting fibrosis. In this cross-sectional study, patients with chronic hepatitis C and pretreatment advanced fibrosis or cirrhosis treated successfully at Karolinska University Hospital with an interferon-containing regimen underwent liver stiffness measurement with FibroScan. The impact of potential risk factors for persisting fibrosis was estimated. We included 269 patients with a median follow-up time of 7.7 years (range 0-20), 84 with a follow-up time of ≥10 years. Patients with pretreatment cirrhosis had a significantly higher median liver stiffness level (8.5 kPa 95% CI 7-9.1) at follow-up, than patients with advanced fibrosis (6 kPa 95% CI 5.5-6.4). A majority improved their fibrosis stage after sustained virological response, but 24% had persisting advanced fibrosis with a liver stiffness level of ≥ 9.5 kPa. Among patients with pretreatment cirrhosis, the proportion with persisting advanced fibrosis diminished with longer follow-up time, from 48% after <5 years to 21% after >10 years. The main risk factors for persisting advanced fibrosis were pretreatment cirrhosis, high age and body mass index. In conclusion, fibrosis improves substantially during long-term follow-up after sustained virological response in hepatitis C patients with pretreatment advanced liver fibrosis. Lifestyle intervention to decrease weight in obese persons and treatment before establishment of cirrhosis should therefore be recommended to avoid persistence of advanced fibrosis after virological cure.