Hepatitis C: Complications

The following are the most important diseases or complications that may be contributed to by hepatitis C:

Eyes and eye appendages (H00-H59).

• Ulcerative keratitis (PUK; inflammation of the cornea of the eye with ulceration) in the context of hepatitis C-associated cryoglobulinemia (form of vascular inflammation resulting from deposition of immune complexes in the small vessels)

Endocrine, nutritional, and metabolic diseases (E00-E90).

• Hashimoto’s thyroiditis – autoimmune disease leading to chronic thyroiditis.

Blood, blood-forming organs – immune system (D50-D90).

• Cryoglobulinemia – chronic recurrent immune complex vasculitis (vascular immune disease) characterized by evidence of abnormal cold-precipitating serum proteins (cold antibodies); this regularly leads to renal dysfunction.
• Purpura (skin hemorrhage).
• Porphyria cutanea tarda – disease that occurs due to excess of various proteins (aminolevulinic acid and porphobilinogen).

Skin and subcutaneous (L00-L99).

• Pruritus (itching)

Liver, gallbladder, and bile ducts-pancreas (pancreas) (K70-K77; K80-K87).

• Acute liver failure
• Chronic hepatitis C (approximately 70% of hepatitis C patients).
• Liver cirrhosis (irreversible damage to the liver leading to gradual connective tissue remodeling of the liver with impairment of liver function)
  • Approximately 2-35% of patients with a chronic course after 20-25 years (doctrine).
  • Study by fibrosis-4 index (FIB-4; considered: Age, ALT (GPT), AST (GOT), platelets; values > 3, 5 are considered liver cirrhosis): 15.1% of patients developed liver cirrhosis after 5 years, and 18.4% after 10 years.

Musculoskeletal system and connective tissue (M00-M99).

• Arthritis (inflammation of the joints)
• Sjögren’s syndrome (group of sicca syndromes) – autoimmune disease from the group of collagenoses, which leads to a chronic inflammatory disease of the exocrine glands, most often the salivary and lacrimal glands; typical sequelae or complications of sicca syndrome are:
  • Keratoconjunctivitis sicca (dry eye syndrome) due to lack of wetting of the cornea and conjunctiva with tear fluid.
  • Increased susceptibility to caries due to xerostomia (dry mouth) due to reduced salivary secretion.
  • Rhinitis sicca (dry nasal mucous membranes), hoarseness and chronic cough irritation and impaired sexual function due to disruption of mucous gland production of the respiratory tract and genital organs.

Neoplasms – tumor diseases (C00-D48).

• Hepatocellular carcinoma (HCC, hepatocellular carcinoma/liver cell cancer).
  • In the presence of existing liver cirrhosis:
    • 5-year cumulative risk of developing hepatocellular carcinoma (HCC) approximately 17%.
    • And diabates mellitus: 6-fold risk of HCC.
  • Even after successful viral elimination, patients with chronic HCV infection have a substantial risk of primary liver carcinoma.
• Patients with chronic hepatitis C have an increased incidence (frequency of new cases) of the following nonhepatic carcinomas:
  • Pancreatic cancer/pancreatic cancer (2.5 [1.7-3.2]).
  • Rectal cancer/bowel cancer (2.1 [1.3-2.8])
  • Renal carcinoma (1.7 [1.1-2.2])
  • Non-Hodgkin lymphoma (NHL) (1.6 [1.2-2.1])
  • Bronchial carcinoma/lung cancer (1.6 [1.3-1.9])

  Age-adjusted mortality (death rate) was significantly higher among patients with carcinomas of the following organs:

  • Liver (RR, 29.6 [95% CI, 29.1-30.1]).
  • Mouth (5.2 [5.1-5.4])
  • Rectum (2.6 [2.5-2.7]), NHL (2.3 [2.2-2.31])
  • Pancreas (1.63 [1.6-1.7])

Symptoms and abnormal clinical and laboratory findings not elsewhere classified (R00-R99).

• Proteinuria (increased excretion of protein in urine) – 7-fold increased risk of developing proteinuria and severe chronic kidney disease.

Genitourinary system (kidneys, urinary tract – reproductive organs) (N00-N99).

• Chronic kidney disease – 7-fold increased risk of developing proteinuria and severe chronic kidney disease.
• Membranoproliferative glomerulonephritis (MPGN) (inflammation of the renal corpuscles).
• Female reproductive disorders (premature ovarian failure/premature cessation of ovarian function).
• Other renal disease – HCV RNA-positive patients have up to a 10-fold increased risk of dying from a renal-related cause of death.

Prognostic factors

• Dialysis patients – significant reduction in life expectancy and quality of life.
• In PEG-IFN alpha/RBV combination treatment, the allele constellation of the IFNL4 gene influences treatment success:
  • SNP: rs12979860 in the IFNL4 gene.
    • Allele constellation: CC (approximately 80% of patients respond to PEG-IFN alpha/RBV combination therapy).
    • Allele constellation: CT (approximately 20-40% of patients respond to PEG-IFN alpha/RBV combination therapy).
    • Allele constellation: TT (approximately 20-25% of patients respond to PEG-IFN alpha/RBV combination therapy).