Estimating the Attributable Fraction of Cirrhosis and Hepatocellular Carcinoma Due to Hepatitis B and C

Erika Duffell; Helena Cortez-Pinto; Marieta Simonova; Olav Dalgard; Elin Hoffmann Dahl; Catherine de Martel; Antons Mozalevskis; Maria Buti; Slava Pavlova; Tnaiq Hadzhilova; Carolina Simões; Krum Katzarov; Otilia Mardh


J Viral Hepat. 2021;28(8):1177-1189. 

In This Article


Patient's Inclusion

Bulgaria. A total of 602 patients presenting with cirrhosis and/or HCC (518 cirrhosis; 84 HCC) at the MMA in Sofia for the period 01.01.2016–31.12.2016 were retrospectively included in the study. MMA is one of the two national liver transplant centres for adult patients in Bulgaria. Of the 602 patients, 398 cirrhotic and 78 HCC patients were admitted to the Department of Gastroenterology, Hepato-Biliary-Pancreatic and Transplant Surgery, and 120 cirrhotic and 6 HCC patients were admitted to the Intensive Care Clinic. Data were extracted from the central electronic system using the ICD-10 coding system for all hospital admissions with the following codes: K74.3, K74.5, K74.4, K.74.6, K74.0 –K74.2 for cirrhosis; and C22.0 for HCC.

Norway. The pilot included 447 patients (434 cirrhosis; 53 with HCC (40 with both)) admitted in 2016 to the Akershus University Hospital, which is located outside of Oslo.

Data were extracted from the electronic system of the hospital using ICD-10 codes covering alcoholic cirrhosis and hepatitis failure, acute and sub-acute hepatitis failure, chronic and unspecified hepatitis failure (K70.3, K70.4, K72.0, K72.1, K72.9); primary and secondary biliary cirrhosis, other unspecified cirrhosis of the liver, other inflammatory and 'other diseases' of the liver, fibrosis and non-alcoholic cirrhosis of the liver (K74.3 - K74.6, K75.4, K76.6, K76.7); HCC and malignant neoplasm of the liver unspecified (C22.0, C22.9) and gastric and oesophageal varices (I85.0, I85.9, I86.4).

Portugal. The first 100 consecutive patients with cirrhosis and also the first 100 with HCC admitted in the Department of Gastroenterology and Hepatology of the Centro Hospitalar Lisboa Norte in Lisbon during 2016 were included in the pilot. Cases were identified through retrospective review of electronic and paper files of medical records of admitted patients with the diagnosis of liver cirrhosis of any aetiology and/or HCC.

Qualitative Assessment of Pilot Roll-out

Bulgaria. The main challenges faced during the pilot were the time needed for reviewing the hospital records and extracting patient data. The investigators highlighted the need to reduce the number of variables collected to simplify the system. The study also demonstrated the importance of having a single dedicated person, if possible, to collect and enter the data in a consistent way.

All patients were screened for HBV and HCV. However, a further challenge identified during the pilot was the lack of data on metabolic diseases found in patient records. Detailed information on history of alcohol use was also often lacking. The reason invoked was that this type of data is difficult to obtain and verify as this is mainly self-reported behaviour reported at the time of hospital admission. Liver transplant candidates were the only patients where alcohol consumption was objectively assessed by a psychiatrist.

A further issue identified was related to the set-up of the local hospital record system, which limits the coding of patients to only two diagnoses. Whilst other concomitant diseases are recorded in hospital admission records, they are not coded electronically into the system. Consequently, patients with cirrhosis or HCC who had multiple pathologies may not have been identified by the system and not included, with implications for the representativeness of the sample.

Norway. During the pilot, the work was delayed due to the long review process for ethical approval and the subsequent process of obtaining permission for access to the hospital data.

The locally applied case definition used to identify cases was broad and identified many patients who subsequently turned out not to have cirrhosis or HCC. Data were collected from both general hospital records and registries of patients undergoing liver transient elastography. Some patients had been coded using different ICD codes throughout the year and a careful review of the files of these patients to avoid duplication was time-consuming.

Some patients had been diagnosed a long time ago or in a different healthcare facility. For these patients, access to diagnosis information and verification of the underlying cause of cirrhosis and HCC was more difficult. Obtaining an accurate history of alcohol use from any patient records was also considered difficult as it is mainly self-reported at admission. The whole process was considered very time-consuming due to the need for manual collection of data from patient files that needed to be cross-checked with other sources.

The investigators warned that the sample of cases identified through the transient elastography registry may be biased towards HCV, as in 2016, HCV patients had regularly attended a transient elastography in order to decide on treatment initiation, whereas patients with other aetiologies might not have been scanned so regularly.

Portugal. The broad case definitions used resulted in the need to review the records of many patients who turned out not to have cirrhosis or HCC. As with the two other sites, the manual review of hospital records was reported to be time-consuming and the local investigators highlighted the need for a simplified protocol for data collection, specifically, less data, concentrating on data meaningful for the aetiological definition of the diseases. The retrieval of data electronically rather than through a review of paper records was identified as the most efficient method of data collection.

Furthermore, in the case of Portugal, data were exclusively retrieved from a specific medical department of the Hospital, the gastroenterology department, which may have led to referral bias as these patients probably had more severe disease, with the majority having decompensation of their liver cirrhosis.

AF Estimates of Cirrhosis and HCC due to HBV and HCV Obtained From Pilot Study and Validity Assessment of Estimates

The results obtained in the pilot sites through the crude analysis were compared to the estimates published by the GBD study and estimates based on a worldwide meta-analysis of case series led by IARC (see Table 1).