. 2023 Apr 26;5(8):100776. doi: 10.1016/j.jhepr.2023.100776

Table 2.

Impact of vaccine-preventable infections in patients with CLD or LT.

Study	Patients included	Underlying condition	Main outcomes
Hepatitis B

Benvegnù L, 1994²²	290 patient with cirrhosis	25% HBsAg positive 69% anti-HCV 26% alcohol abuse	By multivariate analysis, age (p <0.01), positivity for HBsAg and HCV antibodies (p <0.05), male sex (p <0.05), and previous alcohol abuse (p <0.08) were independently related to HCC.
Tsai JF, 1997²³	400 patients with cirrhosis	21% anti-HCV 59% HBsAg positive 10% positive HBsAg and anti-HCV 11% both negative	HCV/HBV co-infection (HR 6.41; 95% CI 1.80-22.80), anti-HCV alone (HR, 3.74; 95% CI 1.07-13.07) and HBsAg alone (HR, 4.06; 95% CI 1.23-13.34) were independent risk factors for HCC.
Zarski JP, 1998²¹	23 patients and 69 age- and sex-matched HBsAg negative patients with chronic HCV	Chronic HCV and HBV subdivided according to HBV DNA replication	Prevalence of cirrhosis was greater in HBV and HCV patients than in patients with HCV alone (p = 0.01). Among HBV and HCV, HCV RNA level was significantly lower in HBV DNA positive than in HBV DNA negative (p = 0.01) patients.
Crespo J, 1999²⁴	136 HBsAg negative	LT recipients	6 patients (4.4%) became HBsAg positive. Two developed acute liver failure, 4 had severe chronic hepatitis related to HBV.
Liaw YF, 2000¹⁹	2 HBV superinfection	Chronic HCV	1 death from hepatic failure. The other recovered with seroclearance of HBsAg, and antibodies to HCV.
Sagnelli E, 2002²⁰	44 HBV acute infection	21 anti-HCV positive 20 anti-HCV negative 3 HBV/HCV concurrent infection	Severe acute hepatitis was more frequent in the chronic HCV carriers than in the control group (28.6% vs. 0%, p <0.05). HBV superinfection strongly and persistently depresses HCV.
Hepatitis A
Vento S, 1998⁴⁷	432 patients with HCV	Chronic HCV	17 cases of HAV superinfection. 7 cases of acute liver failure and 6 deaths.
Pramoolsinsap C, 1999	32 cases of HAV superinfection and 100 cases of isolated HAV	20 HBsAg carrier 8 HBV 4 HCV	All cases with isolated HAV recovered. Fulminant or submassive hepatitis occurred in 11 (55%) of the HBsAg carriers and 4 (33%) of the 12 patients with CLD related to either HBV or HCV.
Pneumococcal disease
Viasus D, 2011⁵⁹	3,420 cases of community-acquired pneumonia	90 cases in patients with cirrhosis compared with non-cirrhotic cases	Impaired consciousness at admission (p <0.001), septic shock (p = 0.011), high-risk Pneumonia Severity Index classes (p = 0.002), bacteraemia (p = 0.023), and early (p = 0.048) and overall (p <0.024) mortality rates were higher in patients with cirrhosis than in patients without cirrhosis.
Kim T, 2016⁶⁰	50 SBP cases due to Streptococcus pneumoniae 100 SBP cases due to other organisms	Cirrhosis	Patients with SPP were more likely to present concurrent bacteraemia (p = 0.002), to present with variceal bleeding (p = 0.02) and the 30-day mortality was significantly lower (p = 0.04).
Baxter R, 2016⁵⁷	1,549 IPD cases from 15,102,047 person-years in the Kaiser Permanente Northern California	Several medical conditions	Highest adjusted RR for IPD were chronic liver disease (RR 2.1, 95% CI 1.5-2.8) and chronic obstructive pulmonary disease (RR 2.1, 95% CI 1.8-2.5).
Imai K, 2018⁵⁸	10.4 million individuals, representing 9.3 million person-years of follow-up in Japan	Eleven medical conditions	Adults aged 50–64 years with an underlying medical condition (rate: 39-212 per 100,000 person-years) had a higher rate of infection than those aged ≥65 years without any condition (rate: 13-93 per 100,000 person-years).
Influenza virus
Duchini A, 2000⁶³	3 cases of influenza A with hepatic decompensation	1 Wilson and 2 alcohol-related liver disease	Two patients had hepatic decompensation and the third had acute hepatocellular damage. All recovered within 1 month.
Vilchez RA, 2000⁶⁸	1 case of influenza A myocarditis	LT recipient	Global hypokinesis and severe impairment of left ventricular function, circulatory compromise, severe liver damage and AKI.
Marzano A, 2013⁶⁵	48 inpatients with A/H1N1/09 infections 44 outpatients with mild influenza-like illness	Inpatients: 21 and 27 with and without cirrhosis Outpatients: without cirrhosis	A/H1N1/09 infection rate did not differ in patients with and without cirrhosis (19% and 15%), but three patients with cirrhosis died while none of patients without cirrhosis died.
Schütte A, 2019⁶⁴	45 inpatients with influenza infection	11 patients with cirrhosis and 34 without	Cirrhotic patients presented higher organ failure scores, lower blood pressure, higher proportion of secondary bacterial infections, ACLF and deaths.
Premkumar M, 2019⁶⁷	110 patient with cirrhosis admitted to ICU with suspected A/H1N1/09 infection	22 A/H1N1/09 positive and 88 influenza-like pneumonia	Death occurred in 82% of patients with A/H1N1/09 compared with 40% of the control group. PaO₂/FiO₂ratio <200 and serum creatinine >1.8 mg/dl were predictors of mortality.
Liu WD, 2020⁶⁶	73 patients with influenza A and 23 with influenza B	Adult patients with several medical conditions	11% and 44% deaths occurred within 30 days in each group. Factors associated with mortality were CLD (HR: 3.94; 95% CI 1.07-14.45) rheumatologic diseases (HR: 7.45; 95% CI 2.34-23.69) and influenza B (HR: 4.33; 95% CI 1.68-11.13).
Tuberculosis
Thulstrup AM, 2000⁹⁰	Cohort of 22,675 patients in Denmark	Cirrhosis	The incidence was 169 per 100,000 person-years of risk. The highest incidence was among men >65 years (246 per 100000 person-years of risk). The 30-day and 1-year case-fatality were 27% and 48%.

Summary of impact of vaccine-preventable infections (excluding COVID-19) in patients with CLD and LT recipients.

AKI, acute kidney injury; CLD, chronic liver disease; HAV, hepatitis A virus; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HR, hazard ratio; ICU, intensive care unit; ICU; IPD, invasive pneumococcal disease; LT, liver transplant; RR, relative risk; SBP, spontaneous bacterial peritonitis; SPP, spontaneous pneumococcal peritonitis.